Pharmacology

Drug Class Summaries

ACE inhibitors

Examples

• Ramipril, perindopril, lisinopril, captopril, enalapril

Classification

• Group 1: active drugs with active metabolites (e.g. captopril)
• Group 2: prodrugs requiring hepatic activation (e.g. ramipril, enalapril)
• Group 3: active drug, no metabolism (e.g. lisinopril)

Indications

• Hypertension
• Heart failure
• Post MI with LV dysfunction

Routes: Oral only

Mechanism of action

• Block the conversion of angiotensin I to angiotensin II by angiotensin converting enzyme
• Leads to decreased angiotensin II induced vasoconstriction, sodium/water retention and aldosterone release

Effects

• Decreased SVR > decreased blood pressure

• Decreased AGT2 and aldosterone > Natriuresis

Side effects

• CNS: headache, dizziness
• CVS: hypotension
• RESP: cough (due to accumulation of bradykinin)
• RENAL: renal impairment, AKI
• GIT: hepatitis, pancreatitis
• OTHER: angioedema/allergy, teratogen

Contraindications

• Avoid use in pregnancy > may lead to foetal renal dysfunction / death

Acid suppressants

Class	Example	MOA	Indications
Antacids	Aluminium hydroxide, calcium carbonate	Neutralise hydrochloric acid secreted by gastric parietal cells (base reacts with acid to produce a salt and water)	Symptomatic relief: - Dyspepsia - GORD
Proton pump inhibitors	Pantoprazole, omeprazole	Binds to H+/K+ ATPase in parietal cells (the final common pathway for gastric acid section) > decreased acid secretion	- Peptic ulcer disease - GORD - Zollinger-Ellison syndrome - Stress ulcer prophylaxis
H2 receptor antagonists	Nizatidine, ranitidine (withdrawn)	Competitively block H2 receptors on parietal cells > reducing gastric acid secretion (decreased H/K ATPase activity).	- Peptic ulcer disease - GORD - Stress ulcer prophylaxis

Antiarrhythmics

Vaughan-Williams classification

Class	Ia	Ib	Ic	II	III	IV
Mechanism	Blocks Na channels	Blocks Na channels	Blocks Na channels	<math display="inline">\beta</math>-adrenergic blockade	Blocks K+ channels	Blocks Ca channels
Example	Procainamide	Lidocaine	Flecainide	Propranolol Esmolol, Atenolol Sotalol	Amiodarone (also I,II,IV effects) Sotalol	Verapamil Diltiazem
Effects on
Phase 0	↓	-	↓	-	-	-
Conduction velocity	↓	-	↓	↓	↓	-
ERP	↑	↓	↑	↓	↑	-
APD	↑	↓	-	↑	↑	↓
QRS duration	↑	-	↑	-	↑	-
QTc	↑	↓	↑	↓	↑	-

Phase 0 of action potential (depolarisation), ERP = effective refractory period, APD = action potential duration

Drugs not included

• Digoxin
• Adenosine

Antibiotics

Inhibitors of cell wall synthesis	Drug example
Beta-lactams	Flucloxacillin
Cephalosporin	Ceftriaxone
Carbapenems	Meropenem
Monobactams	Aztreonam
Glycopeptides	Vancomycin
Inhibitors of cytoplasmic membrane function
Polymyxins	Colistin
Lipopetides	Daptomycin
Inhibitors of nucleic acid synthesis
Quinolones	Ciprofloxacin
Rifamycins	Rifampicin
Nitroimidazoles	Metronidazole
Folate metabolism inhibitors
Folate metabolism inhibitor	Trimethoprim
Inhibitor of protein synthesis
Aminoglycosides	Gentamycin
Tetracyclines	Doxycycline
Lincosamides	Clindamycin
Macrolides	Erythromycin

File:C:\Users\ethan\AppData\Roaming\Typora\typora-user-images\image-20220416160642189.png

Anticoagulants

Class	Example	MOA	Route	Pros	Cons
LMWH	Enoxaparin	LMWH binds to antithrombin 3 > conformational change > increases affinity for inactivating Xa (and weakly thrombin)	SC	- Routine monitoring not needed - Given S/C reliably	- Incomplete reversal with protamine
HMWH	Heparin	HMWH binds to antithrombin 3 > conformational change > increases affinity for inactivating thrombin (factor IIa) and Xa	SC, IV	- Completely reversed with protamine -Rapid onset/offset	- Requires IV infusion for ongoing anticoagulation -Requires monitoring
Direct thrombin inhibitors	Dabigatran	Prodrug. Converted by plasma/liver esterase's to active moiety. Competitive direct thrombin inhibitor > decreased conversion of fibrinogen to fibrin	PO	- Reversal agent (praxbind) - Daily dosing	- Cannot be used for all conditions
Anti-Xa inhibitors	Apixaban, rivaroxaban	Direct Xa inhibitor > Decreased thrombin production > decreased conversion of fibrinogen to fibrin	PO	- Rivaroxaban has lowest risk bleeding	- Apixaban BD dosing - No reversal agent - Not yet approved for all conditions
Vitamin K antagonists	Warfarin	Inhibits the synthesis of vitamin K dependant clotting factors (II, VII, IX, X). Specifically, inhibits vitamin K epoxide reductase (VKORC1) from converting VitK from the oxidised to reduced form, which prevents carboxylation (activation) of clotting factors listed above (as well as protein C and S)	PO	- Can be used for most conditions (including cancer, valvular AF)	- Numerous drug-drug interaction - Variable levels require close monitoring

Antiemetics

Class	Example	MOA	Indications
Serotonin antagonists	Ondansetron	Central and peripheral 5-HT3 receptor antagonism > reduced afferent input to vomiting centre in medulla	- PONV - Radiotherapy - Chemotherapy - General
Corticosteroids	Dexamethasone	MOA unclear. May involve: decreased peripheral 5HT release, PG antagonism	Prevention of N and V (not effective for established)
Dopamine antagonists	Metoclopramide, Droperidol	Central D2 antagonism at chemoreceptor trigger zone > reduced afferent input to vomiting centre in medulla	- PONV - General
Antihistamine	Cyclizine	Competitive H1 antagonism	- Motion sickness - Radiotherapy - PONV - Opioid induced
NK1 antagonist	Aprepitant	Blocks action of substance P in brainstem vagal complexes involved in regulation of vomiting	- Chemotherapy induced
Others	Canabinoids	Thought to act within the vomiting centre	- Chemotherapy

Antihypertensives

Sympatholytic's

Class	Example	MOA
Alpha blockers	Prazosin	<math display="inline">\alpha</math>1 antagonist > arterial and venous vasodilation > ↓ SVR > ↓ BP
Beta blockers	Metoprolol	<math display="inline">\beta</math>1 antagonist > ↓ inotropy + ↓ chronotropy > ↓ BP
Centrally acting	Clonidine	Central <math display="inline">\alpha</math>2 agonist > ↓ SNS tone (via ↓ NA release) > ↓ BP

RAAS inhibitors

Class	Example	MOA
ACE inhibitors	Ramipril	Block the conversion of angiotensin I to angiotensin II by ACE > decreased AG2 > ↓ SVR and ↑ natriuresis > ↓ BP
ARBs	Candesartan	Same as ACEI (above) but blocks AG2 directly.

Calcium channel blockers

Class	Example	MOA
Dihydropyridine	Amlodipine	Blocks L-Type calcium channels in SM > ↓ intracellular Ca > vasodilation > ↓ SVR > ↓ BP
Non-dihydropyridine	Verapamil	Same as dihydropyridines, but additionally preferentially acts on cardiac cells > ↓ HR and ↓ contractility > ↓BP

Diuretics

Class	Example	MOA
Loop diuretic	Frusemide	Blocks to NK2Cl transporter in the aLOH> ↓ Na,K, Cl reabsorption > ↓ medullary tonicity + ↑ Na/Cl delivery to distal tubules > diuresis > ↓ BP
Thiazide diuretic	Hydrochlorothiazide	Blocks Na/Cl cotransporter in DCT > ↓ Na+ and Cl- reabsorption > diuresis > ↓ BP
Potassium sparing diuretic	Spironolactone	Competitive aldosterone antagonist > ↓ Na reabsorption in DCT > diuresis > ↓ BP

Vasodilators

Class	Example	MOA
Nitrates	GTN	Dinitrated to NO > diffuses into SM > binds to guanylyl cyclase > ↑ GMP > ↓ intracellular Ca > vasodilation > ↓ BP
Hydralazine	Hydralazine	Not fully understood. Though to also activate guanylyl cyclase > ↑ GMP > ↓ intracellular Ca > arteriolar vasodilation > ↓ BP

Antiplatelets

Class	Example	MOA
COX inhibitors	Aspirin	Irreversibly inhibits COX on platelets > decreased thromboxane A2 > decreased platelet aggregation
ADP receptor antagonists	Clopidogrel, prasugrel, Ticagrelor	Binds to P2Y12 subtype of the ADP receptor on platelets > prevents glycoprotein IIb/IIIa activation > prevents platelet activation
GP IIb/IIIa receptor antagonists	Abciximab, tirofiban	Directly bind to GP IIb/IIIa and block the final common pathway of platelet aggregation
Phosphodiesterase inhibitors	Dipyridamole	Inhibits platelet adhesion to walls (by inhibiting adenosine uptake). Also inhibits phosphodiesterase activity > increased cAMP > decreased calcium > inhibition of platelet aggregation
Prostacyclin's	Epoprostenol	Binds to IP receptors > increased cAMP > decreased calcium > inhibition of platelet aggregation

Antiplatelet	Route	Elimination	Reversibility	Duration of antiplatelet effect	Adverse effects
Aspirin	PO	Renal (100%)	Irreversible inhibition	Life of platelet (~7 days)	-Haemorrhage - GIT ulcers - Allergy, angioedema, bronchospasm - AKI
Clopidogrel	PO	Renal (50%) Faecal (50%)	Irreversible inhibition	Life of platelet (~7 days)	- Haemorrhage - Non responder (CYP2C19 polymorphism) -CYP450 drug interactions - aplastic anaemia, thrombocytopaenia, anaemia, - GIT ulcers - Rash, urticaria, angioedema, TTP
Prasugrel	PO	Renal (70%) Faecal (30%)	Irreversible inhibition	Life of platelet (~7 days)	- Haemorrhage - Rash, urticaria, angioedema, TTP
Ticagrelor	PO	Faecal (70%) Renal (30%)	Reversible inhibition	2-3 days	- Haemorrhage - Dyspnoea - Rash, urticaria, angioedema, TTP
Abciximab	IV	Renal	Reversible inhibition	1-2 days	- Haemorrhage - ↓ PLTs
Tirofiban	IV	Renal (70%) Faecal (30%)	Reversible inhibition	4-6 hours	Haemorrhage - ↓ PLTs, TTP - Allergy
Dipyridamole	PO	Faecal	Reversible inhibition	1-2 days	- Haemorrhage - Hypotension - GIT upset (nausea, vomiting, diarrhoea) -Rash, urticaria
Epoprostenol	IV	Renal (70%), Faecal (15%)	Reversible inhibition	< 5 mins	- Hypotension, headache, flushing, Haemorrhage

Antipsychotics

1st generation (typical)	2nd generation (atypical)
Examples: haloperidol (Butyrophenones), chlorpromazine (Phenothiazines)	Examples: olanzapine (diazpine), quetiapine (dibenzothiazpine), clozapine
Higher affinity for D2 receptors	5-HT2 antagonism and comparatively less affinity for D2 receptors
Better effect on 'positive' symptoms (hallucinations, delusions, hyperactivity)	Better effect on negative symptoms (apathy, lethargy etc)
More extrapyramidal side effects (EPSE) - dystonia, akathisia, parkinsonism, TD	Fewer EPSE
Less metabolic side effects (weight gain, diabetes, hyperChol etc)	More metabolic side effects

This classification system is particularly flawed..

Aperients & Laxatives

Class	Example	MOA	Time to effect	Adverse effects
Stool softeners	Docusate	Surfactant - reduces tension at oil-water interface > allows water and lipids to penetrate stool > softer	1-3 days (PO)	Abdo cramps, nausea, diarrhoea
Bulk forming laxatives	psyllium (Metamucil)	Absorbs water in colon > increase faecal bulk > stimulates peristaltic activity	2-3 days	Flatulence, bloating, abdominal discomfort
Osmotic laxatives	Glycerol, lactulose, macrogol	Lactulose: broken down by GIT bacteria > lactic+acetic acid > increased osmotic pressure + intraluminal pressure > soft stool + peristalsis Macrogol: osmotic agent > increased water retention in stool	1-3 days (PO) 30 mins (PR)	Abdo pain, nausea, vomiting, diarrhoea, electrolyte imbalances
Stimulant laxatives	Senna	Direct stimulation of colonic mucosa > increase motility and secretions	12 hours (PO) 1 hour (PR)	Diarrhoea, hepatitis, abdo discomfort
Combinations	Docusate with senna	See above	see above	See above

Asthma medications

Class	Example(s)	Mechanism of action	Adverse effects
Common
Gas	Oxygen	Increases FiO2 > increases PAO2 (per Alveolar gas equation) > increased SaO2	Hypercapnia, worsening of V/Q mismatch (through alteration of HPVC), lung damage (free radicals)
<math display="inline">\beta</math>2 agonists	- Salbutamol (short acting) - Salmeterol (long acting) - Adrenaline (non specific agonist)	Acts on B2 receptors (Gs protein coupled receptors) in bronchial smooth muscle cells > activates activates adenyl cyclase-cAMP system > increase cAMP > decreased intracellular Ca / phosphorylation of PKC > SM relaxation / bronchodilation	Tachycardia, Anxiety, tremor, Hypokalaemia, lactic acidosis
Anticholinergics	Ipratropium bromide	Competitive antagonism of muscarinic ACh receptors > bronchodilation + decreased secretions	Dry mouth, N/V, headache, blurred vision
Corticosteroids	- Hydrocortisone (IV) - Prednisone (PO) - Budesonide (inhaled)	Bind to cytoplasmic glucocorticoid receptors > change in gene transcription > down-regulates the synthesis of proinflammatory cytokines / mediators	Short term: hyperglycaemia, hypokalaemia, immunosuppression, insomnia, confusion, psychosis Long term: cushings, osteoporosis, skin thinning, weight gain, immunosuppression
Less common
Electrolyte	Magnesium sulphate	Inhibits L type calcium channels > Bronchial smooth muscle relaxation	Hypotension, muscle weakness
Phencyclidine derivative	Ketamine	Inhibits L type calcium channels > Bronchial smooth muscle relaxation	Hallucinations, sedation,
Methylxanthine derivative	Aminophylline	Phosphodiesterase inhibitor > increased cAMP > decreased Calcium intracellularly > SM relaxation / bronchodilation	Arrhythmias, seizures, hypokalaemia
Gas	Heliox	May improve laminar airflow (through decreased Re number from decreased density)	Cannot be used with FiO2 > 0.4, little evidence
Gas	Inhalational anaesthetics (e.g. sevoflurane)
Leukotriene receptor antagonists	Monteleukast

Beta blockers

Classification of beta blockers

• All beta blockers are competitive antagonists
• Can be classified according to
  • Receptor selectivity
    • Non selective (B1 and B2) e.g. sotalol, propranolol
    • B1 selective e.g. metoprolol, esmolol, atenolol
    • A and B effects: labetalol, carvedilol
  • Membrane stabilising effects
    • Stabilising e.g. Propanolol, metoprolol
    • Non stabilising e.g. atenolol, esmolol, bisoprolol
  • Intrinsic sympathomimetic activity
    • ISA e.g. labetalol, pindolol
    • Non ISA e.g. metoprolol, sotalol, propranolol, esmolol

Effects of beta blockers

• B1 antagonism
  • Heart: decreased inotropy and chronotropy (> decreased BP), decreased myocardial oxygen consumption, decreased AV nodal conduction (dromotropy)
  • Kidneys: decreased renin release > decreased RAAS activation > decreased BP
• B2 antagonism
  • Respiratory: bronchoconstriction
  • Circulation: vasoconstriction
  • Skeletal muscle: reduced glucose uptake
  • Eye: decreased aqueous humour production
• B3 antagonism
  • Adipose tissue: reduced lipolysis

Calcium channel blockers

MOA

• Bind to L-Type calcium channels > block entry of Calcium
• In the SM it leads to vasodilation, in SA/AV node it reduces slope of Phase 0 (slows depolarisation/conductance of AP), and in the myocardium it shortens phase 2 of the AP reducing inotropy
• Variable affinity for: myocardium, SA node, AV node, vascular smooth muscle
• In general dihydropyridines have increased affinity for smooth muscle, whereas the non-dihydropyridines have increased affinity for the heart (SA, AV, myocardium)

Classes

Class	Example	BP	HR	SVR	Contr.	SA node	AV node
Dihydropyridine	Amlodipine, nimodipine, nifedipine	↓	- ↑	↓	-	-	-
Non-dihydropyridine	Diltiazem, verapamil	↓	↓	↓	↓	Slow	Slow

Corticosteroids

Corticosteroids

• Steroid hormones normally produced by the adrenal cortex
• Two main classes of corticosteroids
  • Glucocorticoids (secreted from zona fasciculata and reticularis)
  • Mineralocorticoids (secreted from zona glomerulosa)
• Note: corticosteroids can have both glucocorticoid and mineralocorticoid effects to varying degrees (SEE BELOW)

Steroid	Glucocorticoid (& anti inflammatory) potency	Equivalent dose	Mineralocorticoid activity
Hydrocortisone	1	100mg	1
Prednisone	4	25	0.8
Methylprednisolone	5	20mg	0.5
Dexamethasone	25	4mg	Negligible
Fludrocortisone	10	N/A	125

Crystalloids (fluids)

Crystalloids

• Aqueous solutions of inorganic ions and small organic molecules
• The main solute is glucose or sodium chloride
• The solutions may be isotonic, hypotonic or hypertonic compared to plasma
  • Note most companies report osmolarity, which is different to the effective osmolality seen in vivo, so some iso-osmolar fluids (e.g. dextrose) are actually completely hypotonic.

Colloids

• Homogenous, non-crystalline substance consisting of large molecules (e.g. proteins) suspended in a crystalloid solution

Component	Human plasma	Plasma-lyte-148	Hartmann's	0.9% NaCl	5% Dextrose
Na	135-145	140	131	154	0
Cl	95-105	98	111	154	0
K	3.5-5.3	5	5	0	0
HCO3/precursor	24-32	Lactate (27) Gluconate (23)	29 (lactate)	0	0
Ca	2.2-2.6	0	2	0	0
Mg	0.8-1.2	1.5	0	0	0
Glucose	3.5-5.5	0	0	0	278
pH	7.35-7.45	7.4	6.5	5	4
Osmolarity (mOsm/L) Theoretical	-	295	278	308	278
Osmolality (mOsm/Kg) Effective	275-295	271	256	286	0
Effective tonicity	-	V. mildly hypotonic	Hypotonic	Isotonic	Very hypotonic

There are obviously more crystalloids than this...

Diuretics

Class	Example	Site of action	MOA	Route
Osmotic diuretics	Mannitol	Entire	Freely filtered at glomerulus, but not reabsorbed. Acts osmotically to decrease H2O reabsorption	IV
Carbonic anhydrase inhibitors	Acetazolamide	PCT	Inhibits carbonic anhydrase in PCT > decreased reabsorption of filtered HCO3	PO, IV
Loop diuretics	Frusemide	Loop of Henle	Binds to NK2Cl transporter in the thick ascending limb LOH, leads to decreased Na,K, Cl reabsorption. Impairs counter current multiplier and reduces medullary tonicity	PO, IV
Thiazide diuretics	Hydrochlorothiazide	DCT	Inhibit Na+ and Cl- reabsorption (Na/Cl cotransporter) in the DCT	PO
Aldosterone antagonists	Spironolactone	DCT/CD	Competitive aldosterone antagonist > decreased Na reabsorption (and decreased K excretion)	PO
Potassium sparing diuretic	Amiloride	DCT/CD	Blocks Na/K exchange in DCT > decreased Na/Water reabsorption	PO

Fibrinolytics

	Alteplase	Tenecteplase
Class	Fibrinolytic	Fibrinolytic
Indications	Acute STEMI Acute, unstable, VTE Peripheral arterial thromboembolism	Acute STEMI Acute, unstable, VTE Peripheral arterial thromboembolism
Pharmaceutics	Recombinant version of tissue plasminogen activator (rTPA) Powder + solvent for reconstitution	Modified recombinant version of tissue plasminogen activator Powder + solvent for reconstitution
Routes of administration	IV	IV
Dose	10mg bolus, 90mg infusion over 2 hours (dose adjust if <65kg)	30-50mg IV bolus (with heparin)
Pharmacodynamics
MOA	rTPA becomes active when bound to fibrin, inducing the conversion of plasminogen to plasmin	rTPA becomes active when bound to fibrin, inducing the conversion of plasminogen to plasmin
Effects	Fibrinolysis	Fibrinolysis
Side effects	- Haemorrhage (though less than streptokinase, as more locally acting due to its MOA) - Allergy (angioedema, fever, rash, bronchospasm, anaphylaxis)	- Haemorrhage (though less than streptokinase, as more locally acting due to its MOA) - Allergy (angioedema, fever, rash, bronchospasm, anaphylaxis)
Pharmacokinetics
Onset of effect	Tmax = instant Effect in < 30 mins	T max = instant Effect in 15-30 mins
Absorption	IV only (100% bioavailability)	IV only (100% bioavailability)
Distribution	VOD = 0.1L / Kg	VOD = 0.1L / Kg
Metabolism	Hepatic	Hepatic
Elimination	T 1/2 = < 30 minutes	T 1/2 = 90 mins
Pros/cons	Tenecteplase has/is - Higher fibrin specificity - Longer half life - Better outcomes in some studies - Cheaper - A single push (no infusion)	Tenecteplase has/is - Higher fibrin specificity (modified) - Longer half life - Better outcomes in some studies - Cheaper - A single push (no infusion)

Older fibrinolytics including streptokinase and urokinase are no longer approved in Australia, due to increased adverse events including allergic reactions and prothrombotic events

Hypoglycaemics (oral)

Drug class	Example	Mechanism of action	Important side effects
Commonly used
Biguanides	Metformin	Multiple mechanisms of action. Inhibits mitochondrial respiratory chain > activation of AMPK and reduced cAMP. This: 1) Inhibits hepatic gluconeogenesis 2) increases insulin sensitivity (increases GLUT4 receptors to increase peripheral utilisation), 3) Decreases glucose uptake from GIT	Lactic acidosis (higher risk with renal/liver impairment) due to increased glycolysis and impaired gluconeogenesis leading to lactatemia GIT upset (diarrhoea, nausea, vomiting)
Sulfonylureas	Gliclazide	Inhibit ATP sensitive K channels on pancreatic beta islet cells > depolarisation > Increase insulin secretion	Hypoglycaemia GIT upset Blood dyscrasias Weight gain
DPP-4 inhibitors	Sitagliptin	Inhibit DPP-4 (which normally breaks down GLP-1). GLP-1 stimulates insulin release from pancreas, reduces appetite, delays gastric emptying	Risk of hypoglycaemia Risk of pancreatitis
SGLT-2 inhibitors	Empagliflozin	Inhibits SGLT-2 receptors > decrease glucose reabsorption in the PCT	Osmotic diuresis (Polyuria, polydipsia, dehydration), euglycemic diabetic ketoacidosis, risk of hypoglycaemia, UTIs
Not commonly used
Alpha glucosidase inhibitors	Acarbose	Slows/prevents carbohydrate breakdown and absorption	GIT upset
Thiazolidineodiones	Pioglitazone	Increases insulin sensitivity via PPAR receptors in fat cells	Increased risk of heart failure
Meglitinides	Repaglinide	Similar to sulfonureas, though different receptor	Hypoglycaemia, sig. interaction with antifungals > high levels > hypos

Local anaesthetics

Classified according to the linkage between the hydrophilic and lipophilic groups

	Esters	Amides
Link	Ester link	Amide link
Examples	Cocaine, tetracaine, procaine	Lidocaine, bupivacaine, ropivacaine
Stability in solution	Unstable	More stable
Metabolism	Plasma esterase's	Hepatic (CYP450) dealkylation
Onset	Slow	Faster
Duration	Shorter	Longer
Toxicity	Less likely	More likely
Allergy	Possible	Very rare

Neuromuscular blockers

Major differences in some of the ones in ICU

Name	Rocuronium	Cisatracurium	Suxamethonium	Vecuronium
Class	Aminosteroid	Benzylisoquinolinium derivative	Depolarising NMB	Aminosteroid
Indications	NMB (e.g. RSI, control of ventilation)	NMB (i.e. RSI, control of ventilation)	NMB (i.e. RSI)	NMB (i.e. RSI, control of ventilation)
Pharmaceutics	Clear colourless solution (50mg/5ml vials) Refrigeration (4°C) - 3/12 at room temp	Clear colourless solution (10mg/5ml vials) Stored at 4 degrees	Clear colourless solution (50mg/ml) Stored (4°C) (2/52 at room temp) Precipitates with thiopentone	Unstable in solution > Comes in powder (10mg), dissolved in water (5ml) for use
Routes of administration	IV	IV	IV, IM	IV
Dose	0.6 - 1.2mg/kg (RSI dose)	0.15-0.2mg/kg (RSI) Infusion (titrated to TOF)	RSI: 1-2 mg/kg (IV), 2-3 mg/kg (IM) Not given as infusion > P2 block	0.1mg/kg (RSI)
ED95	0.3mg/kg	0.05mg/kg	0.3mg/kg	0.05mg/kg
Pharmacodynamics
MOA	Non depolarising NMB Inhibits the action of ACh at the NMJ by competitively binding to alpha subunit of nAChR on pre and post junctional membrane	Non depolarising NMB Inhibits the action of ACh at the NMJ by competitively binding to alpha subunit of nAChR on pre and post junctional membrane	Binds to the nACh receptor on motor end plate > depolarisation. Cant be hydrolysed by Acetylcholinesterase in NMJ > sustained depolarisation (i.e. Na channels remain in inactive state)	Non depolarising NMB Inhibits the action of ACh at the NMJ by competitively binding to alpha subunit of nAChR on pre and post junctional membrane
Effects	NMB > paralysis	NMB > muscle paralysis	NMB > paralysis.	NMB > paralysis.
Side effects	Histamine release: none ANS: vagolytic (inc HR) Anaphylaxis (<0.1%) Pain on injection	Histamine release: none ANS: no vagolysis Anaphylaxis (very rare)	Major: anaphylaxis, sux apnoea, malignant hyperthermia Minor: hyperkalaemia, myalgia, bradycardia / arrhythmia Pressure: increased IOP, ICP, intragastric pressure.	Histamine release: rare Vagolysis: none MSK: prolonged use can lead to myopathy
Pharmacokinetics
Onset/Duration	Onset: 45-90s Duration: ~30 mins	Onset: 1-3 min Duration: 30-45 min	Onset: 30s - 60s Duration <10 mins	Onset: 90-120s Duration: 30-45 min
Absorption	No oral absorption	No oral absorption	No oral absorption	No oral absorption
Distribution	VOD = 0.2 L /kg Protein binding = 10%	VOD = 0.15 L/kg Protein binding = 15%	VOD = 0.02 L/Kg Protein binding = 30%	VD 0.25L/kg Protein binding = 10%
Metabolism	Minimal hepatic metabolism (<5%)	Organ independent Hoffman elimination (70-90%) > laudanosine and acrylate (inactive)	Rapid hydrolysis by plasma and liver pseudocholinesterase's (~20% reaches NMJ)	20% Hepatic de-acetylation (active metabolites)
Elimination	Bile 70%, Renal 30% Unchanged drug T 1/2 = 90 mins	Renal / biliary (10%) Inactive metabolites T 1/2 = 30 mins	Minimal renal elimination (rapid metabolism) T 1/2 = 2 mins	70% biliary, 30% urinary T 1/2 = 60mins
Special points	Reversible with sugammadex	Not reversible with sugammadex	May have prolonged duration of action with congenital or acquired (e.g. liver, renal, thyroid disease) pseudocholinesterase deficiency Treatment of malignant hyperthermia is with dantrolene, supportive care	Reversible with sugammadex

Opioids

Drug	Receptor	Duration action	CSHT	VOD	Protein binding	pKa	% ionised (pH 7.4)	Lipid solubility	Equiv dose for 10mg (IV) morphine
Morphine	MOP, weak KOP	4 hr	Modest	3.5L/kg	30%	8	25%	Very low	10mg
Oxycodone	MOP, KOP, DOP	4 hr	Modest	3L/kg	50%	8.4	10%	Very low	6.6mg
Remi-fentanyl	MOP	10 mins	No	0.1L/kg	70%	7.3	70%	Low	50 mcg
Fentanyl	MOP	30 mins	Yes	6L / Kg	90%	8.4	10%	Very high	150 mcg

Oxytocic's

	Oxytocin	Carbetocin	Ergometrine	Carboprost
Class	Oxytocin derivative	Oxytocin derivative	Ergot (oxytocic)	Prostaglandin (oxytocic)
Indication	- Augment labour - PPH	- Augment labour - PPH	- Augment labour (stage 3) - PPH	- Severe PPH
Route	IV, IM	IV	IM, IV	IM
Dose (PPH)	10u bolus > infusion	100ug	0.25mg, q5mins (max 1mg)	250ug q90 mins
MOA	Binds to Gq PCR in uterus > IP3/DAG pathway > uterine contraction	Synthetic oxytocin analogue. MOA similar to oxytocin	Unknown	Synthetic PGF2a analogue > binds to PG receptor > myometrial contraction
Effects	- Uterine contraction - Weak antidiuretic effect	- Uterine contraction - Weak antidiuretic effect	- Uterine contraction	Uterine contraction
Side effects	IMMUNO: Allergic reactions CVS: transient hypotension > reflex tachycardia, arrhythmias, flushing CNS: headache GIT: nausea, vomiting	Nausea and vomiting	CVS: Hypertension GIT: nausea, vomiting, abdominal pain	CVS: Severe hypertension RESP: bronchospasm (rare) GIT: nausea, vomiting, abdominal pain OTHER: fever

Proton pump inhibitors (PPI)

Name	Pantoprazole	Omeprazole
Class	Proton pump inhibitor (PPI)	PPI
Indications	Peptic ulcer disease GORD Zollinger-Ellison syndrome Stress ulcer prophylaxis	Similar
Pharmaceutics	20-40mg PO tablet (enteric coated) Powder for reconstitution (IV)	10-20mg PO tablet (enteric coated) Powder for reconstitution (IV) Racemic mixture R=S enantiomers
Routes of administration	PO, IV	IV, PO, NGT
Dose	20-40mg daily (prophylactic/maintenance) 80mg BD (UGI bleeding due to PUD)	Generally 20mg daily
Pharmacodynamics
MOA	Proton pump inhibitor: Binds to H+/K+ ATPase in parietal cells (the final common pathway for gastric acid section)	Same
Effects	Decreased gastric acid secretion	Similar
Side effects	Generally well tolerated, with multiple nonspecific side effects that are not very common	Similar
Pharmacokinetics
Onset	15 mins (IV), 2 hours (PO)	1 hour (PO)
Absorption	PO bioavailability - 80%	PO bioavailability 40%
Distribution	Protein binding 98% VOD = 0.3L / Kg	Similar
Metabolism	Hepatic CYP450 (demethylation and oxidation) Inactive metabolites 5% of population are slow metabolisers	Hepatic (non CYP 450)
Elimination	Renal (75%) and faecal (25%) elimination T 1/2 = 1 hour	Similar
Special points	No sig. difference in outcomes between PPIs. Omeprazole can be put in NGTs > 6Fr	See prev.

Tocolytics

Class	Beta agonist	CCB	NSAIDs
Example	Salbutamol	Nifedipine	Indometacin
MOA	Activate B2 receptors (GsPCR), ↑ cAMP > activates protein kinase A > inhibition of MLCK > relaxation	Block L-type Ca2+ channels, causing relaxation of SM	Inhibit prostaglandin synthesis (via inhibition of COX1/2) > decreased uterine contraction
Effects	Decrease uterine tone	Decrease uterine tone	Decrease uterine tone
Side effects	CNS: headacge, hyperactivity CVS: tachycardia, palpitations CNS: Anxiety, tremor RENAL: hypokalaemia HAEM: lactatemia, hyperglycaemia	CVS: hypotension, flushing, pulmonary oedema CNS: headache, dizziness GIT: nausea, vomiting	Mother: gastritis, nausea, vomiting, platelet dysfunction, AKI Baby: premature closure of ductus arteriosus

Individual drugs (A-Z)

Acetazolamide

Name	Acetazolamide
Class	Carbonic anhydrase inhibitor / weak diuretic
Indications	Metabolic alkalosis, glaucoma, altitude sickness
Pharmaceutics	White scored tablets (250mg), colourless solution
Routes of administration	PO, IV
Dose	125mg-1g, up to 4 hourly
pKA	pKa 7.2
Pharmacodynamics
MOA	Inhibits carbonic anhydrase in PCT > decreased reabsorption of filtered HCO3
Effects	CNS: decreased IOP by decrease aqueous humour RENAL: diuresis, decreased HCO3 reabsorption (metabolic acidosis),
Side effects	CNS: paraesthesia, fatigue, drowsiness RENAL: hypoNa, HypoK, HyperCl GIT: Nz/Vz/Dz
Pharmacokinetics
Onset	Onset 1-2hrs
Absorption	PO bioavailability 60%
Distribution	95% protein bound VOD = 0.3L/kg
Metabolism	Nil metabolism
Elimination	Renal clearance T 1/2 = 6hrs
Special points

Adenosine

Name	Adenosine
Class	Naturally occurring purine nucleoside / antiarrhythmic (other)
Indications	Diagnostic (can help distinguish between SVT due to re-entry circuits e.g. AVNT and AVRT and AF/Flutter) Therapeutic (can help terminate AVNT/AVRT)
Pharmaceutics	Clear colourless solution (3mg/ml), stored at room temperature
Routes of administration	IV only
Dose	3mg > 6mg > 12mg
pKA
Pharmacodynamics
MOA	Binds to A1 adenosine receptors in SA/AV node > hyperpolarisation > decreased/blocked AV nodal conduction
Effects	CVS: decreased AV nodal conduction
Side effects	RESP: dyspnoea, bronchospasm, tachypnoea CVS: Aflutter/fibrillation, bradycardia, AV block, flushing CNS: 'sense of impending doom', apprehension, light-headedness,
Pharmacokinetics
Onset	Seconds
Absorption	IV only
Distribution	VOD / protein binding data not available
Metabolism	Rapidly deaminated in plasma > inactive metabolites
Elimination	T 1/2 = <10s Metabolites (e.g. uric acid) eliminated in urine
Special points	Contraindicated in 2nd/3rd degree HB or SSS or severe asthma

Adrenaline

Name	Adrenaline
Class	Naturally occurring catecholamine
Indications	Hypotension/shock, bradycardia, cardiac arrest (ALS) Anaphylaxis, bronchoconstriction/airway obstruction With local anaesthetic
Pharmaceutics	Clear solution, light sensitive (brown glass amp) 1:1000 or 1:10,000
Routes of administration	IV, IM, INH, ETT, Topical, subcut
Pharmacodynamics
MOA	Non-selective adrenergic receptor agonist. At low doses B effects dominate, at high doses alpha dominate. Alpha 1 receptor (Gq), alpha 2 (Gi), Beta 1 (Gs) Beta 2 (Gs)
Effects	CVS: vasoconstriction (high doses), vasodilation (low doses), increased inotropy + chronotropy + dromotropy, Tachyarrhythmias, increased myocardial oxygen consumption RESP: bronchodilation, increased minute ventilation, increased pulmonary vascular resistance METABOLIC: hyperglycaemia and increased BMR by stimulating glycogenolysis, lipolysis, gluconeogenesis. Lactataemia CNS: increased MAC and pain threshold GIT: decreased intestinal tone/secretions Other: extravasation > necrosis
Pharmacokinetics
Onset/Offset (IV)	Immediate / immediate
Absorption	Zero oral bioavailability due to GIT inactivation. Variable/erratic ETT absorption.
Distribution	Poor lipid solubility, doesn't cross BBB, crosses placenta
Metabolism	Metabolised by MAO (mitochondria) and COMT (liver, blood, kidney) to VMA and metadrenaline > glucuronidation
Elimination	T 1/2 ~2 mins (due to rapid metabolism) Metabolites (above) are excreted in the urine
Special points

Albumin

Name	Albumin
Class	Colloid (human plasma protein)
Indications	Intravascular volume replacement, low albumin, hepatorenal syndrome, SBP
Pharmaceutics	- 4% or 20% concentrations. Clear/yellow fluid - Hypotonic (osm 260) - Collected by blood donation (whole blood, plasma apheresis) > fractionated (precipitation and chromatography)> pasteurised > partitioned > stored. Stored at < 30 degrees
Routes of administration	IV (requires air vent)
Pharmacodynamics
MOA	Related to volume of fluid (i.e. volume expansion) and role of albumin (oncotic pressure, transport of hormones, drugs, toxins, etc)
Side effects	No risk of bacteria/parasite infections (destroyed during processing), but risk of blood borne viruses (HIV, HepB, HCV) remains. Allergy, fluid overload.
Pharmacokinetics
Absorption	IV only (0% oral bioavailability)
Distribution	Rapid distribution within intravascular space. Small Vd - about 5% leaves per hour
Metabolism	Cellular proteolysis by cysteine protease
Elimination	Degradation by liver and reticuloendothelial system
Special points	- May worsen outcomes in TBI - No need for blood cross matching

Aminophylline

Name	Aminophylline (and Theophylline)
Class	Methylxanthine derivative
Indications	Severe airway obstruction, including acute asthma (less commonly used nowadays)
Pharmaceutics (aminophylline)	Complex of 80% theophylline (active component) and 20% ethylenediamine (improves solubility, no effect). Concentration of 25mg/ml in 10ml vials
Routes of administration	IV (aminophylline) , PO (aminophylline and theophylline)
Dose (Aminophylline)	Loading = 5mg/kg (slow injection) Maintenance = 0.5mg.kg.hr
Pharmacodynamics
MOA	- Non selective phosphodiesterase inhibitors > increased cAMP > Decreased Calcium > SM + bronchial relaxation - Also block adenosine receptors > decreased inflammatory response
Effects	Narrow therapeutic window RESP: Bronchodilation (via SM relaxation), increased respiratory centre sensitivity to CO2, improved diaphragm contractility CNS: headache, irritability, tremor, seizures CVS: palpitations, tachycardia, arrhythmia, increased inotropy/chronotropy GIT: Nausea, vomiting, diarrhoea RENAL: natriuresis
Pharmacokinetics
Absorption	PO bioavailability > 90%
Distribution	Vd = 0.5 L /kg Protein binding = 40%
Metabolism	Hepatic metabolism (90%) via CYP450 mechanisms to active and inactive metabolites. 10% unchanged
Elimination	Renal elimination of active and inactive metabolites Dialysable T 1/2 = 6-12 hours (longer in children)
Special points	Therapeutic concentration 10-20mg/ml

Amiodarone

Name	Amiodarone
Class	Antiarrhythmic (Class III) - However, also has class I, II, and IV activity
Indications	Tachyarrhythmias (e.g. SVT, VT, WPW)
Pharmaceutics	100-200mg tablets Clear solution in 150mg ampoules for dilution in dextrose
Routes of administration	IV and PO
Dose	IV: 5mg/kg, then 15mg/kg infusion / 24hrs. Oral: 200mg TDS (1/52) > BD (1/52) > daily thereafter
pKA	6.6 (highly lipid soluble)
Pharmacodynamics
MOA	- Blocks K channels (Class III effects) prolonging repolarisation and therefore refractory period. - Decreases velocity of Phase 0 by Blocking Na channels (Class I effects) - Non-competitive inhibition of Ca channels prolonging depolarisation + AV nodal conduction time (Class IV effects) - Slows AV/SA nodal conduction via anti-adrenergic activity (Class II effects)
Effects	Rhythm / rate control of tachyarrhythmias
Side effects	Side effects worsen/increase with duration of therapy! RESP: pneumonitis, fibrosis, pleuritis CVS: bradycardia, QT prolongation CNS: peripheral neuropathy, insomnia/sleep disturbance Thyroid: hypo/hyperthyroidism LIVER: cirrhosis, hepatitis, N, V, Abdo pain DERM: photosensitivity, skin discolouration EYE: Corneal microdeposits, visual disturbance Teratogen Drug interactions
Pharmacokinetics
Onset	Immediate (IV), 4 hours (PO)
Absorption	PO bioavailability 40-60%
Distribution	Highly protein bound (>95%) VD: ~5-70L /kg
Metabolism	Hepatic (CYP3A4) with active metabolites (desmethylamiodarone)
Elimination	T1/2 = 1-2 months Faces, skin elimination
Special points	Many drug-drug interactions (e.g. digoxin and warfarin)

Amphotericin

Name	Amphotericin
Class	Polyenes
Indications	Systemic fungal infections
Pharmaceutics	Powder for reconstitution and injection (clear in solution)
Routes of administration	IV, oral lozenges, inhalation
Dose	~1-5mg/kg daily (IV)
pKA
Pharmacodynamics
MOA	Fungicidal. Binds directly to ergosterol > creates transmembrane channels > permeability > death
Coverage	Good activity against almost all fungi/yeasts (inc. aspergillus, candida, crypto)
Side effects	Nephrotoxicity, hypokalaemia, infusion reactions , RTA
Pharmacokinetics
Onset
Absorption	Poor oral bioavailability (hence only given IV)
Distribution	Highly protein bound (90%). Poor tissue penetration. Negligible CSF/urine distribution. VOD - 1L /kg
Metabolism	Minimal hepatic metabolism
Elimination	Renal/faecal elimination. Halflife 15 days.
Special points	Monitoring: renal function

Apixaban

Name	Apixaban
Class	Direct oral anticoagulant (DOAC)
Indications	Treatment and prevention of VTE AF (non-valvular)
Pharmaceutics	Tablet (2.5mg and 5mg tablets)
Routes of administration	PO
Dose	2.5-5mg BD
Pharmacodynamics
MOA	Direct factor Xa inhibitor
Effects	Decreased thrombin production > decreased conversion of fibrinogen > fibrin > decreased thrombus development
Side effects	Increased risk of haemorrhage, anaemia Other: nausea, thrombocytopaenia, abnormal LFTs
Pharmacokinetics
Onset	Peak response ~3hrs post ingestion
Absorption	PO bioavailability = 50%
Distribution	Protein binding = 90% VOD = 0.3L/kg
Metabolism	Hepatic (CYP3A4) Hydroxylation and demethylation
Elimination	Faecal (major) and renal (minor) T 1/2 = 6-12 hours
Monitoring	Modified Anti-Xa assay
Reversal	No direct reversal agents Can use factor replacement (e.g. PTX)

Aspirin

Name	Aspirin
Class	Non-selective COX inhibitor / NSAID
Indications	Analgesia (e.g. migraine) Anti-inflammatory (e.g. injury) Anti-platelet functions (e.g. post AMI, CVA)
Pharmaceutics	75mg - 300mg tablets or capsules, clear solution for injection
Routes of administration	PO, IV
Dose	75-150mg daily for long term management (e.g. post ACS) 600-900mg for acute conditions (e.g. migraine) 250-500mg IV (neurovascular procedures)
pKA	3
Pharmacodynamics
MOA	Irreversibly inhibits COX on platelets > decreased thromboxane A2 and prostacyclin > decreased platelet aggregation
Effects	Analgesia, decreased platelet aggregation, decreased inflammation
Side effects	GIT: gastroduodenal ulcers, Nz, Vz HAEM: coagulopathy, haemorrhage RESP: respiratory alkalosis (tox): OTHER: allergy/bronchospasm/angioedema, Reyes syndrome (children) TOX: uncouples oxidative phosphorylation > lactic acidosis
Pharmacokinetics
Onset / duration	Antiplatelet function (minutes), analgesic (hours) / duration = 6 hrs
Absorption	PO bioavailability 50-75%
Distribution	85% protein bound (mainly albumin) VOD = 0.2L/kg
Metabolism	Readily hydrolysed by intestinal/hepatic/RBC esterase's > salicylate (active)
Elimination	Renal elimination of metabolites (increased with urinary alkalinisation) T 1/2 = 1 hour (parent), 6 hours (metabolites)
Special points	Dialysable

Atropine

Name	Atropine
Class	Naturally occurring tertiary amine. Muscarinic antagonist.
Indications	Bradycardia Organophosphate poisoning Counteract muscarinic effects of anticholinesterases Drying of secretions
Pharmaceutics	Clear colourless solution. 600mcg/ml. Racemic mixture with the L-isomer being active
Routes of administration	IV, IM, topical (eye)
Dose	600mcg - repeated administration can be given
Pharmacodynamics
MOA	Competitive antagonism of muscarinic receptors
Effects	CVS: increased HR (and CO), decreased AV conduction time RESP: bronchodilation, Drying of secretions
Side effects	CNS: Hallucinations, confusion, amnesia, delirium, central anticholinergic syndrome GIT: decreased secretions, delayed GIT motility CVS: may cause initial transient bradycardia when given slowly MSK: inhibits sweating GU: urinary retention
Pharmacokinetics
Onset	Seconds. Duration 2-3hours
Absorption	IV
Distribution	40% protein bound. VOD=4L/kg. Crosses blood brain barrier and placenta
Metabolism	Extensive hepatic hydrolysis into tropine and tropic acid
Elimination	Renal elimination of metabolites. T 1/2 approx 2 hours
Special points

Bupivacaine

Name	Bupivacaine
Class	Amide local anaesthetic
Indications	Local/regional/epidural anaesthesia
Pharmaceutics	Clear colourless solution (0.125%, 0.25%, 0.5%) with/without adrenaline
Routes of administration	SC, epidural
Dose	Toxic dose 2mg/kg
pKA	8.1
Pharmacodynamics
MOA	Binds to, and blocks, internal surface of Na channels > prevents AP
Effects	Local anaesthetic
Side effects	CNS: headache, dizziness, confusion, paraesthesia, reduced LOC, seizures CVS: hypotension, bradycardia, AV Block, arrhythmia CC/CNS ratio = 3 (more cardiotoxic than lidocaine)
Pharmacokinetics
Onset / duration	Intermediate onset (5-10 mins), long duration (~6 hours)
Absorption	Variable depending on vascularity
Distribution	95% protein bound Vd 2.5 L/kg. Crosses BBB
Metabolism	Hepatic (conjugation with glucuronic acid)
Elimination	Renal elimination of active and inactive metabolites T 1/2 = 3 hours
Special points

Calcium (gluconate / chloride)

Name	Calcium Gluconate (10%)	Calcium chloride (10%)
Class	Cation	Cation
Indications	Magnesium toxicity Cardiotoxicity (e.g. hyperK) Severe hypocalcaemia Calcium channel blocker antidote	Magnesium toxicity Cardiotoxicity Severe hypocalcaemia Calcium channel blocker antidote
Pharmaceutics	10mls of 10% calcium gluconate contains: - 1g elemental calcium or - 2.2 mmols calcium Clear colourless solution	10mls of Calcium chloride contains: - 1g elemental calcium or - 6.8mmols calcium Clear colourless solution
Routes of administration	IV	IV (best given centrally)
Dose	10mls calcium gluconate (10%) - May give 2 further doses (30mls total)	10mls calcium chloride
pKA	3.7
pH	6 - 8	5 - 8
Pharmacodynamics
MOA	Physiological functions - Mineralisation of bone - Muscle contraction - Nerve conduction - Second messenger pathways - Cofactor important in clotting cascade	Physiological functions - Mineralisation of bone - Muscle contraction - Nerve conduction - Second messenger pathways - Cofactor important in clotting cascade
Effects	Membrane stabilisation (in hyperK): restores gap between RMP and threshold potential	Membrane stabilisation (in hyperK): restores gap between RMP and threshold potential
Side effects	- Tissue necrosis with extravasation - Vein irritation / pain (less than CaCl) - Hypercalcaemia - Hypotension (rapid injection)	- Tissue necrosis with extravasation - Vein irritation / pain - Hypercalacaemia - Hypotension (rapid injection)
Pharmacokinetics
Onset	Immediate (slower than CaCl)	Immediate (faster than gluconate)
Absorption	N/A	N/A
Distribution	~50% protein binding - Normal serum Ca = 2.2 - 2.6mmols/L	~50% protein binding - Normal serum Ca = 2.2 - 2.6mmols/L
Metabolism	N/A	N/A
Elimination	Renal (50-300mg cleared per day)	Renal (50-300mg cleared per day)
Special points

Carbamazepine

Name	Carbamazepine
Class	Anticonvulsant
Indications	- Epilepsy - Trigeminal neuralgia - Bipolar disorder
Pharmaceutics	IR and MR tablets Oral liquid
Routes of administration	PO
Dose	BD/TDS 400-1.2g daily
Pharmacodynamics
MOA	Stabilises Na channels in their inactive state, thereby inhibiting the generation of further action potentials. Also by stimulating GABAergic inhibitory pathways
Effects	CNS: Anticonvulsant, drowsiness, dizziness, ataxia, headache, diplopia GIT: Nz, Vz, Dz, raised LFTs HAEM: neutropoenia, thrombocytopaenia OTHER: severe skin reactions, teratogen
Pharmacokinetics
Onset	TMax 1.5 hours PO
Absorption	PO bioavailability = 80%
Distribution	Protein binding = 75% VOD = 1L/kg
Metabolism	Hepatic (98%) CYP3A4 Active metabolites
Elimination	Renal (70%) and faecal (30%) elimination T 1/2 = 14 hours (metabolites 30 hours)
Special points

Ceftriaxone

Name	Ceftriaxone
Class	3rd generation cephalosporin
Indications	Empirical treatment of a range of infections (e.g. meningitis, pneumonia) Directed therapy against susceptible bacteria where a more narrow spectrum antibiotic is not suitable (e.g. penicillin allergy)
Pharmaceutics	White/yellow powder for reconstitution
Routes of administration	IV, IM
Dose	1-2g every 12-24 hours (max 4g daily)
Pharmacodynamics
MOA	Binds penicillin binding protein (PBP) on bacterial cell wall → inhibits cell wall synthesis → bactericidal
Spectrum	Broad spectrum with good GP (staph, strep) and GN cover (E.Coli, Klebsiella). Does not cover: ESCAPPM, pseudomonas, MRSA, anaerobes
Side effects	GIT: diarrhoea, nausea, vomiting CNS: dizziness, headache, confusion HAEM: blood dyscrasias IMMUNO: allergic reaction, angioedema, SJS
Pharmacokinetics
Onset	Max dose = end of infusion (IV), max dose = 2 hrs post IM
Absorption	IM and IV bioavailability 100% Poor PO bioavailability
Distribution	Protein binding = 90% VOD = 0.3 L / kg Good CNS penetration (hence useful for meningitis)
Metabolism	Minimal metabolism
Elimination	Renal and faecal elimination T 1/2 = 6 hours
Special points	Monitoring of LFTs

Ciprofloxacin

Name	Ciprofloxacin
Class	Quinolone
Indications	Prostatitis, complicated UTIs, bone/joint infections
Pharmaceutics	Oral tablet, light-yellow power for injection (water diluent)
Routes of administration	IV, PO
Dose	250-750mg BD (PO), 200-400mg BD/TDS (IV)
Pharmacodynamics
MOA	Bactericidal; inhibit bacterial DNA synthesis by blocking DNA gyrase and topoisomerase IV.
Spectrum	Broad spectrum (GN + MSSA). Effective against pseudomonas + anthrax (lol) Effective against some atypicals (legionella). No anaerobe cover.
Side effects	GIT: nausea, vomiting CNS: dizziness, headache CVS: prolonged QT interval, arrhythmias MSK: Myopathy, tendonitis + rupture, arthropathy
Pharmacokinetics
Onset	1-2 hours (PO) for peak effect. Immediately (IV)
Absorption	Oral bioavailability 70%
Distribution	Vd 2.5L/kg. Protein binding 25%, good tissue penetration (except for poor CSF penetration)
Metabolism	Partially hepatic
Elimination	Renal excretion of metabolites. T1/2 3-5 hours.
Special points	Increasing world wide resistance to quinolones.

Cisatracurium

Name	Cisatracurium
Class	Benzylisoquinolinium derivative (NMB)
Indications	NMB (i.e. RSI)
Pharmaceutics	Clear colourless solution (2-5mg/ml) stored at 4 degrees
Routes of administration	IV
Dose	0.15-0.2mg/kg (RSI)
pKA
Pharmacodynamics
MOA	Non-depolarising NMB Inhibits the action of ACh at the NMJ by competitively binding to alpha subunit of nAChR on post junctional membrane
Effects	NMB > muscle paralysis (including apnoea)
Side effects	CVS: rare (<1%) Immune/anaphylaxis: extremely rare (case report stuff)
Pharmacokinetics
Onset / duration	Onset: 1-3 minutes Duration: 30-45 minutes
Absorption	IV only
Distribution	VOD = 0.15 L/kg Protein binding = 15%
Metabolism	Organ independent Hoffman degradation > laudanosine and acrylate (inactive metabolites)
Elimination	Renal (major) and faecal (minor) elimination of inactive metabolites
Special points	Not reversible with sugammadex Can be reversed with anticholinesterases (e.g neostigmine)

Clonidine

Name	Clonidine
Class	Central alpha-adrenergic agonist
Indications	Analgesia/anxiolysis/sedation, hypertension,
Pharmaceutics	White tablet (100mcg) Clear colourless solution (150mcg/ml)
Routes of administration	IV, PO, EPIDURAL
Dose	e.g. 50-200mcg (up to QID)
Pharmacodynamics
MOA	Central Alpha adrenergic agonist (200x affinity for Alpha-2) > decreased SNS tone via decreased NA release > vasodilation, bradycardia > decreased BP Analgesia: Blocks ad and C fibres > decreased pain transmission. Stimulates a2 receptors in dorsal horn > descending inhibition
Effects	CNS: anxiolysis (low doses), sedation, analgesia CVS: hypotension, bradycardia
Side effects	CVS: bradycardia, hypotension (particularly orthostatic) CNS: somnolence, dizziness, fatigue GIT: dry mouth, nausea, constipation RENAL: diuresis secondary to reduced ADH RESP: nasal congestion
Pharmacokinetics
Onset	1-3 hrs (PO)
Absorption	85% PO bioavailability
Distribution	Vd = 2L / kg Protein binding = 30% Lipid solubility: very high - crosses BBB
Metabolism	Hepatic metabolism (cleavage>hydrolysis) > inactive metabolites
Elimination	T 1/2 ~12 hours Renal (2/3) and faecal (1/3)
Special points	Dose reduce in renal impairment

Clopidogrel

Name	Clopidogrel
Class	Antiplatelet / ADP receptor antagonist
Indications	Acute coronary syndromes Stent patency Peripheral vascular disease
Pharmaceutics	75 or 300mg tablets
Routes of administration	PO
Dose	Loading = 300mg, 75mg daily thereafter
Pharmacodynamics
MOA	Prodrug requiring hepatic CYP450 metabolism to convert to active form. Active metabolite irreversibly binds to P2Y12 subtype of the ADP receptor on platelets > prevents glycoprotein IIb/IIIa activation > prevents platelet activation. Effect lasts for lifetime of platelet
Effects	Decreased platelet activation > decreased thrombus formation
Side effects	HAEM: Haemorrhage, aplastic anaemia, neutropaenia, thrombocytopaenia GIT: GI ulcers Idiosyncratic: rash, angioedema, SJS
Pharmacokinetics
Onset / Duration	1 hour / 5-7 days (antiplatelet effect)
Absorption	PO bioavailability = 50%
Distribution	98% protein bound
Metabolism	85% - hepatic esterases (hydrolysed) > inactive drug 15% - CYP450 (oxidised) > active drug
Elimination	Urine (50%), faeces (50%) T 1/2 = 6 hours
Special points	Subgroup of the population are clopidogrel 'non responders' (CYP2C19 polymorphism) in that they poorly metabolise clopidogrel (the prodrug) leading to reduced efficacy as there is less 'active' drug. More common in Chinese (15%) > African/American (5%) > Caucasian patients (2%)

Cyclizine

Name	Cyclizine
Class	Piperazine derivative (antihistamine)
Indications	Nausea due to - Motion sickness - Radiotherapy - PONV - Opioid induced
Pharmaceutics	50mg tablets 50mg/ml solution - pH 3.2 (hence painful with IM injection)
Routes of administration	IV, PO, IM (but very painful)
Dose	25-50mg, 8hrly
Pharmacodynamics
MOA	H1 and ACh antagonism > decreased afferents from chemoreceptor trigger zone > vomiting centre
Effects	Anti-emetic
Side effects	GIT: reduced lower oesophageal sphincter tone CNS: sedation, headache, blurred vision May have mild anticholinergic symptoms (dry mouth, constipation etc)
Pharmacokinetics
Onset	Peak = 2hrs (PO), 30 mins (IV)
Absorption	PO bioavailability = 80%
Distribution	VOD - 14L / kg
Metabolism	Hepatic > inactive metabolites
Elimination	Renal T 1/2 = 7 hours
Special points

Dabigatran

Name	Dabigatran (Pradaxa)
Class	Direct oral anticoagulant (DOAC) / Direct thrombin inhibitor
Indications	Prevention and treatment of VTE Atrial fibrillation
Pharmaceutics	75mg, 110mg and 150mg capsules
Routes of administration	PO
Dose	110/150mg BD
Pharmacodynamics
MOA	Prodrug. Converted by plasma/liver esterase's to active moiety. Competitive direct thrombin inhibitor > decreased conversion of fibrinogen to fibrin
Effects	Decreased conversion of fibrinogen to fibrin by thrombin > decreased thrombus development
Side effects	Haemorrhage Gastritis, dyspepsia, oesophageal ulcers
Pharmacokinetics
Onset	Peak effect 2 hrs
Absorption	PO bioavailability = 5% PPIs can reduce (relative) absorption by 25%
Distribution	Protein binding 35% VOD = 1L/kg
Metabolism	Prodrug converted to active moiety by plasma/liver esterase's ~10% of active moiety is metabolised by liver glucuronidation
Elimination	Renal elimination of unchanged drug (90%) T 1/2 = 12 hours
Special points	Needs dosage adjustment with renal function as there is minimal metabolism of active moiety (~10%) thus relies on kidneys for clearance (contraindicated with CrCl <30ml/min)
Reversal	Praxbind (Idarucizumab) - monoclonal antibody that binds to active dabigatran moiety > stable inactive complex within 5 minutes. 5g single dose

Dexmedetomidine

Name	Dexmedetomidine
Class	Central alpha agonist (sedative)
Indications	Short term sedation and anxiolysis
Pharmaceutics	Clear colourless isotonic solution. Or white powder for dilution
Routes of administration	IV only in AUS
Dose	Infusion (though loading boluses can be given)
pKa	7.1
Pharmacodynamics
MOA	Selective central a2 agonism (predom. at the locus coeruleus and spinal cord)
Effects	CNS: Sedation, anxiolysis, analgesia, decreased CMRO2/CBF CVS: hypotension (rebound hypertension), bradycardia, arrhythmia Other: hyperthermia, confusion, dry mouth
Pharmacokinetics
Onset	~30 mins (without bolus)
Absorption	IV only in Aus. Low PO bioavailability
Distribution	95% protein bound, very lipid soluble Vd = 2L/kg
Metabolism	Biotransformation (direct glucuronidation and CYP450 metabolism) > inactive metabolites
Elimination	Renal excretion (5% stool) t 1/2 = 2 hours
Special points	Atipamezole = antagonist (reversal agent)

Dextrose 5%

Name	5% dextrose (IV)
Class	Crystalloid fluid
Pharmaceutics	Clear solution, various volume bags (e.g. 1L, 500mls)
Osmolality	278 mOsm/kg
Tonicity	Hypotonic (dextrose rapidly metabolised)
Contents	50g dextrose / 1L solution
Pharmacodynamics
MOA	Expands ECF volume and changes body fluid biochemistry
Effects	Increased ECF volume Glucose replacement
Side effects	Fluid overload, cerebral oedema, hyperglycaemia, vein irritation, electrolyte imbalances (e.g. HypoNa)
Pharmacokinetics
Onset	Immediate (IV)
Absorption	IV bioavailability = 100%
Distribution	VOD = 0.6L/Kg > 5% intravascular > 25% interstitial > 70% intracellular
Metabolism	Metabolised by all body tissues (esp liver) into water and CO2
Elimination	Water eliminated renally, CO2 eliminated by lungs

Diazepam

Name	Diazepam
Class	Benzodiazepine (sedative)
Indications	Sedation, anticonvulsant, withdrawal syndromes (including alcohol), anxiolysis
Pharmaceutics	IV: clear solution (5mg/ml) PO: tablets (yellow/white)
Routes of administration	IV, IM, PO, INH
Dose	Dose depends on many pt. factors Usually 5-10mg as premedication. 5-20mg, 2hrly PRN for AWS.
Pharmacodynamics
MOA	Binds to GABAA receptors (ionotropic ligand gated channel) in the CNS. Cl enters > hyperpolarisation.
Effects	CNS: sedation, amnesia, anxiolysis, hypnosis, anticonvulsant effects, decreased cerebral O2 demand, MSK: muscle relaxant
Side effects	CVS: bradycardia, hypotension CNS: confusion, restlessness RESP: respiratory depression/ apnoea
Pharmacokinetics
Onset	Peak effect 5 mins IV Onset PO = 30 mins
Absorption	>90% bioavailability from PO, Nasal, IM
Distribution	95% protein bound Very lipid soluble, crosses BBB and placenta Vd = 1L / kg
Metabolism	Hepatic metabolism by oxidation to desmethydiazepam, oxazepam and temazepam (all active) metabolites
Elimination	Renal excretion of active metabolites T 1/2 = 24-48 hours (parent drug)
Special points	Flumazenil - antagonist (reversal agent) Reduce dose in liver failure / consider alternative BZD

Digoxin

Name	Digoxin
Class	Cardiac glycoside (antiarrhythmic)
Indications	Tachyarrhythmias (e.g. AF, SVT) Heart failure
Pharmaceutics	62.5mcg/250mcg (PO tablets) 25/250 mcg/ml (IV)
Routes of administration	IV and PO
Dose	Generally load with 250-500mcg, then 62.5-125mcg daily thereafter. Digoxin level (0.7 - 1.0) for most conditions.
pKA	7.2
Pharmacodynamics
MOA	Direct cardiac: Inhibits Na/K ATPase > Increased Na > increased Na/Ca exchange activity > increased intracellular Ca > increased inotropy / CO Indirect cardiac: increased PSNS release of ACh at M receptors > slowed conduction at AV node/bundle
Effects	Positive inotropy: Inhibits Na/K ATPase > Increased Na > impairs Na/Ca exchanger > increased intracellular Ca > increased inotropy > increased CO Negative chronotropy and dromotropy: Increased PSNS release of ACh at M receptors > decreases SA node firing (chronotropy) + prolongs AV conduction (dromotropy) > increased diastolic filling time > increased preload > increased SV > increased CO + BP Increased excitability: Increases slope of phase 4 > enhances automaticity of atrial, junctional, ventricular tissue > arrhythmias
Side effects	CVS: May worsen arrhythmia (bradycardia, AV block, bradyarrhythmia's via indirect effects; tachyarrhythmias via increased excitability) GIT: nausea, anorexia, vomiting CNS: dizziness, drowsiness
Pharmacokinetics
Onset	2-3 hours (PO), 10-30mins (IV), duration of action 3-4 days
Absorption	80% oral bioavailability
Distribution	Protein binding 25% VOD 6-7L/kg Highly lipophilic
Metabolism	Minimal hepatic metabolism (15%) Oxidation and conjugation Inactive and active metabolites
Elimination	Renal elimination predominately (70% unchanged) Some faecal and biliary elimination (<15%) T 1/2 = 48 hours
Special points	Reduce dose in renal failure, monitor with dig level. not removed by dialysis

Digoxin antibodies

Name	Digoxin-specific antibodies
Class	Digoxin-specific antibody Fab fragments
Indications	>10mg ingested (adult), >4mg ingested (child) Plasma concentration > 15nM Or digoxin toxicity with cardiac arrest, hyperkalaemia or life threatening dysrhythmias,
Pharmaceutics	Powder (contains 40mg of digoxin-specific Fab fragments) Reconstitute with sterile water
Routes	IV
Dose	Each vial binds ~0.5mg digoxin. If dose not known (5 vials if stable, 10 vials if unstable, 20 vials in arrest) If plasma concentration is known, formulae exist for dosing.
Pharmacodynamics
MOA	Competitive binding with digoxin molecules (higher affinity than Digoxin has with the Na/K ATPase receptor) > decreases free digoxin levels > shifts equilibrium away from binding to receptors
Effects	Decreased digoxin levels
Side effects	reversal of digoxin effects: worsening of cardiac failure, hypotension, Hypo/hyperkalaemia Headache, nausea, vomiting, Allergic responses
Pharmacokinetics
Absorption	IV only
Distribution	VOD = 0.3 L /KG PPB - not known
Metabolism	Nil
Elimination	T 1/2 B = 15-20 hours

Dobutamine

Name	Dobutamine
Class	Inodilator
Indications	Cardiogenic shock / heart failure Cardiac stress testing
Pharmaceutics	Clear colourless solution (12.5mg/ml) Diluted in water
Routes of administration	IV
Dose	Infusion (0.5-20 ug/kg/min)
pKA	10.4
Pharmacodynamics
MOA	B1 and B2 agonist (B1>> B2)
Effects	CVS: increased inotropy, increased chronotropy, increased lusitropy, increased dromotropy, decreased SVR, increased BP, increased risk arrhythmias, increased myocardial oxygen requirement RESP: bronchodilation, CNS: Increased CBF RENAL: Increased RBF
Pharmacokinetics
Onset	< 1 min
Absorption	0% oral bioavailability > destroyed by GIT enzymes > IV only
Distribution	Small Vd (0.2L/Kg) Unknown protein binding
Metabolism	Hepatic and tissue metabolism COMT/MAO > inactive metabolites
Elimination	Renal (70%) and faecal (20%) excretion of metabolites T 1/2 = 2mins
Special points	Does not require SAS approval

Dopamine

Name	Dopamine
Class	Naturally occurring catecholamine (sympathomimetic)
Indications	Acute heart failure, shock
Pharmaceutics	Clear solution 40mg/ml, 5ml ampule, in water
Routes of administration	IV
Dose	1-50 ug/kg/min, increasing ~5ug/kg/min every 10 mins until desired response
pKA	9
Pharmacodynamics
MOA	Low doses: predominant B agonist effects. High doses: predominant a agonist effects Additional D1 and D2 effects (regardless of dose)
Effects	CVS: inotropy, chronotropy, increased CO, increased SVR (high dose), reduced SVR (low dose), coronary vasodilation, increased tachyarrhythmias RENAL: may increase RBF but no change in outcomes (low dose), reduces RBF (high dose, >20mcg/kg/min) GIT: Mesenteric vasodilation, nausea, vomiting MSK: tissue extravasation > necrosis RESP: dyspnoea (pHTN and reduced HPVC) CNS: hallucinations, confusion
Pharmacokinetics
Onset / duration	< 5 mins / 10 mins
Absorption	IV only
Distribution	Does not cross BBB VOD = 2 L / kg
Metabolism	MAO and COMT in liver, kidneys, plasma > inactive metabolites (75%) 25% converted into noradrenaline in nerve terminals by hydroxylation
Elimination	Renal excretion of metabolites T 1/2 = 2 mins
Special points	Treatment with MAOI may prolong activity

Esmolol

Name	Esmolol
Pharmacokinetics
Onset	Immediate (only given IV)
Absorption	0% oral bioavailability
Distribution	VOD 3L/kg 60% protein bound High lipid solubility, can cross BBB
Metabolism	- Rapid - Hydrolysis by RBC esterase > inactive metabolites
Elimination	Renal excretion T 1/2 10 mins

Fentanyl

Name	Fentanyl
Class	Opioid / Synthetic phenylpiperidine derivative
Indications	Analgesia, induction of anaesthesia (blunt cough)
Pharmaceutics	Colourless solution (50ug/ml)
pKa	8.4
Routes of administration	SC, IM, IV, epidural, intrathecal, transdermal
Pharmacodynamics
MOA	Mu-opioid receptor agonist > hyperpolarisation
Effects	Analgesia
Side effects	CVS: bradycardia Resp: respiratory depression, blunted cough reflex GIT: decreased GI motility, nausea/vomiting CNS: Dysphoria, confusion,
Pharmacokinetics
Onset/Offset	Rapid onset (2-5 mins) Rapid offset (30mins)
Absorption	PO bioavailability (33%). Mucosal absorption is poor
Distribution	VOD high = 6L / kg Highly protein bound (90%) Very high lipid solubility
Metabolism	Hepatic metabolism > demethylation > inactive metabolites
Elimination	T 1/2 = 4 hours, prolonged with infusions (CSHT). Excreted in urine

Flucloxacillin

Name	Flucloxacillin
Class	Penicillins (antibiotic)
Indications	Gram positive infections (particularly staph)
Pharmaceutics	Capsule, tablet or white power for reconstitution
Routes of administration	PO, IV,
Dose	250-1g, every 6 hrs
Pharmacodynamics
MOA	Beta-lactam ring binds to penicillin binding protein > prevents crosslinking > cell wall synthesis
Microbial coverage	Narrow spectrum Gram positive bacteria
Side effects	GIT: diarrhoea, nausea, cholestatic hepatitis IMMUNO: penicillin allergy CNS: neurotoxicity Haem: blood dyscrasias
Pharmacokinetics
Absorption	PO bioavailability 70%
Distribution	95% protein bound VOD = 0.3 L /kg CNS penetration with meningitis only
Metabolism	Hepatic metabolism
Elimination	Renal elimination (predominately unchanged) T 1/2 = 1 hour
Monitoring	Monitor LFTs (cessation), renal function (dose adjustment)
Resistance	Can treat b-lactamase producing bacteria, but not MRSA (mecA gene)

Fluconazole

Name	Fluconazole
Class	Azole
Indications	Systemic fungal infections, prophylaxis fungal infections for immunocompromised
Pharmaceutics	Tablet (PO), White powder which is clear and colourless in solution (water, saline).
Routes of administration	PO, IV
Dose	Generally 200-800mg daily for systemic infections, reduced dose local infections or prophylaxis (e.g 50-200mg daily)
pKA
Pharmacodynamics
MOA	Fungicidal. Disrupts ergosterol production (essential for cell membrane formation), by inhibiting the CYP45 enzyme that produces it, leading to increased permeability.
Coverage	Covers: Candida albicans, Cryptococcus Doesn't: Most other fungi/yeast inculding aspergillus
Side effects	CNS: headache CVS: Prolonged QTc RESP: Nil GIT: Raised LFTs, nausea, vomiting, abdo pain HAEM: thrombocytopaenia, leukopaenia RENAL: Nil IMMUNO: rash, allergy, alopecia, anaphylaxis OTHER: Drug interactions (CYP450), teratogen
Pharmacokinetics
Onset	Peak concentrations 1-2hours
Absorption	Great oral bioavailability (>90%)
Distribution	Vd close to that of water. Good CSF penetration. Poorly protein bound (10%)
Metabolism	Not metabolised
Elimination	Renal (unchanged 80%). Halflife ~30 hours
Special points	Monitoring: LFTs, drug interactions

Fludrocortisone

Name	Fludrocortisone
Class	Mineralocorticoid
Indications	Adrenal insufficiency (adjunct with glucocorticoid) Salt losing congenital adrenal hypoplasia Orthostatic hypotension
Pharmaceutics	White 100mcg tablet
Routes of administration	PO
Dose	Initially 50-100mcg/daily
Pharmacodynamics
MOA	Synthetic adrenocortical steroid with potent mineralocorticoid, and modest glucocorticoid effects. Fludrocortisone acts in DCT > increased Na reabsorption (increase K excretion)
Effects	Sodium and water reabsorption Increased MSFP > increased BP
Side effects	CVS: fluid overload, worsening of HF, hypertension Renal: hypokalaemia, hyperglycaemia, metabolic alkalosis GIT: peptic ulcer disease MSK: impaired wound healing, myopathy,
Pharmacokinetics
Onset	T Max <2 hours
Absorption	PO bioavailability 100%
Distribution	Protein binding 40% VOD = 1.25L/kg
Metabolism	Hepatic > inac
Elimination	T 1/2 = 4 hours Renal elimination of inactive metabolites
Special points

Flumazenil

Name	Flumazenil
Class	Imidazo-benzodiazepine
Indications	Reversal of benzodiazepine effects. Though use is rarely indicated and supportive care is often sufficient (given risks associated - see special points)
Pharmaceutics	Clear solution (0.1mg/ml) for injection
Routes of administration	IV only
Dose	0.1mg boluses (up to 2mg)
pKA
Pharmacodynamics
MOA	Competitive benzodiazepine receptor antagonist
Effects	Reversal of BDZ effects (particularly sedation)
Side effects	GIT: Nausea, vomiting CNS: seizures, anxiety, agitation
Pharmacokinetics
Onset	< 2 mins
Absorption	N/A
Distribution	50% protein bound (predominately albumin) Moderate lipid solubility Vd = 1L / kg
Metabolism	Hepatic > inactive metabolites
Elimination	Renal elimination of metabolites T 1/2 = 1 hr
Special points	BDZ resistance following administration. Hence if you develop seizures post administration of flumazenil > cannot readily treat again with BZD. Hence need to use in caution in mixed-drug overdoses (particularly if pro-convulsant drugs are co-ingested e.g. TCAs, amphetamines)

Fresh frozen plasma (FFP)

Name	Fresh frozen plasma (FFP)
Class/description	Blood product / human plasma
Indications	Coagulopathy Plasma exchange ACE-I angioedema, Suxamethonium apnoea
Pharmaceutics
Preparation	1) Separation of whole blood or apheresis 2) Frozen and stored 3) Rethawed in water bath prior to use
Storage (duration)	12 months
Storage conditions	-25<math display="inline">\degree</math>C or below
Contents/factors	Human plasma containing all clotting factors (except fibrinogen)
Volume	250-300mls
pH	7.2-3
Routes of administration	IV
Dose	2-4 units (repeated as needed base of clinical and lab parameters)
Pharmacodynamics
Adverse effects	Blood product, with all the risks associated with this (fluid overload, infection, allergic responses) See alternate note on transfusion reactions
Pros	Contains all necessary clotting factors (except fibrinogen) Less expensive than PTX
Cons	Requires ABO grouping Requires time for thawing etc More fluid, more side effects

Frusemide

Name	Frusemide
Class	Loop diuretic
Indications	Oedema/fluid overload, renal insufficiency, hypertension
Pharmaceutics	Tablet (40mg) Oral solution, 10mg/ml Clear colourless solution, 10mg/ml (light sensitive),
Routes of administration	IV, PO,
Dose	Varies (~40mg daily commonly used for well patients, can be sig. increased)
pKA	3.6 (highly ionised; poorly lipid soluble)
Pharmacodynamics
MOA	Binds to NK2Cl transporter in the thick ascending limb LOH, leads to decreased Na,K, Cl reabsorption > decreased medullary tonicity + Inc Na/Cl delivery to distal tubules > decreased water reabsorption > diuresis
Effects	Renal: diuresis CVS: hypovolaemia, arteriolar vasodilation + decreased preload (=mechanism for improvement of dyspnoea before diuretic effect in APO) Renal: increase in RBF
Side effects	CVS: hypovolaemia, hypotension Renal/metabolic: Metabolic alkalosis, LOW Na, K, Mg, Cl, Ca, increased Cr Ototoxicity, tinnitus, deafness
Pharmacokinetics
Onset	5 mins (IV), 30-60 mins (PO), Effect lasts 6 hours.
Absorption	Bioavailability ~70% (high inter-patient variabi)
Distribution	Vd = 0.1L/Kg, >95% protein bound (albumin)
Metabolism	Hepatic (< 10% metabolised) Glucuronidation > active metabolite
Elimination	Renally cleared (predominately unchanged). T1/2 = 2hrs.
Special points	Deafness can occur with rapid administration in large doses

Gentamicin

Name	Gentamicin
Class	Aminoglycoside
Indications	Severe gram negative infections Empirical therapy sepsis with possible/presumed GN source Directed therapy against susceptible organism
Pharmaceutics	Clear colourless solution (80mg vials, 40mg/ml)
Routes of administration	IV, IM
Dose	Loading: 4-7mg/kg (renally adjusted), may be repeated at 24-48hr mark if needed
Pharmacodynamics
MOA	Bactericidal: Inhibit protein synthesis by irreversibly binding 30S ribosomal subunit
Spectrum	Narrow (GN)
Covers	Most GNs: E.coli, pseudomonas, proteus, klebsiellas, Enterobacter Some GPs: staph
Doesn't cover	Anaerobes Most gram positives
Side effects	CNS: ototoxicity (irreversible in 50% and unpredictable with genetic component) > nausea, vertigo, nystagmus, tinnitus, hearing loss Renal: nephrotoxic (usually reversible and dose/duration dependant) MSK: weakness (decreased prejunctional release of ACh)
Pharmacokinetics
Onset	TMax IM = 30 mins, instant (IV)
Absorption	PO absorption < 5% (IV, IM only)
Distribution	VOD = 0.3L/Kg Protein binding = 15% CNS/Bone/Bile penetration = limited
Metabolism	Not metabolised
Elimination	Renal elimination, GFR limited T 1/2 = 3 hours (normal renal function) Dialyzable
Monitoring	Generally not needed (as usually only 1-2 doses given), can be done for prolonged therapy

Glyceryl trinitrate (GTN)

Name	Glyceryl trinitrate (GTN)
Class	Organic nitrate
Indications	Hypertension, acute pulmonary oedema, angina, ACS/LV failure,
Pharmaceutics	Clear liquid (IV), Patch (transdermal), tablet (SL), spray (SL)
Routes of administration	Sublingual, intravenous, transdermal, PO
Dose	Patch: 5/15 mg/24hr SL: 400mcg PRN IV: titrated to effect
pKA	5.6
Pharmacodynamics
MOA	Prodrug, which is dinitrated to produce active nitric oxide (NO). NO diffuses into smooth muscle cell > binds to guanylyl cyclase > increased cGMP > decreased intracellular Ca > smooth muscle relaxation > vasodilation
Effects	CVS: systemic vasodilation (preferentially venodilation, coronary arterial dilation) > decreased SVR > decreased BP + VR, decreased myocardial O2 consumption (decreased VR > decreased preload), reflex tachycardia CNS: Increased CBF > inc ICP, headache RESP: Bronchodilation (weak), decreased PVR OTHER: flushing, methaemaglobinaemia
Pharmacokinetics
Onset	1-3 mins (SL), <1 min (IV), Patch variable.
Absorption	Oral bioavailability <5% (hepatic high first pass effect) Sublingual spray 40% Sublingual tablet 60%
Distribution	60% protein bound. Vd 3L/kg
Metabolism	Hydrolysis Site: liver + RBC cell wall + vascular cell walls. Active metabolites
Elimination	Renal T 1/2 B = 5 minutes (parent compound).
Special points	Can develop tachyphylaxis (depletion of sulfhydryl groups)

Glycopyrrolate

Name	Glycopyrrolate
Class	Antimuscarinic (anticholinergic) / Quaternary amine
Indications	Bradycardia, antisialagogue
Pharmaceutics	Clear colourless solution (200ug/ml, 1ml amp)
Routes of administration	IV, IM, SC, INH
Dose	200-400ug
Pharmacodynamics
MOA	Competitive, reversible, antagonism of ACh at muscarinic receptors
Effects	RESP: bronchodilation, antisialagogue CVS: reverses vagal bradycardia > tachycardia
Side effects	GIT: Decreased GIT motility, dry mouth, constipation GU: urinary retention CVS: tachycardia Derm: flushing
Pharmacokinetics
Onset / Duration	Onset: < 1 min (IV), 15-30mins (IM) Duration: 3 hours (IV) for vagal reversal effects, 7hrs for antisialagogue effects
Absorption	PO bioavailability <5%
Distribution	Does not cross BBB VOD = 0.5L/kg Protein binding = 40%
Metabolism	Minimal metabolism (hepatic hydrolysis)
Elimination	80% excreted in urine unchanged T 1/2 = 1 hour
Special points

Haloperidol

Name	Haloperidol
Class	Antipsychotic (1st generation)
Indications	Behavioural emergencies, psychosis, intractable nausea/vomiting
Pharmaceutics	PO tablets Clear solution for injection
Routes of administration	PO, IM, IV
Dose	1-5mg IV, 2-30mg IM, 1-10mg PO
Pharmacodynamics
MOA	Antipsychotic actions thought to be mediated by blockade of dopamine (D2 > D1) receptors particularly in the limbic system Also seem to block 5HT2 and H1 receptors and mACh receptors to lesser degrees
Effects / side effects	CNS: apathy, decreased agitation, sedation, LOWERS seizure threshold CVS: QT prolongation MET: weight gain, diabetes, hyperChol Other: neuroepileptic malignant syndrome, extrapyramidal side effects (dystonia, akathisia, parkinsonism, TD) HAEM: leukopaenia GIT: anti-emetic RESP: respiratory depression
Pharmacokinetics
Onset	Peak effects after 3 hours (PO)
Absorption	80% PO bioavailability
Distribution	>90% protein bound VOD = 20L/kg
Metabolism	Hepatic > inactive metabolites
Elimination	Renal (major) and faecal (minor) excretion of metabolites T 1/2 = ~24 hours
Special points

Heparin

Name	HMWH (heparin)	LMWH (enoxaparin)
Class	Anticoagulant	Anticoagulant
Indications	Prophylactic and therapeutic anticoagulation (e.g. AF, DVT, PE, ACS etc)	Prophylactic and therapeutic anticoagulation (e.g. AF, DVT, PE, ACS etc)
Pharmaceutics	MW = 5,000-25,000 Da Clear solution for injection	MW = 5,000 Daltons Clear solution for injection
Routes of administration	IV, SC	SC (main), can also be given IV
Dose	Prophylactic: 5,000 IU BD-TDS Therapeutic: infusion (APTT target)	Therapeutic: 1mg/kg BD or 1.5mg/kg OD Prophylactic: 20-40mg OD
pKA
Pharmacodynamics
MOA	Heparin binds to antithrombin 3 > conformational change > increases affinity for inactivating thrombin (factor IIa) and Factor Xa	Enoxaparin binds to AT-3 > conformational change > increases affinity for inactivating factor Xa (and weakly factor IIa - 4x less activity)
Effects	Anticoagulation	Anticoagulation
Side effects	HAEM: increased risk of haemorrhage, bruising, HITTS (higher than LMWH)	HAEM: increased risk of haemorrhage, bruising, HITTS (lower than HMWH)
Pharmacokinetics
Onset	Immediate (IV), peak 2-4 hrs subcut	Peak effect 3-4 hrs post SC injection
Absorption	PO bioavailability - 0% Variable SC absorption	PO bioavailability - 0% >90% bioavailability post SC injection
Distribution	VOD = 0.1L/kg Lipid solubility: low Protein binding: high Does not cross BBB / placenta	VOD =< 0.1Lkg Protein binding: does not bind to heparin binding proteins
Metabolism	Reticuloendothelial system	Minimal hepatic metabolism
Elimination	Renal elimination (very minimal) - hence preferred in renal failure T 1/2 = 1 hrs	Renal elimination of active and inactive metabolites T 1/2 = 6-12 hours
Special points	Reversal: protamine (1mg = 100IU) - 100% Monitoring: APTT level	Reversal: protamine (<75% efficacy) Monitoring: Anti-Xa level

Hydralazine

Name	Hydralazine
Class	Antihypertensive / vasodilator
Indications	Hypertension
Pharmaceutics	PO tablets (25-50mg) Clear colourless solution for injection (20mg/ml, 1ml amp)
Routes of administration	IV, PO
Dose	2.5 - 20mg IV, can be given 30 minutely 25-100mg BD PO
pKA
Pharmacodynamics
MOA	Relaxation of smooth muscle > decreased SVR - Cellular mechanism not fully understood -Thought to inhibit IP3-DAG pathway > decreased Ca release from SR > decreased phosphorylation
Effects	CVS: reduced arteriolar tone (reduced SVR) --> decreased BP
Side effects	CVS: reflex tachycardia, flushing, palpitations CNS: headache, dizziness, increased CBF HAEM: blood dyscrasias GIT: Nausea, vomiting RENAL: increased RBF but reduced UO
Pharmacokinetics
Onset	1hr (oral) 5-10mins (IV) with peak response 30-60mins (IV)
Absorption	PO bioavailability ~40% (high first pass metabolism)
Distribution	90% protein bound Crosses the placenta
Metabolism	Hepatic (extensive) Acetylated
Elimination	Renal excretion of metabolites T 1/2 =4hrs
Special points

Hydrochlorothiazide

Name	Hydrochlorothiazide
Class	Thiazide / diuretic
Indications	- Hypertension - Fluid overload (heart failure, cirrhosis, nephrotic syndrome)
Pharmaceutics	25mg tablets
Routes of administration	PO
Dose	12.5 - 100mg daily
Pharmacodynamics
MOA	Inhibit Na+ and Cl- reabsorption (Na/Cl cotransporter) in the DCT
Effects	Diuresis, decreased BP
Side effects	CNS: dizziness CVS: hypotension, arrhythmia Electrolyte disturbances: HypoNa, HypoK, HypoCl, HypoMg, HyperCa METABOLIC: hyperglycaemia, dyslipidaemia RENAL: renal impairment HAEM: blood dyscrasias
Pharmacokinetics
Onset	2 hours
Absorption	OBA = 70%
Distribution	VOD = 4 L / Kg Protein binding = 40%
Metabolism	Not metabolised
Elimination	Renally (unchanged) T 1/2 = 12 hours
Special points

Hydrocortisone

Name	Hydrocortisone
Class	Glucocorticoid (endogenous)
Indications	Glucocorticoid insufficiency, allergy/anaphylaxis/asthma, severe septic shock, immunosuppression (e.g. transplant, autoimmune dz)
Pharmaceutics	Tablet or cream (various concentrations) White powder for dilution (water, glucose, saline)
Routes of administration	IV, PO, TOPICAL
Dose	50-200mg QID (commonly in ICU population)
Bio-equivalence	100mg hydrocort = 25mg pred = 20mg methypred = 4mg dex
Pharmacodynamics
MOA	Lipid soluble > crosses cell membrane > binds to intracellular steroid receptors > translocate to nucleus > alters gene transcription > metabolic, anti-inflammatory & immunosuppressive effects in tissue-specific manner
Effects	CNS: sleep disturbance, psychosis, mood changes CVS: Increased BP (mineralocorticoid effect + increased vascular smooth muscle receptor expression to catecholamines) RESP: decreased airway oedema, increased SM response to catecholamines and <math display="inline">\beta</math>2agonists RENAL: Na + water retention (mineralocorticoid effect) Metabolic: Hyperglycaemia, gluconeogenesis, protein catabolism, fat lipolysis and redistribution, adrenal suppression MSK: Osteoporosis, skin thinning Immune: immunosuppression + anti-inflammatory effects (decreased phospholipase, interleukins, WBC migration and function) GIT: Increased risk of peptic ulcers
Pharmacokinetics
Onset	Peak effect 1-2 hours, duration of action 8-12 hours
Absorption	50% oral bioavailability
Distribution	90% protein bound, small Vd (0.5L/kg)
Metabolism	Hepatic > inactive metabolites
Elimination	Metabolites excreted renally. Elimination T1/2 ~2 hour
Special points	Risk of reactivation of latent TB / other infections

Hypertonic (3%) saline

Name	3% Saline
Class
Indications
Pharmaceutics
Routes of administration
Dose
Pharmacodynamics
MOA
Effects/side effects
Pharmacokinetics
Onset / duration
Absorption
Distribution
Metabolism
Elimination
Special points

Ibuprofen

Name	Ibuprofen
Class	NSAID (nonselective)
Indications	Pain (particularly inflammatory in nature)
Pharmaceutics	Tablets (100-400mg), capsules (200mg) or liquid (20mg/mL) or clear solution for injection (100mg/ml) Racemic mixture. R enantiomers converted to active S enantiomer invivo
Routes of administration	PO, IV, Topical (gel)
Dose	400mg TDS (adult), 10mg/kg (max 400mg) TDS (children)
pKA	4.5
Pharmacodynamics
MOA	Reversibly inhibits cyclooxygenase 1 and 2 (COX 1 and 2) enzymes > decreased formation of prostaglandin precursors (thromboxane A2, prostacyclin, prostaglandins)
Effects	CNS: Analgesic, antipyretic and anti inflammatory properties GIT: nausea, dyspepsia, GI ulceration, RENAL: impaired renal function, interstitial nephritis CVS: increased risk of thrombotic events (at high dose) RESP: cough, bronchospasm (related to increased LTs)
Pharmacokinetics
Onset / duration	30-60 minutes / 4 hours
Absorption	PO bioavailability 80%
Distribution	Protein binding 99% (albumin) VOD = 0.2 L / Kg
Metabolism	Hepatic oxidation (CYP450) to inactive metabolites
Elimination	Renal elimination (95%) Inactive metabolites T1/2 = 3 hours
Special points

Insulins

Preparations

Insulin preparation	Example	Onset	Peak	Duration
Ultra-short acting	Insulin Aspart (novorapid)	10 mins	1-2 hours	4-6 hours
Short acting	Neutral insulin (actrapid)	30 mins	2-3 hours	6-8 hours
Intermediate acting	Protophane	1-2 hours	4-6 hours	12-16 hours
Long acting	Insulin glargine (lantus)	1-2 hours	No peak	24 hours
Mixed preparations	Ryzodeg (insulin aspart + degludec) Novomix (insulin aspar + protamine)	10 mins	1 hour	24 hours

Shared properties

Name	Insulins
Class	synthetic polypeptide hormone
Indications	Diabetes, hyperglycaemia, hyperkalaemia, B-blocker toxicity
Pharmaceutics	Clear colourless solutions (generally 100IU/ml)
Routes of administration	SC, IV, (IM but not used in practice)
Dose	Variable, titrated to effect
Pharmacodynamics
MOA	The same pharmacodynamic profile of endogenous insulin Insulin binds to <math display="inline">\alpha</math> subunit of insulin receptor > internalised > altered cellular activity
Effects	Increased: glucose uptake in cells, glycogenesis, protein synthesis Decreased: BSL, gluconeogenesis, lipolysis, proteolysis Cellular shift of potassium (intracellular) due to increased Na/K activity
Side effects	Hypoglycaemia, hypokalaemia, weight gain(long term)
Pharmacokinetics
Onset	Variable depending on preparation
Absorption	No oral absorption (inactivated by GIT enzymes)
Distribution	Protein binding <10% (similar to regular insulin) VOD = < 0.1 L/Kg
Metabolism	Hepatic proteases
Elimination	Renal elimination of inactive metabolites
Monitoring	BSL levels (frequency depends)

Ipratropium bromide

Name	Ipratropium bromide
Class	Anticholinergic (quaternary ammonium derivative of atropine)
Indications	Bronchoconstriction
Pharmaceutics	Aerosol for inhalation, clear colourless solution for neb
Routes of administration	Neb, INH
Dose	Neb: 100-500mcg QID INH: 100-500mcg BD
Pharmacodynamics
MOA	Competitive antagonism of muscarinic ACh receptors > bronchodilation + decreased secretions > improved ventilation > decreased work of breathing
Side effects	RESP: dry mouth, GIT: N, V CNS: headache, blurred vision, pupil dilatation
Pharmacokinetics
Onset/duration	Peak effect 1-2 hours, lasts 6 hours
Absorption	5% inhaled absorbed systemically
Distribution	VOD: 5L/kg Very weak protein binding (~5%) Does not cross BBB
Metabolism	Metabolised in liver by CYP450 > inactive metabolites
Elimination	Metabolites via faeces (main), urine (minor) Elimination half life ~3 hours
Special points

Isoprenaline

Name	Isoprenaline
Class	Synthetic catecholamine
Indications	Bradycardia, heart block
Pharmaceutics	Clear colourless solution (200mcg/ml) 5ml ampules
Routes of administration	IV
Dose	Infusion (1-10mcg/min)
pKA
Pharmacodynamics
MOA	Non selective B-Adrenergic agonist (B1 > B2)
Effects	CVS: increased chronotropy, inotropy, dromotropy, lusitropy, cardiac output, SV, increased SBP / decreased DBP RESP: bronchodilation
Side effects	RESP: Hypoxia (worsened V/Q mismatch, overcomes HPVC) CVS: increased myocardial oxygen demand, decreased SVR > decreased diastolic BP, arrhythmias, tachycardia CNS: anxiety, restlessness, dizziness
Pharmacokinetics
Onset / duration	Immediate (IV) / 10 minutes
Absorption	IV only (poor PO bioavailability due to sig. 1st pass metabolism)
Distribution	Protein binding = 65%
Metabolism	Hepatic (major) and lungs (minor) 3-0 methylation by COMT Inactive metabolites
Elimination	Renal elimination (50-80%) T 1/2 = 5 mins
Special points

Ketamine

Name	Ketamine
Class	Anaesthetic (phencyclidine derivative)
Indications	induction GA, conscious sedation, analgesia, asthma
Pharmaceutics	100mg/ml. Clear colourless solution. Racemic mixture of S and R enantiomers, or S+ enantiomer alone. Water soluble.
Routes of administration	IV/IM/PO/SC/PR
Dose	0-0.25mg/kg/hr (analgesia), 0.-2mg/kg (GA), 0.5mg/kg (sedation)
pKa	7.5
Pharmacodynamics
MOA	NMDA antagonism, weak opioid receptor agonism, weak Ca ch inhibition
Effects	CNS: dissociative anaesthesia, and analgesia and hypnosis. CVS: increased HR/BP, decreased pulmonary and systemic vascular resistance RESP: bronchodilation
Side effects	CNS: emergence reactions including hallucinations, unpleasant dreams. May increase ICP in non vent. pts (via increased CMRO2 >increase CBF. CVS: may increase HR/BP, increased myocardial O2 req. GIT: Nausea, vomiting, increased salivation
Pharmacokinetics
Onset	30s IV, duration of effect 10-20mins
Absorption	Lipid soluble > readily absorbed. But poor OBA (16%) due to 1st pass metabolism
Distribution	Large (~3L/kg) VOD. Small protein binding (~30%). Crosses placenta.
Metabolism	Hepatic (CYP450) Demethylation > norketamine (30% potent) and inactive metabolites
Elimination	Elimination T1/2 = 2 hours. Kidneys (95%), faeces (5%)
Special points	Nil reversal agent

Labetalol

Name	Labetalol
Class	Beta-blocker / antihypertensive
Indications	Hypertension
Pharmaceutics	100/200mg tablets Clear solution - 5mg/ml (10ml) ampoules
Routes of administration	IV, PO
Dose	PO: 100-800mg BD IV: 20mg boluses, infusion 1-2mg/min
Pharmacodynamics
MOA	a1 adrenergic antagonist Non-specific beta adrenergic antagonist
Effects	CVS: decreased chronotropy, inotropy, dromotropy (beta effects), decreased SVR (alpha effects), decreased myocardial oxygen consumption
Side effects	CVS: bradycardia, hypotension (esp orthostatic), heart block RESP: dyspnoea, bronchospasm CNS: dizziness GIT: nausea, raised LFTs
Pharmacokinetics
Onset	1-2 hours (PO)
Absorption	PO bioavailability 25% (extensive 1st pass metabolism)
Distribution	50% protein bound VOD = 8L/kg
Metabolism	Hepatic (extensive) by glucuronide conjugation
Elimination	Renal (50%) and faecal (50%) elimination of inactive metabolites T 1/2 - 6 hours
Special points

Levetiracetam

Name	Levetiracetam
Class	Anticonvulsant
Indications	- Seizure prophylaxis - Focal partial seizures (monotherapy) - Partial/generalised seizures (adjunct) - Status epilepticus
Pharmaceutics	Oral tablet or liquid. Clear solution for injection (500mg)
Routes of administration	PO, IV
Dose	Load = 60mg/kg (Status epilepticus) - max 4.5g 500-2000mg BD (maintenance) - max 4g daily
Pharmacodynamics
MOA	Exact MOA unclear. May modulate neurotransmission by blocking synaptic vesicle protein 2A (contains glutamate > decreased release) as well as effects on Ca channels (decreased depolarisation) and GABA channels
Effects	Prevent hypersynchronization of epileptiform burst firing and propagation of seizure activity
Side effects	CNS: irritability, agitation, anxiety, drowsiness, dizziness, headache, ataxia MSK: weakness/fatigue Other: allergy, angioedema, SJS
Pharmacokinetics
Onset	< 1 hour (PO)
Absorption	Nearly 100% PO bioavailability
Distribution	VOD = 0.5 L / Kg Protein binding = < 5%
Metabolism	Enzymatic hydrolysis ~30% of dose to inactive metabolites
Elimination	Renal excretion - unchanged drug (70%) and metabolites (30%) T 1/2 = 6 hours
Monitoring	No monitoring

Levosimendan

Name	Levosimendan
Class	Calcium sensitizer (Inodilator)
Indications	Increase inotropy in cardiogenic shock / heart failure
Pharmaceutics	Diluted in glucose, clear-yellow
Routes of administration	IV, PO
Dose	Load, then infusion
pKA	6.3
Pharmacodynamics
MOA	- Sensitises troponin C to calcium > increases contractility (without impairing relaxation) - Activates ATP-sensitive K channels in smooth muscle > vasodilation
Effects	Increased chronotropy, increased inotropy, coronary vasodilation, decreased afterload, increased SV and CO, decreased SVR, decreased blood pressure and myocardial oxygen consumption
Side effects	CVS: Hypotension, arrhythmias CNS: Headache, dizziness GIT: Nausea, vomiting
Pharmacokinetics
Onset	1 hour
Absorption	85% oral bioavailability
Distribution	Small Vd (0.3L/kg) 99% protein bound
Metabolism	Hepatic Active metabolites
Elimination	Renal elimination of metabolites T 1/2 of parent drug = 1 hour T 1/2 of active metabolites = 80 hours
Special points	Requires SAS approval in AUS

Lidocaine

Name	Lidocaine (lignocaine)
Class	Amide anaesthetic / Class 1b antiarrhythmic
Indications	Local/regional/epidural anaesthesia, ventricular dysrhythmias, topical anaesthetic (e.g. IDC insertion), analgesia (infusion)
Pharmaceutics	Clear colourless solution (1%, 2%, 4%). Can come with/without adrenaline. Also available as cream/spray
Routes of administration	SC, IV, epidural, inhaled
Dose	Regional Use: Toxic dose 3mg/kg (without adrenaline), 7mg/kg (with adrenaline) IV use: 1mg/kg initially, then ~1-2mg/kg/hr
pKA	7.9, 25% unionised at normal body fluid pH
Pharmacodynamics
MOA	Class 1b anti-arrhythmic: blocks Na channels, raising threshold potential + reducing slope of Phase 0 of action potential, shortened AP Local anaesthetic: binds to, and blocks, internal surface of Na channels
Effects	Analgesic, anaesthetic, anti-arrhythmic
Side effects	CNS: headache, dizziness, confusion, paraesthesia, reduced LOC, seizures CVS: hypotension, bradycardia, AV Block, arrhythmia CC/CNS ratio = 7 (lower number = more cardiotoxic)
Pharmacokinetics
Onset	Rapid onset (1-5 minutes)
Absorption	IV > Epidural > subcut. Oral bioavailability 35%
Distribution	70% protein bound, Vd 0.9L/kg. Crosses BBB
Metabolism	Hepatic, some active metabolites
Elimination	Metabolites excreted in urine. Half life ~90mins. Increased with adrenaline (SC). Reduced in cardiac/hepatic failure.
Special points

Magnesium Sulphate

Name	Magnesium sulphate
Indications	HypoMg Eclampsia/pre-eclampsia Severe asthma (adjunct) Arrhythmias (including TdP) Analgesia adjunct
Pharmaceutics	Clear colourless solution, various concentrations (often 2mmol/ml) for dilution. Precipitates with calcium salts
Routes of administration	IV, IM
Dose	5mmol bolus (torsade's). 4g (16mmols) bolus > 1g/hr thereafter (eclampsia, PET)
Pharmacodynamics
MOA	Essential cation - Essential cofactor in hundreds of enzymatic reactions - Necessary in several steps of glycolysis (ATP production) - NMDA receptor antagonism (increasing seizure threshold) - Inhibits Ach release at NMJ (muscle relaxation) - Smooth muscle relaxation (Inhibits Ca L-type channels)
Effects	CNS: anticonvulsant (NMDA effect) Resp: Bronchodilation (CCB effect > SM relaxation) CVS: Anti-arrhythmic ( decreased conduction velocity due to CCB effect)
Side effects	Related to speed of administration + degree of HyperMg Toxicity generally occurs > 4mmol/L CVS: Hypotension, bradycardia CNS/MSK: hyporeflexia, muscle weakness, CNS depression, potentiates NMBs RESP: respiratory depression GIT: Nausea, vomiting
Pharmacokinetics
Onset	Immediate
Absorption	N/A
Distribution	30% protein bound <1% is in the ECF compartment. Rest is in bones and tissues.
Metabolism	Nil
Elimination	Urine; clearance is proportional to GFR and plasma concentration
Special points	Incompatible with calcium salts > precipitation Drug interaction with NMB agents (potentiation)

Mannitol

Name	Mannitol
Class	Diuretic
Indications	Reduce ICP / IOP
Pharmaceutics	Prepared in water as 10-20% solution Precipitates at low temperatures
Routes of administration	IV
Dose	1g/kg bolus (max 100g)
Pharmacodynamics
MOA	Initially will increase the osmolality -> parenchymal dehydration > decreased ICP. Then is freely filtered at glomerulus, but not reabsorbed in tubules. Acts osmotically to decrease H2O reabsorption.
Effects/side effects	RENAL: osmotic diuresis, electrolyte disturbances (hyperNa, Hypo K) CNS: reduced ICP / IOP (temporary) CVS: initially rise in MSFP/preload/BP (fluid load) which then decreases with diuresis RESP: Pulmonary oedema (due to increased in ECF volume)
Pharmacokinetics
Onset / duration	Onset =15 mins Duration = 4-6 hours
Absorption	Given IV (PO bioavailability - 0%)
Distribution	Does not cross BBB VOD = 0.2L / Kg 75% becomes interstitial fluid, 25% intravascular
Metabolism	Minimal hepatic metabolism
Elimination	Renal elimination (unchanged) T 1/2 = 2-3 hours
Special points

Meropenem

Name	Meropenem
Class	Carbapenem / antibiotic
Indications	Severe bacterial infections (empirical) Directed therapy against susceptible organisms where a narrow spectrum antibiotic is not suitable
Pharmaceutics	White-yellow powder for reconstitution (500mg / 1g vials)
Routes of administration	IV
Dose	1-2g, 8 hourly (dose reduced in renal failure)
pKA
Pharmacodynamics
MOA	Bactericidal, time dependant >MIC Inhibits cell wall synthesis by binding to PBP (inhibits peptidoglycan cross linking)
Spectrum	Broad
Covers	Most GP, Most GN, ESCAPPM, pseudomonas, anaerobes, ESBL
Doesn't cover	MRSA, E. faecalis, stenno,
Adverse effects	GIT: raised LFTs CNS: lowers seizure threshold RENAL: nephritis HAEM: anaemia, thrombocytopaenia, anaemia
Pharmacokinetics
Onset	T Max 1 hours post infusion
Absorption	No PO absorption (IV only)
Distribution	Protein binding - 2% VOD = 0.3L / Kg Good tissue penetration including CNS
Metabolism	Extrahepatic metabolism to inactive metabolites
Elimination	Renal elimination (70%) unchanged Dialyzable T 1/2 = 1 hour
Special points

Metaraminol

Name	Metaraminol
Class	Synthetic non-catecholamine
Indications	Vasopressor (hypotension/shock)
Pharmaceutics	Clear solution. Typically 0.5mg/ml syringes, or 10mg/ml vials.
Routes of administration	IV, IM
Dose	0.5mg boluses, infusion
pKA	8.79
Pharmacodynamics
MOA	Direct and indirect alpha-1 agonism (very weak B agonism)
Effects	CVS: peripheral vasoconstriction > increased SVR > increased BP. Also increased PVR. Reflex bradycardia.
Side effects	CVS: Increased afterload > worsen heart failure, bradycardia
Pharmacokinetics
Onset	Immediate
Absorption	IV (though some oral bioavailability)
Distribution	VOD = 4L/kg 45% protein bound
Metabolism	Not metabolised
Elimination	Minutes, renal elimination
Special points	Tachyphylaxis (fast( with infusion))

Metoclopramide

Name	Metoclopramide
Class	Antiemetic / Prokinetic
Indications	- Post operative nausea/vomiting / antiemetic (general use) - Prokinetic
Pharmaceutics	Clear solution (5mg/ml). Tablet (10mg)
Routes of administration	IV, PO, IM, SC
Dose	10mg TDS (adults) for short duration (max 5 days)
pKA
Pharmacodynamics
MOA	Central D2 antagonism at chemoreceptor trigger zone > reduced afferent input to vomiting centre in medulla
Effects	Anti-emetic, Prokinetic (acceleration of gastric emptying)
Side effects	EPSE (akathisia, dystonia, tardive dyskinesia), drowsiness, dizziness, headache, arrhythmias
Pharmacokinetics
Onset	Tmax 1 hour (PO), 15 mins (IV)
Absorption	PO bioavailability 80%
Distribution	VOD = 3L / Kg Protein binding 30%
Metabolism	Minimal hepatic metabolism (conjugation)
Elimination	Renal elimination of active and inactive metabolites (85%) T 1/2 = 4 hrs
Special points	- Contraindicated in pheochromocytoma (precipitates pheo crisis), Parkinson's (Blocks Dopamine receptors), GI obstruction/perforation (prokinetic), infants. Avoid in children <20 years old (risk of EPSE)

Metoprolol

Name	Metoprolol
Pharmacokinetics
Onset	Immediate when IV, 1 hour oral
Absorption	95% absorption, 50% oral bioavailability (1st pass effect)
Distribution	VOD 5 L/kg 10% Protein bound High lipid solubility, readily crosses BBB
Metabolism	- Hepatic CYP450 oxidation and hydroxylation - Significant 1st pass metabolism. - Inactive metabolites
Elimination	Renal elimination T 1/2 approx. 4 hours

Metronidazole

Name	Metronidazole
Class	Nitroimidazole / Antibiotic
Indications	Anaerobic bacterial infections (including protozoal infections)
Pharmaceutics	Clear solution (5mg/ml), white tablet (200/400mg), oral liquid, suppository
Routes of administration	PO, IV, PR
Dose	400mg TDS (PO) 500mg TDS (IV)
Pharmacodynamics
MOA	Bactericidal Taken up by anaerobic bacteria > reduced > promotes accumulation of cytotoxic intermediates and free radicals > DNA cell degradation / impaired synthesis
Spectrum	Narrow
Covers	Anaerobes (including C.diff and protozoal infections such as trichomoniasis and giardiasis)
Doesn't cover	Aerobic infections
Adverse effects	Nausea, vomiting, metallic taste in mouth Disulfiram reaction with ETOH (nausea, flushing, hypotension, headache) Hypersensitivity reactions (angioedema, SJS, anaphylaxis) CNS toxicity (prolonged course) leading to seizures, encephalopathy
Pharmacokinetics
Onset	Tmax, 1hour (PO), instant (IV)
Absorption	100% PO bioavailability, 80% (PR)
Distribution	VOD - 0.5L / Kg Protein binding 20% Good tissue (including CNS, abscess, pleural fluid) penetration
Metabolism	Extensive hepatic metabolism by oxidation and conjugation to inactive and active metabolites
Elimination	Renal elimination (80%) and faecal elimination (20%) T 1/2 = 8 hours
Special points

Morphine

Name	Morphine
Class	Opioid analgesic
Indications	Severe pain
Pharmaceutics	Clear colourless solution for injection (various conc), white tablets (various conc), MR tablets, liquid (various conc)
Routes of administration	IM, IV, SC, PO, intrathecal/epidural
Dose	Variable
pKa	8
Pharmacodynamics
MOA	MOP agonist, weak KP and DOP activity (GPCR)
Effects	CNS: Analgesia, sedation, euphoria CVS: bradycardia, hypotension (histamine release > decreased SVR) RESP: respiratory depression (decreased CO2 sensitivity, decreased stimulation of pre-botzinger complex) GIT: decreased peristalsis. N/V. constipation MSK: pruritis GU: urinary retention
Pharmacokinetics
Peak effect / duration	5-10 mins (IV), 30 mins (IM) / duration = 4 hours
Absorption	PO bioavailability = 30% (readily absorbed, high first pass metabolism)
Distribution	Protein binding = 30% VOD = 3L/kg Crosses placenta, poor CNS penetration
Metabolism	Hepatic Glucuronidation > M3G (major) and M6G (potent, active) Also demethylation, conjugation, dealk.. Inactive and active metabolites
Elimination	Renal (90%) and faecal (10%) elimination of active metabolites T 1/2 = 2 hours
Special points	Reversal with naloxone Hydromorphone does not seem to produce M6G via metabolism (does produce M3G) so seems to have a more favourable PK profile for ESRF patients (less sedative side effects). Still accumlates though!

Midazolam

Name	Midazolam
Class	Benzodiazepine (sedative)
Indications	Anaesthesia, sedation, treatment of seizures, anxiolysis, amnesia, hypnosis
Pharmaceutics	IV: clear solution, pH 3.5. Diluted in water.
Routes of administration	IV, IM, S/C, intranasal, buccal
Dose	Dose depends on many pt. factors. 1-5mg premedication. 2.5-10mg seizures. Infusions.
pKa	6.5
Pharmacodynamics
MOA	Midazolam (BZD) binds to GABAA receptors (ionotropic ligand gated channel) in the CNS. Cl enters > hyperpolarisation.
Effects	CNS: sedation, amnesia, anxiolysis, hypnosis, anticonvulsant effects, decreased cerebral O2 demand, MSK: muscle relaxant
Side effects	CVS: bradycardia, hypotension CNS: confusion, restlessness RESP: respiratory depression/ apnoea
Pharmacokinetics
Onset	peak effect 2-3 minutes (IV)
Absorption	~40% oral bioavailability Absorbed well, but sig. 1st pass metabolism
Distribution	95% protein bound, very lipid soluble Vd = 1L / kg
Metabolism	Hepatic metabolism by hydroxylation Active (1-a hydroxymidazolam) and inactive metabolites
Elimination	Renal excretion T 1/2 = 4 hours
Special points	Flumazenil - antagonist (reversal agent)

Milrinone

Name	Milrinone
Class	Phosphodiesterase inhibitor
Indications	Heart failure / cardiogenic shock
Pharmaceutics	Clear/Yellow solution, 10 ml ampoules (1mg/ml)
Routes of administration	IV only (in AUS)
Pharmacodynamics
MOA	PDE III inhibition > decreased cAMP breakdown > increased Ca
Effects	CVS: increased inotropy, increased lusitropy, increased dromotoropy, no direct increased chronotropy > reflex tachycardia, vasodilation > decreased SVR > hypotension, arrhythmogenic CNS: increased CBF, headache RESP: bronchospasm HAEM: thrombocytopaenia IMMUNO: Anaphylaxis
Pharmacokinetics
Onset/Offset	5-10 minutes / 3 hours
Absorption	Readily absorbed orally with OBA 90% (tablets not available in AUS)
Distribution	Small VOD = 0.4L/kg, protein binding 70%
Metabolism	Minimal hepatic metabolism (10%)
Elimination	Renal excretion (unchanged >80%). T1/2 = 3 hours
Special points	Dose adjust in renal failure

N-Acetylcysteine

Name	N-acetylcysteine
Class
Indications
Pharmaceutics
Routes of administration
Dose
pKA
Pharmacodynamics
MOA
Effects
Side effects
Pharmacokinetics
Onset
Absorption
Distribution
Metabolism
Elimination
Special points

Naloxone

Name	Naloxone
Class	Opioid antagonist
Indications	Opioid toxicity / overdose
Pharmaceutics	Clear colourless solution 1ml vial containing 400mcg naloxone
Routes of administration	IV, IM, SC, intranasal
Dose	100-400mcg IV bolus, repeated as needed Infusion 0.5mg/kg/hr
Pharmacodynamics
MOA	Pure, competitive, opioid receptor antagonist Affinity: MOP > KOP > DOP
Effects	CNS: Reverses the analgesia and sedation effects of opioids
Side effects	CNS: Pain, opioid withdrawal (inc seizures) CVS: Pain > abrupt increased HR/BP > pulmonary oedema
Pharmacokinetics
Onset / offset	Inset: < 2 minutes (IV) Offset: 1-4 hours (variable) > shorter than PO opioids > need further dosing
Absorption	PO bioavailability < 5% - inactivated IN = 50%
Distribution	50% Protein bound VOD = 3L / kg Crosses placenta
Metabolism	Hepatic glucuronidation > Inactive metabolites
Elimination	T 1/2 = 1-2 hours Renal elimination
Special points	Can be combined orally with opioids (e.g Targin) to reduced constipation due to local effects of opioid antagonism in GIT

Neostigmine

Name	Neostigmine
Class	Anticholinesterase / quaternary amine
Indications	Reversal of non depolarising NMB Myasthenia gravis
Pharmaceutics	Clear colourless solution (2.5mg/ml)
Routes of administration	PO, IV
Dose	50mcg/kg (max 5mg) for reversal of NMB
Pharmacodynamics
MOA	Competitive cholinesterase inhibitor
Effects	CNS: reversal of non depolarising NMB RESP: bronchospasm GIT: Increases salivation and motility, diarrhoea CVS: bradycardia, decreased CO
Pharmacokinetics
Onset	< 1 min (IV)
Absorption	Poor oral bioavailability (~2%)
Distribution	VOD = 0.5L/Kg Protein binding = 20%
Metabolism	Hepatic
Elimination	Renal unchanged (50-80%) T 1/2 - 1 hour
Special points	May need adjunct atropine to minimise muscarinic effects (e.g. bradycardia)

Nimodipine

Name	Nimodipine
Class	Calcium channel blocker (Dihydropyridine)
Indications	Aneurysmal subarachnoid haemorrhage Hypertension
Pharmaceutics	Yellow film coated tablet (30mg) Clear/slight yellow solution for injection (10mg/50ml)
Routes of administration	PO, IV
Dose	60mg 4hrly (PO) 20mcg/kg/hour (IV infusion)
Pharmacodynamics
MOA	Nimodipine blocks voltage gated L type calcium channel blockers with a preference for action on cerebral blood vessels > vasodilation. Exact mechanism by which nimodipine improves outcomes in aSAH is unclear
Effects	CVS: bradycardia, hypotension (reduced SVR), decreased CO, hypotension CNS: headache, dizziness, increased CBF GIT: nausea, constipation Other: idiosyncratic reactions e.g. SJS
Pharmacokinetics
Onset	< 1 hour (PO)
Absorption	PO bioavailability = 15%
Distribution	Protein binding >95% VOD - 0.5L - 1L / Kg Very lipophilic > crosses BBB
Metabolism	Extensive hepatic metabolism (CYP3A4) with high first pass effect Inactive metabolites
Elimination	Renal (predominant) and faecal elimination of inactive metabolites T 1/2 = 2 hours
Special points

Nitric oxide (NO)

Name	Nitric oxide
Class	Pulmonary vasodilator
Indications	ARDS, Right heart failure, pHTN
Pharmaceutics	Colourless, odourless, gas (100ppm NO, 800ppm N2) Stored in aluminium cylinders
Routes of administration	Inhaled (via the inspiratory limb of an ETT)
Dose	Typically 5-20ppm - titrated to minimal effective dose
Pharmacodynamics
MOA	Binds to guanyl cyclase in cytosol > Increases cGMP > reduction in intracellular Ca > relaxation of SM. As inhaled > selectively vasodilates well ventilated alveoli
Effects	RESP: pulmonary artery vasodilation in ventilated lung regions > improves V/Q matching > dec. WOB, bronchodilation CVS: decreased mPAP > decreased RV afterload > decreased RV strain/VO2 and increased RV SV > increased LV preload
Side effects	Rebound pHTN upon cessation (due to accumulation of vasoconstrictors now unopposed) LV failure in patients with impaired LV (due to increased LV preload, with improved RV function) Vasodilatory effects (flushing, headache, hypotension, dizziness) AKI, thrombocytopenia, metHb (all rare at <20ppm)
Pharmacokinetics
Onset	< 1 minute
Absorption	Rapidly absorbed in pulmonary circulation due to high lipid solubility
Distribution	Minimal systemic distribution Rapidly binds to Hb (thus 'highly protein bound')
Metabolism	Reacts with oxyHb to produce methaemoglobin and nitrates.
Elimination	Metabolites (main metabolite = nitrate) are renally excreted T 1/2 = 5 seconds
Special points

Noradrenaline

Name	Noradrenaline
Class	Endogenous catecholamine
Indications	Vasopressor (Hypotension/shock)
Pharmaceutics	Clear solution. 1:1000 (1mg/ml). Brown vial or ampoule (prevent light oxidation). Diluted in dextrose.
Routes of administration	IV only (central vein)
Dose	Infusion titrated to effect (generally 0 - 0.5 mcg/kg/min)
pKA	8.85
Pharmacodynamics
MOA	Predominately Alpha 1 agonism. Some beta adrenergic receptor agonism. a1 > B1 > B2
Effects	CVS: peripheral vasoconstriction > increased SVR > inc. BP, reflex bradycardia, increased afterload (from SVR) > decreased CO (minor), increased myocardial O2 consumption, no sig. change in dromotropy, lusitropy or inotropy CNS: decreased CBF (depending on BP), headache RESP: increased PVR, bronchodilation GIT/RENAL/uterine: vasoconstriction > decreased BF MSK: extravasation > necrosis
Pharmacokinetics
Onset	< 1 min
Absorption	IV only (0% oral bioavailability)
Distribution	Does not cross BBB. Vd = 0.1L/kg Protein binding = 25%
Metabolism	Readily metabolised by MAO and COMT into inactive metabolites (VMA, normetadrenaline). 25% taken up in lungs.
Elimination	Excreted in urine as inactive metabolites (>85%). Half life ~2 mins
Special points	Tachyphylaxis (slow) Effect exaggerated in patients taking MAOI (less breakdown)

Normal saline (0.9%)

Name	0.9% normal saline (IV)
Class	Crystalloid fluid
Pharmaceutics	Clear solution, various volume bags (e.g. 100ml, 500mls, 1L)
Osmolality	308 mOsm / Kg (calculated) 286 mOsm/kg (measured)
Tonicity	Isotonic
Contents	9g NaCl / 1L solution
Pharmacodynamics
MOA	Expands the ECF volume and changes biochemistry of body fluids
Effects	Increased ECF volume
Side effects	Fluid overload, hyperchloraemic metabolic acidosis, electrolyte imbalances
Pharmacokinetics
Onset	Immediate (IV)
Absorption	IV bioavailability = 100%
Distribution	VOD = 0.2 L/Kg > 25% intravascular > 75% interstitial
Metabolism	Not metabolised
Elimination	Renal

Octreotide

Name	Octreotide
Class	Synthetic somatostatin analogue
Indications	Adjunct therapy for bleeding oesophageal varices - crit care use Treatment of GIT neuroendocrine tumours Acromegaly
Pharmaceutics	Clear solution (50-500mcg/ml ampoules)
Routes of administration	IV / SC / IM
Dose	Infusion per local protocol (for varices) - One example: 50mcg bolus > 50mcg/hr infusion thereafter
Pharmacodynamics
MOA	Synthetic analogue of somatostatin with duration of action 30X longer. It inhibits the secretion of various hormones including: serotonin, gastrin, growth hormones, insulin, glucagon, motilin.
Effects (desired)	Constricts splanchnic arterioles > decreased splanchnic and portal venous blood flow (thought to be due to the inhibition of glucagon which is a vasodilator)
Side effects	GIT: Abdominal pain, nausea, vomiting, diarrhoea, pancreatitis, hepatitis ENDO: hyper/hypoglycaemia, hypothyroidism CVS: arrhythmias, conduction disorders
Pharmacokinetics
Onset	30 mins (SC), immediate (IV)
Absorption	Poor oral absorption > given IM/IV/SC
Distribution	Protein binding = 65% VOD = 0.2L / KG
Metabolism	Extensive hepatic metabolism
Elimination	Predominately renal excretion T 1/2 - 1.5hrs
Special points

Ondansetron

Name	Ondansetron
Class	Anti-emetic / 5HT3 Antagonist
Indications	- PONV - Radiotherapy - Chemotherapy - General
Pharmaceutics	Tablets/wafers (4-8mg), clear solution for injection (2mg.ml)
Routes of administration	PO, SL, IV, IM
Dose	4-8mg , 8 hourly (max 24mg/24 hours)
Pharmacodynamics
MOA	Central and peripheral 5-HT3 receptor antagonism > reduced afferent input to vomiting centre in medulla
Effects	Anti-emetic properties
Side effects	CNS: headache, dizziness CVS: bradycardia, prolonged QT GIT: constipation, raised LFTs Other: serotonin syndrome (toxicity)
Pharmacokinetics
Onset	15 mins (IV), 30 mins (PO, SL)
Absorption	PO bioavailability 60% (PO) Subject to reasonable 1st pass metabolism
Distribution	Protein binding = 75% VOD = 2.5L/kg
Metabolism	Hepatic (significant) by hydroxylation and conjugation > inactive metabolites
Elimination	Faecal (major) and renal (minor) elimination of metabolites T 1/2 = 4 hours
Special points

Oxycodone

Name	Oxycodone
Class	Semi synthetic opioid (phenanthrene)
Indications	Pain (Analgesia)
Pharmaceutics	White tablet (IR, MR), various strengths Clear, colourless solution (10mg/ml)
Routes of administration	PO, IV, SC, IM, epidural
Dose	Variable (age, comorbidities, tolerance etc) Eg. PO 5-10mg PRN 4hrly or IV 1mg 5 minutes PRN
Morphine equivalence	1.5 x morphine (10mg oxycodone = 15mg morphine )
Pharmacodynamics
MOA	MOP (Gi PCR) in cerebral cortex, basal ganglia, periaqueductal grey Weak KOP/DOP activity
Effects	CNS: Analgesia, sedation, euphoria, dysphoria/confusion, miosis CVS: bradycardia/hypotension RESP: respiratory depression, depressed cough reflex GIT: decreased peristalsis. N/V. constipation MSK: pruritis GU: urinary retention
Side effects	Everything listed above that is is not analgesia
Pharmacokinetics
Onset	Peak 5 mins (IV), duration 4 hrs
Absorption	80% oral bioavailability, pKa 8.5
Distribution	~50% protein bound, VOD = ~3L/Kg, crosses placenta and BBB
Metabolism	Hepatic metabolism (CYP3A4) Demethylation to noroxycodone, oxymorphone Further glucuronidation > elimination
Elimination	T 1/2 B = 2-4hrs, Excreted in urine
Reversal	Naloxone (100mcg IV boluses, PRN 3 minutely)

Oxygen

Name	Oxygen
Class	Naturally occurring gas
Indications	Improve FiO2 / hypoxia CO poisoning Pneumothorax Decompression sickness
Pharmaceutics	Gas, stored in cylinders (various forms) Colourless, tasteless, odourless Flammable
Routes of administration	Inhaled
Dose	0.21 - 1.0 FiO2 (generally targeting SaO2 >94%; or 88-92% on CO2 retainers; though exact target not entirely evidenced based)
Pharmacodynamics
MOA	Oxygen delivery > aerobic metabolism
Effects	RESP: improved oxygen saturations (may also improve DO2), decreased respiratory drive, pulmonary toxicity (free radical generation), may worsen V/Q mismatch, absorption atelectasis, Hypercapnoea (CO2 retainers) CVS: decreased pulmonary vascular resistance (vasodilation) due to reversal of HPV, increased HR/SV/SVR in setting of hypoxia (via chemoreceptor reflex) > increased CO and BP, coronary vasoconstriction CNS: anxiety, nausea, seizures (hyperbaric hyperoxia) MET: oxidative phosphorylation > ATP production
Pharmacokinetics
Absorption	Diffusion across the alveolar capillary membrane. Rate of diffusion is governed by Fick's Law and is therefore proportional to the lung area, gas diffusion constant, partial pressure gradient and inversely proportional to membrane thickness
Distribution	Bound to plasma Hb (98%) Dissolved in plasma (<2%) - related to Henrys Law
Metabolism	Metabolised in mitochondria during the Citric acid cycle, to produce ATP and generate CO2
Elimination	Exhalation of CO2 via lungs
Special points	Note: hypercapnoea in CO2 retainers who are given oxygen is due to reversal of HPVC leading to worse V/Q mismatch + the addition of the Haldane effect. While there is a very modest decrease in minute ventilation (per the O2-Min vent curve), CO2 retainers already have a baseline increased minute ventilation and this effect is again, very, minor. I.e. supressing the 'hypoxic drive' is old school dogma.

Paracetamol

Name	Paracetamol
Class	Grouped with NSAIDS (though not true NSAID) / Analgesic
Indications	Pain, fever
Pharmaceutics	Various forms: tablets, capsules, MR tablets, syrup, combination with other drugs, suppository IV: clear colourless solution (10mg/ml)
Routes of administration	IV, PR, PO
Dose	Weight > 50kg: 500mg - 1g, 6 hourly (max 4g daily) Weight < 50kg: 15mg/kg every 6 hourly (max 60mg/kg/day)
Pharmacodynamics
MOA	MOA not entirely clear. Analgesic effect may be due to: inhibition of central PG synthesis by COX -3 and modulation 5-HT and endocannabinoid pathways Antipyretic effect may be due to : decreased PG synthesis in hypothalamus by COX-3
Effects	CNS: analgesia, antipyretic GIT: raised LFTs, hepatitis (in toxicity/excess) due to glutathione depletion CVS: hypotension with IV dosing (probably related to excipient mannitol)
Pharmacokinetics
Onset	~30 mins (PO), < 10 mins (IV)
Absorption	Rapid absorption in small bowel PO bioavailability = 85%
Distribution	Protein binding = 10% VOD = 1L /Kg
Metabolism	Extensive (>95%) hepatic conjugation with glucuronide and sulfate. Small amounts of oxidation > NAPQI If conjugation mechanisms are saturated (e.g. paracetamol toxicity) > increased oxidative pathways > increased NAPQI (toxic metabolite) > exhausts hepatic glutathione (antioxidant) > liver damage
Elimination	Renal elimination (>95%) of inactive metabolites T 1/2 = 3 hours Dialysable
Special points	Toxicity can be treated with N-acetylcysteine which is hydrolysed in vivo to glutathione > replenishing hepatic glutathione > decreased hepatic damage

Phenytoin

Name	Phenytoin
Class	Anticonvulsant
Indications	- Seizure prophylaxis - Epilepsy (simple-complex and focal-generalised) - Status epilepticus
Pharmaceutics	Capsules, syrup, clear IV solution for injection Precipitates in dextrose
Routes of administration	PO, IV
Dose	15-20mg/kg load Usual therapeutic troughs are 40-80umol/L (10-20mg/L)
Pharmacodynamics
MOA	Stabilises Na channels in their inactive state, thereby inhibiting the generation of further action potentials. Also decreases Ca entry > increased GABA activity.
Effects	Prevents propagation of seizure activity
Side effects	CVS: hypotension, heart block GIT: Nausea, vomiting CNS: ataxia, confusion, nystagmus, visual disturbance Other: acne, hirsutism, blood dyscrasias, gingival hypertrophy Pregnancy = teratogenic Many drug-drug interactions
Pharmacokinetics
Onset	Slow oral absorption (1-3 hours onset)
Absorption	PO bioavailability = 90%
Distribution	VOD= 1L/kg Protein binding >90%
Metabolism	- Hepatic hydroxylation by CYP450 system (saturable) - Wide patient variation (10% population are slow hydroxylators; CYP2C19 polymorphism) - Inactive metabolites
Elimination	Renal elimination of metabolites T 1/2 = 12 hours
Monitoring	Phenytoin level 40-80umol/L (trough)

Phosphate IV

Name	Phosphate
Class
Indications
Pharmaceutics
Routes of administration
Dose
pKA
Pharmacodynamics
MOA
Effects
Side effects
Pharmacokinetics
Onset
Absorption
Distribution
Metabolism
Elimination
Special points

Piperacillin-tazobactam

Name	Piperacillin-tazobactam
Class	Semi-synthetic penicillin (piperacillin) B-lactamase inhibitor (tazobactam)
Indications	Pseudomonal infection Broad spectrum antimicrobial cover of severe infections/sepsis
Pharmaceutics	White powder (2.25 -4.5g / vial), reconstitutes in water/NaCl/glucose
Routes of administration	IV, IM
Dose	4g/0.5g 8hrly 4g/0.5g 6hrly (pseudomonas cover) Dose reduced renal failure
Pharmacodynamics
MOA	Piperacillin: bactericidal - inhibits cell wall synthesis by preventing cross linking of peptidoglycans by replacing the natural substrate (D-ala-D-ala) with their B-lactam ring Tazobactam: B lactamase inhibitor (prevents piperacillin degradation)
Antimicrobial cover	Broad spectrum coverage of gram positive bacteria, gram negative bacteria, anaerobes. Covers pseudomonas. Doesn't cover: MRSA, VRE, ESBL, atypicals, ESCAPPM
Side effects	GIT: diarrhoea, nausea, vomiting Renal: AKI Allergy (up to 10%), rash most common, skin eruptions/SJS and anaphylaxis (<1/10,000)
Pharmacokinetics
Absorption	Minimal oral absorption > given IV Peak concentrations immediately after dose. IM Bioavailability = 75%
Distribution	Very good tissue penetration (minimal CNS without active inflammation) VOD 0.2L kg Low protein binding (20%)
Metabolism	Piperacillin: not metabolised Tazobactam: metabolised to M1, an inactive metabolite
Elimination	Renal (80% unchanged) T1/2 = 1 hour
Special points	Removed by haemodialysis

Platelets (pooled)

Name	Pooled platelets
Class/description	Blood product
Indications	Thrombocytopaenia, platelet dysfunction
Pharmaceutics
Preparation	Collected by apheresis of whole blood Platelets harvested from poo of buffy coats (from 4 identical ABO donations) Leucodepletion + irradiation Bacterial screening
Storage (duration)	Up to 7 days
Storage conditions	22 degrees - prevents deformation Bag that allows gas exchange (prevents CO2/lactate accumulation) Agitated (prevents clotting) pH controlled -prevents degranulation
Contents/factors	Pooled platelets from multiple donors
Volume	~350 mls (per pool of leucocyte deplete platelets)
pH	7.0
Routes of administration	IV
Dose	Usually 1 pool per time. Targeting PLT counts > 30 with bleeding or >50 with severe bleeding or DIC >100 with bleeding at critical sites (brain, eyes)
Pharmacodynamics
MOA + Effects	Primary (platelet plug) and secondary haemostasis (cell based model coagulation)
Side effects	Blood product, with all the risks associated with this (fluid overload, infection, allergic responses). See alternate note on transfusion reactions

Potassium IV

Name	Potassium
Class
Indications
Pharmaceutics
Routes of administration
Dose
pKA
Pharmacodynamics
MOA
Effects
Side effects
Pharmacokinetics
Onset
Absorption
Distribution
Metabolism
Elimination
Special points

Prazosin

Name	Prazosin
Class	Alpha1 blocker / Antihypertensive
Indications	Hypertension Raynaud's syndrome BPH
Pharmaceutics	White tablets (1,2,5mg)
Routes of administration	PO
Dose	1mg - 20mg daily in 2-3 divided doses Dose gradually up titrated from 0.5mg BD/TDS
Pharmacodynamics
MOA	alpha 1 adrenergic receptor antagonist
Effects	CVS: Peripheral arterial and venous vasodilation > decreased SVR GU: relaxes bladder trigone and sphincter > improved urinary flow
Side effects	CVS: hypotension (particularly orthostatic), syncope, flushing CNS: fatigue, headache, vertigo
Pharmacokinetics
Onset	30-60 minutes
Absorption	PO bioavailability 60%
Distribution	Highly protein bound (95%) VOD = 0.5 L /Kg
Metabolism	Extensive hepatic metabolism (demethylation and conjugation) to inactive + active metabolites
Elimination	T 1/2 = 3 hours Faecal elimination
Special points

Prostacyclin's (epoprostenol and iloprost)

Name	Prostacyclin's
Class	Pulmonary vasodilator / prostacyclin analogues
Indications	Pulmonary arterial hypertension with RV failure Rescue therapy in severe ARDS (INH) Others: Raynaud's, limb ischaemia
Pharmaceutics	Iloprost is an analogue of prostacyclin (aka epoprostenol) with greater chemical stability. 1500mcg/50 ml = 30mcg/ml (at RNSH). Powder for reconstitution and injection or nebulisation (epo), clear nebulising solution (ilo)
Routes of administration	IV, INH
Dose	50 nanograms/kg/min, continuous (AT RNSH)
Pharmacodynamics
MOA	Binds to prostacyclin receptor (IP receptor) > Activates GPCR > increases cAMP (via adenyl cyclase) > decreased platelet activation and increased SM relaxation
Effects	RESP: pulmonary arterial vasodilation > improve V/Q matching + oxygenation in ARDS if inhaled (goes to ventilated regions only), but may worsen it if given intravenously (goes to all pulmonary blood vessels > worsening shunt) HAEM: inhibition of platelet aggregation > increased risk bleeding CVS: flushing, hypotension, reflex tachycardia, decreased pulmonary vascular resistance and mPAP > decreased RV afterload (may improve CO in RHF) CNS: headache, increased CBF
Pharmacokinetics
Onset	Seconds-minutes
Absorption	Not determined
Distribution	VD = 0.4L/kg (epo), 0.7L/kg (ilo) Protein binding = 60% (ilo)
Metabolism	Hydrolysis and enzymatic degradation in blood
Elimination	T 1/2 < 5 mins (epoprostenol), 20-30mins (iloprost) Renal (70%) and faecal (15%) elimination
Special points	Terminology - Prostacyclin is also called Prostaglandin I2 or PGI2 - When prostacyclin is used as a drug it is often called epoprostenol (which is just a synthetic analogue of naturally occurring prostacyclin) - Iloprost is a prostacyclin analogue, which is pharmacologically equivalent to epoprostenol, but with greater chemical stability (can be stored in solution and has greater half life) You would use inhaled prostacyclins in ARDS (improves V/Q mismatch) and intravenous in severe PAH with RV failure (if there are no ventilation issues, as it would worsen V/Q mismatch)

Protamine

Name	Protamine sulfate
Class	Heparin antagonist / Antidote
Indications	Heparin, dalteparin or enoxaparin reversal
Pharmaceutics	Clear colourless solution (10mg/ml) Basic protein prepared from fish sperm
Routes of administration	Slow IV injection (10 mins). Too fast = anaphylactoid reaction
Dose	1mg protamine will neutralise 100IU heparin. Exact dose will depend on method of delivery of heparin (e.g. IV bolus vs infusion vs SC) and the type (e.g. LMWH vs HMWH)
Pharmacodynamics
MOA	Combines with heparin to form a stable inactive complex
Effects	Complete reversal of HMWH and 75% reversal of LWMH anticoagulant effects
Side effects	- Hypersensitive reactions including cardiovascular collapse (hypotension, bradycardia), due to histamine release - Pulmonary hypertension (complement and thromboxane release) leading to severe pulmonary oedema
Pharmacokinetics
Onset	Immediate (IV only)
Absorption	IV only
Distribution	VOD = 0.2 L / KG
Metabolism	Protamine/heparin complexes are partially metabolised by fibrinolysin, but are otherwise cleared by reticuloendothelial system
Elimination	T 1/2 - 5 minutes
Special points	Cannot use in patients with fish allergies

Prothrombinex

Name	Prothrombinex
Description	Human plasma derivative containing a concentrate of specific clotting factors
Preparation	1) Separation of whole blood or apheresis 2) Separation of clotting factors II, IX and X via ion exchange chromatography 3) Freeze dried powder
Indications	Warfarin reversal Correction of coagulopathy from factor II, IX or X deficiency
Pharmaceutics	Glass vial with powdered concentrate for reconstitution with water. Generally 500U per vial. Refrigerated
Storage	Stored for 6 months in fridge <6 degrees
Routes of administration	IV
Dose	25-50 u/kg
Contents/factors	Contains factors II, IX, X (500 units each)
Adverse effects	Allergic or anaphylactic reactions Thrombosis in predisposed individuals
Pros	Does not need group/crossmatch (therefore available for immediate use) Smaller fluid volume
Cons	Factor 7 absent More expensive than FFP

Propofol

Name	Propofol
Class	Phenolic derivative (IV anaesthetic)
Indications	Anaesthesia, sedation
Pharmaceutics	White, opaque, liquid emulsion. Contains soybean oil, egg lecithin, glycerol. Poor water solubility / high lipid solubility
Routes of administration	IV
Dose	RSI 1-2mg/kg. Infusion (0-10mg/kg/hr)
pKa	11 (almost completely unionised)
Pharmacodynamics
MOA	Propofol binds to Beta subunit of GABAA receptor > Cl enters > hyperpolarisation
Effects	CNS: sedation, anaesthesia, amnesia, hypnosis, anti-epileptic, decreased CMRO2/CBF/ICP, injection site pain CVS: decreased SVR > hypotension, bradycardia, decreased inotropy > decreased CO RESP: respiratory depression, apnoea RENAL: green urine MET: high lipids Toxicity: Propofol infusion syndrome
Pharmacokinetics
Onset	Seconds
Absorption	IV Only (high first pass metabolism)
Distribution	98% protein bound (albumin) VOD 4L/kg Readily crosses BBB
Metabolism	Predominately hepatic (but also renal and extra-hepatic) Glucuronide conjugation (major), phase 1 reactions (minor) Inactive metabolites
Elimination	Renal excretion T 1/2B = 8 hours
Special points	No reversal agent

Quetiapine

Name	Quetiapine
Class	2nd generation antipsychotic
Indications	Psychosis, generalised anxiety disorders, major depression
Pharmaceutics	Tablets (IR and MR formulations)
Routes of administration	PO
Dose	Starting dose: 12.5-25mg BD Max dose: 400mg BD
Pharmacodynamics
MOA	Atypical antipsychotic. Exact mechanism unclear. Shows activity at 5-HT2, D2 and D1 receptors (5HT2 > D2)
Effects	Reduced "positive" symptoms of psychosis, including agitation, hallucinations, delusion.
Side effects	CNS: somnolence, neuroleptic malignant syndrome, extrapyramidal side effects (dystonia, akathisia, parkinsonism, TD) CVS: tachycardia, postural hypotension MET: weight gain HAEM: leukopaenia
Pharmacokinetics
Onset	TMax 1.5 hrs
Absorption	100% PO bioavailability
Distribution	Protein binding 85% VOD = 10L / Kg
Metabolism	Extensive hepatic metabolism (sulfoxidation by CYP3A4) Active and inactive metabolites
Elimination	Renal elimination (75%), faecal (25%) T 1/2 = 6 hours (parent), 12 hours (metabolites)
Special points

Red blood cells (RBCs)

Name	pRBCs
Class/description	Blood product
Indications	Anaemia
Pharmaceutics
Preparation	Whole blood is centrifuged, plasma removed Leucodepletion by filtration Double washed with SAGM solution to remove proteins/Ab/EUCs Suspended in SAGM solution to preserve life
Storage (duration)	42 days
Storage conditions	2<math display="inline">\degree</math>C to 6<math display="inline">\degree</math>C Stored with SAGM (saline, adenine {ATP source}, glucose {substrate for glycolysis}, mannitol {resists haemolysis}) and citrate (prevents clotting)
Contents/factors	Red blood cells
Volume	~250mls
pH
Routes of administration	IV
Dose	1-2 units at a time, generally targeting specific Hb concentration
Pharmacodynamics
MOA + Effects	Increases Hb level by replacement
Side effects	Blood product, with all the risks associated with this (fluid overload, infection, allergic responses). See alternate note on transfusion reactions

Remifentanyl

Name	Remifentanyl
Class	Opioid Synthetic phenylpiperidine derivative
Indications	Intravenous anaesthesia, Analgesia
Pharmaceutics	Crystalline white powder for reconstitution
pKa	7.3
Routes of administration	IV, intranasal
Pharmacodynamics
MOA	Mu-opioid receptor agonist > hyperpolarisation
Effects	Analgesia
Side effects	CVS: bradycardia + hypotension Resp: respiratory depression GIT: Decreased GI motility MSK muscle rigidity at high doses
Pharmacokinetics
Onset/Offset	Rapid onset (1 mins) Rapid offset (5-10mins)
Absorption	PO Bioavailability (0%). Mucosal absorption is rapid
Distribution	VOD low = 0.1L/kg Highly protein bound (70%) Very lipid solubility
Metabolism	Ester hydrolysis by plasma and tissue esterases > inactive metabolites
Elimination	T 1/2 5 mins. No CSHT Excreted in urine

Rocuronium

Name	Rocuronium
Class	Aminosteroid NMB / non depolarising NMB
Indications	NMB (e.g. intubation, assist with difficult mechanical ventilation)
Pharmaceutics	Clear colourless solution (10mg/ml, 5ml vial) Shelf life prolonged when refrigerated
Routes of administration	IV
Dose	0.6 - 1.2mg/kg (RSI dose)
pKA
Pharmacodynamics
MOA	Inhibit the action of ACh at the NMJ by competitively binding to alpha subunit of nAChR on post junctional membrane
Effects	neuromuscular block > paralysis, apnoea
Side effects	CVS: tachycardia (in high doses, rare otherwise) IMMUNE: anaphylaxis (<0.1%)
Pharmacokinetics
Onset / duration	Onset: 45-90s (faster with higher doses) Duration: ~30-45 mins
Absorption	IV only
Distribution	VOD = 0.2 L /kg Protein binding = 10% Doesn't cross BBB
Metabolism	Minimal hepatic metabolism (<5%)
Elimination	Bile 70%, Renal 30% Excreted unchanged T 1/2 - 1 - 1.5hrs
Special points	Reversible with sugammadex and anticholinesterases (e.g. neostigmine)

Salbutamol

Name	Salbutamol
Class	Short acting B2 agonist (synthetic sympathomimetic amine)
Indications	Bronchoconstriction, hyperkalaemia, tocolytic
Pharmaceutics	Clear solution for neb, solution for IV (post dilution), powder / aerosol for inhalation, PO tablets
Routes of administration	Neb, IV, INH, PO
Dose	2.5mg-5mg PRN (Neb) 200-400mcg PRN (INH) 0.5mcg/kg/min (infusion)
Pharmacodynamics
MOA	B2 agonism > increased cAMP > decreased Ca > bronchial smooth muscle relaxation > decreased airway resistance > improved ventilation > decreased work of breathing
Side effects	CNS: anxiety, tremor, headache, hyperactivity CVS: tachycardia, palpitations MET: hypoK (stimulates Na/K ATPAse), lactic acidosis
Pharmacokinetics
Onset/duration	Immediate, fast offset (mins)
Absorption	50% PO bioavailability, <20% Inhaled
Distribution	VOD: ~2L/kg 10% protein bound Can cross placenta
Metabolism	Metabolised in liver > inactive 4-O-sulfate (active)
Elimination	Metabolites via urine (80%) + faeces (20%) T 1/2 ~ 4 hours
Special points

Sodium bicarbonate

Name	Sodium Bicarbonate
Class
Indications	Severe NAGMA, alkalinisation of urine (salicylate toxicity), hyperkalaemia, TCA overdose (Na channel blocking effects)
Pharmaceutics	Tablet, capsules, effervescent granules Clear colourless solution (various concentrations e.g, 4.2%, 8.4%) which can be hypertonic or isotonic
Routes of administration	PO, IV
Dose	1mmol/kg IV = 1ml/kg of 8.4% (cardiac arrest due to hyperK)
Pharmacodynamics
MOA	Dissociates into Na and HCO3. The HCO3 functions as a buffer in the bicarbonate-carbonic acid buffering system (raising pH). The Na increases the strong ion difference in plasma (raising pH)
Effects	Increases pH, alkalinisation of urine
Side effects	Hypokalaemia, hypocalcaemia, hypernatremia Fluid overload (Large doses IV) Extravasation tissue injury (IV) Metabolic alkalosis (overdose)
Pharmacokinetics
Onset	Immediate
Absorption	NA
Distribution	Intravascular space
Metabolism	<math display="inline">CO_2 \; + H_2O \; \leftrightarrow \; H_2CO_3 \; \leftrightarrow \; HCO_3^- \; + H^+</math>
Elimination	Renal (bicarbonate), lungs (as CO2)
Special points	Incompatible with calcium /magnesium salts (precipitates)

Sodium nitroprusside

Name	Sodium nitroprusside
Class	Nitrate vasodilator
Indications	Hypertensive emergencies (or need for strict BP control)
Pharmaceutics	IV solution (50mg/2mL) Light sensitive
Routes of administration	IV only (non PVC giving sets)
Dose	Titrated to effect (0-2mcg/kg/min)
pKA	3.3
Pharmacodynamics
MOA	Prodrug Reacts with sulfhydryl groups on erythrocytes (as well as albumin and other proteins) to produce NO NO diffuses into cell > incr cGMP > decreased Ca > SM relaxation
Effects	CVS: arterial + venous dilation > decreased SVR > decreased BP + afterload, rebound hypertension (withdrawal), hypotension, RESP: impairs HPVC > worsened V/Q matching > hypoxia, CNS: cerebral vasodilation > raised ICP / headache GI: ileus Metabolic: acidosis, cyanide toxicity (high doses)
Pharmacokinetics
Onset/offset	Immediate onset + offset
Absorption	0% oral bioavailability
Distribution	Rapidly distributes among the intravascular space (small VOD)
Metabolism	Nitroprusside > cyanide > prussic acid > thiocyanate Site: RBC (and liver secondarily)
Elimination	Metabolites via urine (major) T 1/2 = 3 mins
Special points

Sodium valproate

Name	Sodium valproate (valproic acid)
Class	Anticonvulsant
Indications	- Migraine - Epilepsy (simple-complex and focal-generalised) - Status epilepticus
Pharmaceutics	Enteric coated tablets, oral liquid Powder for reconstitution
Routes of administration	IV, PO
Dose	15-30mg/kg in divided doses
Pharmacodynamics
MOA	Stabilises Na channels in their inactive state, thereby inhibiting the generation of further action potentials. Also by stimulating GABAergic inhibitory pathways
Effects	Anticonvulsant
Side effects	GIT: Nausea, dyspepsia, liver failure, pancreatitis HAEM: thrombocytopaenia, neutropoenia CNS: drowsiness, dizziness, ataxia Other: teratogen, hair loss
Pharmacokinetics
Onset	TMax 2 hrs (PO), immediate (IV)
Absorption	PO bioavailability = 90%
Distribution	Protein binding 70-90% (lower in critically ill) VOD = 0.2L / Kg
Metabolism	Hepatic metabolism (glucuronidation) to active and inactive metabolites
Elimination	Renal elimination of metabolites (85%) T 1/2 = 14 hours
Special points	Monitor LFTs first 6 months given risk of liver failure

Sotalol

Name	Sotalol
Class	B-blocker
Indications	tachyarrhythmias (e.g. AF, SVT) and ventricular arrhythmias
Pharmaceutics	80+160mg PO tablets. IV in racemix mixture of enantiomers (through SAS).
Routes of administration	PO, IV (via SAS)
Dose	40-160mg PO BD
pKA	9.8
Pharmacodynamics
MOA	1) Non selective B-blocker (class II) > decreased chronotropy and inotropy 2) Class III activity (K channel blocker) > prolonged refractory period + repolarisation > slow AV conduction and lengthens QT
Side effects	CVS: precipitation of tDP, bradycardia, prolonged QT int, tachyarrhythmias, hypotension, chest pain, exacerbation of heart failure RESP: bronchospasm, dyspnoea CNS: dizziness, drowsiness, fatigue and lethargy GIT: nausea, dyspepsia, abdominal pain, diarrhoea, vomiting
Pharmacokinetics
Onset/duration	2-3 hours (PO)
Absorption	95% oral bioavailability
Distribution	No protein binding VOD 1-2L/kg
Metabolism	Nil
Elimination	T 1/2 12 hours Urine excretion (unchanged)
Special points	Reduce dose in renal failure Requires SAS for IV

Spironolactone

Name	Spironolactone
Class	Diuretic / Aldosterone antagonist
Indications	- Hyperaldosteronism - Hypertension - Heart failure - Hirsutism (females)
Pharmaceutics	25/100mg tablets (film coated)
Routes of administration	PO
Dose	Hypertension: 12.5-50mg daily (up to 200mg daily for androgen indications)
Pharmacodynamics
MOA	Competitive aldosterone antagonist (and weak androgen antagonist). Renally aldosterone stimulates Na+ reabsorption in DCT, which in turn stimulates K+ secretion.
Effects	RENAL: diuresis METABOLIC: anti-androgen effect
Side effects	RENAL: HyperK, HypoN, HypoCl, acidosis, renal impairment GIT: diarrhoea, nausea, vomiting METABOLIC: impotence, gynecomastia, menstrual irregularities, alopecia
Pharmacokinetics
Onset	2-4 hours
Absorption	Oral bioavailability 80% (1st pass metabolism)
Distribution	Protein binding 90% VOD = ~2L/kg
Metabolism	Hepatic metabolism > active metabolites
Elimination	Renal (50%) and faecal (30%) elimination of metabolites T 1/2 = 2 hours (parent drug), 14 hours (active metabolites)
Special points	Risk of hyperkalaemia (hence often used with a loop diuretic)

Sugammadex

Name	Sugammadex
Class	<math display="inline">\gamma</math>-cyclodextrin / NMB reversal agent
Indications	Reversal of NMJ block by rocuronium, vecuronium
Pharmaceutics	Clear solution (100mg.ml) in 2ml or 5ml vials
Routes of administration	IV
Dose	2mg/kg if ToF > 2 4mg/kg if PTC > 2 Emergency reversal: 16mg/kg
Pharmacodynamics
MOA	Forms a complex with rocuronium/ vecuronium > inactivates them
Effects	Reversal of NMJ block
Side effects	Hypersensitive reactions (including anaphylaxis) < 1% PONV
Pharmacokinetics
Onset	< 3 mins
Absorption	IV only
Distribution	No protein binding VOD - 0.2L / Kg
Metabolism	Not metabolised
Elimination	Renal elimination of active drug-NMB complex T 1/2 = 2 hours
Special points	Interacts with COCP > need alternate contraception for 7 days

Suxamethonium

Name	Suxamethonium (succinylcholine)
Class	Depolarising muscle relaxant
Indications	Facilitate endotracheal intubation during anaesthesia (i.e. RSI)
Pharmaceutics	Clear colourless solution (50mg/ml), needs refrigeration (4°C) or else lasts only a couple of weeks at room temp
Routes of administration	IV, IM
Dose	1-2 mg/kg (IV), 2-3 mg/kg (IM)
Pharmacodynamics
MOA	Binds to the nACh receptor on motor end plate > depolarisation. Cannot be hydrolyed by Acetylcholinesterase in NMJ > sustained depolarisation (i.e. Na channels remain in open-inactive state) > muscle relaxation
Effects	Flaccid paralysis.
Side effects	Major: anaphylaxis, suxamethonium apnoea, malignant hyperthermia Minor: hyperkalaemia, myalgia, bradycardia/arrhythmia Pressure: increased IOP, ICP, intragastric pressure.
Pharmacokinetics
Onset	Onset 30s - 60s, duration <10 mins
Absorption	-
Distribution	30% protein bound Vd = 0.02 L/Kg
Metabolism	Rapid hydrolysis by plasma and liver psuedocholinesterase's (~20% reaches NMJ)
Elimination	Minimal renal elimination (due to rapid metabolism)
Special points	May have prolonged duration of action with congenital or acquired (e.g. liver, renal, thyroid disease) pseudocholinesterase deficiency Treatment of malignant hyperthermia is with dantrolene (+ cooling + supportive care)

TPN

Overview

• TPN is the delivery of nutrients into the venous circulation to replace enteral requirements

Indications

• Patients who are unable to be fed via enteral route for prolonged periods of time (e.g. >72 hours)
• May include patients who fail trial of enteral feeding or other contraindications (e.g. GI obstruction, severe pancreatitis, short gut syndromes)

Daily nutritional requirements (major)

Nutrient	Requirement (kg/day)
H2O	30mls
Energy	25-30 kcal
Protein	1g (higher in critically ill, 1.5g)
Glucose	2g
Lipids	1g
Na	1-2 mmol
K	1mmol
Ca / Mg	0.1mmol
PO4	0.4 mmol

Requirements vary according to physiological (e.g. age, gender, body size, activity levels) and pathological (e.g. burns, sepsis, renal failure, hepatic failure) factors

Composition of TPN (various formulations exist)

• Glucose

  • Typically supplies around 60-70% of daily caloric needs (~1400KCal)

    • Typically 50% dextrose used (824mls = 412g = 3.4 kCal/g)

• Lipid

  • Typically supplies around 30-40% daily caloric needs (~600Kcal)

  • Can be olive oil, soybean, fish oil based (10% lipid = 1.1kcal/ml = 545mls needed)

• Protein (Amino acids)

  • Will contribute to energy source + provides essential amino acids

  • L-amino acids used only (generally 10% solution, i.e. 100g/L)

  • Typically 1.5g/kg/day in critically ill (~100g protein / day)

• Electrolytes (Na, K, Mg, Ca, Cl, PO4)

  • TPN solutions can come with/without electrolytes and adjusted

• Vitamins, trace elements

  • Micronutrients are added in appropriate amounts to the bag for adequate daily intake

  • Thiamine, folic acid and vitK are vulnerable to depletion and additional may be needed

• Water

  • In solution, though insufficient for daily requirements

  • Hyperosmolar solution due to above nutrients

Side effects / complications

• Delivery device / vascular access related
  • Infection, pneumothorax, thrombosis, air embolism
• Fluid/electrolyte disturbances
  • Fluid overload
  • Electrolyte derangements, shifts and refeeding syndrome
  • Acid base disturbances
• Metabolic disturbances
  • Hypoglycaemia, hyperglycaemia (dose related issues due to over/under feeding)
  • Hyperlipidaemia

Tranexamic acid (TXA)

Name	Tranexamic acid
Class	Antifibrinolytic
Indications	Trauma (within 3 hours) Cardiac/obstetric/orthopaedic surgery Haemorrhage/Coagulopathy
Pharmaceutics	500mg Tablets (PO) Clear colourless solution (100mg/ml) for injection (IV)
Routes of administration	PO, IV, IM, TOP, INH
Dose	0.5 - 1 g (slow IV push) --> infusion of 1g over 8 hrs (if needed)
pKA
Pharmacodynamics
MOA	Competitive inhibition of activation of plasminogen into plasmin by binding to lysine binding sites
Effects	HAEM: Decreased fibrinolysis, prothrombotic complications in those patients with risk factors GIT: nausea, vomiting, diarrhoea CNS: seizures, headache, dizziness (dose related) CVS: hypotension (rapid administration)
Pharmacokinetics
Onset / duration	Immediate (IV), 1 hour (IM), 2 hours (PO) Duration = 18-24 hours
Absorption	PO bioavailability = 50%, IM/IV bioavailability 100%
Distribution	Protein binding: very low (<5%) VOD = 0.3L / kg
Metabolism	Minimal (<5%) hepatic metabolism Inactive metabolites
Elimination	Renal elimination of active drug (95% unchanged) T 1/2 = 2hrs (IV), 12 hrs (PO)
Special points	Dose reduce in renal failure

Vancomycin

Name	Vancomycin
Class	Glycopeptides (antibiotic)
Indications	Severe gram positive infections,MRSA, C.diff
Pharmaceutics	White powder for reconstitution
Routes of administration	PO, IV, PR, intrathecal
Dose	Dose/interval adjusted according to desired peak/trough levels
Pharmacodynamics
MOA	Inhibits cell wall synthesis by binding to D-ala-D-Ala portion of growing cell wall
Microbial coverage	Gram positives, including MRSA. C diff coverage
Side effects	CNS: ototoxicity (dizziness, vertigo, tinnitus) - risk higher when given with aminoglycosides or with prolonged used RENAL: nephrotoxicity (dose related + increased with coadministration of aminoglycosides) HAEM: thrombocytopaenia, leukopenia IMMUNO: red man syndrome (erythematous rash, pruritis, hypotension) due to histamine rele
Pharmacokinetics
Absorption	PO bioavailability <1%. Only given orally for C. diff infections > local effect.
Distribution	Poor CSF penetration (requires higher dosing) VOD = 0.5L / kg 50% protein bound
Metabolism	No metabolism
Elimination	Unchanged in the urine T 1/2 = 6 hrs
Monitoring	Renal function > dose adjustment Trough levels to guide therapy
Resistance	Cannot treat VRE (VanA/B resistance genes)

Vasopressin (argipressin)

Name	Vasopressin (argipressin)
Class	Endogenous nonapeptide
Indications	Hypotension/shock (catecholamine sparing)
Pharmaceutics	Clear colourless solution (20units/ml)
Routes of administration	IV infusion (central vein)
Dose	2.4 units/hr (for vasopressor support) - At lower doses has predominant V1 activity, V2 activity at higher doses
pKA	10.3
Pharmacodynamics
MOA / effects	Physiologically secreted by PVN of hypothalamus > stored in posterior pituitary > secreted in response to hypovolaemia + increased osmolality → V1 receptor (blood vessels) agonism > Vasoconstriction > increased SVR > increased BP → V2 receptor (collecting ducts of nephrons) agonism > increased water reabsorption > increased BP → V2 receptor (endothelial cells) agonism > increased vWF release and Factor VIII activity
Side effects	CVS: ACS, angina, arrhythmias HAEM: Excessive platelet aggregation / thrombosis RENAL: Hyponatraemia (increased water reabsorption > Na reabsorption) GIT: abdominal pain , nausea, vomiting DERM: Ischaemia from vasoconstriction Allergic reactions (bronchospasm, urticarial rash, anaphylaxis)
Pharmacokinetics
Onset	Fast (~15 mins)
Absorption	IV only (0% oral bioavailability as inactivated by trypsin)
Distribution	No (or very minimal) protein binding Vd 0.2L/Kg
Metabolism	Extensive hepatic and renal metabolism by serine proteases and oxido-reductase enzymes > inactive metabolites
Elimination	Renal elimination T 1/2 <10 minutes

Vasopressin analogues

• Desmopressin (DDAVP)
  • Indications: central diabetes insipidus, vWD, slowing correction of hyponatraemia
  • Route: IV, IN, SC, PO, IM
  • MOA: predominately V₂ mediated effects (limited V₁ effects) > increased H₂O reabsorption + increased vWF and Factor VIII activity. Minimal effects on vasoconstriction activity
  • Similar PK to argipressin except it is not metabolised, has a longer T _1/2
• Terlipressin
  • Indication: variceal bleeding, hepatorenal syndrome
  • Route: IV
  • MOA: predominately V₁ mediated effects > splanchnic vasoconstriction > decreased portal venous pressure. Minimal effects of platelet aggregation or fluid absorption
  • Similar PK to argipressin except it is not metabolised, has a longer T_1/2

Vecuronium

Name	Vecuronium
Class	Aminosteroid / neuromuscular b
Indications	Muscle relaxant; intubation, control of ICP, assist ventilation,
Pharmaceutics	Potentially unstable in solution Comes in powder (10mg), dissolved in water (5ml) for use
Routes of administration	IV
Dose	Intubation: 0.1mg/kg
Pharmacodynamics
MOA	Non depolarising muscle relaxant; Competitive antagonism of ACh at N2 receptors on PSM of NMJ
Effects	MSK: NMJ blockage (paralysis) CVS: nil RESP: Apnoea
Side effects	MSK: prolonged use can lead to myopathy Rare for histamine release (anaphylaxis, hypotension)
Pharmacokinetics
Onset/duration	90-120s; 30-45 minutes
Distribution	Doesn't cross BBB; VD 0.23L/kg
Metabolism	20% hepatic de-acetylation
Elimination	70% biliary, 30% urinary
Reversal	Can be reversed with sugammadex

Verapamil

Name	Verapamil
Class	Non-dihydropyridine calcium channel blocker
Indications	SVT, Atrial fibrillation (without WPW), atrial flutter, hypertension
Pharmaceutics	Film coated and MR tablets Solution for injection (2.5mg/ml) Racemic mixture
Routes of administration	PO, IV
Dose	80-160mg BD/TDS
Pharmacodynamics
MOA	Bind to L-Type calcium channels in smooth muscle and myocardial cells (myocardial > SM cells)> block entry of Calcium In the SM it leads to vasodilation, in SA/AV node it reduces slope of Phase 0 of AP, in the myocardium it shortens phase 2 of the AP
Effects	CVS: decreased HR, BP, SVR and contractility. Slowed SA and AV nodal conduction.
Side effects	CVS: precipitate another arrhythmia (e.g. VT), heart failure (given negative inotropic properties), bradycardia, AV block, hypotension, flushing CNS: cerebral artery vasodilation > increased ICP, headache<
Pharmacokinetics
Onset	Onset 1 hour (PO), 2 mins (IV)
Absorption	Well absorbed, but high 1st pass metabolism (25% PO bioavailability)
Distribution	Protein binding = 90% VOD = 4L / Kg
Metabolism	hepatic CYP450 metabolism (demethylation, dealkylation) > active (norverapamil) and inactive metabolites
Elimination	T 1/2 = 6 hours (IR) Renal (75%) and faecal (15%) elimination of inactive metabolites
Special points

Warfarin

Name	Warfarin
Class	Oral anticoagulant (Vitamin K antagonist)
Indications	Systemic anticoagulation, e.g. in prophylaxis/treatment of thromboembolism
Pharmaceutics	Racemic mixture of two enantiomers R and S, with the S isomer more biologically active. There are two preparations (coumadin and marevan) but they are not interchangeable
Routes of administration	Oral
Dose	Varies; titrated to INR
Pharmacodynamics
MOA	Inhibits the synthesis of vitamin K dependant clotting factors (II, VII, IX, X). Specifically, inhibits vitamin K epoxide reductase (VKORC1) from converting VitK from the oxidised to reduced form, which prevents carboxylation (activation) of clotting factors listed above (as well as protein C and S)
Effects	Anticoagulation
Side effects	Haemorrhage, teratogenicity (1st trimester), foetal haemorrhage (3rd trimester), drug interactions
Pharmacokinetics
Onset	Initial onset 24 hours. Peak onset is 72 hours (as existing clotting factors not affected by warfarin)
Absorption	100% oral bioavailability
Distribution	99% protein bound, small VD 0.14L/Kg
Metabolism	Complete hepatic metabolism CYP450 hydroxylation Inactive metabolites
Elimination	Renal elimination of metabolites T 12 = 72 hours
Reversal	Vitamin K, FFP, Prothrombinex, cessation+time