2019A
Question 1
Question
Describe the pharmacology of lignocaine.
Example answer
Name | Lidocaine (lignocaine) |
---|---|
Class | Amide anaesthetic / Class 1b antiarrhythmic |
Indications | Local/regional/epidural anaesthesia, ventricular dysrhythmias |
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 |
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 |
Examiner comments
16% of candidates passed this question.
Comprehensive answers included uses (including antiarrhythmic action and a role in analgesia), physical properties and preparations, pharmacodynamics and pharmacokinetics. Its mode of action should also have been described. Many candidates focussed on toxicity and its management but provided little information on pharmacodynamics and pharmacokinetics, commonly omitting factors which affect its systemic absorption. Other common omissions were the dose required for its local anaesthetic effect and for its antiarrhythmic effect
Online resources for this question
Similar questions
Question 17, 2014 (1st sitting)
Question 2, 2021 (2nd sitting)
Question 2
Question
Outline the components required to measure blood pressure from an intra-arterial catheter (75% of marks). What information (other than blood pressure) may be gained from an arterial line trace (25% of marks)?
Example answer
Components
- Intra-arterial catheter
- narrow (generally 18-22G) and relatively short - minimises resonance
- Provides conduit to transmit blood pressure wave to circuit
- Fluid filled tubing
- Permits hydraulic coupling of mechanical signical
- Non compressible fluid filled (usually saline) tubing minimises damping
- Counterpressure bag with flush system
- pressure of~300mmHg - counteracts arterial pressure
- Fluid provides slow continuous infusion to maintain catheter patency (prevent clots etc)
- Can be used for diagnostic/trouble shooting purposes with 'fast flush test'
- An electrical transducer
- Usually a Wheatstone bridge peizoresistive transducer
- Movement of the diaphragm caused by arterial pressure changes leads to stretching/compression of the strain gauges and is converted into an electrical signal
- Placed at phlebostatic axis and requires calibration
- Microprocessor + amplifier
- Processor uses Fourier analysis to break down the waveform into component sine waves which are reconstructed with 8-10 harmonic sine waves
- Amplifies signal
- Cabling
- To transmit the information/electrical signals
- Monitor
- To visualise the information (including pressures and waveform)
- 3 way tap
- Allows sampling of arterial blood for diagnostic purposes
- Allows 'zeroing' to atmosphere for calibration
Information gained
- Heart rate
- Heart rhythm - regular or irregular
- Blood pressures - Systolic pressure, diastolic pressure, mean arterial pressures, pulse pressures
- Pulse pressure variation
- Issues with system - Dampened trace may indicate kinks, bubbles, clots in the circuit
- Cardiac output, stroke volume, stroke volume variation by pulse contour analysis (e.g. FloTrac)
- Waveform may indicate underlying pathology with modest accuracy (e.g. collapsing wave in AS)
Examiner comments
44% of candidates passed this question.
Most of the marks were allocated to the components of the measuring system (as detailed in the question), hence a level of detail was required. An explanation of how the various components work was required; e.g. hydraulic coupling and transducers. Some candidates forgot to include heart rate as a piece of information derived from the trace.
Online resources for this question
Similar questions
- Previous questions on damping/resonance - nil on arterial line setup.
Question 3
Question
Compare and contrast fresh frozen plasma and prothrombin complex concentrate
Example answer
Name | FFP | Prothrombinex |
---|---|---|
Description | Human plasma including all coagulation factors | Human plasma derivative containing a concentrate of specific clotting factors |
Preparation | 1) Separation of whole blood or apheresis 2) Frozen and stored |
1) Separation of whole blood or apheresis 2) Separation of clotting factors II, IX and X via ion exchange chromatography |
Indications | Coagulopathy Plasma exchange |
Warfarin reversal Correction of coagulopathy from factor II, IX or X deficiency |
Pharmaceutics | 250-300ml bags, labelled with donor blood types | Glass vial with powdered concentrate for reconstitution with water. Generally 500U per vial Contains small amount of heparin |
Storage | Stored for 12 months | Stored for 6 months |
Routes of administration | IV | IV |
Dose | 2-4 units (varies) | 25-50 u/kg |
Contraindications | ABO incompatibility | DIC, HITS (contains heparin), liver failure |
Contents/factors | All clotting factors (except fibrinogen) | Contains factors II, IX, X (500 units each) |
Adverse effects | Blood product, with all the risks associated with this (fluid overload, infection, allergic responses) | Allergic or anaphylactic reactions Thrombosis in predisposed individuals |
Pros | Contains all necessary clotting factors Less expensive than PTX |
Does not need group/crossmatch (therefore available for immediate use) Smaller fluid volume |
Cons | Requires ABO grouping Requires time for thawing etc |
Factor 7 absent More expensive than FFP |
Examiner comments
10% of candidates passed this question.
Very few answers included details on prothrombin complex concentrate which meant it was difficult to score well. Useful headings included preparation and administration, dose, indications and adverse effects. Not many candidates knew the dose of FFP, and few were able to describe the preparation/production of the product. Few candidates knew the factors available from either product. Commonly missed was the need for ABO typing for FFP and that Prothrombin complex concentrate did not require this.
Online resources for this question
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Question 4
Question
Outline the functional anatomy of the kidney (40% of marks). Outline the regulation of renal blood flow (60% of marks)
Example answer
Gross anatomy of kidney
- Gross anatomy
- Paired retroperitoneal organ
- Sits at ~ T12-L3 (right lower than left)
- Structure
- Outer fibrous capsule > Outer 'cortex' > Inner 'medulla' > renal pelvis
- Blood supply
- Arterial: renal arteries from abdominal aorta
- Venous: renal veins > IVC
- Innervation
- SNS (T9-13)
Functional anatomy
- The nephron is the basic functional unit of kidney (~1-2 million nephrons per kidney)
- 85% of nephrons are predominately located in cortex (cortical nephrons)
- 15% are juxtamedullary and extend deep into the medulla.
- Nephron structure
- Renal corpuscle (filtration): with glomerulus + bowman's capsule
- Juxtaglomerular apparatus (adjustments to GFR): contains macula densa, JG cells, mesangial cells
- Tubular system (reabsorption/regulation): PCT > LOH > DCT
- Collecting duct system
- Vascular
- Afferent arteriole: blood supply to individual nephron
- Efferent arteriole: carries blood away from individual nephron
Renal blood flow regulation
- Normal RBF = ~20% of CO (~1L / min), predominately distributed to cortex > medulla
- Kidneys are able to autoregulate (maintain constant blood flow) across a wide range of MAP (~70-170mmhg)
- Myogenic regulation
- Intrinsic constriction of afferent arterioles in response to increased transmural pressure of vessel wall (e.g. increased BP)
- Tubuloglomerular feedback
- Regulated by macula densa
- Increased perfusion pressure > Increased Na/Cl sensed by macula densa > adenosine released > constriction > decreased GFR. Vice versa (except NO is released with decreased Na/Cl delivery to vasodilate and increased GFR)
- Neuronal control
- SNS activation > afferent and efferent arteriole constriction > decreased flow
- Hormonal control
- Renin-angiotensin system: Renin released (SNS stimulation, hypotension, decreased Na at JGA) > increased AG1 > increased AG2 > constriction of arterioles > decreased RBF/GFR
Examiner comments
71% of candidates passed this question.
It was expected that answers include sections on the blood supply, the nephron (including the difference between the cortical and juxta-medullary nephrons) and innervation. A number of candidates failed to quantify renal blood flow and to define autoregulation. The concept that it’s the flow that’s regulated was not described by some. Tubuloglomerular feedback was generally described correctly but a reasonable number had the blood flow increasing when an increased sodium was sensed at the macula densa.
Online resources for this question
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- Renal blood flow and autoregulation
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Question 5
Question
Define volume of distribution (15% of marks). Outline the factors affecting volume of distribution (60% of marks) and explain how it may be measured (25% of marks).
Example answer
Volume of distribution
- The theoretical volume in which an amount of drug would distribute to produce an observed plasma concentration
- Note: Does not correspond to any real volume. Can often exceed total body water
Measurement
Assumes that
The drug is evenly distributed (often not the case)
Metabolism and elimination have not taken place (often not the case)
Requires drug dose to be given, then plasma samples to be taken
Semilogarithmic plasma concentration vs time curve plotted.
In a single compartment model, VOD can then be calculated as VOD = dose given / plasma concentration at time 0 (which is back extrapolated on the curve from 1st time point.)
Factors affecting volume of distribution
- Patient factors
- Age: decreasing water content with age = decreased Vd (water soluble drugs)
- TBW: decreases with age = decreased Vd (water soluble drugs)
- Fat %: increased body fat = increased Vd of lipophilic drugs
- Gender: women generally have lower Vd (water soluble drugs) due to lower TBW but higher Vd for fat soluble drugs
- Drug factors
- Molecular size: decreased size = increased Vd
- Lipid solubility: increased lipophilicity = increased Vd
- pKa: basic drug in low pKa = increased Vd
- Protein binding: increased protein binding = decreased Vd
- Charge: ionised molecules > may be traped in central compartment > decreased Vd
- Logistical factors
- Timing of measurement
- Modelling used (e.g. single compartment)
- Pathological factors
- Renal failure/hepatic failure: may lead to low protein = decreased Vd
- Oedema, ascites - reservoir for water soluble drugs
Examiner comments
51% of candidates passed this question.
The first two parts of the question were reasonably done. Most candidates had well-structured answers which included drug factors and patient factors. In addition to listing the factors it was expected candidates state how these factors affect volume of distribution. Explaining how volume of distribution is determined was not so well done.
Online resources for this question
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- Question 12, 2015 (second sitting)
Question 6
Question
Outline the physiology of the adrenal gland (70% of marks). Describe the actions of aldosterone (30% of marks).
Example answer
Adrenal gland
- Paired organs, immediately superior to kidneys
- Broken up into an outer adrenal cortex (80%) and an inner adrenal medulla (20%)
Adrenal cortex
- Three zones of cells
- Zona glomerulosa
- Outermost zone of cortex
- Synthesises mineralocorticoids (e.g. aldosterone)
- Important for regulation of electrolytes (Na, K) and water balance
- Regulated by ACTH from anterior pituitary, angiotensin II and plasma potassium levels
- Zone fasiculata
- Secretes glucocorticoids (e.g. cortisol ~95% of activity)
- Widely important, particularly for metabolism and cardiovascular function (HR, BP etc)
- Regulated by ACTH from the anterior pituitary gland
- Zona reticularis
- Innermost zone of cortex
- Secretes androgen precursors (e.g. DHEA) which get converted into testosterone and oestrogen
- Regulated by ACTH and androgen stimulating hormones
Adrenal medulla
- Innermost portion of the adrenal gland
- Responsible for producing catecholamines (adrenaline, noradrenaline)
- Chromaffin cells (modified neuroendocrine cells) are responsible for storing/synthesising the catecholamines
- Regulated by SNS activity from T5-T11 (thus stress, hypoglycaemia, etc can activate)
Aldosterone
Primary mineralocorticoid hormone from adrenal gland (90% of activity)
Actions of aldosterone
Increases reabsorption of Na in the DCT and CD (principle cells)
Increases secretion of potassium in the DCT and CD (principle cells)
Increased Na reabsorption in sweat glands, salivary glands and GIT
Increases ECF volume (by increased H2O reabsorption by osmosis with the Na)
Increased H+ excretion in DCT (leads to Cl reabsorption and metabolic alkalosis)
Examiner comments
43% of candidates passed this question.
Lack of breadth and detail were in many of the answers. Physiology of the adrenal gland includes an outline of the adrenal medulla, the types of chromaffin cells, hormones secreted and how secretion is stimulated. The three zones of the adrenal cortex should have been outlined including substances secreted, their function and again how their secretion is stimulated. The actions of aldosterone should have been described; a comment on sodium and water excretion was insufficient to attain many marks for this section. The extra-renal actions of aldosterone were missing from most answers.
Online resources for this question
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Question 7
Question
Compare and contrast the pharmacokinetics and pharmacodynamics of midazolam and dexmedetomidine.
Example answer
Name | Midazolam | Dexmedetomidine | Notes |
---|---|---|---|
Class | Benzodiazepine (sedative) | Central alpha agonist (sedative) | Diff. classes |
Indications | Anaesthesia, sedation, treatment of seizures, anxiolysis | Short term sedation and anxiolysis | Dexmed = short term and no anticonvulsant / amnesic properties |
Pharmaceutics | IV: clear solution, pH 3.5. Diluted in water. | Clear colourless isotonic solution. Or white powder for dilution | |
Routes of administration | IV, IM, S/C, intranasal, buccal, PO | IV only in AUS | Midaz has more routes available |
Dose | Dose depends on many pt. factors. 1-5mg premedication. 2.5-10mg seizures. Infusions. | Infusion (though loading boluses can be given) | |
pKa | 6.5 | 7.1 | |
Pharmacodynamics | |||
MOA | Midazolam (BZD) binds to GABAA receptors (ionotropic ligand gated channel) in the CNS. Cl enters > hyperpolarisation. | Selective central a2 agonism (predom. at the locus coeruleus and spinal cord) | Different receptors |
Effects | CNS: sedation, amnesia, anticonvulsant effects, decreased cerebral O2 demand | CNS: Sedation, anxiolysis | No amnesia with dexmed |
Side effects | CVS: bradycardia, hypotension CNS: confusion, restlessness |
CVS: hypotension, bradycardia Other: hyperthermia, confusion, dry mouth |
Bradycardia worse with dexmed. No Resp depression with dexmed. |
Pharmacokinetics | |||
Onset | peak effect 2-3 minutes (IV) | ~30 mins (without bolus) | Midaz = quicker onset |
Absorption | ~40% oral bioavailability Absorbed well, but sig. 1st pass metabolism |
IV only in Aus. Low PO bioavailability | Midaz has greater PO bioavailability |
Distribution | 95% protein bound, very lipid soluble Vd = 1L / kg |
95% protein bound, very lipid soluble Vd = 1.3L/kg |
Similar |
Metabolism | Hepatic metabolism by hydroxylation Active (1-a hydroxymidazolam) and inactive metabolites |
Biotransformation (direct glucuronidation and CYP450 metabolism) > inactive metabolites | Midas has active metabolites |
Elimination | Renal excretion T 1/2 = 4 hours |
Renal excretion (5% stool) t 1/2 = 2 hours |
Similar |
Special points | Flumazenil - antagonist (reversal agent) | Atipamezole = antagonist (reversal agent) |
Examiner comments
27% of candidates passed this question.
Most candidates used the effective tabular format presenting pharmacokinetics and pharmacodynamics of each drug side by side. Many answers demonstrated a lack of correct detail with respect to the pharmacokinetics and pharmacodynamics of these two level 1 drugs. Many included pharmaceutics which attracted no marks as it was not asked.
Online resources for this question
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- Midazolam
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Question 8
Question
Compare and contrast the measurement (40% of marks) and interpretation (60% of marks) of both central venous and mixed venous oxygen saturations.
Example answer
Central venous oxygen saturations (ScvO2)
- The oxygen saturation of haemoglobin at the cavo-atrial junction
- Normally measured using a CVC
- ScvO2 is normally ~70% (slightly lower than SmvO2 in well patients due to higher oxygen extraction from upper body)
- ScvO2 is used as a surrogate for SmvO2 as it is more accessible for most ICU patients as need a CVC not PAC
Mixed venous oxygen saturation (SmvO2)
- The oxygen saturation of haemoglobin when measured in the pulmonary artery (after venous mixing in the right ventricle)
- Measured using a pulmonary artery catheter
- SmvO2 is normally ~75%
- SmvO2 provides better idea of whole body venous O2 sats (blood from SVC, IVC and coronary sinus)
- Can be used to estimate the cardiac output via the modified fick equation
- CO = oxygen consumption / (Oxygen content arterial blood - oxygen content mixed venous blood)
Measurement
- Both can be measured using the same methods
- Intermittent sampling
- ABG: derivation of the SvO2 value from the PO2, pH and pCO2, using the oxygen-haemoglobin dissociation curve.
- Co-oximetry: measures absorption of near-IR light by haemoglobin species, and the use of the Beer-Lambert law to calculate the concentrations of oxyhaemoglobin and deoxyhaemoglobin
- Continuous monitoring
- Using a CVC or PAC with with fibre optic reflectance spectrophotometer
- Near IR light reflectance strength used to determine ratio of Oxy and deoxy Hb
- Intermittent sampling
Interpretation of ScvO2 / SmvO2
- Increased saturation
- Anaesthesia
- Septic shock
- Cyanide toxicity
- High output cardiac failure
- Hypothermia
- Severe liver disease
- Decreased saturation
- Cardiogenic shock
- Septic shock
- Hyperthermia
- Importantly, not sensitive to regional hypoxia/dysoxia
Evidence
- No evidence to support targeting ScvO2 or SmvO2 saturations at present
Examiner comments
8% of candidates passed this question.
Many candidates did not appreciate that ScvO2 refers to SVC / RA junction venous oximetry and not femoral or peripheral venous oximetry. Methods of measurement such as co-oximetry and reflectance spectrophotometry needed to be explained. Marks were awarded for the normal values. Discussion of the relationship between ScvO2 and SmvO2 and changes during shock attracted marks. Better answers quoted the modified Fick equation and related this to cardiac output and factors affecting oxygen consumption versus delivery.
Online resources for this question
- Ohs intensive care (monitoring oxygen chapter)
- CICM Wrecks
- Jennys Jam Jar
- Deranged Physiology
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Question 9
Question
Classify antibiotics with respect to their mechanism of action (50% of marks). Outline the mechanisms of antimicrobial resistance (50% of marks). Give specific examples of each.
Example answer
Classification of antibiotics
- Inhibitors of cell wall synthesis
- Beta-lactams: e.g. flucloxacillin
- Cephalosporins: e.g. ceftriaxone
- Carbapenems: e.g. meropenem
- Monobactams: eg. aztreonam
- Glycopeptides e.g. vancomycin
- Inhibitors of cytoplasmic membrane function
- Polymyxins: e.g. colistin
- Lipopetides e.g daptomycin
- Inhibitors of nucleic acid synthesis
- Quinolones e.g ciprofloxacin
- Rifamycins e.g. rifampicin
- Nitroimidazoles e.g. metronidazole
- Folate metabolism inhibitors
- e.g. trimethoprim
- Inhibitor of protein synthesis
- Aminoglycosides: e.g. gentamycin
- Tetracyclines: doxycycline
- Lincosamides: e.g clindamycin
- Macrolides: e.g. erythromycin
Antimicrobial resistance
- Occurs when the maximal level of drug tolerated in insufficient to inhibit growth
- Broadly occurs via genetic alteration or changes to protein expression
Mechanisms of resistance
- Prevent access to drug target
- Decrease permeability
- E.g. pseudomonas aeruginosa resistance to carbapenems due to reduction in porins
- Active efflux of drug
- Efflux pumps > extrude antibiotics (eg. fluoroquinolone resistance with E.coli)
- Decrease permeability
- Alter antibiotic target site
- Alteration to Peptidoglycan binding site protein, reducing affinity of drug.
- E.g. Vancomycin and VRE (e.g. E. faecium)
- Modification / inactivation of drug
- E.g. ESBL and penicillin's/cephalosporins whereby b-lactamases hydrolyse B-lactam rings
- Modification of metabolic pathways
- Metabolic pathways bypass site of antibiotic action
- E.g. Bactrim resistance (synthesise their own folic acid)
Examiner comments
70% of candidates passed this question.
This question was well answered. Marks were awarded for correct pairing of mechanism of action and resistance with examples of drug class. Few mentioned the mechanisms by which resistance is present; acquired or generated.
Online resources for this question
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- Question 5, 2020 (1st sitting)
Question 10
Question
Outline the sequence of haemostatic events after injury to a blood vessel wall (50% of marks). Discuss the role of naturally occurring anticoagulants in preventing clot formation in-vivo (50% of marks).
Example answer
- Vascular constriction
- Occurs instantly, lasts a few minutes
- Due to
- Local myogenic spasm
- Nervous reflexes
- Release of local vasoconstrictors (e.g. Thromboxane A2)
- Limits the amount of haemorrhage and creates environment suitable for clot formation
Primary haemostasis (platelet plug formation)
Platelet adhesion
Exposed vWF in endothelium binds to glycoprotein receptor complex on platelets
Platelet GP1a binds to subendothelial collagen fibres by vWF bridge
Platelet activation
Activated following exposure to tissue factor, vWF and collagen
Results in them
Changing shape (large, more irregular, pseudopod formation) > assists with clot formation
Release molecules (Thromboxane A2, ADP, serotonin) > vasoconstricts + activates platelets
Platelet aggregation
Activated platelets bind fibringoen, vWF and fibronectin forming a soft platelet plug
Secondary haemostasis (clot formation)
Two main models: classical (in vitro) model and modern cell based (in vivo) model
Cell based model
Initiation
Vessel damage exposes plasma to tissue factor
tissue factor binds to and activates factor VII
TF-Factor VIIa complex activates factor X
Factor X activates prothrombin > thrombin (small amounts)
amplification
This causes local activation of platelets (via vWF), Factor V, Factor VIII and factor XI
This greatly accelerates the production of thrombin around the surface of the platelets
Propagation
Begins with formation of tenase complexes on platelet surfaces (IXa-VIIIa) which greatly increases the rate of Factor X activation
The large amounts of Xa interacts with factor Va forming prothrombinase complex (Va-Xa) which catalyses the conversion of prothrombin to thrombin
Positive feedback loop
Natural anticoagulants --> prevent unnecessary coagulation
- Antithrombin 3
- Inactivates IIa and Xa
- Protein C
- Inactivates Va and VIIa
- Protein S
- Cofactor for upregulating protein C
- Thrombomodulin
- Bound to the endothelial membrane
- Binds thrombin and activates protein C
- Heparan
- Activates AT-3, which in turn inactivates thrombin
Examiner comments
40% of candidates passed this question.
This question was best answered in a chronological manner. Many candidates omitted initial vasoconstriction and its mechanism. The platelet plug and formation of the clot should have then been described followed by the fate of the clot, including in-growth of fibroblasts. Strictly, fibrinolysis is a system for repairing / limiting clot propagation after the fact. Anticoagulants refer to antithrombin III, heparin, thrombomodulin and protein C and S. An explanation of the interaction of these naturally occurring anticoagulants was expected. The clotting factors that are specifically inhibited was expected as part of the discussion. The glycocalyx and vessel wall also plays a role in preventing coagulation.
Online resources for this question
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Question 11
Question
Describe the physiology of cerebrospinal fluid (CSF) (60% of marks). Describe the anatomy relevant to performing a lumbar puncture (40% of marks).
Example answer
CSF
- ECF located in the ventricles and subarachnoid space
- volume: ~2ml/kg
- Divided evenly between the cranium and spinal column
Formation
- Constantly produced (~24mls/hr)
- Produced by choroid plexus (70%) and capillary endothelial cells (30%)
- Produced by a combination of ultrafiltration (via fenestrated choroidal capillaries) and active secretion
Composition relative to plasma
- Similar: Na, osmolality, HCO3
- Increased: Cl, Mg, CO2
- Decreased: pretty much everything else
Circulation
- CSF flows from lateral ventricles > foramen of Monro > 3rd ventricle > Sylvian aqueduct > 4th ventricle > cisterna magna (via foramen megendie and luschka) > spreads between spinal/cranial subarachnoid spaces
Reabsorption
Reabsorption by the arachnoid villi located predominately in the dural walls of the sagittal + sigmoid sinuses (one way valves)
Reabsorbed at ~24mls/hr
Functions
- Mechanical protection: low specific gravity of CSF > decreased effective weight of brain > no contact with skull base + less inertia forces
- Buffering of ICP - CSF can be displaced / reabsorbed to offset increase in ICP
- Stable extracellular environment for neuronal activit
- Control of respiration: pH regulates respiration via central chemoreceptors
- Nutrition: supply of oxygen, sugars, amino acids to supply the brain
Anatomy of LP
- Positioning:
- lateral decubitus or sitting position
- Level:
- L2-5 possible (below conus medullaris)
- L3/4 or L4/5 are recommended (safety).
- Surface landmarks:
- Line between iliac crests (Tuffiers line) = L4/5
- Line between PSISs = L3/4
- Central positioning by spinous processes'
- Angle of needle
- Toward umbilicus (~15 degrees)
- Order of tissues/structures passed through by needle
- Skin
- Subcut tissue
- Supraspinous ligament
- Interspinous ligament
- Ligamentum flavum
- Epidural space
- Dura mater
- Arachnoid mater
- Subarachnoid space = CSF
Examiner comments
86% of candidates passed this question.
Better answers had a structure with headings such as function, formation, circulation, absorption and composition with dot point facts under each heading. The second part of the question lent itself to a diagram with labelling which scored well. Precise surface anatomy and mentioning all layers from the skin to the sub-arachnoid space scored well
Online resources for this question
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Question 12
Question
Compare and contrast the pharmacology of salbutamol and ipratropium bromide.
Example answer
Name | Salbutamol | Ipratropium bromide | Notes |
---|---|---|---|
Class | Short acting B2 agonist (synthetic sympathomimetic amine) | Anticholinergic (quaternary ammonium derivative of atropine) | |
Indications | Bronchoconstriction, hyperkalaemia, tocolytic | Bronchoconstriction | |
Pharmaceutics | Clear solution for neb, solution for IV (post dilution), powder / aerosol for inhalation, PO tablets | Aerosol for inhalation, clear colourless solution for neb | |
Routes of administration | Neb, IV, INH, PO | Neb, INH | Salbutamol can be given IV |
Dose | 2.5mg-5mg PRN (Neb) 200-400mcg PRN (INH) |
Neb: 100-500mcg QID INH: 100-500mcg BD |
Salbutamol given more regularly |
Pharmacodynamics | |||
MOA | B2 agonism > increased cAMP > decreased Ca > bronchial smooth muscle relaxation | Competitive antagonism of muscarinic ACh receptors > bronchodilation + decreased secretions | Can be used synergistically (different MOA) |
Side effects | CNS: anxiety, tremor RESP: reverses HPVC |
RESP: dry mouth, N, V CNS: headache, blurred vision |
|
Pharmacokinetics | |||
Onset/duration | Immediate, fast offset (mins) | Peak effect 1-2 hours, lasts 6 hours | Ipratropium has slow onset, longer duration of effect |
Absorption | 50% bioavailability | 5% inhaled absorbed systemically | Salbutamol can be given PO |
Distribution | VOD: ~150L/kg 10% protein bound |
VOD: 4-5L/kg Very weak protein binding |
Salbutamol crosses placenta |
Metabolism | Metabolised in liver > inactive + active metabolites | Metabolised in liver by CYP450 > inactive | Salbutamol has active metabolites |
Elimination | Metabolites via urine + faecesT 1/2: 4 hours |
Metabolites via urine + faecesElimination half life 3 hours |
Similar |
Special points |
Examiner comments
46% of candidates passed this question.
Overall candidates had a superficial knowledge of these level 1 drugs. To pass candidates needed to identify points of difference and overlap in various areas such as structure, pharmaceutics, pharmacokinetics, pharmacodynamics, mechanism of action, adverse effects and contraindications.
Online resources for this question
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- Bronchodilators more broadly have been asked for in
- Question 4, 2016 (2nd sitting)
- Question 11, 2014 (2nd sitting)
- Question 9, 2010 (1st sitting)
Question 13
Question
Classify circulatory shock and provide examples (40% of marks). Outline the cardiovascular responses (60% of marks).
Example answer
Shock
- Life threatening, generalised maldistribution of blood flow resulting in failure to deliver and/or utilise oxygen, leading to tissue dysoxia.
Classifications
- Hypovolaemic
- Caused by intravascular volume depletion
- Includes haemorrhage, fluid loss (e.g. dehydration) and fluid shifts (e.g. pancreatitis)
- Cardiogenic
- Caused by cardiac pump failure or dysfunction
- Includes: cardiomyopathy, ACS, arrhythmia, valve failure
- Distributive
- Caused by significant peripheral vascular dilation leading to fall in PVR
- Includes: sepsis, inflammation (e.g. post cardiopulmonary bypass), anaphylaxis, neurogenic (e.g. high spinal cord injury)
- Obstructive
- Caused by circulatory obstruction/impedance
- Includes: tamponade, tension pneumothorax, pulmonary embolism
Cardiovascular response to circulatory shock
Stimulus | Sensor | Integrator | Effector |
---|---|---|---|
Hypotension | Baroreceptors | Nucleus of the solitary tract (NTS) | - CNX inhibition (increased HR) - SNS activation (vasoconstriction, redistribution of BV, increased CO) - RAAS activation |
Decreased VO2 | Aortic arch chemoreceptors | NTS | As above |
Decreased circulatory volume | Atrial myocytes | - | Decreased release ANP |
Decreased circulatory volume | Baroreceptors | Hypothalamus | Increased release of vasopressin |
Decreased circulatory volume | Renal JG cells | - | Increased release of renin, RAAS activation |
Inadequate tissue perfusion | vascular SM and endothelium | - | Autoregulatory vasodilation |
Examiner comments
83% of candidates passed this question.
Answers should have included the various types of shock and provided clear examples. Cardiovascular responses including sensor, integrator, effector mechanisms were necessary to pass.
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Question 14
Question
Compare and contrast the mechanism of action, pharmacokinetics and adverse effects of digoxin and sotalol.
Example answer
Name | Digoxin | Sotalol | Notes |
---|---|---|---|
Class | Cardiac glycoside (antiarrhythmic) | B-blocker | Different class |
Indications | tachyarrhythmias (e.g. AF, SVT), heart failure | tachyarrhythmias (e.g. AF, SVT) and ventricular arrhythmias | Sotalol can be used for ventricular arrhythmias |
Pharmaceutics | 62.5mcg/250mcg (PO tablets), 25/250 mcg/ml (IV) | 80+160mg PO tablets. IV in racemix mixture of enantiomers (through SAS). | Digoxin available IV |
Routes of administration | IV and PO | PO, IV (via SAS) | |
Dose | Generally load with 250-500mcg, then 62.5-125mcg daily thereafter | 40-160mg PO BD | No loading for sotalol |
pKA | 7.2 | 9.8 | |
Pharmacodynamics | |||
MOA | Direct cardiac: inhibits Na/K ATPase > increased Ca > positive inotropic effect + increased refractory period Indirect cardiac: increased PSNS release of ACh at M receptors > slowed conduction at AV node/bundle |
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 |
Dig = increased inotropy and short QT Sotalol = decreased inotropy + prolonged QT |
Side effects | CVS: May worsen arrhythmia (lead to VF), AV block, shortened QT interval, scooped ST, TWI, bradycardia GIT: nausea, anorexia, vomiting |
CVS: precipitation of tDP, bradycardia, prolonged QT int, bradycardia, hypotension Resp: bronchospasm |
Dig shortens Qt, sotalol prolongs it. |
Pharmacokinetics | |||
Onset/duration | 2-3 hours (PO), 10-30mins (IV), duration of action 3-4 days | 2-3 hours (PO) | Similar onset |
Absorption | 80% oral bioavailability | 95% oral bioavailability | Both have good OBA |
Distribution | Protein binding 25% VOD 6-7L/kg |
No protein binding VOD 1-2L/kg |
Dig = larger VOD and protein binding |
Metabolism | minimal hepatic metabolism (15%) | Nil | |
Elimination | T 1/2 48 hours urine excretion (70% unchanged) |
T 1/2 12 hours Urine excretion (unchanged) |
Dig lasts longer in system |
Special points | Reduce dose in renal failure, monitor with dig level. not removed by dialysis | Reduce dose in renal failure Requires SAS for IV |
Both require renal adjustment |
Examiner comments
19% of candidates passed this question.
Good answers listed class and the multiple mechanisms of action for both these antiarrhythmics, briefly outlining relevant downstream physiological effects and contrasting effects on inotropy. Knowledge of specific pharmacokinetic parameters of these agents was generally lacking. Clinically relevant adverse effects were frequently omitted (e.g. prolonged QT/Torsades for sotalol, hypokalaemia potentiating toxicity of digoxin).
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Question 15
Question
Describe the physiology of the NMDA (N-Methyl D-aspartate) receptor (40% of marks). Outline the pharmacology of ketamine (60% of marks).
Example answer
NMDA receptor
- Structure
- Tetrameric, ligand gated, transmembrane receptor
- Location
- Abundant in the CNS (brain, spinal cord)
- Ion permeability
- Ca, Na, K
- Activated by
- Glutamate (excitatory neurotransmitter) and glycine
- Activation leads to removal of central Mg plus (Na/Ca in, K out) > EPSP
- Blocked by
- Ketamine, Mg, memantidine
Name | Ketamine |
---|---|
Class | Anaesthetic (phencyclidine derivative) |
Indications | induction GA, conscious sedation, analgesia, |
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), 1-2mg/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. CVS: increased HR/BP, decreased pulmonary and systemic vascular resistance, |
Side effects | CNS: emergence reactions including hallucinations, unpleasant dreams. may increase ICP in non ventilated patients CVS: may increase HR/BP, increased myocardial O2 req. |
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 (5L/kg) VOD. small protein binding (25%). Crosses placenta. |
Metabolism | Metabolised by CYP450 > majority inactive metabolites (norketamine active) |
Elimination | Elimination T1/2 = 2 hours. Kidneys (95%), faeces (5%) |
Special points |
Examiner comments
49% of candidates passed this question.
The NMDA receptor is a ligand gated voltage dependent ion channel located on post synaptic membranes throughout the CNS, with glutamate, an excitatory neurotransmitter, its natural ligand. A brief description of its structure, roles of glycine and magnesium, ions conducted, result of activation, role in memory and learning and agonists/antagonists was expected. Detail on structure and functions of the receptor were a common omission.
Ketamine, a phencyclidine derivative, is a non-competitive antagonist at the NMDA receptor. It is presented as a racemic mixture or as the single S(+) enantiomer (2-3 X potency). Administration routes and doses scored marks. Pharmacodynamics were generally well covered including CVS (direct and indirect effects), CNS (anaesthesia, analgesia, amnesia, delirium, effects on CBF and ICP) respiratory (bronchodilator with preservation of airway reflexes) GIT effects (salivation, N and V). Knowledge of specific pharmacokinetic parameters was less well covered, including low oral bioavailability and protein binding and active metabolite (norketamine).
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Question 4, 2018 (2nd sitting)
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Question 16
Question
Describe the role of carbon dioxide in the control of alveolar ventilation
Example answer
SENSORS
Peripheral chemoreceptors
- Located in the carotid body
- Sense a rise in PaCO2 (as well as a fall in PaO2 or pH)
- Afferent nerve = CN IX
- Located in the aortic body
- Sense a rise in PaCO2 (or fall in PaO2)
- Afferent nerve CN X
Central chemoreceptors
- Located in the ventral medulla near the respiratory centre
- Stimulated by a fall in pH of the CSF
- The most important mediator of the change in pH is PaCO2 which freely diffuses across the blood-brain-barrier and dissociates into H+
- The reduced buffering capacity (HCO3 cannot pass the BBB) make these receptors very sensitive to change in CSF pH
CENTRAL PROCESSOR
- Respiratory centre in the medulla and pons
- Nucleus retroambigualis --> Expiratory muscle control via UMN
- Nucleus parambigualis --> Inspiratory muscle control via UMN
- Nucleus ambigualis --> Pharyngeal/laryngeal muscles via CN 9/10
- pre-Botzinger complex --> respiratory pacemaker
EFFECTORS
- Muscles of respiration (diaphragm, intercostals, accessory muscles etc)
Ventilatory response to CO2 change
- Linear response (increase in PaCO2 = increase in minute ventilation)
- Left shift: metabolic acidosis, hypoxia
- Right shift: sleep, anaesthesia, opiates
Examiner comments
57% of candidates passed this question.
Better answers considered the role of CO2 in the control of alveolar ventilation in terms of sensors, central processing and effectors - with an emphasis on sensors. Features of central and peripheral chemoreceptors should have been described in detail. The PCO2/ventilation response curve is best described using a graph, with key features of the curve identified (including gradient and axes). Various factors affecting the gradient of this curve and how CO2 affects the response to hypoxic drive should be described.
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Question 17
Question
Explain the physiology of neuromuscular transmission
Example answer
Neuromuscular junction (NMJ)
- Synapse between a motor neuron and a muscle cell
- Components
- Terminal bouton of nerve axon
- Synaptic cleft
- Junctional folds
- Motor end plate
- The neurotransmitter of the NMJ is acetylcholine (Ach) which is synthesised in the nerve axoplasm
Neuromuscular transmission
- Action potential depolarised nerve terminal
- Voltage gated calcium channels open & calcium enters
- Calcium influx, triggers synaptic vesicles to release Ach into the synaptic cleft via exocytosis
- ACh diffuses across the synaptic cleft and binds to post-synaptic nicotinic receptors
- Nicotinic ACh receptors (nAChR) are transmembrane ligand gated, ion channel linked receptors
- Activation of nAChR leads to Na influx, which depolarises the cell (excitatory post synaptic potential)
- Muscle contraction occurs via muscle excitation-contraction coupling
- ACh is subsequently metabolised by acetylcholinesterase (into Acetyl CoA and choline) and the NMJ returns to its resting state
Examiner comments
60% of candidates passed this question.
Description of sequential events from axon conduction to detail at the neuromuscular junction was required. Well-constructed answers defined neuromuscular transmission, elucidated the structure of the neuromuscular junction (best done with a detailed diagram), described the central importance of acetylcholine, including synthesis, storage, receptors, and degradation. An ideal answer also described both pre-synaptic (e.g. voltage-gated calcium channels, exocytosis of vesicles) and post-synaptic events (acetylcholine receptors, end plate potentials, and the events that lead to excitation-contraction coupling in skeletal muscle).
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Question 18
Question
Describe the pharmacology of frusemide
Example answer
Name | Furosemide |
---|---|
Class | Loop diuretic |
Indications | Oedema/fluid overload, renal insufficiency, hypertension |
Pharmaceutics | Tablet, clear colourless solution (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) |
Side effects | CVS: hypovolaemia, hypotension Renal/metabolic: Metabolic alkalosis, LOW Na, K, Mg, Cl, Ca, increased Cr |
Pharmacokinetics | |
Onset | 5 mins (IV), 30-60 mins (PO), Effect lasts 6 hours. |
Absorption | Bioavailability varies person-person (40-80%) |
Distribution | Vd = 0.1L/Kg, 95% protein bound (albumin) |
Metabolism | < 50% metabolised renally into active metabolite |
Elimination | Renally cleared (predominately unchanged). T1/2 ~90 mins. |
Special points | Deafness can occur with rapid administration in large doses |
Examiner comments
13% of candidates passed this question.
The majority of answers were well structured, some using tables and others using key headings. In general, for a commonly used drug that is listed in the syllabus as Level 1 of understanding, detailed information was lacking. In particular, mechanism of action, dose threshold and ceiling effect and pharmacokinetics lacked detail and/or accuracy.
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Question 19
Question
Describe the effects of ageing on the respiratory system.
Example answer
Age relate changes | Effects of change |
---|---|
Airway - Increased airway reactivity |
- Increased risk of bronchospasm - Reduced clearance of secretions |
Chest wall - Calcification of costal ligaments |
- Decreased chest wall compliance - Reduced vital capacity |
Respiratory muscles - Decreased muscle mass/strength |
- Decreased FEV1 - Fatigue develops faster |
Lungs - Senile emphysema (hyperinflation) |
- Increased lung compliance - Increased dead space |
Gas exchange -Increased alveolar-capillary membrane thickness |
- Decline in DLCO - Decreased surface area for gas exchange |
Control of ventilation - Decrease in efferent neural output to respiratory muscles |
- Reduction in response to hypoxia and hypercarbia -Decrease in Vt --> increase in RR to maintain MV |
Work of breathing | Overall increased due to the net effect of the above changes |
Examiner comments
5% of candidates passed this question.
Answers should have included the effects of ageing on the efficiency of gas exchange, how the expected PaO2 changes with age, and its causation. Anatomical changes should have been included as should changes in lung volumes, particularly the significance of an increased closing volume. Marks were not awarded for the effects of disease states.
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Question 20
Question
Describe the cardiovascular effects of positive pressure ventilation on a patient who has received a long acting muscle relaxant.
Example answer
Overview
- Normal spontaneous ventilation generates negative intrapleural pressure
- PPV has numerous cardiovascular implications
Effects of PPV
- Left ventricle
- Decreased preload
- Decreased afterload
- Right ventricle
- Decreased preload
- Increased afterload
Mechanism of PPV effects
- Right heart
- Increased intrathoracic pressure (ITP) is transmitted to central veins + right atrium (RA)
- Leads to increased RA pressure > impairs venous return > decreased RV preload
- Leads to increased pulmonary vascular resistance > increased RV afterload
- Increased RV afterload + reduced RV preload > decreased RV stroke volume
- Increased RV afterload leads to increased RV end diastolic pressure
- If RVEDP is greater than LVEDP > bulging of IV septum into LV > ventricular interdependence
- Increased intrathoracic pressure (ITP) is transmitted to central veins + right atrium (RA)
- Left heart
- Decreased preload
- Due to reduced RV stroke volume and ventricular interdependence (explained above)
- Decreased afterload
- PPV > reduction in LV end systolic transmural pressure > decreased afterload (Law of LaPlace)
- Decreased preload
Net effect on cardiac output
- If the patient has normal LV
- Net decrease in CO
- Decreased preload has overall greater impact compared to decreased afterload
- If the patient has impaired LV
- Net increase in CO
- Decrease in afterload has overall greater impact, compared to decreased preload
Examiner comments
33% of candidates passed this question.
Structured answers separating effects of positive pressure on right and left ventricle, on preload and on afterload were expected. Overall there was a lack of depth and many candidates referred to pathological states such as the failing heart. Simply stating that positive pressure ventilation reduced right ventricular venous return and/or left ventricular afterload, without some additional explanation was not sufficient to achieve a pass level.
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