2008 First Sitting

2008A 01: 2 candidates (66%) passed this question. Main points expected for a pass included: Actions and mechanism of actions of paracetamol. These include inhibition of cylooxygenase (COX) activity and prevention of prostaglandin (PG) production. More marks were given for mention of a central COX 1 variant as the possible enzyme responsible for paracetamol’s central versus peripheral effects. Knowledge of the central sites of action was expected. Outline of toxicity. Candidates were expected to demonstrate knowledge of toxic doses, conditions enhancing toxicity (alcohol intake, chronic use etc), and the mechanism of hepatic toxicity and other organ toxicity (especially renal). A detailed list of clinical features of toxicity was not required. Management of toxicity. Candidates performed well in this section with good knowledge of timing, toxic doses, use of paracetamol levels and the nomogram to determine whether N-acetylcysteine should be administered. Mechanism of action of NAC was expected. Mention of monitoring (liver failure) and supportive therapy gained marks, but detailed explanations were not required Syllabus G2e2c Stoelting 4th edition page 285 Rand Dale 5th page 244

2008A 02: 1 candidate (33%) passed this question. Candidates were expected to mention the differences between heparin and enoxaparin and to explain why these differences existed and their implications. For example: heparin Pharmacokinetics - MW3000-30000. Large variability has significant effects on: • mechanism of action (IIa, IXa, Xa) • dosing( 2/3 molecules in dose have no active binding sites) • bioavailability poor,T1/2 short (rapid uptake by PF4/endo cells/macrophages and proteins of high MW components) = poor predictability and dose response both IV and SC, mandates monitoring IV T1/2 1-2 hours: S/C 2-3 daily doses. Continuous IV – advantage is fast offset. enoxaparin - MW3000-5000. Inhibits Xa only. • bioavailability (100%),longer T1/2 no uptake/protein binding • predictable activity and dose response = decreased need for monitoring, reliable SC • No need for IV use T1/2 4-5 hours, 1-2 daily dosing, but no fast offset. Better answers were in tabular format under each heading. Higher marks were awarded for mentioning of monitoring pitfalls such as heparin resistance, measuring Xa levels in a timely fashion, and the efficacy and pitfalls of protamine with each agent. Syallabus J2 2a Reference: Stoelting 505-511 Katzung 546-548

2008A 03: No candidates (0%) passed this question. The main points expected for a pass included a brief description of the following: • The system components • The principles of light absorbance and the Beer-Lambert Law • The differential absorbance of Hb species in red/infrared spectrum, and their use to calculate the amount of reduced and oxygenated Hb present • LED emitting 660/940/off cycles at 450-900Hz, averages data over several cycles to eliminate ambient light, and detect pulsatile and non pulsatile elements • Pulse added absorption of each cycle compared as ratio “R” at different wavelengths • Calibration curve to compare “R” to SaO2 data from healthy volunteers • The limitations of the technique including: - quality of product, bias, precision and accuracy - insensitivity to PaO2 - false readings and their causes Diagrams gained marks only with sufficient labelling and explanation. Syllabus S2f

No candidates (0%) passed this question. The majority of the information required for this question is covered within the general pharmacology section of the syllabus. The main points expected for a pass were: Mention and discussion of pharmacokinetic factors such as drug absorption, volume of distribution, clearance, protein binding, dosing frequency and drug level sampling. Mention and discussion of pharmacodynamic factors such as drug sensitivity, and therapeutic range. Clinical relevance of a drug concentration (e.g. peak or trough level, total or free drug, etc). Candidates often failed to frame their answer to the question that was asked. Candidates could have made a greater use of illustrations and examples of drugs to help answer the question. Among other relevant listed references, candidates should seek information from within the text books - Basic and Clinical Pharmacology by B. G Katzung and Pharmacology by H. P Rang, J. M Ritter and M. M Dale.

2008A 05: 1 candidate (33%) passed this question The main points expected for a pass were: • Description of the relationship of CO2; O2; MAP and Cerebral metabolism with cerebral blood flow. The use of graphs, correctly labelled, and associated free text would be an effective means of portraying this information. • The effect of other factors such as intracranial pressure, cerebral venous pressure, vascular calibre, blood viscosity and regional blood flow differences. Syllabus C1f2c

2008A 06: No candidates (0%) passed this question. The main points expected for a pass were: Range, regional pulmonary differences and gradients of V/Q ratios. Definitions of shunt (V/Q = 0) and dead space (V/Q = ∞). Explanation of why and how V/Q mismatch lowers arterial P a O 2 (majority of pulmonary blood flow being from basal regions, shape of haemoglobin disassociation curve). Explanation of why and how V/Q mismatch lowers arterial P a CO 2 (majority of pulmonary blood flow being from basal regions, predominately linear shape of CO 2 disassociation curve within the physiological range of P a CO 2 values). Again, the use of illustrations would be very useful aids as part of a good answer. Candidates often failed to frame their answer to the question that was asked and deviated to areas not directly sought after by the question. This resulted in wasted time and opportunities for marks. Syllabus B1g Reference Nunn 4th edition page 165-187

2008A 07: 1 candidate (33%) passed this question. The main points expected for a pass were: • The components of plasma calcium are diffusible Ca ( free and complexed ) and nondiffusible Ca (protein bound ). Only the plasma free Ca is physiologically active and regulated by homeostatic mechanisms. Plasma free Ca is also affected by plasma pH and albumin concentration. • The distribution of Ca in the body and the fact that ECF Ca is less than 0.1% of total body Ca. ECF and hence plasma Ca is the result of a balance between dietary intake, gastrointestinal absorption and excretion, renal excretion and exchange with bone Ca. • Tight hormonal regulation of GIT absorption, bone exchange and renal excretion mainly by parathyroid hormone and calcitriol. Also expected were details of the actions of PTH on bone and the kidney and the actions of calcitriol on the gut and bone. No candidates described the feedback control mechanisms involving PTH and calcitriol. Additional marks were given for mention of other hormones that have a lesser effect on plasma Ca concentration. The second part of the question on the mechanism of action of biphosphonates was poorly answered. Syllabus N 2i

2008A 08: 1 candidate (33%) passed this question The main concept required was that the renal excretion of water is basic to the maintenance of constant body water conditions. This renal water excretion is controlled by multiple factors that influence glomerular filtration and tubular reabsorption. Also the kidney has mechanisms that allow it to eliminate excess water by excreting a dilute urine or to conserve water by excreting a concentrated urine. Better answers provided details of the large GFR and the renal tubular handling of water. Also the creation of the hyperosmolar medullary interstitium by the counter current multiplier system, the special characteristics of the Loop of Henle that cause solutes to be trapped in the renal medulla and the resulting delivery of a hypoosmolar tubular fluid to the collecting ducts. Finally the variation in water permeability of the collecting ducts under the influence of ADH. Extra marks were awarded for details on ADH including its origin, secretion, regulation and mechanism of action and the concept of electrolyte free water clearance. Some candidates confused aquaporins with vasopressin receptors. Other candidates produced long and irrelevant descriptions of the renin angiotensin system which gained no extra marks. Syllabus D1 2f

2008A 09: 1 candidate (33%) passed this question. The three main anticonvulsant mechanisms required were: Sodium channel blockers. These promote the inactive state of voltage activated Na channels. Sodium channels are unable to open for a period of time making the neuron more refractory to action potential generation. Rapid repetitive firing is diminished and spread of electrical activity to adjacent brain areas is suppressed. Examples: phenytoin, carbamazepine, lamotrgine, Na valproate Drugs that enhance GABA mediated synaptic inhibition. This increases the influx of chloride ions into the cell and hyperpolarizes the neuron. 3 mechanisms: a. Act on GABA receptor. Example: benzodiazepines, barbiturates. b. Inhibit GABA transporter and reduce neuronal GABA reuptake. Example: tiagabine. c. Promote GABA release. Example: gabapentin. Drugs that inhibit Calcium channels. Limit activation of voltage activated Ca channel known as the T current. Example.: Na valproate Other mechanisms of action with examples if described earned extra marks. These included glutamate /NMDA receptor inhibition. Example: magnesium. Syllabus G2f

2008A 10: 1 candidate (33%) passed this question. The main points candidates were expected to cover included: A discussion of the non-linear relationship between O2 content and partial pressure and the factors which affect this relationship. No candidate included this. Modification of the Fick equation as it relates mixed-venous oxygen to delivery and consumption. The components of delivery should have been described and use of the O2 flux equation would have been helpful. Additional marks were available for describing how these might change in physiological and pathological states. Candidates frequently interchanged content and partial pressure, without clearly displaying how these are related. Normal values were not provided. The O2 flux equation, when included, was often written incorrectly. No consideration was given to normal variations, such as pregnancy or exercise Reference: Nunn 5th edition pages 267 to 269, page 493 Syllabus: B1h Gas transport in the blood 2a

2008A 11: No candidates (0%) passed this question The main points candidates were expected to cover included: • A description of the central and peripheral chemoreceptors, their predominant stimuli and effect on ventilation. • PaCO2 as the main influence on normal ventilation, the near-linear relationship to minute ventilation around the normal range, and how CO2 produces this effect. • PaO2 and pH and their sites of action. • Other stimuli to ventilation – exercise, pregnancy, temperature, baroreceptors. Candidates frequently confused central and peripheral receptor activities and failed to provide any relative significance to the major factor(s). The use of a graph relating the main factors to minute ventilation would have been helpful. Syllabus B1c 1 Reference: Nunn 6th edition 60-68, Kam 1st edition 92-98

2008A 12: No candidates (0%) passed this question. Candidates could use a number of different classifications, however, were required to include all of the major groups of agents. Most made some mention of the sympathomimetics, however failed to sub-classify these, or confused catecols versus non-catecols, or naturally occurring versus synthetic agents. Other agents, such as phosphodiesterase inhibitors, calcium sensitisers, cardiac glycosides, or calcium itself received minimal attention. Mechanisms of action required more than listing adrenergic receptor types. Some listing or discussion of the sub-cellular mechanisms was necessary. Comment about intracellular calcium being the final common end-point would have scored additional marks Syllabus C2d 2 Reference: Stoelting 4th edition 293-320, Katzung 10th edition 121- 198, Rang and Dale 6th edition 168-187 290-291

2008A 13: No candidates (0%) passed this question. It was expected candidates would describe that both these are surrogate measures for Glomerular filtration rate. Credit was given for clear definitions, formula and normal values (such as plasma clearance is the volume of plasma cleared per unit time). It was expected candidates could explain that serum creatinine results from a balance of creatinine produced and excreted and hence the slow response time and limitations for its use because of changes in both production and excretion. Extra credit was given for appreciating the non linear relationship between changes in serum creatinine and creatinine clearance and that significant changes in glomerular filtration can occur before this is reflected in the serum creatinine. Comment on the problems of dilution with acute changes in fluid balance and that tubular secretion of creatinine can occur when the serum creatinine concentration is high both gained extra marks. Syllabus D1 2 Reference Ganong 22nd edition 699-728

2008A 14: No candidates (0%) passed this question. It was expected candidates could define and distinguish between these terms with a specific comment that disinfectants are applied to inanimate objects and antiseptics can be applied to living tissue. The advantages and disadvantages could be addressed either tabulated or discussed in point form, either was acceptable. It was expected answers would include a comment on each agent and specifically address areas such as general spectrum of activity, speed of onset ( agents that need to dry to be effective versus those with more rapid onset), duration of effect ( residual activity), limitations of use and potential hazards. Marks were awarded for identifying Glutaraldehyde as a disinfectant (as opposed to the other antiseptic agents) and its use for cleaning equipment such as endoscopes with the precautions required for potential toxicity. Additional credit was given for discussion of relevant facts such as the proven benefit for chlorhexidine skin preparation for central venous line insertion. Candidates are referred to several of the recommended texts which cover this area well.

2008A 16: No candidates (0%) passed this question. A correct description of the vascular anatomy; the contribution and composition of hepatic artery and portal vein flow to total hepatic flow and how this is regulated would be awarded with a pass. An answer that expanded on these main points received additional marks. The interdependence of hepatic artery and portal vein flow was not appreciated by any candidate. Either candidates knew the answer to this question or they did not. Some candidate(s) tried to guess at what the anatomy might be. This attracted no marks. Many candidates lacked sufficient knowledge to pass this question. Syllabus I 2 d&g

2008A 17: No candidates (0%) passed this question. The main points candidates were expected to cover included a brief definition of renal clearance followed by a description of the drug factors that affect this (filtration, secretion and reabsorption), recognition that GFR and protein binding was important in the answer. A brief description of gentamicin kinetics that affect dosing regimens and a statement that dosing would be guided by calculated GFR and measured drug levels wold round out a good answer. Correct elaboration of the above factors were rewarded with additional marks. Candidates failing this question submitted answers where concepts were randomly mentioned with no attempt to integrate these into a cohesive answer that demonstrated an understanding of the topic. Writing random words without examples or explanations did not demonstrate sufficient understanding to be rewarded with marks. Again, many answers lacked sufficient detail in the answer. Syllabus - Pharmacokinetics

2008A 18: 1 candidate (33%) passed this question. The main points candidates were expected to mention were the major drug groups (antacids, H2 antagonists, proton pump blockers), describe their mechanism of action; briefly mention relevant pharmacokinetics and then briefly discuss the potential problems and interactions when using them. Additional credit was given for answers providing more detail. Many answers did not mention antacids or prostaglandin analogues, choosing only to discuss H2 receptor blockers and proton pump blockers. Even then, many answers included incorrect pharmacokinetic data. Drug interactions were rarely mentioned. A discussion of normal gastric acid secretion was not asked for and was not rewarded with marks. Syllabus Q2a

2008A 19: 1 candidate (33%) passed this question. This question required description of the SA node, its primary role and generation of the pacemaker potential and the influence of the autonomic nervous system. A diagram of the conducting pathways, highlighting specialized tissues with fast or slow conduction velocities would have been appropriate. The importance of the AV node in preventing retrograde conduction and high rates conducted to the ventricles (>220 / min) was often neglected in answers. A discussion of the Purkinje Fibres with particular reference to the absolute and relative refractory periods was essential. Additional marks were awarded for mention of the atrial internodal pathways, conduction within the ventricles from the endocardial to epicardial surfaces and the significance of the compensatory pause in response to ectopic beats. Syllabus C1b 2.a, b; Reference: Cardiovascular Physiology, “Electrical Activity of the Heart” (Chapter 2), Berne and Levy.

2008A 21: 1 candidate (33%) passed this question. The main points candidates were expected to cover included a detailed discussion of the ABO antigens, the evolution of IgM antibodies to these antigens and the prevalence of blood groups in the general population. Answers tabulating blood groups against expected antigens and antibodies present as well as agglutination reactions to anti-sera were most effective. Discussion of the saline agglutination test was essential and extra marks were awarded for mention of the Coombs test. Candidates were required to demonstrate an understanding of cross-matching, specifically the testing of donor red blood cells against recipient serum. Syllabus J1 2.a References: Review of Medical Physiology (Chapter 27), 22nd ed. Ganong, pp. 537-539.

2008A 22: No candidates (0%) passed this question. The main points candidates were expected to know included the passive and active mechanisms that regulate the transfer of drugs across placenta and the potential clinical implications of drugs use in pregnancy in order to pass this question. Good answers to this question included examples to all the possible mechanisms that can affect the transport of drugs across placenta. The common omissions were degree of ionisation, active transporters, placental metabolism, explanation on the interaction between protein binding and ionisation of a drug in regulating placenta transfer, and the expected molecular size or weight of a drug that affects passive placental transfer of the drug.

2008A 23: 2 candidates (66%) passed this question. Candidates were expected to know the different hormonal responses to hypovolaemia The possible approach to this question can be either by explaining the hormonal response in terms of time sequence or by different hormonal systems. Good answers to this question included how different hormonal responses are activated and mediated. The common omissions were secretion of erythropoietin within 24 hours of haemorrhage, role of macula densa and juxtaglomercular apparatus, interactions between baroreceptors and sympathetic nervous system with the secretion of ADH, cortisol, glucagon and catecholamines. Syllabus: C1g 2b Reference: Kam 1st edition 156, 212, Guyton 11th edition 342,287-280

2008A 24: 2 candidates (66%) passed this question. Candidates were expected to draw and label a diagram showing the relationship between pressure and volume during the different phases of the left ventricular contraction and relaxation (or systole and diastole) Good answers to this question consisted of a well-labelled graph with appropriate scale on both x and y-axes showing all the important events during systole and diastole of the left ventricle. The common omissions were rapid and slow ejection phase during systole, when aortic valve closes, stroke volume, ejection fraction, end-systolic pressure volume line showing the contractility of the left ventricle. Some candidates appeared to have confusion about which line shows contractility and which line shows left ventricular after load. Syllabus C1c Reference: Kam 1st edition 115-121, Guyton 11th edition 110 VIVAs A. Pharmaceutics B. Pharmacokinetics C. Pharmacodynamics D. Variability in Drug Response E. Cellular Physiology F. Respiratory G. CVS You are considering starting a patient on captopril. Discuss the pharmacology of this drug. Name this molecule? How can we make this molecule biologically active? - Phenylethylamine - precursor of catecholamines Identify features on diagram of fetal circulation What equipment do you require to measure cardiac output via thermodilution techniques? H. Renal ABG - Metabolic alkalosis with resp compensation - Renal physiology I. Body Fluids and Electrolytes Outline the distribution of total body water J. Acid Base K. Neuro Describe the physiology of pain with respect to its mediators and pathways. L. Musculoskeletal M. ANS N. Liver O. GIT P. Nutrition and Metabolism Q. Haematology R. Thermoregulation S. Immunology T. Microbiology How are bacteria classified? U. Endocrine V. Obstetrics W. Measurement and Monitoring X. Procedures