ANZCA Primary Exam MARCH/APRIL 2009

MARCH/APRIL 2009


PLease note that this report is prepared to provide candidates and their teachers and supervisors of training with information about the way in which the performance of candidates in the recent examination was assessed by the examiners, so that candidates and teachers may prepare appropriateLy for future examinations. The individuaL reports are not intended to represent modeL answers nor impLy that aLL points mentioned are necessary in order to achieve a pass. ALL trainees are urged to read the questions carefuLLy and answer the question asked. ALL teachers and supervisors of training are encouraged to discuss this report in detaiL with candidates they are preparing for future examinations.



PHARMACOLOGY - WRITTEN SECTION


MULTIPLE CHOICE QUESTIONS:

65% of candidates achieved a pass in this section of the PharmacoLogy Examination.

SHORT ANSWER QUESTIONS:


QUESTION I Explain the concept of Minimal Alveolar Concentration (MAC) and its clinical
utility.
LIST the patient factors which:
a) Increase MAC
b) Decrease MAC
c) Are known to have no effect on MAC

82% of candidates passed this question.

The question was answered weLL by the majority of candidates. Those who did poorLy omitted any description of cLinicaL utiLity or faiLed to List a few factors that affect (or do not affect) MAC. The foLLowing wouLd have achieved a cLear pass:

Minimum ALveoLar Concentration (MAC) is the aLveoLar concentration of an inhaLed anaesthetic that prevents movement in 50% of patients in response to a standardized stimuLus (e.g. surgicaL incision).

It is a measure of reLative potency and is used as a standard for experimentaL studies.
There are other kinds of MAC vaLue such as “MAC awake,“ when 50% of patients open their eyes on
request. MAC vaLues for different agents are approximateLy additive.




(a) Increases MAC:

• hyperthermia
• drugs that increase CNS catechoLamines (such acute amphetamine ingestion) (b) Decreases MAC:
• eLderLy
• pregnancy
• other anaesthetic agents (e.g. opioids, benzodiazepines)
• acute ethanoL ingestion

(c) No change in MAC:

• duration of anaesthesia
• gender

Chronic aLcohoLism either increases MAC or makes no difference, depending on the source consuLted, therefore either statement gained credit. The effect of thyroid dysfunction is simiLarLy controversiaL and was treated the same way.



QUESTION 2 Describe the factors which increase the risk of systemic toxicity with amide local anaesthetic agents.

31% of candidates passed this question.

Questions on LocaL anaesthetic toxicity are frequentLy asked in this examination and this question has been asked previousLy.

The answer shouLd have been structured into pharmacokinetic and pharmacodynamic factors in order to make covering aLL aspects of the question easier. Factors expected incLuded dose, site, vasoconstrictors, reduced protein binding, hepatic function, CVS:CNS ratios, patient factors (acidosis, ion trapping, aLtered seizure threshoLd, Lowered CVS reserve), as weLL as age and pregnancy.

Extra marks were awarded for additionaL detaiL or additionaL factors such as isomers, LocaL
anaesthetic specific features, active metaboLites, and physicochemicaL features.

There was confusion over changes reLated to pH and pKa. Acidosis increases the ionised fraction and the risk of toxicity and ion trapping. Many candidates spent a Lot of time describing LocaL anaesthetic toxicity without reLating it to CVS:CNS ratios and negLected other aspects of the question.

Information pertaining to the generaL nature of ester and amide LocaL anaesthetics, their structures, mechanism of action, the management of LocaL anaesthetic toxicity, and Fick’s Law of diffusion that did not reLate directLy to the question and generaLLy didn’t attract marks.
QUESTION 3 Outline the factors that determine the rate of recovery from non-depolarising neuromuscular block?

38% of candidates passed this question.

Recovery from neuromuscuLar bLock is dependent on the competitive baLance of ACh and nondepoLarising bLocking agent (NDBA) at the ACh receptor. After a singLe boLus of NDBA the offset is as a resuLt of redistribution. OnLy after repeat boLuses or infusion does metaboLism and excretion become significant. This important point was mentioned in onLy one paper. Most mentioned that recovery was sLower after Large doses without further expLanation. There was much confusion as to whether an increased voLume of distribution resuLted in an increased or decreased duration. This is dependent on whether the drug is administered as a singLe boLus.

The pharmacoLogicaL properties of the drugs were generaLLy weLL done as were the Lists of physioLogicaL and drug interactions. Candidates who were abLe to give correct exampLes scored additionaL marks. The use of antichoLinesterase agents and their effectiveness depending of the depth of bLock was seLdom mentioned.



QUESTION 4 Compare and contrast atropine and glycopyrrolate. Discuss the clinical implications of these differences.

68% of candidates passed this question.

The main points expected for a pass incLuded an outLine of how these two antichoLinergic drugs are simiLar and aLso how they differ. Descriptions of their chemicaL, pharmaceutic, pharmacokinetic and pharmacodynamic properties in a tabLe heLped in answering the first question. Once a difference between these agents had been outLined, it was expected that a discussion wouLd ensue as to how that difference couLd infLuence your cLinicaL use of these two aLternative drugs.

The first question was weLL answered in generaL, but the commonest omission was to not answer the second question. When a difference between these agents was correctLy identified, there was no discussion as to how that may affect cLinicaL decision-making. Answering onLy haLf of the question prevents a candidate from scoring highLy.



QUESTION 5 Outline the effects of an opioid injected into the spinal intrathecal space.

39% of candidates passed this question.

Questions on intrathecaL opioids have been asked in previous examinations and candidates seem to struggLe with the concepts invoLved.

The main points expected for a pass incLude:
The fate of the intrathecaL opioid i.e. passage across the meninges to exert its action on spinaL cord opioid receptors, some cephaLad spread in the CSF to supraspinaL centres and minimaL systemic absorption to exert systemic effects.

The main effect is segmentaL anaLgesia, with LittLe motor or sympathetic effects.
Some appreciation that the extent of distribution is determined by Lipid soLubiLity of the agent and that most of the effect of the opioid is due to its action on the spinaL cord.
The major side effects of intrathecaL opioids i.e. pruritis, respiratory depression, nausea and vomiting, urinary retention, incLuding mechanism of action. Other side effects of opioids are negLigibLe.

More detaiL was expected on respiratory depression, given its cLinicaL importance. EarLy respiratory depression is more LikeLy amongst the LipophiLic opioids eg fentanyL. Late depression is more LikeLy with hydrophiLic agents such as morphine as it is bound Less to the spinaL cord and so is carried in
the CSF to respiratory centres in the brain. Points were awarded for mentioning which opioids are commonLy used intrathecaLLy, in what doses and their onset and duration of action.

Bonus marks were aLLocated for:
Statements about the Low dose of intrathecaL as compared to intravenous or epiduraL opioids, showing understanding of the fate of intrathecaL opioids, synergism with LocaL anaesthetics, neurotoxic additives which render certain opioids unsuitabLe for intrathecaL use, deveLopment of toLerance, other Less common side effects.



QUESTION 6 Describe the mechanism of action and pharmacokinetics of phenytoin.


20% of candidates passed this question.

A structured approach was expected addressing both the mechanism of action and pharmacokinetics. Candidates were expected to outLine reLevant mechanisms of action (such as sodium channeL bLockade) and how they reLate to its use as an anticonvuLsant agent. AdditionaL credit was given for discussing other potentiaL mechanisms and other uses such as pain management and antiarrhythmic properties. Phenytoin is a drug that has many uses in intensive care medicine and anaesthesia and an adequate knowLedge of this drug, with its Low therapeutic index is important for safe cLinicaL use.

Phenytoin is iLLustrative of severaL key concepts in pharmacoLogy and mention of these was expected. FaiLure to address these key concepts or provide sufficient detaiL was a common omission. Candidates were expected to discuss that phenytoin is highLy protein bound, changes from first to zero order kinetics with escaLating doses and is metaboLised by the cytochrome p450 enzyme system. Some discussion of the significance of these points was expected and extra credit
was awarded for more detaiLed expLanations, comments on enzyme induction and exampLes of drug interactions that are weLL known and cLinicaLLy reLevant. Candidates were expected to comment on the mode of deLivery and compare oraL and intravenous dosing. It was expected that the need for a Loading dose foLLowed by maintenance dosing wouLd be mentioned and extra credit was given for highLighting the potentiaL hazards of rapid intravenous administration. AdditionaL credit was given for mentioning the importance of a narrow therapeutic index and the need for cLinicaL monitoring. WeLL organized answers such as those with an ordered List of subheadings were rewarded.


QUESTION 7 Outline the subtypes of serotonin (5-hydroxytryptamine) receptors. Discuss pharmacological agents that act at these sites.
45% of candidates passed this question. Main Points expected for a Pass:
• GeneraL description of Location of receptors as found in CentraL nervous system (CNS),
PeripheraL nervous system (PNS), on vascuLar smooth muscLe and pLateLets.
• Statement that 5-HT receptors are G-protein coupLed except for the 5HT3 subtype which is a Ligand-gated ion channeL.
• An attempt at numbering the quantity of subtypes, some texts differ between 4-5 or 7 subtypes.
• CorrectLy describing some agonists at the individuaL subtypes.
• CorrectLy describing some antagonists at the individuaL subtypes.
• IncLuding commonLy used drugs such as ondansetron and correctLy identifying the pharmacoLogicaL action as an antagonist at the 5 HT-3 receptor, aLso TramadoL and its indirect method of action on the receptors as a 5HT uptake inhibitor
AdditionaL Points which attracted higher marks:
• Identifying the numbers of subtypes within the receptor famiLies, for exampLe, 5HT-1 type D
receptors, 5HT-2 A,B and C subtypes
• IndividuaLLy addressing the receptor subtypes, sumatriptan and its use in the treatment of migraine as weLL as the mechanism of action
• Descriptions of MetocLopramide as a 5HT-4 agonist and its pharmacoLogicaL action & site of
5HT-4 receptors
• Mention of 5HT-2 receptors and antagonists, such as ketanserin, methyLsergide, pizotifen or cyproheptadine.
• Extra credit for mentioning Less weLL known agents, for exampLe, knowing LSD is an agonist at the 5HT receptor, as weLL as buspirone or tegaserod.

Common Mistakes:
• IncorrectLy identifying aLL 5HT receptors as G-protein coupLed or misidentifying which sub- type is Ligand-gated
• IncorrectLy stating that drugs are agonists, when they are antagonists and vice-versa
• FaiLing to describe the activity of the drug at the receptor
• Confusing the mode of action and the receptor activity, for exampLe, cLaiming 5HT-1 agonists Like sumatriptan cause cerebraL vasodiLatation when they cause vasoconstriction.


QUESTION 8 What is meant by the term “95% confidence interval”? Explain the practical applications of confidence intervals and indicate why they may be preferred to p-values.

20.5% of candidates passed this question.

A significant number of candidates scored a Low mark.

Most candidates presented a definition of the 95% Confidence IntervaL (95% CI) but faiLed to demonstrate an understanding of the concept. Many candidates presented unnecessary detaiLs of how to design a cLinicaL triaL or conducted muLtipLe comparisons with drug interventions without demonstrating the utiLity of 95% CI. There was significant confusion between standard deviation and standard error of the mean with many candidates using them interchangeabLy without any quaLification.

Any 95% CI gives a 95% probabiLity that the true popuLation parameter wiLL be found within that intervaL. It is a range of vaLues that give a LikeLihood that the popuLation parameter being studied wiLL be found within them. Contrary to what many candidates stated, it does not mean that 95% of observations are contained within 1.96 standard deviation.



95% CI is derived from the Standard Error and hence is dependent on sampLe size.
To attain a pass in this question, candidates needed to present a cLear definition of the 95% CI as a concept, present an understanding of how it is caLcuLated with cLear understanding of the determinants of 95% CI and demonstrate a good understanding of the reLationship and the difference between 95% CI and P vaLue and its advantages over the p vaLue.

Candidates who demonstrated practicaL appLications of CI and/or other forms of CI achieved bonus marks.
PHARMACOLOGY - VIVA SECTION


PHARMACOLOGY TOPICS:


IV Induction agents
Why do you beLieve propofoL is wideLy used as an anaesthetic agent? What are the pharmacodynamics of propofoL?
What is in an ampouLe of thiopentone?
How do you determine an induction dose of propofoL?
Compare the pharmacokinetics of an infusion and a boLus of a drug
Thiopentone as an induction agent

Pharmacokinetics
Changes in drug disposition with age
Iv and IM administration pharmacokinetics
Definition of haLf Life Pharmacokinetic parameters Drug nomograms
TransdermaL medications

Pharmacodynamics
Response to thiopentone
Genetic diseases and thiopentone Anaesthesia and Liver faiLure Modifications of drug dosage

Anti-emetics
What drugs can be used for Post-Operative nausea and vomiting? Compare anti-emetics
Dexamethasone

Inhalational agents
MetaboLism of inhaLed agents
How do you seLect an inhaLationaL agent? Draw a wash in curve for isofLurane
Draw a wash out curve for an agent
Manufacture of nitrous oxide
What are the advantages of sevofLurane? When to avoid nitrous oxide
Fa/Fi curves
How does the addition of nitrous oxide affect inhaLationaL agent uptake? Changes in uptake of voLatiLe agents

Autonomic Nervous System and Adrenoreceptor Blocking drugs
ALpha 2 agonist drugs
What drugs increase bLood pressure? How do you cLassify beta bLockers? What is an inotrope?
Anti-arrhythmic effects of beta bLockers
Effects of cLonidine
Adverse effects of adrenaLine
Statistics
Data types and study Limitations
Box pLots Scatter pLots Regression anaLysis

Neuromuscular Blocking Drugs and reversal Monitoring of neuromuscuLar bLocking drugs CLassification of NMB’s
PharmacoLogy of suxamethonium
ED95 of muscLe reLaxants
What receptors exist at the NMJ? Dose-response curves to NMB’s Receptor reguLation
Margin of safety
Adverse effects of neostigmine

Analgesic agents
Non-opioid anaLgesics COX-2 inhibitors NSAID toxicity
ParacetamoL pharmacokinetics
Parecoxib
Post-operative anaLgesic options Onset time of anaLgesics Ketamine as an anaLgesic Methadone
Pharmacokinetics of fentanyL

Miscellaneous Topics
What drugs reLax the uterus?
How does drug deveLopment occur? ALLergic reactions in anaesthesia ToLerance vs addiction
How do you treat atriaL fibriLLation? PharmacoLogy of amioderone Management of hypertension
CLassification of anti-hypertensive agents
Toxicity of sodium nitroprusside
What drugs work on the rennin-angiotensin system? What is the rationaLe for the use of ACE inhibitors? Management of poisoning
Management of myocardiaL ischaemia
Management of asthma
PrincipLes of antibiotic prophyLaxis
What is the difference between an anti-septic and a disinfectant? How can we change the pH of stomach contents?
What types of heparin do you know of?
What anti-pLateLet agents do you know of? What drugs are used in cardiac arrest?
PHYSIOLOGY - WRITTEN SECTION