Examiner’s Report on SAQs – Pharmacology – November 2013

General Comments
75 candidates sat for the written pharmacology examination in October 2013. 46 candidates
(61.3%) passed the written section and were called to the viva voce in November 2013. The
pass rate for the SAQ was 68% indicating that more candidates would have been called to the
viva voce if the MCQ pass rate had been better.

Of the 46 candidates that came for the viva voce in November 2013, 89% passed the
pharmacology portion of the Part I exam. This indicates that candidates who passed showed
better preparation of the topic, which translated into a pass in both the written and oral
sections.

Given below are some remarks made by the examiners, which should help candidates in their
preparation for the next examination.
Question 1
a) Explain zero and first order kinetics by using examples. (6 marks)
b) Discuss the pharmacokinetics of drugs administered via the rectal route.
(4 marks)

51% of the candidates passed this question. Most candidates could give the definition of zero
order and first order kinetics. First order kinetics is also called linear kinetics but a few
candidates thought that linear kinetics is zero order kinetics. Zero order kinetics is also
known as saturation kinetics and that the process will proceed to first order when substrate
level drops. Marks were awarded for graphs with correctly labelled axis. Examples of both
were mostly given correctly. A few good answers had both concentration-time curve and a
log concentration-time curve for first order kinetics as well as mentioning the exponential
relationship C = Coe-kt.

For rectal administration of drugs, good answers include Fick’s principle of diffusion and
further mentioning that surface area for drug absorption is low for rectal mucosa. Other
factors decreasing absorption include presence of faecal material, metabolism by intestinal
flora and diarrhoea. Advantages: when no intravenous access is available, in unconscious
patients, in patients who are fasting and causes less nausea and vomiting. Bioavailability is
variable (less than oral) and therefore, higher concentration and larger doses are required; 2X
- 10X; 50% bypass the liver, depending on where it is inserted: proximal rectum is drained by
superior haemorrhoidal vein (via inferior mesenteric vein) which eventually drains into portal
vein and distal rectum is drained by inferior haemorrhoidal vein which is a systemic vein.
Examples of drugs that can be administered rectally are barbiturates, diazepam, ketamine,
midazolam, paracetamol and diclofenac.
Question 2

This question consisted of three parts:

a) Describe the mechanism of action of propofol (2 marks)

b) How is it eliminated? (2 marks)
c) Discuss its suitability for total intravenous anaesthesia) (6 marks)

Only 66% of the candidates passed this question. As propofol is the intravenous agent of
choice in our practice, it was expected that more candidates would score in this question. The
first two sections (a & b) needed factual knowledge, while the third section needed the
application of knowledge of the pharmacokinetic and pharmacodynamic properties of
propofol that makes it a suitable agent for its use in total intravenous anaesthesia. (TIVA)

a) Most candidates were able to describe the mechanism of action of propofol, which is
activation of the β sub unit of the GABA A receptor of the neurons of the CNS – via the
Chloride channel and passed this section. A mention of the regulatory role of the glycine
receptors would have obtained full marks in this section.

b) Propofol is metabolized in the liver to glucouronides and excreted in the urine. There is
significant extra hepatic metabolism mainly in the lung. Less than 1% is excreted unchanged
in the urine.

c) The properties of propofol that makes it a suitable agent for TIVA include the following:
The metabolites of propofol are not active.
High clearance rates from the plasma because of both hepatic and extra-hepatic
metabolism
The availability of pharmacokinetic models such as the Marsh / Schneider models
which can be used with sophisticated computerized pumps to provide effect / plasma
site concentration of the drug accurately (Target controlled infusion); – so an
overdose and subsequently longer wake up time can be avoided.
The use of BIS monitoring can increase the chances of keeping the patient asleep
while maintaining the lowest dose needed to prevent awareness, while ensuring rapid
awakening.
 The context sensitive half time (CSHT) of propofol does not go up too much even
after several hours of infusion unlike that of fentanyl – thus making is suitable for
TIVA. (Marks were awarded for a diagram showing the CSHT)

There were several good answers.

Common errors among those who did not pass the question included concentrating only on
the clinical aspects of TIVA such as indications for TIVA, providing details of how the
computerized pump should be set up, pain on injection and how that be avoided. This was at
the expense of not answering the question asked; I.e. the pharmacological principles behind
the suitability of propofol for TIVA. (This was a pharmacology paper!)
Several candidates quoted the distribution half life of propofol which is short, but failed to
realize that this rapid offset is for the bolus administration of propofol and not for TIVA
when a steady infusion is needed.

Pharmacological principles of drugs are learnt so that it can be applied in a clinical setting.
Candidates are also advised to read questions carefully and only answer to the point– as
marks were not given for these clinical considerations when the other reasons for discussion
as noted about were not given.
Question 3

Discuss the mechanisms responsible for the side-effects of NSAIDs

Around 85% candidates passed this question. The good pass percentage was expected as
NSAIDs are commonly used analgesics in the operating theatre.

Candidates were expected to draw the prostaglandin synthesis pathway with the respective
enzymes to understand the mechanisms of COX inhibition. Surprisingly, not many candidates
classified NSAIDs into traditional (non-selective) COX-1 and COX-2 inhibitors and COX-2
specific inhibitors. Only some candidates provided examples for both type of NSAIDs.

The major side-effects required to be discussed were the gastrointestinal disturbances, platelet
function and bleeding risks, impairment of renal function, bronchospasm and vascular risk
(MI and stroke) particularly with the COX-2 inhibitors.

The effects of NSAIDs on renal function were not clearly understood. Its effects on the
glomerular filtration rate (GFR), in particular in patients with hypovolaemia was not
mentioned by most candidates. Vascular risks (MI and strokes), associated with long term use
of NSAIDs and Coxibs were also not well covered.
Question 4

a) Classify anti Arrhythmic drugs according to their mode of action and give examples.
(5 marks)
b) Discuss the effect of Amiodarone. (5 marks)

68% of students passed this question. Most of those who did well used the Singh Vaughan-
Williams Classification to answer the question. Those who discussed the mode of action with
correct examples obtained good marks. Extra marks were given to those who mentioned the
miscellaneous drugs not included in this classification such as digoxin.

Some candidates used the types of arrhythmias, such as SVT and VT, to name the drugs. This
was also acceptable, however with this approach there is a distinct possibility of missing
certain group of drugs, especially the drugs in Class 1.
Students who discussed the side effects of Amiodorone, systematically according to affected
organs, obtained good marks. The expected side effects that needed to be mentioned are its
effects on the cardiovascular, pulmonary, hepatic systems; its effect on the eye, thyroid, skin
and possible drug interactions.
Question 5 (Statistics)

a) What do you understand by sensitivity, specificity, Positive Predictive Value (PPV) and
Negative Predictive Value (NPV) of a test? (6 marks)

b) How can the sensitivity and specificity of two diagnostic tests be compared? (4 marks)

A total of 72 (96%) candidates attempted this question out of 75 candidates taking the
pharmacology SAQ paper. 3 candidates did not attempt it at all, hence had 0 marks for this
question.

Only 35 candidates (42.67%) passed. Most of the candidates in this group who passed were
able to give the correct definition and formulae for sensitivity, specificity, positive predictive
value (PPV) and negative predictive value (NPV). The 2x2 table labelled with disease/
investigation was quite well drawn. This shows that their basic knowledge for the foundation
of diagnostic and screening tests in statistics is fairly sound. By answering part a) of this
question itself, these candidates had already gained their passing mark.

However, 43 candidates (57.33%) failed to obtain a pass mark. The candidates in this group
were not able to define or provide the formulae. Some of them had totally wrong definitions
or formulae. For example, PPV was answered with the total positive result as the nominator
instead of understanding it correctly as the denominator. Additionally if from the start, one
definition/ formula was wrong; it cascaded into all the others. This implies that either they
were confused with the entire concept under the duress of exam or they had not grasped the
foundation at all.

None of the candidates answered part b) well. Not one candidate drew the Receiver-operating
curve (ROC) to illustrate the correlation between sensitivity and specificity. They were some
attempts to compare in words how a test can be more sensitive or more specific for screening
or diagnostic purposes respectively. A few also mentioned and gave the formula to describe
how prevalence affects specificity. The mere mention or some form of discussion was
awarded with marks for their effort.

Overall, the pass for this question was poor, indicating that the foundation of basic statistics
is not strong.
Question 6:

List agents that can reduce bronchomotor tone and explain their mechanisms of action.
(10 marks)

This question was answered well by most of the students in which 84% passed this question.
This question was a straightforward pharmacology question, to test student’s knowledge of
drugs which reduce bronchomotor tone.

Candidates were required to list and then explain the mechanism of action of only drugs that
have been used to reduce bronchomotor tone. It was not required to list drugs that are used
to treat bronchial asthma or treat bronchospasm.

Selective β2 agonists e.g. salbutamol, phosphodiesterase inhibitors e.g. aminophylline and

anticholinergic e.g. ipratropium bromide are on top of the list. The question required that the
mechanism of actions of these drugs be discussed in detail.

Other drugs e.g. ketamine, volatile agents, Mg SO4 should also be included along with their
mechanisms of action. Many candidates included steroids in their answer. Steroids do not
cause bronchodilatation, it may reduce the inflammatory effect but do not have any direct
action on the smooth muscle of the bronchial tree. Similarly, montelucast (leucotriene
receptor antagonist- LTRA) and other mast cells stabilizers do not have any direct action on
bronchomotor tone.

It was interesting to note that one candidate included suxamethonium as an agent used to
reduce bronchomotor tone!
 CONJOINT PRIMARY EXAMINATION

DOCTOR OF ANAESTHESIOLOGY & CRITICAL CARE, UNIVERSITI KEBANGSAAN MALAYSIA

MASTERS OF ANAESTHESIOLOGY, UNIVERSITI MALAYA
M.MED (ANAESTHESIOLOGY), UNIVERSITI SAINS MALAYSIA
M.MED (ANAESTHESIOLOGY), UNIVERSITI PUTRA MALAYSIA

APRIL 2014

EXAMINERS’ REPORT

PHARMACOLOGY
SHORT ANSWER QUESTIONS
General Comments

110 candidates sat for the written pharmacology examination in April 2014 held in UKM;
the first conjoint examination among 4 universities consisting of UKM, UM, USM and UPM.
52 candidates (47.3%) passed the written section and will be called for the viva voce in
May 2014.

50 candidates passed the MCQs with a pass rate of 45.5% while 45 candidates passed the
SAQs with a pass rate of 40.9%. Overall, only 36 candidates (32.7%) passed both the MCQs
and SAQs.

Given below are some remarks made by the examiners, which can be used as a guide for
fellow lecturers/future examiners and especially to help guide candidates in their
preparation for the next examination.

2
Question 1:

Outline why ketamine may be more useful as a perioperative analgesic than as an agent for
general anaesthesia. (10 marks)

In general, candidates did fairly well and understood the pharmacology of Ketamine BUT only a
handful answered precisely to what was asked. Answers in general were not organized and the
points were haphazardly arranged. Many wrote about its mechanism of action and pharmacokinetic
parameters over several pages which was not the key to getting more marks. A number of
candidates wrote on the many demerits of Ketamine as a general anaesthetic agent i.e. non-ideal
characteristics of an intravenous induction agent in relative to other agents, which were also off-
track. For example, many mentioned that Ketamine has a slower onset of action; no end-point
towards loss of consciousness; has a prolonged context sensitive half-time which makes it
unsuitable for use in Total Intravenous Anaesthesia (TIVA/TCI), all of which clearly comparing it to
other intravenous anaesthetic agents and not comparing the two indications in question.

Requirements for this question revolves around characteristics of Ketamine over the two uses:
Points against its use as an anaesthetic agent.
Points for its use as an analgesic agent.

Points against Ketamine when used at anaesthetic doses involve issues surrounding its side-effects
which include hallucinations and emergence delirium; increased sympathetic tone, but direct
myocardial depressant effects; increased cerebral blood flow and potential increase in intracranial
pressure; increased intraocular pressure; increased salivation and respiratory secretions.

Points supporting its usefulness at analgesic doses include acknowledging that it provides intense
analgesia with a single perioperative dose lasting up to 48 hours and effectively at a much lower
dose than anaesthesia; active metabolite norketamine providing supplemental analgesic property
(30% potency of parent compound); acts as NMDA receptor antagonist in the brain and spinal cord
which modulates pain information; some activity on opioid receptors; known to be beneficial in
combination with opioids (opioid-sparing effect); prevent hyperalgesia and progression to chronic
pain; less respiratory depression due to lower effective doses used.
Overall, 61.8% of the candidates passed this question. 12 candidates had marks of more than 7.As
this was a question on Ketamine which is one of the commonly asked intravenous induction agents,
it was expected that the passing rate would be higher.
3
Question 2:

Compare and contrast the pharmacokinetics of dexmedetomidine and midazolam. (4 marks)

Out line the clinical applications and side effects of both drugs. (6 marks)

22 out of 110 candidates (20%) failed this question. This good passing rate of 80% was expected
considering that midazolam is frequently used and dexmedetomidine is increasingly popular in the
intensive care units. The average mark was 5.5 / 10 , with only 2 candidates scoring 8.25.

The pharmacokinetics part was generally well answered for midazolam but not for
dexmedetomidine. A few candidates were unsure of the mechanism of action of dexmedetomidine;
wrongly stating it as an α1 agonist, α2 antagonist or a β1 agonist. Most knew the action of midazolam
on the GABA receptor. However, a few wrongly stated it to be a barbiturate, or acting on the NMDA
receptor.

The pharmacokinetic aspects of midazolam should have been better answered. Common errors
were that metabolites of midazolam were inactive; midazolam was not highly protein bound and
dexmedetomidine was metabolised by plasma esterases. Many did not even know its elimination
half life.

While many knew that dexmedetomidine is used as a sedative agent in the intensive care setting,
few highlighted its superiority over midazolam in terms of not being a respiratory depressant; not
predisposing to delirium; having an analgesic component and that patients are calmer and able to
be extubated even with an ongoing infusion. A few candidates wrongly stated that it is a useful
induction agent. Although the clinical uses of midazolam were generally well answered, many
incorrectly stated that it causes retrograde instead of anterograde amnesia.

Hypotension and bradycardia are well known side effects of dexmedetomidine but not many
emphasized that it should not bolused, and it should be used with caution in certain states such as
bradyarrhythmias and shock. A few even suggested that giving a bolus dose will allow steady state
to be achieved faster!

Midazolam side effects were generally confined to being a respiratory depressant and causing
apnoea at high doses. Not many included its potential to cause delirium, paradoxical agitation,
tolerance and withdrawal.

In summary, this was a rather straightforward question, asking for factual comparative
pharmacokinetic knowledge and clinical aspects of both drugs.

4
Question 3:

a) Describe the physicochemical properties and side effects of Halothane which makes it
non-ideal as an inhalational agent. (7 marks)

b) Briefly describe the second gas effect. (3marks)

51.8% of the candidates passed this question. Although halothane is no longer used in Malaysia, it is
still an inhalational agent that is elaborated on in current anaesthesia textbooks and frequently
described in comparative pharmacology with the current inhalational agents used. Candidates
should understand the ideal properties of volatile inhalational agents and apply these facts as to
why halothane has been phased out. Candidates who could apply these concepts, scored better in
this question.

The first part of this question requires candidates to list down the physicochemical properties and
the side effects of halothane that renders it non-ideal as an inhalational agent. Many candidates did
not answer well in the physicochemical properties of halothane, such as the instability of halothane
to light and the corrosiveness of it to metal. Majority of the candidates just listed the side effects of
halothane as a drug, without correlating and discussing why halothane is non-ideal as an
inhalational agent.

Candidates who gave good answers listed down the physicochemical properties and gave further
explanation with regards to reasons why Halothane is not an ideal inhalational agent. For example,
merely stating that the blood gas partition coefficient of halothane is 2.4 is not enough. The
candidates are expected to explain that this will lead to slow onset/offset of action with halothane.
Good answers explained the side effects of halothane according to the pharmacodynamic effects
according to CNS, CVS, Respiratory, GIT, Musculoskeletal system and etc. Poor answers
unnecessarily elaborated on the criteria of an “ideal” inhalational agent.

The second part of the question requires the candidates to define the second gas effect, explain its
underlying mechanism of action and the clinical use of the second gas effect. Many candidates were
confused on the concept of second gas and first gas. Candidates also did not explain that the
mechanisms of second gas effect are due to a direct result of concentration effect by the rapid
uptake of nitrous oxide and augmented alveolar ventilation. Some of the candidates drew diagrams
for the mechanism of second gas effect, without proper explanation. The clinical use of second gas
effect (to reduce induction time) was also not stated by many candidates.
5
Question 4:

Compare and contrast the cardiovascular effects of noradrenaline, dobutamine and

milrinone. (10 marks)

A hundred and ten candidates sat for this paper. However 3 candidates did not even attempt to
answer the question. Overall, 54.6% candidates passed the question.

Most candidates did not compare and contrast the 3 drugs. Putting the 3 drugs in table form did not
necessarily mean that comparisons were made, especially when only symbols of ↑ / ↓ / ± / + / -
were used without any explanation or discussion. Most candidates ended up wrote short notes on
individual drugs.

The knowledge on each of these drugs was very shallow like as if the candidates had never seen or
used the drugs before. Examples of incorrect facts were: noradrenaline can cause significant
tachycardia; dobutamine causes vasoconstriction and milrinone increases systemic vascular
resistance.

Majority had poor knowledge on milrinone. Candidates either did not attempt to write anything on
it or facts given were wrong and contradicting. Similarly, mechanism of action on noradrenaline
and dobutamine were poorly explained; wrong receptors quoted and most facts were contradicting
and unrelated to one another. For example, concepts of contractility – cardiac output/stroke
volume/blood pressure/heart rate were individually commented and were not compared among
the 3 drugs.

Candidates did mention on vasoconstriction and vasodilation but did not comment or relate it to
systemic vascular resistance and very few commented on pulmonary vasculature effects. Terms for
example vasopressor, inotrope and inodilator were not used. Standard abbreviations for CVS terms
i.e. systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), cardiac
output/cardiac index (CO/CI), were incorrectly used.

Overall, sadly, the question was not well answered by majority of the candidates.

6
Question 5:

Classify the drugs commonly used for aspiration prophylaxis. Elaborate on their
mechanisms of action and adverse effects. (10 marks)

40.9% of the candidates passed this question.

The classes of commonly used drugs are

1. Gastrointestinal stimulant/prokinetic agent e.g. metoclopramide

2. Gastric acid secretion inhibitor e.g. ranitidine
3. Non-particulate antacid e.g. sodium citrate

The key to answering this question well is to emphasize on commonly used drugs instead of
writing down almost every single drug in gastrointestinal pharmacology.

Candidates are advised to think back on the common drugs used in their anaesthetic practice as
asked in the question and advised to use only generic names of drugs instead of trade names. Better
candidates answered to the point and were able to ‘zero in’ on the common drugs used. Marks were
awarded for the following points:

Metoclopramide as a dopamine (D2) antagonist.

Actions – as a prokinetic agent (increases gastric emptying/gastric motility);

increases lower esophageal sphincter (LES) tone; coordinates gastric-pyloric-small intestinal motor
function; augments acetylcholine release and sensitises the muscarinic receptors along the gastro-
intestinal tract; exerts an anti-emetic effect by inhibiting D2 receptors in the chemoreceptor trigger
zone at higher doses of 25 – 50 mg.

Side-effects include various extrapyramidal effects e.g. dystonia, oculogyric crisis; rarely
precipitating neuroleptic malignant syndrome.

Some candidates contradicted their points by writing decreases LES tone and increasing gastric
transit time. Some even wrote about metoclopramide reducing gastric acidity. Erythromycin is used
as a prokinetic agent and not for acid aspiration prophylaxis.

Ranitidine

Actions – specific and competitive histamine (H2) receptor antagonist at gastric parietal cells;
reduction of both acidity (H+) and volume of gastric acid; no effects on gastric emptying time or
lower esophageal sphincter tone.

Side-effects include cardiac arrhythmias with rapid administration; need for a reduced dose in
renal impairment and to be avoided in porphyria. Rarely may cause thrombocytopenia, leucopenia,
anaphylaxis and liver dysfunction.

7
Many candidates wrote on cimetidine which is very rarely used in anaesthetic practice nowadays
due to its many side-effects compared to ranitidine. Marks were not awarded for points pertaining
to cimetidine.

Sodium Citrate

Non-particulate antacid, neutralizes gastric acidity with limited duration of action; usually given
less than 10 minutes before induction of anaesthesia. Effective duration is variable and dependent
on gastric content and gastric emptying time. Side-effects are minimal except for the taste and
nausea related to it.

Many candidates included mist magnesium trisilicate despite mentioning that it is a particulate
antacid, hardly ideal to be used for aspiration prophylaxis! Some have the misconception that
antacids will form a gastric mucosal barrier, wrongly quoting the mechanism of action of sucralfate.
Marks were not awarded for inclusion of other drugs used for prophylaxis against peptic ulceration
e.g. proton pump inhibitors, anti-muscarinic agents, prostaglandin analogues, sucralfate and
bismuth. Marks were also not awarded for inclusion of all the anti-emetic drugs like H1-blockers,
phenothiazines, butyrophenones, anticholinergics, 5-HT3 inhibitors, dexamethasone and
anaesthetic agents like propofol, midazolam and suxamethonium.

8
Question 6:

Outline the potential advantages and disadvantages of perioperative beta-blockade.

(10 marks)

Surprisingly, this question was generally not well answered by the majority of candidates
considering how frequently beta blockers are used perioperatively. One of the possible reasons
could be due to poor time allocation to this question being the last on the list. This is evident by the
lack of structure to the answers and sometimes illegible handwriting. Most candidates answered
this question in a very clinical Final Exam format with very little pharmacology details as required
in a Primary Exam.

Even though it is not compulsory to write a brief introduction nor classification, marks were given
for this effort. Some candidates described the pharmacokinetics of beta blockers at length without
highlighting their advantages and disadvantages.No marks were given for this.

Important marks were given for mentioning the anti-hypertensive and anti-arrhythmic properties
of beta blockers together with their mechanisms of action. Improvement of myocardial oxygen
balance leading to a lower incidence of ischaemia should also be mentioned. The mechanisms such
as reduced myocardial oxygen demand because of reduced workload and increased diastolic filling
time to allow better myocardial oxygen supply were expected. Bonus marks were given for
mentioning reduced long term mortality in patients at risk of coronary artery disease and the anti-
hyperthyroidism effects. Sadly, very few candidates managed this part in a comprehensive manner.

Candidates could perform better in the second half of the question. Majority of candidates
mentioned bronchospasm, bradycardia and hypotension which may be resistant to vasopressors.
Brief mention of the side-effects in metabolism and masking effects of hypoglycaemia and
inadequate anaesthesia were also given marks.

Overall, the passing rate for this question was only 39.1%.

Compiled by:
Dr. Nurlia Yahya
Chief Internal Examiner for Pharmacology
UKM

25 April 2014
9
 CONJOINT MASTERS OF ANAESTHESIOLOGY EXAMINATIONS
DOCTOR OF ANAESTHESIOLOGY & CRITICAL CARE (UKM) Dr.Anaesth & CritCare
MASTER OF ANAESTHESIOLOGY (UM) M.Anaes
MASTER OF MEDICINE (USM) M.Med (Anaes)
MASTER OF MEDICINE (UPM) M.Med (Anaes)
SAQ - 28th Oct 2014
The number of candidates that sat for pharmacology paper for this exam were sixty one. Fifty
four of them also sat for physiology paper.

There were six SAQ questions.

EXAMINERS’ REPORT PHARMACOLOGY SAQ

Question 1

a) Outline, with examples the physicochemical factors affecting drug distribution. (6 marks)
b) Discuss the distribution of drugs across the blood brain barrier. (4 marks)

This question was generally well answered by the candidates with 75% pass. The highest and
lowest mark scored was 7.5 / 10 and 3/10 respectively.

Generally the physicochemical factors affecting drug distribution were well covered with good
examples given. A few candidates included the Fick’s Law of Diffusion and drug formulation
as factors affecting distribution in the body, which did not earn them any marks. Of course
regional blood flow do play a role in drug distribution but since the question only requires
physicochemical properties, no mark was given.

Part b was less well answered. Very few mentioned active transport and facilitated diffusion as
prominent methods of molecule transfer, though many recognized the significance of a
disrupted blood brain barrier (BBB) on drug transfer. No candidate answered cerebral blood
flow being the limiting factor for transfer of lipid soluble drugs. Similiarly, for hydrophilic drugs,
increasing the dose may improve transport across the BBB was not mentioned. A few implied
that mannitol requires a disrupted BBB for it to exert its effects.
Question 2

Describe the effects of inhalational agents on the central nervous system (10 marks).

Only 19.7% of candidates passed this question even though a core pharmacology drug that is
used daily has been asked.

Most candidates misinterpreted the question and spent a lot of time describing the wash-in and
wash-out curves without obtaining marks for their efforts. Answers were also one to two pages
long with minimal points. This could only be explained by a general lack of understanding in
such an important topic and the expectation asked in this question.

Marks were allocated for mention of maintenance in anaesthesia and any of its postulated
mechanisms as the introduction. Important points included changes in CMRO2, cerebral blood
flow, autoregulation, cerebral protection and its possible mechanisms including pre- or post-
ischaemic conditioning. The effects on the intracranial pressure, CSF production or
reabsorption, EEG changes, seizure threshold or activity are also facts that are typically
mentioned in any anaesthetic textbooks under the effects of volatile agents in the central
nervous system. Marks were also given to any others mentioned such as central respiratory
centre depression, reduced central sympathetic outflow, evoked potentials, possible cognitive
dysfunction, analgesic effect by nitrous oxide, nausea and vomiting.

Candidates really need to re-evaluate their understanding and source of material for their
pharmacology subject. They are expected to know such a fundamental knowledge in depth
since dispensing inhalational anesthetic is the mainstay of our daily practice.

Question 3

(a) How are drugs metabolized in the liver and what factors influence it? (5 marks)

(b) Outline the effects of liver failure on the pharmacokinetics of drugs. (5 marks)

61% of candidates passed this question.

For section (a), candidates were required to state the Phase I and Phase II reactions with
appropriate examples. Among the factors which may affect the hepatic metabolism of drugs
include: genetic polymorphism, age, hepatic function (including hepatic failure, activity of
hepatic metabolizing enzymes and changes in hepatic blood flow), protein binding and
environmental factors such as smoking and alcohol consumption. Additional marks were
awarded for relevant and correct examples. The metabolic reactions were generally well-
answered, but the majority of candidates repeated word for word of textbook descriptions
without demonstrating their understanding in answering the question. There were a few
surprisingly weak candidates who failed to even mention this basic concept of Phase I and
Phase II reactions.

Candidates who spent unnecessary time elaborating on kinetic orders in drug metabolism and
elimination as well as functional anatomy of liver were not relevant to the question and
therefore not awarded any marks. Some were also confused about the importance of hepatic
enzyme induction and enzyme inhibition stating wrong examples.

For section (b), candidates were required to explain the effects of hepatic failure on
pharmacokinetics of drugs which involves:

i) Absorption

ii) Volume of distribution in terms of protein binding and how it is affected by increased total
body water

iii) The extent of hepatic first pass metabolism and its effect on bioavailability

iv) Clearance of drugs by its reduced metabolic effect that will prolong the half life of drugs

v) Others including plasma cholinesterase and renal excretion of free drug.

Additional marks were given to suitable examples used to illustrate the facts mentioned.

A lot of answers included pharmacodynamic changes such as potentiation of anaesthetic drugs

in hepatic encephalopathy. These were not given any marks. Some facts were given without
further explanation or followed by a wrong one especially for changes in protein binding and
volume of distribution. Inappropriate examples to support their answers were also frequently
given. Dose requirements of lipid soluble drugs such as propofol and thiopentone were thought
to be increased following the changes in volume of distribution by a few candidates. This
concept has to be clarified as such a dose adjustment may possibly affect the clinical outcome
adversely. The general significance of hepatic first pass metabolism was not well understood by
some candidates. It was mentioned that due to hepatic failure, hepatic first pass metabolism
was reduced and subsequently clinical effects of drugs were attenuated since hepatic first pass
metabolism was thought to increase the drugs bioavailability. This fact was not substantiated
by any valid examples.
Question 4

a) Briefly describe the pharmacodynamic interactions between two drugs when administered
together? (3 marks)

b) Explain the drug interactions affecting neuromuscular blocking agents. (7 marks)

Only around 40% of candidates passed this question.

In part a, the candidates were expected to very briefly explain the pharmacodynamics
relationship between two drugs ie additive, synergistic, potentiation and antagonism. Examples
for each will be rewarded with additional marks and only a few candidates drew and labeled
isobologram correctly. Most of the candidates did badly in this section.

In part b, the candidates should list common drugs that known to have interactions with
depolarizing or non-depolarising muscle relaxants (DMRs, NDMRs) pharmacodynamically.
Surprisingly, many candidates were not able to write a complete list of these drugs. Most of
them listed the drugs without proper explanation for the mechanisms responsible for the
interactions. Very few mentioned the relationship between NDMRs-NDMRs and NDMRs –
DMRs. Most common agents mentioned were the inhalationals, Mg, lithium, neostigmine, LAs,
antibiotic and Ca channel blocker. Other interactions that would garnered marks were
antiarrhythmic(quinidine), sugammadex, frusemide and benzodiazepines.
Question 5

a) Describe the mechanisms of action and side effects of heparin. (5 marks)

b) Briefly explain how protamine reverses heparin and list its side effects. Draw a log-dose
response curve of heparin with the presence of protamine. (5 marks)

27 candidates out of 61 (44%) pass this question.

Candidates were expected to describe the interaction between heparin and antithrombin III (AT
III) and the subsequent effects from this interaction. In addition, the effects of heparin on
various activated clotting factors such as IXa, Xa, XIa and XIIa should be included in the answer.
Inhibition of platelet aggregation by a higher concentration of heparin was also expected from
the candidates. The interaction between heparin and AT III was not well understood by some
candidates, as it was thought that such interaction would inhibit the AT III. In some answers,
interaction between these two was mentioned but there was no discussion on further
consequences from this interaction. Some candidates unnecessarily wrote on coagulation
pathway which was not required in the question. Majority of the candidates have correctly
mentioned haemorrhage and thrombocytopaenia as side effects of heparin. Brief discussion on
mechanism of HIT was awarded additional marks. Beside these, other side effects of heparin
include hypotension, osteoporosis, alopecia and hyperkalaemia secondary to action on
aldosterone.

In part b, candidates were expected to mention protamine being a highly basic cationic
structure can act as a reversal agent to heparin by combining with acidic molecule of heparin to
form inactive stable salt solution. Most of the candidates did not mention the dose required (1
mg to 100 i.u) to reverse the effect of heparin probably because of lack of exposure to this
drug. Side effects of protamine may include hypotension, allergic reaction and bleeding. Only
small number mentioned pulmonary hypertension as its side effect. The relationship between
protamine and heparin is described as a non-competitive, irreversible antagonism, thus the log-
dose response curve depicting this relationship will be rewarded full mark.
Question 6

Write short notes on :

a) Oxycodone
b) Parecoxib

This question had a 68% passing rate with the highest mark of 6.5/10 and the lowest mark of
2/10.

In general, the candidates only know Oxycodone superficially. Common misconceptions include
it being a prodrug, partial µ agonist, an aqueous form of Morphine and used only in chronic
pain settings. The pharmacokinetics and mechanism of action of Oxycodone was poorly
answered, not many mentioned slow release preparation of the drug and its advantages over
Morphine.

The question on Parecoxib was generally better answered. Almost all candidates knew it is a
prodrug to Valdecoxib, formulation, dosing and pharmacokinetics. However, few candidates
included its selectivity ratio correctly. While the general side effects of NSAIDs is well
recognized, very few mentioned the skin hypersensitivity reactions that may occur like Steven
Johnson Syndrome.
 EXAMINATION REPORT

CONJOINT PRIMARY EXAMINATION

APRIL 2015

Master of Anaesthesiology (UM)

Doctor of Anaesthesiology and Critical Care (UKM)
Master of Medicine (Anaesthesiology) USM
Master of Medicine (Anaesthesiology) UPM
Master of Medicine (Anaesthesiology) IIUM
 
           
        PHARMACOLOGY  
 
________________________________________________________________________    
 
WRITTEN  SECTION    
________________________________________________________________________    
 
MULTIPLE  CHOICE  QUESTIONS:    

31.9% of candidates achieved a pass in this section of the Examination.

 
 
SHORT  ANSWER  QUESTIONS:  
   
1.   (a)   Outline  the  mechanism  of  spontaneous  recovery  from  neuromuscular      
    blockade  following  the  administration  of  rocuronium.  (1  mark)  
(b)   Which  classes  of  drugs  can  be  used  to  antagonise  the  action  of      
    rocuronium  and  briefly  describe  their  mechanism  of  actions.    (4  marks)  
  (c)   What  are  the  advantages  and  disadvantages  of  these  antagonist  drugs.    
    (5  marks)        

1
  
 
  87%  of  the  candidates  passed  this  question  
 
  This   question   was   generally   well   answered   by   the   candidates   with   87%   pass.   The  
  highest  and  lowest  marks  scored  were  8.0/10  and  3.0/10  respectively.  
 
 
For  Part  (a),  the  candidate  spent  unnecessary  time  describing  rocuronium  and  its  action  
at  the  neuromuscular  junction  which  did  not  carry  any  mark.  Ironically,  the  candidates  
spent  less  time  outlining  the  mechanism  of  spontaneous  recovery  from  neuromuscular  
blockade,  which  was  actually  what  the  examiners  were  looking  for.  Fortunate  for  them,  
this  part  (a)  only  carried  1  mark.  
 
Part   (b)   was   better   answered,   in   particular   on   anticholinesterase   with   neostigmine   as  
example,   its   action   in   inhibiting   acetylcholinesterase   at   the   neuromuscular   junction,  
formation  of  intermediate  compound  (carbamylated  enzyme  complex)  and  the  resulting  
increase   in   acetylcholine   at   neuromuscular   junction.   Most   candidates   answered  
sufficiently  well  on  this  part  but  there  were  quite  a  number  of  candidates  who  wasted  
unnecessary  time  elaborating  on  organo-­‐phosphates  and  some  other  irrelevant  agents.  
Most   candidates   were   also   able   to   answer   selective   relaxant   binding   agent,  
sugammadex   well,   mentioning   its   role   in   encapsulating   or   chelating   lipophilic   steroidal  
NMBs   such   as   rocuronium   (and   vecuronium).   Many   candidates   also   described   the  
structure,   hollow   circular   molecule   composed   of   8   oligosaccharides.   Only   1   candidate  
mentioned  the  role  of  Van  der  Waal  forces  and  covalent  bonding  that  binds  the  complex  
together.  
 
In   part   (c),   the   candidates   were   expected   to   write   on   the   advantages   and   disadvantages  
of  these  2  groups  of  antagonists.    Most  candidates  answered  this  part  well,  mentioning  
the   cholinergic   side   effects   in   usage   of   anticholinesterses,   the   need   of   adding  
anticholinergics,   usage   of   antagonists   in   renal   failures,   ability   and   inabilty   to   reverse  
deep   block,   reversal   action   on   specific   group   of   relaxants,   comparing   cost   and   easy  
availability  of  these  reversal  agents  and  many  other  notable  side  effects.  Majority  of  the  
candidates  got  good  marks  discussing  the  above  points  in  this  section.    
   
 
 
2.   (a)   How  does  the  kidney  excrete  drugs?  (7  marks)  
  (b)    How  might  chronic  renal  failure  affect  drug  handling  (3  marks)  
 
  18%  of  the  candidates  passed  this  question  
 
Section   (a):  The   main   points   candidates   were   expected   to  cover   included  the  interaction  
of  three  processes  of  renal  exretion  (filtration,  secretion  and  reabsorption)  and  followed  
by   description   of   factors   that   affect   this.   Most   of   candidates   were   able   to   recognize   that  
rate   of   filtration   is   governed   by   GFR,   and   filtration   of   drugs   are   influenced   by   size   (MW<  
60,000   Daltons),   electrical   charges   (positively   charged   molecules.>   neutral   molecules   >  
negatively  charged)  and  also  amount  of  protein  binding.  

2
 The  other  two  processes  were  often  mentioned  but  not  elaborated  well.  Many  answers  
did  not  mention  tubular  secretion  is  most  effective  mechanism  for  drug  elimination  as  
transport   is   against   electrochemical   gradient.   They   also   often   forgot   the   following  
points:   rate   is   governed   by   renal   blood   flow,   is   energy   dependent   process   and   carrier-­‐
mediated  for  acidic  drugs  and  basic  drugs.    
Most   candidates   were   able   to   mention   passive   tubular   reabsorption   process   but   only  
half   were   able   to   discuss   the   changes   in   urinary   pH   will   affect   the   amount   of   passive  
reabsorption  by  altering  the  degree  of  ionization  as  many  drugs  are  weak  acids  or  bases.    
Candidates   failing   this   question   submitted   answers   where   concepts   were   randomly  
mentioned   and   did   not   demonstrate   sufficient   understanding   of   this   important   basic  
pharmacology  topic.  
 
Section  (b)  In  general,  this  part  of  question  was  not  well  answered  by  candidates.  They  
were   expected   to   mention   the   pharmacokinetics   parameters   in   patients   with   chronic  
renal   failure   that   may   influence   drugs   handling   such   as   hypoalbuminameia,   increased  
volume   of   distribution,   failure   to   excrete   drug   or   toxic   metabolites   and   reduced   renal  
drug   metabolism.   Marks   are   also   given   if   candidates   mentioned   the   need   to   increase  
loading  dose  and  adjustment  of  maintenance  dose  such  as  dose  reduction  or  increased  
iinterval.    
 
 
 
3. (a)     What  is  a  drug  interaction  and  how  common  is  it?  (1  mark)        
(b)     How   can   drug   interactions   be   classified   and   give   examples   from  
  perioperative  practice  for  each  interaction.    (8  marks)        
(c)     How   would   you   investigate   whether   the   effects   of   propofol   and  
  remifentanil  infused  together  simply  additive  or  synergistic?   (1  mark)    
 
19.8  %  of  candidates  passed  this  question.  
 
 
For   section   (a),   candidates   were   required   to   define   drug   interaction.   In   order   to   have  
drug   interaction,   drugs   usually   have   to   be   administered   concurrently   and   because   of  
this,   drug   effects   were   modified   or   altered.   Many   candidates   have   ignored   the   point  
that  drug  interaction  caused  a  change  in  drug  effects.  It  was  estimated  that  1  in  6  drug  
charts  contain  a  significant  drug  interaction.  
 
For  section  (b),  candidates  were  required  to  classify  the  drug  interactions  into  headings  
like   physicochemical   (precipitation,   adsorption,   chelation   and   neutralization),  
pharmacokinetic   (absorption,   distribution,   metabolism   &   excretion)   and  
pharmacodynamic   (summation,   synergism,   potentiation   &   antagonism)   with  
explanation  of  the  interaction  and  appropriate  examples.  Some  of  the  candidates  have  
shown   confusion   over   drug   interaction   and   drug   action   by   quoting   the   interaction  
between  a  drug  and  a  particular  drug  receptor  in  the  answer  for  this  section.  Too  much  
time   was   spent   by   some   to   discuss   drug   antagonism   through   a   classification   of   drug  
antagonism  followed  by  a  lengthy  and  detailed  explanation  on  each  type  of  antagonism.  
Quite   a   number   of   candidates   have   put   in   a   lot   of   efforts   in   elaborating  
pharmacodynamic   drug   interactions   without   any   discussion   on   physicochemical   and  
pharmacokinetic   drug   interactions.   A   few   of   the   candidates   have   included   drug  

3
 reactions   in   their   answer   (e.g.   idiosyncrasy,   anaphylaxis)   in   which   no   marks   were  
awarded.  
 
For   section   (c),   candidates   were   expected   to   mention   isobologram   as   a   means   to  
investigate   the   drug   interaction   between   propofol   and   remifentanil.   This   should   be  
followed   by   a   simple   elaboration   to   explain   the   reason   why   these   drugs   interact  
synergistically.   There   were   candidates   who   could   not   reproduce   the   isobologram  
correctly   and   quite   a   number   of   candidates   failed   to   mention   isobologram   in   their  
answer.   Candidates   were   not   expected   to   produce   a   detailed   explanation   of   the  
methodology  used  to  investigate  the  interaction  of  these  drugs.  Short  notes  on  propofol  
and  remifentanil  were  not  expected  in  this  section.  
 
 
   
4.     20mls   of   0.5%   bupivacaine   is   inadvertently   administered   intravenously   over   15  
  seconds  to  a  60  year  old,  60kg  woman.    
  (a)   Describe  the  potential  complications  and  mechanisms  of  these.  (6marks)  
  (b)   Briefly  outline  the  acute  management  of  the  potential    complications.    
    (4  marks)  
 
  38.8%  of  the  candidates  passed  this  question  
   
In   part   (a)   the   question   asks   for   the   potential   complications   which   are   cardiovascular  
and  CNS  toxicity.  Most  of  the  candidates  were  able  to  describe  the  signs  and  symptoms  
of   CNS   and   CVS   toxicity.   However,   many   did   not   give   accurate   accounts   of   the  
mechanisms   of   the   toxicity.   Candidates   were   required   to   mention   the   correct   CC/CNS  
ratio   for   bupivacaine   with   an   explanation   of   the   significance   of   this   ratio,   the   potency  
and   blockade   of   Na   channels   ‘fast-­‐in-­‐slow-­‐out’   effects   of   bupivacaine.   There   were  
confusion  between  the  maximum  safe  dosing  and  toxic  doses.  Common  errors  included  
providing   large   amount   of   irrelevant   information   on   the   clinical   indications   of   LA,   LA  
allergy  and  tissue  toxicity,  metabolism  and  excretion  of    LA.    
 
In  part  (b)  the  management  of  severe  LA  toxicity  were  poorly  answered.    
In  the  immediate  management,  most  candidates  realized  the  importance  of  maintaining  
the  airway  and,  if  necessary,  secure  it  with  a  tracheal  tube  and  to  give  100%  oxygen  and  
ensure   adequate   lung   ventilation.   However,   the   importance   of   calling   for   help   and  
stopping  the  LA  injection,  and  control  of  seizures  were  omitted  by  many.  Only  a  minority  
of   the   candidates   wrote   about   the   treatment   of   circulatory   arrest   with   CPR   and  
treatment  of  arrhythmias  which  can  be  refractory.    Most  of  the  candidates  mentioned  
the  use  of  intralipid  emulsion  but  the  dosage  were  often  stated  incorrectly.  
 
Reference:  AAGBI  Safety  Guideline.  Management  of  Severe  Local  Anaesthetic  Toxicity  
 
 
 
5.   (a)   Describe  the  structure  activity  relationship  of  desflurane.    (4  marks)  
  (b)   Discuss  the  adverse  effects  that  may  occur  with  the  administration      
    of  desflurane.    (6  marks)  
 

4
   34%  of  the  candidates  passed  this  question.  
 
In  general,  unexpectedly  this  question  was  poorly  answered.    
 
Section  (a):  In  the  first  section  many  did  not  understand  the  concept  of  structure-­‐activity  
relationship.  To  obtain  a  pass  in  this  section,  candidates  should  be  able  to  describe  and  
discuss   the   chemical   structure   of   desflurane   in   comparison   to   the   other   halogenated  
ether  e.g.  isoflurane.  
 
The  candidates  are  expected  to  discuss  these  differences  in  relation  to  the:  
1)  Saturated  vapour  pressure  and  its  implication  
2)  Blood  gas  solubility  and  its  implication  
3)  Its  stability  and  potency  
 
Section  (b):  Many  candidates  approached  this  section  in  a  disorganized  manner.  Better  
answers   include   a   discussion   on   the   adverse   effects   by   systems   and   those   effects  
peculiar  to  desflurane.    
The  following  adverse  effects  needed  to  be  covered  for  a  clear  pass.  Weightage  is  given  
to  the  more  important  systems:    
 
CVS    
Desflurane   reduces   systemic   vascular   resistance   and   thus   mean   arterial   pressure   in   a  
dose  dependent  manner,  however  cardiac  output  is  usually  compensated  by  an  increase  
in  heart  rate.  
Sudden   increases   in   the   inspired   concentration   of   desflurane   can   cause   a   marked  
sympathetic   response   with   tachycardia,   hypertension   and   activation   of   the   renin-­‐
angiotensin  system.    
 
RS:    
There   is   a   dose-­‐dependent   reduction   in   tidal   volume   and   increase   in   respiratory   rate  
(overall  decrease  minute  ventilation)    
Desflurane  is  pungent  and  can  cause  coughing  and  breathe  holding  so  it  is  infrequently  
used  for  inhalational  induction.  
It  can  increase  airways  resistance  (especially  in  smokers).  

CNS:  
Cerebral   blood   flow   increases   above   1.0   MAC   but   the   rise   in   intracranial   pressure   is  
quite  small  (about  7mmHg).    
At  higher  doses  there  is  uncoupling  of  oxygen  supply  and  demand.    
 
GIT    
It   can   cause   a   fulminant   antibody-­‐mediated   hepatitis   (like   halothane)   through  
neoantigen  formation  from  metabolites,  but  this  is  very  rare   –  probably  due  to  the  very  
low  rate  of  metabolism.  
 
Others  
It  reduces  uterine  tone  (potentially  worsening  postpartum  haemorrhage).  
It  is  a  trigger  for  malignant  hyperthermia.  
It   can   interact   with   carbon   dioxide   absorbents   to   produce   toxic   levels   of   carbon  

5
 monoxide   (especially   with   high   temperatures   and   low   flows   over   desiccated   Baralyme  
®).    
 
   
 
6.       Write  short  notes  on  the  following:  
 
            a)  Ephedrine  (5  marks)  
           b)  Ondansetron  (5marks)  
 
  25.6%  of  the  candidates  passed  this  question  
 
  Most   of   the   candidates   lack   “in-­‐depth   knowledge”   of   both   drugs   which   are   used  
 commonly  in  our  anaesthectic  practice.  
 
  (a)  Ephedrine  :  
  Some   candidates   were   unsure   if   the   drug   was   a   catecholamine   or   not.   None   of   the  
candidates   mentioned   about   its   isomers.   Many   identified   it   as   an   inotrope   rather   than   a  
vasopressor.     Surprisingly   few   stated   that   it   has   both   direct   and   indirect   action.   Some  
candidates   were   unclear   of   the   definition   of   indirect   action   saying   that   it   was   a   β-­‐
receptor   effect.   None   mentioned   its   action   on   β3   receptors   found   on   adipose   tissues.  
Many   however,   understood   the   concept   of   tachyphylaxis   associated   with   its   use.   Few  
wrongly  mentioned  that  it  causes  reflex  bradycardia.  
 
  Only  a  few  knew  that  it  has  good  oral  bioavailability,  is  frequently  used  in  combination  
with   antihistamines   as   a   nasal   decongestant   and   that   it   may   be   administered  
intranasally.   Many   assumed   100%   bioavailability   stating   that   the   drug   could   only   be  
administered  intravenously.  Many  did  not  include  the  fact  that  it  is  not  metabolised  by  
MAO   or   COMT   and   therefore   has   a   longer   duration   of   action.   A   few   inaccurately  
included  Neuroleptic  Malignant  Syndrome  as  a  result  of  interaction  between  ephedrine  
and  other  drugs.    
 
  Candidates  could  have  done  better  in  stating  its  clinical  uses,  where  quite  a  number  of  
candidates   did   not   mention   any   uses   at   all,   especially   highlighting   its   use   in   post  
subarachnoid  block  hypotension.  Special  mention  about  it  causing  a  less  favourable  fetal  
blood   gas   profile   compared   to   pure   α   agonists   like   phenylephrine   would   have   earned  
them  more  marks.  Quite  a  number  of  candidates  inaccurately  identified  ephedrine  as  an  
emergency   drug   used   during   resuscitation.   Few   acknowledged   its   antiemetic   and  
bronchodilating  effect  and  its  important  in  drug  interactions  with  MAOI  drugs.  
 
  (b)  Ondansetron  :  
  Some   candidates   were   sadly   confused,   writing   all   about   omeprazole   instead   and   quite   a  
few  inaccurately  mentioned  that  ondansetron  was  used  to  treat  gastritis  and  had  effects  
on  gastric  motility.  While  many  rightly  identified  it  as  a  5-­‐HT3  antagonist,  quite  a  number  
of  candidates  wrongly  stated  that  it  acts  on  either  H2,   cholinergic  or  anti  dopaminergic  
receptors  instead.  
 
  Many   merely   mentioned   metabolism   in   the   liver   and   excretion   in   the   urine   without  
further   elaboration   which   would   be   expected   at   postgraduate   level.     Only   a   few  

6
 mentioned   that   it   does   not   cause   extrapyramidal   symptoms   which   is   one   of   its   clear  
advantages  –  in  fact  a  few  mentioned  that  it    causes  involuntary  movements.  Not  many  
understood   that   while   it   is   useful   for   PONV   and   chemotherapy/radiation   induced  
emesis,   it   is   not   effective   in   motion   sickness.   Its   side   effects,   dose   and   dosing   interval  
however  were  well  answered.  
 
 
 
   
 
 
 
 
This  Examination  Report  is  prepared  by  the  Primary  Conjoint  Pharmacology  Examiners:  
 
Professor  Dato’  Dr.  Wang  Chew  Yin  (Chief  Examiner)  
Professor  Nik  Abdullah  Nik  Mohamad  
Professor  Ramani  Vijayan  
Prof.  Madya    Mohd  Basri  Mat  Nor  
Dr.  Nurlia  bt  Yahya  
Dr.  Ina  Ismiarti  bt  Shariffuddin  
Dr.  Azarinah  Izaham  
Dr.  Wan  Rahiza  Wan  Mat  
Dr.  Nikman  Ahmad  
Dr.  Noor  Airini  Ibrahim  
Dr.  T.C  Lim  
Dr.  Imran  bin  Osman  
 
 
 
 
 
 
 
 

7
PHARMACOLOGY EXAMINATION REPORT NOVEMBER
2015

General Comments
87 candidates sat for the written pharmacology examination in October
2015 held in University Malaya. 46 candidates (52.9%) passed the
written section and were called to the viva voce in November 2015. Of
the 46 candidates that came for the viva voce, 38 candidates (82.6%)
passed the pharmacology portion of the Part I exam.

Given below are some remarks made by the examiners, which should
help candidates in their preparation for the next examination.
Question 1:
Discuss how different mechanisms of drug actions and give examples.
(10 marks)

50% candidates passed this question. Highest mark was 8.5.

This is a question on basic principles of pharmacology. A good answer
required candidates to think broadly about all four mechanisms in which
drugs produce their effects. One possible classification is via receptors or
non-receptors actions. A good answer to this question required candidates
to explain the four main mechanisms of drug actions with examples:
1. Actions dependent on physicochemical properties e.g. antacids and
chelating agents (desferoxamine and iron).
2. Enzyme inhibition – enzymes are biological protein, which catalysed
chemical reaction but remains unchanged. Enzymes inhibition can be
competitive (e.g. edrophonium) or non-competitive (e.g. aspirin).
3. Voltage gated ion channels – involved in the conduction of action
potentials in excitable tissues. Examples are local anaesthetics
(lignocaine) block Na channel, calcium channel blockers (diltiazem) act
on vascular smooth muscle ion channels and antiarrhythmics block
myocardial ion channels.
4. Receptors activation – receptor is a protein, often integral to a
membrane containing a region which a ligand binds specifically to elicit a
response. They may be grouped into three classes:
i) Altered ion permeability,
ii) Production of intermediate messengers (G-protein coupled receptor
e.g. BB, tyrosine kinase e.g. insulin and guanylyl cyclase system
e.g. NO).
iii) Regulation of gene transcription (e.g. steroids, thyroid hormone)

Very often in those who failed this question did not mention the non-
receptor mechanisms, in particular enzyme inhibition. It is very important
to think broadly and classify the mechanisms into receptors and non-
receptors. Another common mistake was failure to mention correct
examples of the drug action they described.
About 15% of candidates failed badly because they misunderstood the
question completely by discussing the types of drug-receptor interaction
i.e. affinity and intrinsic activity instead of mechanisms of drug action.
They described the receptor agonism and antagonism in too much detail
and this is not required. The candidates could not be given any mark if
they approached the question this way.

Question 2:

Discuss how pharmacokinetic and pharmacodynamics properties of

drugs are altered with ageing. Give relevant examples. (10 marks)

Only 25% of candidates passed this question.

The question asked the changes expected in a healthy elderly, thus

diseased states and drugs interaction will not gather any marks. A good
answer on changes in pharmacokinetics should include all parameters
affected ie. absorption, distribution, metabolism and elimination.

Many candidates did not write about the importance of first-pass

metabolism towards the bioavailability that result in increasing serum
concentration of drugs. The volume of distribution of drugs were affected
by the relative reduction in TBW:fat ratio in elderly. The changes should
be clearly stated with regards to the lipophilic or hydrophilic drugs to
attract full marks. The answers should include the clinical application of
these changes with relevant examples.

Many candidates rightfully mentioned regarding the reduction in liver

and renal clearance, however, how these changes came about was lacking,
i.e. reduction of liver blood flow and reduction in GFR. Examples and its
clinical implication especially with drugs with narrow therapeutic index
were lacking in most candidates.

Pharmacodynamics changes mainly involved the CNS and CVS. The

increased sensitivity towards drugs affecting the CNS is particularly
important in daily anaesthetic practice. Again most candidates were too
fixated with opioids and forgetting about other important drugs such as
benzodiazepines, induction agents and volatiles anaesthetics. The
candidates are also expected to explain the changes of β-receptor
sensitivity and how these changes affect the CVS.

QUESTION 3

a) Classify antiemetic drugs used for post-operative nausea vomiting

(PONV) and briefly discuss their mechanisms of actions. (6 marks)

b) List the adverse effects associated with these drugs. (4 marks)

40.4% of candidates achieved a pass in this question

Part A

Some candidates did not answer the questions correctly by explaining the
risk factors associated with PONV, anaesthetic drugs that can prevent
PONV, anti-aspiration prophylaxis and the physiology of vomiting.

Most were able to classify the main group of antiemetics but did poorly
describing the mechanism of actions. A few candidates mistook D1 with
D2 receptors, H1 with H2 receptors and serotonin as histamine by giving
the wrong example of drugs. Dopamine and serotonin antagonists have
central and peripheral actions, in which some candidates missed to
explain.

Many did mention propofol (sub-induction dose), dexamethasone and

NK-1 antagonist, which carry extra marks.

Treatment with naloxone for opioid-induced nausea and vomiting was not
accepted as an answer.

Part B

Most candidates were not able to clearly and concisely list down the
adverse effects of antiemetics. By just writing down extrapyramidal and
anticholinergic effects without elaborating the signs and symptoms, the
candidates gained less marks.

Common and important adverse effects for each class of antiemetics must
be listed down to gain a pass mark. Rare side effects rather than adverse
effects do not gain any marks e.g. pain on injection, mydriasis. Serotonin
syndrome/crisis was not accepted because it is a drug interaction and not
an adverse effect.

Question 4:

a) Define Minimum Alveolar Concentration (MAC). (1 mark)

b) Outline the factors that influence it. (6 marks)
c) Briefly explain MAC-BAR and MAC awake and the application of
these terms. (3 marks)

66% of the candidates achieved a pass in this question.

For definition of MAC, the answer requires the candidates to mention the
conditions that are required specifically:
MAC is defined as the minimum alveolar concentration of a volatile agent
in 100% oxygen, at steady state that prevents reaction to a standard
surgical stimulus (skin incision) in 50% of patients at 1 atmosphere.

Overall many candidates could outline the factors that influence MAC
and hence were able to get the full marks and passed this question.
Unfortunately, there were a few candidates who had misunderstood this
part of the question and focused wrongly on the factors that affect the rise
of FA/FI instead of MAC itself. This answer would not be awarded any
marks at all.

In the third part of the question, candidates were expected to briefly

explain MAC BAR and MAC awake and their applications. A definition
of both MAC BAR and MAC awake, with appropriate range of level and
their clinical application in daily anaesthetic practice were expected.
Many candidates were confused on the concept of MAC awake and hence
gave a wrong application of it in daily practice.
Question 5:

A. Briefly outline the mechanism of action of non-depolarising

neuromuscular blockers at the neuromuscular junction. (2 marks)

83.7% passed this question.

The answer requires the candidate to mention that non-depolarising

neuromuscular blocker (NDMB) is a competitive antagonist at the
nicotinic acetylcholine receptor (nAChR). By binding to nAChR, will
prevent depolarization of motor end-plate and prevent transmission of
action potential. Both α-subunits must be simultaneously occupied by
acetylcholine; if only one of them is occupied, then the channel remains
closed. This is the basis for preventing depolarization by antagonists.
NDMRs act by binding to either or both α-subunits and thus preventing
acetylcholine from binding and opening the channel. More than 75% of
the postsynaptic receptors have to be blocked before there is a failure of
muscle contraction.

B. Discuss the factors that prolong the duration of action of non-

depolarizing neuromuscular blocking agents. (8 marks)

Marks were awarded for the following factors:

Prior administration of acetylcholine
Inhalational agents
pH changes: metabolic acidosis (and lesser extent respiratory acidosis)
Hypothermia
Age: Elderly and neonate
Electrolyte imbalance: Hypokalemia, Hypermagnesemia, Hypocalcemia
Neuromuscular diseases e.g. Myasthenia gravis
Organ dysfunction: Renal and hepatic dysfunction which will reduce
clearance
Drug interaction: examples
 Antibiotics e.g. aminoglycosides
Diuretics
Local anaesthetics
Anti-arrhythmics e.g. quinidine

The questions were generally well answered. A few candidates

commented that neuromuscular blockade by NDMB is called Phase II
Block as there were some similarities with the features of both.

Question 6:

6. List classes of drugs that maybe used to manage an intraoperative

hypertensive crisis and briefly outline their mechanisms of action.
[10 marks]

Only 29% of the candidates passed this question. Many candidates

merely regurgitated the whole list of antihypertensive drugs as their
answer, failing to appreciate that what was required was a discussion on
the drugs that can be used in the intraoperative setting.
This was applied pharmacology giving preference only to drugs that were
easily available during the conduct of anaesthesia, given intravenously or
via inhalational route for a rapid, titratrable effect. Drugs with slower
onset and given via oral route were not accepted as answers. Apart from
specific antihypertensive drugs, many candidates failed to list intravenous
induction agents like propofol, which may be a direct cardiodepressant,
vagolytic and a vasodilator. Volatile agents like sevoflurane, isoflurane
and halothane may bring down blood pressure via various mechanisms.
Opiods such as remifentanil and fentanil were also frequently left out
from many answers.
Other accepted classes of drugs included β blockers, α2 agonist,
nitrovasodilator, hydralazine derivatives, non-selective α blocker,
magnesium sulphate and calcium channel blockers, with appropriate and
correct mechanisms of cations. These groups of drugs were frequently
mentioned by candidates though surprisingly many attributed
vasodilatory properties of β blockers rather than negative chronotropy
and inotropy effects to lowering blood pressure.
A number of candidates spent time writing on the management of
hypertensive crisis, which did not carry any marks for this
pharmacological essay. A number of candidates confused “α1 agonist”
and “α2 antagonist” plus their examples and a few classified hydralazine
as calcium channel blocker. A number of candidates wrongly attributed
morphine’s histamine release as a means of lowering blood pressure.

This Examination Report is prepared by the Primary Conjoint

Pharmacology Examiners.
Pharmacology november 2016

1. (a) What is an isomer? (1 mark)

(b) What types of isomerism are there? Give examples of each type (5 marks)
(c) How does isomerism influence the behavior of anaesthetic drugs? (4 marks)

This question was answered reasonably well by the candidates. About 70% of them passed and the
highest mark achieved was a perfect 10. Most candidates could define what isomerism is with its
broad classification was clearly illustrated. Tautomerism with its examples was mentioned in most of
the answers but stereoisomers (geometric and optical) were not fully understood by majority of the
candidates. The nomenclature of R (rectus) and S (sinister) were not well explained and sometime
was confused with the old classification of laevo- and dextro- in the optical isomers. However, most of
the candidates were able to list out important anaesthetic drugs which function and action are
influenced by isomerism. The candidates would be expected to list out and explained the significance
of isomerism in common drugs such as bupivacaine, ketamine, warfarin, barbiturates, tramadol and
midazolam in their answer.

2. Using a three-compartment model, explain the pharmacokinetics of

propofol
(a) following a single intravenous bolus . (4 marks)
(b) in a target-controlled infusion (TCI). (6 marks)

29.9% of candidates passed this question.

The question evaluates the basic understanding of a three-compartment pharmacokinetic model in two
clinical scenarios related to the administration of propofol; a) following a bolus dose and b) in a target-
controlled infusion (TCI).

For section (a) candidates are required to describe the three distinctive phases following a single
bolus dose namely, a rapid distribution phase (phase 1) followed by a slow distribution phase (phase
2) and finally elimination or terminal phase (phase 3). Marks were also allotted for description of the
various compartments involved and correctly labeled diagram of either a three-compartment model or
plasma concentration-time curve.

For section (b) explanation of the pharmacokinetic process during the loading, maintenance and
termination of TCI are expected. A mention of at least two of commonly used TCI models, the
necessary patient’s parameters to calculate the loading dose needed to achieve the infusion target,
either at plasma or tissue level are all required. The discussion on intercompartmental distribution and
clearance as factors governing maintenance rate plus relevance of context sensitive half time (CSHT)
were awarded marks, as well as a correctly labeled diagram.

Most candidates displayed only superficial knowledge about the topic. Some wasted time with
irrelevant preamble about propofol’s formulation and structure, while some merely listed the whole
pharmacokinetic processes of administration, distribution, metabolism and excretion of propofol
without due reference to the context of the question. Few candidates showed a totally wrong
understanding of the concept while quite a number explained the one compartment model instead.

Candidates lost marks when no diagrams were used to illustrate text, no mention of CSHT was made
and discussion about the importance of loading dose was omitted. Few candidates wrongly attributed
loading dose to maintenance of plasma levels in the steady state and many did not include how a
loading dose was determined.

1
The better candidates showed good grasp of the concept of propofol distribution between the central
and peripheral compartments and the stages involved in setting up the various doses in a TCI.

3. (a) Describe the mechanisms of action of Non-Steroidal Anti-Inflammatory Drugs

(NSAIDs). (2 marks)
(b) Explain the clinical effects of NSAIDs? (5 marks)
(c) Outline the advantages and disadvantages of using COX-2 selective agents.
(3 marks)

A total of 115 candidates sat for this paper. 88 candidates (76.5%) passed and 27 (23.5%) failed.

Part (a) asked candidates to describe the mechanism of NSAIDS.

Majority of the candidates managed to describe the basic pathway of inhibition of cyclooxygenase
pathway resulting in reduction of prostaglandin productions. Many also made the distinction between
the constitutive COX1 and the inducible COX2 isoenzymes. However, many candidates did not
attempt to draw the pathway. Additional marks were only given when the pathway is drawn and details
such as phospholipids, thromboxanes, prostaglandins, prostacyclins in the cyclooxygenase pathway
and leukotriene production in the lipoxygenase pathway were mentioned.

Part (b) asked the candidates to explain the clinical effects of NSAIDS.

Most candidates stated the common clinical effects and gave brief explanations to these effects.
However, many were not exhaustive in listing the effects, and marks could not be given for this
missing information. Many did not mention the irreversibility of TXA2 inhibition by aspirin which was
unique to prevent arterial thromboembolism.

Part (c) asked the candidates to outline the advantages and disadvantages of using COX2 selective
agents.

Most candidates did reasonably well in this part and gave a fair account of the advantages and
disadvantages of COX2 inhibitors. A fifth of the candidates did not complete this section and were very
rudimentary in their answers, probably due to time constraint. Only two candidates mentioned the
effect of COX2 inhibitors on bone healing.

4. (a) Describe the Vaughan-Williams classification of anti-arrhythmic drugs giving

examples of drugs for each class. (6 marks)
(b) What are the limitations of the Vaughan-Williams classifications? (3 marks)
(c) Which anti-arrhythmic drugs do not fit into the Vaughan-Williams classification?
(1 mark)

89.74% of candidates passed this question.

Most of the candidates were able to describe the Vaughan-Williams classification. Marks were given
for correct explanations of the mechanisms of each class of the anti-arrhythmic drugs with correctly
named examples of drugs.

Answers given in table form and explanations given in graphical drawing of action potential of
myocardium were also accepted.

A few candidates classified drugs in wrong groups and were not specific in explaining the
classification. Common mistakes included wrong drugs or wrong spelling of drugs. Many candidates
were able to list the limitations of Vaughan-Williams classification, which included:

• Drugs that exhibited effects of another class (with example: amiodarone, sotalol).
• Same class of drugs producing different effects.
• Non-relation of the classification to anatomical or clinical usage of anti-arrhythmic drugs.

2
Most candidates were able to give the answers of drugs not listed into the original Vaughan-William
classification. Adenosine, magnesium sulphate and digoxin were the accepted answers.

5. (a) Describe the mechanisms of action of steroids. (2 marks)

(b) List and briefly describe the clinical use of glucocorticoids, with appropriate
examples, in your daily anaesthesia practice. (8 marks)

Only 3.4% of candidates passed this question. Despite glucocorticoids being widely used in
anaesthesia and critical care, the low pass rate showed that most candidates have lack of
understanding on the therapeutic use of glucocorticoids.

The first part of the question requires candidates to describe the mechanism of action (MOA) of steroid
drugs. Steroid molecules diffuse across the cell membrane of target cells and bind to the steroid
receptors in the cytoplasm. The steroid-receptor complex are then released into the nucleus to bind to
the specific nucleotide sequences along the DNA, which will increase or decrease mRNA and then
affect gene transcription and synthesis of specific proteins that carry out biological functions.

Majority was not able to give concise and accurate descriptions of the MOA. Many candidates made
mistake by describing steroid’s anti-inflammatory effect and its action on the arachidonic acid pathway.
Also no marks were given for explaining steroid hormone effects on the physiological functions.

In the second part of the question, candidates were expected to explain the clinical use of
glucocorticoids in their normal practice. Some candidates missed out by not writing adequate
explanations and occasionally gave incorrect justifications for glucocorticoids use. They also did not
give correct examples of drugs and the standard doses for every indication.

List of clinical uses that was accepted is as follows:

1. Intra-operative supplementation for patients with adrenal insufficiency.

2. Septic shock.
3. Allergy/anaphylactic reaction.
4. Post-operative nausea and vomiting.
5. Difficult intubation and airway oedema.
6. Bronchospasm and hyper reactive airway conditions.
7. Pain management including epidural steroid injection and analgesic adjunct.
8. Raised intracranial pressure due to space occupying lesion.
9. Immunosupression including post organ transplant and autoimmune diseases

Bonus marks were given for the use of glucocorticoids in thyrotoxicosis and mediastinal mass.

Answers that would not gain any marks include:

a. Justification for its use in septic shock was wrongly explained i.e as anti-inflammatory /
indirect vasopressor / suppression of SIRS.
b. Various medical indications e.g. eczema, foetal lung prematurity, post-chemotherapy
antiemesis.
c. Use in ENT and oral surgery without mentioning airway oedema.
d. Use in spinal shock and cord oedema – weak clinical evidence.
e. Other orthopaedic uses e.g. intra-articular injection.
f. Used as radiological contrast prophylaxis.
g. Dexamethasone suppression test.
h. Anti-microbial adjunct therapy.

A few candidates were clearly wrong to state giving glucocorticoids after induction using etomidate due
to adrenal suppression, and dextrose solution as glucocorticoids that could enhance gluconeogenesis.

3
Some candidates went completely off the track by describing glucocorticoids physicochemical
properties and adverse effects.

6. (a) How does warfarin exert its anticoagulant effect? (5 marks)

(b) Give examples of drug interactions that may enhance the effect of warfarin.
(3 marks)
(c) Explain how the effects of warfarin can be reversed? (2 marks)

38% candidates passed this question

(a) How does warfarin exert its anticoagulant effect?

Majority of candidates rightfully mentioned that warfarin inhibits production of the vitamin K dependent
(II, VII, IX and X) clotting factors, however forgot the fact that warfarin also reduces the production of
anticoagulants protein C and S. Warfarin has an initial paradoxical procoagulant effect as
anticoagulant factors are depleted first. Marks are also given for mechanism of action i.e. it inhibits vit
K returning to its reduced form thereby preventing the factors production. The candidates should
describe the anticoagulant effect of warfarin which results from a balance between partially inhibited
synthesis and degradation rate of vit K dependent clotting factors. Only about a quarter of candidates
highlighted the effect of different half-lives of coagulation factors on the actions of warfarin which takes
up to 72 hours to exert its full effect.

(b) Give examples of drug interactions that may enhance the effect of warfarin.

This section was quite well answered by candidates. There are three important drug interactions. Most
candidates remembered the first two pharmacokinetic interactions i.e. the effect of another highly
protein bound drugs that can displace warfarin thus increase its free fraction. The second interaction is
the effect of enzyme inhibitors on hepatic metabolism (e.g. cimetidine, erythromycin etc.) that may
potentiate warfarin’s effect. However, the pharmacodynamics interactions i.e. synergism with heparin
or NSAIDs were often missed.

(c) Explain how the effects of warfarin can be reversed?

This part was answered poorly by candidates. Not many candidates mentioned about withholding
warfarin and monitor INR. They should explain how fresh frozen plasma and vitamin K administration
reversed the bleeding patients with prolonged INR. Marks were also given for administration of
prothrombin complex concentrates (PCC) or activated factor VII (Novo seven). About 10 candidates
thought that warfarin effects could be reversed by protamine.

This Examination Report is prepared by the Primary Conjoint Pharmacology Examiners &
Markers:

Professor Dr. Nik Abdullah Nik Mohamad (USM, Chief Examiner)

Associate Professor Dato’ Dr. Mohd Basri Mat Nor (IIUM)
Dr. Laila Ab. Mukmin (USM)
Dr. Khairul Amir Zainuddin (UKM)
Dr. Noorjahan Haneem Md Hashim (UM)
Dr. Imran Osman (UPM)
Professor Dato’ Dr. Mohd Ariff Osman (IIUM)
Dr. Ariffin Marzuki Mokhtar (USM)
Dr. Liu Chian Yong (UKM)
Dr. Lai Hou Yee (UM)
Dr. Noor Airini Ibrahim (UPM)
Dr. Loo Su Yin (MOH)
Professor Dr. Lim Thiam Aun (UPM) (contribution on MCQ Item Analysis)

4
 EXAMINATION REPORT

CONJOINT PRIMARY EXAMINATION

APR/MAY 2017

Master of Medicine (Anaesthesiology) USM

Doctor of Anaesthesiology and Critical Care (UKM)
Master of Anaesthesiology (UM)
Master of Medicine (Anaesthesiology) UPM
Master of Medicine (Anaesthesiology) IIUM

PHARMACOLOGY

A total of 163 candidates were balloted for the pharmacology written examination but
only 158 candidates sat for the examination. Out of these, 96 (58.89%)* candidates
passed and proceed to viva voce examination. 84 (51.53%)* candidates passed
MCQ and 78 (47.85%)* candidates passed SAQ examinations.

A total of 96 candidates sat for pharmacology viva voce examination. 75 (78.13%)

candidates sat for both pharmacology and physiology viva, while 21 (21.88%)
candidates sat for pharmacology viva only. Out of these, 82 (85.42%) candidates
passed pharmacology viva voce examination. The overall passing rate for
pharmacology examination is 50.31%*.

(*) Percentage from the total candidates balloted (163 candidates) for the
pharmacology written examination.

WRITTEN SECTION

A. MULTIPLE CHOICE QUESTIONS (MCQs):

60 MCQs were set, including seven (7) marker questions with difficulty index (DI) >
50%. Below are the item analyses based on the actual number of candidates (158
candidates) who had sat for MCQ examination;

1. Taking the paper as a whole:

• Average Difficulty Index (DI) = 0.65 (Ranging from 0.37 to 0.93) (target:
0.3-0.7)
• Average Discriminating Index (R) = 0.15 (Target: 0.2 and above)
• 16 (26.67%) of the 60 questions were with (R) of 0.2 and above
 2. Analysis question by question:
• 19 (31.67%) easy questions (DI > 0.7)
• Nil difficult questions (DI<0.3)
• 41 (68.33%) “normal” questions (DI between 0.3-0.7). Ideally only these
questions give a meaningful Discriminating Index (R)
• Average ‘R’ for optimal questions = 0.14 (below target)
• 9 (21.95%) ‘normal’ questions were with ‘R’ of 0.2 and above

3. Analysis response by response (i.e. A to E of each question):

• 140 easy responses (46.67%)
• 28 difficult responses (9.33%)
• 132 ‘normal’ responses (44.0%)
• 56 ‘normal’ responses (18.67%) have an “R” value of 0.2 and above

Conclusion: As a whole, MCQ examination has a difficulty index within the desired
range. However, only 26.7% of the MCQs were able to discriminate the candidates.

B. SHORT ANSWER QUESTIONS (SAQs):

1. a) Describe how ‘context-sensitive half time’ of a drug differs from its

‘half-life’ (4 marks)
b) Explain the properties of propofol that makes it suitable as a
sedative agent (6 marks)
This question was passed by 51.5% of candidates.

In part (a), the answers that would gain marks are:

Definitions of CSHT and half-life, the different determinants of CSHT and half-life,
relevant formulas and graph to compare the context sensitive half time of various
drugs and graph of half-life with correctly labeled axis. Many candidates were
confused on definition of ‘context-sensitive half time’.Many defined that ‘it is the
time taken for plasma concentration to reduce to half of its initial concentration
at steady state when the infusion is stopped’. As drug infusion can be terminated
at any time, steady state may or may not be achieved but the concept of context
sensitive half time is applicable in drugs infused for any duration. Elaborated
examples on drugs with regards to their CSHT and half-life are not expected and
will not gain marks.

In part (b), candidates were expected to relate the ideal properties of propofol as
sedative agent and not as induction agent.

Many candidates also just listed all the properties of propofol without relating it to
why propofol is suitable as a sedative agent. Regurgitation of numbers and facts
 without reference to what would make propofol useful as a sedative agent would
not gain marks. For example, a statement that says, propofol has a fast onset of
action (sedation) with out explanation relating it to its high lipid solubility, high k eo
and relation of its pKa and physiological pH would not gain marks.Good answers
also relate the pharmacodynamics properties to the relevant group of patients. For
example, Propofol causes reduction in CMRO 2 , hence useful for sedation for
patient ventilated with traumatic brain injury etc.Drawing the structure of propofol
and elaborating on its mechanism of action would not gain marks.

2. Briefly describe the roles of plasma esterases on drugs used in anaesthesia.

(10 marks)

115 out of 158 (72.8%) candidates passed this question with 9/10 as the highest
marks and zero as the lowest mark (question was not attempted). Although many
passed this question but on average the marks ranged from 5-6/10.

Plasma esterase are enzymes that can be found in abundance in the body. It
hydrolases ester bonds in many drugs used in anaesthesia. Many candidates did not
give brief description of the types of plasma esterase and sites of where it can be
found. Good candidates described the different types of esterase i.e. plasma
cholinesterase, red blood cell cholinesterase and non-specific cholinesterase and
described its role on the relevant drugs used in anaesthesia.

Some candidates list the associated drugs and later described its metabolism. That is
not how the question should be answered. The question wants the candidate to
describe the specific roles of each of the different esterase and describe the
metabolism of the associated drugs. For example; The plasma cholinesterase will
metabolise mivacurium but not acetylcholinesterase. The rate of its hydrolysis is 70-
90% of that of succinylcholine. Patients with cholinesterase variants respond similarly
to both mivacurium and succinylcholine.

A few candidates gave wrong facts, for example; non-specific esterase metabolise
mivacurium, or plasma cholinesterase metabolise amide local anesthetic agent (it
should be ester local anesthetic eg procaine, chloroprocaine). Many failed to mention
that plasma or pseudocholinesterase also metabolise etomidate, aspirin and
methylprednisolone.

Surprisingly, almost all candidates were able to describe red blood cell
cholinesterase and the metabolism of esmolol in details. Candidates were also able
to describe well the metabolism of remifentanil by non-specific esterase.
Unfortunately, there were many candidates who misspelled remifentanil as
‘remifentanyl’.

Overall, most candidates understood the question and able to answer them. Although
there were a few who were unable to produce any answer. Majority of candidates did
not answer in a systematic way and were unorganised. Most facts were briefly
mentioned without further description on how plasma esterase affect the metabolism
of the anesthetic drugs.The candidates’ answers were mostly superficial with
inadequate facts.

3. a) What is an adverse drug reaction (ADR)? (1 mark)

b) Briefly explain the types of adverse drug reactions with relevant
examples. (5 marks)
c) Briefly dicuss the risk factors for an ADR . (4 marks)

45.6% of candidates passed this question .

Many candidates generally knew that it is an unintended and undesirable response

to a medication but few appreciated that an ADR occurs at normal doses and not
part of an overdose presentation. WHO defines ADR as ‘a response to a medicine
which is noxious and unintended and occurs at doses normally used in man ‘.

Candidates were expected to know the main coventional classification which are
dose related and non- dose related. They were also expected to describe important
features of of these two classes and provide relevant examples. A good answer
would be to describe dose-related ADRs as common, easily predictable as they are
related to the pharmacological action of the drug and has lower mortality , example
being hypotension following propofol. A non-dose related ADR is relatively
uncommon, unpredictable, carries higher mortality and unrelated to the cation of the
drug. An example being Suxamethonium apnoea or Steven Johnson Syndrome
following exposure to trimethoprim and sulfamethoxazole.

Over the years, the two common classification has expanded to encompass dose
and time relation, withdrawals and failure of therapy and marks are given to all these
aspects if discussed correctly. Some candidates confused ADR from an adverse
drug incident which occurs as a result of wrong route,dose or patient. No marks were
given for strategies to reduce human error, classification into pharmacokinetic and
pharmacodynamic factors and drug monitoring strategies to prevent overdose.

The discussion on risk factors for ADR was much better done. Many candidates
correctly listed extremes of age , polypharmacy, pharmacogenetics, gender,
comorbidities , obesity , pregnancy and the immune system, and followed them up
with relevant discussions .

4. a) Compare & contrast the wash out curves and recovery from anaesthesia
for desflurane and sevoflurane. (6 marks)
b) Briefly describe diffusion hypoxia with the use of nitrous oxide. (4 marks)
62% of candidates passed this question.

a. This question asked the elimination kinetic of anaesthetic recovery for both
desflurane and sevoflurane using the washout curves.
Candidates are expected to correctly labelled the wash out curve and to explain the
graph in details.

A good answer to this question required candidates

1) to explain the similarities and differences of properties for both agents that
influence the wash out curves. These include the exponential decay pattern
shown in the graph, the blood:gas partition co-efficient (blood solubility) and
oil:gas partition co-efficient (tissue deposits /compartmental distribution).
Candidates ought to explain why one agents exhibit comparatively faster
recovery profile.
2) to correctly illustrate the kinetic of the relationship between blood solubility and
tissue distribution and attribute these properties to the recovery profile
Quite a number of candidates wrote on the factors affecting uptake of volatile agents,
while few candidates drew the wash in curve instead, indicating that these
candidates were unable to fully grasp the kinetic differences between induction and
recovery of a volatile anaesthetic agent.

While some candidates offer an explanation of recovery profile using the percentage
of alveolar partial pressure decrement of volatile agents over time, marks cannot be
rewarded.

b. This question asked the candidate to explain the mechanism of diffusion hypoxia
when nitrous oxide is used and how to overcome it.

Majority of the candidates were able to explain this phenomena and relates with the
particular properties of nitrous oxide versus other gases. However, some candidates
explained the other effect of nitrous oxide in which no mark will be rewarded, such as
the second gas effect and concentration effect, only minimally answering the
question.

5. Write short notes on

a) Paracetamol toxicity (5 marks)
b) Intrathecal morphine (5 marks)
A total of 82.2 % passed this question. This question tested pharmacological aspects
of common clinical scenarios.

Question on paracetamol toxicity requires candidate to discuss the metabolism of

paracetamol and changes when toxic doses were ingested. The mention of toxic
metabolite N-acetyl-p-benzoquinone imine (NAPQI) and its effect on liver, the clinical
features of paracetamol toxicity and specific therapies such as N-acetyl cysteine and
methionine were awarded marks. Many candidates wrote on general pharmacology
of paracetamol but were awarded marks only at the discussions on toxicity part.
Common mistakes of the candidates included wrongly named NAPQI and mistakes
in typical doses of paracetamol that could cause toxicity.

Question on intrathecal morphine tested candidates’ understanding of morphine

hydrophilicity (compared to other opioids) when injected into cerebrospinal fluid
(CSF) and its effects following cephalad spread of CSF. The mention of usual clinical
usages and dosages of intrathecal morphine were also awarded with marks. Marks
were also given to discussions on side effects of intrathecal morphine. Many
candidates wasted time writing on general pharmacology of morphine and its
systemic effects without specifically discussing its effects intrathecally. Some
discussed on various opioids injected intrathecally. Other common mistakes included
wrongly written dosage and confusion on caudal/cephalad spread.

Generally, candidates who gave generic answers on general pharmacology of

paracetamol and morphine without specifically addressing the toxicity of paracetamol
and morphine administered intrathecally wasted a lot of their time and effort. All
candidates are encouraged to write legibly especially during written examinations.

6. Discuss the agents used in the acute management of hypertension in

pregnancy. (10 marks)

21.5% of candidates passed this question.

Marks were awarded for statements that these drugs are safe for both mothers and
foetus, preferably in intravenous form, and oral forms are acceptable only if they have
good bioavailability. Since the drugs are indicated in an acute condition, they have to
have fast onset and titratable to effect.

Marks were awarded for correct drugs, its mechanism of action with the correct dose
and side effects, both maternal and foetal. Examples of these drugs are, but not
limited to, intravenous beta blockers, hydralazine and calcium channel blockers.
Though many candidates appropriately named magnesium sulphate, its role is for
prevention and treatment of eclampsia were not mentioned by many.

Oral Methyldopa was also mentioned. Though it is usually indicated for chronic blood
pressure control, it may be used/continued in the acute phase with hydralazine.

Candidates should also write example of drugs that are not suitable due to their
effects on uterine contraction, volume status or maternal and foetal toxicity. E.g
frusemide (can be used if the PE patient has pulmonary oedema) and ACE inhibitors
with complication stated.
This Examination Report is prepared by the Primary Conjoint Pharmacology
Examiners & markers:

Dr. Laila Ab Mukmin (USM, Chief Examiner)

Associate Professor Dr. Saedah Ali (USM)

Professor Dato’ Dr. Mohd Ariff Osman (IIUM)

Dr. Liu Chian Yong (UKM)

Associate Professor Dr. Ina Ismiarti Shariffuddin (UM)

Dr. Noor Airini Ibrahim (UPM)

Dr. Ariffin Marzuki Mokhtar (USM)

Associate Professor Dr. Raha Abdul Rahman (UKM)

Dr. Azarinah Izaham (UKM)

Dr. Noor Jahan Haneem Md Hashim (UM)

Dr. Lim Teng Cheow (MOH)

 EXAMINATION REPORT

CONJOINT PRIMARY EXAMINATION

OCT/NOV 2017

Master of Medicine (Anaesthesiology) USM

Doctor of Anaesthesiology and Critical Care (UKM)
Master of Anaesthesiology (UM)
Master of Medicine (Anaesthesiology) UPM
Master of Medicine (Anaesthesiology) IIUM

PHARMACOLOGY

A total of 82 candidates were balloted for the pharmacology written examination but
only 80 candidates sat for the examination. Out of these, 39 (48.75%)* candidates
passed and proceed to viva voce examination. 30 (37.5%)* candidates passed MCQ
and 41 (51.25%)* candidates passed SAQ examinations.

A total of 39 candidates sat for pharmacology viva voce examination. 14 (35.9%)

candidates sat for both pharmacology and physiology viva, while 25 (64.1%)
candidates sat for pharmacology viva only. Out of these, 38 (97.44%) candidates
passed pharmacology viva voce examination. The overall passing rate for
pharmacology examination is 47.5%*.

(*) Percentage from the total candidates actually sat for the pharmacology written
examination (80 candidates).

WRITTEN SECTION

A. MULTIPLE CHOICE QUESTIONS (MCQs):

60 MCQs were set, including six (6) marker questions with difficulty index (DI) > 50%.
Below are the item analyses based on the actual number of candidates (80) who had
sat for MCQ examination;

1. Taking the paper as a whole:

• Average Difficulty Index (DI) = 0.62 (Ranging from 0.34 to 0.85) (target:
0.3-0.7)
• Average Discriminating Index (R) = 0.14 (Target: 0.2 and above)
• 13 (21.67%) of the 60 questions were with (R) of 0.2 and above
 2. Analysis question by question:
• 16 (26.67%) easy questions (DI > 0.7)
• Nil difficult questions (DI<0.3)
• 44 (73.33%) “normal” questions (DI between 0.3-0.7). Ideally only these
questions give a meaningful Discriminating Index (R)
• Average ‘R’ for ‘normal’ questions = 0.14 (below target)
• 9 (20.45%) ‘normal’ questions were with ‘R’ of 0.2 and above
• 13 (21.67%) of 60 questions were with ‘R’ of 0.2 and above

3. Analysis response by response (i.e. A to E of each question):

• 129 easy responses (43%)
• 39 difficult responses (13%)
• 132 ‘normal’ responses (44.0%)
• 62 ‘normal’ responses (20.67%) have an “R” value of 0.2 and above

Conclusion: As a whole, MCQ examination has a difficulty index within the desired
range. However, only 21.67% of the MCQs were able to discriminate the candidates.
B. SHORT ANSWER QUESTIONS (SAQs):

1. Outline the role of the liver in the drug pharmacokinetics

(10 marks)

67.5% of candidates passed this question.

The keywords for this question are liver and pharmacokinetics. Pharmacokinetic comprises of
absorption, distribution, metabolism and excretion. Therefore, the answer scheme must cover
all of these important headings. One major mistake made by the candidate was to confine the
answer to metabolism section only. The maximum mark for this section is only three and it is
not sufficient to pass this question.

For absorption, candidates should be able to explain first pass metabolism and hepatic
extraction ratio (HER). First pass metabolism should be defined and its effect on bioavailability
should be discussed. Many candidates forgot to mention HER and factors affecting it. Factors
affecting HER are hepatic blood flow, uptake into the hepatocytes and the enzyme metabolic
capacity within the hepatocytes.

Protein synthesis by the liver is important (albumin and alpha acid glycoprotein). Volume of
distribution (Vd) is also dependent on degree of protein binding. Protein binding hold the drugs
in the plasma and prevent movement into the tissue. If protein synthesis function is affected,
there will be more free drugs. If the drugs have saturation kinetics, it may cause toxicity. On
the other hand, free drugs will be exposed to metabolism and excretion and thus results in
lower plasma concentration.

Liver metabolism produces a more polar molecule that can be excreted via the bile or urine.
2. Describe the pharmacological interaction(s) between

a) chronic cigarette smoking and theophylline

(2 marks)
b) verapamil and propranolol
(2 marks)
c) aspirin and sodium bicarbonate
(2 marks)
d) a monoamine oxidase inhibitor (MAOI) and pethidine
(4 marks)

37.5 % of candidates passed this question.

As a general, knowledge of the candidates regarding this question (pharmacological

interactions) are inadequate and this reflected for poor performance on this question. Most of
the candidates failed to correlate the pharmacological interactions of smoking with theophylline
and aspirin with sodium bicarbonate. Most of candidates confused regarding cytochrome as
enzyme inducer in liver, even some of the candidates mentioned as an enzyme inhibitor.

For the b) question, majority of the candidates failed to mention about additive effects and risk
of AV block. However, majority of candidates managed to write about effects of hypotension
and low cardiac output. Regarding c) question, most of the candidates failed to relate aspirin
with alkalinization of urine. Surprisingly, there are candidates who mentioned about
alkalinization of the gut after oral sodium bicarbonate.

The interaction between MAOI and pethidine which carry 4 marks also was not performed well
by the candidates. Only few candidates mentioned about an excitatory and depressive form of
drug interaction. There were also only few candidates mentioned about serotonin syndrome.
For the question d) the candidates were expected to give a better answer because the
interactions between MAOI and pethidine are common question asked in the exam.
3. a) Define effective dose.
(2 mark)
b) Using the log dose-response curve, illustrate and describe the effective
dose of an inhaled anaesthetic agent.
(5 marks)
c) List the factors that decrease the effective dose of an anaesthetic agent.
(4 marks)

43.75% of candidates passed this question.

In order to obtain a pass for this question, candidates were required to have good
understanding of the general concept of effective dose (ED) applied to inhalational agents in
association with log dose-response curve. 39 candidates (48.75%) identified ED for
inhalational agents as the dose (alveolar concentration) of inhalational agents that prevent
movement in 50% of the population who were subjected to standard surgical stimulus (skin
incision) at standard pressure (1atmosphere) i.e. Minimum Alveolar Concentrations (MAC)
which is ED50 in the Log dose-response curve. Peculiarly, there were candidates that thought
M in MAC is “mean” instead of “minimum”. In section (a), definition of effective dose was poorly
stated. Only one candidate defined effective dose correctly. In section (b), 11 (13.75%)
candidates were not able to produce a log dose-response curve for an inhalational agent.
Those who did, majority did not label the axes specifically in relation to inhalational agent. Only
6.25% of candidates knew the unit for the alveolar concentration of inhalational agent that
signifies the X-axis. 47.5% of candidates did not denote ED50 or MAC on the X-axis. Only 10%
of candidates recognised that the response (Y-axis) is percentage of population immobile or
do not move following a standard stimulus (skin incision). Furthermore, only five candidates
labelled the Y-axis response was observed at 1 atmosphere. There were candidates that
logged and denote ED50 on Y-axis. Marks were not awarded when candidates described MAC
without indicating that it is ED50. Among those who did indicate that ED50 is MAC, only
26.25% described MAC precisely. In section (c), candidates who understood ED50 is MAC
would list factors that decrease effective dose of inhalational agent as factors that decrease
MAC. Some candidates deduced that factors decrease effective dose of inhalational agents
are equivalent to factors that increase MAC. In conclusion, this question reflected the depth of
understanding and knowledge of the candidates in regards to the concept of ED and how it
was applied to inhalational agents, and how it was shown in the log dose-response curve.
4. Write short notes on
a) suxamethonium apnoea
(5 marks)
b) characteristics of neuromuscular blockade reversal of neostigmine and
sugammadex
(5 marks)

61.25% of candidates passed this question.

4 a). A good answer to this question required candidates

1) to adequately define the terminology and explain with examples the underlying
pathophysiology such as; a) atypical/abnormal pseudocholinesterase (now commonly
referred to as plasma butyrylcholinesterase, b) acquired causes that results in plasma
butyrylcholinesterase deficiency such as burn, pregnancy, severe liver dysfunction, and
c) others such as drug interactions (MAOI, neostigmine).

2) to explain the diagnosis and the clinical implications of suxamethonium apnoea,

especially with regards to the apneic time related to the severity.

Majority of candidates described correctly the genetic/hereditory factors affecting the synthesis
of plasma butyrylcholinesterase, the diagnosis and the subsequent effects on the apnoeic
time.Few were able to explain satisfactorily the other factors (acquired) involved. Candidates
who failed this part of question were either not answering adequately or were only focused on
explaining the genetic etiology and the mechanism of action of succinylcholine.

4 b). This question asked the candidate to describe and focus on the characteristics of
neuromuscular blockade reversal of neostigmine and sugammadex.

Candidates are expected to explain the indication and timing of reversal with each agent,
correct dosage, antagonism to which neuromuscular blockade agents, and their mechanism
of actions.

Majority of the candidates were able to explain indication, timing, antagonism to which class
of neuromuscular blockade and mechanism of actions. However, few candidates who failed
this part of question had focused solely on the mechanism of action for both drugs without
describing the clinical process of these reversal agents.
5. a) Describe with examples the relationship between structures of local
anaesthetic agents and their pharmacological activities.
(5 marks)
b) List the factors that increase the risk of systemic toxicity of local
anaesthetic drugs.
(5 marks)

90% candidates passed this question.

The aim of this question is to assess the candidates’ knowledge of the structure-activity
relationship of local anaesthetic agents. Most candidates were able to describe the 3 chains
structure of LA agents. Marks were only awarded if the significance of the 3 chains on the
pharmacologic activity of the LA, i.e. lipophilic aromatic ring confers the efficacy, intermediate
chain is the basis of classification and site of metabolism and the hydrophilic tertiary amine
chain confers its potency and toxicity. Many candidates mention the importance of the
intermediate chain on the metabolism of the agents, but failed to mention the site on this chain.

The expected explanation also includes the effect of modification of these three basic chains
on the potency, onset of action, duration of action and undesired effects of the agents and their
metabolites. These must be co-related with the physicochemical properties of the agents: lipid
solubility, protein binding, intrinsic vasodilatory activity and isomerism. Marks are awarded if
the correct examples are used to highlight these differences. Only 5 candidates explained the
importance of pKa on the onset of action of these drugs and a small minority of candidates
were able to co-relate the duration of action with the effect of protein binding, isomerism and
intrinsic vasodilator activity. Many candidates were able to write the S- enantiomer as the safer
isomer, but did not explain the mechanism of this property.

A common misconception amongst candidates include the piperidine ring of piperoxycyclide

LAs (mepivacaine, ropivacaine and bupivacaine) are structures on the lipophilic aromatic
benzene ring, rather than on the hydrophilic hydrocarbon chain.
At least 2 candidates used atracurium and rocuronium as examples of ester LA and
aminosteroid LAs, which, of course did not receive any marks.
Most candidates answered part (b) well.

Candidates were expected to list the risk factors of LA systemic toxicity. These do not include
the adverse effects due to allergies and trauma during injection. Candidates were expected to
classify their answers according to drug (which include the physicochemical properties,
pharmacokinetics and pharmacodynamics effects) and patient factors.
In conclusion, the candidates must be able to co-relate the properties of a drug and their PK
and PD profile, and be able to predict the risk of LAST.
6. a) Classify with examples the drugs commonly used to treat acute exacerbation of
bronchial asthma (AEBA), and list their common side effects.
(5 marks)

b) Draw the nephron and

i. label the site(s) of action of drugs that induce diuresis.
ii. indicates on the drawing, the mechanism of action for each of the diuretics.
(5 marks)

77.50% of candidates passed this question.

Part (a): Generally, this question was answered well. Most candidates were able to list down
the common drugs used to treat asthma but only few had categorised the drugs into two broad
groups i.e bronchodilators and anti-inflammatories. This was to ascertain whether the
candidates knew the underlying concept of asthma pharmacotherapy. Some omitted
corticosteroids in their answers.

Many candidates also listed down drugs that are not common or which are used in the critical
care settings. This showed that they did not read the question properly beforehand as it was
clearly printed in bold letters.

There were some who wrote extensively on the mechanism of actions of the drugs, which did
not gain any mark, as it was not part of the question.

Part (b): This question was also answered well by most candidates.

A few candidates made mistake in stating osmotic diuretic site of action is at the glomerulus.
Some candidates did not describe the mechanism of action accurately such as the action of
carbonic anhydrase inhibitor on bicarbonate reabsorption, the multiple actions of potassium-
sparing diuretic, and not able to name the correct ion channels for loop and thiazide diuretics.

This report is prepared by:

Dr Laila Ab Mukmin (Chief examiner)

Prof. Dr. Shamsul Kamalrujan Hassan
Prof. Madya Dato’ Dr. Basri Mat Nor
Dato’ Dr. Wan Rahiza Wan Mat
Dr. Noorjahan Haneem Md Hashim
Dr. Imran Osman
Prof. Dr. Nik Abdullah Nik Mohamad
Dr. Liu Chian Yong
Dr. Azarinah Izaham
Dr. Chaw Sook Hui
Dr. Mohamad Rasydan Abdul Ghani
Dr. Khoo Teik Hooi
 CONJOINT PRIMARY (Part 1) EXAMINATION

MASTER OF MEDICINE (ANAESTHESIOLOGY) UPM

DOCTOR OF ANAESTHESIOLOGY AND CRITICAL CARE (UKM)

MASTER OF ANAESTHESIOLOGY (UM)

MASTER OF MEDICINE (ANAESTHESIOLOGY) USM

MASTER OF MEDICINE (ANAESTHESIOLOGY) IIUM

PHARMACOLOGY
(Short Answer Questions)

April 2018

EXAMINERS’ REPORT

1
Question 1
a) How does pregnancy at term influence the (4 marks)
pharmacokinetics of anaesthetic drugs?
b) What factors influence the rate of transfer of drugs across (4 marks)
the placenta?
c) How do these factors explain the adverse effects of (2 marks)
pethidine and local anaesthetics on the foetus when
administered during labour?

60.9% of candidates passed this question.

PART A
This section requires candidates to explain how physiological changes in pregnancy affect
absorption, distribution, metabolism and excretion of anaesthetic drugs. Some candidates
gave wrong example of drugs or mentioning non-anaesthetic drugs.

Candidates also did not get adequate marks if the concept was wrongly described. For
example, reduced gastric emptying increases absorption of drugs BOTH in the stomach and
upper GIT. Some failed to explain clearly how pregnancy affects the speed of onset of
inhalational agents.

Most candidates did not mention regarding:

• high cardiac output and vasodilation increase uptake of drugs given

subcutaneous/intramuscular/neuraxial.
• Increased in LDH, transaminases and cytochrome P450 activity increases
metabolism of drugs highly dependent on liver metabolism.
• Increased in cardiac output and liver blood flow increases liver clearance of drugs.

Also, worth noting some candidates gave examples of drugs such as warfarin and phenytoin
which are contraindicated in pregnancy.
PART B

Generally, this section was answered well by the candidates. Some candidates only listed
down the Fick’s laws of diffusion variables without mentioning how each factor influences the
rate of transfer of drugs across placenta.

Although this section only requires candidates to recall facts, most did not manage to give all
the answers and obtain full mark.

PART C

This section only carries two marks, but it was answered poorly by the candidates, showing
lack of understanding of this subject matter. Most candidates grouped together both pethidine
and local anaesthetics in their explanations regarding ion trapping. Only few students
mentioned pethidine’s high lipid solubility allowing significant transfer across placenta and that
norpethidine accumulates in foetus.

2
Question 2
a) What are the advantages of total intravenous anaesthesia (3 marks)
(TIVA)?
b) What is the ideal agent for TIVA and why? (2 marks)
c) Briefly describe the pharmacokinetic models used in a (5 marks)
target-controlled infusion (TCI). What variables are used in
calculating the loading dose and maintenance dose in TCI?

66.9% of candidates passed this question.

Part A

Majority of the candidates managed to answer this part well describing the advantages TIVA
over inhalational methods (volatile & nitrous oxide). These include avoiding production of
fluoride ions associated with newer volatile agents, minimizing incidence of post-operative
nausea and vomiting, distension of air-filled spaces within the patient, post-operative diffusion
hypoxaemia. TIVA also avoiding problems or complication associated with volatile agents
such as malignant hyperthermia. This technique of anaesthesia is also helpful in spine surgery
involving neuro monitoring (MEP & SSEP), helpful for procedures such as bronchoscopy and
the avoidance of occupational exposure and environmental pollution.

Part B

Most candidates stated correctly that propofol is an ideal agent. However, there were
significant number of candidates that mentioned remifentanil as the ideal agent. Most
candidates describe the properties of ideal agent including short acting with short half-life,
minimal accumulation resulting in faster recovery, high metabolic clearance and rapid
elimination giving a context insensitive half-time even after prolonged infusion. Propofol also
provide smooth rapid induction with no excitation or emergence phenomenon. There is no
interaction with opioids especially remifentanil, no toxic or histamine release, stable and non-
reactive with plastic, glass and metal and environmentally safe.

Part C

Most candidates did fairly well in this part and able to briefly describe the pharmacokinetic
models available for used in TCI. Majority mentioned that TCI designs are based on 3
compartment pharmacokinetic model and the Marsh and Schneider model used for propofol
infusion together with the patient’s data needed to be entered into the two models. Majority of
the candidates also mentioned the variables used in calculating the loading and maintenance
dose.

3
Question 3
a) How do antimuscarinic drugs work? List eight examples of (3 marks)
their clinical use.
b) Using a table, compare and contrast atropine and (5 marks)
glycopyrrolate.
c) What is anticholinergic syndrome and what (2 marks)
pharmacological agents can be used to treat it?

72.2% of candidates passed this question.

Part A

Candidates were required to state that antimuscarinics are competitive antagonists of

acetylcholine at muscarinic acetylcholine receptors (mAChR). mAChR are located in
postganglionic target tissues innervated by the parasympathetic nervous system and also
sympathetic nervous system in the sweat glands. Many wasted time giving details of
muscarinic receptors subtypes and mechanism of actions without mentioning they are
competitive antagonists. Almost none discussed the location of muscarinic receptors.

Clinical usage of antimuscarinic was generally well listed except only a few included use as
anti-parkinsonian drug (benztropine and benzhexol). A few candidates wrongly answered use
of anticholinesterase instead.

Part B

Majority of candidates answered this section well especially in comparing the

pharmacodynamics section with regards to anti-sialagogue, tachycardia and sedation effects.
However very few compared anti-emetic, mydriatic and bronchodilatory effects. Not many
were able to answer pharmacokinetics section correctly. Only a few candidates compared
correctly the bioavailability, volume of distribution, clearance, half-life and placental transfer of
these drugs.

Part C

Marks were awarded for correct description of anticholinergic syndrome including the central
and peripheral features, causative drugs (only atropine and hyoscine) with correct treatment
which is physostigmine and/or benzodiazepine. A few confused anti-cholinergic syndromes
with cholinergic crisis and with extrapyramidal side effects. Not many appreciated that among
the anticholinesterases, only physostigmine is able to cross the blood barrier and suitable for
treating this syndrome.

4
Question 4
Compare and contrast the pharmacology of atracurium and (10marks)
rocuronium. Relate your answers to their clinical
applications.

9.3% of candidates passed this question.

Candidates are required to compare and contrast the pharmacology of these two drugs and
elaborate the clinical relevance of these features. Marks are allocated for discussion on
various aspects of pharmacology of these drugs i.e. physicochemical, pharmacokinetic and
pharmacodynamics properties as well the clinical implications of these properties in various
clinical uses, physiological and pathological conditions.

Physicochemical properties:

As these drugs are usually available in acidic aqueous formulations, this fact can be used to
explain their convenience in administration, interaction with drugs prepared in basic medium
and probably pain upon injection.

The limited lipid solubility and the hydrophilicity of these drugs lead to no central nervous
system effects and insignificant transfer across the placenta. They are considered suitable in
pregnant patients requiring surgeries such as Caesarean Section under general anaesthesia.
These solubility properties restrict their volume of distribution, confining their molecules to the
extracellular compartment. As a result, reduction in the extracellular volume including plasma
such as in hypovolaemia may cause an increased plasma concentration, altering the relative
potency of these drugs and their clinical action.

Pharmacokinetics

In terms of metabolism and elimination, the metabolism of atracurium is non-organ dependent,

while rocuronium is mainly excreted unchanged in bile and kidneys. In view of organ-
dependent routes of elimination, rocuronium is less suitable to be used in patients with hepatic
or renal dysfunction as compared to atracurium.

Pharmacodynamics

Mechanism of action

These drugs are competitive antagonists of acetylcholine at the neuromuscular junction,

causing skeletal muscle relaxation. Due to their non-depolarising mechanism of action,
administration of these drugs to achieve muscle relaxation avoids the unwanted adverse
effects of depolarising agents.

Potency of these drugs, expressed as their ED95 values, affects the clinical dose, onset of
action and duration of action. Comparison of clinical potency, supported by appropriate figures
of ED95 is expected. A brief explanation the significance of how the lower potency of
rocuronium administered affects its onset of action is expected. Typical onset time after an
intubating dose (expressed as related to ED95) of each drug as well as the expected clinical
duration of action are expected as well. The clinical onset can be hastened with an increased

5
dose, and how this increased dose affects the clinical use (including limitations of use) and
duration of action of these drugs should be discussed.

Reversibility of action / clinical effects

The action of these drugs at the neuromuscular junction can be reversed with
anticholinesterases e.g. neostigmine. The availability of sugammadex as the alternative
reversal agent for rocuronium should be mentioned as well.

Extra junctional effects of drugs

There are no direct cardiovascular effects caused by either of these agents. Atracurium may
cause transient hypotension and tachycardia commonly related to histamine dose. The risk of
histamine release due to atracurium is increased with faster rate of administration as well as
larger dose used. For this same reason, rocuronium is preferred in patients with asthma.
Lastly, critical illness myopathy is likely to be seen, more likely in patients on prolonged
infusion of steroid-based neuromuscular relaxants such as rocuronium. The exact mechanism
of this phenomenon is unknown generally.

Physiological conditions and drug interaction affecting the action of these drugs are also
awarded marks.

Though majority of the candidates compared the pharmacology of both drugs successfully,
these answers have failed to discuss the relevant clinical correlations. For example, both drugs
are described to be highly water soluble, but many did not mention the role of hydrophilicity in
the distribution of these drugs and the absence of central nervous system and foetal effects.

A significant proportion of candidates discussed at length the pharmaceutical or

physicochemical details of each drug, but did not relate how these features affect the clinical
use. Mistakes were noted on the concentration of each drug in the typical commercial
preparations, and surprisingly atracurium was noted to be available in 2.5 mg/mL, 5 mg/mL
and 25 mg/mL preparations. Rocuronium was said to be available in 50 mg/mL aqueous
preparation as well as powder form. Some also mentioned that atracurium is available as
racemic mixture which may indicate misunderstanding of concept of isomerism. Lengthy
discussion of features of non-depolarizing neuromuscular blockade including the findings from
neuromuscular monitoring was found in some of the answers, which again is not required
generally in the answer.

The organ-dependent and organ-independent routes of metabolism and elimination were

generally well described. The impacts of this difference in metabolism and elimination of
atracurium and rocuronium on selection of neuromuscular relaxant in patients with organ
dysfunction were well-answered.

Concept of ED95 is of utmost importance in the pharmacology of neuromuscular relaxants.

Confusion existed among the candidates as some thought that ED95 is a variable parameter,
so different values of ED95 were quoted for scenarios of elective intubation and rapid sequence
induction. Some failed to appreciate that ED95 is a measure of potency, as these figures were
well described in the answer without further comparison of clinical potency. A significant
proportion of candidates have given the ED95 wrongly, for example ED95 of atracurium was
quoted to be 0.05, 0.1-0.15, 0.3-0.4 and 0.5 mg/kg. A significant proportion of answers

6
suggested that atracurium and rocuronium are equipotent, or rocuronium is more potent that
atracurium clinically. Due to the incorrect figure of ED95, intubating dose could not be answered
correctly. Some failed to realize that intubating dose can be expressed in terms of ED95 while
some failed to appreciate that typical intubating dose is 2x ED95. As a result, 4x ED95 of
atracurium was quoted to be the typical intubating dose. The onset time and clinical duration
of an intubating dose of these drugs were misquoted in some of the answers.

With regards to the reversal of residual effects of atracurium and rocuronium, many candidates
neglected to point the use of neostigmine as the reversal agent for rocuronium. Sugammadex
was mentioned in all the answers and it was stated to be the only drug to reverse the effects
of rocuronium.

Histamine release is mentioned in all the answers, but the impact of histamine release on the
respiratory and cardiovascular systems are not discussed. Histamine release was noted to
cause bradycardia commonly in quite a significant proportion of the answers. Mostly all have
not realized that benzylisoquinoline compounds like atracurium may promote the non-
immunologic release of histamine that can cause a reduction in systemic blood pressure and
bronchoconstriction in susceptible patients. This direct non-immunologic release of histamine
may probably be the main mechanism involved as compared to anaphylactic reaction.
Histamine release is related to immunologic mechanism in almost all of the answers. Nearly
none has answered that atracurium doses in excess of 2-3 ED95 are required to produce
significant histamine release.

Critical illness myopathy was often missed out in the answer, and only a few candidates have
successfully mentioned this side effect. Candidates are expected to know the common risks
associated with this effect, and compare the incidence of critical illness myopathy among these
two drugs. None seemed to have included these in the answers.

7
Question 5
a) Classify anti-platelet drugs with examples. For each (4 marks)
classification, describe its mechanism of action.
b) Describe the mechanism of action of protamine when used (6 marks)
for heparin reversal. Outline the side-effects of protamine.

51% of candidates passed this question.

Most candidates were able to mention all four main classifications. Extra marks will be
obtained if example of each class is given. For different mechanisms of action, candidates
have to be specific in their description. The statement like reducing platelet aggregation and
inhibition of platelet adhesion can be true for COX inhibitor (e.g. aspirin) but not for other
classes of anti-platelet drugs. Some candidates included diagram to enhance their answers.

Few candidates did not read the question properly and confused with anti-coagulants. No
marks are given for this answer.

Mechanism of action of protamine when used for heparin reversal is mainly by neutralisation
effect of heparin. Strongly basic protamine (with its positive charge) + strongly acid heparin
(negatively charge) forms inactive complex that is removed by reticuloendothelial system.
Most candidates have a basic understanding on this mechanism of action. In addition,
protamine also inhibits formation and activity of thromboplastin (extrinsic pathway). Marks are
given if the dose of protamine is given i.e. 1 mg protamine sulphate is required to reverse 100
units of heparin.

For adverse effects, there are three major groups i.e. cardiovascular, allergic reactions and
anticoagulation. To obtain full marks, candidates need to include brief description for the
adverse effects e.g. allergic reactions in patients previously received insulin containing
protamine and those who are allergic to fish; anticoagulation effect because when protamine
is given in excess it has some anticoagulation effect; hypotension due to histamine release
and etc.

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Question 6
Write short notes on:
a) Metoclopramide (5 marks)
b) Dantrolene (5 marks)

Only 32.5% of candidates passed this question which was surprising considering that
metoclopramide is a commonly used drug and dantrolene should be known to all anaesthetists
who use inhalational agents and suxamethonium in their clinical practice! Being the last
question answered also probably led to the rushed and inadequate answers given by most
candidates.

Part A

Many candidates only remembered that it was an antiemetic. Many forgot its important
prokinetic function which is the basis of its use in aspiration prophylaxis (although listing it as
one of its many uses in clinical practice). Where the mechanism of action is concerned,
candidates should be more specific in elaboration of the specific receptors involved (D2, 5HT3,
5HT4) and if it was an agonist or antagonist at the receptors. Only a few mentioned its effect
on the lower oesophageal sphincter tone. Some candidates incorrectly mentioned that
metoclopramide reduced gastric acid secretions and decreased gastric motility! Few
candidates mentioned correctly the dosage used for antiemetic or prokinetic use. Most
mentioned the important side-effects, like potentially causing extrapyramidal symptoms
(oculogyric crisis, akinesia) but did not elaborate that it occurred more commonly in the young
/ elderly / at high doses or with renal impairment; sedation; the ability to trigger neuroleptic
malignant syndrome; acute conduction abnormalities / hypotension / tachy- and bradycardias
but neglected to mention that it occurs following rapid administration of the drug. Few
mentioned that it should be avoided in porphyria and the drug interactions it may cause by
inhibiting plasma cholinesterase activity.

Part B

The knowledge on dantrolene was generally very poor among the candidates. Some chose
to describe on malignant hyperthermia (MH) itself instead of concentrating on the drug per se.
Although majority knew its uses, there were two candidates who incorrectly mentioned that it
was a definitive treatment for local anaesthetic toxicity! A few mentioned that it was a
neuromuscular blocking agent! Some obviously have not read about nor seen the bottle before
and thought it was a prepared solution. Many did not mention that it needs to be reconstituted
ONLY with 60 ml of sterile water and no other solution. Few mentioned that it is highly alkaline
in solution (pH 9.5), thus highly irritant when extravasated and the need to protect the solution
from light after reconstitution. Mechanism of action should be more precise on its direct action
on excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor
and decreasing the amount of calcium released from the sarcoplasmic reticulum. Most
neglected to mention that it does not alter neuromuscular transmission and that therapeutic
doses have no effect on cardiac or smooth muscle. Majority did not know the appropriate
dosage to use in management of MH. Some even quoted a huge initial bolus of 50 mg/kg and
while some confidently ‘quoted’ AAGBI guidelines, the doses mentioned were incorrect. Few
mentioned about the recrudescence which occurs in about 25% of cases and need to

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continue dantrolene and the dosage required, for at least 24 hours depending on response to
treatment. Some mentioned the drug interaction with calcium channel blockers but did not
mention what happens if the drugs are given together. Candidates badly need to read up and
revise on this life saving drug as anaesthetists need to be able to recognise the MH crisis and
know how to use dantrolene appropriately.

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