The Hong Kong College of Anaesthesiologists

Intermediate Fellowship Examination

February / March 2023
Examiners' Report - Pharmacology

General
Nine (out of 19, 47.4%) candidates passed the written examination.
Fourteen (out of 19, 73.7%) candidates passed oral examination.
Overall, fourteen (out of 19, 73.7%) candidates passed the Pharmacology section of
the Intermediate Examination.

Written
Question 1
Describe how peripheral nerve stimulator is used in assessing the depth of
neuromuscular blockade WITH NON-DEPOLARISING muscle relaxants (85%)
AND patients’ feasibility for reversal (15%).

(12 out of 19 candidates passed this question)

Main points expected
- Describe the various functions of nerve stimulator, e.g., TOF, PTC and DBS
- Describe how these functions can monitor the depth of neuromuscular blockade
- Describe whether their ability to monitor on the depth of blockade is related to
assessment on feasibility on reversal
Comments
- Some candidates wasted time on describing how to apply nerve stimulator, e.g. on
ulnar nerve
- Most candidates failed to demonstrate how DBS is superior to TOF in view of
assessing the suitability on extubation
- Most candidates can point out that a TOF count of at least 2 is needed for effective
reversal

Question 2
Outline the pharmacokinetic profile of oral paracetamol (60%). Discuss how
other drug(s) can alter its pharmacokinetic profile (40%).

(2 out of 19 candidates passed this question)

Main points expected
- PK profiles of oral paracetamol, including its absorption (site, rate and
bioavailability), protein binding, metabolism and clearance
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- Various factors affecting these PK profiles, e.g., gastric emptying, renal impairment
- Drugs that affecting these PK profiles, e.g., alternation of the gastric emptying time,
inhibition of the liver glucuronization, and activation of the P450 enzyme system
Comments
- Failed to mention bioavailability of oral paracetamol is dose-dependent
- Failed to point out the paracetamol is absorbed in small intestine
- Failed to mention gastric emptying, therefore any drug, will affect the rate of
absorption (amount of absorption is not affected)
- Failed to demonstrate that the clearance of paracetamol is not greatly affected by
renal impairment

Question 3
Describe and Explain SIX opioid effects on the central nervous system.

(10 out of 19 candidates passed this question)

Main points expected
- Describe six pharmacodynamic effects of opioid on central nervous system,
including its clinical therapeutic effect and adverse effect, how and when to occur
- Give explanation based on opioid’s mechanism and site of action
Comments
- Some candidates described the opioid effect on peripheral system which could not
score marks e.g. GI motility, histamine release
- Failed to describe opioid effect on temperature regulation, sleep architecture,
muscle tone

Question 4
Define and describe the term second messenger (50%). Give an example of β1
adrenergic agonist and describe the corresponding second messenger system
involved for clinical actions (50%).

(8 out of 19 candidates passed this question)

Main points expected
- Describe main characteristics and function of second messenger system, including
activation, synthesis, action, degradation of the intermediate molecules.
- Describe how β1 adrenergic agonist trigger the second messenger system and
produce clinical effect.

Comments

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- Some candidates wasted time on listing various types of second messenger system
- Failed to mention regulation of intermediate molecules, which can be used to
amplify or dampen response.
- Most candidates can describe well on β1 adrenergic agonist second messenger
system, but some candidates wasted time on describing other adrenergic receptor
action

Question 5
With regard to glyceryl trinitrate (GTN):
a) Describe the cellular mechanism of GTN in the management of
myocardial ischaemia (30%).
b) Explain the effects of GTN on cardiovascular system and its effect on
myocardial oxygen consumption (30%).
c) Explain the rationale of administration of GTN as sublingual route
(25%).
d) Describe the changes in therapeutic effect after repeated doses of GTN.
Explain the underlying mechanism (15%).

(15 out of 19 candidates passed this question)

The question on glyceryl trinitrate was well answered with most candidates scoring a
good pass. The question specifically had a number of sub headings to allow candidates
to focus the responses. Everybody seemed to quite clearly understand that GTN acts as
a nitric oxide donor by a direct action on cyclic GMP. After release from the GTN
molecule, the NO molecule needs an intermediary to exert its effect. There are a
number of candidates, but sulfhydryl groups seem to be the main contender. Exhaustion
of these following repeated thought to be the mechanism of tachyphylaxis. One area of
disagreement concerns the primary site of action. While there is no doubt that all
vascular smooth muscle is affected to some degree or other, it is the venous system that
seems the main target. This be no dilation, with subsequent reduction in preload in the
main effect of the drug. Arterial system can be affected at higher doses leading to
hypotension. The effect on coronary vessels is thought to be minimal

Question 6
Describe the risk factors for systemic toxicity with Amide local anaesthetic
agents.

(17 out of 19 candidates passed this question)

Questions on local anaesthetic toxicity come up quite often, and as such the standard

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of answers was expected high. There is a lot of materials to be considered, so a good
plan is essential. Most candidates stuck to pharmacodynamic and pharmacokinetic
principles, and included the importance of stereoselectivity in drug design and the
addition of vasoconstrictors impact toxicity. Importantly the site of injection, and the
amount of substance injected were also crucial, and it squally considered under the
heading of “patient factors”. Overall, a well performing question.

Question 7
Explain the differences of Propofol induction in a 70-year-old man and a
4-year-old child respectively with respect to dosage (33.3%), onset time (33.3%)
and duration of action/offset time (33.3%).

(7 out of 19 candidates passed this question)

Majority of candidates only received a fair pass in this question. It is important to
understand the pharmacokinetics of such a commonly used drug in anaesthesia. The
induction dose is largely determined by the volume of distribution and it is different in
young and elderly patients. Common dosage is preferably answered, e.g. a higher
induction dose for pediatric patients 3-4mg/kg is usually given. The onset time of
Propofol is determined by the cardiac output which is obviously different between the
young and elderly. Finally the duration or offset is affected by redistribution and
effect site sensitivity.

Question 8
The following statement is made in a scientific journal.
“After administration of the new anti-hypertensive drug the systolic blood
pressure in group A (n=100) was 110 ± 10 mm Hg (mean ± standard deviation).
In the control group B (n=100) the systolic blood pressure was 130 ± 20 mm Hg
(mean ± standard deviation).”
a) Define the terms “mean” and “standard deviation” (detailed equations
are not required) (45%).
b) Assuming both populations are normally distributed, draw a population
graph for groups A and B incorporating the statistical data detailed above
(55%).

(17 out of 19 candidates passed this question)

This was a straightforward question with a passing rate of more than 90%. Most
candidates depicted a correct normal distribution curves for group A and B with
different mean and standard deviation labeled. However, some could not

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demonstration an equal area under curve (AUC) for both groups.

Question 9
Compare and contrast the Mechanism of Action, Clinical Applications, and
Major Side effects of Loop diuretics and Thiazides-like diuretics.

(10 out of 19 candidates passed this question)

Most candidates were able to describe the site of action and key mechanism of loop
diuretics and thiazide-like diuretics. Some have mistaken blockage of the Na/K
cotransporter as the mechanism of action for thiazide-like diuretics. However, few
candidates could describe the differences and point out the underlying mechanism that
leads to the differences. Regarding clinical application, although there are similarities
in the usage of the two diuretics, many candidates made no difference between the
applications of both diuretics at all. Most of the candidates were able to tell major
side-effects of the two diuretics.

Question 10
Compare and Contrast the Pharmacology of Ondansetron and Metoclopramide.
(Exact value of PKa and Vd not required)

(6 out of 19 candidates passed this question)

Answers were in general lack of accuracy, comprehensiveness and depth of
understanding. For example, a lot of candidates wrote non-specific descriptions like
both drugs were metabolized by liver and excreted by kidney. A few candidates
realized that IM and SC routes are also available for both drugs. The mechanism of
action of both drugs centrally were well understood while peripherally were poorly
understood. Very few candidates could point out the antagonistic effect of
ondansetron on other serotonin receptor agonists such as SSRI and tramadol, and the
increase in serotonin level in CNS could potentiate serotonin syndrome.

Question 11
a) Describe the process of production of nitrous oxide (50%).
b) Describe and Explain the undesirable effects of nitrous oxide on the
cardiovascular and hematological systems (50%).

(11 out of 19 candidates passed this question)

Candidates perform poorly in the first part of the question. Majority of the candidates
were not able to describe the preparation of Nitrous Oxide. Main points required for a

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pass include heating ammonium nitrate at 270C, impurities removed by cooling the
gas and passing it through water, gas then dried and cooled to -40 and stored under
pressure in steel cylinders, and bonus marks if candidates can mention its critical
temperature in relations to its storage condition.
As for second part of the question, most candidates were able to describe different
side effects of N2O on cardiovascular system and haematological system respectively.
Better candidates were able to mention increase in PVR and elevated homocysteine
effects on the cardiovascular system.

Question 12
Describe the mechanism of action of Anticholinesterases (50%). Give FOUR
clinical indications (20%). Explain the advantages of using pyridostigmine over
neostigmine in treating Myasthenia Gravis (30%).

(15 out of 19 candidates passed this question)

Most candidates were able to describe the mechanism of action of anticholinesterases
and their clinical indications. Better candidates could classify anticholinesterases into
reversible and irreversible categories, explain with underlying molecular principles,
and gave correct examples respectively.
Yet, most candidates were not able to give appropriate advantages of pyridostigmine
over neostigmine in treating MG. Candidates very often mixed up the onset time,
half-life, and the potency between the 2 drugs. (Oral pyridostigmine has a faster onset
time, longer half-life, and is less potent, thus making it easier to adjust for dosing
schedule and titrate its adverse effects.)

Viva
Table 1
One examiner was on site while the other was online. There was no major technical
problem throughout the examination.

Gastrointestinal Drugs & Drug Metabolism

The topics regarding gastrointestinal drugs were about agents that reduce gastric acidity
and antacids. These were generally well handled. The last topic examined liver
metabolism and did provide a challenge to some. Some candidates seemed to not fully
understand the importance of polymorphism in drug metabolism with regard to either
codeine or tramadol. All but four candidates passed this section.

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Volatile agents
Most candidates were able to describe and explain the factors in wash-in of
Desflurane and N2O. Some candidates confused between vessel rich group and vessel
poor group during wash-in phase, so could not explain correctly on the effect of
cardiac output and various partition coefficient. Use of Desflurane, compared to
Sevoflurane, in prolonged surgery benefits more in wash-out phases instead of
wash-in phases. Candidates were commonly found to say whatever they know instead
answering specific pharmacokinetic and pharmacodynamic advantages and
disadvantages on use of Desflurane in prolonged surgery.

Anticoagulants
Most candidates were able to describe the difference between unfractionated heparin
and LMWH. Only few candidates were aware the dose dependent difference in
metabolism and elimination half-life of UFH. To monitor UFH side effect, most
candidates focused on over-coagulation but idiosyncratic thrombocytopenia, infusion
related reaction, potential liver impairment are also important.

Table 2
Muscle Relaxants
Candidates did well on the mechanism of action and side effects of suxamethonium.
The mechanism of action of dantrolene was also well answered. It was surprising that
a few candidates did not know the presentation and dosage of dantrolene needed to
treat malignant hyperthermia.
Quite a number of candidates did not know that rocuronium was mainly eliminated
from the body via the biliary route.
Pharmacology of sugammadex and factors affecting the dosage of sugammadex for
neuromuscular reversal were well answered.

Drugs acting on the Uterus

Pharmacokinetics of oxytocin and carbetocin was generally well answered. Most
candidates can list the other group of drugs used to treat postpartum haemorrhage.
Many candidates were not aware that ergometrine (syntometrine) can be given
intramuscularly, which is an advantage over syntocinon when no intravenous access is
available.
All candidates did well on the classification of tocolytics but quite a number of them
could not explain clearly on the mechanism of action of calcium channel blockers in
treating preterm labour and the benefits of calcium channel blockers over

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beta-agonists in inhibiting preterm labour include prolongation of pregnancy, fewer
serious neonatal morbidities etc.

Opioid
This question was generally well answered. Pharmacokinetics for “everyday drugs”
should be studied thoroughly and thus marking was very strict. A few candidates
could correctly make conversion of morphine from oral form to Intrathecal form.

Oral hypoglycemic agents

Perioperative medicine is definitely important in our daily practice. And it is our
responsibilities to keep ourselves up to date with these drugs. Only a few candidates
could not classify the three oral hypoglycemic agents. Most of the candidates showed
understanding of SGLT2 inhibitors and their potential side effects. Ironically, only 1
candidate knows what SGLT2 stands for!

- End -

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