BT_PO 1.109 Outline the pharmacological treatment of peptic ulcer disease and reflux

If you are doing an endoscopy list then it is highly likely that a PPI will feature on your patient’s medication list. They account for a significant percentage of the drug budget still despite being off patent. Indeed for the year 2016-2017 a PPI was the third and fourth most frequently prescribed drug in Australia (statins accounted for the top two slots). I can remember as a junior doctor that you needed to have endoscopically proven reflux before you could prescribe this new fangled stuff called  omeprazole (it wasn’t that long ago).

I have used Goodman and Gilman. The first four statements are important and the next few are less so.

T/F  PPIs can cause gastric polyposis*

T/F  PPIs reversibly inhibit parietal cell H K ATPase

T/F  PPIs are well absorbed by the stomach

T/F  Sucralfate is preferred as ulcer prophylaxis in ICU pts because it is not associated with the development of nosocomial pneumonia

less important now…

T/F  Sucralfate is a prostaglandin analogue

T/F. Misoprostol inhibits acid production and stimulates mucus production

T/F  Esomeprazole is the S-isomer of omeprazole and is a pro drug like all PPIs

T/F  Omeprazole has the potential for multiple drug interactions due to inhibition of the 2C19 cytochrome

T/F  PPIs can make you anaemic

T/F  there is an association between long term PPI use and dementia

*doesn’t stop some gastroenterologists from biopsying them.

BT_GS 1.22 Describe the mechanisms of action and potential adverse effects of buffers, anti-oxidants, anti-microbial and solubilising agents added to drugs

There is one reference in the Primary Exam Reading List  which is a journal article not a book.  Pharmaceutics for the anaesthetist was written by a former Chair of the Primary Exam and contains material not available in the usual anaesthetic pharmacology textbooks (which is why it is still on the reading list even though it was published in 2001).

Interestingly, this article mentions cyclodextrins in the context of solubilising lipophilic drugs and 17 yrs later a cyclodextrin is a popular drug in anaesthetic practice but not in the way the article predicted.

T/F Water is considered a non-polar solvent

T/F Ethylene glycol is safe for use a solubilising agent

T/F 1 ml of oil emulsified in water results in a droplet surface area of approximately 500 m²

T/F Lyophilisation is used to prevent hydrolytic degradation of drugs

T/F Trace amounts of oxygen in an ampoule can be enough to initiate the oxidation process

T/F Propofol has anti-oxidant properties

T/F Hydrolysis, oxidation, isomerisation and exposure to ultraviolet light can reduce the potency of drugs

T/F Preservatives are substances added to pharmaceutical products to prevent degradation

T/F Hypotonic and hypertonic solutions can cause pain on injection, thrombophlebitis, haemolysis

T/F Intrathecal use of preservative containing drugs is strongly associated with neurotoxicity

T/F pH adjustment of drug preparations is done for many reasons which can be difficult to determine


How is drug X presented?  This is a old favourite in the vivas and definitely reveals those candidates who have used drug X and those who haven’t.  There is no specific LO today but a post next week will cover BT_GS 1.22.

The questions in today’s post are not true/false and there is no specific reference.  I expect you should be able to find the answers from simple observation, experimentation, consultation with your consultants or from the product information leaflets*.

*Ask your anaesthetic assistant or the pharmacist in your hospital.

Do you know the difference between a vial and an ampoule?  Where does a ‘minim’ fit in?  (hint: ‘eyes’)

Which drugs require reconstitution?  Which drug is more soluble: parecoxib or cefazolin?

What are the contents of an ampoule of:

  • propofol?
  • thiopentone?
  • local anaesthetics for intrathecal administration? What is NOT in these ampoules?

What happens in the injection port if you inject suxamethonium straight after thiopentone?*  Are there any other combination of drugs which have the same effect?

*Not really examinable in the Primary Exam but an important point for practice

Which drugs are dangerous if a whole ampoule is administered and for which would this be annoying but not life threatening?


Some numbers you should all know…

After years of supervising and quizzing trainees, I am disappointed to report that many of them do not know the answers to the following questions.

I suggest that you should know the answers to all of the statements below and not require a calculator to compute the answer.

  1. One cubic metre is equivalent to X litres.
  2. One bar is equivalent to X mmHg and Y kilopascals.
  3. A 0.25% solution contains X mg per ml.
  4. 10mls of 1% lignocaine with 1 in 200,000 adrenaline contains X micrograms of adrenaline.
  5. A size 2.5 LMA is recommended for children weighing between X and Y kg.
  6. I put 3mg noradrenaline in dextrose to make up a total volume of 50mls*. I put the syringe in the driver and start it at 10mls/hr. This is equivalent to X micrograms per minute.
  7. The intubating dose of cisatracurium** is X mg/kg
  8. The patient weighs 150kg and is 180cm tall. The intubating dose of rocuronium is X mg***.

Fortunately, you will not be required to perform basic arithmetic in the vivas. It will often be asked of you in clinical practice however.

*This is a pretty standard dilution for inotropes. The answer may explain why.

**Yes, some people do use relaxants other than roc.

***This might be a trick question.

BT_GS 1.5 Explain the law of mass action and describe affinity and dissociation constants

The law of mass action states that the rate of a reaction is proportional to the concentration of the reacting substrates     T/F

The affinity constant (Ka) is a measure strength of drug-receptor binding    T/F

The dissociation constant (Kd) is a measure of the the tendency for the drug-receptor complex to split    T/F

Ka is the molar concentration of the drug at which 50% of receptors are bound at equilibrium     T/F

Kd is the molar concentration of the drug at which 50% of receptors are bound at equilibrium    T/F


BT_GS 1.1 Explain the concept of drug action with respect to: Receptor theory, Enzyme interactions, Physico-chemical interactions

All drug receptors are proteins         T/F

In general, drugs binding to receptors cause a conformational change     T/F

Physiologic response is directly proportional to the number of receptors bound by drug   T/F

An enzyme is a biological catalyst  that increases the speed of a reaction without being consumed in the reaction itself   T/F

A zero-order reaction is one whose rate is independent of the concentration of the reacting components and is, therefore, constant     T/F

The Michaelis-Menten equation can model the velocity of both zero-order and first order reactions   T/F


The following is an (incomplete) list of a few ‘types’ of receptors I could think of or find in a few textbooks I perused.  I am sure you can add to this list.
Stretch receptors
Metabotropic receptors
Ionotropic receptors
Drug receptors
Hormonal receptors
Neurotransmitter receptors
Sensory receptors
Can you provide a definition of a ‘receptor’ that covers the list above?
Which of these would not fit with the usual idea of a ligand/receptor interaction?
There was a time when the concept of a receptor did not exist but now we use the word almost every day.
How did we get from then to now, i.e. what is the evidence for the existence of receptors?
There are six LO’s relevant to receptor theory.  A number have been covered before and there are two that will be covered is the next two posts.
BT_GS 1.1 Explain the concept of drug action with respect to: Receptor theory, Enzyme interactions, Physico-chemical interactions
BT_GS 1.5 Explain the law of mass action and describe affinity and dissociation constants
I know BT_GS 1.21 does not mention receptors but it is related to the main question of this post. Can you explain how?
These two eBooks on the ANZCA Library website have comprehensive sections on receptor theory:
Rang & Dale’s Pharmacology 8e Ch 2 How drugs act: general principles. (Probably the better of the two)
Goodman & Gilman The Pharmacological Basis of Therapeutics 13e Ch 3
This historical article may help with the ‘evidence’ question above: The receptor concept: pharmacology’s big idea
This website has a useful summary on the ‘Receptor Theory of Drug Action’ page.  On this  website, you will also find a link to the 2017 CICM Primary Syllabus.
If you think the CICM syllabus seems similar to the ANZCA Primary Exam LO’s (Appendix Two) – you would be right – the CICM syllabus was created from the old ANZCA Primary Exam Syllabus.
Which one do you prefer?


BT_PO 1.101 Outline the pharmacology of drugs acting via effects on serotonin or serotonin receptors



Possibly the commonest regular medication that the under fifty year old female patient is likely to be on is an antidepressant. Although not a core topic, some knowledge about these drugs is helpful as they do have some perioperative management implications.

The side effect profile of most of these compounds includes most of the conditions that they are prescribed for  T/F

Concurrent administration of tramadol is likely to cause serotonin syndrome  T/F

Sumatriptan is a 5HT-3 receptor anatgonist  T/F

Sertraline can cause severe hyponatraemia  T/F

Perioperative use of SSRIs doubles the likelihood of getting an allogenic blood product transfusion T/F


BT_PM 1.28 Describe the pharmacology of anticonvulsants relevant to pain medicine, including gabapentin and carbamazepine

These drugs are minor players in terms of exam worthiness but are certainly frequently seen and prescribed by anaesthetists – and not just on pain rounds either. According to the PBS report for 2016-2017- of the ten most expensive drugs by cost to the government, pregabalin (autocorrect wanted me to type ‘prefab alien’!) comes in at number eight and cost the taxpayer $160 million. As an aside most of the other drugs featuring in this list are used to treat hepatitis C. I thought they would have been chemotherapy agents.

Only a few statements below and you probably should know the answers for practical purposes if nothing else. G and G and Stoelting were the references used.

T/F  carbamazepine induces multiple hepatic cytochromes including those responsible for its own metabolism

T/F  gabapentin and pregabalin are GABA agonists*

T/F  no one knows how gabapentin and pregabalin really work*

T/F  gabapentin and pregabalin are renally excreted unchanged

T/F  sedation is the commonest adverse effect with these drugs and usually resolves with time

* Yup, both these statements can’t be correct.

BT_PM 1.25 Describe in detail pharmacology of paracetamol including mode of action, clinical utility, metabolism and toxicity, advantages and disadvantages of different routes of administration**


I fondly recall Martin Tramer (Swiss anaesthesiologist famous for the numerous systematic reviews he has performed) speaking at a NZSA conference in Dunedin a decade ago. Someone asked him about IV paracetamol (it was novel at the time) and he said, “Ah yes, a formulation for which there is no indication.” I agreed with him at the time and I still (mostly) do. Indeed at the time the intravenous formulation cost 10000 times as much as a tablet! (It’s still two hundred times as much now.) I somewhat unkindly see it as something the recovery nurse can administer while waiting for the opioid or NSAID to work. Nonetheless paracetamol is ubiquitous for the anaesthetist and the primary curriculum rightly expects detailed knowledge of this drug. The answers to all of these statements except the last one can be found in Goodman and Gilman however you have to look up ‘acetaminophen’ in the index.

T/F  the bioavailability of oral paracetamol is similar to that of the IV formulation

T/F  paracetamol reliably has an opioid sparing effect but does not reliably reduce opioid related adverse effects

T/F  paracetamol is extensively metabolised by the liver and mostly undergoes conjugation

T/F  paracetamol is an NSAID

T/F small amounts of the hepatotoxic metabolite NAPQI are normally produced with therapeutic doses of paracetamol

T/F N-acetylcysteine acts to replenish hepatic stores of glutathione in the management of paracetamol toxicity

T/F you are less likely to die of a paracetamol overdose if you take it in the morning*

*It has always astonished me that one pack of paracetamol is potentially fatal if taken all at once and that so few people have killed themselves with it despite its ready availability. Many drugs display chronobiology, i.e. variability in their activity/ metabolism/ toxicity depending on the time of day. Paracetamol is similarly affected according to a study on mice. Mice given an overdose of paracetamol in the morning had virtually no adverse effects whereas those given it in the evening were likely to die. Researchers attribute this to circadian variations in the hepatic cytochrome activity and glutathione production in anticipation of when the mouse is most likely to eat (which is nighttime for them).

**I can’t think of any circumstances why an anaesthetist would want to administer paracetamol rectally (so there is a role for IV paracetamol…)