Describe the factors which contribute to inter-individual variability in drug response
seen with an induction dose of an intravenous anaesthetic drug.
This question required the candidate to provide some detail why a given dose of intravenous anaesthetic administered for the purpose of induction may result in a variable response between individuals. A logical division into pharmacokinetic and pharmacodynamic factors pertaining to the drug and how these are impacted by patient physiology, citing appropriate examples, was expected. Extremes of age, pregnancy, low and high cardiac output states, sympathetic tone, body habitus and factors impacting on drug redistribution and elimination should have been addressed. Extra marks were awarded for relevant discussion of pharmacogenetics. Discussion of the “bolus effect” versus slow infusion of an induction drug, relative to these factors should have been included. Mention of drug interactions, idiosyncratic reactions and relevant pathophysiology impairing organ function reserve was appropriate. The consequences of variability in drug response in terms of over- / underdosing, haemodynamic compromise, respiratory depression, delayed recovery and allergic
reactions needed emphasis to demonstrate understanding of the significance of predisposing
factors.
Effective answers to this question utilised either clear headings, or a tabular format, dividing what is a large topic into discrete areas. The lack of a structured approach to this question was invariably unsuccessful.
Syllabus Ref: G2a 2.c,d,e,f,g
Suggested Reading: Pharmacology and Physiology in Anaesthetic Practice / R K Stoelting – 4th ed - 2006. Chapters 4,6.
This SAQ, like the near-identical Question 2 from the second paper of 2011, was plagiarised in its entirety from the ANZCA primary (2005 and 2006). The ANZCA examiners comments are actually slightly better, and can be found on Kerry Brandis' website.
Pharmacokinetic factors | |
Administration and absorption |
Physiological factors
Pathological factors
|
Distribution |
Physiological factors
Pathological factors
|
Metabolism |
Physiological factors
Pathological factors
|
Elimination |
Physiological factors
Pathological factors
|
Pharmacodynamic factors | |
Physiological factors
Pharmacological factors
Pathological factors
|
Searle, R., and P. M. Hopkins. "Pharmacogenomic variability and anaesthesia." British journal of anaesthesia 103.1 (2009): 14-25.
Hoffman, WILLIAM D., et al. "Factors that determine the hemodynamic response to inhalation anesthetics." Journal of Applied Physiology 70.5 (1991): 2155-2163.
Smith, Stephen E., and Michael D. Rawlins. Variability in human drug response. Elsevier, 2013.