Viva B(iv)b

This viva is relevant to Section B(v) of the 2017 CICM Primary Syllabus, which expects the exam candidate to "describe the concepts of effect-site and context sensitive half time". 

Define the term "biotransformation"

"Chemical alteration of an agent (drug) that occurs by virtue of the sojourn of the agent in a biological system".
The Pharmacology and Experimental Therapeutics Department Glossary at Boston University School of Medicine

What are Phase I and Phase II biotransformation reactions?

Characteristics of Phase I reactions:

  • these reactions expose or introduce a functional group (–OH, –NH2, – SH or –COOH)
  • They usually result in a small increase in hydrophilicity.

Examples of Phase I reactions:

  • Hydrolysis
  • Reduction
  • Oxidation.

Characteristics of Phase II reactions:

  • The products are supposed to be significantly more hydrophilic than the original substrate

Examples of Phase II reactions:

  • Glucouronidation
  • Sulfation
  • Acetylation
  • Methylation
  • Conjugation with glutathione
  • Conjugation with amino acids eg. taurine, glutamine, glycine
What is meant by the term "first order kinetics"?

"First-order kinetics... is where a constant fraction of drug in the body is eliminated per unit of time"-  college answer to  Question 5(p.2) from the second paper of 2009. 

first order elimination kinetics on a linear scale

 When doubling the concentration of reagents also doubles the reaction rate, the increase in rate is by a factor of 2 (2 to the first power, or 21). That "first power" gives rise to the term "first order". In that fashion, one can have a "second order" reaction where doubling the concentration of reagents quadruples the reaction rate (i.e 2 to the second power, 22).

What is mean by the term "zero order elimination"?

In chemistry, when doubling the concentration of reagents has no effect on the reaction rate, the increase in rate is by a factor of 0 (i.e. 20). This is zero-order kinetics. The relationship of concentration to reaction rate can therefore be plotted as a straight line.

What is an example of a drug cleared with zero-order elimination kinetics?
  • Ethanol is a classic example
What is mean by the term "Michaelis-Menten elimination kinetics"?

Michaelis-Menten kinetics  describes enzymatic reactions where a maximum rate of reaction is reached when drug concentration achieves 100% enzyme saturation.

Thus, when the patient is receiving regular doses of the drug, if the concentration is already high then relatively small changes in the dose will produce a disproportionately large change in drug concentration.

What is mean by the term "Non-linear elimination kinetics"?

Non-linear elimination kinetics is the term which describes drug clearance by Michaelis-Menten processes, where a drug at low concentration is cleared by first-order kinetics and at high concentrations by zero order kinetics (eg. phenytoin or ethanol). 


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Rangno, R. E., J. H. Kreeft, and D. S. Sitar. "Ethanol ‘dose‐dependent’elimination: Michaelis‐Menten v classical kinetic analysis." British Journal of Clinical Pharmacology 12.5 (1981): 667-673.

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