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. 

 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).