Learning Objects : Lifelong Application

RLO: Clinical impact of changes in drug clearance

Resources

Title/link	Description
RLO:Introduction to drug clearance	Provides a definition of clearance, and a basic explanation of the factors which influence it.
RLO: Half-life of drugs	Explains the half-life of drugs and its relationship with volume of distribution and clearance.
RLO: Volume of distribution	Explains the pharmacological concept of Vd, and how it is calculated.
Inheritance and drug response (also available in pdf format)	Article published in the New England Journal of Medicine in 2003.
Interactive clinical pharmacology	A site developed in the Department of Clinical Pharmacology, Christchurch Hospital/School of Medicine, New Zealand.
Pharmacokinetics in Older Adults - Geriatrics	MSD Manual Professional Edition (msdmanuals.com)

Glossary

Clearance: The rate of drug elimination divided by the plasma concentration of the drug.

Conjugating enzyme systems: Enzyme systems involved in the attachment of a polar group, such as glucuronyl, a sulphate, a methyl, an acetyl or a glutathione to an active drug. Conjugation is a Phase II metabolism reaction.

Cytochrome P450: Drug metabolising enzymes that are embedded in the smooth endoplasmic reticulum of liver cells.

Genetic polymorphisms: Changes in the genetic code which occur in a population and result in the production of enzymes, particularly cytochrome P450 enzymes, which may as a result be more or less active than the norm.

Glomerular filtration: One of three processes which are critical for renal clearance. Involves the filtration of 20% of renal plasma flow through the glomerular capillaries, thus allowing drug molecules to diffuse into the glomerular filtrate.

Half-life: The time taken for the plasma concentration of a drug to reduce by 50%.

Phase I metabolism: Phase I metabolism reactions are catalysed by cytochrome P450 enzymes. These reactions are catabolic, and the products can be more chemically reactive.

Phase II metabolism: Phase II reactions involve conjugation. The resulting conjugate is almost always pharmacologically inactive and less lipid soluble.

Metabolism: The enzymatic conversion of one chemical entity to another in order to make it less lipid soluble, hence easier to excrete.

Proton Pump Inhibitors: A group of drugs which act to reduce acid secretion in the stomach by irreversibly inhibiting the H+/K+ ATPase enzyme or proton pump.

Therapeutic index: A measure of a drug's value, taking into account not only its useful properties, but also its toxic effects; a simple measure of benefit versus risk.

Tricyclic antidepressants: A group of antidepressant drugs which share a similar chemical and side effects; they act to prevent the reuptake of both noradrenaline and serotonin in the synapse. They aksi act as antagonists at muscarinic and histamine receptors.

Tubular secretion: One of three processes which are critical for renal clearance. Involves the transfer of drug molecules to the tubular lumen by two independent, non-selective carrier systems.