Blog #3

• What factors may affect the absorption and distribution of sedative-hypnotic drugs? What is the clinical significance thereof?

Different kinetics like: lipophilicity, biotransformation and elimination half-life affect the absorption and distribution of these drugs. Lipophilicity determines the rate at which the drug is absorbed and distributed, more lipophilic drugs are absorbed faster and are distributed through the body at a faster rate and thus have a rapid onset of action. Metabolism also has an effect on absorption and distribution, less lipophilic drugs are not affected or metabolised by the hepatic microsomal enzymes and can be excreted by the kidneys where more lipophilic drugs form active metabolites and must undergo oxidation and conjugation to be excreted in the urine. The elimination half-life also has an clinical significance because the shorter the elimination half-life the faster the drug is excreted and the faster it must be absorbed.

• What is meant by redistribution and what is the significance thereof?

The drug is redistributed from the brain to other tissue in the body. Highly lipid soluble drugs are absorbed and are distributed to the brain quite fast where they are then redistributed to the heart, kidneys and other body tissues then muscle and fats where these drugs can create a deppo-preparation so they are released in the body systematically over long periods of time

• How are the BDs metabolized? Name the various steps in the process.

1. Dealkylation
2. Oxidation
3. Conjugation

• Which BDs are converted to active metabolites? What is the significance thereof?

1. Diazepam
2. Chlorazepate
3. Prazepam
4. Chlordiazepoxide
5. Ketazolam

These drugs are metabolized by the hepatic microsomal enzymes, especially the Cytochrome P450 enzyme, these drugs undergo oxidation and conjugation to form an active metabolite that contributes to the drug effect. In patients with impaired liver enzyme function, like: the elderly, neonates, patients with liver cirrhosis and patients receiving therapy with Cytochrome P450 enzyme inhibitors, these drugs can be dangerous because the cannot be metabolised properly.

• Which BDs are not dependent on the cytochrome P450 oxidative enzymes for metabolism? What are the advantages thereof?

1. Oxazepam
2. Lorazepam
3. Temazepam
4. Lormetazepam

These drugs are not affected or metabolised by the hepatic microsomal enzymes and can be excreted by the kidneys. These drugs can be given to patients with impaired liver enzyme function, like: the elderly, neonates, patients with liver cirrhosis and patients receiving therapy with Cytochrome P450 enzyme inhibitors.

• What is enzyme induction? Which of the sedative hypnotic drugs are known for this? What is the clinical significance of enzyme induction?

Enzyme induction is when the drug causes an increase in production of specific enzymes that increase the metabolism of the drug. Enzyme induction causes a decrease in the amount of drug in the body’s circulation and thus causes a decrease in the effect of the drug on the body. Enzyme induction typically takes place with barbiturates like phenobarbitone and meprobamate the effect being lighter suppression of the central nervous system and lighter sedation.