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

The rate of absorption is determined by the lipophilicity of the drugs, the higher the lipophilicity the faster the onset of action and distribution of the drug and its central nervous system effects (the faster it will work in on the patient’s body). The lower the lipophilicity the slower the absorption and distribution.

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

• Redistribution happens from the brain to the rest of the body. Drugs that are very lipophilic are absorbed and distributed to the brain fast and is then redistributed to other parts of the body like the heart,kidneys and lungs where the drugs can have a depot preparation and thus be released systemically in time.
• How are BD’s metabolized?

1. Dealkylation
2. Oxidation
3. Conjugation

• Which BD’s are converted to active metabolites and what is the significance thereof?

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

These drugs are converted to active metabolites because they are metabolized by the hepatic microsomal enzymes (CYTP450) they undergo oxidation and conjugation. This active metabolite contributes to the drug effect. These drugs can however be dangerous when it is not metabolized in patients that receive therapy of CYTP450 inhibitors like patients with impaired liver enzyme function, the elderly and neonates.

• Which BD’s 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 metabolized by CYTP450, thus they can be given to patients with liver cirrhosis, elderly and neonates because they are not affected by cytochrome P450 and is the drug of choice for these patients.
• 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 the metabolism of  specific enzymes that increase the metabolism of the drug. This causes a decrease in the amount of drug that circulates in the body and thus means that there will be a decrease in the effect that the drug should have on the body. Enzyme induction usually takes place in barbiturates like phenobarbitone and meprobamate.