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

The rate of absorption and distribution is determined by the fat solubility of the drugs. Therefore the higher the lipid solubility, the faster the drug will reach the break.

The clinical significance will therefore be the starting time of the specific drug, because the faster a drug is absorbed and distributed, the faster it will start working and exert effects.

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

Redistribution is when a drug moves from its original place of action to other tissue and there an accumulation occurs, it forms a storage site and results in the medication being administered to the body for a longer period of time. It is important to take this into account when administering the drugs as they can cause several unwanted effects.

The importance of this is that when the drug has moved from the brain to other tissues, such as the adipose tissue, it can cause a depot that ultimately affects the rate of release of the drug. The altered rate of release will eventually also have an effect on the rate at which the drugs are eliminated from the body.

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

Benzodiazepines are biotransformed by liver microsomal enzymes under normal conditions in these three steps.

1 - Dealkylation (The process gives rise to the formation of active metabolites)

2 - Oxidation (The process takes place in the liver and the enzyme Sit. P450 converts the drug to active metabolites)

3 - Conjugation (Phase two where the active metabolites are metabolised with Glucuronic acid to form an inactive metabolite)

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

Diazepam, Chlorazepate, Prazepam, Chlorodiazepoxide, Ketazolam.

The importance of this is therefore that the active metabolites that are formed prolong the duration of action of the drugs.

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

Oksazepam, Lorazepam, Temazepam, Lormetazepam. 
Advantages of these drugs, they are considered as selectives which have reduced cytochrome P450 activity so that metabolism can still take place adequately. For example, in the elderly ,in neonates and even people with liver cirrhosis the Sit. P450 activity decreases.

• 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 an increase in the biosynthesis of the catalyzing enzyme. Examples include cimetidine, ketoconazole, erythromycin, fluvoxamine. THe mportance of enzyme induction is that it can accelerate the breakdown of drugs that can be important in toxicization.