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

Lipophilicity is one of the factors that may affect absorption and distribution of these drugs. Lipid solubility plays a vital role in determining the rate at which a particular sedative-hypnotic enters the central nervous system. This process is thus responsible for the rapid onset of action of triazolam. Drugs that exert high lipophilicity have a rapid onset of action whereas drugs with lower lipophilicity does not have a rapid onset of action.

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

Redistribution occurs when a drug gets absorbed in the systematic circulation and thus gets distributed to certain organs of the body. In case of highly soluble drugs it gets distributed to the brain heart and kidney. The significance thereof is to ensure that the drug gets distributed to the organs

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

Benzodiazepines are metabolized by hepatic microsomal enzymes. The process consists of:

• Dealkylation to active metabolites.
• Oxidation by the cytochrome P450 enzymes to an active metabolite.
• Conjugation (Phase II) of the oxidised metabolite with glucuronic acid to form an inactive metabolite.

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

Benzodiazepines are converted to desmethyldiazepam which includes:

Diazepam, Chlorazepate, Prazepam, Chlordiazepoxide and Ketazolam. These active metabolites thus leads to extension of duration of action.

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

Oxazepam, Lorazepam, Temazepam,Lormetazepam are the drugs that do not depend on oxidative enzymes for metabolism. These drugs plays an advantage to the patients that suffer from liver cirrhosis, elderly, neonates and patients that make use of CYP-P450 inhibitors thus they do not require oxidative enzyme to induce an effect.

6. 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 a drug increases the metabolic processes of the enzyme. Phenobarbital and Meprobamate are known as enzyme inducers. The clinical significance is when an enzyme induce causes an increase in metabolism of the drug which causes drug decrease in the systematic circulation therefore decrease in the therapeutic effect.