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

Rate is determined by lipophilicity, therefore high lipid solubility = rapid absorption from the gastrointestinal tract and good distribution of the drug to the brain. 

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

Redistribution means that the drug goes to the brain and is then distributed to the rest of the tissues. This is significant because it determines the duration of action of the drug.

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

By hepatic microsomal enzymes. This process includes:

• 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.

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

Diazepam, Clorazepate, Prazepam, Chlordiazepoxide and Ketazolam are all examples of benzodiazepines that are converted to an active metabolite. Active metabolites are important because they contribute to the extension of the duration of action.

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

Oxazepam, Lorazepam, Temazepam, Lormetazepam. These drugs benefit patients that suffer from liver cirrhosis, geriatrics, neonates and patients that make use of CYP-P450 inhibitors, due to the drugs not having an effect on the levels of CYP-P450 because it does not require the enzyme to produce an effect.

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

Enzyme induction - when a drug increases the production of an enzyme that will lead to an increase in the rate of metabolism of the drug.

Barbiturates and meprobamate are known for this action and are significant in increasing drug metabolism, therefore a decrease of drug in the systemic circulation causing a decrease in the overall therapeutic effect.