STUDY UNIT 2.3 

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

Various factors including lipophilicity. This plays a major role in determining the rate at which a particular sedative-hypnotic enters the CNS

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

Highly lipid soluble drugs distribute to the brain, heart and kidneys immediately followed by muscle and fats it is quickly excreted and a depot is formed in fat or tissue where the drug will be slowly released.

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

Step by step biotransformation by hepatic microsomal enzymes.

1. Dealkylation: active metabolites
2. Oxidation: CYP450 active metabolites
3. Conjugation: Phase II of oxidised metabolite with glucuronic acid to form inactive metabolite.

• Which BDs are converted to active metabolites? What is the significance thereof?
  • • Diazepam
    • Chlorazepate
    • Prazepma
    • Chlordiazepoxide
    • Ketazolam

Active metabolites contribute to extended duration of action and cumulative effects with multiple doses. Important in elderly and neonates etc.

               

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

Oxazepam 

Lorazepam 

Tamezepam 

Lormetazepam 

Advantage is that they can act as drugs of choice in elderly, neonates, liver cirrhosis and therapy with P450 enzyme.

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