1. What factors may effect the absorption and distribution of sedatives-hypnotic drug? What is the clinical significance thereof?

Due to highly lipophilic nature of the Blood Brain Barrier (BBB) the most important factor of absorption and distribution of sedative hypnotic drugs are the lipophilicity of the drugs. Also, the lipophilicity of the drugs effects the onset of action of the drugs. Drugs with a high lipophilicity easily cross the BBB and exert much more easily an effect on the CNS.

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

The redistribution of drugs is the absorption of drugs (high lipophilicity) in the systemic circulation and distribution of it to other organs such as the brain heart and kidneys. Then after it goes into muscle and fatty tissue forming a depot effect which result in a longer duration of the drug which is also the importance of redistribution.

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

BDs are metabolised by the hepatic microsomal enzymes. 

• Step1: Dealkylation to active metabolites. Also desmethyldiazapam is formed.
• Step 2: Microsomal Oxidation by CYT P450 enzymes to an active metabolite. Active metabolite desmethyldiazapam gets oxidised resulting in Oxazepam.
• Step 3: Conjugation (phase II) of the Oxazepam metabolite with glucuronic acid to form an inactive metabolite forming glucuronides, which are water-soluble and are excreted in urine

4. Which BDs are converted to active  metabolites? What are the importance of that?

Diazepam, Cholarazepam,  Prazepam, Chlorodiazepoxide, ketazolam. It lengthens the duration of action of the drugs.

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

Oxazepam, Lorazepam, Temazepam, Lormetazpem. It's beneificial to those patients having liver cirrhosis, elder people, neonates, and patients are on CYP-P450 inhibtors.

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

When a drug increases the production of an enzyme which increases their rate of of metabolism. Barbiturates and meprobamate are known for this. This means the drug has a great metabolism rate  which lead to a lesser concentration of the drug in the circulation system, finally decreasing the therapeutic effect.

Bertram G. Katzung 2018, B Basic & Clinical Pharmacology, Lange, McGraw hill, University of California, San Francisco.