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

1.lipophilicity, more lipophilic a drug the faster it is absorbed and reaches the target tissue. more distributed 

2.  biotransformation hepatic microsomal enzymes 

3. elimination half life may differ, this causes some BDs to be eliminated faster than others

 

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

Redistribution means the drug is redistributed from one tissue to other tissues 

A drug like thiopentone which is used as an induction anesthetic, high lipophilic,quickly moves from the brain to other tissues such as the muscle tissue. it can a depot effect in other tissues as it is not easily removed because of its lipophilicity

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

they are metabolized by biotransformation by hepatic microsomal enzymes 

1.  dealkylation: active metabolites 

2. oxidation: cytochrome p450, active metabolite

3. conjugation ( phase 2) of oxidised metabolite with glucuronide acid to form an inactive metabolite 

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

diazepam 

clorazepate

prazepam

chlorodiazepam

ketazolam 

if you get active metabolites contribute to extended duration of action increase elimination half life to greater than 40hours

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

oxazepam 

lorazepam 

temazepam

lormetazepam

drugs of choice where cytochrome p450 activity is reduced, especially in elderly, neonates and in patients with liver cirrhosis 

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

Enzyme induction refers to 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 . they decrease the therapeutic effect by increasing the metabolism and decrease the overall drug in the systemic circulation