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

• The lipophilicity of the drug. The more lipophilic a drug is, the faster the drug is absorbed and the faster the drug can produce effects

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

• Redistribution is the process where a drug is absorbed systemically and distributed to other parts of the body like the fatty tissues 

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

• The metabolism of Benzodiazepines is made possible by the microsomal liver enzymes. Metabolism consists of three steps: 
  • Dealkylation where active metabolites are produced
  • Oxidation where the drug is also converted into active metabolites 
  • Conjugation where the metabolites are made more aqueous soluble so that they can be excreted by the kidneys 

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

• Only the drugs containing Desmethyldiazepam (Diazepam, Clorozepate, Prazepam, Chloridiazepoxide, Ketazolam) undergo the process and are turned into active metabolites. This is important for us because the active metabolites can extend the duration of action of the drug 

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

• Oxazepam, Lorazepam, Temazepam and Lormetazepam. These drugs have the advantage of being used when a patient has decreased liver function especially elderly patients, neonates, patients with liver cirrhosis or patients who are using cytochrome P450 inhibitors 

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 induces an enzyme, it is known as enzyme induction. drugs like Phenobarbital and Meprobomate are known for this. By increasing/inducing the enzyme, the metabolism of the drug will be quicker, which will have a decrease in the elimination half-life and then duration of action of the drug