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

Rates of absorption of sedative hypnotics differ. It depends on factors such as lipophilicity. Lipid solubility plays a major role in determining the rate at which a particular sedative hypnotic enters the CNS. This property is responsible for the rapid onset of the effects of triazolam, thiopental and the newer hypnotics. Lipophilic drugs are absorbed into the blood much faster. The higher a drugs lipophilicity, the more rapid its onset following administration and therefore the greater the effect exerted in the central nervous system. All sedative hypnotics can cross the placental barrier during pregnancy. Examples of drugs with a rapid onset of action in the CNS: eszopiclone, zaleplon and zolpidem. 

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

Redistribution is when a lipid soluble drug that was initially distributed and absorbed by vascular organs and the brain, gets withdrawn from these sites by less vascular and highly perfused tissues, such as skeletal muscles. 

How are the BD'S metabolized? Name the various steps in the process

Benzodiazepines are metabolized step-by-step by hepatic microsomal enzymes. The steps include:

1. Dealkylation to active metabolites
2. Oxidation to active metabolites through CYP450
3. Conjugation (Phase II) of oxidized metabolite with glucuronic acid to form inactive metabolite.  

Which BD's are converted to active metabolites? What is the significance thereof? 

Diazepam, Chlorazepate, Prazepam, Chlordiazepoxide, Ketazolam are converted to Desmethyldiazepam. Desmethyldiazepam is then oxidized to Oxazepam. Active metabolites contribute to the extended duration of action. Cumulative effects with multiple doses. 

Which BD's are not dependent on CYP450 oxidative enzymes for metabolism? What are the advantages thereof?

Oxazepam, Lorazepam, Temazepam and Lormetazepam are not dependent on cytochrome P450 to exert an effect and they do not undergo dealkylation or oxidation. This is useful in patients with liver cirrhosis, elderly, neonates and patients undergoing therapy with CYP450 inhibitors. 

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

Enzyme induction is when a drug administered increases the production of a specific enzyme, this enzyme increases the rate of drug metabolism and thus decreases the effect the drug has in the body. Examples of enzyme inducers: phenobarbital and meprobamate. These drugs increase the rate of drug clearance. 

Source:

Katzung, B.G. 2018. Basic & Clinical Pharmacology. 14th ed. New York: Mc Graw Hill Education