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

Lipophilicity plays a big role because it determines how fast  a drug will be absorbed and start to work (onset  of action), because the BBB is lipophilic; for example like thiopental and triazolam that is quickly absorbed and starts to show effect rapidly.

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

Redistribution means that the drug moves form the brain to other tissues (mostly occur with lipid soluble drugs) and it means that a drug is not eliminated right away but creates a depo-effect when it is distributed from the other tissues (for example adipose tissue).

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

It occurs via hepatic microsomal enzymes in the liver

Steps:

1. Dealkylation – where active metabolites are formed
2. Oxidation – where active metabolites are also formed and dependent on metabolism by Cytochrome P450 enzymes
3. Conjugation – where metabolite is rendered inactive so it can be excreted by the kidneys

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

• Diazepam
• Chlorazepate
• Prazepam
• Chlordiazepoxide
• Ketazolam

Formation of active metabolites can lead to prolonging the duration the drug will be active in the system

It can also cause cumulative effects when multiple doses are adminestered

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

• Oxazepam
• Lorazepam
• Temazepam
• Lormetazepam

The elderly, people with liver cirrhosis and neonates whose cytochrome P450 is not working optimally can use these drugs

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

It is when the activity of an enzyme for example is enhanced to decrease bioavailability of a drug and increases its clearance thus, reduces its effectiveness.

Barbiturates increase enzyme action when used for long duration of time

Brand, L. 2021. FKLG Study unit 2: Sedative-hypnotic drugs. Potchefstroom: NWU, Potchefstroom campus.

Katzung, B.G. 2018. Basic & Clinical Pharmacology. 14^th ed. New York: McGraw-Hill Education

Zevin, S., 2019. Cytochrome P450 Inducer - an overview | ScienceDirect Topics. Sciencedirect.com. https://www.sciencedirect.com/topics/medicine-and-dentistry/cytochrome-p450-inducer#:~:text=Cytochrome%20P%2D450%20enzyme%20inducers,St.&text=Grapefruit%20juice%2C%20which%20inhibits%20some,of%20some%20dihydropyridine%20calcium%20antagonists. Accessed 6 March 2021.