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

• The tempo of absorption and distribution is influenced by the lipid solubility of the drugs, meaning that a higher lipid solubility would mean faster absorption and distribution.
• The clinical significance of this would be that the rate of absorption and distribution influences the onset of action of a drug.

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

• Redistribution means the distribution or movement of the drugs from the brain to the other organs. This happens with highly lipid soluble drugs are distributed to the brain, heart, kidneys etc and then immediately followed by the muscle and fats.
• The significance of this is that certain drugs can cause a depo effect if it takes too long to be redistributed, this would cause a longer time for elimination to take place etc.

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

• BD’s are metabolized by means of a step by step biotransformation by hepatic microsomal enzymes.
  • Step 1: Dealkylation, this causes the formation of active metabolites
  • Step 2: Oxidation, this step happens in the liver with Cytochrome P450 enzyme which transform the drug into the active metabolite.
  • Step 3: Conjugation, conjugation of the active metabolites with glucuronic acid happens to form the inactive metabolite, which then gets excreted.

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

• Diazepam, Chlorazepate, Prazepam, Chlordiazepoxide and Ketazolam are converted to active metabolites.
• The clinical significance is that when drugs are turned into active metabolites, this extends the drug’s duration of action.

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

• Oxazepam, Lorazepam, Temazepam, and Lormetazepam are not dependant on CYP450 for metabolism.
• The advantages of this is that these drugs can be given to people who have a decrease in CYP450 activity like babies, geriatrics, people with liver cirrhosis etc.

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 induces the production of an enzyme, which causes increase in the metabolism and liver elimination of the drug.
• Barbiturates are known for this, specifically Phenobarbitone.
• The clinical significance of this would be that there is an increase in some drugs’ elimination and metabolism but this could also cause a decrease in the effectivity of the drug.

Resources:

Brand, L. 2021. Sedative Hypnotic drugs. Study Unit 2[PowerPoint Presentation]. Unpublished lecture notes on eFundi, FKLG 312. Potchefstroom, NWU.