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

• The lipophilicity of the BDs determines the rate at which it is absorbed. If the drug has high lipophilicity, then it is strongly absorbed and if the drug has low lipophilicity, then it has a low absorption rate.
• Lipophilicity also affects the distribution. The more lipid-soluble a drug is, the faster it is distributed throughout the body. Therefore, the less lipid-soluble a drug is, the slower the distribution throughout the body.
• This is clinically significant because this shows that the more lipid-soluble a drug is, the faster an effect will be seen (onset), but the shorter the duration of action

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

• Redistribution means that the drug goes to the brain and then to the rest of the tissues
• This is significant because it determines the duration of action of the drug

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

1. Dealkylation: active metabolites are formed
2. Oxidation: the active metabolites are oxidised by the cytochrome P450 enzyme
3. Conjugation: the oxidised active metabolites bind to glucuronic acid and form the inactive metabolite (which are aqueous-soluble and can easily be excreted)

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

• Triazolam, zolpidem and zaleplon
• These are significant because these drugs have increased lipophilicity, resulting in a rapid onset of action

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

• Oxazepam, lorazepam, temazepam and bromazepam
• There are many advantages to these drugs: they can be used in the elderly, neonates, in patients with liver cirrhosis and when cytochrome P450 enzyme inhibitors are used

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 induces (initiates) its own metabolism
• Phenobarbital and meprobamate are drugs that are enzyme inducers
• Enzyme induction is clinically important because this phenomenon is responsible for many drug interactions and increasing the metabolic rate of itself or other drugs