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

In the case of Barbiturates: The more lipid soluble the drug is the easier and faster it will be reabsorbed and redistributed (Thiopentone is an example).

Meaning therapeutic effect will be seen quicker, because lipid soluble drugs redistribute to brain.

Benzodiapines’ lipophilicity is also important for absorption.

High lipophilicity	Less lipid soluble
- Tiazolam - Zolpidem - Zaleplon	- Oxazepam - Lorazepam - Temazepam - Bromazepam

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

Highly lipid-soluble drugs given by intravenous or inhalation methods are initially distributed to organs with high blood flow. Later, muscle and fat tissues will take up the drug—plasma concentration falls and the drug is withdrawn from these sites.

Significance is the fact that the drug will be easier absorbed and a quicker therapeutic effect that is reached.

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

BDs are metabolised by hepatic microsomal enzymes. There are three steps namely: Dealkylation, Oxidation and Conjugation

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

Diazepam, Chlorazepate, Prazepam, Chloridiazepoxide and Ketazolam

These active metabolites that are formed can lead to a cumulative effect that can have a toxic effect or an effect for an extended duration.

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

Oxazepam, Lorazepam, Themazepam, Lormetazepam

These drugs are usually the drug of choice in geriatric and neonate patients (they do not have the best liver function), in patients that have liver cirrhosis or patients that already use P450 enzyme inhibitors. Thus all the above mentioned has decreased Cyt P450, so if the drug they take do not need to be broken down by this enzyme it is good, otherwise the drugs will accumulate in the bloodstream and have a toxic effect.

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

Enzyme induction can be defined as the increase in the biosynthesis of catalytically active enzyme following exposure of the organism to chemical agents or physiological conditions.

Therefore: Metabolism increases

- clearance takes place faster

- clearance t½ is shorter.

Enzyme induction will lead to a shorter half live in some benzodiazepines especially Diazepam, this effect is also seen in Carbamazepine and Phenobarbital.