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

•  Lipophilicity= higher lipid soluble drugs are have a rapid onset of action because they are absorbed much quicker and they are distributed easily and faster to different parts of the brain.
• Alkalinity/ acidity= more alkaline drugs are absorbed and distributed faster and thus have a faster elimination rate.
• Enzymatic metabolism= drugs which are not metabolized in the liver by enzymes are absorbed and distributed more faster than those which are metabolized by the liver.

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

• Redistribution is the distribution of highly lipid soluble drugs to different parts of the body like to the brain, heart, kidneys, followed by muscles and then fats.
• This is to achieve the desired therapeutic effect of the drug in the body (all the necessary parts of the body) and to ensure the effectivity of the drug.

3. How are the BD's metabolized? Name the various steps in the process.

The metabolism of BD's occurs in various steps, which include:

• Dealkylation: this step leads to the formation of active metabolites which accumulate and are more effective.
• Oxidation: this step involved the metabolism of the BD's by the Cytochrome P450 enzyme to active metabolites.
• Coagulation: this step is known as the phase 2 metabolism of BD's where the BD's are made aqueous soluble, where the oxidized metabolite is coagulated with glucuronic acid to form an inactive metabolite, which is then excreted in the urine.  

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

BD's which are converted to active metabolites, through des-methyl-diazepam include: 

• Diazepam, Chlorazepate, Prazepam, Chlordiazepoxide, Ketazolam
• The active metabolite formed contributes to the extension of the duration of action and a cumulative effect with multiple doses.

5. Which BD's are not dependent on the Cytochrome P450 oxidative enzymes for metabolism? What is the advantages thereof?

BD's which are independent of the CytP450 oxidative enzymes include:

• Oxazepam, Lorazepam, Temazepam, Lormetazepam

The advantages of these drugs is that they are enzyme inducers on their own and are therefore the drugs of choice in patients where CytP450 activity is reduced like in the elderly, neonates, patients with liver cirrhosis and in combination therapies with P450 enzyme inhibitors.

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

• Enzyme induction is the ability of a drug to induce its own enzymatic activity and its own metabolism occurs. 
• Drugs which are known for this are BD's such as Oxazepam, Lorazepam, Temazepam and Lormetazepam.  
• The significance of this enzyme induction is that these drugs are safer to use in combination therapy with P450 enzyme inhibitors because that will not affect its metabolism, as well as in patients with liver cirrhosis because that will not cause liver toxicity and also its safe in geriatric patients and neonates.