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.

1. What does anterograde amnesia mean and which drugs can cause this effect?

• Being unable to remember events which occur during the drug's duration of action.
• Drugs which can cause this effect are benzodiazepines.

2. Name the effects of the sedative-hypnotic drugs on the normal sleep pattern and explain their significance to the patient.

• BDs has a small decreasing effect on REM sleep and in high dosages the decrease REM sleep.
• BDs also increase the duration of phase 2 NREM sleep and decrease the duration of phase 4 NREM sleep. 
• Zolpidem also decreases REM sleep but has minimal effect on SWS.
• The significance on these drugs to the patients it is to help with reducing time to fall asleep and to increase total sleep duration only in patients who normally sleep less than 6 hours every night.

3. Which of the sedative-hypnotic drugs are used as a supplementary therapy in anesthesia? Can you explain why?

• Barbiturates and BDs such as midazolam, diazepam and lorazepam. 

 4. Which of the sedative-hypnotic drugs are used as anticonvulsants?

• High doses of barbiturates and certain BDs ( diazepam, lorazepam in Status epilepticus). 
• Other drugs such as phenobarbitone, clonazepam, clobazam have selective anticonvulsive effects.

5. What is the mechanism of muscle-relaxing effects of some of the carbamates and the BDs?

• They inhibit polysynaptic reflexes. They block impulses from motor neuron endings to skeletal muscle. 

6. Discuss the effects of the sedative-hypnotic drugs on the respiratory and cardiovascular system. 

• Sedative-hypnotics can cause significant respiratory depression more especially in patients with pulmonary disease and as well as cardiovascular depression in patients with cardiovascular disease.
• These effects are usually marked with IV administration.
• High doses can cause death due to the depression of the medullary respiratory center. 
• These effects are accompanied by difficulty in breathing or obstruction in airway, lung failure, or decrease in heart rate and cardiac contractility and consequently heart failure.