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

Anterograde amnesia  is the inability to remember what happened during the duration of action of the drug and it is caused by benzodiazepines (Katzung, 2018:388).

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

The effects of older sedative-hypnotic drugs and benzodiazepines on normal sleep patterns are:

• the time to fall asleep  (latency of sleep onset)  is decreased
• stage 2 NREM (non-rapid eye movement) sleep duration is increased
• REM (rapid eye movement) sleep duration is decreased
• stage 4 NREM slow-waved sleep duration is decreased

Latency is decreased to persistent sleep by new hypnotics.

Zolpidem decreases REM sleep but do not have a big effect on slow-wave sleep.

Zaleplon decreases the latency of sleep onset but do not have a big effect on total sleep time, NREM or REM sleep.

Eszopiclone increases the total sleep time mostly by increases in stage 2 NREM sleep, but do not have a big effect on sleep patterns at low doses. It decreases REM sleep at the highest recommended dose.

Suvorexant decreases the time to persistent sleep and also increases the total time of sleep.

Clinically useful effects are more rapid onset of sleep and stage 2 prolongation. The deliberate interruption of REM sleep leads to anxiety  as well as irritability  that is followed by a rebound increase in REM sleep.  A similar pattern to this rebound increase in REM sleep can occur after abrupt cessation of drug treatment with older sedative-hypnotics, especially high doses of short duration of action drugs (like triazolam). There is not much evidence  of REM rebound when zolpidem and other new hypnotics are discontinued after use of recommended doses. However, higher doses of zolpidem and zaleplon can cause rebound insomnia. Except for reductions that may occur in slow-wave sleep, there are no reports of disturbances in the secretion of pituitary or adrenal hormones when barbiturates or benzodiazepines are used as hynotics. Sedative-hypnotics that are used for more than 1 to 2 weeks lead to some tolerance to their effects on sleep patterns (Katzung, 2018: 388).

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

• Benzodiazepines (diazepam, lorazepam, midazolam) – these drugs are used intravenously in anesthesia and often in combination with other agents. When benzodiazepines are given in large doses as a supplementary therapy anaesthesia, it can contribute to a persistent postanesthetic respiratory depression. This might be related to their relatively long half-lives ond the formation of active metbolites. These actions can usually be reversed with flumazenil (Katzung, 2018:389).
• Barbiturates (thiopental and methohexital) – these are very lipid–soluble, thus these drugs penetrate brain tissue rapidly after intravenous administration. This caracteristic favours their use for the induction of anesthesia. Fast tissue redistribution accounts for the short duration of action of these drugs, which is useful in recovery from anesthesia (Katzung, 2018:388).

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

• Benzodiazepines useful in the management of seizures (clonazepam, nitrazepam, lorazepam, diazepam) (Katzung, 2018:389).
• Barbiturates useful in the treatment of generalized tonic-clonic seizures, but not the drugs of first choice (phenobarbital, metharbital) (Katzung, 2018:389).

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

These drugs have inhibitory effects on polisynaptic reflexes and internuncial transmission. At high doses, these drugs can depress transmission at the skeletal neuromuscular junction. This leads to muscle relaxation (Katzung, 2018:389).

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

When hypnotic doses of sedative-hypnotics are given to healthy patients, their effects on respiration are comparable to changes during natural sleep. At therapeutic doses, sedative-hypnotics can cause respiratory depression in patients with pulmonary disease. These are dose-related effects on respiration . Depression of the medullary respiratory center is usually the cause of death due to overdose of sedative-hypnotics (Katzung, 2018:389).

When doses up to those causing hypnosis are given to healthy patients, no significant effects on the cardiovascular system are observed.

However, in hypovolemic states, in patients with heart failure and other diseases that impair cardiovascular function, normal doses of hypnotics can lead to cardiovascular depression, probably as a result of actions on the medullary vasomotor centers. When toxic doses are given, myocardial contractility and vascular tone may both be depressed by central and peripheral effects, possibly by facilitation of the actions of adenosine that leads to circulatory collapse.

Respiratory and cardiovascular effects are more marked when sedative-hypnotics are administered intravenously (Katzung, 2018:389).

References

Katzung, B.G.  2018.  Basic & Clinical Pharmacology.  14th ed. New York: McGraw-Hill Education.