HEALTH AND MEDICAL PRODUCTS:INSOMNIATR EATMENTS.

INSOMNIATR EATMENTS

Insomnia typically refers to abnormal wakefulness, shortened sleeping periods, difficulty in getting to sleep, or early awakening with an inability to return to sleep. This condition may be a reflection of normal age- related changes (e.g., decline in melatonin hormone production by the pineal gland), illness or physical discomfort, stimulants such as caffeine or drugs, or the effects of jet lag in the case of frequent travelers. How- ever, a common cause of insomnia tends to be psychological disturbance (e.g., stress, depression, anxiety). Mild insomnia may be relieved by a soothing activity such as reading or listening to relaxing music. Chronic (long-term) or severe insomnia usually requires treatment of the under- lying physical or psychological disorder, along with the use of sedatives and hypnotic drugs if the sleeplessness impairs the ability to obtain the quantity and quality of sleep needed for the person to both function adequately during the daytime and maintain a sense of well-being. Interestingly, sleep requirements in healthy individuals tend to vary from four to nine hours a day; thus, it is difficult to determine the exact amount of sleep needed for normal functionality by every person.

Many over-the-counter oral sedative-hypnotic drugs targeted for the treatment of mild to moderate insomnia include the active ingredient diphenhydramine hydrochloride. This compound is an H1 antagonist of the ethanolamine class and acts as an antihistamine by competing with free histamine for binding at H1 receptor sites. Other members of the ethanolamine class include compounds such as carbinoxamine, clemastine, doxylamine, and phenyltoloxamine. Ethanolamine H1 antagonists such as diphenhydramine HCl have significant anticholinergic and antimuscarinic activity and produce marked drowsiness and/or sedation in most individuals via depression of the CNS. The altered level of consciousness manifested within the CNS, as caused by diphenhydramine HCl, results from central cortical and subcortical muscarinic receptor antagonism. Diphenhydramine HCl causes both a decrease in sleep latency and an in- crease in sleep duration (slow-wave sleep). This drug also decreases the rate of rapid eye movement sleep during slow wave (deep) sleep. The degree of CNS manifestation (i.e., sedation) is related to the drug’s ability to cross the blood-brain barrier, which normally protects the brain from exposure to particular substances traveling within the bloodstream.

Anticholinergic agents diminish the effects of the neurotransmitter acetylcholine, a substance produced by the body that is responsible for certain nervous system activities. Diphenhydramine HCl provides a competitive reversible blockade of muscarinic receptors, thereby inhibiting cholinergic neurotransmission via acetylcholine at muscarinic receptor sites. The term “muscarinic” indicates that the receptor can be stimulated by muscarine, a toxin produced by some poisonous mushrooms (e.g., Amanita muscaria). Muscarinic receptors are located at cholinergic neuroeffector junctions in the parasympathetic and sympathetic di- visions of the autonomic nervous system, which is involved with the involuntary control of physiological body processes. The cholinergic neu- roeffector junctions, which are types of chemical synapses, involve the re- lease of the neurotransmitter acetylcholine from presynaptic neurons to postsynaptic effector cells to allow for communication between the ner- vous system and other parts of the body. Muscarinic receptors present at neuroeffector junctions may produce either an excitation or an inhibition response, depending on the nature of the enzymes activated when acetyl- choline normally binds to the receptor.

The maximum sedative effect of diphenhydramine HCl usually occurs between one and three hours after oral administration, with the duration of action ranging from four to six hours. Thus, because of its ability to induce drowsiness, diphenhydramine HCl is promoted as an over-the- counter hypnotic to be used as a short-term sleep aid. Prolonged use of diphenhydramine HCl can result in the development of tolerance, which may lead to reduced sedative effects. Therefore, chronic use of such medications is not recommended, as long-term continuation of the recommended drug dose may not alleviate insomnia. In addition, increased blood serum concentrations of diphenhydramine HCl, present as a result of ingestion beyond the recommended dose, can result in general systemic toxicity and overall bodily harm.