Diphenhydramine, sedative properties

Many Hj-receptor blocking drugs have sedative properties, and some have been used in over-the-counter sleep aids. The most widely used Hj-blocking drugs for sleep induction are diphenhydramine, promethazine, and pyrilamine. 

The prototype antihistamine of this group is diphenhydramine. It has antimuscarinic and pronounced central sedative properties and also an antitussive effect. The mechanism of the latter is unclear, but diphenhydramine is a common ingredient of propriety preparations for the treatment of coughs and colds. It is an effective anti-emetic, especially useful for prevention and treatment of motion sickness. Because of its anticholinergic properties it is occasionally used in the treatment of mild forms of Parkinson s disease. It is also of use in the treatment of drug-induced extrapyramidal effects. Piperazine derivatives... 

Iatrogenic Reactions broadly refer to any adverse reactions that are unintentionally produced by physicians in their patients. For example, one of the side effects of many antihistaminic preparations (Hj antagonists) such as ethanolamine derivatives (prototype diphenhydramine) is heavy sedation. Although sedation may be desirable for some patients, it may interfere with daytime activities, and this needs to be considered when prescribing such medications. Other antihistaminic preparations (also 11 antagonists) such as piperidine derivatives (prototypes terfenadine or astemizole) have no sedative properties (Figure 3.2). 

Histamine-1 receptor antagonists (e.g., diphenhydramine) and antidepressants with high histamine-1 blockade (e.g., doxepin and amitriptyline) have been used for acute sleep disturbances but may cause anticholinergic side effects, daytime sedation, and weight gain. Trazodone, a serotonin-2A and ai -adrenergic antagonist, has sedative properties at lower doses and may be useful to promote sleep. The chronic use of benzodiazepines is not recommended for insomnia... 

The most common side effect of the antihistaminics is sedation, and all of them cause it to varying degrees. For example, diphenhydramine, dimenhydrinate, and promethazine cause marked sedation, but pyrilamine produces only moderate sedation. Chlorpheniramine, meclizine, and cyclizine have mild sedative properties, while terfenadine, astemizole, loratadine, and cetirizine are nonsedating. 

Diphenhydramine is an Hj-antihistaminic agent with anticholinergic and sedative properties. Diphenhydramine (25 to 50 mg t.i.d.) is indicated in allergic conjunctivitis, urticaria, and angioedema resulting from food, blood, or plasma in combination with epinephrine in anaphylactic... 

It was soon found that excellent anti-histaminic drugs could be based on ethanolamine instead of ethylenediamine and a notable example from the United States was diphenhydramine (9.56) ( Benadryl ). Members of this class couple their anti-histaminic effect with sedative properties and are prescribed when a high degree of somnolence is advantageous. There is only one ionizing group (pA 9.0). 

The sedative property which is so highly expressed in diphenhydramine existed in a less measure in other antihistamines. In an endeavour to lessen it, to help those who need medication at times when they must be alert, chlor-phenamine (9.57) (chlorpheniramine, Chlortrimeton ) was introduced. In this type, the second polar atom (N or O) has been eliminated from the aliphatic chain. The pAa values (4.0 and 9.2) resemble those of earlier compounds. Another type with a decreased incidence of drowsiness has the two nitrogen atoms of ethylenediamine joined by two saturated carbon atoms to give a piperazine ring. Chlorcyclizine 9.56a) ( Histantin , Diparalene ) provides an example. The search for Hi antagonists that could not cross the blood-brain barrier, and hence would be non-sedative, has produced the sterically-hindered astemizole ( Hismanol ) which is l-(p-fluorobenzyl)-2-[l-(l-/ methoxyphen-ethyl)-4-piperidylamino]benzimidazole, used for hay fever (Laduron et al., 1982). 

Several Hi histamine antagonists (e.g., diphenhydramine, promethazine, and hydroxyzine) have been used as sedative-hypnotics, since they produce some degree of sedation. While this sedation is usually considered a side effect of their antihistaminic activity, in some cases the sedation is sufficient to allow the drugs to be used in the treatment of anxiety and sleep disturbances. For these drugs, the anxiolytic properties are thought to be a direct consequence of their ability to produce sedation. 

Adolescent boys may be more vulnerable to acute dystonia than adults. Although these adverse effects can be treated with anticholinergic agents, dose reduction should also be considered. For acute dystonia, diphenhydramine (25 to 50 mg) may be given orally or intramuscularly, as can equivalent doses of benztropine (1 to 2 mg/day). Diphenhydramine has both sedative and anticholinergic properties, with the former being helpful in calming the patient whereas the latter reverses the reaction itself. 

Nonprescription antihistamines with sedating properties, such as diphenhydramine and doxylamine (see p. 422), are effective in treating mild types of insomnia. However, these drugs are usually ineffective for all but the milder form of situational insomnia. Further, they have numerous undesirable side effects that make them less useful than the benzodiazepines. These sedative antihistamines are marketed in numerous over-the-counter products. 

Drugs employed have sedative or hypnotic properties with a rapid onset and induce memory loss during the period when the drug is active. The most-prevalent drugs detected, apart from alcohol, are the benzodiazepines and h5 notics (zolpidem and zopiclone). A wide range of other drugs, such as GHB, ketamine, sildenafil, methadone, buprenorphine, diphenhydramine, trimeprazine, acepromazine, thiopental, pentobarb, doxylamine, and cyamemazine, have also been reported in DFC cases. 

---