Diphenhydramine properties

Antihistamines such as diphenhydramine are known for their sedating properties and are frequently used over-the-counter medications (usual doses 25-50 mg) for difficulty sleeping. Diphenhydramine is approved by the FDA for the treatment of insomnia and can be effective at reducing sleep latency and increasing sleep time.43 However, diphenhydramine produces undesirable anticholinergic effects and carryover sedation that limit its use. As with TCAs and BZDRAs, diphenhydramine should be used with caution in the elderly. Valerian root is an herbal sleep remedy that has inconsistent effects on sleep but may reduce sleep latency and efficiency at commonly used doses of 400 to 900 mg valerian extract. Ramelteon, a new melatonin receptor agonist, is indicated for insomnia characterized by difficulty with sleep onset. The recommended dose is 8 mg at bedtime. Ramelteon is not a controlled substance and thus may be a viable option for patients with a history of substance abuse. 

Motion sickness. Effective prophylaxis can be achieved with the parasympatholytic scopolamine (p. 106) and H antihistamines (p. 114) of the diphenyl-methane type (e.g., diphenhydramine, meclizine). Antiemetic activity is not a property shared by all parasympatho-lytics or antihistamines. The efficacy of the drugs mentioned depends on the actual situation of the in vidual (gastric filling, ethanol consumption), environ-... 

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. 

The antihistamine diphenhydramine (Benadry/), because it has anticholinergic properties, is used for mild parkinsonism and with the elderly, who may not be able to tolerate the more potent anticholinergics, levodopa, or the dopamine agonists. 

Diphenhydramine is known to be at least partially effective in Parkinson s disease, perhaps because of its anticholinergic 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. 

Geriatric Considerations - Summary Diphenhydramine is a first-generation etha-nolamine antihistamine with potent Hj-receptor antagonism. It also has significant anticholinergric properties and causes somnolence at normal doses. Older adults taking this drug are at risk of dizziness and hypotension and diphenhydramine would... 

Anticholinergics and antihistamines chlorpheniramine (Chlor-Trimeton), diphenhydramine (Benadryl), hydroxyzine (Vistaril and Atarax), cyproheptadine (Periactin), promethazine (Phenergan), dexchlorpheniramine (Polaramine) All nonprescription and many prescription antihistamines may have potent anticholinergic properties. Nonanticholinergic antihistamines are preferred in elderly patients when treating allergic reactions. High... 

Antimotion sickness effect Several Hj-antagonists have significant property in preventing motion sickness. This effect was first observed with drug, dimenhydrinate and subsequently with other drugs like diphenhydramine, promethazine and other piperazine derivatives. 

Antiparkinsonism Based on anticholinergic property, some H -antagonists such as diphenhydramine can be used in the early stages of treatment of parkinsonism. 

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. 

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... 

Cyclizine has antimuscarinic properties and is a potent anti-emetic, effective for the control of postoperative and drug-induced nausea and vomiting. It has been used to prevent motion sickness, although diphenhydramine and promethazine are more effective. It is available in oral and parenteral formulations. In contrast to many other first-generation antihistamines sedation is not marked. It is available in tablet form as the hydrochloride and in injectable form as the lactate. Because of its anticholinergic action, blurred vision and dry mouth are associated with clinical doses. When given by rapid intravenous injection tachycardia may be a problem. Meclozine is a related drug which, like cyclizine, is used primarily for motion sickness. 

Elevations of TCA levels may occur when combined with CYP2D6 inhibitors or from constitutional factors. About 7% of the Caucasian population in the USA has a CYP2D6 polymorphism that is associated with slow metabolism of TCAs and other 2D6 substrates. Combination of a known CYP2D6 inhibitor and a TCA in a patient who is a slow metabolizer may result in additive effects. Such an interaction has been implicated, though rarely, in cases of TCA toxicity. There may also be additive TCA effects such as anticholinergic or antihistamine effects when combined with other agents that share these properties such as benztropine or diphenhydramine. Similarly, antihypertensive drugs may exacerbate the orthostatic hypotension induced by TCAs. 

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). 

Antihistaminic drugs with anticholinergic properties (e.g., diphenhydramine)... 

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. 

Ortho-substitution decreases the antihistamine effects, but increases the antimuscarinic properties the ortho-methyl analogue of diphenhydramine (orphenadrine) was successfully introduced as an anti-Parkinson medicament. 

The introduction of two para-substituents reduce strongly the antihistamine properties, indicating that the two phenyl nuclei have different functions in binding to the receptor. This observation is confirmed by the large difference in activity between the enantiomers of 4, 41-CH3-diphenhydramine. 

Of the systemic antihistamines, the ethanolamines, including diphenhydramine, have significant antimuscarinic activity. In addition, the antipsychotic agents, particularly the phenothiazines such as thioridazine (Mellaril), have well-dociunented anticholinergic properties. Therapeutic doses of tricyclic antidepressants, like amitriptyline hydrochloride (Elavil) and imipramine (Tofranil), produce significant anticholinergic actions and thus have the potential for ocular side effects. 

Table 4 Mechanical properties of Eudragit ElOO films containing diphenhydramine HCL (DPH) and lidocaine HCL (L-HCL)...

In a human lung epithelial cell line, in which histamine increased the intracellular calcium concentration and the formation of eicosanoids, this response was antagonized by the histamine Hi receptor antagonist diphenhydramine but unaffected by the H2 receptor antagonist cimetidine. Fenspiride inhibited Hi receptor-induced calcium increase. Histamine also caused a biphasic increase in arachidonic acid release, which was inhibited by fenspiride. This study suggests a further mechanism that would promote antiinflammatory and bronchodilator properties. 

The toxicity of antihistamines is related to their anticholinergic (antimuscarinic) activity. The action of acetylcholine at the muscarinic receptors is blocked, resulting in signs and symptoms of anticholinergic poisoning. Diphenhydramine may produce direct toxicity unrelated to its anticholinergic properties. 

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