Antihistamine side effects

Chlorpheniramine maleate Medical use Antihistaminic. Side effects drowsiness, headache, xerostomia, anorexia. 

Two newer potent selective H -antagonists, terfenadine (23) (132) and astemizole (24) (133), have been developed which have neither the sedative nor the anticholinergic Habilities of the earlier agents. Both of these compounds have proven efficacious in the treatment of hay fever and produce very few side effects, prompting a re-evaluation of the role of antihistamines in asthma treatment. 

Diphenhydramine [58-73-1] (55) was originally developed as an antihistamine and was first used clinically for this purpose in 1946 (see HiSTAMlNE AND HISTAMINE antagonists). In addition to this primary effect, however, central antitussive activity has also been demonstrated in animals (75,76) and in humans (77). Its antitussive activity is about half that of codeine. Drowsiness is the most frequent side effect. Diphenhydramine can be prepared as follows (78) ... 

Since there was some evidence that these compounds owe their action to interference with the action of histamine, this class has earned the soubriquet "antihistamines." This class of drugs is further characterized by a spectrum of side effects which occur to a greater or lesser degree in various members. These include antispasmodic action, sedative action, analgesia, and antiemetic effects. The side effects of some of these agents are sufficiently pronounced so that the compounds are prescribed for that effect proper. Antihistamines, for example, are used as the sedative-hypnotic component in some over-the-counter sleeping pills. 

Since many of the uses of antihistamines involve conditions such as rashes, which should be treatable by local application, there is some rationale for developing drugs for topical use. The known side effects of antihistamines could in principle be avoided if the drug were functionalized so as to avoid systemic absorption. The known poor absorption of quaternary salts make such derivatives attractive for nonabsorbable antihistamines for topical use. Thus, reaction of the well-known anti his-taminic drug promethazine (104) with methyl chloride leads... 

The sedation side effect commonly observed on administration of classical antihistaminic drugs has been attributed in part to the ease with which many of these compounds cross the blood brain barrier. There have been developed recently a series of agoits, for example, terfenadine (198), which cause reduced sedation by virtue of decreased penetration into the CNS. This is achieved by making them more hydrophilic. Synthesis of a related compound, ebastine (197),... 

As sedation is one of the major side effects associated with antihistamines, the test compounds were also evaluated for their sedative potentials. This was determined by measuring the reduction in locomotor activity using an ac-tophotometer [6,7]. The test compounds and the reference standards (chlorpheniramine maleate and cetirizine) were administrated orally at a dose of 5 mg/kg in 1% CMC. 

There is still debate whether oral antihistamines control ocular allergy as well as topical antihistamines. Topical antihistamines are recommended before oral agent in step therapy because of the increased risk of systemic side effects with oral drugs. Additionally, topical antihistamines provide faster relief of ocular symptoms. Consider oral antihistamines... 

Whether due to their antihistaminic activity or their sedative side effects, pruritus caused by contact dermatitis can be relieved with the use of sedating oral antihistamines such as... 

Medications for symptomatic relief from vertigo consist of antiemetics, benzodiazepines and antihistamines. They are all mostly aimed at the psychological consequences of dizziness and can all have highly unfavourable side effects, for example, sedation, anticholinergic effects and insomnia. The psychological consequences of dizziness in elderly should rather be treated with information about the condition, supportive help actions and increased social activities, than with drugs. 

Jarisch R, Goetz M, Aberer W, Sidl R, Stabel A, Zajc J, Fordos A Reduction of side effects of specific immunotherapy by premedication with antihistamines and reduction of maximal dosage to 50,000 SQ-U/ml. Arbeiten aus dem Paul-Ehrlich Institut 1988 82 163-175. 

With long-term use, the most problematic side effect is weight gain. However, many antihistamines including diphenhydramine also possess potent anticholinergic effects. This can cause dry mouth, blurred vision, constipation, confusion, and urinary retention. Because anticholinergic effects are especially problematic for the elderly, we advise against the routine use of antihistamines to treat elderly patients with insomnia. 

Medications that enhance norepinephrine activity are used to treat depression and ADHD. Boosting norepinephrine can also produce numerous side effects including nervousness and anxiety, insomnia, and loss of appetite. With mirtazapine and the TCAs, these side effects are usually not a problem because these antidepressants also block histamine receptors. Their antihistamine effects promote increased appetite and drowsiness that tend to offset the side effects that might be experienced from increased norepinephrine activity. 

Significant side effects have been estimated to occur in about 5% of patients on TCAs, most of these effects being attributed to their antimuscarinic properties, for example, blurred vision, dry mouth, tachycardia and disturbed gastrointestinal and urinary tract function. Orthostatic hypotension due to the block of alphai adrenoceptors and sedation resulting from antihistaminic activity frequently occur at therapeutic doses, particularly in the elderly. Excessive sweating is also a fairly common phenomenon, but its precise mechanism is uncertain. In the elderly patient, the precipitation of prostatic hypertrophy and glaucoma by the TCAs is also a frequent cause of concern. 

Bupropion should not be administered with sedating antihistamines because of the increased risk of seizures. Bupropion is used for smoking cessation therapy and may cause insomnia as a side-effect. Patients are advised to avoid taking bupropion dose at bedtime. 

Domperidone is a dopamine antagonist that acts on the chemoreceptor trigger zone. It can therefore be used as an anti-emetic in nausea and vomiting, for example, to counteract side-effects of cytotoxic therapy and to treat nausea associated with dopaminergic drugs used in Parkinson s disease. Unlike hyoscine butlybromide and antihistamines, domperidone is ineffective in motion sickness. 

Central Motor restlessness, progressing to maniacal agitation, psychic disturbances, disorientation, and hallucinations. Elderly subjects are more sensitive to such central effects, in this context, the diversity of drugs producing atropine-like side effects should be borne in mind e.g., tricyclic antidepressants, neuroleptics, antihistamines, antiarrhythmics, antiparkinsonian agents. 

Antihistamines are popular as nonprescription (over-the-counter) sleep remedies (e.g., diphenhydramine, doxylamine, p. 114), in which case their sedative side effect is used as the principal effect. 

Principal side effects are gastrointestinal and central nervous system symptoms, including drowsiness, dizziness, and diarrhea. Zolpidem may increase the depressant effects of other sedative drugs, such as the an-tipsychotics, tricyclic antidepressants, and antihistamines. 

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