Sedative effects of antihistamines

It is known that amphetamines may counter the sedative effect of antihistamines and other sedating agents. Amphetamines raise blood pressure, so abusers who take prescription anti-hypertension pills do not get the full benefit from those anti-hypertensives. 

Roth T, Roehrs T, Koshorek G, Sicklesteel J, Zorick F. Sedative effects of antihistamines. J Allergy Chn Immunol... 

The sedative effects of antihistamines can be useful in patients who suffer from sleeplessness caused by the symptoms of allergic rhinitis. In these patients, a bedtime dose may prove beneficial. However, they may cause residual daytime sedation, decreased alertness, and performance impairment. " ... 

Side effects. This term should be restricted to the undesirable but unavoidable pharmacological actions of the drug (e.g., sedative effects of antihistaminic drugs). 

Sleep and sedative effects of the atypical antipsychotics could be related to different mechanisms antagonism of 5-HT2 receptors, antihistaminic and antimus-carinic effects, and probably an a-1 noradrenergic effect. The difference in the effect on sleep between risperidone and haloperidol may be due to their differential actions on serotoninergic receptors (Trampus and Ongini 1990 Trampus et al. 1993). 

Knowledge of the physiological role of histamine in the CNS and evidence for the existence of discrete neuronal networks that could be called histaminergic are still evolving. Histamine-mediated hypothermia, emesis, and hypertension have been shown to exist, and the well-known sedative effects of Hj antihistamines are centrally mediated. 

Not everyone reacts to antihistamine-containing sleep aids the same way. Some people, particularly those of Asian descent, are less sensitive to the sedative effects of these medications. Others can have reactions that are opposite to the intended effect of inducing sleepiness—some people feel nervous, jittery, anxious, restless, or agitated after taking antihistamines. This is particularly true in elderly persons and young children. Others can experience a morning hangover effect, characterized by sleepiness, headache, dry mouth, constipation, and blurred vision. 

For the reasons given in the Purpose/Rationale section above, barbiturate interaction tests yield useful information not readily provided by the other procedures in the core battery. Furthermore, the data obtained are highly correlated with results that could be expected in man. To our knowledge, no sleep enhancing agent used in man has been found inactive in a barbiturate interaction procedure. Conversely, no clinically known enhancer of wakefulness, for example caffeine, amphetamine and modafinil, has failed to reduce or abolish barbiturate-induced sleep. Potential to cause drowsiness, as is observed with many antihistamines, is also clearly picked up in barbiturate interaction procedures as are the potential sedative effects of a variety of neuroleptics. 

All muscle relaxing agents should be given with caution to anyone who is taking other drugs. The muscle relaxers will enhance the sedative effects of many other classes of drugs such as antihistamines, antidepressants, sedatives, other muscle relaxants, and tranquilizers. 

Spontaneous reports of suspected adverse effects of antihistamines have been analysed (15). The drugs were divided into two groups, sedative and non-sedative. Adverse reactions profiles were broadly similar in the two groups. 

Table 1 The sedative, anticholinergic, and QT prolonging effects of antihistamines (all rINNs, except where stated) ...

The sedative and anticholinergic effects of antihistamines, when known, are summarized in Table 1. 

To counteract the sedative effects of the classic antihistamines, combinations with stimulants, such as pemoline and prolintane, have been tried. The efficacy of such combinations has not been proven, but additional adverse effects such as irritability (120) and hallucinations (121) have been observed. 

Didier A, Doussau-Thuron S, Murris-Espin M. Comparative analysis of the sedative effects of mequita-zine and other antihistaminic drugs review of the literature. Curr Ther Res Clin Exp 2000 61 770-80. 

Richardson GS, Roehrs TA, Rosenthal L, Koshorek G, Roth T. Tolerance to daytime sedative effects of Hi antihistamines. J Clin Psychopharmacol 2002 22(5) 511-15. 

Benztropine Mesylate, USP. Benztropine mesylate. 3o-(diphenylmethoxy)-1 otH.SatH-ttopane methane.sulfonaic (Cogentin), has anticholinergic, antihistaminic. and local anesthetic properties. Its anticholineigic effect makes it applicable as an antiparkinsonian agent. It is about as potent an anticholinergic as atropine and shares some of the side effects of this drug, such as mydriasis and dryness of mouth. Importantly, however, it does not produce central stimulation but instead exerts the characteristic. sedative effect of the antihistamine.s. 

Interactions the sedative effects of antidepressants, anxiolytics and hypnotics are likely to be enhanced by antihistamines, as are the antimuscarinic actions and side-effects of drugs such as trihexyphenidyl, orphenadrine, tricyclic antidepressants and phenothiazines. 

Hindmarch I. CNS effects of antihistamines is there a third generation of non-sedative drugs Clin Exp Allergy Rev 2002 2 26-31. 

As with other sedative antihistamines (see MAOIs + Antihistamines , above), the UK manufacturers of cyproheptadine also say that MAOIs prolong and intensify the antimuscarinic effects of antihistamines, but fhere seems to be no clinical data to support this. 

Drug interactions sedatives/hypnotics, opioids, barbiturates, antihistamines, alcohol, neuroleptics, anticonvulsants, and SSRIs can all enhance the sedative effects of BNZs. 

In addition to their ability to bind with the Hi receptors, these antihistamines also bind with receptors in the central nervous system, causing undesired side effects such as sedation (drowsiness). All of these compounds, called first-generation antihistamines, cause these undesired side effects. The sedative effect of first-generation antihistamines has been attributed to their ability to cross the blood-brain barrier, allowing them to interactwith receptors in the central nervous system. 

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. 

The short-acting clomethia2ole [533-45-9] (1), sometimes used as therapy for sleep disorders ia older patients, shares with barbiturates a risk of overdose and dependence. Antihistamines, such as hydroxy2iae [68-88-2] (2), are also sometimes used as mild sedatives (see HiSTAMlNES AND HISTAMINE antagonists). Antidepressants and antipsychotics which have sedative effects are used to treat insomnia when the sleep disorder is a symptom of some underlyiag psychiatric disorder. 

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. 

---