Antihistamines sedative effects

Antihistamine Sedative effects Antihistaminic activity Anticholinergic activity Antiemetic effects... 

Reboxetine. Most of the activity of rehoxetine resides in the 5.5 isomer (The marketed compound is RR and 55.) It is claimed to he superior to fluoxetine in severe depression. It is marketed in Europe. At least three tricyclic compounds, desipramine. nortriptyline, and the technically tetracyclic maprotiline are SNERIs. They, of course, have typical characteristic TCA side effects but lower anticholinergic and H -antihistaminic (sedative) effects than dimethyl compounds. SNERIs arc clinically effective antidepressants. 

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. 

There is an increase in anticholinergic effects when antihistamines are administered with the monamine oxidase inhibitors (MAOIs) and additive sedative effects if administered with central nervous system depressants (eg, narcotic analgesics or alcohol). When cimetidine and loratadine are administered together there is a risk for increased loratadine levels. 

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). 

Promethazine is an antihistamine, which leads to sedation and is therefore used in motion sickness when a sedative effect is desired. 

Coadministration of ritonavir with certain nonsedating antihistamines, sedative hypnotics, antiarrhythmics, or ergot alkaloid preparations may result in potentially serious and/or life-threatening adverse reactions due to possible effects of ritonavir on the hepatic metabolism of certain drugs (see Contraindications). 

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. 

Considerable work has been devoted to the search for agents devoid of the sedative effect that accompanied some of the earlier antihistamines. One stratagem for achieving that comprises adding a function that will diminish the likelihood that the dmg will cross the blood-brain barrier. The antistamine emedastine (41-3), for example, incorporates a terminal ether that can be potentially metabolized to a carboxylic acid. Alkylation of the imidazole (41-1), available from imidazol-2-one by reaction with phosphoms oxychloride, with the chloroether (41-2) leads to a reaction on nitrogen to afford (41-3). Displacement of the enol chloride in that intermediate with A-methyl-l-4-diazepine (41-4) leads to emedastine (41- 5) [43]. 

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. 

The quinazolone methaqualone (129 R = Me) was introduced as a sedative in 1965. It also has anticonvulsant and muscle-relaxant properties, but it has produced problems of addiction. Sedative effects are also produced by many antihistamines, and by tranquilizers of the benzodiazepine group. 

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. 

Other classes of drugs not included in Figure 22-3 that may exert sedative effects include most antipsychotic and many antidepressant drugs and certain antihistaminic agents (eg, hydroxyzine, promethazine). As discussed in other chapters, these agents differ from conventional sedative-hypnotics in both their effects and their major therapeutic uses. Since they commonly exert marked effects on the peripheral autonomic nervous system, they are sometimes referred to as "sedative-autonomic" drugs. Certain antihistaminics with sedative effects are available in over-the-counter sleep aids. Their autonomic properties and their long durations of action can result in adverse effects. 

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