Central nervous system antihistamine effects

Loring DW, Meador KJ. (1989). Central nervous system effects of antihistamines on evoked potentials. Ann Allergy. 63(6) Pt 2 604-8. 

Phenindamine is an antihistamine that is reputed to cause stimulation rather than sedation in some patients. However, in one small study the central nervous system effects of phenindamine were intermediate between those of terfenadine and diphenhydramine (1). 

There is an increased central nervous system (CNS) depressant effect when the skeletal muscle relaxants are administered with other CNS depressants, such as alcohol, antihistamines, opiates, and sedatives. There is an additive anticholinergic effect when cyclobenzaprine is administered with other drugs with anticholinergic effects (eg, antihistamines, antidepressants, atropine, haloperidol). See Chapter 30 for information on diazepam. 

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. 

There is an increased risk for bone marrow suppression when levamisole or hydroxyurea are administered witii other antineoplastic dni. Use of levamisole witii phenytoin increases die risk of phenytoin toxicity. Pegaspargase may alter drug response of the anticoagulants. When procarbazine is administered with other central nervous system (CNS) depressants, such as alcohol, antidepressants, antihistamines, opiates, or the sedatives, an additive CNS effect may be seen. Procarbazine may potentiate hypoglycemia when administered witii insulin or oral antidiabetic dru . ... 

Tharion, WJ, McMenemy, DJ and Rauch, TM (1994) Antihistamine effects on the central nervous system, cognitive performance and subjective states. Neurophsychobiol. 29 97-104. 

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. 

Antihistamines, which penetrate into the central nervous system, have a non-specific sedative action, i.e. they can induce subjectively unpleasant side effects. 

The use of antihistamines can be traced back to the beginning of 1940s. The applications of the first-generation antihistamines were limited since they cause significant adverse effects such as sedation, memory impairment and psychomotor dysfunction. The second-generation antihistamines have significantly fewer central nervous system (CNS) adverse effects because they penetrate the blood-brain barrier much less extensively. 

Substituted phenothiazines are antihistaminics and show powerful depressant effects on the central nervous system. Two well-known drugs of this type are promethazine (287) and chloropromazine (288). Phenothiazine itself is a veterinary anthelmintic agent as well as an insecticide, and methylene blue (284 R = Me) has long been used as a biological stain. 

The tertiary members of these classes (Figure 8-2) are often used for their effects on the eye or the central nervous system. Many antihistaminic (see Chapter 16 Histamine, Serotonin, the Ergot Alkaloids), antipsychotic (see Chapter 29 Antipsychotic Agents Lithium), and antidepressant (see Chapter 30 Antidepressant Agents) drugs have similar structures and, predictably, significant antimuscarinic effects. 

In humans, a prominent effect of cocaine consists in increased vigilance and elevated mood. While cocaine itself is not used clinically, several catecholamine and serotonin reuptake blockers are used as antidepressants. Imipramine (Figure 10.13) is a classic but not so very specific in addition to inhibiting the reuptake of serotonin and of norepinephrine, it also has antihistaminic and antimuscarinic activity. This will lead to side effects in both the central nervous system and the peripheral autonomic system. A prominent one is the causation or deterioration of cardiac arrhythmias due to its antimuscarinic action. 

Figure 13-3 Potential adverse effects of Hi antihistamines through central nervous system and effect on various receptors and through ion channels. (Igr = rapid component of the delayed rectifier potassium current.) (Adapted with permission from Simons PER.Advances in Hi-antihistamines. N Engl J Med 2004 351 2204.)...

Central nervous system depressant drugs including benzodiazepines, several Hj-receptor antihistamines, alcohol, phenothiazines, antiepilepsy drugs interact to augment their sedative effects. 

Feldman W, Shanon A, Leiken L, Ham-pong A, Peterson R. Central nervous system side-effects of antihistamines in schoolchildren. Rhinol Suppl 1992 13 13-19. 

Efavirenz is a non-nucleoside reverse transcriptase inhibitor with excellent inhibitory activity against HTV-l. Its most frequent adverse effects involve the central nervous system and the skin (1). At the start of therapy, dizziness, insomnia, or fatigue is observed in most patients, and headache and even psychotic reactions have also been observed. A maculopapular rash is seen in about 10%. These adverse effects usually vanish within the first 2-4 weeks of therapy (2). About 1-2% of individuals stop taking efavirenz because of neurological or dermatological adverse events. Administration of efavirenz at bedtime reduces the incidence of severe adverse effects, and the rash can be managed by short-term antihistamines or topical corticosteroids (1). Nausea and vomiting are less often observed than in patients treated with zidovudine, lamivudine, or indinavir. 

Although it has been thought to have relatively little stimulant effect on the central nervous system, phenylpropanolamine can produce restlessness, anxiety, insomnia, and tremor its central stimulant effects are in practice often masked by manufacturers practice of combining it with an antihistamine. 

Dextromethorphan is the methylated dextro-isomer of levorphanol. Unlike the L-isomer, it has no analgesic properties. Dextromethorphan acts on the central nervous system (CNS) to elevate the cough threshold. It retains only the antitussive activity of other morphine derivatives. Administration of dextromethorphan may be associated with histamine release. Dextromethorphan is often present in multisymptom products with a combination of ingredients. Toxic effects of concurrent agents such as antihistamines, decongestants, analgesics, and/or alcohol may be exhibited. 

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