Histamine receptor antagonists adverse effects

The new second-generation antihistamines are more selective Hi histamine receptor antagonists, and many of them have additional anti-aUergic properties in vivo, for example they reduce the release of inflammatory mediators or inhibit the recruitment of inflammatory cells (3-7). They also enter the brain less well and are therefore less likely to cause central adverse effects. 

The unwanted effects of histamine injections can be partially blocked by Hi histamine receptor antagonists, which were once used to prevent systemic adverse effects of histamine when it was used to stimulate gastric acid secretion, which is mediated by H2 receptors. 

The adverse effects profile of the proton pump inhibitors during short-term administration (under 12 weeks) is similar to that reported with short-term use of histamine receptor antagonists. The type and frequency of adverse effects reported with lansoprazole, omeprazole, pantoprazole, and rabeprazole are comparable. The most common adverse effects include headache, diarrhea, nausea, abdominal pain, constipation, dizziness, and skin rashes. 

In anesthesia drugs from several groups are used as premedication. Pre-anesthetic medication can decrease the anesthetic doses which otherwise would be required to induce anesthesia and so decrease the risk for adverse effects. Pre-anesthetic medication will increase the rate of induction of anesthesia and can reduce pre-operative pain and anxiety. Drugs include benzodiazepines for sedation and their muscle relaxant properties, opiates for pain relieve and anticholinergics or histamine Hi receptor antagonists against nausea and vomiting. Neuroleptics are also used as premedication for their antiemetic effects. 

Phentolamine is a potent competitive antagonist at both K and k2 receptors (Table 10-1). Phentolamine reduces peripheral resistance through blockade of K receptors and possibly k2 receptors on vascular smooth muscle. Its cardiac stimulation is due to antagonism of presynaptic k2 receptors (leading to enhanced release of norepinephrine from sympathetic nerves) and sympathetic activation from baroreflex mechanisms. Phentolamine also has minor inhibitory effects at serotonin receptors and agonist effects at muscarinic and Hi and H2 histamine receptors. Phentolamine s principal adverse effects are related to cardiac stimulation, which may cause severe tachycardia, arrhythmias, and myocardial ischemia. Phentolamine has been used in the treatment of pheochromocytoma. Unfortunately oral and intravenous formulations of phentolamine are no longer consistently available in the United States. 

Common adverse effects of the TCAs, including dry mouth and constipation, are attributable to the potent antimuscarinic effects of many of these drugs. The TCAs also tend to be potent antagonists of the histamine Hi receptor. TCAs such as... 

Fexofenadine is indicated for the relief of the symptoms of allergic rhinitis in adults and children 12 years of age and older. Fexofenadine is a selective antagonist of the Hi histamine receptor in the periphery of the body. Experimental studies demonstrated that the drug does not cross the blood-brain barrier. Fexofenadine is rapidly absorbed following oral administration. Very little of the drug is metabolized, with 80 percent excreted in the feces, and 11 percent in the urine. Its half-life is about 15 hours. In patients older than 65 years, the peak concentration was twice that of normal volunteers less than 65 years old. Renal impairment also results in increased plasma levels. Adverse effects are mild and infrequent, and include drowsiness, dyspepsia and fatigue. 

Honig P, Baraniuk JN. Adverse effects of Hl-receptor antagonists in the cardiovascular system. In Simons FER, editor. Histamine and Hl-receptor Antagonists in Allergic Disease. New York Marcel Dekker Inc, 1996 383 12. 

Nizatidine is a histamine H2 receptor antagonist. Experience with it is still too hmited to make valid comparisons with its earher congeners. Data sheet warnings of possible adverse effects refer to skin rash, nrticaria, somnolence, and thrombocytopenia. Nizatidine is said not to give problems with drug interactions or to affect androgen status. 

In a prospective, randomized, double-blind, placebo-controlled study in 30 patients who required vancomycin chemoprophylaxis before elective arthroplasty, oral pretreatment with either a histamine Hi receptor antagonist (diphenhydramine 1 mg/kg) or a histamine H2 receptor antagonist (cimetidine 4 mg/kg) significantly reduced the histamine-related adverse effects of rapid vancomycin infusion (18). 

The most commonly occurring adverse effects caused by vancomycin are referred to collectively as red man syndrome. Reactions may range from mild pruritus, erythema, and flushing of the upper body to angioedema and rarely hypotension and cardiovascular collapse. Reactions may be prevented or their severity decreased by extending the infusion time and/or premedication with histamine H, and H2 receptor antagonists. 

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