Antihistamines, first-generation

Antihistamine first generation H, blocker prototype Tox mild sedation, little antimuscarinic action. 

Chlorpheniramine 4 mg every 4-6 hours Preferred agent if first-generation antihistamines are to... 

First-generation antihistamines are effective, but associated sedation and psychomotor impairment limit chronic use. Efficacy and safety of second-generation antihistamines in children have been demonstrated in clinical trials.33 Cetirizine is indicated for children 6 months of age and older, loratadine for children 2 years of age and older, and fexofenadine for children 6 years of age and older.15... 

The hypothesis of the role of HA in wakefulness stems from the observation that administration of the classical antihistamines (i.e. H3 receptor antagonists) induced sedation. These first-generation antihistamines, used to treat inflammatory reactions, could cross the blood-brain barrier and block the central Hi receptor (White Rumbold, 1988). The first study examining the effect of antihistamines on sleep-wakefulness in cats reported an increase in NREM sleep and a decrease in REM sleep (Jewett, 1968). Similar results were also obtained in dogs (Wauquier et ah, 1981) and humans (Risberg et ah, 1975 Bassano Caille, 1979 Nicholson et ah, 1985 Adam Oswald, 1986). Intraventricular application of HA in the anesthetized rat caused a dose-dependent decrease in the duration of narcosis, whereas intraventricular application of HA in conscious... 

Intranasal corticosteroids are the most effective treatment for allergic rhinitis during pregnancy. Beclomethasone and budesonide have been used most. Nasal cromolyn and first-generation antihistamines (chlorpheniramine, tripelennamine, and hydroxyzine) are also considered first-line therapy. Loratadine and cetirizine have not been as extensively studied. 

Mianserin was the first of the second-generation antidepressants to be developed. It lacked the amine reuptake inhibitory and MAOI actions of the first-generation drugs and also lacked the cardiotoxicity and anticholinergic activity of the TCAs. However, it was sedative (antihistaminic), caused postural hypotension (alpha-1 blockade) and also caused blood dyscrasias and agranulocytosis in a small number of patients. This has limited the use of mianserin in recent years. 

First-generation FIj antihistamines are the oldest antihistaminergic drugs and are relatively inexpensive and widely available. Representatives of first-generation Hj antihistamines are ... 

Cimetidine is a representative of first-generation antihistamine drugs that block H2 receptors. The main pharmacological effect of cimetidine is the suppression of gastric juice secretion associated with H2 receptors of the stomach walls. It suppresses both basal and stimulated hyckochloric acid produced by food as well as histamine and gastrine, which simultaneously lower pepsin activity. 

First-generation antihistamines Flypersensitivity to specific or structurally related antihistamines newborns or premature infants nursing mothers monoamine oxidase (MAO) therapy pregnancy (hydroxyzine) angle-closure glaucoma, stenosing peptic ulcer, symptomatic prostatic hypertrophy, bladder neck obstruction, pyloroduodenal obstruction, elderly, debilitated patients (cyproheptadine). 

The Hi-antagonists are classified as either first- or second-generation compounds. Second-generation antihistamines have lipophilicity and ionization profiles that make them less able to cross the blood-brain barrier thus they produce dramatically less sedation than do the first-generation drugs. 

Many of these drugs have effects that are not mediated by Hi-receptors (Table 38.2). The antimuscarinic activity of several first-generation Hj-blockers may account for their effectiveness in combating motion sickness and their limited ability to suppress parkinsonian symptoms. The phenothiazines have some capacity to block a-adrenoceptors, whereas cyproheptadine Periactin) is an antagonist at serotonin receptors. Diphenhydramine Benadryl), pyrilamine (Ryna), and promethazine Phen-ergan) are effective local anesthetics. Many second-generation antihistamines also have been found to inhibit the non-histamine-mediated release of various... 

Geriatric Considerations - Summary Brompheniramine is a first-generation al-kylamine antihistamine with potent Hj receptor antagonism, it has anticholinergic activity and can cause somnolence. Older adults taking this drug are at risk of dizziness and hypotension. 

The first generation Hi blockers (including diphenhydramine and hydroxyzine) cross the blood-brain barrier. Subsequent generations of antihistamines have been developed so that they do not cross the blood-brain barrier, and therefore are not effective as sedatives or anxiolytics. 

The first-generation antihistamines include diphenhydramine and hydroxyzine. They are both well absorbed from the GI tract, and peak plasma concentrations occur within 2 to 3 hours. 

Cyclizine has antimuscarinic properties and is a potent anti-emetic, effective for the control of postoperative and drug-induced nausea and vomiting. It has been used to prevent motion sickness, although diphenhydramine and promethazine are more effective. It is available in oral and parenteral formulations. In contrast to many other first-generation antihistamines sedation is not marked. It is available in tablet form as the hydrochloride and in injectable form as the lactate. Because of its anticholinergic action, blurred vision and dry mouth are associated with clinical doses. When given by rapid intravenous injection tachycardia may be a problem. Meclozine is a related drug which, like cyclizine, is used primarily for motion sickness. 

First-generation H -receptor blockers are among the most extensively promoted and used over-the-counter drugs. The prevalence of allergic conditions and the relative safety of the drugs contribute to this heavy use. The fact that they do cause sedation contributes to heavy prescribing of second-generation antihistamines. 

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