Antihistamines second-generation

Cost inexpensive over-the-counter formulations are available for both HI antihistamines and H2 antihistamines. Second-generation HI antihistamines are generally more expensive than first-generation and may not be covered by insurance carriers due to the availability of over-the-counter formulations. 

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... 

Mild or intermittent symptoms are treated with second-generation antihistamines. 

Second-generation nonsedating antihistamines (e.g., loratadine) are not associated with erectile dysfunction. 

This second-generation histamine HI receptor blocker was put on the world market in the 1980s for the relief of symptoms associated with seasonal allergic rhinitis and chronic idiopathic urticaria [14], Janssen Pharmaceuticals marketed this dmg under the brand name Hismanal. The major benefit of these antihistamines was their... 

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. 

These include trazodone and a derivative of its metabolite nefazodone, both of which are strongly sedative, an effect which has been attributed to their potent alpha-1 receptor antagonism rather than to any antihistaminic effects. A main advantage of these drugs in the treatment of depression is that they appear to improve the sleep profile of the depressed patient. Their antidepressant activity is associated with their weak 5-HT reuptake inhibition and also a weak alpha-2 antagonism. However, unlike most of the second-generation antidepressants, neither drug is effective in the treatment of severely depressed patients. Furthermore, there is some evidence that trazodone can cause arrythmias, and priapism, in elderly patients. 

Second-generation antihistamines Flypersensitivity to specific or structurally related antihistamines. Desloratadine is contraindicated in those who are hypersensitive to loratadine. Cetirizine is contraindicated in those who are hypersensitive to hydroxyzine. 

Ohradovic, T, Dobson, G.G., Shingaki, T, Kungu, T. and Hidalgo, I.J. (2006) Assessment of the first and second generation antihistamines brain penetration and role of P-glycoprotein. Pharmaceutical Research, 24, 318—327. 

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. 

At therapeutic doses, the first- and second-generation antihistamines are equilibrium-competitive inhibitors of Hi-receptor-mediated responses. Certain second-generation drugs are noncompetitive inhibitors at high concentrations. Both first- and second-generation compounds have negligible abilities to block the H2-, H3-, or H4-receptors. The therapeutic effectiveness of these... 

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... 

Although the antihistamines are not useful as primary agents in the treatment of asthma, a number of studies have shown that the second-generation compounds are effective as adjunctive therapies in asthmatic patients with concomitant rhinitis, urticaria, or dermatitis. Cetirizine has been used to prevent the progression from atopic dermatitis to asthma in young children. 

Nicolas JM. The metabolic profile of second-generation antihistamines. Allergy 2000 55 46-52. 

Walsh GM et al. New insights into the second-generation antihistamines. Drugs 2001 61 207-236. 

Geriatric Considerations - Summary Clearance and half-life are altered in older adults therefore reduce starting dose. More sedating than fexofenadine and lorata-dine consider an alternate second-generation antihistamine. 

The second generation H -receptor antagonist cetirizine is a reacemate consisting of equal quantities of 2 enantiomers, levocetirizine [(R)-enantiomer] and dextrocetirizine [(S)-enantiomer]. In vitro and human pharmacodynamic studies have provided evidence that levocetirizine is the more active enantiomer, accounting for most or all clinical antihistaminic activity of racemic cetirizine this activity of levocetirizine is seen at half the dose of cetirizine. 

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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