Antiallergic Drugs » why-histamine-antagonists-are-not-given-for-bronchial-asthma

Drugs used for the temporary relief of the symptoms and allergy caused by allergic rhinitis, hay fever and allergy symptoms.

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April 13, 2011 – 5:26 am

Cetirizine competitively antagonizes histamine at the H1-receptor

site and is indicated in the symptomatic relief of symptoms (e.g.,

nasal, nonnasal) associated with seasonal and perennial allergic

rhinitis; treatment of uncomplicated skin manifestations of chronic

idiopathic urticaria. Histamine is a potent

vasodilator, bronchial smooth-muscle constrictor, and stimulant of

nociceptive itch nerves. In addition to histamine, multiple chemical

itch mediators can act as pruritogens on C-fibers, including

neuropeptides, prostaglandins, serotonin, acetylcholine, and bradykinin.

Furthermore, new receptor systems such as vanilloid, opioid, and

canna-binoid receptors on cutaneous sensory nerve fibers that may

modulate itch offer novel targets for antipruritic therapy.

Histamine is in mast cells, basophils, and platelets. Human skin mast cells express H1( H2, and H4 receptors, but not H3 receptors. H1 and H2 receptors are involved in wheal formation and erythema, whereas only

H1-receptor agonists cause pruritus. Complete blockade of H1-receptors

does not totally relieve itching, and combinations of H1 and H2 blockers may be superior to H1 blockers alone.

Oral antihistamines, particularly H1-receptor antagonists, have some

anticholinergic activity and are sedating, making them useful for the

control of pruritus. First-generation sedating H1-receptor antagonists

include hydroxyzine hydrochloride (Atarax), which is given in a dose of 0.5 mg / kg every 6 hours; diphenhydramine (Benadryl; others); promethazine (Phenergan); and cyproheptadine (Periactin). Doxepin (Adapin,

Sinequan), which has tricyclic antidepressant and sedative

antihistamine effects, is a good alternative for severe pruritus. A

topical formulation of doxepin also is available as a 5% cream

(Zonalon), which can be used in conjunction with low- to

moderate-potency topical glucocorticoids. The systemic effect from

topical doxepin is comparable with that of low-dose oral therapy.

Second-generation H1-receptor antagonists lack anticholinergic side

effects and are described as nonsedating largely because they do not

cross the blood-brain barrier. They include cetirizine (Zyrtec),

loratadine (Claratin), desloratidine (Clarinex), and fexofenadine

hydrochloride (Allegra). Although second-generation nonsedating

H1-receptor blockers are as effective as the first-generation H1

blockers, they are metabolized by CYP3A4 and, to a lesser extent, by

CYP2D6, and should not be coadministered with medications that inhibit

these enzymes (e.g., imidazole antifungals and macrolide antibiotics).

H2-receptor blockers include cimetidine (Tagamet),

ranitidine (Zantac), famotidine (Pepcid), and nizatidine (Axid). Besides

their use in combination with H1-receptor blockers for pruritus, the H2-receptor

blockers have immunomodu-lating effects, and this property has been

exploited in children to treat warts. Drug allergy may develop when H1

antagonists are given orally but results more commonly from topical

application. Allergic dermatitis is not uncommon; other hypersensitivity

reactions include drug fever and photosensitization. Hematological

complications such as leukopenia, agranulocytosis, and hemolytic anemia

are very rare. Because H1 antihistamines cross the placenta,

caution must be used when they are taken by women who are or may become

pregnant. Several antihistamines (e.g., azelastine, hydroxyzine, and

fexofenadine) showed teratogenic effects in animal studies, whereas

others (e.g., chlorpheniramine, diphenhydramine, cetirizine, and

loratadine) did not. Antihistamines can be excreted in small amounts in

breast milk, and first-generation antihistamines taken by lactating

mothers may cause symptoms in the nursing infant such as irritability,

drowsiness, or respiratory depression. Because H1 antagonists interfere with skin tests for allergy, they must be withdrawn well before such tests are performed.

Cetirizine is indicated in the treatment of pollen-associated asthma

in individuals with angioedema, atopic dermatitis, and certain types of

physical urticaria such as delayed pressure urticaria, dermatographia,

and cold urticaria. Terfenadine, astemizole, loratadine, and cetirizine

are second-generation antihistaminic agents that are relatively

nonsedating. Cetirizine is a carboxylated metabolite of hydroxyzine

(Vistaril), a piperazine derivative H1-receptor antagonist. Cetirizine

inhibits both histamine release and eosinophil chemotaxis during the

secondary phase of the allergic response. It reduces inflammatory cell

infiltration (i.e., eosinophils, neutrophils, basophils) by 75% during

the late-phase response.

Cetirizine 10 mg is more potent than terfenadine 60 mg, loratadine

(Claritin) 10 mg, and chlorpheniramine (e.g., Chlor-Trimeton) 6 mg, and

equal in potency to diphenhydramine (e.g., Benadryl) 50 mg, hydroxyzine

25 mg, and terfenadine 180 mg. Cetirizine is absorbed well when given

orally, is bound to plasma protein to the extent of 93%, does not cross

the blood-brain barrier, has an elimination half-life of 7 to 10 hours,

and is excreted mostly unchanged in the urine. The half-life of

cetirizine is increased in renal impairment, requiring smaller dosage.



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