antihistamin

Table 16–2. Some H1 Antihistaminic Drugs in Clinical Use. Drugs

Usual Adult Dose Anticholinergic Activity

Comments

FIRST-GENERATION ANTIHISTAMINES Ethanolamines Carbinoxamine (Clistin)

4–8 mg

+++

Slight to moderate sedation

50 mg

+++

Marked sedation; anti-motion sickness activity

25–50 mg

+++

Marked sedation; anti-motion sickness activity

25–50 mg

+

Moderate sedation

Hydroxyzine (Atarax, etc)

15–100 mg

nd

Marked sedation

Cyclizine (Marezine)

25–50 mg

–

Slight sedation; anti-motion sickness activity

Meclizine (Bonine, etc)

25–50 mg

–

Slight sedation; anti-motion sickness activity

Brompheniramine (Dimetane, etc)

4–8 mg

+

Slight sedation

Chlorpheniramine (Chlor-Trimeton, etc)

4–8 mg

+

Slight sedation; common component of OTC "cold" medication

10–25 mg

+++

Marked sedation; antiemetic;

4 mg

+

Moderate sedation; also has antiserotonin activity

60 mg

–

Loratadine (Claritin)

10 mg

–

Cetirizine (Zyrtec)

5–10 mg

–

Dimenhydrinate (salt of diphenhydramine) (Dramamine) Diphenhydramine (Benadryl, etc) Ethylaminediamine Tripelennamine (PBZ, etc) Piperazine derivatives

Alkylamines

Phenothiazine derivative Promethazine (Phenergan, etc)

block

Miscellaneous Cyproheptadine (Periactin, etc) SECOND-GENERATION ANTIHISTAMINES Piperidine Fexofenadine (Allegra) Miscellaneous Longer action

Table 63–1. Clinical Comparisons of H2-Receptor Blockers. Drug

Relative Potency

Dose to Achieve > 50% Usual Dose for Acute Acid Inhibition for 10 Duodenal or Gastric Hours Ulcer

Usual Dose for Gastroesophageal Reflux Disease

Usual Dose for Prevention of Stress-Related Bleeding

Cimetidine 1

400–800 mg

800 mg HS or 400 mg bid

800 mg bid

50 mg/h continuous infusion

Ranitidine

4–10x

150 mg

300 mg HS or 150 mg bid

150 mg bid

6.25 mg/h continuous infusion or 50 mg IV every 6– 8h

Nizatidine

4–10x

150 mg

300 mg HS or 150 mg bid

150 mg bid

Not available

20 mg

40 mg HS or 20 mg bid

20 mg bid

20 mg IV every 12 h

Famotidine 20–50x

H1 and H2 Receptors. Once released, histamine can exert local or widespread effects on smooth muscles and glands. It contracts many smooth muscles, such as those of the bronchi and gut, but markedly relaxes others, including those in small blood vessels. Histamine also is a potent stimulus of gastric acid secretion (see above). Other, less prominent effects include formation of edema and stimulation of sensory nerve endings. Bronchoconstriction and contraction of the gut are mediated by H1 receptors. Gastric secretion results from the activation of H2 receptors and, accordingly, can be inhibited by H 2-receptor antagonists. Some responses, such as vascular dilation, are mediated by both H 1- and H2-receptor stimulation. H3 and H4 Receptors. H3 receptors are expressed mainly in the CNS, especially in the basal ganglia, hippocampus, and cortex. H3 receptors function as autoreceptors on histaminergic neurons, much like presynaptic 2 receptors, inhibiting histamine release and modulating the release of other neurotransmitters. H 3 antagonists promote wakefulness; conversely, H 3 agonists promote sleep. H3 receptors appear to have high constitutive activity; thus histamine release may be tonically inhibited, and inverse agonists may reduce receptor activation and increase histamine release from histaminergic neurons. H 4 receptors are on immune active cells such as eosinophils and neutrophils, as well as in the gastrointestinal (GI) tract and CNS. Activation of H4 receptors on eosinophils induces a cellular shape change, chemotaxis, and up-regulation of adhesion molecules such as CD11b/CD18 and intercellular adhesion molecule (ICAM)-1, suggesting that the histamine released from mast cells acts at H4 receptors to recruit eosinophils. H4 antagonists may be useful inhibitors of allergic and inflammatory responses.