Page 297 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 16 Histamine, Serotonin, & the Ergot Alkaloids 283

TABLE 16–2 Some H antihistaminic drugs in clinical use.
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Drugs Usual Adult Dose Anticholinergic Activity Comments
FIRST-GENERATION ANTIHISTAMINES
Ethanolamines
Carbinoxamine (Clistin) 4–8 mg +++ Slight to moderate sedation
Dimenhydrinate (salt of 50 mg +++ Marked sedation; anti-motion sickness activity
diphenhydramine) (Dramamine)
Diphenhydramine (Benadryl, etc) 25–50 mg +++ Marked sedation; anti-motion sickness activity
Piperazine derivatives
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
Alkylamines
Brompheniramine (Dimetane, etc) 4–8 mg + Slight sedation
Chlorpheniramine (Chlor-Trimeton, 4–8 mg + Slight sedation; common component of OTC “cold”
etc) medication
Phenothiazine derivative
Promethazine (Phenergan, etc) 10–25 mg +++ Marked sedation; antiemetic; α-block
Miscellaneous
Cyproheptadine (Periactin, etc) 4 mg + Moderate sedation; significant antiserotonin activity;
mixed evidence for use as an appetite stimulant
SECOND-GENERATION ANTIHISTAMINES
Piperidine
Fexofenadine (Allegra, etc) 60 mg —
Miscellaneous
Loratadine (Claritin, etc), 10 mg (desloratadine, — Longer action; used at 5 mg dosage
desloratadine (Clarinex) 5 mg)
Cetirizine (Zyrtec, etc) 5–10 mg —
nd, no data found.

drug group. Nevertheless, its structure resembles that of the pheno- CLINICAL PHARMACOLOGY OF
thiazine antihistamines, and it is a potent H -blocking agent. H -RECEPTOR ANTAGONISTS
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7. Local anesthesia—Several first-generation H antagonists
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are potent local anesthetics. They block sodium channels in excit- Clinical Uses
able membranes in the same fashion as procaine and lidocaine. First-generation H -receptor blockers are still commonly used
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Diphenhydramine and promethazine are actually more potent over-the-counter drugs. The prevalence of allergic conditions
than procaine as local anesthetics. They are occasionally used to and the relative safety of the drugs contribute to this heavy use.
produce local anesthesia in patients allergic to conventional local However, the fact that they do cause sedation contributes to heavy
anesthetic drugs. A small number of these agents also block potas- prescribing as well as over-the-counter use of second-generation
sium channels; this action is discussed below (see Toxicity). antihistamines.

8. Other actions—Certain H antagonists, eg, cetirizine, inhibit
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mast cell release of histamine and some other mediators of inflam- A. Allergic Reactions
mation. This action is not due to H -receptor blockade and may The H antihistaminic agents are often the first drugs used to
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reflect an H -receptor effect (see below). The mechanism is not prevent or treat the symptoms of allergic reactions. In allergic
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fully understood but could play a role in the beneficial effects of rhinitis (hay fever), the H antagonists are second-line drugs
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these drugs in the treatment of allergies such as rhinitis. A few after glucocorticoids administered by nasal spray. In urticaria, in
H antagonists (eg, terfenadine, acrivastine) have been shown to which histamine is the primary mediator, the H 1 antagonists are
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inhibit the P-glycoprotein transporter found in cancer cells, the the drugs of choice and are often quite effective if given before
epithelium of the gut, and the capillaries of the brain. The signifi- exposure. However, in bronchial asthma, which involves several
cance of this effect is not known. mediators, the H antagonists are largely ineffective.
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