DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Table 32–2
Preparations and Dosage of Representative H 1
Receptor Antagonists a (Continued)
CLASS AND
DURATION
NONPROPRIETARY OF ACTION, SINGLE DOSE
NAME TRADE NAME HOURS b PREPARATIONS c (ADULT)
Phthalazinones
Azelastine HCl d ASTELIN 12-24 T Two sprays/nostril
Piperidines
Levocabastine HCl LIVOSTIN 6-12 T One drop/eye
Ketotifen fumarate ZADITOR 8-12 T One drop/eye
Loratadine CLARITIN 24 O, L 10 mg
Desloratadine CLARINEX, AERIUS 24 O 5 mg
Ebastine EBASTEL 24 O 10-20 mg
Mizolastine MIZOLLEN 24 O 10 mg
Fexofenadine HCl ALLEGRA, TELFAST 12-24 O 60-180 mg
HCl, hydrochloride.
a
For a discussion of phenothiazines, see Chapter 16.
b
The duration of action of H 1
antihistamines by objective assessment of suppression of histamine- or allergen-induced symptoms is longer than might
be expected from measurement of plasma concentrations or terminal elimination t 1/2
values. For a more complete discussion, see Simons, 2003.
c
Preparations are designated as follows: O, oral solids; L, oral liquids; I, injection; S, suppository; SR, sustained release; T, topical. Many H 1
receptor
antagonists also are available in preparations that contain multiple drugs.
d
Has mild sedating effects.
e
Dimenhydrinate is a combination of diphenhydramine and 8-chlorotheophylline in equal molecular proportions.
f
Trade-name drug also contains other medications.
g
Also has anti-serotonin properties.
U.S.), azelastine (ASTELIN, ASTEPRO, nasal spray; OPTIVAR, ophthalmic
drops), emedastine (EMADINE, drops), epinastine (ELESTAT, drops),
ketotifen (ZADITOR, drops), and olopatadine (PATANOL, drops;
PATANASE, spray) are effective in allergic conjunctivitis and rhinitis.
H 1
antihistamines have been investigated for potential anti-inflammatory
properties because histamine releases inflammatory
cytokines and eicosanoids, increases expression of endothelial adhesion
molecules, and activates the pro-inflammatory transcription
factor NF-κB (Holgate et al., 2003; Thurmond et al., 2008).
Although H 1
antihistamines do exhibit a variety of anti-inflammatory
effects in vitro and in animal models, in many cases the doses
required are higher than those normally achieved therapeutically,
and clinical effectiveness has not been proven (Holgate et al., 2003;
Thurmond et al., 2008). Rupatadine is a second-generation H 1
antagonist (available in many countries outside the U.S.) that also
blocks receptors for the inflammatory phospholipid, PAF (Mullol et
al., 2008). Although rupatadine appears to have broader anti-inflammatory
effects than other antihistamines, the clinical relevance of
these properties is unclear.
Certain allergic dermatoses respond favorably to H 1
antagonists.
The benefit is most striking in acute urticaria. Chronic urticaria
can be less responsive but also may require higher doses than has
been approved for rhinitis (Siebenhaar et al., 2009; Kaplan, 2002).
Furthermore, the combined use of H 1
and H 2
antagonists sometimes
is effective when therapy with an H 1
antagonist alone has failed.
Angioedema also responds to treatment with H 1
antagonists, but the
paramount importance of epinephrine in the severe attack must be
re-emphasized, especially in life-threatening laryngeal edema
(Chapter 12). In this setting, it may be appropriate to also administer
an H 1
antagonist intravenously.
H 1
antagonists have a place in the treatment of pruritus. Some
relief may be obtained in many patients with atopic and contact dermatitis
(although topical corticosteroids are more effective) and in
such diverse conditions as insect bites and poison ivy. Pruritus without
an allergic basis sometimes responds to antihistamine therapy.
However, the possibility of producing allergic dermatitis with local
application of H 1
antagonists must be recognized. The urticarial and
edematous lesions of serum sickness respond to H 1
antagonists, but
fever and arthralgia often do not.
Many drug reactions attributable to allergic phenomena
respond to therapy with H 1
antagonists, particularly those characterized
by itch, urticaria, and angioedema. However, explosive release
of histamine generally calls for treatment with epinephrine, with H 1
antagonists being accorded a subsidiary role. Nevertheless, prophylactic
treatment with an H 1
antagonist may reduce symptoms to a tolerable
level when a drug known to be a histamine liberator is to
be given.
Common Cold. H 1
antagonists are without value in combating the
common cold. The weak anticholinergic effects of the older agents
may tend to lessen rhinorrhea, but this drying effect may do more
harm than good, as may their tendency to induce somnolence.