Antihistamines: a review

306 I. J‡uregui Presa Volume 14
Fig. 2. Ventricular tachycardia of the "torsades de pointes" variety. Simultaneous recording of leads I, II, III and V1.
our country 10 . Their plasma half-life is about 24
hours, the same as the duration of the suppression
of the skin test with histamine 57 (Table II). The
rationale for their retarded-release formulations
("Repetabs") is mainly to delay the plasma concentration
peak in order to reduce the adverse
CNS 4 effects representing the main problem of
these drugs: at therapeutic dosages they cause
somnolence, abatement of the reflexes and electroencephalographic
(EEG) changes 58 .
Diphenhydramine. In Spain, this drug is at present
only available in some anticatarrhal associations
and as an hypnotic 10 because of the intensity
of its CNS effects 58 . Its derivative dimenhydrinate
is widely used in our country as an antikinetotic.
Clemastine. This is the prototype of the ethanolamines,
the same chemical family as diphenhydramine,
in Spain. It is currently available only
for oral administration 10 . Its plasma half-life is 7-
12 hours, with a skin test suppression period of
12-24 hours. Its anticholinergic, antidopaminergic
and antiserotoninergic affects are similar to those
of the other "classical" antihistamines 9 .
Cyproheptadine and azatadine. With a very
close structural correlation between them, the two
classical piperidines are characterised by their
potent antiserotoninergic, anticholinergic and
sedative effects. The first one of these effects has
been taken advantage of for indications such as
Cushing's syndrome, the carcinoid syndrome or
vascular migraine 9 , and also in the management of
hypo-orexia 10 . Azatadine is the parent compound
of loratadine.
Hydroxyzine. This drug has an elimination halflife
of 14-20 hours in the adult and concentrates
rapidly in the skin, so that sustained high skin
concentrations can be observed after both single
and multiple dosing; it can inhibit the response to
histamine during at least 36 hours after a single
dose in healthy adult subjects 4 . It is classically
considered to be the most effective antihistamine
for the management of pruritus 59 , an effect that is
in part attributable to its potent sedative action
(which has been taken advantage of for therapeutic
purposes).
Cinarizine and flunarizine. These classical
piperazines, which are structurally different from
hydroxyzine and cetirizine, have been mostly
used for their antikinetotic activity. Flunarizine is
the bi-fluorinated derivative of cinarizine and also
has a calcium channel-blocking action 6 ; it is used
for prophylaxis of migraine and vertigo and in the
management of cerebral and peripheral vascular
conditions.
Promethazine. An ethylamine derivative of
phenothiazine, this compound has the same sedative
characteristics of other phenothiazine drugs,
together with potent antihistamine and antikineto-