Histamine and Antihistaminic Agents 217
- Action on central nervous system:
Majority of antihistaminic drugs
produce variable degree of CNS
depression i.e. sedation, drowsiness and
sleep. Drugs like diphenhydramine,
promethazine are potent sedatives and
is often accompanied by inability to
concentrate.
The newer H 1 -antagonists such as
terfenadine and astemizole are claimed to
have little or no sedative action. Astemizole
is also claimed to be free of autonomic
blocking effects. Loratidine is claimed to
have little autonomic and CNS blocking
effects.
- Antimotion sickness effect: Several
H 1 -antagonists have significant
property in preventing motion
sickness. This effect was first observed
with drug, dimenhydrinate and
subsequently with other drugs like
diphenhydramine, promethazine and
other piperazine derivatives.
- Anticholinergic effects: Many of the
H 1 -antagonists also tend to inhibit
responses to acetylcholine that are
mediated by muscarinic receptors. The
newer agents, terfenadine and
astemizole have no effect on
muscarinic receptors.
- Adrenergic blocking effect: H 1 -
antagonists, specially of phenothiazine
subgroups have weak alpha-receptor
blocking effect.
- Antiparkinsonism effects: Because of
anticholinergic property, some H 1 -
antagonists have significant
suppressant effect on the parkinsonism
like symptoms.
- Local anaesthesia: Most of the H 1
antagonists block sodium channels in
excitable membranes in the same way as
procaine and lignocaine. The drugs like
diphenhydramine and promethazine are
occassionally used to produce local
anaesthesia in patients allergic to local
anaesthetic drugs.
- Antiserotonin effect: Drugs, like
cyproheptadine is promoted as an
antiserotonin agent.
Pharmacokinetics
H 1 -antagonists are well absorbed from
the gastrointestinal tract. Following oral
administration, antihistaminic effect is
manifested within 30 minutes, peak plasma
concentration is achieved in 2 to 3 hours and
effects usually last 4 to 6 hours. However,
drugs in piperazine subgroups especially
chlorcyclizine and meclizine, the actions
persists for 8 to 12 and 12 to 24 hours
respectively.
The drugs are mainly metabolized in the
liver by hydroxylation and glucuronide
conjugation, widely distributed throughout
the body and excreted in the urine.
Adverse Reactions
The most common side effect, common
to all H 1 antagonists other than terfenadine
and astemizole is sedation. Other untoward
reactions include fatigue, dizziness, tinnitus,
lassitude, blurred vision, diplopia, euphoria,
nervousness, tremor and insomnia.
Side effects include loss of appetite,
nausea, vomiting, epigastric distress,
constipation or diarrhoea. Side effects due
to antimuscarinic actions of H 1 -antagonists
include dryness of mouth, bladder
disturbances.
