Review of Pharmacology - 9E (2015)

Autacoids
All second generation antihistaminics are metabolized to active products except cetirizine
and mizolastine. It possesses additional anti-allergic mechanisms like inhibition of
release of cytotoxic mediators from platelets and inhibition of chemotaxis. Some
persons acquire sedative effects with cetirizine. Levocetirizine is l-isomer of cetirizine
that is more potent and less sedative.
• Azelastine possesses maximum topical activity and can be given by nasal spray for
allergic rhinitis.
• Mizolastine, ebastine, levocabastine, rupatidine, acrivastine and olopatadine are other
second generation antihistaminic agents.
• Olopatadine is a recently approved topical H 1
-antihistaminic used as nasal spray for
seasonal allergic rhinitis.
• Alcaftadine is approved as ophthalmic solution for allergic conjunctivitis.
Serotonin
5-hydroxytryptamine (serotonin) is synthesized from tryptophan. It is produced by
hydroxylation followed by decarboxylation of tryptophan; steps similar to catecholamine
synthesis. It is similarly stored in the vesicles and its action is terminated by reuptake. It acts
by activation of several serotonin receptors (5- HT 1
- HT 7
receptors).
Actions
• On i.v. injection, it produces triphasic response on blood pressure. Early sharp fall
(due to Bezold Jarisch reflex), then brief rise (due to vasoconstriction) followed by
prolonged fall (due to arteriolar dilation) in blood pressure is seen.
• Serotonin is a powerful stimulator of smooth muscles. It increases peristalsis and
constricts bronchi.
It has gastroprotective action by decreasing acid secretion and increasing mucus production.
5-HT is involved in regulation of sleep, cognition, behaviour and mood.
Serotonin increases platelet aggregation.
Receptors
Presynaptic
autoreceptor
5 HT 1
5 HT 2A/2C
5 HT 3
5 HT 4
5 HT 1A
5 HT 1B/1D
Cause constriction of cranial
vessels
Responsible for most of the
direct actions of serotonin
Inotropic receptor (all
others 5 HT receptors are
G-protein coupled receptors)
Some authorities describe
the term 3rd generation
antihistaminics for the active
enantiomer (like levo-cetirizine)
or metabolite (e.g. desloratidine
and fexofenadine) of 2nd
generation drugs.
Triphasic response of serotonin
• Early sharp fall (due to Bezold
Jarisch reflex)
• Then brief rise (due to vasoconstriction)
• Followed by prolonged fall
(due to arteriolar dilation)
Present in GIT
Responsible for the
increase in peristalsis
General Autacoids Pharmacology
Modulates the realse
of serotonin
Ketanserin and ritanserin
(antagonists) are useful as
antihypertensive agents
Mediates most of the reflex
and indirect actions of serotonin
Partial agonist of this
receptor (buspirone,
isapirone, gepirone)
are useful as antianxiety
drugs
Agonists at this receptor
(sumatriptan, naratriptan)
are useful for the treatment
of acute migraine
attacks
Clozapine and risperidone
are atypical antipsychotic
agents that act through
antagonistic activity at this
receptor.
Antagonists like ondansetron,
grainsetron and tropisetron
are the agents of
choice for chemotherapy
induced vomiting
Agonists (cisapride,
mosapride, renzapride,
tegaserod) are useful in
the treatment of gastroesophageal
reflux disease
Non-Selective Drugs
• Cyproheptadine: It blocks 5 HT 2A,
H 1
and muscarinic receptors. It increases appetite
and can be used in children to promote weight gain.
• Methysergide: It is a 5 HT 2A/2C
antagonist and a 5 HT 1
agonist. It is indicated for the
prophylaxis of migraine attacks but prolonged use can result in pulmonary, endocardial
and retroperitoneal fibrosis.
• LSD: It is an ergot derivative and a powerful hallucinogen. It acts as an agonist at
several serotonin receptors including 5 HT 1A
, 5 HT 2A/2C and 5 HT 5-7 receptors.
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