Antihistamine Drugs

 Autacoids
• Histamine and serotonin, along with prostaglandins,
belong to a group of endogenous compounds called
autacoids.
• They all have the common feature of being formed by
the tissues on which they act and, therefore, function
as local hormones.
• The autacoids also differ from circulating hormones in
that they are produced by many tissues rather than in
specific endocrine glands.

 Histamine
• Histamine is a chemical messenger mostly generated
in mast cells.
• It is present in practically all tissues, with significant
amounts in the lungs, skin, blood vessels & GI tract.
• It also occurs as a component of venoms and in
secretions from insect stings.
• Histamine mediates a wide range of cellular
responses, including allergic and inflammatory
reactions, gastric acid secretion, and
neurotransmission in parts of the brain.
• Histamine has no clinical applications, but agents that
inhibit the action of histamine (antihistamines) have
important therapeutic applications.

 Histamine and antihistamine:
• Storage: it is stored in mast cells in the skin, lungs,
and GIT.
• Release:
• histamine is just one of several chemical mediators
released in response to stimuli:
1. Antigen-antibody reaction (allergy or immunity
reaction).
2. Insect bites and snake venom.
3. Drugs: some drugs such as morphine,
succinylcholine, and atropine (large and toxic doses)
may induce histamine release.

 Action of Histamine on different Organs
• Histamine released in response to certain stimuli
exerts its effects by binding to various types of
histamine receptors (H1, H2, H3, and H4).
1. Smooth muscle fibers such as bronchi, GIT & uterus
(Spasmogenic effect).
2. Endothelium of Blood vessels: (Vasodilatation).
3. Stomach: histamine stimulates (HCl-secretion).
4. CNS: Alertness.
5. Skin and sensory nerve endings: Triple response:
wheal, redness, & flare or halo (Itching, urticaria).

 Histamine antagonists (Anti-Histamine)
A. H1-Antagonists = used as Antiallergic (Anti-histaminics).
1. First Generation = Sedating Anti-histaminic drugs,
ex.: Diphenhydramine, Chlorpheniramine maleate (in
common cold medications), Cyproheptadine (acts
as a
serotonin antagonist, resulting in appetite
stimulation).
2. Second Generation = Non-sedating Antihistaminic
drugs, ex.: Fexofenadine, Cetirizine, Loratadine.
B. H2-Antagonists = used in the treatment of peptic ulcer.
• Example: Cimetidine, Famotidine, Ranitidine, Nizatidine.

 Therapeutic uses
1. Allergic and inflammatory conditions
• H1-blockers are useful in treating and preventing
allergic reactions. For example, allergic rhinitis and
urticaria.
2. Motion sickness and nausea
• Along with the antimuscarinic agent scopolamine,
certain H1-blockers, such as dimenhydrinate &
promethazine are effective for preventing the
symptoms of motion sickness.
• They are usually not effective if symptoms are already
present and, thus, should be taken prior to expected
travel.
3. Insomnia

 Adverse effects:
1. Sedation and drowsiness.
The use of first-generation H1 antihistamines is
contraindicated in the treatment of individuals
working in jobs in which wakefulness is critical.
2. Atropine-like adverse effects (anticholinergic
effects) as dry mouth, constipation, urine
retention, tachycardia, and elevation of
intraocular pressure IOP).
• Headache is the most common adverse
reaction associated with second-generation
antihistamines.

• Inhibitors of Histamine release:
1. Glucocorticoids: inhibit antibody formation and antigen-
antibody reaction, and accordingly inhibit histamine
release.
2. Mast Cell Stabilizers act as degranulation inhibitors,
ex: disodium cromoglycate (cromolyn) and nedocromil.
3. Physiological Antagonist: Adrenaline is the physiological
antagonist of histamine (2 different agents acting on 2
different receptors causing 2 opposing actions).
4. H1-Antagonists (Antihistaminic-Antiallergic)
Antihistaminic drugs are used in the treatment of allergic
conditions such as skin rash, urticaria, edema,
anaphylactic shock.

 Notes:
• Anti-histaminic drugs are not essential in the
treatment of bronchial asthma because of the
insignificant role of histamine.
• Epinephrine acts via β2 receptors on smooth
muscle, causing relaxation. Therefore,
epinephrine is the drug of choice in treating
systemic anaphylaxis and other conditions that
involve massive release of histamine.
• Treatment of anaphylactic shock includes:
Adrenaline + Corticosteroid + Antihistaminic.

THE END