Histamine is a biogenic amine present in many tissues that functions as a neurotransmitter and is involved in inflammatory and hypersensitivity reactions. It is synthesized from the amino acid histidine. Histamine acts through multiple receptor subtypes and is involved in various physiological processes like gastric acid secretion, smooth muscle contraction, and allergic responses. Antihistamines competitively inhibit histamine receptors, with first generation antihistamines having sedative effects and second generation ones having minimal side effects. They are used to treat allergic disorders, as antiemetics, and for gastric acid reduction with H2 blockers. Concerns have been raised about impurities in the H2 blocker ranitidine. While H3

1. HISTAMINES AND ANTIHISTAMINES
PHARMACOLOGY
Dr. S P SRINIVAS NAYAK, PharmD, RPh, (Msc), (PGDND)
ASSISTANT PROFESSOR, DEPT. OF PHARMACY PRACTICE, PU.

2. HISTAMINES AND ANTIHISTAMINES PHARMACOLOGY
● Histamine is a biogenic amine present in many animal and plant tissues
that function as neurotransmitters and are also found in non-neural
tissues, have complex physiologic and pathologic effects through
multiple receptor subtypes, and are often released locally.
● It is also present in venoms and stinging secretions. It is synthesized by
decarboxylation of the amino acid, histidine. Histamine is mainly present in
storage granules of mast cells in tissues like skin, lungs, liver, gastric mucosa,
placenta, etc. It is one of the mediators involved in inflammatory and
hypersensitivity reactions.

3. HISTAMINE
● Histamine occurs in plants as well as in animal tissues and is a
component of some venoms and stinging secretions.
● Histamine is formed by decarboxylation of the amino acid l-
histidine, a reaction catalyzed in mammalian tissues by the enzyme
histidine decarboxylase. Once formed, histamine is either stored or
rapidly inactivated. Very little histamine is excreted unchanged

6. ACTIONS OF HISTAMINES
1. Nervous system: Histamine is a powerful stimulant of sensory nerve
endings, especially those mediating pain and itching the urticarial
response and reactions to insect and nettle stings.
2. Cardiovascular system: in humans, injection or infusion of histamine
causes a decrease in BP and an increase in heart rate, vasodilation.
3. Bronchiolar smooth muscle: Causes bronchoconstriction mediated by
H1 receptors. patients with asthma are very sensitive to histamine.
4. GIT: smooth muscle contraction, acid secretion, and diarrhoea.
5. Pregnancy: pregnant women suffering anaphylactic reactions may abort
as a result of histamine-induced contractions.
6. Secretory tissue: a powerful stimulant of gastric acid secretion by
activation of H2 receptors on gastric parietal cells.
7. The “triple response”: Intradermal injection of histamine causes a
characteristic red spot, edema, and flare response.

7. ANTIHISTAMINES
● H1-receptor antagonists (classical antihistamines) lessen
histamine-mediated symptoms of allergic reaction.
Mainly used for allergic reactions.
● H2-receptor antagonists reduce gastric acidity.
Clinically has benefits in peptic ulcers and hyper acid secretion.
● H3 and H4-receptor antagonists have no therapeutic indication.

9. CLASSIFICATION DEPENDING ON
SEDATION
● Highly sedating— diphenhydramine, dimenhydrinate,doxylamine,
embramine, promethazine and hydroxyzine.
● Moderately sedating— pheniramine, antazoline, trimeprazine,
meclizine and buclizine.
● Mildly sedating— chlorpheniramine, methdilazine, mepyramine,
dimethindene, triprolidine, mebhydroline, cyclizine and clemastine.
● Non-sedating— terfenadine, astemizole, cetirizine and loratidine.
● Anti-vertiginous— cinnarizine.

12. FIRST-GEN. H1-BLOCKERS
● (CNS) depression —sedation and drowsiness. some antihistamines have
antiemetic and antiparkinsonian effects.
● They have antiallergic action, hence most of the manifestations of Type-I
reactions are suppressed.
● They have anticholinergic actions —dryness of mouth, blurring of vision,
constipation, urinary retention, etc.
H1-antihistamines are well absorbed after oral and parenteral administration.
They are distributed widely throughout the body, metabolized extensively in
liver and excreted in urine.
● Adverse effects
● sedation, drowsiness, lack of concentration, headache, fatigue, weakness,
lassitude, incoordination, etc.
● Anticholinergic side effects such as dryness of mouth, blurring of vision,
constipation and urinary retention..
● Allergic reactions may occur rarely with these agents, especially contact
dermatitis on topical application.

13. SECOND-GEN. H1-BLOCKERS
● Cetirizine, loratadine, azelastine and fexofenadine are highly
selective for H1-receptors and have the following properties.
They: Have no anticholinergic effects,
Lack antiemetic effect.
Do not cross blood–brain barrier (BBB), hence cause minimal/no
drowsiness.,
Do not impair psychomotor performance.
Are relatively expensive.

15. DRUG INTERACTIONS
● Lethal ventricular arrhythmias occurred with terfenadine or
astemizole, in combination with ketoconazole, itraconazole, or
macrolide antibiotics such as erythromycin. These antimicrobial drugs
inhibit the metabolism of many drugs by CYP3A4 and cause significant
increases in blood concentrations of the antihistamines.
● Grapefruit juice also inhibits CYP3A4 and has been shown to increase
blood levels of terfenadine significantly.
● Both terfenadine and astemizole were withdrawn from the US market in
recognition of these problems. Where still available, terfenadine and
astemizole should be considered to be contraindicated in patients taking
ketoconazole, itraconazole, or macrolides and in patients with liver
disease.

16. USES OF ANTIHISTAMINES(H1)
● Uses: various allergic disorders—rhinitis, dermatitis, conjunctivitis,
urticaria, eczema, drug and food allergies.
● Preanaesthetic medication: Promethazine is used for its sedative
and anticholinergic effects.
● As antiemetic: Promethazine, diphenhydramine, dimenhydrinate,
etc. are useful for prophylaxis of motion sickness, Parkinsonism,
controlling vertigo in Meniere’s disease, blood transfusion and
saline infusion reactions
● Sedative and hypnotic: H1-antihistamines (e.g. promethazine and
diphenhydramine) are used to induce sleep, especially in children
during minor surgical procedures.

17. H-2 BLOCKERS
● Histamine-2 receptor antagonists competitively inhibit the interaction
of histamine with H2 receptors. They are highly selective and have
little or minimal effect on H1 or other receptors. H2 antagonists
mainly interfere with gastric secretion.
● Important examples of this group of drugs used widely in the
treatment of peptic and duodenal ulcer, include
● cimetidine,
● ranitidine,
● famotidine,
● nizatidine and
● roxatidine.

19. IMP
. POINTS OF H2 BLOCKERS
Cimetidine is the enzyme inhbitor and increases amitryptiline, benzodiazepines,
carbamazepine, imipramine, lignocaine, nifedipine, phenytoin, quinidine, terfenadine,
theophylline, verapamil and warfarin levels, Gynaecomastia, Teratogenecity and increased
prolactin levels may be seen following therapeutic doses of cimetidine.
H2 blockers can produce bradycardia, hypotension, AV block and sinus arrest (especially
with rapid IV administration),
haematologic (agranulocytosis, pancytopenia, aplastic anaemia, and thrombocytopenia)
and dermatologic (including Stevens-Johnson syndrome, toxic epidermal necrolysis).
Cimetidine, ranitidine, and famotidine have been associated with drug-induced fever,
which typically resolves within 48 to 72 hours after discontinuation of the drug and The most
consistent adverse reaction reported with famotidine is a severe, throbbing headache.
H2 antagonists compete with creatinine and certain drugs (eg, procainamide) for renal
tubular secretion

20. CONTROVERSIES OF ZANTAC
The U.S. Food and Drug Administration announced it is requesting
manufacturers withdraw all prescription and over-the-counter (OTC)
ranitidine drugs from the market immediately. This is the latest step in an
ongoing investigation of a contaminant known as N-
Nitrosodimethylamine (NDMA) in ranitidine medications (commonly
known by the brand name Zantac).

21. H3 AND H4 BLOCKERS
● Although no selective H3 or H4 ligands are presently available for
general clinical use, there is great interest in their therapeutic potential.
● H3-selective ligands may be of value in sleep disorders, narcolepsy,
obesity, and cognitive and psychiatric disorders. Tiprolisant, H3-
blocker, has been shown to reduce sleep cycles in mutant mice and in
humans with narcolepsy.
● No selective H4 ligand is available for use in humans, Several studies
have suggested that H4-receptor antagonists may be useful in pruritus,
asthma, allergic rhinitis, and pain conditions.

22. THANK YOU