Antihistaminic Agent, Gastric Proton
Pump inhibitor, Anti-neoplastic Agents
Prof. Arti P. Bhetariya
Ph.D. Scholar
School of Pharmacy
Dr. Subhash University,
Junagadh
Histamine
Hormone(Autocoid)
A compound which is released by cells(WBC) in response to
injury and in allergic and inflammatory reactions, causing
contraction of smooth muscle and dilation of capillaries.
Produced by basophils and by mast cells found in nearby
connective tissues.
Released from cells in response to an antibody called
immunoglobulin E (IgE).
Production and secretion of
Histamine
H1 Smooth muscle Contraction Diphenhydramine
(Intestine, uterus, airway) hydrochloride*
Blood vessels Vasodilation Cetirizine
Levocetrazine
Brain Transmitter Cromolyn sodium
CNS Stimulation Azatidine maleate
Triprolidine hydrochloride
H2 Gastric gland Acid secretion
Heart A- + chronotrophy
V- + inotrophy Cimetidine*,
Uterus Relaxation Famotidine,
Ranitidin
Blood vessels Vasodilation
Brain Transmitter
H3 Lung, spleen, skin, gastric Decrease histamine Impromidine
mucosa, brain release Thioperamide
Ileum Inhibit Ach release
Histamine Receptors
There are four types of histamine receptor:
H1, H2, H3 and H4
G Protein Coupled Receptor(GPCR) family (8, 16–20)
Histamine produced allergic reaction by binding with
respected Receptor.
Antihistaminic agent
are the drugs that which counteract the action of
histamine.
Antihistaminic Agents
• H1 antagonist:
First generation
Amino alkyl ether
Ethylene diamine
Propylamines (Alkylamines)
Piprazines
Phenothiazine
Second generation
• H2 antagonist:
▫ Gastric Acid inhibitors
▫ Proton Pump Inhibitors
Classification H1 Antagonist:
1. Aminoalkyl ether analogues:
Diphenhydramine hydrochloride(HCl),
Dimenhydrinate, Doxylamines cuccinate, Clemastine
fumarate, Diphenylphyraline HCl
2. Ethylenediamine derivatives
Tripelenamine HCl
3. Propylamines
▫ Chlorpheniramine maleate, Triprolidine HCl,
Phenidamine tartarate
Hydrochloride(HCl), Succinate, maleate, tartarate, fumarate represent the Salt form of drug.
4. Phenothiazine derivative:
▫ Azatidine maleate, Cyproheptadine HCl
Tricyclic ring(Phenothiazine)
▫ Promethazine HCl, Trimeprazine tartrate
5. Piprazines(Cyclic base chain analogues)
▫ Buclizine HCl, Meclizine HCl, Chlorcyclizine HCl
Second Generation: Non-Sedative
▫ Cetirizine, Levocetrazine, Cromolyn sodium, Astemizole,
Loratadine
FDA-approved- H-1 Antihistamines
Aminoalkyl Ether Piprazines
▫ Diphenhydramine ChlorCyclizine
▫ Dimenhydrinate Meclizine
▫ Doxylamine
Phenothiazines
• Ethylenediamine Promethazine
• Tripelenamine
Second generation:
Alkylamines(Propylamines) Cetirizine
▫ Chlorpheniramine Cromolyn sodium
▫ Triprolidine
Antihistaminic agent-FDA-approved Indications
H-1 Antihistamines H-2 Antihistamines
• Allergic rhinitis(Hey fever) •Peptic ulcer
• Allergic conjunctivitis •Acid reflux
• Allergic dermatological
reaction(s) •Gastritis
• Sinusitis •Zollinger Ellison syndrome
• Urticaria(hives)
• Angioedema
• Atopic dermatitis
• Bronchitis
• Motion sickness
• Nausea
• Vomiting
Aminoalkyl Ether:
Diphenhydramine hydrochloride (HCl)
Dimenhydrinate(Active form)
Doxylamine
Diphenhydramine hydrochloride*
Relieve red, irritated, itchy,
watery eyes; sneezing; and runny
nose caused by hay fever,
allergies, or the common cold.
-HBr
Doxylamines succinate Dimenhydrinate
Used to manage and
treat nausea and the antiemetic drug :
vomiting of The combination with
pregnancy (NVP), [Diphenhydramine]
allergic rhinitis, and +
insomnia. [Dimenhydrinate]
Tripelenamine HCl
2. Ethylenediamine derivatives
Tripelenamine HCl
To treat hypersensitivity
reactions, coughs, and the
common cold.
3.Alkylamines
Triprolidine hydrochloride, Chlorpheniramine
Pyridine
Triprolidine is used for treatment of:
Allergies
Hay fever
Common cold
Watery eyes
Runny nose
Sneezing
Pyrrolidine
Triprolidine hydrochloride
3.Alkylamines
Triprolidine hydrochloride, Chlorpheniramine
4. Phenothiazines
Manage and treat
Promethazine hydrochloride
allergic conditions,
nausea and vomiting,
motion sickness, and
sedation.
Uses for nausea and
vomiting in
pregnancy.
Promethazine hydrochloride
5. Piperazines:
ChlorCyclizine, Meclizine
Piperazine
Chlorcyclizine HCl
Meclizine
Used to treat ASTHMA; HAY FEVER;
URTICARIA; and RHINITIS; and also
in veterinary applications
Levocetrazine
Cetirizine
CH2CH2OCH2COOH
Treat symptoms associated Effective in the treatment of
with chronic allergic rhinitis allergic rhinitis, chronic
and uncomplicated cases of urticaria, and pollen-induced
chronic idiopathic urticaria. asthma.
Cromolyn sodium
Inhibits the release of Histamine
Oral
Eye drops
Nasal solution
Nebulizer
FDA-approved medication used for prophylaxis of mild to
Moderate Bronchial Asthma and adjunctive treatment of allergic
rhinitis and systemic mast cell disease (mastocytosis) in
pediatric patients and adults.
H2 antagonist:
▫ Gastric Acid inhibitors
Cimetidine*, Ranitidine, Famotidine
▫ Proton Pump Inhibitors
Omeprazole, Lansoprazole, Rabeprazole,
Pantoprazole
H2 antagonist GuanylHistamine
Histamine
• Imidazole derivative- Cimetidine*
• Substituted furans- Ranitidine*
• Guanidino-thiazole group- Famotidine*
• Substituted thiazoles- Nizatidine
• Aminoalkylphenoxy series- Roxatidine
Use
To treat
Stomach Ulcers (gastric and duodenal),
Erosive Esophagitis (heartburn or acid indigestion),
Gastroesophageal Reflux Disease (GERD),
Zollinger-ellison syndrome(tumor)
Mechanism of action
Normally, after a meal,
Gastrin stimulates Histamine release
Which binds to Histamine H2 receptors on gastric parietal
cells
The activation of Adenylate Cyclase,
Increase intracellular cAMP levels,
Activates protein kinase A (PKA),
The stimulate of H+/K+ ATPase pump,
Acid Secretion
Mechanism of action
H2 blockers function as competitive antagonists.
H2RAs decrease gastric acid secretion by
Competitively blocked H2 receptor
Histamine cannot act
Decrease cAMP formation
Reduced acid secretion
Cimetidine
1-cyano-2-methyl-3-[2-[(5-methyl-
1H-imidazol-4
yl)methylsulfanyl]ethyl]guanidine
Ranitidine*
Famotidine
Gastric Proton pump inhibitors:
Omeprazole, Lansoprazole, Rabeprazole, Pantoprazole
The Proton-Pump Inhibitor drugs (PPIs)
have eclipsed the H2 blockers as the most
commonly prescribed agents to reduce
stomach acid for short-term treatment.
The H,K-ATPase is the final step of acid
secretion, therefore an inhibitor of this
enzyme is more effective than receptor
antagonists.
Mechanism of Action:
The enzyme uses extracellular
K+ in order to secrete acid by
the exchange of cytoplasmic
hydronium with this K+.
Proton pump inhibitors
(PPIs) block the gastric
H,K-ATPase, inhibiting
gastric acid secretion.
Omeprazole
Lansoprazole
Rabeprazole
Pantoprazole
Discuss in detail about gastric proton pump inhibitors along with its mechanism
of action. or Write a note on proton pump inhibitors (02)
Give synthetic scheme and use of Diphenhydramine hydrochloride.(05)
Give synthetic scheme and use of cimetidine.(05)
Write the chemical structure and use of following any two drugs(02)
Classify H1-receptor antagonist.
Complete The Given Reaction(02)
What are anti-histaminic? How they act? Classify them with examples and
Use.(10)
