Antihistamine

(Histamine Antagonist)
I. HISTORY

1927- C.H. Best et. al isolates Histamine from many tissues in the body ("histos" - tissue)
1929 - Lewis describe that histamine is released following tissue injury & contributes to the
inflammatory reaction
1932 - R. Bartosch demonstrates the role of Histamine in allergic (hypersensitivity) reactions
1937 - D. Bovet & A. Stub (Pasteur Institute) first utilizes an antihistamine to lessen an allergic reaction
1944 - D. Bovet introduces the anthistamine Pyrilamine mealate
1946 - E.P Loew introduces the anthistamine Diphenhydramine
1972 - J.W Black describes two types of Histamine Receptors: H1 and H2 Receptors

Il. PHYSIOLOGIC ROLE OF HISTAMINE

A. Histamine is synthesized from the amino acid histadine

B. Histamine is stored in Mast cells and Basophil WBC's, also present in plants, many venoms and
stinging secretions
C. Many agents can trigger the release of Histamine from Mast cells and Basophil WBC's
1.foreign antigens ("allergens")
2. certain drugs (ex.morphine , dextran)
3. endogenous chemical mediators (ex. kinins)
D. Histamine can act on 2 different types of Receptors:
1. H1 - Receptors
a. local vasodilation
b. inc. capillary permeability -- > --> redness & swelling
- itching eyes
-pricking, tingling sensation
2. H2 Receptors:
-inc. gastric secretion

lll. HISTAMINE ANTAGONIST ("Antihistamines")

A. H1- Blockers
1. Prototype: Diphenhydramine, USP (Benadryl®)
a. Chemistry:
-H1- Antihistamines must possess an ethylamine group
( - CH2-CH2-N=) like Histamine itself does
b. Pharmacodynamics:
- H1 Antihistamine block the H1 -Receptors and also
Acetylcholine Receptors in the CNS ("anticholinergic action")
c. Clinical Uses:
(1)Used to treat Allergic & Inflammatory Reactions
a. allergic rhinitis
b. urticaria
c. burning tongue syndrome & geographic tongue

(2) Used to treat and prevent Motion Sickness

a. beneficial in alleviating vertigo & nausea ("anti-emetic")
b. effect produced by the anti-cholinergic action on the CNS

(3.) Used as a Sedative

Nytol® , Compoz® , SleepEze®, Sleepinal®, Sominex®

(4.) Used as Cough Suppressants

Benylin®, Tusstat®

d. Pharmacokinetics:
1. rapid onset action (within 15 min. ) after oral administration
2.duration of action about 4 hours
3. action terminated by metabolism in Liver
4. excreted in the urine & in mother's milk
e. Adverse Reactions:

-most due to blocking of ACh Receptors in the CNS sedation & fatigue
dry mouth & throat (xerostomia)
nasal stuffiness
loss of appetite (anorexia)

f. Cautions & Contraindications

1. patient with:
(a) glucoma
(b) pregnancy
2. patient on:
(a) CNS Depressants
(b) Sedatives & Alcohol

g. Preparations & Dosages:

50 m q. 4 h. Benadryl ®
2% Benadryl ® , Topical Spray
Benadryl ®; Allermax®; Banophen®; Belix®; Bena-D®; Benahist®; Ben-Allergin®; Benoject®;
Benylin®, Bydramine®; Compoz®; Dermamycin®; Diahust®; Diphen®; Diphenhist®;
Dormarex®; Dormin®; Dyrexin®; Genahist®; Hydramine®; Hydramyn®; Hyrexin®; Nidryl®; Nordryl®;
Nytol®; Phendryl®; SleepEze®; Sleepinal®; Sominex®; Tusstat®; Twilite®; Wehdryl®
Caladryl ®
1% diphendydramine
8% calamine
0.1% camphor

2. Other H1 -Antihistamines:

a. clemastine (Tavist®)
b. clorpheniramine (Chlor-Trimeton®; Teldrin®; Polarmine®;
c. pyrilamine (Allertoc®; Histalon®; Neo-Anteigan®; Neo-p
Pyramine®)
d.methapyrine (Histadyl®)
e. dexchlorpheniramine (Polaramine®)
f. brompheniramine (Dimetane®)
g. tripolidine (Actidil®; Actifed®)
h.promethazine,USP (Phenergan®; Phendadoz®; Promethegan®)
1. blocks histamine, adrenergic & dopamine receptor sites
2. used as an antihistamine, anti-emetic,anti-motion sickness
i. dimenhydrinate (Dramamine ®)
j. cyclizine (Merezine®)
k. meclizine (Dramamine ®)
l. hydroxyzine (Vistaril®; Atarax®; Oratrax®)
m.second-Generation (peripherl) H1-Antihistamine

Prototype:Cetirizine (Zyrtec®)

(1.) H1-Antihistamine that does not cross the Blood-Brain-Barrier, and thus does not produce such anti-
cholinergic side-effect such as sedation
(2.) erythromycin inhibits it's metabolism
(3.) dose:5-10 mg qd
(4.) Other Second-Generation H1 Antihistamines:
(a.) fexofenadine (Allegra®)
-erythromycin inhibits it's metabolism
(b.) loratadine (Claritin®)
10 mg qd
(c.) desloratadine (Clarinex®)
3.OTC Antihistamine Cold Preparations:

a. Actifed®
2.5 mg tripolidine
60mg pseudoephedrine
b. Allerest®
2mg Chlorpheniramine
50mg phenylpropanolamine
c. Corcidan®
2mg Chlorpheniramine
325mg Acetaminophen
d. Co-Tylenol
2mg Chlorpheniramine
325mg Acetaminophen
30mg Pseudoephedrine
e. Sine-Off ®
2mg Chlorpheniramine
325mg Acetaminophen
19 mg Pseudoephedrine
f. Sinutab®
22mg Phenytoloxamine
325mg Acetaminophen
25mg Phenylpropanolamine
g. Triaminic®
6.25 mg/5 ml Pyrilamine maleate
12.5 mg/5ml Phenylpropanolamine

GASTRO-INTESTINAL DRUGS

Background: G-I Disease

1.Peptic Ulcer Disease

a. up to 10% of US population

b. causes:

(1.) the bacterium Helicobacter pylon (previously called Campylobater pylon)

a. Helicobacter produces urease which splits urea into ammono, which damages the protective
mucus layer of the stomach
 b. Stress, smoking, alcohol, caffeine & NSAIDs can impair mucosal defensive mechanism (including
dec. gastric mucosal blood flow)

(2.) use of aspirin & other NSAIDs

(3.) hypersecretion of HCl (incl. Zollinger-Ellison Syndrome; a gastrin-producing tumor of the

pancreas)

2. Chronic inflammatory Bowel Disease (IBD)

(Crohn's Disease; ulcerative colitis)
-use of sulfasalazine as anti-bacterial agent
(combination of Sulfapyridine + Aminosalicylic use of Methotrecate (Rheumatrex®)

TREATMENT of GERD

l. Oral Symptoms:
-tooth erosion, irritation of buccal mucosa, glossitis, burning mouth, ulceration of Pillars & Pharynge
walls
ll. Anti-acidy
A. used in treatment of acute gastritis ("heartburn", upset stomach) & ulcers
B. antacids tend to inhibit the absorption of :
1. Tetracyclines
2. Digitalis
3. Iron
4. Indomethicin
C. sodium bicarbonate
D. magnesium hydroxide & aluminum hydroxide (Maalox®)
-may cause diarrhea or constipation
E. calcium carbonate & magnesium hydroxide (Rolaids®, Mylanta®)
-may cause constipation
G. sucralfate [aluminum hyrdroxide] (Carafate®) - may cause constipation
ll. Simeticone
-breaks up gas pockets --> --> releives flatulence (gas)
lll. H2-Blockers
A. Prototype : Famotidine, USP [Pepcid®]
1. Pharmacodynamics:
--H2-Antihistamines block the H2-receptors --> -->
dec. Gastric Acid Secretions
(stimulated by food, caffeine & Gastin secretion)
2. Used in the treatment of excess gastric secretion)
( incl. duodenal ulcers & Zollinger-Ellison Syndrome)
B. Other H2-Blockers:
1. nizatidine (Azid®)
2. ranitidine (Zantac®)
3. cimetidine (Tagamet®)

lV. Proton-Pump Inhibators

A. directly inhibit the active transport pump that secretes H+ from parietal cells
B. especially used for erosive esophagitis associated with GERD
C. Include
1.lansoprazole (Prevacid®)
2. esomeprazole (Nexium®)
3.pantoprazole (Protonix®)
4.omeprazole (Prilosec®)
5. rabeprazole ( AcipHex®)

TREATMENT OF CONSTIPATION
I. Osmotic Laxatives
A. Osmotic Laxatives causes water retentions in stool
B. Polyethylene Glycol 3350 (GlycoLax®,MiraLax®)