Histamine​ ​ or ​B-imidazolylethylamine
→ from L-histidine by histidine
decarboxylase
→ associated with allergic and gastric
hypersecretory disorders
→ achiral molecule
Nomenclature
Histamine or 4(5-)(2-aminoethyl)imidazole,
composed of imidazole heterocycle and
ethylamine side chain
Ratio of tautomers is dependent on
presence of imidazole rings
Index pA2​ is defined as the inverse of the
logarithm of the molar concentration of the
antagonist that reduces the response of a
double dose of the agonist to that of a single
one. The ​more potent H1-antihistamines
exhibit a pA2 value significantly higher than
6 hyperemesis gravidarum (nausea of
H1​-involves in pruritus ,pain,
vasodilation,hypotension, flushing and
headache
H2​-mediate gastric acid secretion, vascular
permeability, hypotension, flushing,
headache, tachycardia, chronotropic and
inotropic activity
H3-​ prevent excessive bronchoconstriction;
mediate pruritus and may be involved in the
control of neurogenic inflammation
H4​- involved in the differentiation of
hematopoietic cells and to modulate
immune function
Antihistamine
→ drugs that block actions of histamine at
H1 receptor
Lipophilicity due to presence of 2 aryl rings
and amino moieties
First generation Antihistamine Class
Ethanolamines
→ ​presence of CHO moiety and carbon
atom
→ ​Diphenhydramine​ is the ​prototype
→ significant anticholinergic activity, as
antiemetic, motion sickness,anti-Parkinson
Diphenhydramine (Bendaryl)
→ exhibits antidyskinetic, antiemetic,
antitussive and antimuscarinic, and sedative
properties
→ sleep aid if OTC
→ most common side effect is drowsiness,
and the concurrent use of alcohol and other
CNS depressants should be avoided.
Dimenhydrinate (Dramamine)
→ ​ the 8-chlorotheophyllinate (theoclate)
salt of diphenhydramine
→ for nausea of motion sickness and for
​ .5 hour before
pregnancy); taken at least 0
beginning a trip
Bromodiphenhydramine HCl (Ambodryl)
→more lipid soluble and was twice as
effective than diphenhydramine
Doxylamine Succinate (Decapryn)
→ ​for relief of seasonal rhinitis and as night
time sedative. Alcohol should be avoided
Carbinoxamine Maleate (Clistin)
→​bitter bimaleate salt
→ potent antihistaminic
→ has only one oxygen atom
Clemastine Fumarate (Tavist)
→ ​long duration of action; has central
cholinergic blocking activity and
antimuscarinic activity
→ dextrorotatory clemastine

Diphenylpyraline HCl (Hispril, Diafen)
→​potent antihistaminic, structurally related
to diphenhydramine
Ethylenediamines
→ presence of nitrogen connecting atom
and 2 carbon atom chain
→ are diarylethylenediamines except
antazoline
→ ​Phenbenzamine​ is the ​prototype
→low anticholinergic and emetic action
Tripelennamine Citrate and HCl
→ ​First ethylenediamine developed
Pyrilamine Maleate
→ less potent antihistamine but highly
potent in antagonizing histamine-induced
contractions of guinea pig
→ not chewed but taken with food
→ has methoxy group in para
Methapyrilene HCl (Histadyl)
→ has 2-thiophene-methylene group
→ ​carcinogen
Thonzylamine HCl
→ ​less toxic than tripelennamine
Antazoline Phosphate
→ ​contains N-benzylanilino group
→ ​less active than other antihistamine, lack
local irritation
→ twice local anesthetic potency of
procaine
Piperazine (Cyclizines)
→ considered ethylenediamine derivatives
with CHN group and carbon chain, nitrogen
atom
→ potent antihistamine with high potential to
cause drowsiness and psychomotor and
cognitive dysfunction
→ slow onset but long duration of action
→ as antiemetics and antivertigo and tx of
motion sickness
Cyclizine HCl (Marezine)
→​light sensitive; IM inj
→ ​prophylaxis and tx of motion sickness
Chlorcyclizine HCl
→​light sensitive; symptomatic relief of
urticaria and hay fever
Meclizine HCl (Bonine, Antivert)
→ ​potent antihistamine used for
antinauseant and tx of motion sickness
associated with vertigo
Buclizine HCl (Bucladin)
→ ​has CNS depressant, antiemetic and
antihistamine
Propylamines
→ Monoaminopropyl or alkylamine
derivatives
→ structurally by an sp3 or sp2
→ referred as pheniramines
→ most active H1 antagonist; fewer
anticholinergic and CNS side effects
→ long half lives and once a day tx
Pheniramine Maleate (Trimeton)
→ ​least potent member
Chlorpheniramine Maleate
Dexchlorpheniramine Maleate
Dexbrompheniramine Maleate.
→ ​antihistaminic activity in the dextro
isomer
Pyrrobutamine Phosphate
→ ​long acting but slow onset of action
→ antihistaminic activity due to the
geometric isomer in which the
pyrrolidinomethyl group is trans to the
2-pyridyl group
Phenindamine Tartrate
→ ​ an unsaturated propylamine derivative
Dimethindene Maleate
→ ​antihistaminic activity resides mainly in
the levorotatory isomer.
Phenothiazines
→ antihistaminic and sedating action
→ a potent antiemetic, anticholinergic, and
significantly potentiates the action of
analgesic and other sedative drugs.
Promethazine Hydrochloride
→ ​moderately potent antihistamine
Trimeprazine Tartrate
→ antihistaminic action is 1.5 to 5 times that
of promethazine.
→ antipruritic action that may be unrelated
to its histamine-antagonizing properties
Methdilazine
→is used in chewable tablets
HCl ​has ​antipruritic effect
DIBENZOCYCLOHEPTENES AND
DIBENZOCYCLOHEPTANES
→ ​phenothiazine analog
Cyproheptadine Hydrochloride
→ ​both antihistamine and antiserotonin
activity and is used as an antipruritic agent
→ used off-label for​ nightmares associated
with post traumatic stress disorder,
prevention of migraine, suppression of
vascular headaches, and appetite
stimulation. ​Sedation​ is the most prominent
side effect
Azatadine Maleate
→potent, long-acting antihistaminic with
antiserotonin activity
→ three times the potency of
chiorpheniramine in the isolated guinea pig
Second-Generation Antihistamines
→ nonsedating and receptor selective
Acrivastine
→an alkene acid derivative of triprolidine
Cetirizine and levocetirizine
→oxidation metabolites of hydroxyzine
→ ​ zwitterionic and relatively polar
→ associated with dose-related
somnolence
Desloratadine
→an oxidation hydrolysis metabolite of
loratadine
Fexofenadine
→ an oxidative metabolite of terfenadine
H2 Antagonist
→ ​Cimetidine ​has a weak antiandrogenic
effect and may cause gynecomastia
→ ​Famotidine​ is a thiazole bioisotere of
cimetidine that contains a guanidine
substituent that may mimic the imizadole of
cimetidine.
→ ​Ranitidine​ is more potent than
cimetidine, but less potent than famotidine
→ ​Nizatidine​ is a thaizole derivative of
raniditine
 → ​exhibits both antisecretory and
cytoprotectant effects
Proton Pump Inhibitors → prevent NSAID-induced gastric ulcer
→ tx gastric hypersecretory disorders → can cause miscarriage
→ high pKa undergo protonation faster
→ more effective in short term healing of
duodenal ulcer than H2 blockers

Omeprazole (Losec)
→ ​5-methoxy-2-(4-methoxy-3,
5-dimethyl-2-pyridinyl)methyl) sulfinyl)-1H
benzimidazole
→ ​delayed release capsule
→ tx of heartburn, GERD, duodenal ulcer,
erosive esophagitis, gastric ulcer
→ antisecretory action 24-72 hrs

Esomeprazole Magnesium (Nexium)

→ ​the S-enantiomer of omeprazole

Lansoprazole (Prevacid)
→ ​prodrug

Pantoprazole
→ ​food delays its absorption but do not alter
bioavailability
→ distributed in extracellular fluid
Rabeprazole (Aciphex)
→ ​food does not affect
→ H.pylori eradication (Rabeprazole,
amoxicillin and clarithromycin)

Sucralfate (Carafate)
→ ​antiulcer effect local rather than systemic
→ has buffering capacity
→ binds to ulcer site to form protective
barrier that prevent exposure of lesion to
acid and pepsin
AE:constipation

Prostaglandins

Misoprostol