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HISTAMINE
Storage Sites
Highest amounts in mast cells
Basophils Skin Lung Intestinal mucosa Stomach Brain
Rlease Primary mechanism during allergic
reactions IgE antibody interacts with antigen on the surface of mast cells
Enzymes as trypsin or drugs as morphine liberate histamine without prior sensitization
Inhibition of release with β2 agonists
SYNTHESIS & INACTIVATIONTION
H 2
H 1
H 3
H
istamine Mediator
NeurotransmitterCNSANS
H 3
+
+
+
H 1
-ve presynaptic autoregulation
ReceptorType
Major Tissue Locations Major Biologic Effects
H1smooth muscle, endothelial cells
acute allergic responses
H2gastric parietal
cellssecretion of gastric acid
H3central nervous
systemmodulating neurotransmission
H4
mast cells, eosinophils, T
cellsregulating immune responses
Histamine receptors
Histamine receptors antagonists
Diphenhydramin
( First generation)
Clinical uses :
Insomnia
Motion sickness
H1 antagonists
Loratadine (Second
generation)
Non-sedatingClinical uses Allergic conditions : allergic rhinitis ConjunctivitisUrticaria
H1 antagonists
Cimetidine
Inhibitor of gastric acid secretion Used in the treatment of :
peptic ulcers
H2 antagonists
BETAHISTINE
Used in treatment of : vertigo in middle ear
H3 antagonists
EICOSANOIDS
INHIBITORS OF EICOSANOIDS
Phospholipids Phospholipase A2
Arachidonic Acid
Prostaglandins PGE2, PGD2, PGF2
Thromboxane (TXA2)
Prostacyclin (PGI2)
COX1 & COX2
LeukotrienesLTA4, B4, D4, C4
Lipoxygenase
Drugs
NSAIDs
Corticosteroids
Zileuton
ACTIONS
Vascular smooth muscles:
Potent vasoconstrictor.
PGE2 and PGI2
Thromboxane A2
Potent vasodilators.
Blood:
PGE2 and PGI2
inhibit platelet aggregation
TXA2 a potent inducer of platelet aggregation.
One of the chemical mediators in inflammatory reactions.
Inflammation:
-PGF2
-LTs and thromboxane are potent bronchoconstrictors in man → allergic bronchospasm .
Bronchial smooth muscle:
-PGE2 cause dilatation.
Uterine smooth muscle:
PGE2 and PGF2 → Menstruation/ Dysmenorrhea/ Labor contractions
- PGE2 and PGF2 and LTs
GIT smooth muscle:
GITmotility
GIT secretions:
PGE2 , PGE1 PGI2
↓acid and pepsinogen secretion .
mucin, water and bicarbonate & Blood flow.
PGE2 and PGI2 increase renal blood flow and diuresis.
Kideny
Central and peripheral nervous systems
Fever: PGE1 and PGE2 increase body temperature.
CLINICAL USES OF PGS ANALOGS
Carboprost
PGF2α ( analog)
1) Abortifacient:
Trigger abortion in first trimester.
2) For postpartum haemorrhage
vasoconstriction + uterine muscle contraction
(PGF2α analog )
eye drops in open angle glaucoma.
↓ IOP by enhancing outflow of the aqueous humar.
Latanoprost
Alprostadil
(PGE1analog)
1 -Injected in corpus cavernosum of the penis for some forms of male impotence.
2 -In congenital heart anomalies
to keep the patent ductus arteriosus until
surgery .
Misoprostol
(PGE1 analog)
Peptic ulcer
Thank you