HISTAMINE

Storage Sites Highest amounts in mast cells BasophilsSkinLung Intestinal mucosa StomachBrain

RELEASE

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 β 2 agonists

SYNTHESIS & INACTIVATIONTION

H 2 H 1 H 3 H istamine Mediator Neurotransmitter CNS ANS H H 1 -ve presynaptic autoregulation

Receptor Type Major Tissue Locations Major Biologic Effects H1H1 smooth muscle, endothelial cells acute allergic responses H2H2 gastric parietal cellssecretion of gastric acid H3H3 central nervous systemmodulating neurotransmission H4H4 mast cells, eosinophils, T cells regulating immune responses Histamine receptors

Histamine receptors antagonists

Diphenhydramin ( First generation) Diphenhydramin ( First generation) Clinical uses : Insomnia Motion sickness H 1 antagonists

Loratadine (Second generation) Loratadine (Second generation) Non-sedating Clinical uses Allergic conditions : allergic rhinitis Conjunctivitis Urticaria H 1 antagonists

Cimetidine Cimetidine Inhibitor of gastric acid secretion Used in the treatment of : peptic ulcers H 2 antagonists

BETAHISTINE Used in treatment of : vertigo in middle ear H 3 antagonists

EICOSANOIDS

INHIBITORS OF EICOSANOIDS

Phospholipids Phospholipase A 2 Arachidonic Acid Prostaglandins PGE2, PGD2, PGF2  Thromboxane (TXA2) Prostacyclin (PGI2) COX1 & COX2 Leukotrienes LTA4, B4, D4, C4 Lipoxygenase Drugs NSAIDs Corticosteroids Zileuton

ACTIONS

Vascular smooth muscles: Potent vasoconstrictor. PGE 2 and PGI 2 Thromboxane A 2 Potent vasodilators.

Blood: PGE 2 and PGI 2 inhibit platelet aggregation TXA2 a potent inducer of platelet aggregation.

 One of the chemical mediators in inflammatory reactions. Inflammation:

-PGF 2  -LTs and thromboxane are potent bronchoconstrictors in man → allergic bronchospasm. Bronchial smooth muscle: - PGE 2 cause dilatation.

Uterine smooth muscle: PGE 2 and PGF 2  → Menstruation/ Dysmenorrhea/ Labor contractions

- PGE 2 and PGF 2  and LTs GIT smooth muscle:  GIT motility

GIT secretions: PGE 2, PGE 1 PGI 2 ↓ 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: PGE 1 and PGE 2 increase body temperature.

CLINICAL USES OF PGS ANALOGS

Carboprost PGF 2 α ( analog) 1)Abortifacient: Trigger abortion in first trimester.

2) For postpartum haemorrhage vasoconstriction + uterine muscle contraction

(PGF 2 α analog ) eye drops in open angle glaucoma. ↓ IOP by enhancing outflow of the aqueous humar. Latanoprost

Alprostadil (PGE 1 analog) 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  (PGE 1 analog) Peptic ulcer

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