HISTAMINE. Storage Sites Highest amounts in mast cells BasophilsSkinLung Intestinal mucosa...

HISTAMINE

Storage Sites

Highest amounts in mast cells

Basophils Skin Lung Intestinal mucosa Stomach Brain

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 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