histamine

definition

decarboxylation producy of histidne

stored in mast cells and basophils

lungs - GIT - skin

histamine release

allergy as a result of an antigen reaction

trauma

drugs like : morphine - succinylcholine - tubocurarine - atracurium - mivacarium

smoke venom

H1

endothelium - smooth muscle - brain postsynaptic - skin in sensory nerve endings

it increase IPE and DAG → VD occurs by release NO → increase cGMP

they produce →

BV = vasodilatation

decrease BP

increase permeability

bronchoconstriction

contraction of GIT and uterus

skin = itching - hives and urticaria

H2

gastric mucosa - cardiac mucosa - endothelium - brain postsynaptic

increase cAMP → stimulate adenylcycase enzyme

can produce →

increase gastric HCL - pepsin

increase chronotropic and increase inotropic

VD

H3

inhibit adenylcyclase so it decreases cAMP

postsynaptic - myentric plexus

can produce →

decrease transmitter release from histaminergic and other neurons

H4

decrease cAMP - Ca++

eosinophils - neutrophils - CD4 T cells

stimulation → modulate production of some blood cells

mediate effects on cytokines

effects of histamine can be antagonized by

physiological antagonism → adrenaline

competitive antagonism → antihistamic drugs

prevention of release →glucocorticoids

desensitization

first generation antagonist

strong sedative effect

block autonomic receptors

lipid soluble - pass BBB

metabolized by liver

duration = 4 -6 hours

excreted by kidney and milk

2nd generation antagonists

fexofandine

loratadine

cetirizine

---

longer duration = 12 - 24 hours

no sedation

no anti-emetic effects

no anti-serotonin effect

no block for autonomic receptors

no pass for BBB

action of antihistamic

H1 blocking action

CNS depressant action

antiemetic action and anti-motion sickness

atropine like action

antiparkinson action

quinidine like action - membrane stabilizing action - local anesthetic action

anti-serotonin action

uses

allergic reactions → allergic rhinitis - common col preparations - urticaria - atopic dermatits - angioedema

vomiting → cyclizine - meclizine

motion sickness prophylaxis → diphenhydramine - promethazine - cyclizine - meclizine

sedative and hypnotics → sleeping aids - promethazine - diphenhydramine

adverse effects

sedation - dizziness - CNS depressions - excitation in children and some adults

hallucination - excitment - convulsions - coma

dry mouth -constipation → atropine like action

teratogenic

allergy