histamine pharmacology
DESCRIPTION
TRANSCRIPT
Histamine
Histidine
Histamine
histidine decarboxylase
Non–mast cell sites epidermis, gastric mucosa, neurons within the CNS
granules of MAST cells
mediator of allergy, inflammation, gastric acid secretion
Histamine receptors GPCRs
H1 receptor
-IP3 ,DAG ↑
-bronchoconstriction-Vasodilation via NO
-Brain , Ganglia
H2 receptor
↑cAMP
Acid secretion
Vasodilation
Brain , Heart
H3 – cAMP↓presynaptic in Brain - ↓histamine release H4
Histamine
Blood vessels
H1 – vasodilation -via release of NO from endothelium–short lasting
H2 –vascular smooth muscles -vasodilation –sustained
Intradermal histamine –triple response of Lewis
Red spot , Wheal , Flare
Increase capillary permeability
Itching
Histamine
H1 - smooth muscle contraction Bronchoconstriction
CNS – histamine as neurotransmitter H1 - ↓appetite , ↑wakefulness
H2 - gastric gland –acid secretion
Histamine -Role in Allergic responses
Immediate hypersensitivity reaction - IgE
Mast cell
Antigen
IgE
Histamine release
Urticaria
Angioedema
Anaphylactic shock
UrticariaAngioedema
Histamine
Synthesis
Storage
Receptors – H1 ,2 ,3 ,4
Blood vessels , Triple responseAcid secretion
Allergic responses
H1 receptor antagonists
1st generation
-sedation
- antichollinergic property
2nd generation
-absence of sedation
-devoid of antichollinergic effects
1st generation H1 antagonists
Highly sedative Promethazine , Dimenhydrinate
Moderately sedative
Pheniramine , Meclizine Mild sedative Chlorpheniramine , Clemastine
H1 receptor antagonists
ACTIONS
Antagonism of Histamine effects Like bronchoconstriction , triple response , itching → blocked
Antiallergic action
Control of urticaria , itching , angioedema
H1 receptor antagonists
ACTIONS
Anticholinergic effects High – Promethazine , Dimenhydrinate , Pheniramine
CNS depression – 1st generation
H1 receptor antagonists
Adverse effects
Sedation ,↓alertness Motor incoordination Tendency to fall sleep
Anticholinergic Blurred vision Constipation Dry mouth Urinary retention ABCD & U
H1 receptor antagonists
2nd generationMinimal sedation
No anticholinergic effects
Additional antiallergic mechanisms
FexofenadineLoratidine
Cetrizine
EbastineRupatidine
Use Allergic rhinitis & conjunctivitis , Urticaria
H1 receptor antagonists
USES Allergic disordersUrticaria , Angioedema , Conjunctivitis , Rhinitis
supportive in anaphylactic shock
Itching (Pruritus)Chlorpheniramine Diphenhydramine
Common Cold
H1 receptor antagonists
USES
Motion sickness Promethazine , Diphenhydramine , Meclizine
Morning sickness (vomiting of early pregnancy)
Doxylamine , Meclizine
Vertigo Cinnarizine – H1 antihistaminic , anticholinergic ,anti 5-HT vasodilator
Dimenhydrinate , Promethazine
H1 receptor antagonists
USES
Parkinsonism Promethazine - anticholinergic effect
H1 receptor antagonists
USES
Cough suppressionChlorpheniramine , Diphenhydramine
Let’s reviseH1 receptor antagonists
1st , 2nd generations
Difference
Adverse effects -sedation
Uses - many
Today's question
Terfinadine , Astemizole –Antihistaminics
Banned – WHY ???