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 ???