2. Histamine
Histidine
Histamine
histidine
decarboxylase

3. Non–mast cell sites
epidermis, gastric mucosa,
neurons within the CNS
granules of MAST cells

4. mediator of allergy, inflammation, gastric acid secretion

5. Histamine receptors GPCRs
H1 receptor
-IP3 ,DAG ↑
-bronchoconstriction
-Vasodilation via NO
-Brain , Ganglia

6. H2 receptor
↑cAMP
Acid secretion
Vasodilation
Brain , Heart
H3 – cAMP↓
presynaptic in Brain - ↓histamine release H4

7. Histamine
Blood vessels
H1 – vasodilation
-via release of NO from endothelium–short lasting
H2 –vascular smooth muscles -vasodilation –sustained

8. Intradermal histamine
–triple response of Lewis
Red spot , Wheal , Flare
Increase capillary
permeability
Itching

9. Histamine
H1 - smooth muscle contraction
Bronchoconstriction
CNS – histamine as neurotransmitter
H1 - ↓appetite , ↑wakefulness
H2 - gastric gland –acid secretion

10. Histamine -Role in Allergic responses
Immediate hypersensitivity reaction - IgE
Mast cell
Antigen
IgE
Histamine
release
Urticaria
Angioedema
Anaphylactic shock

11. UrticariaAngioedema

12. Histamine
Synthesis
Storage
Receptors – H1 ,2 ,3 ,4
Blood vessels , Triple response
Acid secretion
Allergic responses

13. H1 receptor antagonists
1st generation
-sedation
- antichollinergic property
2nd generation
-absence of sedation
-devoid of
antichollinergic
effects

14. 1st generation H1 antagonists
Highly sedative
Promethazine , Dimenhydrinate
Moderately sedative
Pheniramine , Meclizine
Mild sedative
Chlorpheniramine , Clemastine

15. H1 receptor antagonists
ACTIONS
Antagonism of Histamine effects
Like bronchoconstriction , triple response , itching → blocked
Antiallergic action
Control of urticaria , itching , angioedema

16. H1 receptor antagonists
ACTIONS
Anticholinergic effects
High
– Promethazine , Dimenhydrinate , Pheniramine
CNS depression
– 1st generation

17. H1 receptor antagonists
Adverse effects
Sedation ,↓alertness
Motor incoordination
Tendency to fall sleep

18. Anticholinergic
Blurred vision Constipation Dry mouth
Urinary retention ABCD & U

19. H1 receptor antagonists
2nd generation
Minimal sedation
No anticholinergic
effects
Additional antiallergic
mechanisms
Fexofenadine
Loratidine
Cetrizine
Ebastine
Rupatidine
Use
Allergic rhinitis & conjunctivitis , Urticaria

20. H1 receptor antagonists
USES
Allergic disorders
Urticaria , Angioedema , Conjunctivitis , Rhinitis
supportive in anaphylactic shock
Itching (Pruritus)
Chlorpheniramine
Diphenhydramine
Common Cold

21. H1 receptor antagonists
USES
Motion sickness
Promethazine , Diphenhydramine , Meclizine
Morning sickness (vomiting of early pregnancy)
Doxylamine , Meclizine

22. Vertigo
Cinnarizine– H1 antihistaminic , anticholinergic ,anti 5-HT
vasodilator
Dimenhydrinate , Promethazine
H1 receptor antagonists
USES

23. Parkinsonism
Promethazine - anticholinergic effect
H1 receptor antagonists
USES
Cough suppression
Chlorpheniramine , Diphenhydramine

24. Let’s revise
H1 receptor antagonists
1st , 2nd generations
Difference
Adverse effects -sedation
Uses - many

25. Today's question
Terfinadine , Astemizole –Antihistaminics
Banned – WHY ???