Histamine and antihistaminics with various drugs

Pathophysiology of histamine and drugs acting on histamine

1. HISTAMINE & ANTIHISTAMINES DEPARTMENT OF PHARMACOLOGY.

2. PURPOSE STATEMENT At the end of this lecture the student will be able to Classify Antihistamines Explain Mechanism of Action Describe Clinical Profile of Antihistamines

3. Sr.No Learning Objectives Domain Level Criteria Condition 01. History of histamine & antihistamines Cognitive M.K - - 02. Structure of histamine Biosynthesis , storage & release Cognitive N.T.K - - 03. Pharmacological action Physiological role Uses of histamine Cognitive M.K - - 04. Classification of antihistaminic Pharmacological action Cognitive M.K - - 05. Side effects and toxicity And Uses Cognitive M.K - - At the end of this lecture student should be able to M.K = Must know ; N.T.K = Nice to know ; D.T.K = Desirable to know

4. Histamine Histamine is a imidazole derivative( B imidazole ethylamine.) Distributed in Skin , G.I.T. Mucosa ,Lung, Brain,C.S.F.,Bone Marrow. Also in Venoms, Sting secretion Histamine is also distributed in: Mast Cells in all peripheral tissues of the body . Basophils which circulate in the blood. Histaminocytes in stomach. Histaminergic neuron in brain.

5. RELEASE: ▬▬▬▬▬▬▬ ↓ ↓ IMMUNOLOGICAL CHEMICAL

6. PHARMACOLOGICAL ACTIONS H 1 RECEPTOR MEDIATED Blood vessels- Urticarial response Visceral smooth muscle- Bronchoconstriction Glands- increase secreation Adrenal medula -stimulate to release NE CNS-Wakefulness

7. PATHOPHYSIOLOGICAL ROLE Gastric secretion Allergic phenomenon As transmitter Inflammation Tissue growth and repair Headache

8. H 1 & H 2 RECEPTOR MEDIATED ACTION Blood vessels- Fall in B.P.(EDRF) Increase permeability of post capillary venule Headache Heart-Positive chronotropic and inotropic effect Histamine injected intradermally-Lewis triple response

9. CLINICAL USES POSITIVE CONTROL INJECTION- SKIN ALLERGY TESTING BETAHISTINE- SELECTIVE HISTAMINE ANALOGUE USED IN VERTIGO TESTING SECRETING CAPACITY OF STOMACH HYPERACTIVITY OF ASTHMATICS DIAGNOSIS OF PHEOCHROMOCYTOMA

10. Adverse Effects : Hypotension Headache Wheal formation Brochoconstriction Gastric acidity Intestinal cramp Flushing Contraindications : Asthma Peptic ulcer

11. Classification Highly sedative ---------- Moderately sedative Mild sedative Second generation

12. PHARMACOLOGICAL ACTION Antagonism of histamine Antiallergic reaction-Immediate hypersensitiviy type 1 reaction CNS depression Second generation non sedating H1 prevent motion sickness- promethazine Anticholinergic action Local anaesthetic-pheniramine Fall in B.P on I.V. injection

13. Dipheniramine hydrochloride Relieve allergic rhinitis (seasonal allergy) symptoms including sneezing, runny nose, itching, and watery eyes Relieve itching and swelling associated with uncomplicated allergic skin reactions. Control coughs due to colds or allergy

14. Side Effects : Sedation Motor incoordination Fatigue Tendency to fall asleep Anticholinergic effect Epigastric distress Headache Dermatitis Teratogenic-cyclizine & fexofenadine

15. Second generation H 1 -receptor antagonists Loratadine It has long lasting effects and does not cause drowsiness because it does not cross the BBB It is the only drug of its class available over the counter Terfenadine It was formerly used to treat allergic conditions In the 1990’s it was removed from the market due to the increased risk of cardiac arrythmias

16. Cetrizine Metabolite of hydroxyzine , affinity for peripheral H 1 receptor, inhibits release of histamine & of cytotoxic mediators from platelets,eosinophils during secondary phase of allergic reaction t ½ - 7- 10 hrs . Indications : Upper respiratory allergies, urticaria , atopic dermatitis , seasonal asthma.

17. fexofinadine Eliminated anticholinergic and antiadrenergic effects via bulky groups. Researches also show that fexofenadine cannot cross the blood-brain barrier (note the polar COOH and OH).

18. Third generation H 1 -receptor antagonists These drugs are derived from second generation antihistamines They are either the active enantiomer or metabolite of the second generation drug designed to have increased efficacy and fewer side effects

19. USES : Allergic disorders Pruritides Common cold Motion sickness Vertigo Preanaesthetic medication Cough Parkinsonism Acute muscle distonia As sedative, hypnotic, anxiolytics

20. Summary : Histamine is released from mast cells and causes some allergic disorders which may be life threatening . Antihistaminics are the drugs that blocks the action of histamine and relieves some allergic conditions.

21. THANK YOU !