2. INTRODUCTION
 Naturally occuring substances – termed as local
harmones which originate from diffuse tissues &
produce intense pharmacological action near their
site of formation & release.
 Auto’s=Self ; akos= remedy/ medicinal agent.

3. CLASSIFICATION
 Based on chemical nature;
 1.BIOGENIC / ENDOGENOUS AMINES: Histamine,
5-HT.
 2.POLYPEPTIDES:Bradykinin, sub-p.
 3.LIPID SOLUBLE ORGANIC ACIDS/ PHOSPHO
LIPID DERIVATIVES:
 (A).EICOSINOIDS: PG’S, PC’S, LT’S, TX’S.
 (B).PAF.

4. HISTAMINE
 Tissue amine.
 Histos- Tissue.
 DISTRIBUTION: Widely distributed in almost all
mammal tissues & in venom of bees & wasps.
 SYNTHESIS: In mammals formed by Decarboxylation
of Histidine in prescence of Histidine decarboxylase.
 STORAGE: Present in platelets, leucocytes, basophills
& mastcells.
 Mainly in mastcells & basophills due to presence of
his.decarboxylase, specialised storage granules.

5. MECHANISM OF ACTION
 Acts through 4 receptors viz : H1, H2, H3, H4 – all
belonging to family GPCR.
 Activation of H1 receptors :
 Activation of H2 receptors:

6. PHARMACOLOGICAL ACTIONS
 CVS: (A). BLOOD VESSELS: In herbivores – Sys & Pul
vasoconstriction.
 In humans Pul.vasodilation.
 Acts by 3 ways: (a).Activation of H1 receptors on the
endothelial cells cause rapid- short lived vasodilation.
 (b).Activation of H2 receptors in the vascular smooth
muscle causes slower but prolonged vasodilation.
 (c).Relaxation of smooth muscle of capillaries &
venules leading to their dilation and fall in BP.

7. PHARMACOLOGICAL ACTIONS
 (B).BP: Therapeutic doses induces hypotension, short
lived.
 Large doses –prolonged hypotension.
 Hypotension left untreated may cause irreversible
shock & death.
 Histamine induced hypotension is partially reversed
by anti-histaminics & completely reversed by
adrenaline.

8. PHARMACOLOGICAL ACTIONS
 TRIPLE RESPONSE; When given (20mcg) ID develops
a triple response :
 (a).FLUSH(RED REACTION): Red line r spot develop
with in 10sec, due to local dilation of capillaries &
venules.
 (b).WHEAL: Local swelling due to edema, mottled
reddening around injury.
 Lasts about 1 1/2min.
 Due to increased permeability of capillaries 7 post
capillary venules with consequent xtravasation of
fluid.

9. PHARMACOLOGICAL ACTIONS
 (c).FLARE: Redness with irregular margins spreads out
from injury.
 Triple response is part of normal reaction to injury.
 Its prevention is used to evaluate anti-histaminic activity
of a new drug.
 (C).HEART:Increases sinus rate (+ve chronotropic action)
 Increases the amplitude of ventricular contraction
(+inotropic effect)
 Decreases AV conduction time & increases coronary blood
flow, high conc. induce ven.fibrillation.

10. PHARMACOLOGICAL ACTIONS
 (D)SMOOTH MUSCLE: Stimulates smooth muscles
of various tissues by direct action(H1).
 Bronchial & Uterine smooth muscle – highly sensitive.
 GIT & Ureteral smooth muscle – respond moderately.
 Thru H1 receptor – gall bladder contraction ,
 H2 receptor – gall bladder relaxation.
 ‘H’ –induced bronchospasm – antagonised by
adrenaline, isoprenaline & aminophylline but not by
anti-histaminics r atropine.

11. PHARMACOLOGICAL ACTIONS
 ENDOCRINE GLANDS: Important physiological
mediator of gastric acid secretion.
 CNS: Doesn’t cross BBB, ‘H’ constituted in 2types of
cells – Histaminergic neurones & Mast cells.
 Considered as ‘Waking amine’- increase in sensitivity
of large cerebral areas to excitatory inputs.
 IMMUNOMODULATION: Increases Humoral &
Cellular immunity by various receptors , H1- cellular
immunity , H2- Humoral immunity.

12. A,D,M,E:
 Stable compound & absorbed from all sites .
 Rapidly under go first pass metabolism in liver.
 Metabolism varies acc.to: animal spcs, sex , organ
studied.
 Chemically it is B-Imidazolyl etylamine.
 End products of metabolism include N-Methyl
imidazole aectic acid, N-acetyl histamine.

13. ADR
 Due to pharmacological actions: hypotension, visual
disturbances, dyspnea, diarrhoea.
 Man, Gunea pig- extremely sensitive.
 Rats & Mice – highly resistant.
 Large dose causes – severe nausea, gripping, headache
& sweating.
 USES:Study of gastric acid secretion.

14. ANTI-HISTAMINICS
 Certain phenolic ether – anti-histaminic properties.
 CLASSIFICATION: By two ways Clinically &
Chemically.
 (A).CLINICAL CLASSIFICATION:
 1.POTENT & SEDATIVE: Diphenhydramine,
Promethazine.
 2.POTENT & LESS SEDATIVE: Cyclizine, Meclizine.
 3.LESS POTENT & LESS SEDATIVE: Antazoline,
Cinnarizine.
 4.NON SEDATIVE: Loratidine, Cetirizine.

15. CHEMICAL CLASSIFICATION
 General formula:
 Based on configuration of ‘X’ classified as :
 1. ETHANOLAMINES(X=‘O’): Diphenhydramine,
Doxylamine.
 2.ETHYLENE DIAMINES(X=‘N’): Mepiramine, Antazoline.
(show negligible anti-cholinergic & anti-emetic efcts)
 3.ALKYL AMINES (X=‘C’): Chloropheneramine,
Triprolidine.
 4.PIPERAZINES: (X=‘C’ in conjunction with piperazine
ring): Cinnarizine, Cetirizine.

16. CHEMICAL CLASSIFICATION
 5.PHENO THIAZINES (X=‘N’ as apart of
phenothiazine nucleus): Promethazine, Trimeprazine,
show potent anti-emetic effect.
 6.PIPERIDINES: Loratadine, Fexofenadine.
 7.DIBENZOXYPINES: Doxepine (Tricyclic anti
depressant) shows potent anti-histaminic properties.

17. ‘H’- ANTAGONISTIC ACTIONS
 1.ANTI-HISTAMINIC ACTIONS: Competatively block
‘H’ at various sites.
 Antgonize stimulant action of ‘H’ on: Smooth muscle
of GIT, bronchi, uterus & bld.ves.
 Reduce ‘H’ induced triple response.
 Anti-allergic & anti-inflammatory actions involve:
(a). Inhibition of release of mediators from mastcells,
basophills.
 (b).Down regulation of H1-receptors.
 Don’t antgonize CVS actions of ‘H’.

18. ANTAGONISTIC ACTIONS
 OTHER ACTIONS: Related to their blocking of 5-HT
& A1-Adreno receptors.
 1.SEDATION & HYPNOSIS: CNS depression –
common side effect.
 Induce varying degrees of sedation, drowsiness &
sleep.
 2.CNS STIMULATION: Stimulation is less ,
conventional doses of Promethazine cause
restlessness, tremors & insomnia.

19. ANTAGONISTIC ACTIONS
 3. ON ANS: First gen. anti-histaminics show
muscarinic blocking activity, second gen. anti-
histaminics doesn’t show these actions.
 4.ANTI-EMETIC & ANTI-MOTION SICKNESS:
Diphenhydramine & Promethazine block
histaminergic signals from the vestibular nucleus to
vomiting center.
 5.ANTI-PARKINSONIAN EFFECTS: Central anti-
muscarinic actions useful in treating parkinsonism.

20. ANTAGONISTIC ACTIONS
 6.CVS: Rapid IV administration of Diphenhydramine,
Antazoline may produce dose related prolongation of
QT interval due to membrane stabilising effect.
 7.LOCAL ANAESTHESIA: Promethazine,
Diphenhydramine exhibit local anaesthetic activity.
 A,D,M,E: Well absorbed orally & parenterally.
 Anti-histaminic effect starts with in 15-30 min, peaks
by 1hr & lasts for 3-6hrs.
 Meclizine- action persists for 12-24hrs.

21. ANTAGONISTIC ACTIONS
 A,DM,E: First gen compounds metabolised by
CYP3A4 in liver.
 H1-antagonists induce hepatic microsomal enzymes,
facilitating their own metabolism.
 ADR: Mild,
 1.CNS: Sedation & Hypnosis, Fatigue.
 In children less than 2yrs- Promethazine cause
Apnoea.
 ANTI-MUSCARINIC EFFECTS: Dry mouth, blurred
vision, bladder disturbances & rarely impotence.

22. ADR:
 GIT: Nausea, vomiting, epi-gastric distress.
 MISC: May produce allergic manifestations despite of
their anti-allergic & anti-inflammatory properties.

23. THERAPEUTIC USES
Used in treatment of : 1.Allergic disorders,
2.Reagenic allergy,
3. Allergic conjunctivitis ,
4. Mastocytosis,
5.Other uses (a).As hypnotics,
(b).As anti-emetics,
(c).In parkinsonism,
(d).In motion sickness & vertigo,
(e).Anti-tussives,
(f).Local anaesthetics.