AUTOCOIDS

By
Shiva
B.Pharmacy
Shiva.pharmacist@gmail.co
m

INTRODUCTION
Naturally occuring substances termed as

local harmones which originate from diffuse

tissues & produce intense pharmacological
action near their site of formation & release.
Autos=Self ; akos= remedy/ medicinal agent.

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: PGS, PCS, LTS, TXS.
(B).PAF.

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.

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:

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

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.

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.

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.

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

PHARMACOLOGICAL
ACTIONS
ENDOCRINE GLANDS: Important physiological

mediator of gastric acid secretion.

CNS: Doesnt 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 , H1cellular immunity , H2- Humoral immunity.

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.

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.

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.

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 & antiemetic efcts)
3.ALKYL AMINES (X=C): Chloropheneramine,
Triprolidine.
4.PIPERAZINES: (X=C in conjunction with
piperazine ring): Cinnarizine, Cetirizine.

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.

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.
Dont antgonize CVS actions of H.

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.

ANTAGONISTIC ACTIONS
3. ON ANS: First gen. anti-histaminics show

muscarinic blocking activity, second gen. antihistaminics doesnt 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 antimuscarinic actions useful in treating
parkinsonism.

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.

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.

ADR:
GIT: Nausea, vomiting, epi-gastric distress.
MISC: May produce allergic manifestations

despite of their anti-allergic & antiinflammatory properties.

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.

THANK YOU