AUTACOIDS-
its Phramacological and
Pathophysiological role in the body
What are autacoids?
● Gk. autos- self, akos-remedy or medicinal agents.
● Diverse circulating or locally acting hormone like
substances,
● originate from different tissues
● produce intense biological activities near their site
of synthesis or release.
Hormone vs. Autacoids
● Produced in glands Produced in tissue.
● May act on distant organs Localised in action
● Act slowly Act rapidly, has shorter
duration of action
Classification-
CHEMICAL
STRUCTURE
Peptide
Lipid
Amine autacoids
derived
autacoids autacoids
Kinins(Bradykini
n and Kallidin Eicosanoids(
Histamine PG, LT, TXA)
Angiotensins
Platelet
Serotonin/ Tachykinins activating
5HT
factor
Cytokines
Amine autacoids
Histamine
● Gk. word, histos- tissue.
● Imidazole derivative biogenic
amine.
● Widely distributed in animal tissue.
● Cellular level- mostly storage granules of mast cell and
basophils.
● Diff. tissues- skin, GI mucosa, nose ,mouth, lung, liver
and placenta etc.
● Non mast cell histamine- gastric mucosa, epidermis,
growing tissues & brain.
Synthesis & storage-
● Stored in - mast cell, basophil.
● Non mast cell- continuously produced but not
stored.
Release-
● From mast cell- secretory/ degranulation
Extrusion of
Chemical, Rise in contents of
mechanical, intracellular granules by
physiological Ca2+ level exocytosis
stimulation (degranulation
)
Metabolism & excretion-
● Excreted through
urin.
Mechanism of action-
● Histamine receptors-4 subtype.
Physiological & pharmacological role
1. On CVS-
● Dilation of smaller blood vessels, decrease Peripheral
resistance and fall in BP.
● Capillary permeability- increases, resulting oedema
formation.
● In Heart- produces both chronotropic & inotropic effect.
● Triple response- I/D,
Reddening- vasodialtory effect.
Wheal- increase in capillary permeability
Flare- stimulation of axonal reflexes, causes
Vasodilation indirectly
Contd.
● Histamine headache- dilation of cranial blood
vessel.
2.Smooth muscle-
● Respiratory system- bronchoconstriction
● GI system- intestinal hypermotility
3.Exocrine glands-
● Gastric secretion increase.
● Some stimulant effect on lachrymal, salivary,
bronchial and pancreatic exocrine glands.
Patho- physiological roles-
Allergic reaction & anaphylaxis-
01
Inflammation-
02
Gastric secretion
03
Neurotransmission
04
Tissue repair and growth
05
Regulation of microcirculation
06
Malignancies and tumours.
07
Histamine analogues-
1. BETAZOLE
2. PENTAGASTRIN
3.BETAHISTINE
Histamine blocking drugs-
Works in 3 way
1. Prevention or reduction of histamine release
from sensitized mast cells.
2. Use of physiological antagonists.
3. Histamine receptor antagonists- competitively
blocking,
H1 receptor antagonist-
● based on chemical structure
● First generation-
1. Ethanolamines – Eg: Diphenhydramine
2. Ethylenediamines - Eg: Triplenamine
3. Alkylamines - Eg: Chlorpheniramine
4. Piperazines - Eg: Cyclizine
5. Phenothiazines - Eg: Promethazine
● Second generation
1. Alkylamines - Eg: Acrivastin
2. Piperazines - Eg: Terfenadine, Cetirizine
H1 receptor antagonist-
● based on sedation-
● First generation
1. High sedation - Eg: Diphenhydramine ,
Dimenhydramine,Promethazine
2. Moderate sedation - Eg: Pheniramine, Antazoline,
Trimeprazine, Cyproheptadine
3. Low sedation - Eg: Chlorpheniramine, Mepyramine
● Second generation
1. No sedation - Eg: Terfenadine,Astemizole,
Loratadine,Cetirizine
2. Anti vertigo - Eg: Cinnarizine
PHARMACOLOGICAL ACTIONS OF ANTIHISTAMINES
● Antagonism of histamine - block the histamine induced,
bronchoconstriction, intestinal contraction and other smooth
muscles and the triple response.
● Fall of blood pressure can be blocked
● Antiallergic action
● On central nervous systema
1. The older (first generation) antihistamincs produce variable
degree of CNS depression.
2. some antihistaminics are used for preventing motion sickness,
to reduce tremors, rigidity and sialorrhoea of Parkinsonism.
● Anticholinergic action- Antagonistic to muscarinic actions of
acetylcholine.
H2 RECEPTOR ANTAGONIST
● Cimetidine, Ranitidine, famotidine, Roxatidine,
Nizatidine, Loxatidine
● most popular drugs for peptic ulcer.
● H2 antagonists block histamine gastric secretion,
cardiac stimulation (in guinea pigs), uterine
relaxation (in rat), and bronchial relaxation
● Have antiulcerogenic effect
● Gastric ulceration due to NSAIDs, cholinergic
and histaminergic agents is prevented
SEROTONIN
● serotonin/5-hydroxytryptamine /5HT-
biogenic amines
● Chemical name- β-
aminoethyl 5-hydroxyindole.
● Primarily found- GIT, platelets, CNS.
● Act as a neurotransmitter in the CNS
● Regulation of smooth muscle function in GIT & CVS,&
in platelets formation.
● enteramine/vasotonin.
● 80% - enterochromaffin cells of GI tract.
● Precursor for melatonin
Synthesis-
Stored
mainly on
enterochro
mafin cells
& neuron.
Metabolism-
5-HIAA, major
metabolite of
serotonin -
excreted in
urine serve as
indicator
Mechanism of action
● Receptor mediated.
Physiological and pharmacological effects
1. On cardiovascular system
● Arterioles are constricted by its action on the smooth
muscles.
● In rapid intravenous injection - a triphasic curve in
blood pressure
early sharp fall - stimulation of coronary
chemoreceptor
an brief rise - vasoconstriction
prolonged fall - arteriolar dilation and extravasation of
fluid.
Physiological and pharmacological effects
2.On smooth muscles-
● stimulates the gastrointestinal tract ,increases the peristalsis
● o Bronchial smooth muscles are also constricted,
3.On glands-
● inhibits gastric secretion and increases mucous production.
● ulcer protective effect.
4.On platelets-
● change in the shape of platelets and is a weak aggregator.
5.On central nervous system- NT & neuromodulator
Exogenous administration- effects are not much pronounced.
Pathophysiological role
● Neurotransmitter-
● Inflammation and allergy
● Gastrointestinal function- regulation of peristalsis
● Nausea and vomiting- mainly through 5HT3 receptors
● Haemostasis- platelet aggregation and
vasoconstriction.
● Carcinoid syndrome- tumour of enterochromaffin
cells.
Serotonin receptor agonists-
1.Non selective serotonin receptor agonists-
● Metoclopramide
● D-lysergic acid- diethylamide(LSD)
● Psilocin
2. selective serotonin receptor agonists-
● Azapirones
● Triptans
● Benzamides
● Norfenfluramine
● Lorcaserin
Serotonin receptor antagonists-
1.Non selective serotonin receptor antagonists-
● Ergot alkaloids-ergotamine
● Atypical antipsychotics- clozapine, olanzapine,
risperidone
● Phenothiazines
● Beta adrenoceptor blocker- alprenolol, pindolol,
cyanopindolol,iodocyanopindilol, oxprenolol
● Cyproheptadine
● Yohimbine
● ketanserin
Serotonin receptor antagonists-
2. selective serotonin receptor agonists-
● Ritanserin
● Agomelatine
● Lecozotan
● piboserod
