Autacoids and their

antagonists
Presented by
Mr. C.D.Deshmukh,
M.Pharm, MBA
Lecturer,
Maharashtra institute of Pharmacy,
Pune
Contents
Autocoids
Histamine Synthesis, Release, Storage, Role
Effect on various systems
Side effect and toxicity
Pharmacokinetic
Antihistaminics
First generation antihistaminics and pharmacology
Second generation antihistaminics and pharmacology
References
Autacoids
Derived from /Greek autos-self, akos-healing substance or remedy.
These are diverse substances produced by wide variety of cells, having
intense biological activity but generally act locally at the site of synthesis
and release
They are called local hormones but differ from hormones in that
hormones secreted by endocrine glands and transported via blood.
nvolved in no of physiological and pathological processes and serve as
transmitters /modulators in nervous system
1) Amines autacoids- Histamine, 5-hydroxytryptamine
2) Lipid derived autacoids- PG, LT and platelet activating factor
3) Peptide autacoids: Plasma kinins, Angiotensin
Histamine
Histamine was introduced by Dale in 20
th
century
t is tissue amine and present in animal tissues and plants.
istamine is an organic nitrogen compound involved in local immune
responses as well as regulating physiological function in the gut and acting
as a neurotransmitter
Stored in granules of mast cells and basophiles
Skin, gastric and intestinal mucosa, lungs, liver and placenta contain
histamine.
Also present in blood, most body secretions, venoms and fluids.
mplicated as mediated of hypersensitivity reactions and tissue injuries.
Synthesis, Storage and destruction
t is beta imidazolylethyl amine
Synthesized locally from amino acid histidine
Degraded rapidly by oxidation and methylation
n mast cells histamine present with protein and heparin
Histamine is not effective orally as liver degrades all histamine that is
absorbed by intestine.
Histamine receptors
Receptors Functions Antagonist
leum contraction
Modulate circadian cycle
Systemic vasodilatation
Bronchoconstriction (asthma)
H1-receptor antagonists
Diphenhydramine
Loratadine
cetrizine
Maintain sinus rhythm
Secrete gastric acid
Smooth muscle relaxation, antibody
production
H2 receptor antagonist
Cimetidine, ranitidine
Neurotransmitters in CNS H3 receptor antagonist
Ciproxifan
Clobenpropit
Thioperamide
Mediate mast cell chemotaxis Thioperamide
Pharmacology
. BIood vesseI
All blood vessels dilated e.g arterioles, capillaries and venules
Larger arteries and veins are constricted by H1 receptor action.
On s.c. increase in HR and CO, fall in BP produced. v fall in BP
. eart
Direct effect of histamine on heart is not seen but isolated heart is
stimulated
Rate and force of contraction is increased due to H2 action.
. Smooth muscIe
Causes bronchoconstriction, so not given in asthma
Guinea pig uterus is contracted but rats relaxed due to H1 action
4, Iand
Histamine causes marked increased in gastric secretion, acid and pepsin
ncreases other secretions also
. Sensory nerve ending
tching occurs when histamine injected iv, higher doses cause pain
6. AdrenaI meduIIa
Release of adr occurs causing rise in BP
7. CNS
Histamine does not penetrate BBB so no effects
Role in the body
. SIeep reguIation
Histaminergic action is known to modulate sleep. Classically,
antihistamines (H1 histamine receptor antagonists) produce sleep.
. astric acid secretion
Histamine has role in gastric acid secretion by activating proton pump.
. As transmitter
t initiates sensation of itch and pain at sensory nerve ending.
nvolved in maintaining wakefulness,
Regulates body temp,
Cardiovascualr functions,
Thirst,
Hormone release
Suppress appetite.
nfIammation
Mediator of vasodilatation and other changes that occur during
inflammation
t promotes adhesion of leucocyte at inflammatory site
. Suppressive effect:
Convulsion, drug sensitization, denervation supersensitivity, ischemic
lesions and stress.
6. Tissue growth and repair
7. eadache.
8. AIIergic phenomena-
Causative in urticaria, angioedema, bronchoconstriction, and shock.
H
1
Antihistaminics (Histamine antagonist)
These drugs competitively antagonize action of histamine at H1 receptors
H1 antihistamines are used as treatment for symptoms of allergies such as
runny nose
Other uses of H1 antihistamines help with symptoms of local inflammation
that results from various conditions, such as insect stings, even if there is no
allergic reaction.
Other commonly used examples of antihistamines include the H
2
antagonists (Cimetidine) which are widely used for the treatment of acid
reflux and stomach ulcers as they decrease gastric acid production.
Drugs, Dose and Preparations
. ighIy sedative
Diphenhydramine 25-50 mg oral Benadryl
Dimenhydrinate 25-50 mg oral Dramamine
Promethazine 25-50 mg oral Phenergan
Hydroxyzine 25-50 mg oral Atarax
. ModerateIy sedative
Pheniramine 25-50 mg oral Avil
Cyproheptadine 4 mg oral Practin, ciplactin
Meclizine 25-50 mg oral Diligan
Buclizine 25-50 mg oral Longifene
. MiId sedative
Chlorpheniramine 2-4 mg (0.1 mg/kg) Piriton, Cadistin
Dexchlorpheniramine 2 Mg oral Palaramine
Dimethindene 1 Mg oral Foristal
Triprolodine 2.5 Mg oral Astidil
Cyclizine 50 mg oral Marezine
Clemastine 1-2 mg oral Tavegil
. Second generation
Fexofenadin 120-180 mg Allergra, Altiva
Loratadine 10 mg oral Lorfast
Ceirizine 10 mg oral Deslor
Levoceterizine 5-10 mg oral Levisiz
Pharmacological Actions
. Antagonism of histamine
Block histamine induced bronchoconstriction of intestinal and other
smooth muscle
Fall in BP produced by histamine is blocked
Pretreatment with these drugs protects animal from death caused by iv
inj of large doses of histamine
Constriction of large blood vessels is also antagonized.
. AntiaIIergic action
Hypersensitivity is suppressed
Urticaria, itching, angioedema are well controlled.
Fall in BP prevented.
CNS
Older antihistamines produce variable degree of CNS depression by
penetrating BBB
Restlessness or insomnia is produced.
Effective in preventing motion sickness.
AntichoIinergic action
Many H1 blockers in addition antagonize muscarinic actions of Ach.
LocaI Anesthetic
Some drugs like pheniramine, have strong while others have weak
membrane stabilizing property.
6 BP
Most antihistaminics cause fall in BP on iv inj
Pharmacokinetics
Well absorbed orally and parenterally
Metabolized in liver and excreted in urine
Distributed in body and enter brain
Newer compounds penetrate brain poorly
Duration of action 4-6 hours, except Meclizine
Side effect and toxicity
irst generation antihistaminics
Tolerance
Sedation
Diminished alertness and
concentration,
Light headedness
Motor incoordination
Fatigue and tendancy to fall
asleep
Second generation antihistaminics
Dryness of mouth
Alteration of bowel movement
Urinary hesitancy and blurring of
vision
Overdose
Central excitation,
Tremors
Hallucinations
Muscular coordination
Convulsion
Flushing
Hypotension
Death due to cardiovascular and
respiratory failure.
Second generation
Advantages
No anticholinergic side effect
No CNS depression
Not imprai psychomotor function
No sleepiness
Not penetrate alcohol
Drugs
Fexofenadine
Loratadine
Cetirizine
Levocetirizine
mizolastine
ndications
Allergic rhinitis and conjunctivitis,
hay fever, pollinosis
Control sneezing, runny and
blocked nose and red watering
itchy eyes
Urticaria, atopic aczema
Acute allergic reactions.
Uses
Allergic
Common cold, motion sickness
Vertigo
antipruritic
References
Essentials of medical pharmacology by Tripathi, 6
th
edition, Page 150-161
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