Autacoids_Public Health.pdf from Technical university

It explains about autacoids in pharmacology

1. Biogenic Amines( Autacoids)

2. INTRODUCTION
Autacoids are chemical mediators that are synthesized and function in a localized tissue or
area and participate in physiological responses to injury.
They act only locally and therefore also termed “local hormone.”
They do not function as the classical blood-borne hormones.
They are short-lived and rapidly degraded.
Autacoids modulateBlood flow in specific tissues
Secretory processes, for example, histamine on gastric acid formation.
Smooth muscle function.
They play a key role in allergy, inflammation, smooth muscle function, pain, and certain
types of drug reactions (Anaphylaxis).
Biogenic amines: Histamine, serotonin (5-hydroxytryptamine)
Lipid-derived autacoids Prostaglandins

3. A. BIOGENIC AMINES
A. Histamine. Histamine is widely distributed in tissues and its
concentration and rate of synthesis varies greatly from tissue to
tissue.
The primary tissue sites storing histamine are the lungs, skin,
mucosal layer of the stomach and basophils.
Allergic responses in the skin and lungs are due in part to histamine
release from mast cells.
Histamine is also found in CNS where it may act as a
neurotransmitter.
Many venoms and insect stings contain histamine, as well as other
biologically active substances.
Histamine normally does not reach the systemic circulation since it is
metabolized by enzymes in the gut wall and liver.

4. When they are released ?
a. Immune release.When sensitized mast cells or basophils are
exposed to the proper antigen release histamine.
b. Drug-induced release. Drugs, usually strong bases (morphine,
polymyxin, codeine, lidocaine, penicillin), and/or their vehicles
are capable of releasing histamine.
c. Plant and animal stingsare capable of releasing histamine,
which is an important component of the physiologic reaction
(erythema, pain, and itch) to these stings.
d. Physical injury such as heat, cold, or trauma can disrupt the
mast cells thereby releasing histamine

5. Histamine Receptors
 Four classes of receptors (H1, H 2, H 3, and H4) mediate the action of
histamine.
 a. H1-receptors mediate the following effects:
(1) Contraction of smooth muscle
(2) Relaxation of vascular smooth muscle (those lining the blood vessels)
(3) H1-receptors mediate contraction of bronchiolar and intestinal smooth
muscle, vasodilation of small arteries and veins, increased capillary
permeability and pruritus.
 H2-receptor primarily mediates gastric acid secretion and
vasodilatation. (1) Agonists include 4-methylhistamine and dimaprit. (2) H2-
Antihistamines include: cimetidine, ranitidine, famotidine, and nizatidine.

6. Physiological roles
Gastric acid secretion. Histamine is the most important regulator of
gastric acid secretion and it stimulates secretion via H2 receptors
Allergic reactions and anaphylactic shock.The binding of antigenic
substances to IgEmolecules on mast cells causes the release of
histamine.
Inflammation. Histamine may be involved in the vasodilation observed
in the inflammatory process.
Neurotransmission. Histamine is a neurotransmitter in various brain
areas and is involved in activating sensory nerves resulting in pain and
itch sensations
Microcirculation. Histamine relaxes arterioles and increases capillary
permeability

7. a. Cardiovascular system
Histamine dilates arterioles, capillaries, and venulescausing decrease
in peripheral resistance (vasodilatation), resulting in hypotension.
There is stimulation of cardiac activity involving a direct action and
reflex activation of the sympathetic nervous system, which is
activated by the low blood pressure.(homeostasis)
There is an increase in capillary permeability and so fluid and protein
pass across the basement membrane to produce edema.
b. Respiratory system.
Respiratory smooth muscle is contracted in most species via H1-receptors
There is also stimulation of glandular secretion and prostaglandin
formation. Asthmatics are generally more sensitive to histamine than
normal animals.

8. Glandular tissue.
Histamine can stimulate glandular tissues to increase secretion.
Histamines increase gastric acid and pepsin secretion from the gastric mucosa via H2-receptors.
Insect and plant stings mimic many of these responses.
(1)A reddening at the site of injection is due to dilation of the small arterioles.
(2)Dilation of arterioles extends beyond injection site.
(3)Swelling occurs at the injection site due to increased capillary permeability, which is
due to H1-receptor-mediated contraction of endothelial cells.
(4)The intradermal injection of histamine causes pain and itching by stimulation of H1-
receptors on sensory nerve endings.

9. Therapeutic uses of histamine agonists
Histamine phosphate can be used for diagnostic purposes for testing of gastric
acid secretion.
b. Betazoleis an analogof histamine, which is an H2-receptor agonist.
Betazolestimulates gastric acid production.

10. B. ANTIHISTAMINES.
Therapeutically useful antihistamine drugs are H1-antihistamines and H2-antihistamines. 1.
H1-antihistamines were the first type of antihistaminic drugs discovered and are sometimes
referred to as the classical antihistaminics.
a. Mechanism of action.
H1-antihistamines act as antagonists to the histamines.
b.Classification of H1-antihistamines. AntiHistaminecan be broadly classified into two
groups based on usage:
(1) first-generation H1-antihistamines and
(2) Second generation H1-antihistamines.
Most frequently used first-generation H1-antihistamines are diphenhydramine,
chlorpheniramine, meclizine, promethazine, and cyproheptadine. These drugs are unionized
drugs at physiological pH and easily cross the blood–brain barrier (BBB). Therefore, they
produce CNS side effects, in particular, sedation.
Commonly used second-generation drugs are loratadine(Claritin), cetirizine (ZyrtecR), and
fexofenadine (Allegra R).
This class of drugs is ionized at physiological pH and is difficult to cross BBB and therefore
does not form sedation side effects

11. c. Pharmacologic effects of H1-antihistamines
(1) Relaxation of contracted bronchiolar smooth muscle.
(2) Relaxation of contracted intestinal smooth muscle.
(3) Inhibition of histamine-induced vasodilation and increased capillary permeability and
thereby blocking formation of edema.
(4) Inhibition of itch sensation by prevention of stimulation of sensory nerves.
Other pharmacologic effects of H1-antihistamines.
(1) Sedation is a common effect of first-generation H1-antihistamines
(2) Antimuscariniceffects are prominent for some H1-antihistamines, for example,
diphenhydramine and promethazine, which decrease secretions and relax smooth muscles.
(3) Antimotionsickness (antiemetic) effects. All H1-antihistamine have this effect

12. Therapeutic uses.
H1-antihistamines are administered orally, parenterally, or topically for
the following conditions.
(1) Treatment of patients with allergic conditions and to reduce the
effects due to histamine. Conditions benefited from H1-antihistamines
include: (a) pruritus (b) Allergic reactions to drugs (c) Anaphylaxis
(2) Prevention of motion sickness. Diphenhydramine, dimenhydrinate, and
meclizine are more effective in preventing motion sickness than other H1-
antihistamines.
(3) Sedation induction. Promethazine and diphenhydramine are the most
potent for inducing sedation.

13. Pharmacokinetics
All H1-antihistamines are effectively absorbed following oral
administration
The first-generation antihistamines are excreted primarily by the kidneys
as metabolites.
The second-generation antihistamines that cause least or no sedation are
excreted more into faeces when compared with the first-generation
drugs.
Adverse effects
(1) CNS depression (lethargy) are the most common but they may
diminish with time. The performance of working individuals may be
adversely affected.
(2) Antimuscariniceffects (dry mouth, urinary retention) occur with many
H1antihistamines.

14. H2-ANTIHISTAMINES
H2-ANTIHISTAMINEScontain imidazole ring with uncharged side chains and are
smaller than H1-antihistamines.
b. Pharmacologic effects. H 2-antihistamines competitively inhibits histamine
(H2-receptors) in parietal cell and thereby decreases gastric acid production.
c. Therapeutic uses.
H 2-antihistamines are administered orally to treat gastric and duodenal ulcers,
drug-induced erosive gastritis. Cimetidine is least potent among the four H2-
antihistamines.
d. Pharmacokinetics
All the drugs are well absorbed when administered orally.
All the drugs are well distributed in the body, with 10–20% bound by plasma
proteins. (3) Cimetidine, ranitidine, and famotidine are metabolized by
cytochrome P450 enzymes. Only <10% of nizatidineis metabolized by CYP450
enzymes.
(4) All the drugs are excreted by the kidneys as the primary route.

15. B. LIPID-DERIVED AUTACOIDS
PROSTAGLANDINS (PGS)
They are not stored but are synthesized in response to appropriate stimuli and enter the
extracellular space.
The PGs are short-lived molecules and exert their actions in the region where they are
synthesized.
Actions of prostaglandins PGE 2 and PGF2 alpha
Smooth muscle (a) Blood vessels. PGE2 relax arteriolar smooth muscle and promote
vasodilatation. PGF2α are vasoconstrictors (b) Gut. PGE2 and PGF2α contract longitudinal
muscle, (c) Bronchioles. PGE1, PGE2, and PGI2 relax respiratory smooth muscle.
d) Reproductive system (a) Female. PGF2α is the luteolytichormone produced by the ovaries
and endometrium, which causes ovulation and regression of corpus luteum(luteolysis).
In the prepartumperiod, PGF2α initiates luteolysis, which decrease plasma progesterone levels.
PGF2α is a stimulant of myometrium and is involved in parturition.
PGF2α-induced luteolysisand myometrialcontractions are use therapeutically to control
reproduction.

16. Therapeutic uses
Only PGE and PGF2α analogsare used therapeutically in animal health.
(1) Misoprostol
It is a PGE1 analogthat has two functions which make it a useful protective agent for the GI tract. It
directly inhibits gastric acid secretion by parietal cells and it facilitates PGE-mediated mucosal
defences and healing in response to GI injuries.
It is therefore used to treat gastric ulceration when caused by NSAIDs.
(2) Dinoprostand cloprostenol.Dinoprostis the drug name for PGF2α and cloprostenolis a synthetic
PGF2α analog.
They are used to induce luteolysisfor the control of estrouscycle, to terminate pregnancy, and to
induce parturition.
(3) Precautions to the use of PGF2α drugs:
(a) People with respiratory or GI disorders may be compromised by the bronchoconstriction and
stimulation of the GI motility by the PGF2α compounds. Older individuals may exhibit exacerbated
vasoconstriction associated complications.
(b) Women of child-bearing age or who are pregnant, persons with asthma, or respiratory disease
should use extreme caution in handling these drugs as they are readily absorbed via the skin. If contact
with the skin is made, the skin must be washed immediately with soap and water.