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CONTENTS
Introduction to opioid Autocoids.
Classification of Opioids.
Physiological and pathological role of opioid autocoids.
Uses of Opioids.
Adverse effects of opioids.
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INTRODUCTION:
Autacoid : Auta - self , Coid - Healing
Autacoid is self healing substances.
Autacoids also known as local harmones , and mostly originated from
diffused tissues and transported to various target sites.
Autacoids play an important role in physiological and pathological process
and act as neurotransmitters and neuromodulators.
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OPIOIDS
Opioid is a psychoactive chemical that works by binding to opioid receptors
which are found principally in the CNS , PNS and GIT.
The receptors in these organ system mediate both the benificial and side
effects of opiods.
Opioid drug function as agonist , partial agonist , antagonist.
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The physiological and pathological role of opioid autocoids:
Opioids divide into two types- endogenous and exogenous. Some endogenous
opioids that bind to the receptors are enkephalins, endorphins, endomorphins,
dynorphins, and nociception/orphanin.
Exogenous opioids like morphine, heroin, and fentanyl are substances that are
introduced into the body and bind to the same receptors as the endogenous opioids.
Five types of opioid receptors have been discovered-mu receptor (MOR), kappa
receptor (KOR), delta receptor (DOR), nociception receptor (NOR) and zeta receptor
(ZOR).
Within these different types are a subset of subtypes, mu1, mu2, mu3, kappa1,
kappa2, kappa3, delta1, and delta2.
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Mu1,2,3 receptors (MOR) bind to endogenous ligands - beta-endorphin,
Endo morphin 1 and 2 .
The mu-1 receptor is responsible for analgesia and dependence. The mu-2 receptor is
vital for euphoria, dependence, respiratory depression, miosis, decreased digestive
tract motility/constipation.
Mu-3 receptor causes vasodilation.
Kappa receptors (KOR) bind to dynorphin A and B. They provide analgesia, diuresis,
and dysphoria.
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Delta receptors (DOR) bind to enkephalins (precursor being Pro enkephalin).
They play a role in analgesia and reduction in gastric motility.
Nociceptin receptors (NOR) bind to nociceptin/orphanin causing analgesia
and hyperalgesia (depending on the concentration).
Zeta receptors (ZOR) regulate developmental events in a variety of normal
and tumorigenic tissues and cells.
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Physiological actions of opioid autocoids:
a. Analgesia- Endogenous and exogenous opioid autacoids cause analgesia.
b. MOR play a central role in reducing the stress response through inhibition
of secretion of norepinephrine.
c. Mood and reward- Presence of high density of MOR in the limbic system
(emotional center) regulates mood and rendering these receptors potential
targets to treat mood disorders like anxiety and depression. MOR stimulation,
through its inhibition of GABA secretion, results in the release of dopamine.
Dopamine is responsible for the rewarding effects produced by opioid
Administration.
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Pathological actions of opioid autocoids:
a. Respiratory Depression- Opioid receptors are abundant in the respiratory
center. Stimulation of these receptors leads to irregular and slow breathing.
b. Constipation- Opioid receptor activation by agonists causes slowing of
propulsive motility of the gut mediated through inhibition of acetylcholine.
c. Orthostatic Hypotension and Syncope- Opioid receptors are present in
cardiac tissue; their activation leads to hyperpolarization of membranes and
activation of the vagus nerve.
These changes result in peripheral vasodilation and bradycardia, which
ultimately causes hypotension.
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d. Endocrine Abnormalities- Stimulation of opioid receptors located in the
hypothalamus inhibits GnRH release, which results in reduced estrogen and
testosterone secretion.
• Hence, chronic activation of these receptors leads to osteoporosis and sexual
dysfunction, presenting as decreased libido, infertility, and increased bone
fragility.
e. Immune Dysfunction- Opioid receptors are present on immune cells, namely
natural killer (NK) cells, and phagocytes, and their stimulation leads to repression
of their activity resulting in blunting of the immune response and delayed wound
healing.
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f. Sleep Changes- Activation of opioid receptors in the reticular formation alters
normal sleep pattern.
• Opioid agonists through stimulation of these receptors increase the duration
of light sleep, consequently decreasing deep and REM sleep duration.
g. Mood Changes- Chronic stimulation of MOR in the neurons of hippocampal
region leading to mood dysregulation.
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ORGAN SYSTEM EFFECTS:
Analgesia: Pain consists of both sensory and emotional components. Opioids
reduce both aspects of the pain.
Euphorbia: Pleasant floating sensation with lessened anxiety and distress.
Dysphoria: An unpleasant state characterized by restlessness and malaise,
may sometimes occur.
Sedation: Drowsiness and clouding of mentation are frequent concomitants
of opioid action. Combination of Morphine with other deep sleep.
Cough suppression
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Respiratory depression:
It is dose related.
Mepedridine produces less respiratory depression, in newborn infants.
Miosis:
No tolerance develops for miosis
It is valuable in the diagnosis of opiod overdose.
Gastrointestinal tract:
Constipation
Biliary tract and renal:
Constriction of biliary smooth muscle, results in biliary colic.
Increased sphincher tone may ppt urinary retention.
