OPIOID ANALGESICS AND
ANTAGONISTS
Department of Pharmacology
Medical School Padjadjaran University
OPIOIDS are natural or synthetic compounds
produce morphine like effects
Opiates are drugs obtained from the juice of opium
poppy
Action : Binding to specific receptors in the CNS
effect that mimic the action of endogenous pepetide
neurotransmitters (= opiopeptines) e.g. enkephalins
and endorphin
Many other effects
Primary use Relief intense pain and its anxiety
Euphoric properties DRUG ABUSE
OPIOID RESEPTORS
1. On the membranes of certain cells in the CNS
2. On nerve terminals in the periphery
3. On the cells of the GIT
The terms of the receptors :
Mu, kappa, delta and sigma each exhibits a
different specificity
Mu and kappa analgesics properties
Enkephalins more selectively interact with
delta receptors in the periphery
Sigma receptors less specific can also bind
non opioid agents (hallucinogen)
Sigma is responsible for the
associated effects with opioids e.i
hallucination and dysphoria
Naloxone is an antagonist to mu, kappa,
delata but not to sigma
All opioid receptors :
1. Coupled to inhibitory G protein
2. Inhibit adenyl cyclase
3. Associated with ion channels to
increase K+ efflux hyperpolarization
or reduce Ca++ influx impeding
Opioid agonists and antagonists are :
1. STRONG AGONISTS : morphine, meperidine,
methadone, fentanyl-sufentanil,heroin
2. MODERATE AGONISTS : propoxyphen,
codeine
3. MIXED AGONISTS-ANTAGONISTS :
pentazocine, buprenorphine
4. ANTAGONISTS : naloxone, naltrexone
Actions of agonists and antagonists at opioid
receptors
Mor, Her, Cod, Fent
Pentazocine
Mainly at mu recept.
Agonist at kappa
Partial antagonist at mu
+
Mu
Kappa
Sigma
Antagonists act at mu, kappa, sigma receptors
Action of drugs :
At Mu receptors : 1. Suprapinal analgesia
2. Respiratory depression
3. Euphoria / sedation
4. Physical dependence
5. Decreased GIT motility
6. Pupil constriction
Kappa receptors :
1. Spinal analgesia
2. Sedation/dysphoria
3. Pupil constriction
Sigma receptors :
1. Dysphoria
2. Hallucination
3. Psychomimetic effects
4. Pupil dilatation
Distribution of opioid receptors :
1. Brainstem : Resp., cough, nausea, vomit, BP, pupil,
stomach secretions
2. Medial thalamus : deep pain that is poorly localized
and emotionnaly influenced
3. Spinal cord on substantia gelatinosa : sensory
information, painful afferent stimuli decrease
4. Hypothalamus : affect neuroendocrine secretion
Distribution of opioid receptors (cont.)
5. Limbic system :concentrate in amygdala,
influence emotional behaviour
6. Periphery : inhibit Ca++ dependent release of
excitatory pro inflammatory substance (e.g
Substance P) from these nerve endings
7. Immuno cells : the role has not been determined
Morphine
Crude opium contains major analgesic morphine
and lower concentration of codein
Both have high affinity to Mu, varying to Kappa
and Delta and low to Sigma receptors
The prototype agonist
Mechanism of action :
Interacting with opioid receptors in CNS and GIT :
Hyper polarization of nerve cells
Inhibition of nerve firing
Presynaptic inhibition of Transmitter release
Acts at Mu receptor in substantia gelatinosa
Spinal Cord
Mechanism of action (cont.)
Inhibits the release of any excitatory trnsmitters
from nerve terminals carrying nociceptive
(painful) stimuli
ACTION of morphine
1. Analgesia result of raising threshold at SC
level and altering the brains perception of
pain (aware the presence of pain but the
sensation is not unpleasant
2. Respiration : reduction of sensitivity of neurons in
Resp. center to CO2 respiratory depression (with
ordinary dose). Higher dose cause respiratory cease, if
dose more higher (OD) death.
3. Depression of cough reflex. Morphine and codeine
are antitussive. The receptor is defferent than those
involved in analgesia.
4. Miosis result from stimuli of Mu and Kappa
receptors. Morphine excites the Edinger-Westfal of
acculomotor nerve enhanced stimuli of
parasympathic nerve to the eyes.
All addicts pinpoint pupil
specific
Emesis caused by stimulating the CTZ ; this
symptom is not unpleasant
GIT : mophine relief diarrhea and dysentery
smoot muscle : motility
, tone
Billiary tract Pressure
Anal sphincter tone
constipation
Cardiovascular, very high dose gives effects
hypotension, bradycardia
Respiratory depression + CO2 retention
cerebral vessels dilates pressure of CSF
Morphine is contraindicated in severe brain injury
Histamine release : urticaria, sweating,
vasodilatation, bronchodilatation (Asthmatics is
CI)
Hormonal actions :
Inhibits releas of GTHR, CTRH
Decreases the concentration of LH, FSH,
ACTH, FSH, beta endorphine
Decreases Testosteron and Cortison
Increases Prolactin and GH
Increase ADH urinary retention
THERAPEUTIC USES
As an analgesia. When pain is present and needed
sleep, morphine is supplements to benzodiazepin
to induce sleeping.
Antidiarrhea
