Opoid Analgesics and

Antagonists

By.
Dr. Shahid Ali
Kill the pain
before it kill
your patient
Introduction

 For mild to moderate pain i.e headache or arthritic pain

NSAIDS can be use

 Neurogenic pain best respond to tricyclic anti-depressants i.e
AMITRYPTYLINE or serotonin norepinephrine reuptake
inhibitors i.e DULOXETINE
Cont…
 Severe and malignant pain can be managed best by

OPOIDS
 Opoids obtaine from juice of opium poppy

 Use in severe chronic malignant pain

Site of action of opoids

 They act on specific receptors that lie in CNS

OPOID RECEPTORS .
• Mu
• Kappa
• Delta
 These receptors are g-protein mediated

 Inhibit adenylyl cyclase

Mode of action
 Produce response by 2 mechanisms

 1. They cause hyperpolarization by k+ efflux

 2. reducing ca++ influx reduce neuronal impulse generation

Distribution of receptors
1. Brainstem . Receptors mediate cough, respiration,
nausea and vomiting

2. Medial thalamus. Receptors for perceiving deep

pain

3. Spinal cord. Receptors lie in substantia gelitinosa

integrate sensory information
Cont…
 Hypothalamus. Receptors effect neuroendocrine
secretion

 Limbic system. Receptors lie in amygdala do not

perceive pain stimuli but influence emotional behaviour

 Peripheral action . Opoids also inhibit pain

generating impulses by inhibiting ca++ influx
Classification
 Strong agonists
• Morphine
• Alfentanyl
• Fentanyl
• Heroin
• Sufentanil
• mepridine
Cont…
 Moderate agonsts.
• Codiene

• Antagonists
 Naloxone
 Naltrexone
Cont…
 Mixed agonists antagonist and partial
agonists
• Buprenorphine
• Butorphanol
• Nalbuphine
• Pentazocin
Morphine
 Have great affinity for mu receptors

 Less activity for delta and kappa receptors

 Have greatest analgesic activity

Mode of action
 Act in CNS

 Cause hyperpolarization of of nerve cells

 Act on lamina 1 and 2 of substantia gelatinosa of spinal cord

and dec release of substance P
ACTIONS
 Analgesia . Dec pain perception in brain and increases
threshold of pain in spinal cord
If patient is free of pain it can cause unpleasent effect i.e nausea
and vomiting

 Eye {Miosis} . cause pinpoint pupil by exciting

edinger-westphal nucleus of occulomotor nerve

 Respiration. Causes respiratory depression

Cont…
 Euphoria . By stimulation of ventral tegmentum

 Cough reflex. Dec cough act as anti-tussive drug

 Emesis . Directly stimulates chemoreceptor trigger zone

in area prostrema cause vomiting

 Cvs can cause bradycardia and hypotension

Cont….
 G.I.T . relieves diarrhea and dysentry so produce constipation

 HISTAMINE RELEASE . Can cause bronchoconstriction

and vasodilatation

 It can effect conc of many hormone dec urinary voiding reflex so

catheterization may require

 Inc antidiuretic hormone can lead to urinary retention

Clinical uses
 Analgesia

 Diarrhea

 Relief of cough

 Acute pulmonary edema

pharmacokinetics
 Oral absorption is less due to first pass effect

 Mostly used as I.V I.M OR SUBCUTANEOUS

 Distribute well to all body tissues INCLUDING FEATUS

 Dependence is more common with use of morphine

 Conjugation occur in liver excretion through urine mostly and

small amount in bile
Cont…
 Duration of action is 4 to 6 hours

 Neonates and pregnancy are contraindications

Adverse effects
 Respiratory depression common cause of death in acute
morphine poisining

 Vomiting, hypotensive effects allergic

 Contraindicated in head injury due to dilatation of cerebral

vessels
Tolerance and physical dependence
 Repeated use may cause tolerance to analgesic , respiratory
depressant and euphoric effect

 Drug interactions. Phenothiazines and MAO INHIBITORS

may increase depressant action of morphine
Methadone
 Synthetic compound equally effective as morphine but t1/2 is
longer
 Well absorb orally , metabolized in liver excretes in urine
 Action mediated by µ receptor less euphoric effect
 Clinical uses
 Analgesic
 Withdrawal of morphine and heroin
 Anti-diarrheal

Can cause miosis and respiratory depression action persist for 24 hrs
Fentanyl, Sufentanyl,
Remifentanyl,Sufentanyl
 Fentanyl is 100 times potent then morphine
 Used in obstretics for analgesia during anesthesia
 Due to short duration of action transdermal patch
can be used in cancerous patients

 SUFENTANYL IS MORE POTENT THEN ALL MEMBERS

- FENTANYL duration of action 15 to 30 mins.
MEPRIDINE
 Synthetic compound , different action as compare to
morphine
 Dilates pupils
 No action on CVS when used orally , I/V mepridine can
cause peripheral dilatation and inc cardiac rate
 Clinical uses
• analgesic effect in obstretics
Pharmacokinetics: well absorb orally metabolized to
normepridine in liver excretes in urine
 Tremors muscle twitching and convulsions

 Anxiety

 Hypotension

 Dry mouth and blurred vision

 Mepridine MAO INHIBITORS

HEROIN
 Common drug of abuse

 Deacetylated product of morphine

 More euphoric effect due to lipid solubility

 No clinical use

 Anti-dote is naltrexone ( orally) for withdrawal

 Naltrexone is hepatotoxic it can be used for opoid detoxification in
combination with clonidine and buprenorphine

PENTAZOCIN ,NALBUPHINE, BUPRENORPHINE
BUTORPHANOL (mixed drugs)
 Pentazocin act as antagonist at Ðand µreceptor agonist at kappa
receptor
 Can be used orally or parenterally for analgesia , less euphoric
effect respiratory depression,
 Inc work load on heart specially for angina patients
 Inc B.P, hallucinations nightmares, tachycardia dizziness are
adverse effects

 Nalbuphine and butorphenol not available in oral use less side

effects and no effect on heart as compare to pentazocin
Dependence and tolerance is common with
pentazocin
 Buprenorphine can be use in opoid detoxification due to its
partial agonist action
 Long duration of action less sedation and respiratory
depression , used as sublingually or parenterally
 Metabolize in liver excretion through bile and urine

 Respiratory depression , nausea and dizziness are adverse

effects
Codiene, propoxyphene, oxycodone
 Weak opoids commonly used as anti-tussive
 All effects are less
 Weak analgesic activity
 Propoxyphene is less potent then codeine
 Well absorb orally

 Hallucination ,confusion and cardiorespiratory depression are

serious adverse effects when used with alcohol.(propoxyphne
 Anti-dot for propoxyphene is naloxone
THANKYOU