Opioid Drugs

OPIOID DRUGS


OPIOID DRUGS

  • Substances obtained from crude extracts of Papaver somniferum (poppy plant).

Main clinical uses:

  • Used as analgesic agents – 
    • Relieves visceral, dull & constant pain, more effectively than inflammatory pain.

Opioid receptors:

  • Three receptors – 
    • µ, κ and δ receptors.
  • µ receptor – 
    • Opioids produce dependence, mainly euphoric action.           
  • κ receptors – 
    • Mediates psychomimetic effects, mainly dysphoria action.

Actions of receptors: 

µ receptors

κ receptors

δ receptors

Sedation

Dysphoria (Psychomimetic effects)

Spinal analgesia

Analgesia

Constipation

Modulation of hormone

Euphoria

Analgesia

NT release

Miosis

 

 

Truncal rigidity

 

 

Respiratory depression

 

 


Opioid drugs:

Pure opioids

Mixed agonist-antagonist drugs Opioid antagonists
Morphine –

  • Prototype opioid;
  • Acts as agonistic activity on µ, κ and δ receptors
 

Buprenorphine

Naloxone

 

Methadone Butorphanol Naltrexone
Pethidine Nalbuphine Nalmefene
Codeine Pentazocine Methylnaltrexone
Heroin Dezocine Alvimopan
Oxycodone Tramadol (Partial agonist) Naloxegol
Hydrocodone    
Other important drugs:

Propoxyphene, 

Hydromorphone, 

Oxymorphone, 

Levorphanol, 

Meperidine

   

Endogenous peptides:

  • Endorphins, dynorphins, enkephalins & Nociceptin.
  • Acts on opioid receptors producing analgesic effects.
  • Endorphins act on µ receptor; Dynorphins acts on κ receptor; Enkephalins acts on δ receptors.
  • Nociceptin – Acts on nociceptin/orphanin FQ (N/OFQ) or orphanin-like-receptors  (ORL).

Route of administration:

  • Morphine – Administered by oral, rectal, i.v., i.m., intrathecal or epidural routes.
  • Fentanyl – Applied as transdermal patch; also administered by buccal transmucosal route.
  • Butorphanol – Only opioid available in nasal formulation.

1. PURE OPIOIDS:

  • Drugs included:
    • Morphine, methadone, pethidine, levorphanol, codeine, hydrocodone, oxycodone, propoxyphene & Heroin (diacetylmorphine).
    • Highly lipid soluble drugs – Fentanyl, alfentanyl & sufentanil.
    • Strong opioid agonists – Morphine, hydromorphone & oxymorphone.
    • Heroin (diacetylmorphine) – Potent & fast acting opioid; with high risk of abuse potential.

Actions of opioid:

CNS actions:

  • Morphine: 
    • Acts on µ, κ and δ receptors.
    • Produce marked sedation.
    • Spinal & supraspinal analgesia. 
    • Produce respiratory depression, cough suppression & miosis.
    • Main feature for opioid poisoning diagnosis – Pinpoint pupil.
  • Pethidine & Fentanyl – 
    • Produces less sedation.
  • Highly lipid soluble drugs (fentanyl, alfentanil & sufentanil) – 
    • Causes truncal rigidity on rapid i.v. infusion.
    • Results in nausea & vomiting – By cetirizine stimulation.

Peripheral effects:

  • No direct effect on heart, except pethidine & pentazocine.
  • Increases heart rate.
  • Decreases BP – Due to vasomotor system depression & histamine release.
  • Constipation – Due to decreased motility & increased GIT tone.
  • Alvimopan – 
    • Peripheral opioid antagonist.
    • Mainly for paralytic ileus.
    • Bacause of increased intrabiliary pressure by constricting biliary smooth muscle.

Uses of pure opioids:

  • Morphine (i.v.) – 
    • Useful in myocardial infarction, acute pulmonary edema & pre-anesthetic medication.
  • Codeine, pholcodine, dextromethorphan & noscapine – 
    • Effective cough suppressants. 
  • Loperamide & diphenoxylate – 
    • Used for non-infective diarrhea treatment.
  • Highly lipid soluble drugs (fentanyl, alfentanil, sufentanil) – 
    • Used as adjuncts to other anesthetic agents.
  • Pethidine – 
    • Used to reduce shivering after anesthesia [Its action on α2 receptor].
  • Dextromethorphan – 
    • Devoid of constipating action, unlike other drugs.

Contraindications of opioids:

  • Used cautiously in patients with pulmonary, hepatic or renal dysfunction.
  • Cautious use in infants & elderly.
  • In hypothyroidism – Show exaggerated response to opioids.
  • In pregnancy – Prolonged opioid use –> Causes in-utero physical dependence of fetus & precipitates severe withdrawal symptoms after birth.
  • Morphine –
    • Absolute contraindication in head injury.
    • Due to increased intracranial tension, respiratory depression & causes CO retention.
    • Interferes with neurological function assessment – Masks important pupillary signs – Mainly causes miosis.
    • In extremes of age i.e., very young and elderly persons.
    • In bronchial asthma because it can cause respiratory depression and worsen the condition.
    • In biliary colic – By increasing intrabiliary pressure worsens pain of biliary colic.
  • Pethidine & pentazocine – 
    • In MI.

Important points on individual drugs:

  • Methadone – 
    • Long-acting opioid analgesic.
    • Administered by oral, i.v., s.c. & rectal routes.
    • Potent agonistic actions at µ receptors; blocks NMDA receptors & monoamines reuptake.
    • Relieves neuropathic & cancer pain – Uncontrolled with morphine.
    • Due to its long t1/2, development of dependence & very slow tolerance – Hence, useful for opioid abuse treatment & opioid rotation therapy.
  • Pethidine & pentazocine – 
    • Possess anticholinergic activity –> Causes tachycardia.
    • Relatively safer in biliary colic – Due to anticholinergic properties.
    • Accumulation of active metabolite of pethidine (norpethidine) can produce seizures.
  • Propoxyphene – 
    • Least potent & least efficacious analgesic agent.
  • Diphenoxylate, difenoxin (its active metabolite) & loperamide – 
    • Useful for diarrhea.
  • Nalbuphine – 
    • Shows ceiling effect to its respiratory depressant action.
  • Buprenorphine dissociates slowly from µ receptors & is resistant to naloxone reversal.
  • Butorphanol, pentazocine & dezocine – 
    • Has psychomimetic effects with κ-agonistic activity.
  • Ziconotide:
    • Intrathecal analgesia.
    • Acts by blocking voltage-gated N-type Ca2+ channels.
  • Tramadol – 
    • Weak µ-receptor agonist.
    • Inhibits NA & 5-HT reuptake.
    • At high doses – seizures.
    • Analgesic action abolished by 5-HT antagonists (ondansetron).
  • Tapentadol (new drug) – 
    • µ-receptor agonistic action & NA reuptake inhibiting action.
  • Opioid tolerance: Develops all opioids actions except constipation, convulsions & pupil constriction.

MIXED AGONISTS-ANTAGONIST DRUGS:

Drugs included:

  • Buprenorphine
  • Nalbuphine
  • Pentazocine
  • Dezocine
  • Butorphanol

Drugs & receptors:

  • Nalbuphine, pentazocine & dezocine: κ-agonists and µ-receptor antagonists
  • Buprenorphine: Partial agonist at µ receptor; Mild κ- and δ-antagonistic property.
  • Butorphanol – Predominant κ-agonist

Uses:

  • Analgesic.
  • As methadone alternative – For opioid withdrawal management.
  • Nalbuphine, pentazocine & dezocine – Produces psychomimetic effects with hallucinations, nightmares & anxiety.
  • Butorphanol – Produces equivalent analgesia; more sedative than morphine.

Exam Important

OPIOID DRUGS

  • Opioid drugs are substances obtained from crude extracts of Papaver somniferum (poppy plant).
  • Main used as analgesic agents.
  • Opioid receptors include, µ, κ and δ receptors.
  • Pure opioid includes Morphine, Methadone, Heroin, Hydromorphone, Oxymorphone, Pethidine, Codeine, Hydrocodone & Oxycodone.
  • Mixed agonist-antagonist drugs include BuprenorphineButorphanol, Nalbuphine, Pentazocine & Tramadol.
  • Opioid antagonists includes Naloxone, Naltrexone, Nalmefene & Naloxegol.
  • Endogenous peptides include Endorphins, dynorphins, enkephalins & Nociceptin.
  • Endorphins act on µ receptor; Dynorphins acts on κ receptor; Enkephalins acts on δ receptors.
  • Morphine – Administered by oral, rectal, i.v., i.m., intrathecal or epidural routes.
  • Fentanyl – Applied as transdermal patch; also administered by buccal transmucosal route.
  • Butorphanol – Only opioid available in nasal formulation.
  • Morphine acts on µ, κ and δ receptors.
  • Morphine produce respiratory depression, cough suppression & miosis.
  • Main feature for opioid poisoning diagnosis – Pinpoint pupil.
  • Highly lipid soluble drugs include fentanyl, alfentanil & sufentanil.
  • Fentanyl, alfentanil & sufentanil causes truncal rigidity on rapid i.v. infusion.
  • Pure opioids peripherally cause increased heart rate, decreases BP & constipation.
  • Alvimopan, a peripheral opioid antagonist, mainly used for paralytic ileus, because of increased intrabiliary pressure, by constricting biliary smooth muscle.
  • Morphine (i.v.) used in myocardial infarction, acute pulmonary edema & pre-anesthetic medication.
  • Codeine, pholcodine, dextromethorphan & noscapine are effective cough suppressants.
  • Loperamide & diphenoxylate used for non-infective diarrhea treatment.
  • Highly lipid soluble drugs (fentanyl, alfentanil, sufentanil) are used as adjuncts to other anaesthetic agents.
  • Pethidine are used to reduce shivering after anaesthesia, due to its action on α2 receptor.
  • Dextromethorphan is a drug devoid of constipating action.
  • During pregnancy, prolonged opioid use –> Causes in-utero physical dependence of fetus & precipitates severe withdrawal symptoms after birth.
  • Morphine is absolutely contraindicated in head injury, due to increased intracranial tension, respiratory depression & causes CO retention, in extremes of age i.e., very young and elderly persons, in bronchial asthma because it can cause respiratory depression and worsen the condition & in biliary colic by increasing intrabiliary pressure worsens pain of biliary colic.
  • Morphine mainly interferes with neurological function assessment & masks important pupillary signs, resulting in miosis.
  • Pethidine & pentazocine is contraindicated in MI.
  • Methadone is a long-acting opioid analgesic, with potent agonistic actions at µ receptors.
  • Methadone relieves neuropathic & cancer pain – Uncontrolled with morphine.
  • Methadone useful for opioid abuse treatment & opioid rotation therapy – mainly due to its long t 1/2, development of dependence & very slow tolerance.
  • Pethidine & pentazocine are relatively safer in biliary colic, due to anticholinergic properties.
  • Accumulation of active metabolite of pethidine (norpethidine) can produce seizures.
  • Propoxyphene is least potent & least efficacious analgesic agent.
  • Diphenoxylate, difenoxin are useful for diarrhea.
  • Nalbuphine shows ceiling effect to its respiratory depressant action.
  • Buprenorphine dissociates slowly from µ receptors & is resistant to naloxone reversal.
  • Butorphanol, pentazocine & dezocine have psychomimetic effects with κ-agonistic activity.
  • Ziconotide are intrathecal analgesia, acts by blocking voltage-gated N-type Ca2+ channels.
  • Tramadol are weak µ-receptor agonist.
  • Tapentadol is a new drug with µ-receptor agonistic action & NA reuptake inhibiting action.
  • Mixed agonists antagonist drugs included Buprenorphine, Nalbuphine, Pentazocine, Dezocine & Butorphanol.
  • Nalbuphine, pentazocine & dezocine are κ-agonists and µ-receptor antagonists.
  • Buprenorphine are partial µ-receptor agonist with mild κ- and δ-antagonistic property.
  • Butorphanol is predominant κ-agonist.
  • Nalbuphine, pentazocine & dezocine produces psychomimetic effects with hallucinations, nightmares & anxiety.
  • Butorphanol is more sedative than morphine.

 

Don’t Forget to Solve all the previous Year Question asked on OPIOID DRUGS

Module Below Start Quiz

This site uses Akismet to reduce spam. Learn how your comment data is processed.

%d bloggers like this:
Malcare WordPress Security