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

Leave a Reply

%d bloggers like this:
Malcare WordPress Security