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  1. Sir William Osler called morphine-God’s own medicine
  2. Serturner isolated morphine-1803 from juice of poppy plant, naming it after Morpheus, the Greek god of dreams.
  3. Morphine remains the standard against which all drugs that have strong analgesic action are compared.

Juice Of Poppy Plant (Papaver somniferum and P. album).

After incision, the poppy seedpod exudes a white substance that turns into a brown gum that is crude opium, that contains many alkaloids.

  1. Moprhine (10 %)                    
  2. Papaverine                    
  3. Thebaine

Endogenous opioids

  1. Pro-opio-melanocortins (beta-endorphins, ACTH, MSH, beta-lipotrophins)
  2. Preproenkephalins (met-enkephalin, leu-enkephalin)
  3. Preprodynorphin (dynorphin A & B, neoendorphins)

Opioid receptors

All are GPCRs:



Endorphins (endogenous ligand)

ïïand subspinal μïSedation (supraspinal μ



ïïand subspinal κïAnalgesia (supraspinal κ



Analgesia (subspinal)
Affective behaviour

Orphanin-opiod like receptor subtype 1

Nociceptin / Orphanin FQ

Pro- and anti-nociceptive activity
Drug reward, learning, mood, anxiety, and cough processes, and parkinsonism.



  1. Opioids reduce release of substance-P from substantia gelatinosa
  2. Increase permeability to K- Cellular hyperpolarization occurs



  1. Pure Agonists
    1. Morphine                                        
    2. Codeine                          
    3. Pethidine                          
    4. Pentazocine
    5. Fentanyl                                            
    6. Remifentanyl                  
    7. Sufentanyl                      
    8. Alfentanyl
    9. Methadone                                     
  2. Pure Antagonists
    1. Naloxone                          
    2. Naltrexone                      
    3. Nalmefene
  3. Partial/weak μ Agonist + κ Antagonist
    1. Buprenorphine
  4. Agonists-antagonists (κ Analgesics): Mnemonic – PNB
    1. Pentazocine                    
    2. Nalbuphine                        
    3. ​Butorphanol



  1. Opioids-lipid soluble
  2. Well absorbed
  3. High first pass metabolism
    1. Pethidine forms norpethidine
    2. Morphine forms morphine-6-glucoronide (more potent)
    3. Heroin-morphnine
  4. Fentanyl-transdermal opioid
  5. Remifentanil-shortest opioid; half life=10-20 minutes, metabolized by esterases
  6. Alfentanil & Sufentanil
  • Most protein bound opioids

Buprenorphine–longest acting opioid; half life=8 hours

  1. Binds very tightly to mu receptors
  2. Action therefore is not reversed even by naloxone

Pharmacological Actions:

  1. Brain
    1. Sedation                  
    2. Analgesia                                                                        
    3. Euphoria          
    4. Nausea              
    5. Meiosis                    
    6. Respiratory depression (dose dependent)                
    7. Anti-cough
  2. Endocrinal

    1. Decrease release of LH/FSH/GH
    2. Increase release of prolactin
      1. Reproductive functions remain impaired in addicts
  3. Hypothalamus
    1. Decrease body temperature-hypothermia can occur in overdose
  4. Skin
    1. Flushing of skin
    2. Itching on facial skin (Nasolabial folds)
      1. Angioedema like picture can occur
      2. Effects occur due to histamine release
  5. Heart
    1. Bradycardia can occur
    2. Occurs due to AV node blocking tendency of opioids
      1. Preoperative opioid use is most common cause of intraoperative bradycardia
  6. Blood vessels
    1. Vasodilatation
  7. Chest
    1. Increase in muscle tone of chest muscles-’rigid chest wall’ syndrome
      1. Maximum chance occurs with fentanyl
    2. Ventilation suffers; pneumonia can occur
      1. Opioids therefore are avoided in chest wall diseases such as rib fractures/myasthenia gravis
  8. Lungs
    1. Shifting of blood; from lungs to systemic circulation
      1. Action is responsible for relief of pulmonary edema where morphine is acutely effective
  9. Gut
    1. Increase tone of circular muscles, decrease tone of longitudinal muscles
    2. Increase tone of anal sphincter
    3. Inattention to defecation reflex
      1. Actions contribute to constipation  
  10. Hepato-billary tract
    1. Contraction of sphincter of oddi
    2. Billiary colic can occur
      1. Opioids therefore are avoided in undiagnosed abdominal pain
  11. Ureter
    1. Contraction
  12. Urinary bladder
    1. Contraction of detrusor
    2. Contraction of uretheral sphincter

Therapeutic Uses-

  1. Morphine
    1. Acute pulmonary edema
    2. Pain of terminal illness
      1. Full therapeutic doses should be used without bothering for side effects
    3. Chronic cancer pain
      1. Drug is used orally
    4. Epidural analgesia
    5. Pain of AMI
    6. Tetralogy of Fallot
2. Contraindications
  1. Head injury
  2. Asthma
  3. Chest wall disorders - Rib fractures, myasthenia
  4. Intestinal obstruction
  5. Bilary colic
  6. Ureteric colic
  7. Acute pancreatitis
  8. BPH
  9. Hypotension
  10. Personality disorders
3. Overdose
  1. Fatal dose-60 mg
  2. DOC-Naloxone
    1. Short acting
    2. Redistribution
  1. Pethidine
    1. Visceral analgesia
      1. Shorter acting than morphine
      2. Less respiratory depressant
      3. Avoided with MAO inhibitors
        C/I-RENAL FAILURE (NORPETHIDINE SYNDROME)---- ppt. of Seizures
    2. Metabolism: 99% to Pethidinic acid by MAO-A
      1% to Norpethidine through demethylase and excreted through Kidney
    3. ‘Atypical opioid’
      1. No anti-cough activity                    
      2. No nausea/vomiting
      3. Less biliary spasm                        
      4. Less ureteric contraction
      5. Mydriasis can occur                      
      6. Tacycardia occurs
  2. Pentazocine
    Similar to pethidine and both have anticholinergic property, hence C/I in MI
  3. Dezocine
    1. Mu agonist
    2. More potent than morphine
    3. More respiratory depressant than morphine
    4. Less likely to provoke bilary spasm
    5. More protein bound than morphine 
  4. Buprenorphine
    1. Mu partial agonist
      1. Longest acting
      2. Used in opioid detoxification (long acting Benzodiazepines also used)
      3. Effects not even reversed by naloxone
  5. Methadone
    1. Longer acting than morphine, also blocks NMDA receptors, reuptake of monoamines
    2. Less severe withdrawal than morphine
    3. Less addicting than morphine
    4. More potent than morphine
    5. High first pass; many D/I
    6. Used as methadone maintenance therapy after opioid withdrawal
  6. Newer opioids
    1. Remifentanil
      1. Pain relief in anesthesia
    2. Alfentanil
      1. Opioid of choice-’day care surgery’
    3. Sufentanil
      1. Blunting of sympathetic response following intubations
    4. Fentanyl
      1. Transdermal analgesia  
  7. Naloxone
    Pure antagonist
    Short acting. Ineffective orally, hence only parenteral route
    May ppt. withdrawal in Opioid dependence (life threatening)
    DOC: Acute opioid poisoning, but needs repetitive dosing
    Neonatal Resuscitation if mother is opioid dependant
  8. Naltrexone
    1. More potent, Orally active
    2. Longer acting (half life=48 hours)
    3. DOC: maintenance in Acute opioid poisoning, prevent relapse after de-addiction
    4. Reduces craving among alcoholics
      Anti-impotence drug

Opioid De-addiction:


1) Treatment of withdrawal symptoms


2) Prevention of withdrawal symptoms


3) Prevention of Relapse


Other alcohol anti-craving agents are:

  1. DOC - Acamproste (NMDA blocker)
  2. Others:
    1. Topiramate (carbonic anhydrase inhibitor)
    2. Fluoxetine (SSRI)
    3. Chlordiazepoxide (DOC) for alcohol withdrawal
    4. Disulfiram (DOC-detoxification)
    5. Diazepam (DOC-delirium tremens)

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