Opioid Analgesics
BY
PROF. AZZA EL-MEDANY
CLASSIFICATION




Natural ( Morphine)
Semisynthetic ( Codine )
Synthetic ( Mepiridine, Methadone,
Fentanyl, Tramadol )
Another Classification





Strong agonist
Moderate agonists
Mixed agonists /antagonists
Pure antagonist
Mechanism of actions




Binding to opioid receptors (mu,delta,
kappa ,sigma ) at presynaptic nerve fibres
resulting in ...
Morphine ( Natural & Strong
agonist)
PHARMACOKINETICS :
 ROUTES OF ADMINISTRATION
 METABOLISM
 DISTRIBUTION
 EXCRETION
Routes of administration





Oral absorption is erratic
IMI , SC injection are preferred
Chronic pain , slow release ...
Metabolism & excretion


In liver to active metabolite ( morphine -6
glucuronide & morphine -3 glucuronide



Half-life
...
Pharmacological actions


Analgesia
Without loss of consciousness
Severe type of pain
Sedation
Euphoria
Respiration






Respiratory depressant which is dose
dependent
Large dose causes respiratory failure &
death
Reduce t...
Eye


Miosis ( pin point pupil)
Through mu & kappa receptors at
Edinger westphal neuclus of 3rd
nerve
Cough center


Antitussive
Potent depressant for cough center
Histamine release


From mast cells ( urticaria, sweating ,
vasodilataion , bronchospasm )
Endocrinal effect


Decrease : LH, FSH, ACTH ,
testosterone



Increase : Prolactin, growth hormone,
ADH leading to urin...
Nausea & Vomiting


Stimulation of CRTZ
GIT





Constipation
Constrict biliary smooth muscle may
result in biliary colics
Sphincter of Oddi may constrict
resu...
Urinary System




Decrease in renal function
Urine retention
Spasm of smooth muscles of ureter
causing renal colics
Uterus


Prolong labor
CVS


Large dose causing hypotension &
bradycardia



With respiratory depression & retention
of CO2 causing cerebral va...
CLINICAL USES









CANCER PAIN
SEVERE BURN
SEVERE VISCERAL PAIN ( except, renal &
biliary colics , acute pancr...
ADVERSE EFFECTS









RESPIRATORY DEPRESSION
NAUESEA & VOMITING
CONSTIPATION
URINE RETENTION
HYPOTENSION
ALLERG...
Withdrawal manifestations






Severe body ache
Insomnia
Diarrhea
Goose flesh
Lacrimation
CONTRAINDICATIONS






HEAD INJURY
PREGNANCY
BRONCHIAL ASTHMA or impaired
pulmonary function
Liver & Kidney diseases...
Continue





Old people are more sensitive
( decrease in metabolism , lean body
mass & renal function )
Not given to i...
Meperidine ( Pethidine)




Synthetic
Strong agonist
More effective on kappa receptors
PHARMACOKINETICS








Well absorbed orally
(Has a high oral bioavailability )
Given also by IMI
Half-life ( short ...
Pharmacological Actions






Less analgesic , less constipating
( weak effect ) , less depressant on
foetal respirati...
CLINICAL USES







Cancer pain
Severe burn
Severe visceral pain( renal & biliary
colics )
Obstetric analgesia
Prean...
ADVERSE EFFECTS








Tremors & Convulsions
Hyperthermia
Hypotension
Tolerance & Addiction
Burred vision
Dry mout...
METHADONE






SYNTHETIC OPIOID
POTENT ANALGESIC AS MORPHINE
GIVEN BY ORAL , I.V., S.C., AND
RECTAL
HAS A HIGHER ORAL...
CONTINUE






LONG PLASMA HALF- LIFE ( 24 hrs )
LESS EUPHORIC THAN MORPHINE
PRODUCES MILD WITHDRAWAL
SYMPTOMS
TOLERAN...
CLINICAL USES


Control withdrawal symptoms of
dependant abusers from heroin &
morphine



Neuropathic & cancer pain
CODEINE







Synthesized commercially from
morphine
Less analgesic & euphoric than
morphine
Given orally
Potent an...
DEXTROMETHORPHAN





FREE OF ANALGESIC & ADDICTIVE
EFFECTS
LESS CONSTIPATING THAN CODEINE
POTENT AS ANTITUSSIVE
Fentanyl







Synthetic drug
More potent as analgesic than
morphine
Rapid onset & very short duration of
action (1...
Sufentanyl, Alfentanyl &
Remifentanil



Sufentanyl more potent than fentanyl
Other two are less potent with shorter
dur...
Heroin






Strong agonist
Crosses BBB
Converted to morphine
No medical use
Strong addicting drug
TRAMADOL ( Synthetis )






Centrally acting analgesic through
inhibition uptake of norepinephrine &
serotonin
Binds ...
CONTINUE




Given orally ( high oral bioavailability)
& by different other routes
Used in :
mild & moderate acute & chr...
ADVERSE EFFECTS &
CONTRAINDICATIONS






Seizures , Nausea , Dry mouth,
Dizziness , Sedation
Less adverse effects on r...
Loperamide




Can not cross BBB
Lacking analgesic effect
Used for treatment of chronic diarrhea
OPIOIDS WITH MIXED
RECEPTORS ACTIONS








BUPRENORPHINE
Partial Mu receptor agonist
Long duration of action
Poor ...
CONTINUE






Acts as morphine in normal patient &
precipitate withdrawal symptoms in
morphine users.
Causes less : se...
Pentazocine








Agonist at KAPPA & antagonist at MU
Receptors
Given orally or parentrally
Has a short duration of...
Adverse effects









Hallucination , nightmares , convulsions
Increase Blood Pressure & Heart rate
Precipitate ...
OPIOID ANTAGONISTS







NALOXONE
PURE ANTAGONIST AT MU RECEPTORS
HAS a rapid onset of action (SECONDS ) &
Short dur...
NOTICE


Naloxone completely reverse
respiratory depression produced by
opioid over doses ,
Incompletely reverse their an...
Naltrexone




Has a Long duration of action (10 HRS )
Given Orally
Used clinically in :
1- Treatment of chronic Alcoho...
OPIOID ANTAGONISTS







In normal individual do not produce any
effect.
IN dependent individual Precipitate
withdraw...
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Opioid analgesics 2-prof azza

  1. 1. Opioid Analgesics BY PROF. AZZA EL-MEDANY
  2. 2. CLASSIFICATION    Natural ( Morphine) Semisynthetic ( Codine ) Synthetic ( Mepiridine, Methadone, Fentanyl, Tramadol )
  3. 3. Another Classification     Strong agonist Moderate agonists Mixed agonists /antagonists Pure antagonist
  4. 4. Mechanism of actions   Binding to opioid receptors (mu,delta, kappa ,sigma ) at presynaptic nerve fibres resulting in decreasing calcium influx leading to decrease in releasing excitatory neurotransmitters Post synaptic activation of receptors increase potassium efflux (hyperpolarization )
  5. 5. Morphine ( Natural & Strong agonist) PHARMACOKINETICS :  ROUTES OF ADMINISTRATION  METABOLISM  DISTRIBUTION  EXCRETION
  6. 6. Routes of administration     Oral absorption is erratic IMI , SC injection are preferred Chronic pain , slow release preparation Non medical route , inhalation of powder or smoke
  7. 7. Metabolism & excretion  In liver to active metabolite ( morphine -6 glucuronide & morphine -3 glucuronide  Half-life 4-6 hours. Crosses BBB & placental barrier Excreted in urine  
  8. 8. Pharmacological actions  Analgesia Without loss of consciousness Severe type of pain
  9. 9. Sedation Euphoria
  10. 10. Respiration    Respiratory depressant which is dose dependent Large dose causes respiratory failure & death Reduce the sensitivity of respiratory center to CO2
  11. 11. Eye  Miosis ( pin point pupil) Through mu & kappa receptors at Edinger westphal neuclus of 3rd nerve
  12. 12. Cough center  Antitussive Potent depressant for cough center
  13. 13. Histamine release  From mast cells ( urticaria, sweating , vasodilataion , bronchospasm )
  14. 14. Endocrinal effect  Decrease : LH, FSH, ACTH , testosterone  Increase : Prolactin, growth hormone, ADH leading to urine retention
  15. 15. Nausea & Vomiting  Stimulation of CRTZ
  16. 16. GIT    Constipation Constrict biliary smooth muscle may result in biliary colics Sphincter of Oddi may constrict resulting in reflux of biliary & pancreatic secretions & elevated plasma lipase & amylase
  17. 17. Urinary System    Decrease in renal function Urine retention Spasm of smooth muscles of ureter causing renal colics
  18. 18. Uterus  Prolong labor
  19. 19. CVS  Large dose causing hypotension & bradycardia  With respiratory depression & retention of CO2 causing cerebral vasodilataion & ↑ in CSF pressure
  20. 20. CLINICAL USES         CANCER PAIN SEVERE BURN SEVERE VISCERAL PAIN ( except, renal & biliary colics , acute pancreatitis ) DIARRHOEA COUGH ACUTE PULMONARY OEDEMA Myocardial ischemia PREANAESTHETIC MADICATION
  21. 21. ADVERSE EFFECTS         RESPIRATORY DEPRESSION NAUESEA & VOMITING CONSTIPATION URINE RETENTION HYPOTENSION ALLERGY TOLERANCE ( not to mitotic, convulsant, or constipating effects ) ADDICTION ( abstinence syndrome)
  22. 22. Withdrawal manifestations      Severe body ache Insomnia Diarrhea Goose flesh Lacrimation
  23. 23. CONTRAINDICATIONS      HEAD INJURY PREGNANCY BRONCHIAL ASTHMA or impaired pulmonary function Liver & Kidney diseases (including renal& biliary colics ) Endocrine diseases ( myxedema & adrenal insufficiency)
  24. 24. Continue    Old people are more sensitive ( decrease in metabolism , lean body mass & renal function ) Not given to infants With MAOI
  25. 25. Meperidine ( Pethidine)    Synthetic Strong agonist More effective on kappa receptors
  26. 26. PHARMACOKINETICS      Well absorbed orally (Has a high oral bioavailability ) Given also by IMI Half-life ( short ) 2-4 hours Give an active metabolite which has CNS stimulant effect Excreted in urine
  27. 27. Pharmacological Actions     Less analgesic , less constipating ( weak effect ) , less depressant on foetal respiration than morphine Atropine –like action Smooth muscle relaxant effect No cough suppressant effect
  28. 28. CLINICAL USES      Cancer pain Severe burn Severe visceral pain( renal & biliary colics ) Obstetric analgesia Preanaesthetic medication
  29. 29. ADVERSE EFFECTS        Tremors & Convulsions Hyperthermia Hypotension Tolerance & Addiction Burred vision Dry mouth Urine retention
  30. 30. METHADONE     SYNTHETIC OPIOID POTENT ANALGESIC AS MORPHINE GIVEN BY ORAL , I.V., S.C., AND RECTAL HAS A HIGHER ORAL BIOAVAILABILITY THAN MORPHINE
  31. 31. CONTINUE     LONG PLASMA HALF- LIFE ( 24 hrs ) LESS EUPHORIC THAN MORPHINE PRODUCES MILD WITHDRAWAL SYMPTOMS TOLERANCE & PHYSICAL DEPENDENCE DEVELOP MORE SLOWLY THAN MORPHINE
  32. 32. CLINICAL USES  Control withdrawal symptoms of dependant abusers from heroin & morphine  Neuropathic & cancer pain
  33. 33. CODEINE       Synthesized commercially from morphine Less analgesic & euphoric than morphine Given orally Potent antitussive Always given in combination with aspirin or acetaminophen Addicting drug
  34. 34. DEXTROMETHORPHAN    FREE OF ANALGESIC & ADDICTIVE EFFECTS LESS CONSTIPATING THAN CODEINE POTENT AS ANTITUSSIVE
  35. 35. Fentanyl       Synthetic drug More potent as analgesic than morphine Rapid onset & very short duration of action (15-30 min ) Used as I.V. anaesthesia IN cancer pain as transdermal patches Has a respiratory depressant effect
  36. 36. Sufentanyl, Alfentanyl & Remifentanil   Sufentanyl more potent than fentanyl Other two are less potent with shorter duration of action
  37. 37. Heroin      Strong agonist Crosses BBB Converted to morphine No medical use Strong addicting drug
  38. 38. TRAMADOL ( Synthetis )     Centrally acting analgesic through inhibition uptake of norepinephrine & serotonin Binds to mµ receptor. Less potent as analgesic than morphine Undergoes extensive metabolism
  39. 39. CONTINUE   Given orally ( high oral bioavailability) & by different other routes Used in : mild & moderate acute & chronic visceral pain during labor
  40. 40. ADVERSE EFFECTS & CONTRAINDICATIONS    Seizures , Nausea , Dry mouth, Dizziness , Sedation Less adverse effects on respiratory & C.V.S. Contraindicated in patients with history of epilepsy
  41. 41. Loperamide    Can not cross BBB Lacking analgesic effect Used for treatment of chronic diarrhea
  42. 42. OPIOIDS WITH MIXED RECEPTORS ACTIONS       BUPRENORPHINE Partial Mu receptor agonist Long duration of action Poor oral bioavailability Given parntrally ,Sublingually , Or as nasal spray Excreted in the bile & urine
  43. 43. CONTINUE    Acts as morphine in normal patient & precipitate withdrawal symptoms in morphine users. Causes less : sedation , respiratory depression , hypotension than morphine. Used in detoxification & maintenance of heroin abusers
  44. 44. Pentazocine      Agonist at KAPPA & antagonist at MU Receptors Given orally or parentrally Has a short duration of action Less potent , less euphoric than morphine High doses causes respiratory depression
  45. 45. Adverse effects        Hallucination , nightmares , convulsions Increase Blood Pressure & Heart rate Precipitate withdrawal symptoms when given to patients dependent on morphine CONTRAINDICATIONS With Morphine Heart diseases & Hypertension Epilepsy
  46. 46. OPIOID ANTAGONISTS      NALOXONE PURE ANTAGONIST AT MU RECEPTORS HAS a rapid onset of action (SECONDS ) & Short duration of action (30-60min ) Is available for I.V. route Teatment of OPIOID overdoses ( ACUTE TOXICITY )
  47. 47. NOTICE  Naloxone completely reverse respiratory depression produced by opioid over doses , Incompletely reverse their analgesic effects.
  48. 48. Naltrexone    Has a Long duration of action (10 HRS ) Given Orally Used clinically in : 1- Treatment of chronic Alcoholism 2-Control withdrawal symptoms of addicts 3- Reduce craving for alcohol in chronic alcoholics
  49. 49. OPIOID ANTAGONISTS     In normal individual do not produce any effect. IN dependent individual Precipitate withdrawal symptoms NO Tolerance TO Their Antagonistic action NO withdrawal symptoms When Withdrawn After Chronic Use

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