1. Opioid Analgesics
BY PROF. AZZA EL-MEDANY

2. CLASSIFICATION Natural ( Morphine) Semisynthetic ( Codine )
Synthetic ( Mepiridine, Methadone, Fentanyl, Tramadol )

3. Another Classification
Strong agonist
Moderate agonists
Mixed agonists /antagonists
Pure antagonist

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. Morphine ( Natural & Strong agonist)
PHARMACOKINETICS :
ROUTES OF ADMINISTRATION
METABOLISM
DISTRIBUTION
EXCRETION

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. Metabolism & excretion
In liver to active metabolite ( morphine -6 glucuronide & morphine -3 glucuronide
Half-life hours.
Crosses BBB & placental barrier
Excreted in urine

8. Pharmacological actions
Analgesia
Without loss of consciousness
Severe type of pain

9. Sedation
Euphoria

10. Respiration Respiratory depressant which is dose dependent
Large dose causes respiratory failure & death
Reduce the sensitivity of respiratory center to CO2

11. Eye Miosis ( pin point pupil) Through mu & kappa receptors at
Edinger westphal neuclus of 3rd nerve

12. Cough center
Antitussive
Potent depressant for cough center

13. Histamine release
From mast cells ( urticaria, sweating , vasodilataion , bronchospasm )

14. Endocrinal effect Decrease : LH, FSH, ACTH , testosterone
Increase : Prolactin, growth hormone, ADH leading to urine retention

15. Nausea & Vomiting
Stimulation of CRTZ

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. Urinary System Decrease in renal function Urine retention
Spasm of smooth muscles of ureter causing renal colics

18. Uterus
Prolong labor

19. CVS Large dose causing hypotension & bradycardia
With respiratory depression & retention of CO2 causing cerebral vasodilataion & ↑ in CSF pressure

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. ADVERSE EFFECTS RESPIRATORY DEPRESSION NAUESEA & VOMITING CONSTIPATION
URINE RETENTION
HYPOTENSION
ALLERGY
TOLERANCE ( not to mitotic, convulsant, or constipating effects )
ADDICTION ( abstinence syndrome)

22. Withdrawal manifestations
Severe body ache
Insomnia
Diarrhea
Goose flesh
Lacrimation

23. CONTRAINDICATIONS HEAD INJURY PREGNANCY
BRONCHIAL ASTHMA or impaired pulmonary function
Liver & Kidney diseases (including renal& biliary colics )
Endocrine diseases ( myxedema & adrenal insufficiency)

24. Continue
Old people are more sensitive ( decrease in metabolism , lean body mass & renal function )
Not given to infants
With MAOI

25. Meperidine ( Pethidine)
Synthetic
Strong agonist
More effective on kappa receptors

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. 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. CLINICAL USES Cancer pain Severe burn
Severe visceral pain( renal & biliary colics )
Obstetric analgesia
Preanaesthetic medication

29. ADVERSE EFFECTS Tremors & Convulsions Hyperthermia Hypotension
Tolerance & Addiction
Burred vision
Dry mouth
Urine retention

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. CONTINUE LONG PLASMA HALF- LIFE ( 24 hrs ) LESS EUPHORIC THAN MORPHINE
PRODUCES MILD WITHDRAWAL SYMPTOMS
TOLERANCE & PHYSICAL DEPENDENCE DEVELOP MORE SLOWLY THAN MORPHINE

32. CLINICAL USES
Control withdrawal symptoms of dependant abusers from heroin & morphine
Neuropathic & cancer pain

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. DEXTROMETHORPHAN FREE OF ANALGESIC & ADDICTIVE EFFECTS
LESS CONSTIPATING THAN CODEINE
POTENT AS ANTITUSSIVE

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. Sufentanyl, Alfentanyl & Remifentanil
Sufentanyl more potent than fentanyl
Other two are less potent with shorter duration of action

37. Heroin Strong agonist Crosses BBB Converted to morphine No medical use
Strong addicting drug

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. CONTINUE
Given orally ( high oral bioavailability) & by different other routes
Used in :
mild & moderate acute & chronic visceral pain
during labor

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. Loperamide Can not cross BBB Lacking analgesic effect
Used for treatment of chronic diarrhea

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. 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. 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. 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. 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. NOTICE
Naloxone completely reverse respiratory depression produced by opioid over doses ,
Incompletely reverse their analgesic effects.

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. 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