This document discusses various opioid analgesics, including their classification, mechanisms of action, pharmacokinetics, clinical uses, and adverse effects. It covers both natural opioids like morphine as well as semi-synthetic and synthetic opioids such as codeine, methadone, fentanyl, and tramadol. It also discusses opioid antagonists used to treat overdose, such as naloxone, and opioid dependence, such as naltrexone.

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
4-6 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