This document discusses opioid analgesics, focusing on morphine. It describes opioid receptors and their endogenous ligands. Morphine is classified as a natural opium alkaloid. Its mechanism of action involves activating Gi proteins in opioid receptors to decrease cAMP, reducing cell excitability. Clinically, morphine is used for analgesia but can cause respiratory depression, constipation, and dependence with chronic use. Dependence is treated by substituting methadone and gradually withdrawing it.

1. Opioid Analgesics-1
By Dr. Chintan Doshi

2. INTRODUCTION
• Algesia: is ill-defined, unpleasant sensation, usually
evoked by an external or internal noxious stimulus
• Analgesic: A drug that selectively relieves pain by
acting in the CNS or on peripheral pain mechanisms,
without significantly altering consciousness

3. Opioid Receptors
 opioid receptor types:-
• μ-receptor
• δ-receptor
• κ-receptor
• NOP (Nociceptin Opioid Peptide) receptor

4. Receptor Subtype Endogenous Opioid Peptide Affinity
(mu) Endorphins > enkephalins > dynorphins
(delta) Enkephalins > endorphins and
dynorphins
(kappa) Dynorphins > > endorphins and
enkephalins

5. Classification
1. Natural opium alkaloids:
– Morphine, Codeine
2. Semisynthetic opiates
– Diacetylmorphine (Heroin), Pholcodeine,
Ethylmorphine.
3. Synthetic opioids
– Pethidine (Meperidine)
– Fentanyl, Methadone, Dextropropoxyphene
– Tramadol

6. Cellular Mechanism of Action
• Opioid receptors are linked to G proteins. Activation
of Gi leads to decreased cAMP :Decrease cell
exitability
• Closure of voltage-gated Ca2+ channels on
presynaptic nerve terminals, which decreases
neurotransmitter release

7. Cellular Mechanism of Action Contd.
• Opening of K+ channels causing hyperpolarization
(inhibition) of postsynaptic neurons

9. •Morphine

10. Pharmacological effects
CNS:
 Analgesia: most powerful drug available for relief of
pain
 Euphoria: addict experiences a pleasant floating
sensation and freedom from anxiety and distress.
 Sedation
 Respiratory depression:

11. • Cough suppression: suppression of cough centre in
nucleus of tractus solitarius
• Miosis: results from stimulation of Edinger- Westphal
nucleus causing pin-point pupils.
• Emesis: due to stimulation of brainstem
chemoreceptor trigger zone results in nausea and
vomiting

12.  CVS: No significant direct effect on CVS
 Hypotension may occur if CVS is already stressed.
Due to the peripheral arterial and venous dilation
resulting from histamine release.
 GIT: Decrease intestinal propulsive peristalsis and
stomach motility leads to constipation
 Biliary tract: Constriction of biliary smooth muscles
leads to biliary colic

13. • Uterus: decrease uterine tone lead to prolong labor
• Skin: flushing and warming ,sweating, itching due to
histamine release

14. Clinical uses
• Analgesia for
a. MI
b. Terminal illness
c. surgery
d. obstetrical procedures
e. cancer
f. Burn
• Prevent neurogenic shock and other autonomic
effects of excruciating pain such as that of crush
injuries

15. Contd.
• Preanaesthetic medication
Morphine and pethidine are used in few
selected patients
Produce pre- and postoperative analgesia
smoothen induction
Reduce the dose of anaesthetic required
supplement poor analgesics (thiopentone,
halothane)

16. • Balanced anaesthesia and surgical analgesia
• Relief of anxiety and apprehension
• MI
• Internal bleeding
• Hematemesis

17. Clinical uses Contd.
• Acute pulmonary edema
(a) Reducing preload on heart due to vasodilatation
and peripheral pooling of blood.
(b) Tending to shift blood from pulmonary to
systemic circuit
(c) Allays air hunger by depressing respiratory
centre

18. Clinical uses Contd.
d) Cuts down sympathetic stimulation by
calming the patient, reduces cardiac
work.
• Cough: codeine for dry cough
• Diarrhoea:
– Loperamide & diphenoxylate are used

19. Contraindications
• Infants and the elderly
• Respiratory insufficiency (emphysema, pulmonary
fibrosis, cor pulmonale) sudden deaths have occurred
• Bronchial asthma
• Head injury
– By retaining CO2, it increases intracranial tension which will add
to that caused by head injury itself.
– Even therapeutic doses can cause marked respiratory
depression in these patients.
– Vomiting, miosis and altered mentation produced by morphine
interfere with assessment of progress in head injury cases

20. Contd.
• Hypotensive states and hypovolaemia
• Undiagnosed acute abdominal pain
– Morphine can aggravate certain conditions, e.g.
diverticulitis, biliary colic, pancreatitis.
– Inflamed appendix may rupture.
• Elderly male:urinary retention
• Hypothyroidism, liver and kidney disease
• Unstable personalities

21. Adverse Effects
Side effects
• Sedation
• mental clouding
• Lethargy
• vomiting
• constipation
• Respiratory depression
• blurring vision
• urinary retention

22. Adverse Effects Contd.
• Idiosyncrasy and allergy
– urticaria, swelling of lips occur infrequently
• Apnea of new born:may occur when morphine
is given to the mother during labour.

23. Acute morphine poisoning
• may be accidental, suicidal or seen in drug
abusers
• human lethal dose :250 mg

24. Symptoms
• Coma
• Flaccidity,
• Shallow and occasional breathing
• Cyanosis
• Pinpoint pupil
• Fall in BP and shock
• Death: due to respi. failure

25. Acute morphine poisoning
Treatment:
• Maintain respiration, BP
• Gastric lavage should be done with Pot.
Permanganate to remove unabsorbed drug
• Opioid antagonist, preferably iv naloxone
0.4-0.8 mg repeated every 2-3 min

26. Tolerance and Dependence

27. Tolerance
• partly pharmacokinetic (enhanced rate of
metabolism) but mainly pharmacodynamic
(cellular tolerance)
• Exhibited to most actions, but not to
constipating and miotic actions.

28. Dependence
• Psychological and physical dependence,
• Its abuse liability is rated high
• Withdrawal symtoms:
– Lacrimation, sweating, yawning
– Anxiety, fear, restlessness
– Mydriasis, tremor, insomnia
– Abdominal colic, diarrhoea, dehydration,
– Rise in BP, palpitation and rapid weight loss

29. • Treatment of opioid
dependence

30. • withdrawal of morphine and substitution with
oral methadone (long-acting, orally effective)
• followed by gradual withdrawal of methadone

31. THANK YOU
“ Every form of addiction is bad , no matter whether the
narcotics, be alcoholic or idealism ”