The document discusses opioids such as morphine, codeine, pethidine, fentanyl and methadone. Morphine is described as the prototype opioid analgesic that acts primarily on the central nervous system to produce analgesia, sedation, euphoria and respiratory depression. It also causes constipation, nausea, vomiting and hypotension. Tolerance develops to morphine's effects except for miosis and constipation. Pethidine causes less respiratory depression and histamine release compared to morphine. Fentanyl is 80-100 times more potent than morphine. Methadone has a high oral bioavailability and prolonged duration of action. Opioids are used for pain relief, pre-anesthesia

1. Opioid Analgesics

2. • Opium: A dark brown, resinous material
obtained from poppy (Papaver somniferum)
capsule.
• Morphine is the principal alkaloid in opium
and is widely used till today. Therefore, it is
described as prototype.

4. CNS actions of Morphine
• Analgesia: Morphine is a strong analgesic.
• Sedation
• Mood and subjective effects: euphoria
• Respiratory centre: Morphine depresses
respiratory centre in a dose dependent
manner
• Cough centre: depressed by morphine

5. • Temperature regulating centre: depressed;
hypothermia occurs in cold surroundings
• Vasomotor centre It is depressed at higher
doses and contributes to the fall in BP

6. Morphine stimulates:
• CTZ: Nausea and vomiting
• Edinger Westphal nucleus: miosis
• Vagal centre: stimulated→ bradycardia

7. CVS
• Morphine causes vasodilatation due to:
• (a) histamine release.
• (b) depression of vasomotor centre.
• (c) direct action decreasing tone of blood
vessels.

8. • There is a shift of blood from pulmonary to
systemic circuit due to greater vasodilatation
in the latter.
• Intracranial tension tends to rise as a
consequence of CO2 retention leading to
cerebral vasodilatation.

9. GIT
• Constipation
• a) increases tone and segmentation but
decreases propulsive movements.
• (b) Spasm of pyloric, ileocaecal and anal
sphincters.

10. • urinary retention: tone of both sphinctor and
detrusor muscles is increased.

11. Biliary tract
• Spasm of sphincter of Oddi → intrabiliary
pressure is increased several fold → may
cause biliary colic.

12. Bronchi
• Bronchoconstriction due to histamine release

13. Pharmacokinetics
• oral absorption of morphine is unreliable
because of high and variable first pass
metabolism; oral bioavailability is 1/6th to
1/4th of parenterally administered drug.

14. Side effects
• Sedation
• Vomiting
• Constipation
• Respiratory depression
• blurring of vision
• BP may fall
• urinary retention

15. Idiosyncrasy and allergy
• A local reaction at injection site and
generalized itching may occur due to
histamine release.

16. Acute morphine poisoning
• Manifestations are extensions of the
pharmacological action.
• occasional breathing, cyanosis, pinpoint pupil,
fall in BP and shock.

17. • Treatment: respiratory support (positive
pressure respiration also opposes pulmonary
edema formation)
• maintenance of BP (i.v. fluids,vasoconstrictors)
• Gastric lavage
• Specific antidote: Naloxone 0.4–0.8 mg i.v.
repeated every 2–3 min till respiration picks
up.

18. Tolerance and dependence
• Tolerance is exhibited to most actions, but not
to miosis and constipation.
• Morphine produces pronounced psychological
and physical dependence, its abuse liability is
rated high.

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

20. Precautions and contraindications
• Infants and the elderly are more susceptible to
the respiratory depressant action of
morphine.
• It is dangerous in patients with respiratory
insufficiency (emphysema, pulmonary fibrosis,
cor pulmonale)
• Bronchial asthma: Morphine can precipitate
an attack by its histamine releasing action.

21. Precautions and contraindications
• 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.

22. Precautions and contraindications
• Hypotensive states and hypovolaemia
exaggerate fall in BP due to morphine.

23. Precautions and contraindications
• Undiagnosed acute abdominal pain: morphine
can aggravate certain conditions, e.g. biliary
colic, pancreatitis. Inflamed appendix may
rupture.
• Morphine can be given after the diagnosis is
established.

24. Precautions and contraindications
• Elderly male: chances of urinary retention are
high.

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

26. Codeine
• methyl-morphine
• less potent than morphine (1/10th as
analgesic)
• codeine is more selective cough suppressant
• good activity by the oral route
• Constipation is a prominent side effect when it
is used as analgesic.

27. Pethidine (Meperidine)
• It does not effectively suppress cough.
• Spasmodic action on smooth muscles is less
marked—miosis, constipation and urinary
retention are less prominent.
• It causes less histamine release and is safer in
asthmatics.

28. • Overdose of pethidine produces many
excitatory effects—tremors, mydriasis,
hyperreflexia, delirium, myoclonus and
convulsions.
• This is due to accumulation of norpethidine
which has excitant effects.

29. Fentanyl
• A pethidine congener, 80–100 times more
potent than morphine, both in analgesia and
respiratory depression.
• In the injectable form it is almost exclusively
used in anaesthesia.
• Transdermal fentanyl has become available for
use in cancer/ terminal illness or other types
of chronic pain for patients requiring opioid
analgesia.

30. Methadone
• The most important feature of methadone is high
oral: parenteral activity ratio (1 : 2) and its firm
binding to tissue proteins.
• it cumulates in tissues on repeated
administration—duration of action is
progressively lengthened due to gradual release
from these sites.
• Because of slow and persistent nature of action,
sedative and subjective effects are less intense.

31. • Methadone has been used primarily as
substitution therapy for opioid dependence

32. USES (Of morphine and its congeners)
• As analgesic: indicated in severe pain of any
type.
• It should be given promptly in myocardial
infarction to allay apprehension and reflex
sympathetic stimulation.
• Opioids, especially pethidine, have been
extensively used for obstetric analgesia, but
one must be prepared to deal with the foetal
and maternal complications.

33. • Transdermal fentanyl is a suitable option for
chronic cancer and other terminal illness pain.

34. • Preanaesthetic medication:
• Morphine and pethidine are used in few
selected patients

35. • Balanced anaesthesia and surgical analgesia
• Fentanyl, morphine, pethidine, alfentanil or
sufentanil are an important component of
anaesthetic techniques

36. • Relief of anxiety and apprehension
• Especially in myocardial infarction, internal
bleeding (haematemesis, threatened abortion,
etc.)

37. • Acute left ventricular failure (cardiac asthma)
• Reducing preload on heart due to vasodilatation
and peripheral pooling of blood.
• Tending to shift blood from pulmonary to
systemic circuit; relieves pulmonary congestion
and edema.
• Allays air hunger and dyspnoea by depressing
respiratory centre.
• Cuts down sympathetic stimulation by calming
the patient, thereby reduces cardiac work.

38. • Cough
• Codeine or its substitutes are widely used for
suppressing dry, irritating cough

39. • Diarrhoea
• Loperamide and diphenoxylate

40. Thank You