1. OPIOID ANALGESICS & ANTAGONISTS

3. Narcotics ( or opiates)
MAINLY OBTAINED FROM OPIUM POPPY.
ACT BY BINDING TO SPECIFIC OPIOID RECEPTORS IN THE CNS.
MAINLY USED FOR RELIEVING INTENSE PAIN.
EUPHORIC PROPERTIES
ANTAGONISTS IMPORTANT IN OVERDOSE.

5. OPIOID RECEPTORS
4 TYPES
Mu ( µ )
Kappa ( к )
Delta ( δ )
Sigma ( σ )

6. Mu ( µ )
Location : supraspinal areas of pain modulation (periaqueductal gray, medial thalamic nuclei, hypothalamus, limbic system)
Response : Supraspinal analgesia, euphoria, respiratory depression, sedation, physical dependence, pupil constriction, decreased GI motility.
Abuse potential : High

7. Kappa ( к )
Location: Dorsal horn of spinal gray matter (substantia gelatinosa ); deep layers of cerebral cortex.
Response: Spinal analgesia, sedation, depressed flexor reflexes, pupillary constriction.
Abuse potential: Low

8. Delta ( δ )
Location : Substantia nigra, globus pallidus, corpus striatum, other limbic structures.
Response: Euphoria, sedation
Abuse potential : Low

9. Sigma ( σ ) Location : Hippocampus.
Response : Dysphoria, Hallucinations, cardiovascular stimulation, pupil dilatation.
Abuse potential : Low

10. Other than these responses,
Some of them are involved in depression of cough , ↑ nausea, ↑ vomiting, neuroendocrine actions, maintainance of B.P, control of stomach secretions, and also anti-inflammatory effects.

11. Strong Agonists Morphine Fentanyl Heroin Meperidine Methadone
Sufentanil

12. Moderate Agonists
Codeine
Propoxyphene

13. Mixed agonist - antagonist
Buprenorphine
Pentazocine

14. Antagonists
Naloxone
Naltrexone

15. MORPHINE
Main agonist actions on Mu, and also for Kappa and Sigma receptors
ACTIONS:
- Analgesia – relief of pain without loss of consciousness.
- Euphoria
- Causes Respiration Depression (This is the most common cause of death in acute opioid overdose)

16. - Depression of cough reflex
MIOSIS – PINPOINT PUPIL.
Stimulation of the edinger westphal nucleus of oculomotor nerve which causes parasympathetic stimulation of the eye.
Emesis.—stimulates chemoreceptor trigger zone (CTZ) in area postrema
- GIT : ↓ motility, relieves diarrhea and dysentery
- CVS : high doses cause hypotension and bradycardia

17. - Cerebral vessels dilate - ↑ CSF pressure ( CI – severe brain injury) - Histamine release causes bronchoconstriction, urticaria, sweating and vasodilation. - Hormonal actions – ( increase in prolactin, GH and ADH)

18. Morphine is used legally:
As an analgesic in hospital settings to relieve
Pain in Myocardial Infarction
Pain after surgery
Pain associated with trauma
In the relief of severe chronic pain, e.g.
Cancer pain
Pain from kidney stones
Severe Back pain

19. As an adjunct to general anesthesia
In epidural anesthesia or intrathecal analgesia
For palliative care (i.e. to alleviate pain without curing the underlying reason for it, usually because the latter is found impossible)
As an antitussive for severe cough
In nebulised form, for treatment of dyspnea, although the evidence for efficacy is slim. Evidence is better for other routes .

20. As an anti-diarrheal in chronic conditions (e. g
As an anti-diarrheal in chronic conditions (e.g., for diarrhea associated with AIDS), although loperamide (a non-absorbed opioid acting only on the gut) is the most commonly used opioid for diarrhea.

21. contraindications acute respiratory depression
acute pancreatitis (this may be a result of morphine use as well) because morphine may cause spasm of the sphincter of Oddi and worsen the pain
renal failure (due to accumulation of the metabolite morphine-6-glucuronide)
chemical toxicity (potentially lethal in low tolerance subjects)
raised intracranial pressure, including head injury (exacerbation due pCO2 increases from respiratory depression)

23. SE Sedation Constipation Nausea Vomiting Urinary retention
Potential for addiction
Resp. depression

24. Drug interactions:
MAO Inhibitors (monoamine oxidase inhibitors )
TCA’s(tricyclic antidepressant)
Antipsychotic

25. MEPERIDINE (Pethidine )
MECH : Binds to Kappa receptors.
Actions :
Analgesia
Resp. depression
IV route can cause increase in H.R.
Dilates pupil
Decreases GI motility
↑ CSF pressure

26. USES:
Any kind of analgesia – preferred for labor analgesia
Not used for diarrhea or cough
Can replace morphine or heroin in addicts.
Route : oral and parental
Met : liver
Exe : Urine

27. SE Tremors Muscle twitches Convulsions Dilates pupil
Not given with other neuroleptics and MAO inhibitors.
Cause hypotension – postoperative.

28. METHADONE MECH: More on Mu receptors
Equal potency to Morphine, but less euphoric and longer duration of action.
Actions:
Mostly same as morphine.
Route : oral
Met: Liver
Exe: Urine

29. USES :
Analgesia
Addicts of heroin and morphine – for withdrawal .
SE:
Less severe than morphine.

30. FENTANYL
AROUND 100 TIMES MORE POWERFUL ANALGESIC THAN MORPHINE, SO USED during ANESTHESIA
Rapid action and short duration of action.
Main action is on Mu, and also on kappa sigma receptors.

31. HEROIN 2-3 times more potent than morphine. More euphoria
No therapeutic uses
Addiction

32. PROPOXYPHENE Derivative of Methadone
Analgesic for mild to moderate pain
Sometimes used in combination with aspirin or acetaminophen - ↑ analgesia
Also has antitussive action (used for cough)

33. SE Nausea, Constipation High doses can cause
Resp depression, Convulsion
Confusion, Hallucinations
Cardiotoxicity, Pul. edema
These effects can be antagonized by Naloxone.

34. CODEINE Good antitussive, Less analgesic than morphine Causes euphoria
Sedation
Addiction
So, many of the newer cough medications do not contain codeine
It has been replaced by dextrometharphan

35. PENTAZOCINE AGONIST ON Kappa AND Partial ANTAGONIST ON Mu & delta.
Moderate pain
Oral or parental
Less euphoric than morphine
Not used with morphine.

36. SE At high doses Increase B.P Hallucinations Night mares Tachycardia
Dizziness
Resp depression

37. BUPRENORPHINE AGONIST Mu receptors Parenteral Moderate pain
Morphine withdrawal
SE:
Resp depression
Nausea, dizziness

38. NALOXONE OPIOID ANTAGONIST
Rapidly reverse the effects of opioids, which can increase withdrawal symptoms
Reverse the coma and resp depression of opioid overdose.
IV route – In 30 sec shows significant changes in resp depression and coma.
Precipitates the withdrawal symptoms in morphine and heroin abusers.

39. NALTREXONE SAME AS NALOXONE Longer duration of action than naloxone
Oral route
Used in opiate dependence maintainance programs.