Pharmacology: Opioid Analgesics

1. Classification of Pain:

• By mechanism:

• Neuropathic pain (functional pain): due to nerve damage, abnormal nerve activity.

• Pathological pain

• Pain from psychological origin

• Neuropathic pain includes:

• Somatic pain: skin, bones, muscles,…

• Visceral pain: intestines, pancreas, liver.

• Pain neurotransmitters:

• Substance P

• CGRP

• Pain from psychological origin:

• Due to bodily or internal sensation

• Pain due to obsession

• Atypical, no clear location

• Common pain from psychological origin:

• Hysteria

• Mood disorders.

• Self-hypnosis about illness

• Schizophrenia

2. Medications for treating and controlling pain:

• Opioids

• NSAIDs & paracetamol

• Local anesthetics

• Neuropathic pain relievers

• Other medications

3. Opioids? Opiates?

• Opioids: any substance that has effects similar to morphine.

• Opiates: morphine and substances from opium resin

4. Group of alkaloids from nature:

• Morphine and codeine

5. Group of semi-synthetic from morphine:

• Codeine, codethylin, pholcodin, dextromethorphan.

• Oxymorphine, oxycodon, hydromorphon, diacetylmorphin.

6. Group of synthetic:

• Pethidin, tramadol, methadone, dextropropoxyphen, tentanyl

7. Endogenous opioids:

• Beta-endorphin, dynorphin, Leu-enkaphelin

8. Opioid Mechanism:

• Inhibition of AC leading to reduced cAMP, reducing pain substances like substance P and CGRP.

9. How many types of opioid receptors are there?

• 3 types:

• MOR (most important)

• DOR

• KOR

10. Effects of opioids on MOR receptor:

• Pain relief at the spinal cord, at the spinal cord

• Peripheral pain relief

• Respiratory depression

• Miosis

• Decreased bowel motility

• Euphoria

• Sedation

• Physical dependence

11. Effects of opioids on DOR receptor:

• Pain relief at the spinal cord

• Respiratory depression

• Decreased bowel motility

12. Effects of opioids on KOR receptor:

• Pain relief at the spinal cord

• Peripheral pain relief

• Agitation and hallucinations

• Sedation

13. Full agonists:

• Just learn from above :))))

14. What are endogenous opioids?

• Peptide form

• Distributed widely in the body

15. Opioid absorption:

• Easily passes through SC, IM, dura mater, spinal cord

• Through nasal mucosa, mouth, skin

• PO: good absorption but high first-pass metabolism through the liver

16. Opioid distribution:

• 1/3 binds to plasma proteins.

• Rapidly enters the brain, kidneys, liver, spleen

17. Opioid metabolism:

• Glucuronic conjugation for potent action

• Ester: heroin, remifentanil, meperidin

• Codeine, oxycodon, hydrocodon–> CYP2D6–> stronger

• Phenylpiperidin (meperidin, fentanyl, alfentanil, sufentanil): oxidized through the liver

18. Elimination:

• Glucuronic conjugation

19. Analgesic effect:

• MOR and DOR

• Specific, no loss of consciousness and sensory disturbance.

• Reduce acute and chronic pain

• Poor for pain of nervous system origin

20. Euphoric effect:

• MOR

• Causes extreme pleasure

21. Sedative and hypnotic effect:

• Lower dose than pain relief

• Due to phenanthrene frame, elderly

22. Respiratory depression at therapeutic doses and increases with dose:

• MOR and DOR

• Reduced CO2 response–> Inhibition of respiratory center

• Occurs at therapeutic doses, when the patient is still conscious –> pay attention to asthma, COPD.

23. Inhibition of the cough center in the medulla:

• Not related to pain relief, respiratory depression

• OH phenol at position 3 of morphine

• Causes mucus accumulation and lung collapse

24. Nausea and vomiting:

• MOR

• Stimulation of CTZ in the medulla

25. Miosis:

• Stimulation of oculomotor nerve through MOR and DOR

• Diagnostic criterion for opioid overdose or addiction.

26. Effects on the central nervous system include:

• Pain relief: stimulates MOR and DOR

• Euphoria: stimulates MOR

• Sedation and hypnosis

• Respiratory depression at therapeutic doses and increases with dose: Stimulates MOR and DOR

• Inhibition of the cough center in the medulla

• Nausea and vomiting: Stimulates MOR

• Miosis

27. What effects stimulate MOR on the CNS:

• Pain relief

• Euphoria

• Respiratory depression at therapeutic doses and increases with dose

• Nausea and vomiting

28. What effects stimulate MOR and DOR on the CNS:

• Pain relief

• Respiratory depression at therapeutic doses and increases with dose

29. Peripheral effects:

• Cardiovascular

• Gastrointestinal: Stimulates MOR and DOR

• Urinary, reproductive

30. Effects on the cardiovascular system:

• High doses for anesthesia–> inhibition of the vasomotor center–> hypotension and bradycardia

• When respiratory depression occurs –> cerebral vasodilation–> increased intracranial pressure.

31. Effects on the gastrointestinal system:

• Increased muscle tone and decreased bowel motility–> constipation

• Reduced secretion

32. Effects on the urinary, reproductive system:

• Causes urinary retention and prolongs labor

33. Symptoms of acute poisoning:

• Miosis, hypothermia

34. Symptoms of chronic poisoning:

• Mydriasis, fever.

35. Acute poisoning dose:

• 0.05/0.1-0.3g

36. Indications:

• Pain relief for severe, continuous, acute pain

• Acute pulmonary edema, severe angina pectoris with acute pulmonary edema

37. Cough relief:

• Codeine

• Dextromethorphan

38. Diarrhea treatment:

• Diphenoxylate + atropine

• Loperamide

39. Surgery:

• Premedication: 0.1-0.2mg SC/IM morphine

• Neuroleptanalgesia: Fetanyl + diazepam

40. Chills:

• Meperidin

41. Contraindications for opioids:

• Acute abdominal pain of unknown origin

• Morphine + Pentazocin–> reduced effect, withdrawal syndrome

• Respiratory failure

• Liver and kidney failure

• Head injury

• Alcohol, barbiturate, BZD and other respiratory depressant poisoning.

• Te<5 years old, pregnant women

• Patients with Addison’s disease, hypothyroidism

42. Methadone dosage form:

• PO: 60mg

• IM 10mg

• Rectal (IR)

43. T1/2, methadone indications:

• T1/2: 15-60h

• Indications:

• Chronic pain

• Morphine withdrawal

44. Fentanyl:

• Pain relief is 100 times that of morphine

• Highly lipid soluble

• Causes strong respiratory depression, strong addiction

• Used in neuroleptanalgesia, pain relief for surgery.

• Dosage forms: IV, IM, intrathecal injection, lozenge, inhalation

45. Opioid antagonists:

• Treatment of acute poisoning due to overdose, after surgery with fentanyl.

• Treatment of respiratory depression

• Causes withdrawal syndrome in addicts –> diagnosis of addiction

• Used for therapeutic purposes in patients receiving opioids

• Naloxone, naltrexone: pure antagonists

46. Morphine antagonists:

• Nalorphine

• Naloxone

• Naltrexone

47. Psychotropic pain relievers:

• Amitriptyline

• Fluoxetine

• Mirtazapine

• Sertraline