General Pharmacology

1. General Pharmacology 205b

3. Neuromuscular Blocking Agents (NMBAs) • Cause skeletal muscle weakness or paralysis for purpose of preventing movement

4. Neuromuscular Blocking Agents (NMBAs) • Cause skeletal muscle weakness or paralysis for purpose of preventing movement Two types • Depolarizing agents • Non-depolarizing agents

5. Non-Depolarizing Agents • Produce paralysis and muscle weakness by competing with acetylcholine for binding at the receptor site • Prevention of the binding of acetylcholine prevents depolarization of the site, thereby preventing muscle contraction • Action • Competitive inhibition of acetylcholine at muscle post-synaptic receptor site • Effects felt in 2 to 10 minutes and last for 30 to 60 minutes • May be reversed by cholinesterase inhibitors, e.g., Neostigmine • Generic Name Proprietary Name • Tubocurarine d-tubocurarine • PancuroniumPavulon • MetocurineMetubine • VecuroniumNorcuron • RocuroniumZemuron, Esmeron • Indications • - Need for longer term paralysis • - Patient-ventilator synchrony • - Muscle relaxation during surgery • - Indications • - Reduction of intracranial pressure • - Immobility in trauma patients- • - Minimize oxygen consumption Depolarizing Agents • Bind to acetylcholine receptor sites causing a post-synaptic membrane depolarization • Prevention of repolarization causes the post-synaptic ending to become refractory and unexcitable, resulting in muscle flaccidity Action • Prevents acetylcholine from binding at the receptor site • Shorter acting than non-depolarizing agents • Will cause total muscle paralysis in 60 to 90 seconds that lasts from 10 to 15 minutes • Do not have reversing agents Generic name Proprietary name SuccinylcholineAnectine Indications - Short acting paralytic ideal for intubation or similar procedures

6. Indications for NMBAs • Endotracheal intubation • Muscle relaxation during surgery • Enhancement of patient-ventilator synchrony • Reduction of intracranial pressure in intubated patients • Minimizes oxygen consumption • Facilitation of procedures or diagnostic studies • Maintenance of immobility, e.g., trauma patients (Flail Chest)

7. Depolarizing Agents • Bind to acetylcholine receptor sites causing a post-synaptic membrane depolarization

8. Depolarizing Agents • Prevention of repolarization causes the post-synaptic ending to become refractory and unexcitable, resulting in muscle flaccidity

9. Non-Depolarizing Agents • Produce paralysis and muscle weakness by competing with acetylcholine for binding at the receptor site

10. Non-Depolarizing Agents • Prevention of the binding of acetylcholine prevents depolarization of the site, thereby preventing muscle contraction

11. Indications for NMBAs • Endotracheal intubation • Muscle relaxation during surgery • Enhancement of patient-ventilator synchrony • Reduction of intracranial pressure in intubated patients

12. Indications for NMBAs • Minimize oxygen consumption • Facilitation of procedures or diagnostic studies • Maintenance of immobility, e.g., trauma patients

13. Depolarizing Agents • Generic name • Succinylcholine • Proprietary name • Anectine

14. Depolarizing Agents • Action • Prevents acetylcholine from binding at the receptor site • Shorter acting than non-depolarizing agents

15. Depolarizing Agents • Action • Will cause total muscle paralysis in 60 to 90 seconds that lasts from 10 to 15 minutes • Do not have reversing agents

16. Depolarizing Agents • Indications • Short acting paralytic ideal for intubation or similar procedures

17. Depolarizing Agents • Side effects and hazards • May induce sympathomimetic response • Tachycardia • Increase in blood pressure • Vagal response in repeated dosages leading to bradycardia and hypotension

18. Depolarizing Agents • Side effects and hazards • May induce sympathomimetic response • Make provoke release of histamines • Increase in intracranial pressure in patients with cerebral edema or head trauma

19. Depolarizing Agents • Side effects and hazards • May induce sympathomimetic response • Malignant hyperthermia – caused by genetic defect of muscle metabolism • Hypoventilation

20. Depolarizing Agents • Route of administration • Intravenous administration • Dosage • 1.0 to 1.5 mg/kg

21. Non-Depolarizing Agents

22. Non-Depolarizing Agents • Action • Competitive inhibition of acetylcholine at muscle post-synaptic receptor site • Effects felt in 2 to 10 minutes and last for 30 to 60 minutes • May be reversed by cholinesterase inhibitors, e.g., Neostigmine

23. Non-Depolarizing Agents • Indications • Need for longer term paralysis • Patient-ventilator synchrony • Muscle relaxation during surgery

24. Non-Depolarizing Agents • Indications • Reduction of intracranial pressure • Immobility in trauma patients • Minimize oxygen consumption

25. Non-Depolarizing Agents • Side effects and hazards • Vagolytic effects including tachycardia, increase in mean blood pressure, and increase in release of norepinephrine; seen most with Pancuronium

26. Non-Depolarizing Agents • Side effects and hazards • Release of histamine from mast cells • Vasodilation leading to flushed appearance • Reflex tachycardia • Bronchospasm • Hypoventilation

27. Non-Depolarizing Agents • Route of administration • Intravenous

28. Non-Depolarizing Agents • Dosage • Tubocurarine • 0.5 – 0.6 mg/kg infused at 0.08 – 0.12 mg/kg/hr • Pancuronium • 0.08 – 0.1 mg/kg infused at 1 µg/kg/min • Vecuronium • 0.1 – 0.2 mg/kg infused at 1 µg/kg/min

29. http://www.youtube.com/watch?v=W60QpiDjKag

30. Narcotics and Analgesics • Used for the relief of severe pain

31. Narcotics and Analgesics • Opioid analgesics – high potency • Morphine • Route of administration • Oral: (Adults > 50 kg) – 30 mg q3 – q4 hours • Intravenous: (Adults > 50 kg) • Single Dose: 4 – 10 mg q3 – q4 hours • Continuous: 0.8 – 10 mg/hr • Intramuscular: 4 – 10 mg q3 – q4 hours

32. Narcotics and Analgesics • Opioid Analgesics – high potency • Oxymorphone - (proprietary name – Numorphan) • Route of administration • Intravenous: 0.5 mg q3 – 6 hours • Intramuscular: 1.0 – 1.5 mg q3 – 6 hours

33. Narcotics and Analgesics • Opioid analgesics – high potency • Fentanyl - (proprietary name – Sublimaze) • Route of administration • Intravenous: 2 mcg/kg (moderate); 2 – 20 mcg/kg (high) • Intramuscular: same as IV • LOLLYPOP

34. Narcotics and Analgesics • Opioid analgesics – high potency • Methadone - (proprietary name – Dolophine) • Used to overcome Heroine addiction also • Route of administration • Oral: 10 mg • Intravenous: 5 mg

35. Methadone is mainly used in the treatment of opioid dependence. It has cross-tolerance with other opioids including heroin and morphine, offering very similar effects and a longer duration of effect. Oral doses of methadone can stabilise patients by mitigating opioid withdrawal syndrome. Higher doses of methadone can block the euphoric effects of heroin, morphine, and similar drugs. As a result, properly dosed methadone patients can reduce or stop altogether their use of these substances.

36. Narcotics and Analgesics • Opioid Analgesics – high potency • Hydromorphone - (proprietary name – Dilaudid) • Route of administration • Oral: 4 – 8 mg q3 – 4 hours • Intravenous • Single dose – 1.5 mg q3 – 4 hours • Continuous – 0.2 – 30 mg/hr • Intramuscular: 1.5 mg q3 – 4 hours

37. Narcotics and Analgesics • Opioid analgesics – intermediate potency • Meperidine - (proprietary name – Demerol) • Route of administration • Oral: 50 – 150 mg q3 – 4 hours • Intravenous • Single dose: 50 – 150 mg q3 – 4 hours • Continuous: 15 – 35 mg/hr • Intramuscular: 50 – 150 mg q3 – 4 hours

38. Narcotics and Analgesics • Opioid analgesics – intermediate potency • Oxycodone - (proprietary names – Percolone, Oxycontin; with acetaminophen – Percocet • Route of administration • Oral: 5 – 10 mg q3 – 4 hours • Oral: time release capsule – q12 hours

40. Narcotics and Analgesics • Opioid analgesics – low potency • Codeine - (proprietary name – Paveral) • Route of administration • Oral • Analgesic: 15 – 60 mg q3 – 6 hours • Antitussive: 10 – 20 mg q4 – 6 hours • Intravenous: 15 – 60 mg q4 – 6 hours • Intramuscular: 15 – 60 mg q4 – 6 hours

41. Narcotics and Analgesics • Opioid analgesics – low potency • Diphenoxylate - (proprietary name – Lomotil) • Route of administration • Oral: 5 mg 3 to 4 times daily initially, then 5 mg once Daily as needed

42. Narcotics and Analgesics • Opioid analgesics • Action – not completely understood, but affect neurotransmission at specific sites in the CNS, affect autonomic nervous system transmission

44. Narcotics and Analgesics • Opioid analgesics • Indications • Relief of pain • Fentanyl used as analgesic supplement to general anesthesia • Methadone used as substitute for heroin, etc

45. Narcotics and Analgesics • Opioid analgesics • Side effects and hazards • Hypotension • Transient hyperglycemia • Depression of respiratory system • Cough reflex decreased • Nausea and vomiting

46. Narcotics and Analgesics • Opioid analgesics • Contraindications • Hypersensitivity/allergy to agent • Head trauma

47. Narcotics and Analgesics • Opioid analgesics • Route of administration • Oral (PO) • Intravenous (IV) • Intramuscular (IM) • Subcutaneous (SubQ)

48. Narcotic Antagonists • Action • Competitive replacement of narcotic from receptor site • Indication • Reversal of the effects of a narcotic • http://www.youtube.com/watch?v=U1frPJoWtkw

49. Narcotic Antagonists • Partial antagonists • Side effects • Cause narcotic-like effects in absence of a narcotic • Increased respiratory depression in non-narcotic overdose

50. NarcoticAntagonists • Partial antagonists • Nalorphine - (proprietary name – Nalline) • Route of administration • Initial dose: IV 5 to 10 mg • IV drip: 5 to 10 mg in 5% glucose solution