Narcotics and Analgesics

1. Narcotics and Analgesics Pharmacology By Linda Self

2. Pain • Universal, complex, subjective experience • Number one reason people take medication • Generally is related to some type of tissue damage and serves as a warning signal

3. Scope of the Problem • Increases as Baby Boomers age • 25 million people suffer acute pain related to surgery or injury • Chronic pain affects 250 million Americans • Is a multibillion dollar industry • Much ignorance exists about this complaint

4. Gate Control Theory of Pain • Gate control theory of pain is the idea that physical pain is not a direct result of activation of pain receptor neurons, but rather, its perception is modulated by interaction between different neurons

5. Gate Control Theory of Pain • Nerve fibers (A delta (fast channels)) and C fibers (slow channels) transmit pain impulses from the periphery • Impulses are intercepted in the dorsal horns of the spinal cord, the substantia gelatinosa • In this region, cells can be inhibited or facilitated to the T-cells (trigger cells)

6. Gate Control Theory of Pain cont. • When cells in the substantia gelatinosa are inhibited, the ‘gate’ to the brain is closed • When facilitated, the ‘gate’ to the brain is open

7. Gate Control Theory of Pain • Similar gating mechanisms exist in the nerve fibers descending from the thalamus and the cortex. These areas of the brain regulate thoughts and emotions. Thus, with a pain stimulus, one’s thoughts and emotions can actually modify the pain experience.

8. Pathophysiological Response • Tissue damage activates free nerve endings (nociceptors) of peripheral nerves • Pain signal is transmitted to the spinal cord, hypothalamus, and cerebral cortex • Pain is transmitted to spinal cord by A-delta fibers and C fibers

9. Pathophysiological Response • A-delta fibers transmit fast, sharp, well-localized pain signals • C fibers conduct the pain signal slowly and produce poorly localized, dull, or burning type of pain • Thalamus is the relay station for incoming stimuli, incl. pain

10. Pain Fibers and Pathways • A delta fibers found in the skin and muscle, myelinated, respond to mechanical stimuli. Produce intermittent pain. • C fibers distributed in the muscle as well as the periosteum and the viscera. These fibers are unmyelinated, conduct thermal, chemical and strong mechanical stimuli. Produce persistent pain.

11. Inhibitory and Facilitatory Mechanisms • Neurotransmitters—chemicals that exert inhibitory or excitatory activity at post-synaptic nerve cell membranes. Examples include: acetylcholine, norepinehprine, epinephrine, dopamin, and serotonin. • Neuromodulators—endogenous opiates. Hormones in brain. Alpha endorphins, beta endorphins and enkephalins. Help to relieve pain.

12. Opioid Receptors • Opioid receptors—binding sites not only for endogenous opiates but also for opioid analgesics to relieve pain. Several types of receptors: Mu, Kappa, Delta, Epsilon and Sigma.

13. Mu Receptors • Location: CNS incl. brainstem, limbic system, dorsal horn of spinal cord • Morphine sulfate and morphine sulfate agonists bind to Mu receptors

14. Sources of Pain • Nociceptive—free nerve endings that receive painful stimuli • Neuropathic –damaged nerves

15. Narcotic Analgesics • Relieve moderate to severe pain by inhibiting release of Substance P in central and peripheral nerves; reducing the perception of pain sensation in brain, producting sedation and decreasing emotional upsets associated with pain

16. Narcotic Analgesics • Can be given orally, IM, sub q, IV or even transdermally • Orally are metabolized by liver, excreted by kidney—caution if compromised • Morphine and meperidine produce metabolites • Widespread effects: CNS, Resp., GI

17. Narcotics—Mechanisms of Action • Bind to opioid receptors in brain and SC and even in periphery

18. Indications for Use • Before and during surgery • Before and during invasive diagnostic procedures • During labor and delivery • Tx acute pulmonary edema • Treating severe, nonproductive cough

19. Contraindications to Use • Respiratory depression • Chronic lung disease • Chronic liver or kidney disease • BPH • Increased intracranial pressure • Hypersensitivity reactions

20. Changing Philosophy on Pain • Undermedicated • Titrate to comfort

21. Management Considerations • age-specific considerations • Morphine often drug of choice—non-ceiling. Other nonceiling drugs include: hydromorphone, levorphanol and methadone • Use non-narcotic when able • Combinations may work by different mechanisms thus greater efficacy (e.g. Tylenol w/codeine)

22. Route selections • Oral preferred • IV most rapid—PCA allows self administration. Basal dosage. More effective, requires less dosing. • Epidural, intrathecal or local injection • Can use rectal suppositories or transdermal routes

23. Dosage • Dosages of narcotic analgesics should be reduced for clients receiving other CNS depressants such as other sedative-type drugs, antihistamines or sedating antianxiety medications

24. Scheduling • Give narcotics before encouraging turning, coughing and deep breathing in post-surgical patients • Automatic stop orders after 72h • In acute pain, narcotic analgesics are most effective when given parenterally and at start of pain

25. Individual Drugs • Agonists have activity on mu and kappa opioid receptors • Agonist/antagonists have agonist activity in some receptors; antagonists in others. Have lower abuse potential than pure agonists; because of antagonism—can produce withdrawal symptoms • Antagonists are antidote drugs

26. Agonists • Alfenta (alfentanil)—short duration • Codeine • Sublimaze or Duragesic (Fentanyl)—short duration • Dilaudid (hydromorphone) • Demerol (meperidine)—preferred in urinary and biliary colic, less resp. depression newborns • Morphine • OxyContin

27. Agonists cont. • Darvon (propoxyphene) • Ultram (tramadol) • Methadone

28. Agonists/Antagonists Have lower abuse potential than pure agonists • Buprenex (buprenorphine) • Nubain (nalbuphine) • Talwin (pentazocine) • Stadol (butohanol)—also in nasal spray

29. Antagonists • Revex (nalmefene)—longer duration of action than Narcan • Narcan (naloxone) • ReVia (naltrexone)-used in maintenance of opiate-free states in opiate addicts

30. Dietary and Herbal Supplements • Zostrix (capsaicin)—from cayenne peppers; topical indicated for post-herpetic neuralgia, neuropathic pain=Substance P

31. Cancer • Give on a regular schedule • Oral, rectal and transdermal are preferred over IV • Oxycodone and a non-narcotic analgesic may have additive effects • MS or other for severe pain • Long acting for chronic pain with fast acting meds for “break-through pain” • May use TCAs, anti-emetics, stool regimen

32. Management of Withdrawal Symptoms • Methadone • Clonidine (norepinephrine) • Gradually decrease dosing so not to cause withdrawal s/s

33. Analgesic,Antipyretic, and Anti-inflammatory Drugs • Mechanism of action—inactivate cyclo-oxygenases, enzymes required for the production of prostaglandins • ASA and traditional NSAIDs inhibitboth COX 1 and COX 2 • COX 1 is present in all tissues esp. GI, kidneys, endothelial cells and in platelets

34. Cox 1 cont. Prostaglandins important in: • Protection of kidneys and stomach • Regulate vascular tone and platelets in CV system

35. COX 2 • Found in brain, bone, kidneys, GI tract, and the female reproductive system • Overall, prostaglandins produced by COX 2 are associated with pain and inflammation

36. Actions of the COX’s • Act on hypothalamus to decrease response to pyrogens and reset the thermostat • Prevent prostaglandins from increasing the pain and edema produced by other substances released by damaged cells • COX 1-Antiplatelet activity for life of platelet—7-10 days plus interfere w/blood coagulation and increase risk for bleeding

37. Indications for Use • Treat mild to moderate pain or inflammation • Musculoskeletal disorders; HA; dysmenorrhea, minor trauma and surgery • Low dose ASA for risk of MI or stroke • Celebrex is indicated for familial polyposis

38. Contraindications to Use • PUD • GI or bleeding disorders • Hypersensitivity reactions • Impaired renal function • If allergic to ASA • In children, ASA contraindicated in presence of viruses=Reye’s syndrome • Celebrex if allergic to sulfonamides

39. Reye’s • Seen in children under 15 after an acute viral illness • Results in encephalopathy, fatty infiltration of the liver, pancreas, kidneys, spleen, and lymph nodes • Cause is unknown

40. Contraindications • Toradol (ketoralac) not used in labor and delivery or during any major surgery • OTC preps contraindicated in alcoholics due to possible liver damage

41. Aspirin (ASA) • Home remedy for headaches, colds, influenza and other respiratory infections • For fever • For inflammation • ASA and COX 2 are ok, COX 2 have little effect on platelet function

42. ASA cont. • Poisoning can occur with large doses. Saturate the metabolic pathway, slow elimination and cause drug accumulation • If overdose, measure serum levels • Recognize s/s: N/V, fever, fluid and lyte deficiencies, tinnitus, decreased hearing, hyperventilation, confusion, visual changes>>>>delirium, stupor and coma

43. ASA salicylism • Gastric lavage • Activated charcoal • IV bicarbonate so more rapid excretion • hemodialysis

44. NSAIDS • Propionic acid derivatives such as ibuprofen, ketoprofen (Orudis), naproxen and fenoprofen (Nalfon) • Acetic acid derivatives include indomethacin (Indocin), sulindac (Clinoril) and tolmetin (Tolectin)---these drugs have more severe adverse reactions than the proprionic acid derivatives

45. NSAIDS • IV indomethacin is approved for the tx of patent ductus arteriosus in premature infants. • Remember: patent ductus is a communication between the pulmonary artery and the aorta

46. NSAIDS • Toradol (ketoralac) is used only for pain. Is the only NSAID that can be given by injection. Use limited to 5 days as can cause bleeding. • Oxicam drugs include Mobic (meloxacam) and Feldene (piroxicam) • Celebrex (celecoxib) • Affect bleeding only while drug is still in the system

47. Effects of Nonsteroidals on Other Drugs • Decrease effects of ACEI, beta blockers and diuretics • Affect sodium and water retention • Inhibit renal prostaglandin synthesis

48. Acetaminophen • Equal in effectiveness to ASA in analgesic and antipyretic effects • Lacks anti-inflammatory actions • Ethanol induces drug-metabolizing enzymes in liver. Resulting rapid metabolism of acetaminophen produces enough toxic metabolite to exceed glutathione. Need glutathione to inactivate toxic metabolites. P. 114

49. Acetaminophen Poisoning • Toxicity occurs with 20g or more. • Creates toxic metabolite that is inactivated by glutathione. • OD supply of glutathione is depleted and toxic metabolite damages liver cells • Not to exceed 4g/day • Treatment—gastric lavage, charcoal, antidote is Mucomyst (acetylcysteine). Provides cysteine, a precursor to glutethione.

50. Drugs used in Gout and Hyperuricemia • Zyloprim (allopurinol)—prevents or treats hyperuricemia • Uric acid is formed by purine metabolism and an enzyme xanthine oxidase. Allopurinol prevents formation by inhibiting xanthine oxidase.