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 inhibit both 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.

51. Antigout Medications
Colchicine—used to treat or prevent acute attacks of gout. Drug of choice for acute attacks. Decreases inflammation by affecting leukocytes.
Benemid (probenecid) increases urinary excretion of uric acid. Not effective in acute attacks.
Anturane (sulfinpyrazone) uricosuric similar to Benemid. Not for acute attacks.

52. Guidelines for Treating Gout
Maintenance drugs are Zyloprim, Benemid and Anturane
Colchicine needed for several weeks to prevent acute attacks while serum levels are being lowered
Need high fluid intake, alkaline urine to prevent renal calculi

53. Drugs Used for Migraines
Selective serotonin 5-HT1 receptor agonists
Increase serotonin in the brain
Constrict blood vessels
Contraindicated in patient’s with history of MI,, angina, uncontrolled htn.

54. Drugs used for migraines
Drugs vary in onset with sub q sumatriptan acting the most rapidly and starting within 10 minutes; most clients get relief within 1-2 hours
Drugs are metabolized in the liver by monoamine oxidase or by cytochrome p450 enzymes; sub q administrations causes more adverse effects than the oral drugs

55. Migraine Meds
Ergotamine tartrate—ergot alkaloid used only in tx of migraine
Work by constricting blood vessels
Most effective when given sublingual or by inhalation
Contraindicated in pregnancy, htn, PVD, CAD, renal or hepatic disease and even in severe infections

56. Guidelines for Treating Migraine
Start out with acetaminophen, aspirin, or other NSAIDs
Moderate to severe migraines, sumatriptan or other related drugs are useful
For severe and frequent migraines, prophylaxis is indicated. Use ASA and NSAIDs.

57. Guidelines for Treating migraines
For menstrual migraines, start tx one week before and during menses
Other drugs indicated for tx include beta adrenergic blocking agents such as Inderal

58. Guidelines for Treating Arthritis
Control pain and inflammation
Rest, exercise,and PT
Osteoarthritis—COX1, COX2, glucosamine, intraarticular injections of corticosteroids or hyaluronic acid (Synvisc) to act as shock absorber

59. Rheumatoid Arthritis NSAIDs Corticosteroids
Immunosuppressants—methotrexate
Enbrel, Remicade and Arava. Affect tumor necrosis factor and other cytokines.

60. Questions or Discussion