1. 15
Analgesic, Antipyretic, and Anti-Inflammatory Agents

2. Terms
Analgesics: relieve pain without significantly disturbing consciousness or altering actions of sensory nerves
Antipyretics: reduce fever
Some of these types of drugs also have anti-inflammatory properties

3. Pain
Central nervous system’s reaction to potentially harmful stimuli characterized by physical discomfort
Acute: severe pain with sudden onset; serves as early warning to seek medical help to prevent damage to body
Chronic: lasting a long time or marked by frequent recurrence

4. Pain Stimuli
May result from inflammatory process that causes tissue injury
Histamine, prostaglandins, serotonin, and bradykinin are released and initiate action potential along sensory nerve fiber.
Nociceptors (pain receptors) are activated and message sent to brain cortex.
Appropriate autonomic and reflect responses are activated.

5. Figure 15-1 Reflex responses to pain.

6. Neurotransmitters
Endorphins and enkephalins are neurotransmitters that can bind with opiate receptors in the CNS and inhibit transmission of pain impulses.

7. Figure 15-2 Endogenous analgesic compounds released after pain stimuli.

8. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Group of drugs that include salicylates and antipyretics
Used to relieve inflammation, swelling, stiffness, and joint pain of arthritis; treat menstrual cramps, gout attacks, bursitis, tendonitis, sprains, and muscle strains
Mechanism of action: believed to act by blocking prostaglandin synthesis

9. Aspirin (Bayer, Others): Uses
Most common salicylate
Used as an antipyretic and analgesic to relieve pain of headache, fever, muscular aches and pains
One of safest and most effective drugs to relieve fever

10. Aspirin: Adverse Effects
Uncommon: dyspepsia, nausea, vomiting, occult bleeding
Serious: massive GI hemorrhage at high doses and in elderly patients

11. Aspirin: Contraindications
Avoid in patients with GI disturbances, particularly hemorrhaging ulcers.
Use with caution in patients on anticoagulant therapy or who are taking uricosurics.
Aspirin interacts with antidiabetic drugs and oral anticoagulants.

12. Aspirin and Reye’s Syndrome
Use of aspirin in treatment of fever in children who have chickenpox may cause Reye’s syndrome.
Aspirin should not be prescribed for children who have upper respiratory viral infections or chickenpox.

13. Salicylates and GI Bleeding
Elderly patients who are vulnerable to GI bleeding should not take salicylates.
Patients should request emergency help for bloody urine, loss of hearing or vision, confusion, convulsions, diarrhea, difficulty swallowing, dizziness, severe drowsiness, increased thirst, nausea or vomiting.

14. Aspirin: Patient Information
Advise menstruating women to avoid aspirin if menstrual bleeding is heavy.
Advise pregnant women to avoid aspirin in last trimester and during lactation.
Instruct patients to discontinue aspirin 1 week before or after surgery.
Instruct patients to avoid drinking alcohol while taking aspirin.

15. Ibuprofen (Motrin, Advil): Uses
Nonsalicylate used for analgesic, anti-inflammatory, and antipyretic activities
Rheumatoid arthritis, osteoarthritis, and arthritis
Mild to moderate pain, dysmenorrhea, and fever

16. Ibuprofen: Adverse Effects
Common: nausea, occult blood loss, peptic ulceration, diarrhea, constipation, abdominal pain, dyspepsia, flatulence, heartburn, decreased appetite
Serious: azotemia, cystitis, hematuria, aplastic anemia, hypoglycemia, hyperkalemia

17. Ibuprofen: Contraindications
Avoid in pregnant patients and those with angioedema, nasal polyps, or bronchospastic reaction to NSAIDs.
Use cautiously in patients with GI disorders, hepatic or renal disease, hypertension, or preexisting asthma.
Ibuprofen may interact with antihypertensives, furosemide, and thiazide diuretics.

18. Ibuprofen: Patient Information
Breastfeeding women should not take ibuprofen.
Advise patients to notify their physician if blood appears in stool, vomitus, or urine, or if they have a new skin rash, pruritus, or jaundice.
Warn patients not to consume alcohol or take aspirin or other NSAIDs with ibuprofen.

19. Indomethacin (Indocin): Uses
Treatment of rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, bursitis, tendonitis, gouty arthritis, and patent ductus arteriosus in premature infants

20. Indomethacin: Adverse Effects
Common: GI ulceration, hemorrhage, GI bleeding, increased pain in ulcerative colitis, gastritis, nausea, and vomiting
Serious: hepatic toxicity, aplastic anemia, hemolytic anemia, asthma, urticaria, depression, mental confusion, coma, convulsions

21. Indomethacin: Contraindications
Avoid in patients with history of aspirin- or NSAID-induced asthma, rhinitis, or urticaria.
Avoid in pregnant or breastfeeding women.
Use cautiously in patients with epilepsy, parkinsonism, and hepatic or renal disease.

22. Indomethacin: Contraindications
Interacts with aminoglycosides, cyclosporine, methotrexate, antihypertensives, furosemide, and thiazide diuretics

23. Indomethacin: Patient Information
Advise patients to notify their physician if they develop skin rash, breathing problems, or visual disturbances (signs of hypersensitivity).

24. Selective COX-2 Inhibitors: Mechanism of Action
One group of NSAIDs that selectively inhibits cyclooxygenase-2 (COX-2) (enzymes required to produce prostaglandins from arachidonic acid; appear to be made in macrophages in response to local tissue damage)

25. Table 15-1 Selective COX-2 Inhibitors

26. COX-2 Inhibitors: Uses
Celecoxib (Celebrex): treatment of osteoarthritis and rheumatoid arthritis
Newer COX-2 inhibitor, meloxicam (Mobic) is labeled for treatment of osteoarthritis.

27. COX-2 Inhibitors: Adverse Effects
Common: abdominal pain, dyspepsia, diarrhea
Serious: myocardial infarction and stroke

28. COX-2 Inhibitors: Contraindications
Use cautiously in patients with asthma, hypertension, lower extremity edema, congestive heart failure, or fluid retention, and in pregnant or lactating women.
Avoid in patients with hepatic impairment or advanced renal disease.
Interacts with ACE inhibitors, fluconazole, and lithium.

29. COX-2 Inhibitors: Patient Information
Advise patients to report unexplained weight gain, skin rash, nausea, fatigue, lethargy, jaundice, flu-like symptoms, black tarry stools, or upper GI distress
Instruct patients to avoid aspirin, other NSAIDs, alcohol, and tobacco when taking meloxicam. Avoid celecoxib during the third trimester of pregnancy

30. Acetaminophen (Tylenol): Mechanism of Action
Thought to be inhibition of prostaglandin in peripheral nervous system, making sensory neurons less likely to receive pain signals
Acetaminophen blocks peripheral pain impulses to lesser degree than other NSAIDs; lacks anti-inflammatory action of salicylates.

31. Acetaminophen: Uses
Treatment of musculoskeletal pain, headache, dysmenorrhea, myalgias, neuralgias, arthritic and rheumatic conditions
Reduces fever and discomfort of common cold and viral infections

32. Acetaminophen: Adverse Effects
Usually well-tolerated in therapeutic doses
Long-term use: skin eruptions and urticaria, hypotension, hepatotoxicity
Overdose: hepatotoxicity, coma, internal bleeding (antidote is acetylcysteine)

33. Acetaminophen: Contraindications
Use cautiously in children younger than 3 years.
Avoid in patients with alcoholism, malnutrition, or thrombocytopenia.
Safety during pregnancy and lactation is not established.
Interacts with barbiturates, carbamazepine, phenytoin, and rifampin

34. Acetaminophen: Patient Information
Advise patients to avoid alcohol because regular consumption of alcohol and acetaminophen may cause severe liver damage and even death.

35. Mechanism of Action of Acetaminophen Animation

36. Opiates: Mechanism of Action
Opiates: drugs derived from opium poppies; morphine and codeine
Opioid: general term referring to natural, synthetic, or endogenous morphine-related substances
Analgesic effects produced by binding to opioid receptors (mu, kappa, and delta); mostly affect mu receptors

37. Table 15-2 Classifications of Opioid Analgesics

38. Table 15-2 (continued) Classifications of Opioid Analgesics

39. Table 15-2 (continued) Classifications of Opioid Analgesics

40. Table 15-2 (continued) Classifications of Opioid Analgesics

41. Morphine (Astramorph, Others): Uses
Management of all types of moderate to severe pain
Derivatives are used for cough inhibition, treatment of GI pain, relieving pain of myocardial infarction

42. Morphine: Adverse Effects
Common: nausea and vomiting, constipation, dry mouth, biliary tract spasms, dizziness, sedation, pruritus
Serious: respiratory depression
Physical and psychological dependence

43. Morphine: Contraindications
Avoid in patients with asthma, emphysema, head injury, increased intracranial pressure, severe liver or kidney dysfunction, acute ulcerative colitis, or convulsive disorders.
Use cautiously in patients with prostatic hypertrophy.
Interacts with alcohol, monoamine oxidase inhibitors, meperidine

44. Morphine: Patient Information
Instruct patients not to take morphine if breathing rate is less than 12 breaths per minute or systolic blood pressure is less than 110 mm Hg.
Advise patients to request symptomatic relief for constipation and to drink plenty of water.

45. Mechanism of Action of Morphine Animation

46. Codeine: Uses Used to induce sleep in presence of mild pain
Used as analgesic, sedative, hypnotic, antiperistaltic, and antitussive
Commonly given in combination with aspirin, acetaminophen, and other agents (Schedule III drug in combination)
Schedule II drug (alone)

47. Codeine: Adverse Effects
Common: postural hypotension, nausea and vomiting, constipation, miosis
Serious: cortical and respiratory depression
Tolerance, dependence, and addiction can occur

48. Codeine: Contraindications
Avoid in patients with respiratory insufficiency, bronchial asthma, and increased intracranial pressure.
Interacts with alcohol, cimetidine, antidepressants, and neuroleptics

49. Codeine: Patient Information
Instruct patients to take only as directed because overuse can lead to dependence.
Advise patients to avoid alcohol and other CNS depressants.
Advise patients that urine retention and constipation can occur and to rise slowly from lying position to avoid dizziness.

50. Hydrocodone (Hycodan): Mechanism of Action
Morphine derivative similar to codeine
Suppresses cough reflex by direct action on cough center in medulla
Acts as CNS depressant to relieve moderate to severe pain

51. Hydrocodone: Uses
Used to relieve nonproductive cough and to relieve moderate to severe pain

52. Hydrocodone: Adverse Effects
Common: dry mouth, nausea and vomiting, constipation, sedation, dizziness, drowsiness
Serious: respiratory depression

53. Hydrocodone: Contraindications
Avoid in patients with hypersensitivity or in lactating women.
Use cautiously in patients with asthma, emphysema, history of drug abuse, and respiratory depression.
Interacts with alcohol and other CNS depressants
Can be used in children younger than 1 year and in pregnant women

54. Hydrocodone: Patient Information
Instruct patients to avoid hazardous activities.
Advise patients to drink plenty of fluids and to take only as directed.

55. Oxycodone (OxyContin): Mechanism of Action
Precise mechanism not clear
Binds to specific receptors in various sites of CNS to alter both perception of pain and emotional response to pain
Oxycodone is as potent as morphine and 10–12 times more potent than codeine.
Schedule II drug

56. Oxycodone: Uses
Relief of moderate to severe pain (bursitis, dislocations, simple fractures, other injuries)
Postoperative and postpartum pain

57. Oxycodone: Adverse Effects
Common: euphoria, dysphoria, light-headedness, dizziness, sedation, anorexia, nausea and vomiting, constipation
Serious: jaundice, hepatotoxicity, respiratory depression

58. Oxycodone: Contraindications
Avoid in pregnancy and lactation, and in children.
Use cautiously in patients with alcoholism, renal or hepatic disease, viral infections, ulcerative colitis, gallbladder disease, head injury, acute abdominal conditions, hypothyroidism, prostatic hypertrophy, and respiratory depression.

59. Oxycodone: Contraindications
Interacts with antidepressants, anxiolytics, antihistamines, pain relievers, seizure medications, and muscle relaxants

60. Oxycodone: Patient Information
Instruct patients to avoid hazardous activities and alcohol.
Advise patients to take the drug in the form prescribed without crushing, chewing, or breaking.
Advise patients to take only the dose prescribed.

61. Mechanism of Action of Oxycodone Animation

62. Age Differences in Narcotic Metabolism
Metabolism of narcotics is slower in elderly patients, leading to possible confusion and respiratory depression.
Children and infants eliminate narcotics at a different rate than do adults, so dosing is difficult.

63. Opioid Antagonists
Naloxone (Narcan): prescribed for narcotic overdose, reversal of narcotic respiratory depression
Naltrexone (Trexan, ReVia): adjunct for maintaining opioid-free state in detoxified addicts; management of alcohol dependence

64. Buprenorphine (Buprenex): Mechanism of Action
Synthetic centrally acting narcotic analgesic
Opiate agonist–antagonist
Has high affinity for mu-opioid receptors (agonist action)
Acts as antagonist at kappa-opiate receptors in CNS

65. Buprenorphine: Uses Treatment of moderate to severe postoperative pain
Administered for pain associated with cancer, accidental trauma, urethral calculi, myocardial infarction

66. Buprenorphine: Adverse Effects
Common: sedation, drowsiness, vertigo, dizziness, headache, amnesia, euphoria, insomnia

67. Buprenorphine: Contraindications
Safety during pregnancy, lactation, and in children younger than 13 years is not established
Interacts with alcohol and diazepam

68. Buprenorphine: Patient Information
Instruct patients to avoid driving or engaging in hazardous activities.
Advise patients to avoid alcohol and other CNS depressants.
Advise female patients to not breast feed.

69. Fentanyl (Duragesic, Sublimaze)
Analgesic and sedative used during operative and perioperative periods
Interacts with alcohol, other CNS depressants, monoamine oxidase inhibitors

70. Fentanyl (Duragesic, Sublimaze)
Instruct postoperative patients to report muscle rigidity or weakness; unusual postoperative muscle movement of the extremities, eyes, or neck; or breathing difficulties.

71. Meperidine (Demerol)
Synthetic opioid that acts on the CNS and organs composed of smooth muscle
Principally induces analgesia and sedation
Used preoperatively, to treat moderate to severe pain, as obstetric analgesia and to support anesthesia

72. Meperidine: Adverse Effects
Common: dizziness, sedation, nausea and vomiting, sweating
Serious: respiratory depression or arrest, circulatory depression, shock, cardiac arrest

73. Meperidine: Contraindications
Avoid in patients taking monoamine oxidase inhibitors.
Use cautiously in patients taking other opioid analgesics, general anesthetics, phenothiazines, sedatives, tricyclic antidepressants, and other CNS depressants.

74. Meperidine: Patient Information
Advise patients to move carefully and avoid smoking.
Instruct patients to avoid driving and other hazardous activities until drowsiness and dizziness have passed.
Instruct patients to avoid alcohol and to not breast feed.

75. Methadone (Dolophine)
Synthetic opioid analgesic that binds with opiate receptors in the CNS, altering perception and emotional response to pain
Used for relief of moderate to severe pain and for detoxification of opioid addicts

76. Methadone (Dolophine)
Adverse effects, contraindications, and patient teaching similar to those of fentanyl

77. Pentazocine (Talwin)
Synthetic narcotic agonist–antagonist analgesic (Schedule IV)
Action similar to morphine
For control of moderate to severe pain, preoperative analgesia or sedation, and as supplement to surgical anesthesia

78. Pentazocine (Talwin)
Adverse effects, contraindications, patient information similar to those of other opioids