Pain Management

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CHAPTER 18 Pain Management

I. DefinitionPain is a common condition that manifests as many different forms and severities. Pain is defined as an unpleasant sensory and emotional experience associated with damage to body tissues, including organs, bones, and muscles. Acute pain occurs after tissue injury and often resolves soon after the body has healed. Chronic pain occurs either from continual damage or constant stimulation of nerve fibers lasting at least 6 months. The cause of some chronic pain may not be known. The treatment of pain depends upon the causes of the pain and the individual’s tolerance of pain.

II. Types of Pain The different types of pain include acute pain, chronic pain, nerve pain, nociceptive pain, and psychogenic pain.

A. Acute pain: results from injury to tissues and/or inflammation. Acute pain generally has a sudden onset. For example, after trauma or surgery, acute pain may be accompanied by anxiety or emotional distress.

B. Chronic pain: Pain signals keep firing in the nervous system for weeks, months, even years. Initial injuries, such as an infection, sprained back, or sprained muscle, may cause acute pain that may lead to chronic pain. There may be an ongoing cause of pain, such as in back pain, arthritis, diabetes (diabetic neuropathy), or cancer.

C. Nerve pain (neuropathic pain): pressure or damage to nerves or the spinal cord. Nerve pain can be caused by tumors; injury, such as during surgery or falls; chemical damage, such as with mercury, lead, chemotherapy, and radiation; or viruses, such as herpes zoster (shingles or chicken pox).

D. Nociceptive pain: aching, sharp, or throbbing pain that includes somatic pain (body surface, deep tissues) and visceral pain (not well localized, pressure-like, deep squeezing)

E. Psychogenic pain: mostly related to psychological disorders. Goals of treatment are to improve comfort and physical and psychological function. Treatment includes antidepressants, psychological counseling.

III. Acute Pain Control

A. Pain management required for a short duration (e.g., following surgery, accident)

B. Known end period for required pain management

C. Monitor for addiction

IV. Chronic Pain Control

A. Disease state management (e.g., cancer, rheumatoid arthritis, osteoarthritis)

B. Pain management required for a long period, possibly until end of life

C. Acute control (e.g., breakthrough pain) may be required for short duration events during chronic control

D. Monitor for addiction

V. Pyramid Control

A. Start with mild agents, increase to narcotics

B. Ceiling effect (i.e., a limited dose requirement) with most analgesics

1. Narcotics (opioids) like morphine do not have a ceiling effect.

C. Controlled substances potentially addictive

D. Start with lowest doses possible

VII. Patient Management

A. Identify the source of pain.

B. Eliminate the underlying cause.

C. Select the most effective analgesic with the fewest side effects.

D. Properly titrate the dose for each patient and administer for an appropriate duration.

E. Always consider around-the-clock regimens for acute and chronic pain.

F. Use as-needed regimens for breakthrough pain.

G. Assess for side effects of analgesics (i.e., constipation with opioids).

H. Avoid excessive sedation by titrating the opioids tentatively.

I. Adjust the route of administration to the needs of each patient, using oral administration whenever possible.

J. Use equianalgesic doses when converting from one agent to another and titrate accordingly.

K. Consider antidepressants, anticonvulsants, or opioids for neuropathic pain.

L. Consider a multidisciplinary approach: pharmacologic + nonpharmacologic therapies.

VIII. Pharmacologic Therapies

B. Nonsteroidal anti-inflammatory drugs (NSAIDs) (Table 18-1)

1. Mechanism of action: nonspecific inhibition of cyclooxygenase (COX)-2 and COX-1 receptors, decreasing prostaglandins produced by the arachidonic acid cascade in response to noxious stimuli, thereby decreasing the number of pain impulses received by the central nervous system (CNS)

2. Use lowest effective dose for shortest possible duration; OTC NSAID not to exceed 10 days unless a physician directs otherwise

3. Caution: Avoid in patients with recent coronary artery bypass graft surgery (CABG). Caution in bleeding disorders, hepatic or renal disease, GI disorders; women who are pregnant or lactating or who are trying to conceive

4. Interactions: Methotrexate, medications which increase the risk of bleeding (anticoagulants, e.g., warfarin), medications causing liver or renal damage, medications causing GI disturbance, diuretics, lithium, aspirin,antihypertensive agents

5. Toxicity and side effects: bleeding, upset stomach, ulcers, nausea, vomiting, diarrhea, constipation, fluid retention, edema, tinnitus, increased risk of bleeding, increased risk of Reye syndrome in children

1. Prototype of the salicylates; also a nonsteroidal anti-inflammatory drug (NSAID)

2. Mechanism of action: irreversibly inhibits COX-1 and COX-2, decreasing prostaglandins produced by the arachidonic acid cascade in response to noxious stimuli, thereby decreasing the number of pain impulses received by the CNS

3. Maximum dose 5400 mg per day; less in some situations

4. Caution: bleeding disorders, hepatic and/or renal disease, GI disorders, use in children, pregnancy, fertility, lactation

5. Interactions: other medications that increase the risk of bleeding, medications containing salicylates, medications causing GI disturbance

6. Toxicity and side effects: increased risk of Reye syndrome in children, GI disturbance, GI bleeding and/or mucosal lesions, otic effects (tinnitus and hearing loss at high doses), hepatotoxicity, nephrotoxicity is rare, and increased risk of bleeding

D. COX-2 inhibitors (a subset of NSAID class) (Table 18-2)

1. Mechanism of action: selectively inhibits the activity of the enzyme COX-2, resulting in a decreased prostaglandin production, thereby decreasing the number of pain impulses received by the CNS

2. May have fewer GI effects than COX-1 inhibitors

3. Common side effects: peripheral edema, abdominal pain, diarrhea, dyspepsia, flatulence, nausea, back pain, dizziness, headache, insomnia, pharyngitis, rhinitis, sinusitis

4. Caution: same risks as traditional NSAIDs

5. Avoid in patients with recent coronary artery bypass graft surgery (CABG), creatinine clearance <30 mL/min

6. Interactions: medications that increase the risk of bleeding, hepatotoxic or nephrotoxic medications, medications that cause GI disturbance

7. Toxicity: GI disturbance, hepatotoxicity, nephrotoxicity, increased risk of bleeding GI ulceration, cardiovascular events, including stroke**

E. Narcotic analgesics (Table 18-3)

a. Mechanism of action: binds to opiate receptors in the CNS causing inhibition on ascending pain pathways thereby altering the perception of and response to pain

b. Caution: physically addictive, controlled substances

c. Interactions: additive CNS depression with alcohol

d. Toxicity and side effects: constipation, drowsiness, nausea/vomiting, sedation, itching, difficulty urinating, miosis, toxicity may result in respiratory depression

e. Antidote for opioid overdose: naloxone (Narcan)

3. Hydromorphone (Dilaudid)

a. Mechanism of action: Similar to morphine

1) Faster onset of action and shorter duration of action

2) 8–10 times stronger than morphine

b. Used for moderate to severe pain

4. Codeine (methyl morphine)

a. Mechanism of action: similar to morphine but not as potent and shorter duration of action

b. Combination therapy with other agents in same formulation

c. Also used for suppressive therapy of cough

d. Used for moderate pain

e. Must monitor contents when using multiple agents

f. Schedule II or III

g. Adverse effects: constipation, nausea, and vomiting

5. Synthetic and semisynthetic narcotics

b. Meperidine (Demerol)

1) No maximum dose: must titrate up slowly to lessen side effects, especially respiratory depression

2) Can suppress cough reflex

3) Useful in treatment of rigors

5) Contraindicated for use with monoamine oxidase inhibitors (MAOIs)

6) Adverse effects: itching, sweating, and hypotension (caused by histamine release)

7) Toxic metabolite = normeperidine; patient must have good renal function to use medication

c. Propoxyphene (Darvon)

1) Combination therapy with other agents in same formulation

2) Must monitor contents when using multiple agents

3) Less addictive than opioids

4) Used for moderate pain

6) Adverse effects: constipation, GI upset, CNS disturbance

3. Drugs used in treatment of narcotic dependency

a. Methadone (Dolophine)

1) Mechanism of action: mu-opioid receptor agonist activity; synthetic drug

2) Used for detoxification and maintenance treatment of opioid addiction

3) Also used for pain relief

4) Patients must be in authorized methadone program; prescribers who prescribe for narcotic dependency must have special DEA registration; such registration is not needed for those using methadone for pain

5) High abuse potential

G. Antidepressants used for pain management

1. Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) have been found to provide some relief depending on the type of pain to be treated.

2. Used for chronic pain (e.g., neuropathic pain). Some SSRIs used for fibromyalgia.

3. TCA examples: amitriptyline (Elavil), nortriptyline (Pamelor), desipramine (Norpramin)

4. Narrow therapeutic window for TCA

5. TCAs associated with side effects: sedation, orthostatic hypotension, urinary retention

H. Anticonvulsants used for pain management

1. Used for chronic pain (e.g., neuropathic pain)

2. Liver function tests (LFT) should be obtained at baseline and throughout use with many of these drugs (e.g., phenytoin, valproic acid, carbmazepine).

3. Examples: gabapentin (Neurontin); carbamazepine (Tegretol); phenytoin (Dilantin), valproic acid (Depakote), lamotrigine (Lamictal)

a. Gabapentin is the most promising with the fewest side effects.

1. Initial adult dose: 100 mg twice daily, may titrate up to 1200–2400 mg daily divided in three doses

I. Local anesthetics

1. Topical local anesthetics (e.g., Lidoderm, EMLA) are used for neuropathic pain and postherpetic neuralgia.

2. Use only on intact skin.

1. Over-the-counter (OTC) topical products: Zostrix, Axsain

2. Composed of an extract of chili peppers

3. Also used for rheumatoid arthritis and osteoarthritis

4. Rarely recommended due to overall poor efficacy

5. Adverse effect: burning at site of administration

K. Corticosteroids

1. May be used for neuropathic symptoms when associated with inflammation and edema

a. Also used for bone pain, spinal metastasis, rheumatoid arthritis, other acute inflammatory disorders

2. Example: dexamethasone commonly used

3. Many potential adverse effects: hyperglycemia, insomnia, GI irritation, psychosis, osteoporosis

L. Other neuropathic pain medications

Table 18-1 Nonsteroidal Anti-inflammatory Drugs (NSAID)

NSAID	Usual Oral Adult Doses	Comments
Ibuprofen (Motrin)	200–400 mg PO q4–6h prn	Maximum 1200 mg/day (OTC); 3200 mg/day (R_x)
Naproxen (Aleve, Naprosyn, Anaprox)	200–400 mg PO (initial dose), followed by 200 mg PO q8–12h	Maximum 600 mg/day (OTC); 1000 mg/day (R_x)
Diclofenac (Cataflam, Voltaren)	May initiate with 100 mg PO followed by 50 mg tid Delayed-release, 75–150 mg/day PO in divided doses
Etodolac (Lodine)	Immediate release 200–400 mg PO 6–8h prn	Maximum 1200 mg/day
Fenoprofen (Nalfon)	200 mg PO every 4–6h prn
Flurbiprofen (Ansaid)	Postoperative/dental pain 50 mg PO 4–6h prn
Ketoprofen (Orudis, Orudis KT, Oruvail)	12.5 mg PO 4–6h prn, may initiate with 25 mg	Maximum 75 mg/day (OTC); 300 mg/day (R_x)
Indomethacin	75–150 mg/day PO in 3 or 4 divided doses for 7–14 days
Nabumetone (Relafen)	1000–2000 mg/day PO divided 1 or 2 times
Ketorolac (Toradol)	Only used acutely following IV or IM dosing; give 20 mg × 1 dose, then 10 mg PO 4–6h prn	Maximum 40 mg/day PO; maximum combined duration of parenteral and oral routes is 5 days; if ≥65 years of age OR weight <50 kg do not exceed 10 mg PO 4–6h prn
Piroxicam (Feldene)	20 mg/day PO
Sulindac (Clinoril)	150–200 mg PO twice a day	Maximum 400 mg/day

Table 18-2 COX-2 Inhibitors—Adult Recommended Dose

COX-2 Inhibitors	Dose
Celecoxib (Celebrex)	For acute pain: initial dose 400 mg PO once plus one additional dose of 200 mg PO if needed on the first day; maintenance 200 mg PO twice a day as needed Arthritis, RA: 100–200 mg PO twice a day

Table 18-3 Actions of Opiate Receptors

Opiate Receptor	Action
Mu-1	Analgesia
Mu-2	Respiratory depression Euphoria Physical dependence Constipation
Delta	Analgesia
Sigma	Autonomic stimulation Dysphoria Hallucinations
Kappa	Analgesia Sedation Miosis
Epsilon	Analgesia

PATIENT PROFILE

Patient Initials: PB

Height: 5′ 11”

Allergies: Codeine (rash, itching)

Current: PB was admitted to the hospital via the trauma team with multiple large bone fractures due to a motorcycle accident. He broke his left leg, his left collarbone, some rib bones, and his left radius and ulna in the accident. He also has serious contusions over his body. He had orthopedic surgery for his fractures. One of the main immediate issues for postoperative care is providing adequate pain control as he heals and gets ready for extensive rehabilitation.

Medical History:

No chronic health problems; family practice clinic chart states occasional treatment for seasonal rhinitis (takes nonprescription Claritin during allergy season)

Social History:

Tobacco use: None.

Alcohol use: Frequent, drinks several beers per day

Current Medications: No regular medications at present time at home.

Postoperative medications include:

D5%/1/2NS with 20 mEq KCl per liter at 125 mL/h: each day 1L of these fluids with a vial of multivitamins and thiamine 100 mg

Cefazolin 1 gm IV q8h

Lorazepam 1 mg IV q4–6h as needed (PRN) for anxiety

Pain management consult for ordering of pain medications; morphine 10 mg IV given 10 minutes ago in the post anesthesia care unit (PACU).

PATIENT PROFILE QUESTIONS

2. The pain team decides that morphine will be used for the initial PCA regimen. Which of the following represents a practical initial PCA order for DB?

a. After the initial loading dose for acute pain control, begin morphine PCA at 1 mg bolus with a 10-minute lockout interval.

b. After the initial loading dose for acute pain control, begin morphine PCA at 10 mg bolus with an 8-minute lockout interval.

c. After the initial loading dose for acute pain control, begin morphine PCA at 0.05 mg/kg bolus with a 15-minute lockout interval.

Answer: a. A typical postoperative PCA morphine regimen begins with 0.5–2 mg boluses and 8–10 minute lockout intervals. Answer b would provide too-high and too-frequent dosing for PCA delivery, potentially resulting in overdosage. There is no weight-based analgesia dosage for morphine, and the lockout period is too long for a postoperative patient for option c to be practical.

3. After several weeks, DB is taking food well and recovering nicely despite his injuries. He still needs a significant amount of medication to manage his pain, especially during rehabilitation sessions. He will be released to home with a prescription for Percocet 5/325, 1 tablet PO q6h as needed for pain and a prescription for ibuprofen 400 mg PO q6h for inflammation and pain. What should patient counseling for DB regarding the Percocet prescription include?

I. The risk of medication dependence is overall very low for DB.

II. DB should avoid the use of alcohol because this can increase the side effects of Percocet such as dizziness, drowsiness, and difficulty breathing, or the risk for liver problems.

III. DB should not exceed the recommended dosage for Percocet and not take additional acetaminophen (e.g., Tylenol) because this could result in acetaminophen overdosage.

IV. Percocet may cause constipation; the use of stool softeners and the occasional use of a laxative may be needed to maintain bowel regularity.

a. II and III only

b. I, II, and III

c. All of the above

Answer: c. Appropriate counseling regarding the use of Percocet (oxycodone-acetaminophen combination) would include all of the above points. Patients have a very low risk of dependency when opioids are prescribed for the acute management of pain. Alcohol should be avoided while receiving regular acetaminophen and opioid treatment; this is of concern for DB, who had daily alcohol intake before admission. Acetaminophen overdose can be unintentional because patients may not realize that many products contain acetaminophen; appropriate counseling can help avoid liver problems. Constipation due to opioids is common and may require the occasional use of laxatives.

REVIEW QUESTIONS

(Answers and Rationales on page 369.)

1. Dexamethasone can be used in the treatment of all of the following except?

a. Addison’s disease

d. Cushing’s disease

2. Codeine is metabolized by which of the following enzymes?

a. Sulfotransferase

b. Glutathione transferase

c. Cyclooxygenase

d. Catechol-O-methyltransferase

e. Acetylcholinesterase

3. Which of the following anesthetic/partition coefficient/minimum alveolar concentration would have the fastest onset of action?

a. Isoflurane/1.40/1.15

b. Nitrous oxide/0.47/105

c. Methoxyflurane/12/0.16

d. Enflurane/1.8/1.68

e. Halothane/2.3/0.75

4. Which of the following anesthetic/partition coefficient/minimum alveolar concentration would have the least effect on uterine smooth muscle?

a. Isoflurane/1.40/1.15

b. Nitrous oxide/0.47/105

c. Methoxyflurane/12/0/16

d. Enflurane/1.8/1.68

e. Halothane/2.3/0.75

5. Which of the following anesthetic/partition coefficient/minimum alveolar concentration would have the highest potency?

a. Isoflurane/1.40/1.15

b. Nitrous oxide/0.47/105

c. Methoxyflurane/12/0/16

d. Enflurane/1.8/1.68

e. Halothane/2.3/0.75

6. Which of the following anesthetic/partition coefficient/minimum alveolar concentration would have the lowest potency?

a. Isoflurane/1.40/1.15

b. Nitrous oxide/0.47/105

c. Methoxyflurane/12/0/16

d. Enflurane/1.8/1.68

e. Halothane/2.3/0.75

7. Which of the following statements about acetaminophen is true?

a. It may cause blood dyscrasias.

b. It is safe to use in patients with glucose-6-phosphate dehydrogenase (G6PD).

c. It does not cross the placenta.

d. It inhibits peripheral COX-1 enzymes.

e. Its duration of action is 18–24 hours.

8. Which of the following statements about aspirin is true?

a. Its analgesic duration of action is 18–24 hours.

b. It is primarily excreted in bile.

c. It is hydrolyzed in the bloodstream.

d. Has an onset of action of 120 minutes

e. It may cause hypertension.

9. Which of the following statements regarding acetaminophen is FALSE?

a. It may cause a skin rash.

b. It causes hepatotoxicity in overdose.

c. It is an antipyretic agent.

d. It is safe to use in children with influenza infection.

e. It is an anti-inflammatory agent.

10. Salicylates may be used to treat all of the following EXCEPT a:

a. 6-year-old girl with fever, dry cough, fatigue and muscle aches.

b. 65-year-old woman with stiffening of the wrists and interphalangeal joints.

c. 65-year-old woman with knee pain after a minor fall.

d. 30-year-old man with family history of early-onset myocardial infarction.

e. 25-year-old woman with spasmodic dysmenorrheal.

11. Injection of a local anesthetic into a circulatory vessel may result in which of the following?

a. Circulatory collapse

b. Myocardial depression

c. Respiratory depression

e. All of the above

12. Which of the following is NOT an indication for opioid use?

d. Inflammation

e. Preanesthesia

13. Which of the following statements about meperidine is true?

a. It produces CNS excitation.

b. It crosses the placenta.

c. It is excreted predominately in bile.

d. It may cause hypertension.

e. It may cause dysuria.

14. Which of the following is a neuromuscular blocking agent that may cause muscarinic side effects?

a. Succinylcholine

d. Decamethonium

e. Tubocurarine

15. What is the active ingredient in Toradol?

c. Acetaminophen

e. Amitriptyline

16. Which of the following is NOT a method of administering ketorolac tromethamine (Toradol)?

17. Adverse effects of ketorolac tromethamine (Toradol) include all of the following EXCEPT:

c. abdominal pain.

d. hypotension.

18. Which of the following is safe to take with ketorolac tromethamine (Toradol)?

e. None of the above is safe.

a. can be used to treat gout.

b. can be prescribed as a tablet or suspension.

c. may cause edema.

d. is more than 90% absorbed after oral administration.

e. All of the above

20. Among glucocorticoids, which drug has the shortest duration of acting?

a. Dexamethasone

b. Betamethasone

c. Prednisolone

d. Methylprednisolone

e. Hydrocortisone

a. can be administered IM or IV.

b. has minimal effect on the cardiovascular system.

c. has a duration of action of 30–60 minutes.

22. Which of the following can be administered intra-articularly?

b. Corticosteroids

d. Penicillamine

23. Which of the following drugs may produce drowsiness?

b. Corticosteroids

d. Penicillamine

24. Which of the following is notable for more severe CNS effects than most NSAIDs?

b. Hydroxychloroquine

c. Indomethacin

d. Cyclophosphamide

e. Methotrexate

25. Which of the following is available in enteric-coated tablets?

b. Hydroxychloroquine

c. Indomethacin

d. Cyclophosphamide

e. Methotrexate

26. Aspirin slows secretion of which drug?

b. Hydroxychloroquine

c. Indomethacin

d. Cyclophosphamide

e. Methotrexate

27. Ibuprofen is:

a. A derivative of phenylpropionic acid

b. An anti-inflammatory and analgesic

c. Unsafe in rheumatoid arthritis

d. Only available orally

e. All of the above

28. Which of the following anesthetic/partition coefficient/minimum alveolar concentration should be avoided in epileptic patients?

a. Isoflurane/1.40/1.15

b. Nitrous oxide/0.47/105

c. Methoxyflurane/12/0/16

d. Enflurane/1.8/1.68

e. Halothane/2.3/0.75

29. A 36-year-old man is taken to the emergency department with respiratory depression. Which of the following drugs is a likely culprit?

30. Which of the following statements is correct?

a. Propoxyphene may be used to suppression withdrawal symptoms of heroin.

b. Propoxyphene is not addictive.

c. Methadone is not addictive.

d. Propoxyphene may be discontinued abruptly 1 month after successful heroin cessation.

e. Methadone withdrawal is of shorter duration than heroin withdrawal.

31. Which of the following statements is FALSE?

a. Phenacetin may case renal damage.

b. Meperidine may cause renal damage.

c. Salicylates may cause renal damage.

d. Combinations of analgesics may be more nephrotoxic than single drugs.

e. Phenacetin is metabolized to acetaminophen.

32. Which of the following anesthetic/partition coefficient/minimum alveolar concentration is not used due to nephrotoxicity?

a. Isoflurane/1.40/1.15

b. Nitrous oxide/0.47/105

c. Methoxyflurane/12/0/16

d. Enflurane/1.8/1.68

e. Halothane/2.3/0.75

33. Which of the following causes increased hydrogen ion permeability of the gastric mucosa?

b. Indomethacin

c. Erythromycin

34. What is the antidote for pentazocine overdose?

c. Levallorphan

d. Any of the above

e. None of the above

35. What is the mechanism underlying hemorrhagic gastritis secondary to aspirin therapy?

a. Back diffusion of hydrogen ions across gastric mucosa

b. Inhibition of prostaglandin synthesis

c. Decreased renal salicylate excretion

36. Which of the following may cause increased biliary duct pressure?

d. Carbon tetrachloride

e. Acetazolamide

37. Which of the following may cause analgesic nephropathy?

a. Prolonged use of an NSAID

b. Prolonged use of aspirin combinations

c. Chronic overuse of an NSAID

d. All of the above

e. None of the above

38. Which of the following is NOT true of acetaminophen toxicity?

a. 10 g or more may produce hepatic necrosis in adults.

b. Diuresis may be effective therapy.

c. Liver necrosis is centrilobular and midzonal.

d. Phenacetin was metabolized principally to acetaminophen.

e. Transient azotemia may occur.

39. Which of the following is the most common pulmonary complication associated with opioid ingestion?

a. Interstitial fibrosis

b. Pulmonary calcification

c. Bronchoconstriction

d. Respiratory depression

e. Pleural effusion

40. Which of the following is seen in acute opioid overdose?

b. Pinpoint pupils

c. Respiratory depression

d. All of the above

e. None of the above

41. Which of the following is an effect of opioids?

a. Stimulation of antidiuretic hormone (ADH) secretion

b. Suppression of luteinizing hormone (LH) secretion

c. Suppression of prolactin secretion

42. Which opioid has the shortest duration of action?

d. Hydromorphone

43. Which of the following is an opioid receptor antagonist?

a. Buprenorphine

e. All of the above

44. Which of the following is true?

a. Aspirin is metabolized by both first- and zero-order kinetics.

b. High-dose aspirin can lower serum urate.

c. Aspirin acts via inhibition of cyclooxygenase.

d. All of the above

e. None of the above

45. Which of the following has the shortest duration of action when administered subcutaneously?

d. Hydromorphone

46. Which of the following can be used to prevent abstinence withdrawal syndrome in heroin-addicted patients in the inpatient setting?

e. All of the above

47. Which of the following statements is FALSE?

a. High-dose salicylates may increase serum uric acid.

b. Salicylate effect on platelet aggregation is irreversible.

c. Salicylates inhibit prostaglandin synthetase.

d. Salicylates only act on central cyclooxygenase enzymes.

e. All of the above are true.

48. Which of the following is most likely to produce dysphoria?

49. Which of the following statements about morphine is true?

a. It decreases pupillary light responsiveness.

b. It acts directly on extrinsic muscles of the eye.

c. It acts directly on the smooth muscle of the iris.

d. It produces mydriasis via sympathetic activation.

e. It produces miosis via effects on the oculomotor nerve.

50. Which of the following is inhibited by aspirin?

a. Prostaglandin synthetase and prostaglandin reductase

b. Prostaglandin synthetase and thromboxane synthetase

c. Prostaglandin synthetase and cyclooxygenase

d. Prostaglandin reductase and cyclooxygenase

e. Thromboxane synthetase and cyclooxygenase

51. Which of the following is seen with salicylate overdose?

a. Acid-base disturbances

c. Electrolyte imbalances

52. What is the primary mechanism of death with acetaminophen overdose?

a. Hepatic necrosis

e. Renal necrosis

53. Which of the following is NOT an effect of morphine?

c. Respiratory depression

d. Postural hypotension

e. Behavioral changes

54. Which of the following is NOT true of indomethacin?

a. It can be used to treat bursitis

b. Dosage for rheumatoid arthritis is 25–50 mg, 2 to 3 times per day

c. It may cause indigestion

d. It is not metabolized by the liver

e. It is excreted in both urine and feces

56. A patient undergoing a dental procedure should stop aspirin therapy for how many days before his appointment?

e. It is not necessary to stop aspirin therapy

57. Which of the following has a rapid onset of action and causes involuntary muscle movements?

60. Which opioid has the longest duration of analgesic action?

d. Hydromorphone

e. All have similar durations of analgesic actions

61. Which of the following inhibits cyclooxygenase?

b. Dipyridamole

c. Tranexamic acid

62. The Pain Ladder, a widely accepted three-step approach to implementing the three categories of pain medication, was developed by the?

63. Which of the following anesthetic/partition coefficient/minimum alveolar concentration is most likely to produce hepatitis?

a. Isoflurane/1.40/1.15

b. Nitrous oxide/0.47/105

c. Methoxyflurane/12/0/16

d. Enflurane/1.8/1.68

e. Halothane/2.3/0.75

64. Which of the following has minimal effects on the cardiovasculature and has depressant CNS effects?

65. Which of the following results in cardiac stimulation?

66. All of the following are true of propofol EXCEPT:

a. it is highly lipophilic.

b. the half-life does not correlate with duration of CNS depression.

c. it is useful as a skeletal muscle relaxant.

d. it may result in hypotension.

e. it provides a rapid recovery from anesthesia.

67. All of the following are true of ketamine EXCEPT:

a. it is a strong analgesic.

b. it may cause bronchoconstriction.

c. it may cause hallucinations during recovery.

d. it causes dissociative anesthesia.

e. All of the above are true.

68. All of the following are true of etomidate EXCEPT it:

a. is a potent analgesic and hypnotic.

b. inhibits adrenal function.

c. has no adverse adrenal effects with short-term use.

d. has minimal effects on cardiac function.

e. All of the above are true.

a. is contraindicated in COPD.

b. produces skeletal muscle relaxation.

c. produces analgesia.

d. is useful in treating seizures.

e. is cardiostimulative.

70. All of the following are true of bupivacaine EXCEPT it:

a. is rapidly hydrolyzed by plasma esterase.

b. has a high risk of side effects when used in epidural anesthesia.

c. should not be used in lidocaine-allergic patients.

d. should be used in higher doses for epidural than spinal anesthesia.

e. is metabolized primarily in the liver.

71. The visual analog scale is used to measure pain?

c. Signs and symptoms

e. All of the above

72. Neuropathic pain is classified as?

a. Pain mediated through c-fibers in the sensory nervous system.

b. Pain that is mediated by a normal pain system.

c. Pain that is due to a damaged sensory nervous system.

d. Pain that is imagined or otherwise psychologically mediated.

73. Which of the following is not treated with dexamethasone?

a. Inflammation

c. Addison disease

d. Wilson disease

e. None of the above

74. Which of the following is/are complication(s) of prednisone?

I. Osteonecrosis

II. Hyperglycemia

e. I, II, and III

76. Which of the following NSAID is a prodrug?

78. Which of the following is a side effect of corticosteroids?

a. Telangiectasias

e. All of the above

79. Which of the following statements about hydrocortisone is true?

a. It has a half-life of elimination of 8–12 hours.

b. It is metabolized in the liver.

c. It is predominately excreted in the feces.

81. Which of the following is a common opioid side effect?

a. Constipation

d. Mental confusion

e. All of the above

82. Which of the following opioids is/are used for spinal drug delivery?

d. Hydromorphone

e. All of the above

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CHAPTER 18 Pain Management

I. DefinitionPain is a common condition that manifests as many different forms and severities. Pain is defined as an unpleasant sensory and emotional experience associated with damage to body tissues, including organs, bones, and muscles. Acute pain occurs after tissue injury and often resolves soon after the body has healed. Chronic pain occurs either from continual damage or constant stimulation of nerve fibers lasting at least 6 months. The cause of some chronic pain may not be known. The treatment of pain depends upon the causes of the pain and the individual’s tolerance of pain.

II. Types of Pain The different types of pain include acute pain, chronic pain, nerve pain, nociceptive pain, and psychogenic pain.

A. Acute pain: results from injury to tissues and/or inflammation. Acute pain generally has a sudden onset. For example, after trauma or surgery, acute pain may be accompanied by anxiety or emotional distress.

B. Chronic pain: Pain signals keep firing in the nervous system for weeks, months, even years. Initial injuries, such as an infection, sprained back, or sprained muscle, may cause acute pain that may lead to chronic pain. There may be an ongoing cause of pain, such as in back pain, arthritis, diabetes (diabetic neuropathy), or cancer.

C. Nerve pain (neuropathic pain): pressure or damage to nerves or the spinal cord. Nerve pain can be caused by tumors; injury, such as during surgery or falls; chemical damage, such as with mercury, lead, chemotherapy, and radiation; or viruses, such as herpes zoster (shingles or chicken pox).

D. Nociceptive pain: aching, sharp, or throbbing pain that includes somatic pain (body surface, deep tissues) and visceral pain (not well localized, pressure-like, deep squeezing)

E. Psychogenic pain: mostly related to psychological disorders. Goals of treatment are to improve comfort and physical and psychological function. Treatment includes antidepressants, psychological counseling.

III. Acute Pain Control

A. Pain management required for a short duration (e.g., following surgery, accident)

B. Known end period for required pain management

C. Monitor for addiction

IV. Chronic Pain Control

A. Disease state management (e.g., cancer, rheumatoid arthritis, osteoarthritis)

B. Pain management required for a long period, possibly until end of life

C. Acute control (e.g., breakthrough pain) may be required for short duration events during chronic control

D. Monitor for addiction

V. Pyramid Control

A. Start with mild agents, increase to narcotics

B. Ceiling effect (i.e., a limited dose requirement) with most analgesics

1. Narcotics (opioids) like morphine do not have a ceiling effect.

C. Controlled substances potentially addictive

D. Start with lowest doses possible

VII. Patient Management

A. Identify the source of pain.

B. Eliminate the underlying cause.

C. Select the most effective analgesic with the fewest side effects.

D. Properly titrate the dose for each patient and administer for an appropriate duration.

E. Always consider around-the-clock regimens for acute and chronic pain.

F. Use as-needed regimens for breakthrough pain.

G. Assess for side effects of analgesics (i.e., constipation with opioids).

H. Avoid excessive sedation by titrating the opioids tentatively.

I. Adjust the route of administration to the needs of each patient, using oral administration whenever possible.

J. Use equianalgesic doses when converting from one agent to another and titrate accordingly.

K. Consider antidepressants, anticonvulsants, or opioids for neuropathic pain.

L. Consider a multidisciplinary approach: pharmacologic + nonpharmacologic therapies.

VIII. Pharmacologic Therapies

B. Nonsteroidal anti-inflammatory drugs (NSAIDs) (Table 18-1)

1. Mechanism of action: nonspecific inhibition of cyclooxygenase (COX)-2 and COX-1 receptors, decreasing prostaglandins produced by the arachidonic acid cascade in response to noxious stimuli, thereby decreasing the number of pain impulses received by the central nervous system (CNS)

2. Use lowest effective dose for shortest possible duration; OTC NSAID not to exceed 10 days unless a physician directs otherwise

3. Caution: Avoid in patients with recent coronary artery bypass graft surgery (CABG). Caution in bleeding disorders, hepatic or renal disease, GI disorders; women who are pregnant or lactating or who are trying to conceive

4. Interactions: Methotrexate, medications which increase the risk of bleeding (anticoagulants, e.g., warfarin), medications causing liver or renal damage, medications causing GI disturbance, diuretics, lithium, aspirin,antihypertensive agents

5. Toxicity and side effects: bleeding, upset stomach, ulcers, nausea, vomiting, diarrhea, constipation, fluid retention, edema, tinnitus, increased risk of bleeding, increased risk of Reye syndrome in children

1. Prototype of the salicylates; also a nonsteroidal anti-inflammatory drug (NSAID)

2. Mechanism of action: irreversibly inhibits COX-1 and COX-2, decreasing prostaglandins produced by the arachidonic acid cascade in response to noxious stimuli, thereby decreasing the number of pain impulses received by the CNS

3. Maximum dose 5400 mg per day; less in some situations

4. Caution: bleeding disorders, hepatic and/or renal disease, GI disorders, use in children, pregnancy, fertility, lactation

5. Interactions: other medications that increase the risk of bleeding, medications containing salicylates, medications causing GI disturbance

6. Toxicity and side effects: increased risk of Reye syndrome in children, GI disturbance, GI bleeding and/or mucosal lesions, otic effects (tinnitus and hearing loss at high doses), hepatotoxicity, nephrotoxicity is rare, and increased risk of bleeding

D. COX-2 inhibitors (a subset of NSAID class) (Table 18-2)

1. Mechanism of action: selectively inhibits the activity of the enzyme COX-2, resulting in a decreased prostaglandin production, thereby decreasing the number of pain impulses received by the CNS

2. May have fewer GI effects than COX-1 inhibitors

3. Common side effects: peripheral edema, abdominal pain, diarrhea, dyspepsia, flatulence, nausea, back pain, dizziness, headache, insomnia, pharyngitis, rhinitis, sinusitis

4. Caution: same risks as traditional NSAIDs

5. Avoid in patients with recent coronary artery bypass graft surgery (CABG), creatinine clearance <30 mL/min

6. Interactions: medications that increase the risk of bleeding, hepatotoxic or nephrotoxic medications, medications that cause GI disturbance

7. Toxicity: GI disturbance, hepatotoxicity, nephrotoxicity, increased risk of bleeding GI ulceration, cardiovascular events, including stroke**

E. Narcotic analgesics (Table 18-3)

a. Mechanism of action: binds to opiate receptors in the CNS causing inhibition on ascending pain pathways thereby altering the perception of and response to pain

b. Caution: physically addictive, controlled substances

c. Interactions: additive CNS depression with alcohol

d. Toxicity and side effects: constipation, drowsiness, nausea/vomiting, sedation, itching, difficulty urinating, miosis, toxicity may result in respiratory depression

e. Antidote for opioid overdose: naloxone (Narcan)

3. Hydromorphone (Dilaudid)

a. Mechanism of action: Similar to morphine

1) Faster onset of action and shorter duration of action

2) 8–10 times stronger than morphine

b. Used for moderate to severe pain

4. Codeine (methyl morphine)

a. Mechanism of action: similar to morphine but not as potent and shorter duration of action

b. Combination therapy with other agents in same formulation

c. Also used for suppressive therapy of cough

d. Used for moderate pain

e. Must monitor contents when using multiple agents

f. Schedule II or III

g. Adverse effects: constipation, nausea, and vomiting

5. Synthetic and semisynthetic narcotics

b. Meperidine (Demerol)

1) No maximum dose: must titrate up slowly to lessen side effects, especially respiratory depression

2) Can suppress cough reflex

3) Useful in treatment of rigors

5) Contraindicated for use with monoamine oxidase inhibitors (MAOIs)

6) Adverse effects: itching, sweating, and hypotension (caused by histamine release)

7) Toxic metabolite = normeperidine; patient must have good renal function to use medication

c. Propoxyphene (Darvon)

1) Combination therapy with other agents in same formulation

2) Must monitor contents when using multiple agents

3) Less addictive than opioids

4) Used for moderate pain

6) Adverse effects: constipation, GI upset, CNS disturbance

3. Drugs used in treatment of narcotic dependency

a. Methadone (Dolophine)

1) Mechanism of action: mu-opioid receptor agonist activity; synthetic drug

2) Used for detoxification and maintenance treatment of opioid addiction

3) Also used for pain relief

4) Patients must be in authorized methadone program; prescribers who prescribe for narcotic dependency must have special DEA registration; such registration is not needed for those using methadone for pain

5) High abuse potential

G. Antidepressants used for pain management

1. Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) have been found to provide some relief depending on the type of pain to be treated.

2. Used for chronic pain (e.g., neuropathic pain). Some SSRIs used for fibromyalgia.

3. TCA examples: amitriptyline (Elavil), nortriptyline (Pamelor), desipramine (Norpramin)

4. Narrow therapeutic window for TCA

5. TCAs associated with side effects: sedation, orthostatic hypotension, urinary retention

H. Anticonvulsants used for pain management

1. Used for chronic pain (e.g., neuropathic pain)

2. Liver function tests (LFT) should be obtained at baseline and throughout use with many of these drugs (e.g., phenytoin, valproic acid, carbmazepine).

3. Examples: gabapentin (Neurontin); carbamazepine (Tegretol); phenytoin (Dilantin), valproic acid (Depakote), lamotrigine (Lamictal)

a. Gabapentin is the most promising with the fewest side effects.

1. Initial adult dose: 100 mg twice daily, may titrate up to 1200–2400 mg daily divided in three doses

I. Local anesthetics

1. Topical local anesthetics (e.g., Lidoderm, EMLA) are used for neuropathic pain and postherpetic neuralgia.

2. Use only on intact skin.

1. Over-the-counter (OTC) topical products: Zostrix, Axsain

2. Composed of an extract of chili peppers

3. Also used for rheumatoid arthritis and osteoarthritis

4. Rarely recommended due to overall poor efficacy

5. Adverse effect: burning at site of administration

K. Corticosteroids

1. May be used for neuropathic symptoms when associated with inflammation and edema

a. Also used for bone pain, spinal metastasis, rheumatoid arthritis, other acute inflammatory disorders

2. Example: dexamethasone commonly used

3. Many potential adverse effects: hyperglycemia, insomnia, GI irritation, psychosis, osteoporosis

L. Other neuropathic pain medications

Table 18-1 Nonsteroidal Anti-inflammatory Drugs (NSAID)

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NSAID	Usual Oral Adult Doses	Comments
Ibuprofen (Motrin)	200–400 mg PO q4–6h prn	Maximum 1200 mg/day (OTC); 3200 mg/day (R_x)
Naproxen (Aleve, Naprosyn, Anaprox)

Mosbys Pharmacy Review for the NAPLEX