Pharmacology

10 Pharmacology

Mark S. Greenberg

I. Key Points

– Treating pain early with effective doses results in overall reduction in the consumption of pain meds.

– Adjuncts to opioids for pain: NSAIDs, muscle relaxants, acetaminophen, Tramadol (not a conventional opioid), and centrally acting pain meds (e.g., gabapentin) for neuropathic pain.

– Use of steroids for spinal cord injury remains controversial, but benefits probably do not outweigh risks.

– Deep vein thrombosis (DVT) prophylaxis in spinal cord injury is critical. If prophylactic anticoagulation is contraindicated, then a vena cava interruption filter should be considered.

II. Pain Medication^1,2

– Nonopioid analgesics

• Acetaminophen (APAP)

An effective pain medication that does not inhibit peripheral cyclooxygenase activity, and is therefore not associated with altered platelet function, bronchospasm, or gastric ulceration

Potentiates narcotic pain medication and NSAIDs

The main hazard is hepatic toxicity. Use with caution with active liver disease, with chronic heavy alcohol consumption, and with glucose-6 dehydrogenase deficiency.

• Nonsteroidal antiinflammatory drugs (NSAIDs)

Antiinflammatory and antipyretic

Single PRN doses are effective against pain even without “antiinflammatory dosing.”

Adverse effects include reduction of renal blood flow, platelet function inhibition (permanent with aspirin, temporary with other NSAIDs), and peptic ulcers. Deleterious effect on bone healing is controversial; many surgeons hold off on NSAIDs for two weeks following fusion (a longer hiatus is not appropriate).

Examples of NSAIDs are naproxen (Naprosyn), diclofenac (Voltaren), and ketorolac tromethamine (Toradol). They can be given parenterally (parenteral use should not exceed 3 to 5 days). Oral dosing should be done only as continuation of parenteral dosing, not for routine use as an NSAID.

– Opioid analgesics

• No single agent has been shown to be most effective or best tolerated as a rule, although individual differences may make certain opioids more effective in certain patients. Exception: meperidine has multiple disadvantages and has limited usefulness.

• All produce dose-related respiratory depression. Some lower the seizure threshold. Diversion of prescribed narcotics to sale on the street for recreational use is a burgeoning problem.

• With chronic use, tolerance develops. All may be habit forming.

• Dosing depends more on age and prior narcotic use than on body weight.

– Weak opioids, for mild to moderate pain

• Codeine is typically prescribed in combination with APAP. It is associated with a significant incidence of nausea and vomiting.

• Hydrocodone is available only as a combination drug (e.g., with APAP in Vicodin and Lortab or with ibuprofen in Vicoprofen) in the United States.

– Opioids for moderate to severe pain

• Oral: oxycodone with acetaminophen (Percocet)

• Parenteral (intramuscular [IM] or intravenous [IV]): morphine, hydromorphone (Dilaudid). Monitor for respiratory depression. May be used for patient-controlled analgesia (PCA).

III. Anticoagulation

– Prophylactic anticoagulation

• For patients without risk factors for blood clots, prophylactic anticoagulation for elective spine surgery is not recommended.3

• For spinal cord injuries,⁴ prophylaxis with either

Low-molecular-weight heparin (LMWH), a rotating bed, adjusted-dose heparin, or some combination of these, or

Low-dose (mini-dose) heparin with pneumatic compression stockings or electrical stimulation.

– Treatment for documented DVT or pulmonary embolism (PE)

• Therapeutic anticoagulation with heparin transitioned to warfarin

• Postoperatively: in the first week or two after spinal surgery, because of the risk of spinal hematoma, a vena cava interruption filter is preferred for DVT/PE. But for acute myocardial infarction or cardiac ischemia, therapeutic heparin may have to be used; in this case, monitor patient’s neurologic signs frequently.

IV. Steroids

– Acute nerve injury

– Spinal cord injury protocol still controversial

• The assertion: administration of methylprednisolone according to protocol within 8 hours of a spinal cord injury (SCI) (complete or incomplete) benefits sensory and motor function at 6 weeks, 6 months, and 1 year.5,6

• The controversy: results could not be replicated,⁷ steroid-induced myopathy might have produced a transient initial worsening that was misinterpreted as an improvement when it subsided,⁸ and the risk of side effects (infectious and diabetogenic) is substantial.⁹

• Protocol: within 8 hours of SCI, bolus with methylprednisolone 30 mg/kg IV over 15 minutes, wait 45 minutes, then start a maintenance infusion of 5.4 mg/kg/h typically maintained for 23 hours. Do not start the protocol more than 8 hours postinjury.

• Spine tumors: for acute symptoms of spinal cord compression from metastatic tumor, decadron 10 mg IV or orally every 6 hours for 72 hours, followed by 4 to 6 mg every 6 hours.

– Epidural steroids

• Perioperative epidural steroids after routine surgery for lumbar degenerative disease may result in a small reduction of postoperative pain and length of stay, and increased risk of not returning to work after one year,¹⁰ but most of the evidence originates from studies not using validated outcome assessment and that favor positive results, and further study is recommended (various agents, dosages, and delivery methods were reported).

• As part of pain management

Chronic low back pain: not recommended¹¹; may be used to provide temporary relief in select cases

Acute radiculopathy: prospective studies show varying efficacy¹²

– Low back pain: oral steroids (e.g., steroid dose pack) may provide temporary improvement in symptoms; however, no difference from placebo is found at 1 week or 1 year follow-up. Use caution when combining with NSAIDs because of gastrointestinal (GI) irritation.

V. Muscle Relaxants

– Oral and IV agents used for low back pain have no activity at the neuromuscular junction. They do exhibit some centrally acting analgesic effect that appears to be independent of muscle spasms. The most consistent effect of these drugs is drowsiness/ sedation, which may help the patient rest. Tolerance develops.

– Commonly employed agents include cyclobenzaprine (Flexeril), diazepam (Valium), tizanidine (Zanaflex), and carisoprodol (Soma).

VI. Clinical Pearls

– Pain medication: early treatment with effective doses before pain becomes severe reduces the total quantity of medication needed to control the pain.

Common Clinical Questions

1. Of the following options for DVT prophylaxis in spinal cord injury,

1. Low-dose (mini-dose) heparin alone

2. Low-molecular-weight heparin alone

3. Oral anticoagulation alone

4. Low-dose heparin and pneumatic compression device which are recommended treatments?

A. 1 and 3

B. 2 and 4

C. 1, 2, and 3

D. 4

2. Which of the following drugs or classes of drugs causes a reduction in renal blood flow?

A. NSAIDs