Nonopioid Pain Medications

Key Points

▪
With a better understanding of pain pathways and mechanisms, it has been recognized that ion channels play an important role in the transduction, transmission, and modulation of nociceptive signals. This opens a new avenue of developing novel therapeutic agents for the treatment of acute or chronic pain, particularly neuropathic pain.
▪
Although the exact mechanism of action remains unclear for many drugs listed in this chapter, they often are a component of a multidrug treatment strategy that has been increasingly used for the management of chronic pain conditions.

Introduction

Recent advances in our understanding of pain mechanisms have enabled us to treat acute and chronic pain conditions with a variety of nonopioid pain medications. The option of using nonopioid pain medications is particularly meaningful given the growing global concern over prescription opioid abuse and overdose. Besides acetaminophen and nonsteroidal antiinflammatory drugs (NSAIDs), several new categories of nonopioid pain medications can be used for the management of acute or chronic pain and, in particular, neuropathic pain. Examples of these nonopioid pain medications include drugs that block voltage-sensitive sodium channels and voltage-sensitive calcium channels, facilitate opening of chloride channels, increase function of the endogenous γ-aminobutyric acid (GABA) system, and modulate the N-methyl-D-aspartate (NMDA) receptor activity. In particular, ion channel blockers possess the antihyperalgesic effect by targeting specific mechanisms of pathologic pain, although most analgesics in this category do not necessarily produce the typical analgesic effect (i.e., raising the pain threshold above the normal baseline).

This chapter briefly discusses NSAIDs and acetaminophen and focuses on describing several ion channel blockers that are commonly used in the treatment of pain conditions, as listed in Box 25.1 . They are grouped into two categories: calcium channel blockers and sodium channel blockers.

BOX 25.1

Ion Channel Blockers as Pain Medications (Recommended Dosing)

Calcium Channel Blockers

Gabapentin: Starting dose 100–300 mg/day; titrating up to 1800–3600 mg/day
Pregabalin: Starting dose: 75–150 mg/day; titrating up to 450–600 mg/day
Zonisamide: Starting dose: 50–100 mg/day; titrating up to 450 mg/day
Ziconotide: Starting dose: 0.1 μg/h; titrating up to 0.4 μg/h
Levetiracetam: Starting dose: 250–500 mg/day; titrating up to 2000 mg/day

Sodium Channel Blockers

Lidocaine: Used in a lidocaine test: 1 mg/kg via slow intravenous push or drip
Mexiletine: Starting dose: 150–300 mg/day; titrating up to 600 mg/day
Carbamazepine: Starting dose: 100 mg/day; titrating up to 600 mg/day
Oxcarbazepine: Starting dose: 150 mg/day; titrating up to 900 mg/day
Lamotrigine: Starting dose: 25–50 mg/day; titrating up to 250–500 mg/day
Topiramate: Starting dose: 50–100 mg/day; titrating up to 300–400 mg/day.

Nonsteroidal antiinflammatory drugs

NSAIDs include ibuprofen, naproxen, indomethacin, ketorolac, and diclofenac and are examples of a class of medication commonly used as analgesic to reduce myofascial pain, postoperative pain, and chronic pain conditions. In a recent Cochrane review of 16 randomized, controlled clinical trials (2144 patients), pain relief and function restoration were compared in patients with acute soft tissue injury treated with oral NSAIDs and other oral analgesics including acetaminophen with or without opioids. The analgesic effect was similar between NSAIDs and acetaminophen or opioid, and there were no differences in functional restoration at 7 days, but the patients who were taking opioids reported more adverse side effects. Although acetaminophen, indomethacin, or diclofenac produced similar pain reduction, the combination of acetaminophen and diclofenac showed slightly better pain reduction. Intravenous ketorolac (15 or 30 mg) is a common medication of choice during the early postoperative period if there are no contraindications, such as renal insufficiency. Ketorolac has also been successfully used in pediatric surgical patients. A recent metaanalysis also found that NSAIDs were equivalent to opioids or paracetamol in the relief of acute renal colic pain.

The cyclooxygenase-2 (COX-2) inhibitors are considered an alternative to NSAIDs (mixed COX-1/COX-2 inhibitors) while possessing reduced gastrointestinal side effects. However, COX-2 inhibition is associated with increased risk of adverse cardiovascular events, although recent clinical studies, including the data from the PRECISION trial that examined long-term cardiovascular safety issues, support the notion that both NSAIDs and COX-2 carry a certain degree of cardiovascular risk.

Acetaminophen

For many decades, oral acetaminophen has been widely used as an analgesic to treat mild to moderate pain. Recently, intravenous acetaminophen has become available in the United States. Results of a randomized trial of patients who had colorectal surgery indicated that intravenous acetaminophen decreased postoperative opioid consumption, reduced hospital stay, improved pain control, shortened time to return of bowel function, and lowered the rate of postoperative ileus. Similar results were found after procedures for posterior spinal fusion, craniotomy, vitrectomy, esophagectomy, and total joint arthroplasty.

Compared with an opioids-only option for postoperative pain management in adolescents with idiopathic scoliosis, patients treated with intravenous acetaminophen plus ketorolac consumed less opioids and had less severe constipation. A retrospective analysis of the results of the Premier Database of 61,017 cholecystectomy patients showed that 31,133 (51%) of the patients who received intravenous acetaminophen had experienced a shorter length of hospital stay, a decrease in hospitalization costs, a reduced average daily morphine-equivalent dose, and lower rates of respiratory depression, nausea, and vomiting. However, several studies have failed to show that intravenous acetaminophen achieved the positive results as described here. The hepatic side effect is a significant concern for those with long-term acetaminophen use, particularly with alcohol. A recent analysis of nine prospective cohort studies has also linked long-term acetaminophen use with an increased risk of adverse neurodevelopmental outcomes following prenatal acetaminophen exposure.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here