Selecting a Treatment Regimen
- Acetaminophen should be considered as initial and ongoing pharmacotherapy in the treatment of persistent pain, particularly musculoskeletal pain, owing to its demonstrated effectiveness and good safety profile (1-A).
- Absolute contraindications: liver failure (1-A).
- Relative contraindications and cautions: hepatic insufficiency, chronic alcohol abuse or dependence (2-A).
- Maximum daily recommended dosages of 4 g per 24 hours should not be exceeded and must include “hidden sources” such as from combination pills (2-A). Patients routinely consuming alcoholic beverages should limit to acetaminophen 2 g/d.
- Nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) selective inhibitors may be considered rarely, and with extreme caution, in highly selected individuals (1-A).
- Patient selection: other (safer) therapies have failed; evidence of continuing therapeutic goals not met; ongoing assessment of risks and complications outweighed by therapeutic benefits (3-A).
- Absolute contraindications: current active peptic ulcer disease (3-A), chronic kidney disease (2-A), heart failure (2-B).
- Relative contraindications and cautions: hypertension, Helicobacter pylori, history of peptic ulcer disease, active alcoholism, concomitant use of corticosteroids or selective serotonin reuptake inhibitors (SSRIs) (2-A).
- Older persons taking nonselective NSAIDs and all patients taking a
COX-2 selective inhibitor with aspirin should use a proton pump inhibitor
or misoprostol for gastrointestinal protection (1-A).
- Patients should not take more than one nonselective NSAID or COX-2 selective inhibitor for pain control (3-A).
- Patients taking aspirin for cardioprophylaxis should not use ibuprofen (2-B).
- Naproxyn is the safest of the NSAIDs.
- Most patients taking nonselective NSAIDs and COX-2 selective inhibitors should be routinely assessed for gastrointestinal and renal toxicity, hypertension, heart failure, and other drug–drug and drug–disease interactions (3-A).
- Most patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life due to pain should be considered for opioid therapy (3-A).
- Patients with frequent or continuous pain on a daily basis may be treated with around-the-clock time-contingent dosing aimed at achieving steady-state opioid therapy (3-B).
- Clinicians should anticipate, assess for, and identify potential opioid-associated adverse effects (2-A).
- Maximum safe doses of acetaminophen or NSAIDs should not be exceeded when using fixed-dose opioid combination agents as part of an analgesic regimen (2-A).
- When long-acting opioid preparations are prescribed, breakthrough pain should be anticipated, assessed, and prevented or treated using short-acting immediate-release opioid medications (2-A).
- Only clinicians well-versed in the use and risks of methadone should initiate it. Methadone must be titrated cautiously (2-A).
- Patients taking opioid analgesics should be reassessed for ongoing attainment of therapeutic goals, adverse effects, and safe and responsible medication use (2-A).
Adjuvant Analgesic Drugs
- Most patients with neuropathic pain are candidates for adjuvant
- Patients with fibromyalgia are candidates for a trial of approved adjuvant analgesics (2-A).
- Patients with other types of refractory persistent pain may be candidates for certain adjuvant analgesics (eg, back pain, headache, diffuse bone pain, temporomandibular disorder) (3-B).
- Tertiary tricyclic antidepressants (amitriptyline, imipramine, doxepin) should be avoided because of higher risk for adverse effects
(eg, anti-cholinergic effects, cognitive impairment) (2-A).
- Agents may be used alone, but often the effects are enhanced when used in combination with other pain analgesics and nondrug strategies (2-A).
- Therapy should begin with the lowest possible dose and increase slowly based on response and side effects, with the caveat that some agents have a delayed onset of action and therapeutic benefits are slow to develop. For example, gabapentin may require 2 to 3 weeks for onset of efficacy (2-A).
- An adequate therapeutic trial should be conducted before discontinuation of a seemingly ineffective treatment (3-A).
Table 1. Pharmacological Changes with Aging
|Pharmacological Concern||Change with Normal Aging||Common Disease Effects|
absorption or function
|Slowing of gastrointestinal transit time may prolong effects of continuous-release enteral drugs. Opioid-related bowel dysmotility may be enhanced in older patients.||Disorders that alter gastric pH may reduce absorption of some drugs. Surgically altered anatomy may reduce absorption of some drugs.|
|Transdermal absorption||Under most circumstances, there are few changes in absorption based on age, but this may relate more to different patch technology used.||Temperature and other specific patch technology characteristics may affect absorption.|
|Distribution||Increased fat to lean body weight ratio may increase volume of distribution for fat-soluble drugs.||Aging and obesity may result in longer effective drug half-life.|
|Liver metabolism||Oxidation is variable and may decrease, resulting in prolonged drug half-life. Conjugation usually preserved. First-pass effect usually unchanged. Genetic enzyme polymorphisms may affect some cytochrome enzymes.||Cirrhosis, hepatitis, tumors may disrupt oxidation but usually not conjugation.|
|Renal excretion||Glomerular filtration rate decreases with advancing age in many patients, which results in decreased excretion.||Chronic kidney disease may predispose to renal toxicity.|
|Active metabolites||Reduced renal clearance will prolong effects of metabolites.||Renal disease. Increase in half-life.|
|Anticholinergic side effects||Increased confusion, constipation, incontinence, movement disorders.||Enhanced by neurological disease processes.|