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Influence of Concurrent Medical Conditions on Pharmacotherapies
The presence of other medical conditions in cancer patients and the medications taken for them may influence the choice of analgesic regimen for pain management. Common medications or classes of medications that produce clinically significant drug interactions with opioid analgesics include alcohol (as in elixirs) and other CNS depressants such as phenytoin, as well as rifampin 266 and monoamine oxidise inhibitors such as phenylzine sulfate and isocarboxazid.63
Coexisting conditions also may influence the type and doses of opioid analgesics administered. For example, patients with newly recognized cancer pain who have been recently treated with opioids for another reason, such as surgery, may require higher than the recommended starting doses because they are opioid tolerant. Coagulopathy, neutropenia, and sepsis may contraindicate the use of epidural catheters or other regional anesthetic techniques because the risks of bleeding or "seeding" of infection are increased.
Many patients with cancer undergo surgery as part of their treatment. GI procedures such as gastrectomy and vasectomy may markedly affect drug absorption and increase GI intolerance to some oral drugs. Drug pharmacokinetics can change after surgery because of changes in drug absorption and distribution caused by alterations in body weight, cardiac output, venous capacitance, extravascular fluid shifts, and protein binding. Fever and sepsis in the postoperative period can affect drug disposition, as do shock or trauma. Patients with such conditions may require higher than expected doses of opioids because of severe acute pain. In addition, they may not achieve clinically effective concentrations of opioids in plasma after intramuscular and subcutaneous injections because of the pharmacokinetic alterations described above.
Cancer often occurs in the elderly, who usually have decreased renal function as a normal result of aging. Mild age-related renal insufficiency (decline in glomerular filtration rate) can impede the excretion of the biologically active metabolizes of many opioids, resulting in clinically significant sedation and respiratory depression,414 as well as nausea.193 Meperidine, methadone, levorphano, pentazocine, and propoxyphene have increased bioavailability, prolonged half-lives, and decreased systemic clearance and thus accumulate in patients with hepatic or renal dysfunction. Renal excretion is a major route of elimination not only for opioids but also for their pharmacologically active metabolizes norpropoxyphene, normeperidine, morphine-6-glucuronide, and dihydrocodeine. Hence, in patients with renal dysfunction, doses of the parent compounds should be lowered or given less frequently.
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