Clinical Pharmacology Considerations in Pain Management in Patients with Advanced Kidney Failure

Abstract

Pain is common and poorly managed in patients with advanced CKD, likely due to both under and over prescription of appropriate analgesics. Poorly managed pain contributes to patients' poor quality of life and excessive health care use. There is tremendous variability within and between countries in prescribing patterns of analgesics, suggesting that factors other than patient characteristics account for these differences. This article discusses the pharmacologic management of acute and chronic pain in patients with advanced CKD, and the role analgesics, including opioids, play in the overall approach to pain management.

Keywords: Analgesics, Opioid; Chronic Pain; NSAIDs; Pain Management; Pharmacology, Clinical; Prescriptions; Renal Insufficiency, Chronic; analgesics; chronic kidney disease; opioids; pain; quality of life.

Figure 1.

Metabolic pathways for opioids involve either phase 1 or phase 2 metabolism, which impacts potential for drug interaction and unpredictable clinical response. CYP2D6, cytochrome P450 2D6 enzyme; CYP3A4, cytochrome P450 3A4 enzyme; UGT2B7, UDP-glucuronosyltransferase 2B7.

Figure 2.

Commonly used classes of drugs in patients with CKD that may act as substrates, inhibitors or inducers of CYP3A4 and CYP2D6 and therefore may affect opioid metabolism and effect. CYP2D6, cytochrome P450 2D6 enzyme; CYP3A4, cytochrome P450 3A4 enzyme; SNRIs, serotonin-norepinephrine reuptake inhibitors; TCAs, tricyclic antidepressants.

Figure 3.

Pharmacological management of pain in patients with advanced CKD requires a cautious stepwise approach. N/A, not applicable; NSAID, nonsteroidal anti-inflammatory drug; PO, by mouth; TCAs, tricyclic antidepressants.