title: Non-steroidal anti-inflammatory drug use in chronic pain conditions with special emphasis on the elderly and patients with relevant comorbidities: management and mitigation of risks and adverse effects.
abstract: OBJECTIVE
  Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used drugs, and this widespread use is complicated by safety issues.
  
  
  METHODS
  A Literature review was conducted.
  
  
  RESULTS
  NSAIDs are a leading cause of drug-related morbidity, especially in the elderly and patients with comorbidities. Most adverse effects are related to generalized inhibition of the major targets of NSAIDs: cyclooxygenases I and II. These enzymes are not only involved in pain and inflammation pathogenesis but are also required in the gastrointestinal (GI) tract for mucosal protection and gut motility, and in the kidneys for functional integrity. Thus, the mechanisms of NSAID toxicity are well understood, but the consequences are largely uncontrolled in clinical practice. GI ulcers, including bleeding ulcers, may occur in several percent of all chronic unprotected, high-dose NSAID users. Renal side effects may precipitate renal failure, resulting in acute dialysis and chronic retention. This includes sodium retention, resulting in arterial hypertension, heart failure, and atherosclerotic events. Cardiovascular risk may be tripled by chronic high-dose NSAID use in long-term clinical trials though "real-life studies" indicate lower risk ratios. Off-target side effects include allergic reactions, drug-induced liver injury, and central nervous system effects.
  
  
  CONCLUSIONS
  Management of pain and inflammation must consider those risks and find alternative drugs or approaches to limit the negative impact of NSAIDs on mortality and morbidity. Alternative drugs, low-dose/short-term use, but especially non-pharmacologic approaches, such as physiotherapy, exercise, neurophysiologic measures, and local therapies, need to be further utilized. The appalling equation "less pain-more deaths/morbidity" ultimately necessitates treatment optimization in the individual patient.
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, Clinical Pharmacology Mannheim, Medical Faculty Mannheim, Ruprecht-Karls-University of Heidelberg, Maybachstrasse 14, 68169, Mannheim, Germany, martin.wehling@medma.uni-heidelberg.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Wehling
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D059350:Chronic Pain / Q000188:drug therapy*; D051545:Cyclooxygenase 1 / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D012306:Risk
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D051545:Cyclooxygenase 1