Review article: the pharmacological causes of colon ischaemia

Abstract

Summary Background Colon ischaemia is the most common ischaemic disorder of the gastrointestinal system, can affect any segment of the colon, and may present with a range of symptoms. Diagnosis can be challenging due to symptom overlap with other conditions, varied aetiology, and often rapid and self‐resolving course. Aim To review comprehensively the literature regarding the pharmacological aetiologies of colonic ischaemia to enhance the understanding of the various mechanisms of disease, presentations, distribution, and outcomes. Methods A PubMed search for “colon ischaemia” and “ischaemic colitis” alone as well as in combination with various known pharmacologic causes was performed. Only the highest quality and relevant literature was included in this review. The quality of the literature for each association was rated by the authors and a consensus was made when discrepancies were encountered. Only associations that were deemed “moderate” or “strong” were included. Results The literature considering pharmacologically associated colonic ischaemia is diverse, lacks codification and is characterised by numerous case reports and case series. Constipation‐inducing drugs, digoxin, hormonal therapies, illicit drugs, immunomodulators, laxatives, and NSAIDs were strongly associated with colonic ischaemia. Antimicrobials, appetite suppressants, chemotherapies, decongestants, diuretics, ergot alkaloids, serotonin agents, statins, and vasopressor agents were moderately associated. Conclusions Patients presenting with abdominal pain, diarrhoea, or bloody stool need to be evaluated for the possibility of this condition and treated accordingly. Timely diagnosis is necessary to improve patient outcomes. This review aims to increase awareness among clinicians regarding the presentation of pharmacologically induced colonic ischaemia.

Older patients are significantly more likely to have colon ischaemia‐associated conditions that are chronic and complex

“…It is important to note that of these three drug categories, the one that was most commonly used in both cohorts was constipation‐inducing drugs (64.1% of patients in the younger cohort and 83.8% of patients in the older cohort). One mechanism proposed for the linkage between constipation‐inducing medications and colon ischaemia is that constipation may cause an increase in intracolonic luminal pressure which diminishes colon blood flow and results in mucosal‐to‐serosal shunting of blood with consequent reduction of the arterio‐venous oxygen difference and subsequent decreased mucosal and submucosal oxygen extraction . In a large retrospective analysis, Walker et al found that use of constipation‐inducing drugs was highly prevalent in patients diagnosed with colon ischaemia compared with matched controls.…”

“…One proposed explanation is that antipsychotic medications, particularly clozapine and quetiapine, have significant antiserotonergic and anticholinergic activity which has been shown to lead to altered colon motility and reduction in colonic blood flow . Another suggested theory is that many antipsychotic medications have constipation as a side effect, which in turn is a risk factor for colon ischaemia . In the general population, however, usage of antipsychotic medications in younger patients is significantly less frequent than in older patients, with one study showing significantly fewer patients between the ages 18 and 64 on antipsychotic medications compared with patients aged 65 and above (26.53% vs 39.89%; P = 0.03) .…”

“…There has been a great deal of literature, however, which has identified various associations and risk factors of colon ischaemia. One heavily studied area is the association of colon ischaemia with medications and drugs including antibiotics (most commonly penicillin derivatives, but also macrolides, fluoroquinolones, cephalosporins and tetracycline), chemotherapeutic drugs, constipation‐inducing drugs, decongestants (specifically pseudoephedrine), diuretics, hormonal therapies (oral contraceptives and hormone replacement therapy), immunomodulating agents, antipsychotic drugs, laxatives, selective serotonin reuptake inhibitors and selective serotonin and norepinephrine reuptake inhibitors, nonsteroidal anti‐inflammatory drugs and cocaine…”

Ischemic colitis in an infant with constipation treated with stimulant laxative

“…1 IC associated with stimulant laxatives is believed to result from stimulated colonic motility increasing intraluminal pressure, compressing the splanchnic circulation to decrease colonic perfusion. 3 We therefore believe that the patient's IC arose from constipation and stimulant laxative treatment. To our knowledge, this is the first report of infantile IC complicating constipation.…”

Editorial: older patients are significantly more likely to have colon ischaemia‐associated conditions that are chronic and complex

“…Many studies have demonstrated associations between medications and colon ischaemia, but none has shown direct causality . Some classes of drugs are known to affect the vascular system and, therefore, colonic blood flow.…”