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Pharmacologic agents and colonic ischemia

Pharmacologic agents and colonic ischemia
Drug Evidence Postulated pathogenesis
Moderate evidence
Constipation-inducing drugs
  • Predicted CI in patients with abdominal pain: 2.8 (1.1-7.1)[1]
  • All drugs C-CS: Risk, 0.68 (0.62-1.27)[2]
  • Opioids C-CS: Increased risk, 1.96 (1.43-2.67)[3]
  • Nonopioids C-CS: Increased risk, 1.75 (1.25-2.44)[3]
Reduced blood flow, increased intraluminal pressure[4]
Immunomodulator drugs
  • Antitumor necrosis factor-alpha inhibitors for rheumatoid arthritis from US FDA AERS: 17 probable, 18 possible cases; median age, 62 years*[5]
  • Type 1 interferon:
    • Alpha for hepatitis C: 13 probable, 4 possible cases; median age, 51 years*
    • 11 other reported cases[6]
    • Beta for multiple sclerosis: 19 probable, 20 possible cases; median age, 56 years
    • 10 other reported cases of interferon for hepatitis C (8 cases with age <55 years)[7]
Cytokines affecting thrombogenesis[8]
Illicit drugs
  • Amphetamines: 5 reported cases; age 42 to 50 years[8,9]
  • Cocaine: Used by 19 of 97 (20%) CI patients at two inner-city hospitals; age 44 to 56 years; 37% right-sided and 16% small bowel disease; 26% mortality[10]
  • Many other reported cases of multiple ischemic organs[8]
Vasoconstriction, hypercoagulation, direct endothelial injury[8]
Low evidence
Antibiotics
  • Antibiotic-associated colitis resembles CI, usually right-sided[8]
    C-CS: Increased risk, 3.3 (2.19-4.96)[3]
Altered gut microbiome (eg, Klebsiella oxytoca)[11]
Appetite suppressants
  • Bitter orange (resembles ephedra): 1 reported case[12]
  • Hydroxycut: 1 probable case*[13]
  • Ma huang (mainly ephedrine): 1 reported case[14]
  • Phentermine: 2 reported cases (1 with fenfluramine)[8,15]
  • Xenadrine (bitter orange, ma huang, caffeine, salicin): 1 reported case[16]
Vasoconstriction[8]
Chemotherapeutic drugs
  • R-CHOP: 1 reported case[17]
  • Taxanes: 10 reported cases[8,18-20]
  • Vinorelbine/cisplatin: 1 reported case[8]
  • C-CS: Increased use of taxanes or vinca alkaloids on univariate analysis[3]
Direct epithelial toxicity, inhibited repair of vascular injury[8]
Decongestants
  • Pseudoephedrine: 9 reported cases (6 cases with age <50 years)[8,21]
    C-CS: Risk unaffected, 1.1 (0.3-3.9)[22]
  • Phenylephrine: 1 reported case[23]
Vasoconstriction[8]
Diuretics
  • C-CS: Increased risk, 1.6 (1.2-2.1)[22]
Extracellular volume deficit, lower peripheral vascular resistance, vasoconstriction[8]
Ergot alkaloids (often combined with caffeine)
  • 20 reported cases[8,24]
Vasoconstriction[8]
Hormonal therapies
  • Predominance of women among young patients[25,26], common use of female hormones by female patients[27]
  • Female hormones C-CS: Increased risk, 1.88 (1.30-2.73)[3]
  • Oral contraceptives C-CS: Increased risk, 1.05 (1.00-1.10)[28]; risk unaffected, 0.59 (0.28-1.33)[29]; 0.7 (0.3-1.5)[22]
  • Estrogen replacement C-CS: Risk unaffected, 0.75 (0.67-1.19)[29]; 1.0 (0.7-1.5)[22]
Hypercoagulability, endothelial injury[8]
Laxatives
  • Osmotic agents: 2 reported cases[8]
  • Bisacodyl: 2 reported cases[8]
  • Bisacodyl/polyethylene glycol: 1 reported case of 2 episodes[30]
  • Lubiprostone: 1 reported case[31]
  • All drugs C-CS: Increased risk, 4.73 (3.71-6.02)[28]
Increased motility or rapid intravascular volume deficit, reduced perfusion[8]
Psychotropic drugs
  • 6 reported cases (2 with hypotension)[8,32,33]
  • 10 cases, clinical/pathological data incomplete[34]
  • C-CS: Increased risk, 3.7 (1.3-11.0)[22]
Hypotension, constipation
Serotoninergic drugs
  • 5-hydroxytryptamine1 receptor agonists: 12 cases from US FDA AERS (8 cases with age <50 years)[8,35-37]
  • 5-hydroxytryptamine3 receptor antagonist: 1 case of CI/1000 patient-years of use[38]
  • 5-hydroxytryptamine4 partial agonist: 27 reported cases (drug withdrawn)[39]
For 5-hydroxytryptamine1 receptor agonists vasoconstriction[8]; for other agents various factors[39]
Very low evidence
Digitalis
  • 1 reported case (poisoning)[8]
  • Digoxin C-CS: Increased risk, 3.6 (2.1-6.2)[22]; atrial fibrillation not analyzed; decreased risk, 0.27 (0.083-0.86)[40]
Vasoconstriction
Kayexalate
  • 1 reported case[41]
  • 44 cases of colon injury with incomplete pathological data[42]
Direct toxic effect, various non-drug factors[41,42]
NO-Xplode
  • 1 reported case[43]
Blood shunting to skeletal muscle, hypoperfusion, various non-drug factors[43]
NSAIDs
  • Reported cases not clearly distinguishable from NSAID-induced colopathy[8]
  • C-CS: Risk unaffected, 0.9 (0.6-1.2)[22]; 0.68 (0.62-1.27)[44]
Inhibition of vasodilating prostaglandins, vasoconstriction[8]
Statins
  • 2 reported cases[8,45]
None
Vasopressors
  • 1 reported case[8]
Vasoconstriction
The table provides the pharmacologic agents associated with colonic ischemia. Nonpharmacologic etiologies for colonic ischemia are presented in a separate table.
CI: colon ischemia; C-CS: case-control study (followed by odds ratio [95% confidence interval]); US FDA AERS: United States Food and Drug Administration Adverse Event Reporting System; R-CHOP: rituximab, cyclophosphamide, vincristine, doxorubicin, prednisolone; NSAID: nonsteroidal anti-inflammatory drug.
* Classified by the criteria of Naranjo et al.[13]
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Adapted by permission from Macmillan Publishers Ltd: American Journal of Gastroenterology. Brandt LJ, Feuerstadt P, Longstreth GF, et al. ACG clinical guideline: Epidemiology, risk factors, patterns of presentation, diagnosis, and management of colon ischemia (CI). Am J Gastroenterol 2015; 110:18. Copyright © 2015. www.nature.com/ajg.
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