Ketorolac

Mechanism

💊 Common Business Names

Toradol, Droal, Lixidol, Kerlac, Bongesic.

🔬 Pharmacological Group

Derived from pyrrolizinic acid. Powerful analgesic, non-selective NSAID.

Mechanism of Action

Ketorolac acts as a potent non-selective inhibitor of cyclooxygenases:

• Marked inhibition of COX-1 and COX-2: Although it blocks both isoforms, it has a significantly higher affinity and potency towards COX-1 at therapeutic concentrations. This inhibition decreases the synthesis of prostaglandins in the CNS and in the periphery, interrupting the nociceptive cascade. Its effectiveness in acute pain is extremely high, but the marked depletion of homeostatic prostaglandins in the gastric mucosa explains its high gastrointestinal toxicity.

Pharmacokinetics

Key Pharmacokinetics

Indicators and dose

Dosage and Adjustment

• Adults (under 65 years of age, weight >50 kg and normal kidney function):
  • Parenteral route (IV/IM): 30 mg every 6 hours as needed. Maximum daily parenteral dose: 120 mg/day.
  • Oral Route (continued): 10 mg every 6 or 8 hours. Maximum oral dose: 40 mg/day.
• Elderly Patients (>65 years), Weight less than 50 kg or Mild Renal Failure:
  • Parenteral route: 15 mg every 6 hours. Maximum recommended daily dose: 60 mg/day.
  • Oral: 10 mg every 8 hours (maximum 30 mg/day).
• Adjustment in Kidney Failure:
  • Cl_cr ≥ 60 mL/min: Standard dose adjusted to age/weight.
  • Cl_cr 45-59 mL/min: Reduce the parenteral dose by half (maximum 60 mg/day).
  • Cl_cr < 45 mL/min: Absolutely contraindicated.
• Adjustment in Liver Failure: No adjustment is required for short therapies of 48 hours, but contraindicated in uncontrolled cirrhosis.

Security

Contraindications

• Absolute: History of active peptic ulcer or recurrent gastrointestinal bleeding; suspicion or confirmation of active intracranial hemorrhage; bleeding diatheses or coagulation disorders; moderate to severe renal failure (Cl_cr < 45 mL/min or elevated serum creatinine); pronounced hypovolemia or acute dehydration (risk of irreversible kidney failure); Perioperative analgesic prophylaxis in major surgery with high risk of bleeding.
• Relative: Concomitant use with other NSAIDs, acetylsalicylic acid or oral anticoagulants; analgesic-induced asthma.

Adverse Effects (ADR)

• Common / Moderate: Dyspepsia, nausea, pain at the IM injection site, drowsiness, headache, water retention.
• Rare / Serious: Perforation of the gastric mucosa, massive upper gastrointestinal bleeding (significantly higher risk compared to other NSAIDs). Acute renal failure with papillary necrosis. Thrombocytopenia with prolonged bleeding time.
• Critical Gastrointestinal Risk: Ketorolac has a selectivity quotient that markedly favors the inhibition of COX-1 over COX-2. This intensely and persistently deprives the stomach of its natural cytoprotective barrier of mucus and bicarbonate, facilitating direct ulceration of the gastric mucosa by endogenous hydrochloric acid.

Critical Warning: Temporal Limit of Treatment

To minimize the incidence of serious gastrointestinal and renal adverse effects, the duration of treatment with ketorolac is strictly limited by global regulatory agencies: parenteral treatment (intravenous or intramuscular) should not exceed a maximum of 2 consecutive days, and follow-on adjunctive oral therapy should not be prolonged for more than 5 days. Use beyond these limits is associated with an exponential increase in the rate of gastrointestinal bleeding with risk of death.

Drug Interactions

• Other NSAIDs or Corticosteroids: Additive deleterious effect on the gastrointestinal mucosa. Avoid absolute coadministration.
• Pentoxyfylline: Concomitant use with ketorolac is associated with a marked increase in surgical and gastrointestinal bleeding due to antiplatelet synergism.
• Direct Action Anticoagulants and Heparins: Greater propensity for active bleeding due to annulment of reversible platelet aggregation mediated by thromboxane.

Pregnancy and Breastfeeding

Classified in FDA Category C/D. Absolutely contraindicated during the third trimester of pregnancy and in the peripartum period (inhibits uterine motility and increases the risk of obstetric hemorrhage). Breastfeeding: Compatible with caution; It is excreted in minimal quantities in breast milk, but due to the analgesic potency and systemic risks of the drug, the use of ibuprofen or paracetamol is preferred.