Ketorolac: Mechanism of Action, Uses, Dosage, Side Effects, Drug Interaction

There are several nonsteroidal anti-inflammatory drugs used to treat pain, fever and inflammation. The NSAIDs are classified into several sub-groups. Ketorolac is included in acetic acid derivative of NSAIDs. The used NSAIDs grouped in acetic acid derivative are Indomethacine, Sulindac, Etodolac, Nabumetone and Tolmetic. Ketorolac is being prescribed since 1989. Ketorolac was approved by FDA for use as eye drop 1992 and nasal spray in 2010. Ketorolac is widely used in USA.

Ketorolac

Alternative Name of Ketorolac

Ketorolac is also known as Toradol.

Mechanism of Action of Ketorolac

Ketorolac blocks the action of cyclooxygenase enzyme 1 (COX 1) and 2 (COX 2). Stimulation of COX 1 enzyme increases secretion of prostaglandin in mucosal membrane of stomach and intestine. Similarly, COX 2 enzyme is activated in almost all tissues following injury and infection resulting in increased enzyme prostaglandin secretion.

Prostaglandin induces inflammatory changes in infected and injured tissue. Ketorolac blocks the action of COX 1 and COX 2 enzyme resulting in low or near zero concentration of prostaglandin in inflammatory tissue as well as mucosal membrane.

Uses: Ketorolac is Used For Treatment Of Following Symptoms

Pain- Ketorolac is prescribed for acute and chronic pain caused by soft tissue infection or injuries. Acute pain is also known as nociceptive pain. Nociceptive pain is observed following injuries, surgery and infection. Such pain is treated with toradol. Ketorolac is widely used instead opioids ER for as an analgesics in patient with history of head or chest injury.

Inflammation- Increase secretion of prostaglandin following infection or injuries causes increase secretion of prostaglandin. Prostaglandin initiate inflammation that results in pain, swelling of tissue and increase blood flow. Inflammation often spreads in adjacent tissue and difficult to treat. Toradol (ketorolac) controls as well as decreases secretion of prostaglandin. Low or absence of prostaglandin secretion reduces inflammation.

Fever- Fever is often seen in patient suffering with infection and tissue inflammation. Fever is caused by increased metabolism. The body metabolism in increased because prostaglandin resets the temperature to higher level. Ketorolac resets the temperature to normal level and that helps to reduce metabolism and decrease physiological energy production.

Postoperative pain- Ketorolac used as a premedication for pain and preferred drug in most surgical center. The intramuscular or intravenous ketorolac is given prior to minor surgery. Ketorolac helps to reduced opioid requirement and prevents opioid side effects.

Ketorolac is Used To Treat Following Diseases

Dosage of Ketorolac

Ibuprofen is sold over the shelf in most pharmacies in the form of pills and syrup. The dosage advised is 10 to 15 mg per kg in pediatric cases and 600 mg to 2,400 mg in adult. The strength of pills is 200 mg, 400 mg and 600 mg. Similarly, liquid syrup is prep with concentration of 200 mg to 600 mg per 5 mls.

Ibuprofen is tried at higher dosage and dosage varied between 100 mg / kgm and 400 mg/ kgm. The toxicity is rarely observed at dosage 100 mg / kgm and below. Ketorolac is also used as a nasal spray.

Duration of Action Ketorolac

Ibuprofen helps to relieve pain and fever. The duration of optimum effects after oral consumption of medication is 3 to 4 hours. The peak effect is observed after 2 hours.

Side Effects Caused by Ketorolac

  • Abdominal pain secondary to gastric and intestinal ulcer;
  • Gastric or intestinal bleeding from eroded surface of ulcer;
  • Dizziness;
  • Rash;
  • Bronchospasm;
  • Hypertension;
  • Constipation;
  • Tinnitus- ear ringing;
  • Nystagmus.
  • Ketorolac is Avoided in Patient Suffering with Following Disease:
  • Congestive heart failure and myocardial infarction;
  • Hypertension;
  • Kidney failure;
  • Liver failure;
  • Metabolic acidosis;
  • Avoided in first tri-master;
  • Stroke;
  • Hypersensitivity;
  • Pemphigoid like blistering;
  • Avoided in individual who is consuming frequently alcohol.

Drug Interaction-

Ketorolac binds to serum protein once absorbed in blood. Most drugs then carried within blood to different organs, where drug is release for physiological action. There are several medications binds to protein like albumin and globulin in blood serum. The number of free albumin and globulin in blood serum decreases during ketorolac therapy since ketorolac binds to serum protein. Medication like antihypertensive drugs, diuretics and antibiotics are competing with ketorolac to bind serum protein. Lack of availability of free serum protein results in availability of increase amount of medications in blood. Such condition causes low blood pressure, antibiotic side effects and increase diuretic effect since less protein bound antihypertensive, antibiotics and diuretics drug is circulated in blood.

References

  1. Analgesia and COX-2 inhibition.

    Clin Exp Rheumatol. 2001 Nov-Dec;19, Dionne RA1, Khan AA, Gordon SM.

  2. Ketorolac for Pain Management: A Review of the Clinical Evidence [Internet].

    Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2014 Jun.

  3. Patterns of Ketorolac dosing by emergency physicians.

    World J Emerg Med. 2017;8(1):43-46.

    Soleyman-Zomalan E1, Motov S2, Likourezos A2, Cohen V3, Pushkar I2, Fromm C2.

  4. Safety Considerations in the Use of Ketorolac for Postoperative Pain.

    2017;12(1):67-73. doi: 10.2174/1574886311666160719154420.

    Maslin B1, Lipana L, Roth B, Kodumudi G, Vadivelu N.

  5. Ketorolac tromethamine – routes and clinical implications.

    Pain Pract. 2015 Feb;15(2):175-93. doi: 10.1111/papr.12198. Epub 2014 Apr 16.

    Vadivelu N1, Gowda AM, Urman RD, Jolly S, Kodumudi V, Maria M, Taylor R Jr, Pergolizzi JV Jr.

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