Ketorolac

BRAND NAMES:

Toradol- It contains the active ingredient of ketorolac tromethamine. It is available in the form of tablets used to treat painkillers.

Sprix- It contains the active ingredient of ketorolac tromethamine. It is available in the form of nasal spray.

Acuvail- It contains the active ingredient of ketorolac tromethamine. It is available in the form of an Ophthalmic solution. 

Omidria –It contains the active ingredient of ketorolac and phenylephrine. It is available in the form of an Occular Solution.

MECHANISM OF ACTION:

The exact mechanism of action for ketorolac is not known. Like other NSAIDs, ketorolac blocks cyclooxygenases, which convert arachidonic acid into prostaglandins, prostacyclin, and thromboxane. The inhibition of these substances decreases pain, fever, and inflammation. Ketorolac does so by inhibiting both cyclooxygenase-1 and cyclooxygenase-2. Ketorolac has higher demonstrated potency than most other NSAIDs.

PHARMACOKINETICS:

Absorption: Ketorolac is completely absorbed after oral administration. A high-fat meal can decrease time-to-peak concentrations of ketorolac by approximately 1 hour. Antacids do not impact the extent of absorption. Ketorolac is quickly absorbed following intranasal administration, and the peak plasma concentration is achieved in approximately 30 to 45 minutes.

Distribution: The volume of distribution is approximately 13 liters.

Metabolism: Enzymes involved in phase I metabolism include CYP2C8 and CYPC9, while UDP-glucuronosyltransferase 2B7 is responsible for phase II metabolism. Ketorolac is extensively metabolized in the liver through hydroxylation or conjugation, however, it appears that glucuronic acid conjugation is the primary metabolic process.

Excretion: Ketorolac and metabolites are primarily excreted by the kidney. The elimination half-life ranges from 5 to 6 hours.

PHARMACODYNAMICS: 

Platelets, the stomach mucosa, and the vascular endothelium all contain the COX-1 enzyme, which is always active. The COX-2 enzyme, on the other hand, is inducible and regulates inflammation, pain, and fever levels. As a result, inhibiting the COX-1 enzyme increases the risk of bleeding and stomach ulcers, but inhibiting the COX-2 enzyme confers beneficial anti-inflammatory and analgesic characteristics. Despite its usefulness in pain treatment, ketorolac should not be used long-term because it raises the risk of major side effects such as gastrointestinal bleeding, peptic ulcers, and perforations.

DOSAGE AND ADMINISTRATION:

• Ketorolac tromethamine IV injection solution: 15 mg/ml; 30mg/ml.
• Ketorolac tromethamine IM injection solution: 60mg/ml
• Oral tablets: 10mg.

The administration of ketorolac can be done via oral, nasal spray, IV, or IM routes. The oral version should administered only following IV or IM ketorolac. Ketorolac administration should not continue for longer than 5 days, given an increased risk of cardiac thrombotic events, renal failure, peptic ulcers, and increased risk of bleeding beyond this point.

DRUG INTERACTIONS:

Drug interactions can alter how a medication works or increase the likelihood of major side effects.

• ACE inhibitors (Captopril, Lisinopril)

• Losartan and Valsartan are angiotensin II receptor blockers.

• Prednisone is a corticosteroid.

• Clopidogrel is an anti-platelet medication. 

• Warfarin is a blood thinner. 

• Aspirin and NSAIDs like Ibuprofen or Naproxen are pain relievers.

CONTRAINDICATIONS:

The drug is not recommended during labor and delivery as it negatively affects fetal circulation and decreases uterine contraction. Ketorolac is contraindicated in individuals who have adverse reactions or are allergic to NSAIDs. Ketorolac is contraindicated intraoperatively or preoperatively due to the increased risk of bleeding. Extreme caution is necessary when administering ketorolac to older patients. Ketorolac is contraindicated in coronary artery bypass graft surgery. Ketorolac is contraindicated in patients with renal disease or renal failure because it may increase fluid retention and worsen renal function. GI-related contraindications for ketorolac include patients with active peptic ulcer disease recent  GI bleeding GI bleeding or GI perforations.

SIDE EFFECTS:

•  Ketorolac causes side effects that may include

•  Headache

•  Dizziness

•  Drowsiness

•  Diarrhea

•  Constipation

•  Sweating

•  Ringing in the ear

•  Pain at the injection site

• Small red or purple dots on the skin

Some side effects can be serious and may include

• Yellowing of the skin or eyes

•  Excessive tiredness

•  Unusual bleeding or bruising

•  Lack of energy

•  Loss of appetite

•  Nausea

•  Upper right stomach pain

•  Flu-like symptoms

•  Pale skin

•  Fast heartbeat

OVERDOSE:

Management of overdose is usually supportive care and discontinuation of ketorolac. Arterial blood gas analysis reveals high anion gap metabolic acidosis. There is no anti dote for ketorolac. Hemodialysis is not helpful due to high plasma protein binding. 

Side effects of overdose include

•  Nausea

•  Vomiting

•   Stomach pain

•   Bloody, black, or tarry stools

•   Drowsiness

•   Hives

•   Rash

•   Itching

•   Difficulty swallowing

•  Coma

TOXICITY:

High quantities or prolonged use of ketorolac can lead to hepatotoxicity and nephrotoxicity. In addition, ketorolac can cause multiple skin disorders such as toxic epidermal necrolysis. Anaphylactic shock has been characterized due to ketorolac overdose.

STORAGE:

Store between 20 and 25 degrees Celsius (68 and 77 degrees Fahrenheit). Keep out of direct sunlight.