KERAL 25 mg

Indications

• Pain and inflammation in musculoskeletal disorders
• Pain and inflammation in osteoarthritis
• Pain and inflammation in rheumatoid arthritis
• Pain relief in other mild to moderate pain conditions

Dosage

Children: Refer to BNF for Children for appropriate dosing information.

Adults: Adult: 12.5 mg every 4–6 hours, alternatively 25 mg every 8 hours; maximum 75 mg per day.

Mechanism of action

Dexketoprofen exerts its effects by reducing prostaglandin synthesis through the inhibition of the cyclooxygenase pathway, specifically targeting both COX-1 and COX-2 enzymes. This leads to decreased inflammation and pain signaling in the body.

Pharmacodynamics

As an isomer of ketoprofen, dexketoprofen is recognized for its analgesic and anti-inflammatory effects. It is classified as a propionic acid derivative, which means it shares similar properties with other drugs in this class, providing effective pain relief and reducing inflammation.

Pharmacokinetics

Dexketoprofen is rapidly absorbed after oral administration, with peak plasma concentrations typically occurring within 1-2 hours. It has a half-life of approximately 1-2 hours, allowing for relatively frequent dosing to maintain therapeutic effects. The drug is primarily metabolized in the liver and excreted via the kidneys, and dose adjustments may be necessary in patients with hepatic or renal impairment.

Contra-indications

• History of hypersensitivity to aspirin or any other NSAID
• Active gastrointestinal bleeding
• Active gastrointestinal ulceration
• Cerebrovascular disease
• Inflammatory bowel disease
• Ischaemic heart disease
• Mild to severe heart failure
• Peripheral arterial disease

Adverse effects

• Gastrointestinal discomfort
• Nausea
• Drowsiness
• Fluid retention
• Skin reactions
• Chest pain
• Myocardial infarction
• Depression
• Conjunctivitis
• Constipation

Interactions

• Concurrent use of fluconazole may require dose adjustment
• Risk of renal impairment with other NSAIDs or in patients with renal insufficiency

Precautions

• Use caution in patients with hepatic impairment
• Monitor blood pressure before and during treatment
• Long-term use may reduce female fertility, reversible on stopping treatment

Pregnancy

Avoid, as it is teratogenic in animal studies.

Breast-feeding

Avoid, as it is present in milk in animal studies.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• 100 mg capsules
• 25 mg and 12.5 mg capsules

Indications

• Metabolic acidosis
• Severe hyperkalaemia
• Renal artery stenosis
• Nephrotic syndrome
• Severe heart failure
• Potassium depletion due to diuretics

Dosage

Children: Dosing in children should be appropriate to the body weight and clinical

Adults: Dosage must be tailored to the individual patient's acid-base status and clinical condition. Refer to the BNF for specific dosing guidelines.

Mechanism of action

Trometamol is a weak base that functions as a proton acceptor. Upon intravenous administration, it binds to hydrogen ions and associated acid anions, leading to their excretion in urine. It is capable of combining with lactic, pyruvic, and other metabolic acids, thereby reducing hydrogen ion concentration in the body. The drug's ionized form predominates at physiological pH, allowing it to penetrate cell membranes and interact with intracellular acids. This action increases bicarbonate concentration and decreases carbon dioxide tension, potentially leading to hypoventilation.

Pharmacodynamics

Trometamol reduces acidity in the body by acting on acid-base buffers, thus shifting the balance towards alkalinity. It increases the flow of alkaline urine, enhancing diuresis and electrolyte excretion. The correction of metabolic acidosis can improve various physiological functions, but caution is required due to the potential for respiratory depression caused by decreased carbon dioxide tension.

Pharmacokinetics

Trometamol is administered intravenously and rapidly distributes into extracellular fluids. It is metabolized primarily in the liver, with renal excretion of the resultant salts. The onset of action is typically quick, and the duration of effect depends on the severity of acidosis and the therapeutic context. Monitoring of plasma potassium levels is essential, particularly in patients with renal impairment.

Contra-indications

• Anuria
• Chronic respiratory acidosis

Adverse effects

• Hepatic necrosis in neonates
• Hypoglycaemia
• Respiratory depression

Interactions

• Potassium salts may cause nausea and vomiting
• Drugs exacerbating hyperkalaemia should be reviewed and stopped as appropriate

Precautions

• Extravasation can cause severe tissue damage
• Use with caution in renal impairment due to risk of hyperkalaemia

Pregnancy

Limited information available, management of hyperkalaemia may harm fetus.

Breast-feeding

No information available.

Storage

Store in a cool, dry place. Protect from light.

Formulations

• Solution for infusion (Trometamol 363.4 mg per 1 ml, Tris 36.34% solution for infusion)

Mechanism of action

It is a non-steroidal anti-inflammatory drug (NSAID) that reduces prostaglandin synthesis via inhibition of cyclooxygenase pathway (both COX-1 and COX-2) activity.

Pharmacodynamics

This drug is an isomer of ketoprofen. Dexketoprofen a propionic acid derivative with analgesic, anti-inflammatory, and antipyretic properties.

Mechanism of action

Tromethamine is an alkalinizing agent which acts as a proton (hydrogen ion) acceptor. Tromethamine is a weak base; following IV injection, it attracts and combines with hydrogen ions and their associated acid anions and the resulting salts are excreted in urine. Tromethamine can combine with lactic, pyruvic, and other metabolic acids and with carbonic acid. ... At pH 7.4, approximately 70% of the tromethamine present in plasma is in the ionized (protonated) form; if pH is decreased from pH 7.4, the ionized fraction of the drug is increased. In contrast to the ionized fraction of tromethamine, which upon administration reacts only with acid in the extracellular fluids, the fraction of the dose which remains un-ionized at physiologic pH is thought to be capable of penetrating the cell membrane to combine with intracellular acid. Since administration of tromethamine reduces hydrogen ion concentration, there is a decrease in proton donor and an increase in proton acceptor concentrations in body buffers. In the bicarbonate:carbonic acid buffer, the concentration of dissolved carbon dioxide is decreased (at least until regulatory mechanisms compensate) and the concentration of bicarbonate is increased. The reduction of carbon dioxide tension removes a potent stimulus to breathing and may result in hypoventilation and hypoxia. Tromethamine ... acts as a weak, osmotic diuretic, increasing the flow of alkaline urine containing increased amounts of electrolytes. By removing protons from hydronium ions, ionization of carbonic acid is shifted so as to decrease pCO2 and to increase bicarbonate. Excess bicarbonate is then gradually excreted in kidney. /Tromethamine is an/ especially useful way to manage excessively high pCO2 in respiratory acidosis...