ENDOPROST 125 MCG INJECTION

Indications

• Prevention of uterine atony after caesarean section
• Treatment of postpartum hemorrhage due to uterine atony

Dosage

Adults: 100 micrograms as a single dose, administered by slow intravenous injection over 1 minute, as soon as possible after delivery, preferably before removal of the placenta.

Mechanism of action

Carboprost acts as a potent agonist at the prostaglandin F2α receptor (FP receptor), leading to increased intracellular calcium levels, which in turn stimulates uterine muscle contraction. This mechanism is crucial in controlling uterine atony, a common condition that can lead to significant postpartum hemorrhage.

Pharmacodynamics

As a prostaglandin analogue, Carboprost enhances uterine tone and motility. Its effects are dose-dependent, with higher doses resulting in more pronounced uterine contractions. The medication also has potential effects on other smooth muscle tissues, which may contribute to its side effect profile, including gastrointestinal symptoms.

Pharmacokinetics

Carboprost is administered intravenously, allowing for rapid onset of action. The pharmacokinetics are characterized by a quick distribution phase followed by elimination. It has a half-life of approximately 20 minutes when administered intravenously. Metabolism primarily occurs in the liver, and the drug is excreted in urine. Patients with hepatic or renal impairment may require careful monitoring or dose adjustments.

Contra-indications

• Eclampsia
• Epilepsy
• Pre-eclampsia
• Active hepatic disease
• Severe asthma
• Severe cardiovascular disease

Adverse effects

• Anxiety
• Chest pain
• Chills
• Dizziness
• Dyspnoea
• Feeling hot
• Flushing
• Headache
• Hypotension
• Hyperglycaemia
• Nausea
• Tachycardia
• Vomiting

Precautions

• Caution in patients with renal impairment
• Caution in patients with hepatic impairment
• Caution in patients with a history of asthma or cardiovascular disease
• Caution in patients with migraine
• Caution in patients with hyponatraemia

Pregnancy

Carboprost is used in obstetrics, specifically to prevent uterine atony after delivery.

Breast-feeding

Consult with a healthcare provider; limited data available on the excretion of Carboprost in breast milk.

Storage

Store in a cool, dry place, protected from light. Follow manufacturer's instructions for specific storage conditions.

Formulations

• Solution for injection: Carboprost (as Carboprost trometamol) 250 micrograms per 1 ml

Indications

• Metabolic acidosis
• Acute kidney injury
• Cardiac arrest
• Severe lactic acidosis

Dosage

Children: Refer to BNF for Children for appropriate dosing in paediatric patients.

Adults: Refer to BNF for specific dosing guidelines based on clinical condition and severity of acidosis.

Mechanism of action

Tromethamine functions as a proton acceptor, interacting with hydrogen ions and their associated acid anions. It combines with lactic, pyruvic, and other metabolic acids, as well as carbonic acid, facilitating their excretion in urine. At physiological pH, tromethamine exists in both ionized and un-ionized forms, with the latter capable of penetrating cell membranes to neutralize intracellular acids. By reducing hydrogen ion concentration, tromethamine alters the bicarbonate:carbonic acid buffer system, increasing bicarbonate levels while decreasing carbon dioxide tension, which may lead to hypoventilation.

Pharmacodynamics

As an alkalinizing agent, tromethamine increases bicarbonate concentrations in the blood, thereby helping to correct metabolic acidosis. Its ability to act as a weak osmotic diuretic contributes to increased urine output and the excretion of electrolytes. This dual action is beneficial in managing conditions characterized by acid-base imbalances.

Pharmacokinetics

After intravenous administration, tromethamine is rapidly distributed in the body. It is primarily excreted unchanged in the urine, with its alkalinizing effects lasting until the body's regulatory mechanisms restore acid-base balance. The pharmacokinetics are influenced by the ionization state of the drug, which varies with pH levels.

Adverse effects

• Hypoventilation
• Hypoxia
• Fluid and electrolyte imbalances
• Metabolic alkalosis
• Nausea
• Vomiting

Precautions

• Use with caution in patients with respiratory depression
• Monitor patients for signs of fluid overload
• Assess electrolyte levels regularly during treatment

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Tromethamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether tromethamine is excreted in human milk. Caution should be exercised when administering tromethamine to a nursing mother.

Storage

Store at room temperature, away from light and moisture. Do not freeze.

Formulations

• Injection solution

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...