ENZAPROST T SOLUTION FOR INJECTION (Each ml contains Dinaprost Trometamol 5mg)

Indications

• Induction of labor
• Medical abortion
• Management of missed abortion
• Treatment of postpartum hemorrhage

Dosage

Children: Refer to the BNF for Children for dosing in paediatric populations.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Dinaprost acts by binding to specific prostaglandin receptors, which leads to changes in intracellular calcium levels and subsequent stimulation or inhibition of cyclic AMP accumulation. This interaction results in the contraction of uterine smooth muscle and the regression of the corpus luteum, thus interrupting early pregnancy. The drug exhibits species variation in its effects and has been shown to cause vasodilation when injected into human tissues.

Pharmacodynamics

Dinaprost influences uterine contraction and progesterone output. Its action on the uterine smooth muscles is additive when used in conjunction with oxytocin. The drug’s vasodilatory effects are observed in certain vascular beds, reflecting its complex pharmacological profile which includes both stimulatory and inhibitory roles depending on the tissue and receptor type involved.

Pharmacokinetics

Dinaprost is administered parenterally and exhibits a rapid onset of action. It is metabolized via the eicosanoid metabolic pathway and is subject to degradation by cyclooxygenases. Its pharmacokinetic profile includes a short half-life, necessitating careful dosing and timing in clinical use to ensure effective therapeutic outcomes.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Headache
• Dizziness
• Flushing
• Fever
• Chills
• Uterine hypertonicity

Precautions

• Use with caution in patients with cardiovascular disease
• Monitor for signs of uterine hyperstimulation
• Consider potential effects on blood pressure

Pregnancy

Dinaprost is contraindicated in pregnancy as it can induce uterine contractions and may lead to abortion.

Breast-feeding

The effects of dinaprost during breastfeeding are not well-studied; caution is advised.

Storage

Store at room temperature, away from light and moisture. Protect from freezing.

Formulations

• Injection solution

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

...THERE IS NO SINGLE PROSTAGLANDIN RECEPTOR. ... IT IS POSSIBLE TO DEMONSTRATE CALCIUM DEPENDENCE OF DIVERSE RESPONSES TO PROSTAGLANDINS & TO OBSERVE ALTERED CALCIUM FLUXES. ...PROSTAGLANDINS MAY EITHER STIMULATE OR INHIBIT ACCUM OF CYCLIC AMP. /PROSTAGLANDINS/ RESPONSES TO PROSTAGLANDIN F2ALPHA SHOW SPECIES VARIATION, BUT VASODILATATION HAS BEEN OBSERVED FOLLOWING INJECTION INTO HUMAN BRACHIAL ARTERY OF PGF2ALPHA... SUPERFICIAL VEINS OF HAND ARE CONTRACTED BY PFG2ALPHA... PROMPT SUBSIDENCE OF PROGESTERONE OUTPUT & REGRESSION OF CORPUS LUTEUM FOLLOWS PARENTERAL INJECTION OF PROSTAGLANDIN F2ALPHA... THIS EFFECT INTERRUPTS EARLY PREGNANCY, WHICH IS DEPENDENT ON LUTEAL RATHER THAN PLACENTAL PROGESTERONE. OXYTOCIN & PROSTAGLANDINS AFFECT UTERINE SMOOTH MUSCLES BY DIFFERENT MECHANISMS, & THEIR EFFECTS ARE ADDITIVE. POSSIBLE ADVANTAGES OF THEIR COMBINED USE ARE BEING EXPLORED. /PROSTAGLANDINS/

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...