DIMINAL INJECTION

Indications

• Support in hepatic encephalopathy
• Enhancement of nitrogen balance in catabolic states
• Potential use in improving endothelial function

Dosage

Children: Refer to specific clinical guidelines or product monographs for dosing information tailored to individual patient needs.

Adults: Refer to specific clinical guidelines or product monographs for dosing information tailored to individual patient needs.

Mechanism of action

Diacerturate functions as a precursor to arginine and plays a role in the urea cycle, facilitating the conversion of ammonia to urea, thus aiding in nitrogen disposal. Additionally, it may enhance nitric oxide production, contributing to vasodilation and improved blood flow.

Pharmacodynamics

Diacerturate has been shown to influence various metabolic pathways, particularly those involved in amino acid metabolism and nitrogen balance. Its effects on nitric oxide synthesis may also contribute to improvements in endothelial function and cardiovascular health.

Pharmacokinetics

Diacerturate is absorbed via the gastrointestinal tract, with peak plasma concentrations occurring within a few hours post-administration. It undergoes metabolism primarily in the liver, where it is converted into arginine and other metabolites. The elimination half-life is variable, depending on individual metabolic rates and liver function.

Pregnancy

There is limited data on the use of diacerturate in pregnancy. Caution is advised, and it should only be used if the potential benefits justify the potential risks to the fetus.

Breast-feeding

The safety of diacerturate during breastfeeding has not been established. Caution is recommended, and it should only be used if necessary.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Indications

• Trypanosomiasis (sleeping sickness)
• Nagana in livestock
• Infections caused by Trypanosoma brucei
• Infections caused by Trypanosoma congolense

Dosage

Children: Paediatric dosing of diminazene should be derived from the BNF for Children, taking into account the weight and age of the child. Refer to the BNF for Children for specific dosing recommendations.

Adults: The dosage for adults should be determined based on the specific condition and patient factors. Refer to the BNF for accurate dosing guidelines.

Mechanism of action

Diminazene acts by inhibiting the enzyme dihydrofolate reductase, which is crucial for the synthesis of folate in protozoa. This inhibition disrupts the folate metabolic pathway, leading to a decrease in nucleic acid synthesis and ultimately resulting in the death of the protozoan parasites. Additionally, it may interfere with the mitochondrial function of the parasites, further contributing to its antiparasitic effects.

Pharmacodynamics

The pharmacodynamics of diminazene involve its selective action on trypanosomes, with the drug being less toxic to host cells. It has a high affinity for the target enzyme, allowing for effective suppression of protozoan growth. The drug's therapeutic index is favorable, meaning it can effectively treat infections at doses that are relatively safe for the host.

Pharmacokinetics

Diminazene is well-absorbed following parenteral administration. It is widely distributed throughout the body, with a significant volume of distribution. The drug undergoes hepatic metabolism, and its elimination half-life can vary depending on species and individual health. Excretion is primarily via the urine, with metabolites detected in both urine and feces.

Adverse effects

• Anorexia
• Vomiting
• Diarrhoea
• Lethargy
• Neurological signs (e.g., tremors, ataxia)
• Hypersensitivity reactions

Precautions

• Use with caution in animals with hepatic or renal impairment.
• Monitor for signs of toxicity, especially in cases of overdose.

Pregnancy

Safety during pregnancy has not been established; use only if the benefits outweigh the risks.

Breast-feeding

Safety during breastfeeding has not been established; use with caution.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Injection solution

Indications

• Pain relief
• Fever reduction
• Ear pain
• Testing drug metabolism

Dosage

Children: Refer to the BNF for Children for specific dosing guidance.

Adults: Refer to the BNF for specific dosing guidance.

Mechanism of action

Phenazone acts primarily in the central nervous system (CNS), increasing the pain threshold through the inhibition of cyclooxygenase enzymes, specifically COX-1, COX-2, and COX-3. This inhibition disrupts the synthesis of prostaglandins, which are mediators of pain and inflammation.

Pharmacodynamics

As an analgesic and antipyretic, phenazone serves to alleviate pain and reduce fever. It is frequently employed in pharmacological studies to assess the impact of other drugs or disease states on hepatic drug-metabolizing enzymes, demonstrating its importance in understanding drug interactions and metabolism.

Pharmacokinetics

Phenazone is absorbed well when administered orally. Its distribution in the body is extensive, and it is metabolized primarily in the liver, where it undergoes oxidation. The drug is excreted mainly through the kidneys. The elimination half-life can vary among individuals based on metabolic factors and liver function, necessitating caution in patients with hepatic impairment.

Adverse effects

• Nausea
• Vomiting
• Allergic reactions
• Skin rash
• Dizziness

Precautions

• Use with caution in patients with liver disease
• Monitor for signs of hypersensitivity

Pregnancy

Phenazone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

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

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Oral tablets
• Ear drops

Mechanism of action

Antipyrine is thought to act primarily in the CNS, increasing the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin (PG) synthesis.

Pharmacodynamics

Antipyrine is an analgesic and antipyretic that has been given by mouth and as ear drops. Antipyrine is often used in testing the effects of other drugs or diseases on drug-metabolizing enzymes in the liver. (From Martindale, The Extra Pharmacopoeia, 30th ed, p29)