I.DNOR PLUS

Mechanism of action

Cyanocobalamin serves as a cofactor for methionine synthase and L-methylmalonyl-CoA mutase enzymes. Methionine synthase is essential for the synthesis of purines and pyrimidines that form DNA. L-methylmalonyl-CoA mutase is involved in the degradation of propionate, crucial for fat and protein metabolism. The lack of vitamin B12 results in the accumulation of methylmalonyl CoA, contributing to neurological manifestations. Additionally, it is vital for the synthesis of methionine from homocysteine, and its deficiency can lead to functional folate deficiency, which impacts red blood cell formation.

Pharmacodynamics

Cyanocobalamin corrects vitamin B12 deficiency and alleviates symptoms and laboratory abnormalities associated with pernicious anemia, such as megaloblastic indices, gastrointestinal lesions, and neurological damage. It is essential for growth, cell reproduction, hematopoiesis, nucleoprotein, and myelin synthesis. The drug significantly impacts fat and carbohydrate metabolism, as well as protein synthesis. Rapidly dividing cells, such as those in the bone marrow, have a high demand for vitamin B12. Parenteral administration of cyanocobalamin can quickly reverse the anemia and gastrointestinal symptoms of vitamin B12 deficiency, while also preventing the progression of related neurological damage.

Pharmacokinetics

Cyanocobalamin is absorbed in the intestine, primarily in the ileum, via specific transport mechanisms that may be impaired in individuals with intrinsic factor deficiency (as seen in pernicious anemia). Once absorbed, it is widely distributed in body tissues, with significant concentrations found in the liver, kidneys, and heart. The vitamin is stored in the liver, where it can be released into circulation as needed. Cyanocobalamin undergoes conversion to its active forms, methylcobalamin and adenosylcobalamin, which are utilized in various metabolic processes. The elimination half-life is variable, but it is generally excreted via urine as metabolites

Adverse effects

• Abdominal distension
• Decreased appetite
• Flatulence
• Nausea

Interactions

• Folic acid may interact with cyanocobalamin, especially in cases of megaloblastic anemia caused by folate deficiency.

Precautions

• Should not be given alone for pernicious anemia.
• Use caution in patients with Leber's disease, as it may worsen optic atrophy.

Pregnancy

Cyanocobalamin is essential during pregnancy as it helps prevent neural tube defects. It is advised that females of childbearing potential take 5 mg of folic acid daily before conception and throughout pregnancy.

Breast-feeding

Cyanocobalamin is generally considered safe during breastfeeding, but it is advised to monitor the infant for any adverse effects.

Storage

Store in a cool, dry place, away from direct sunlight. Protect from moisture.

Formulations

• Tablet: 1000 micrograms
• Tablet: 500 micrograms
• Tablet: 100 micrograms
• Oral solution: 50 micrograms per ml
• Solution for injection: 1000 micrograms per ml

Indications

• Hypovolemia
• Shock
• Surgery
• Burns

Dosage

Children: Refer to the specific product information or guidelines for paediatric dosage, as it may vary based on the indication and formulation used.

Adults: Refer to the specific product information or guidelines for adult dosage, as it may vary based on the indication and formulation used.

Mechanism of action

Dextran acts as an osmotic agent. When administered intravenously, it increases plasma volume by drawing water into the vascular space. This expansion of blood volume helps in maintaining blood pressure and improving perfusion to tissues.

Pharmacodynamics

The pharmacodynamics of dextran involves its ability to enhance blood flow and reduce blood viscosity. It can improve rheological properties of blood, thereby facilitating better circulation. Dextran's molecular size allows it to remain in the circulation for an extended period, contributing to its volume-expanding effects.

Pharmacokinetics

Dextran is administered intravenously and is distributed in the vascular compartment. Its elimination occurs through renal filtration, and it is eventually degraded by enzymatic action in the liver. The half-life can vary depending on the molecular weight of the dextran used, with larger molecules generally having a longer half-life.

Contra-indications

• Hypersensitivity to dextran or any component of the formulation
• Severe renal impairment
• Congestive heart failure
• Active bleeding or hemorrhagic disorders

Adverse effects

• Allergic reactions, including anaphylaxis
• Fluid overload
• Hypotension
• Headache
• Nausea and vomiting
• Fever
• Thrombocytopenia
• Acute kidney injury

Interactions

• Anticoagulants - may enhance the effects of anticoagulants leading to increased bleeding risk
• Diuretics - may increase the risk of fluid overload and electrolyte imbalances

Precautions

• Use with caution in patients with cardiovascular disease
• Monitor fluid balance closely in patients with renal impairment
• Careful administration in patients with a history of allergic reactions

Pregnancy

Safety during pregnancy has not been established. Use only if clearly needed and potential benefits justify potential risks.

Breast-feeding

Excretion in human milk is unknown. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Injectable solution for intravenous infusion
• Oral formulations (less common, specific to certain indications)

Indications

• Solvent in pharmaceutical formulations
• Moisturizer and humectant in topical applications
• Potential use in the management of drug solubility issues

Dosage

Children: Refer to specific formulations and clinical guidelines, as dosing varies widely based on the application and formulation.

Adults: Refer to specific formulations and clinical guidelines, as dosing varies widely based on the application and formulation.

Mechanism of action

Glycols, particularly propylene glycol, act as humectants, which help to retain moisture in formulations. They can also enhance the solubility of drugs, aiding in their absorption when used as excipients. Propylene glycol is metabolized in the liver to lactate and subsequently to glucose, providing a source of energy when utilized in metabolic pathways.

Pharmacodynamics

The pharmacodynamics of glycols involve their ability to modulate the viscosity of solutions and enhance the solubility of other compounds. Propylene glycol can also facilitate the absorption of other drugs when used in formulations. It exhibits a low toxicity profile when used appropriately, but excessive systemic exposure can lead to metabolic acidosis and other adverse effects.

Pharmacokinetics

Glycols are rapidly absorbed when administered intravenously or orally. Propylene glycol is metabolized primarily in the liver, with a half-life varying based on the dose and individual metabolism. Renal excretion plays a role in the elimination of metabolites. Accumulation can occur in individuals with impaired liver or kidney function, necessitating careful monitoring of dosing in such populations.

Pregnancy

The safety of glycol in pregnancy is not well established. Consult healthcare professionals before use.

Breast-feeding

Glycol's effects during breastfeeding are not well characterized. Caution is advised.

Storage

Store in a cool, dry place away from direct sunlight and moisture.

Indications

• Plant growth regulation
• Agricultural applications as a growth inhibitor

Dosage

Children: Not applicable.

Adults: Refer to the relevant agricultural guidelines for specific applications.

Mechanism of action

In an in vitro study, propylene acts as a plant growth inhibitor by inhibiting the oxidation of indole-3-acetic acid by peroxidase in the presence of superoxide anion radicals. This inhibition is linked to the activation of an iron complex (compound III) shuttle, which enhances the reaction rate between superoxide and peroxidase, ultimately affecting plant growth processes. Propylene is a less effective inhibitor compared to ethylene.

Pharmacodynamics

The pharmacodynamic effects of propylene are primarily observed in its role as a growth inhibitor in plants. By modulating the oxidation of phytohormones like indole-3-acetic acid, propylene can influence various growth responses in plants, potentially affecting processes such as cell elongation and division.

Pharmacokinetics

Information on the pharmacokinetics of propylene in humans is not well-documented, as its primary uses are industrial and agricultural. Its metabolism may be influenced by environmental factors, and its effects are primarily studied in the context of plant biology rather than human pharmacology.

Mechanism of action

Vitamin B12 serves as a cofactor for _methionine synthase_ and _L-methylmalonyl-CoA mutase_ enzymes. Methionine synthase is essential for the synthesis of purines and pyrimidines that form DNA. L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to _succinyl-CoA_ in the degradation of propionate, an important reaction required for both fat and protein metabolism. It is a lack of vitamin B12 cofactor in the above reaction and the resulting accumulation of methylmalonyl CoA that is believed to be responsible for the neurological manifestations of B12 deficiency. Succinyl-CoA is also necessary for the synthesis of hemoglobin. In tissues, vitamin B12 is required for the synthesis of _methionine_ from homocysteine. Methionine is required for the formation of S-adenosylmethionine, a methyl donor for nearly 100 substrates, comprised of DNA, RNA, hormones, proteins, as well as lipids. Without vitamin B12, tetrahydrofolate cannot be regenerated from 5-methyltetrahydrofolate, and this can lead to functional folate deficiency,. This reaction is dependent on methylcobalamin (vitamin B12) as a co-factor and is also dependent on folate, in which the methyl group of methyltetrahydrofolate is transferred to homocysteine to form _methionine_ and _tetrahydrofolate_. Vitamin B12 incorporates into circulating folic acid into growing red blood cells; retaining the folate in these cells. A deficiency of vitamin B12 and the interruption of this reaction leads to the development of megaloblastic anemia.

Pharmacodynamics

**General effects** Cyanocobalamin corrects vitamin B12 deficiency and improves the symptoms and laboratory abnormalities associated with pernicious anemia (megaloblastic indices, gastrointestinal lesions, and neurologic damage). This drug aids in growth, cell reproduction, hematopoiesis, nucleoprotein, and myelin synthesis. It also plays an important role in fat metabolism, carbohydrate metabolism, as well as protein synthesis. Cells that undergo rapid division (for example, epithelial cells, bone marrow, and myeloid cells) have a high demand for vitamin B12. **Parenteral cyanocobalamin effects** The parenteral administration of vitamin B12 rapidly and completely reverses the megaloblastic anemia and gastrointestinal symptoms of vitamin B12 deficiency. Rapid parenteral administration of vitamin B12 in deficiency related neurological damage prevents the progression of this condition. **Nasal spray effects** In 24 vitamin B12 deficient patients who were already stabilized on intramuscular (IM) vitamin B12 therapy, single daily doses of intranasal cyanocobalamin for 8 weeks lead to serum vitamin B12 concentrations that were within the target therapeutic range (>200 ng/L).

Mechanism of action

In an in vitro study of the mechanism of action of ethylene as a plant growth inhibitor, the effects of ethylene and some of its analogs, including propylene, on the oxidation of indole-3-acetic acid were examined. Ethylene and its analogs inhibited the oxidation of indole-3-acetic acid by peroxidase under conditions where the iron complex (compound III, an oxy-ferrous complex of peroxidase) shuttle was activated. Inhibition occurred only in the presence of the superoxide anion radical 02(-). Spectral and kinetic data indicated that ethylene and its analogs enhanced the rate of reaction of 02(-) with peroxidase; ie, the iron complex (compound III) shuttle, resulting in the formation of compound III. Propylene was a less effective inhibitor than ethylene.