MARIANDINA 10ML SYRUP

Indications

• Folic acid deficiency
• Megaloblastic anemia

Mechanism of action

Folic acid, being biochemically inactive, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase (DHFR). These active forms are then transported into cells where they assist in erythropoiesis, purine and thymidylate synthesis, amino acid interconversion, and the methylation of tRNA. Furthermore, folic acid, with vitamin B12 as a cofactor, aids in normalizing high homocysteine levels by remethylating homocysteine to methionine. The principal biochemical function of folates involves mediating one-carbon transfer reactions, which are crucial for DNA synthesis and repair.

Pharmacodynamics

Folic acid is essential for the synthesis of nucleic acids and the metabolism of amino acids. Its deficiency can result in impaired thymidylate synthesis, leading to defective DNA synthesis, which is associated with megaloblastic and macrocytic anemias. Folic acid is particularly important during periods of rapid cell division and plays a role in cancer protection. As humans cannot synthesize folic acid, dietary intake or supplementation is necessary to prevent deficiencies.

Pharmacokinetics

Folic acid is absorbed primarily in the jejunum of the small intestine, with bioavailability influenced by food composition and other factors. Once absorbed, it is converted to its active forms in the liver and other tissues. The elimination of folate occurs through renal excretion, with a small proportion undergoing enterohepatic recirculation. Adequate intake is essential to maintain optimal levels in the body, especially during increased physiological demands.

Adverse effects

• Allergic reactions
• Rash
• Itching
• Nausea
• Abdominal pain
• Loss of appetite
• Flatulence
• Sleep disturbances

Interactions

• Antiepileptic drugs (e.g., phenytoin) may reduce the effectiveness of folic acid.
• Methotrexate may interfere with folic acid metabolism.
• Sulfasalazine may decrease folate absorption.

Precautions

• Monitor for signs of folate deficiency in patients on long-term medications that interfere with folate metabolism.
• Caution in patients with a history of hypersensitivity to folic acid or its components.

Pregnancy

Folic acid is essential during pregnancy to reduce the risk of neural tube defects and supports fetal development. Recommended supplementation is advised.

Breast-feeding

Folic acid is safe during breastfeeding. Adequate levels are important for both maternal health and infant development.

Storage

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

Formulations

• Tablets
• Syrups
• Injectable formulations

Indications

• Vitamin B3 deficiency
• Hyperlipidemia
• Dyslipidemia

Mechanism of action

Niacin decreases lipids and apolipoprotein B (apo B)-containing lipoproteins by modulating triglyceride synthesis in the liver and inhibiting lipolysis in adipose tissue. It inhibits hepatocyte diacylglycerol acyltransferase-2, preventing the final step of triglyceride synthesis, leading to reduced VLDL production. Additionally, niacin inhibits HDL catabolism receptors, increasing HDL levels and half-life. Acute effects include inhibition of nonesterified fatty acid release from adipocytes and stimulation of prostaglandin release from skin Langerhans cells, although these acute effects diminish over time.

Pharmacodynamics

Niacin is used therapeutically to treat vitamin deficiencies and to manage conditions like hyperlipidemia and dyslipidemia. It effectively reduces levels of VLDL and LDL while increasing HDL levels. Niacin has a wide therapeutic window, with typical oral doses ranging from 500 mg to 2000 mg. Caution is advised in patients with diabetes, renal failure, uncontrolled hypothyroidism, and in elderly patients, particularly when combined with simvastatin or lovastatin, due to an increased risk of myopathy and rhabdomyolysis.

Pharmacokinetics

Niacin is absorbed from the gastrointestinal tract and undergoes hepatic metabolism. It is excreted primarily in the urine. The pharmacokinetics can be affected by factors such as age, renal function, and concomitant medications. Peak plasma concentrations are typically reached within 30 minutes to 2 hours after oral administration, depending on the formulation used.

Contra-indications

• Hypersensitivity to niacin or any of its components
• Active liver disease
• Peptic ulcer disease

Adverse effects

• Flushing
• Itching
• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Hepatotoxicity
• Hyperglycemia
• Gout exacerbation

Interactions

• Increased risk of myopathy and rhabdomyolysis with statins such as simvastatin or lovastatin
• May enhance the effects of antihypertensive medications
• Potential interaction with anticoagulants

Precautions

• Caution in patients with diabetes due to potential for hyperglycemia
• Monitor liver function tests periodically during prolonged therapy
• Use with caution in patients with renal impairment
• Elderly patients may be more susceptible to adverse effects

Pregnancy

Niacin should only be used during pregnancy if clearly needed and the benefits outweigh the risks. Consult with a healthcare provider for individual assessment.

Breast-feeding

Niacin is excreted in breast milk. Caution is advised when administering to nursing mothers, and a decision should be made whether to discontinue breastfeeding or the drug.

Storage

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

Formulations

• Immediate-release tablets
• Extended-release tablets
• Sustained-release tablets

Indications

• Vitamin deficiency
• Nutritional supplementation
• Prevention of certain diseases
• Supporting metabolic functions

Dosage

Children: Refer to specific guidelines for individual vitamins or consult a healthcare professional for personalized dosing recommendations.

Adults: Refer to specific guidelines for individual vitamins or consult a healthcare professional for personalized dosing recommendations.

Mechanism of action

Vitamins function primarily as coenzymes or precursors for enzyme cofactors in various metabolic pathways. For instance, B vitamins are involved in energy metabolism by assisting in the conversion of carbohydrates, fats, and proteins into energy. Vitamin C acts as an antioxidant, protecting cells from damage, and is also crucial for collagen synthesis. Fat-soluble vitamins like A are involved in vision and immune function, while vitamin D regulates calcium and phosphate metabolism.

Pharmacodynamics

Vitamins exert their effects by participating in biochemical reactions and influencing metabolic pathways. For example, vitamin A is vital for vision and immune response, while vitamin D is important for maintaining bone health through its role in calcium absorption. The effects of vitamins can vary significantly depending on their solubility, with water-soluble vitamins typically being excreted more readily than fat-soluble ones, which can accumulate in the body.

Pharmacokinetics

The absorption of vitamins varies; water-soluble vitamins are generally absorbed in the small intestine and excreted in urine, while fat-soluble vitamins require dietary fats for absorption and are stored in the liver and fatty tissues. The bioavailability of vitamins can be affected by dietary composition, age, and health status. Elimination half-lives also differ; for instance, vitamin C has a shorter half-life compared to vitamin A, which can persist in the body for longer periods.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Constipation
• Headache
• Fatigue
• Allergic reactions

Interactions

• Fat-soluble vitamins (A, D, E, K) can accumulate and cause toxicity when taken in excess, especially with other supplements
• Certain medications (e.g., anticoagulants) may interact with vitamin K
• Vitamin C can enhance the absorption of iron supplements

Precautions

• Use caution in patients with kidney disease when taking vitamin D
• Monitor for signs of toxicity with high-dose vitamin supplementation
• Consider dietary sources of vitamins before recommending supplements

Pregnancy

Vitamins are generally considered safe during pregnancy when taken at recommended dosages. However, excessive intake, particularly of fat-soluble vitamins, should be avoided.

Breast-feeding

Most vitamins are safe during breastfeeding at recommended doses, but excessive amounts can affect breast milk composition.

Storage

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

Formulations

• Tablets
• Capsules
• Soft gels
• Powders
• Liquid solutions
• Chewable tablets

Mechanism of action

Folic acid, as it is biochemically inactive, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase (DHFR). These folic acid congeners are transported across cells by receptor-mediated endocytosis where they are needed to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate. Using vitamin B12 as a cofactor, folic acid can normalize high homocysteine levels by remethylation of homocysteine to methionine via methionine synthetase. Folic acid, after conversion to tetrahydrofolic acid, is necessary for normal erythropoiesis, synthesis of purine and thymidylates, metabolism of amino acids such as glycine and methionine, and the metabolism of histidine. The principal biochemical function of folates is the mediation of one-carbon transfer reactions. 5-Methyltetrahydrofolate donates a methyl group to homocystine, in the conversion of homocystine to L-methionine. ... 5,10-Methyltetrahydrofolate is regenerated from tetrahydrofolate via the enzyme serine hydroxymethyltransferase, a reaction, which in addition to producing 5,10-methyltetrahydrofolate, yields glycine. ... 5,10-methyltetrahydrofolate, supplies the one carbon group for the methylation of deoxyuridylic acid to form the DNA precursor thymidylic acid. This reaction is catalyzed by thymidylate synthase and the folate product of the reaction is dihydrofolate. Dihydrofolate is converted to tetrahydrofolate via the enzyme dihydrofolate reductase ...

Pharmacodynamics

Folic acid is a water-soluble B-complex vitamin found in foods such as liver, kidney, yeast, and leafy, green vegetables. Also known as folate or Vitamin B9, folic acid is an essential cofactor for enzymes involved in DNA and RNA synthesis. More specifically, folic acid is required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. Folic acid is the precursor of tetrahydrofolic acid, which is involved as a cofactor for transformylation reactions in the biosynthesis of purines and thymidylates of nucleic acids. Impairment of thymidylate synthesis in patients with folic acid deficiency is thought to account for the defective deoxyribonucleic acid (DNA) synthesis that leads to megaloblast formation and megaloblastic and macrocytic anemias. Folic acid is particularly important during phases of rapid cell division, such as infancy, pregnancy, and erythropoiesis, and plays a protective factor in the development of cancer. As humans are unable to synthesize folic acid endogenously, diet and supplementation is necessary to prevent deficiencies. In order to function properly within the body, folic acid must first be reduced by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). This important pathway, which is required for de novo synthesis of nucleic acids and amino acids, is disrupted by anti-metabolite therapies such as [DB00563] as they function as DHFR inhibitors to prevent DNA synthesis in rapidly dividing cells, and therefore prevent the formation of DHF and THF. In general, folate serum levels below 5 ng/mL indicate folate deficiency, and levels below 2 ng/mL usually result in megaloblastic anemia.

Mechanism of action

Niacin performs a number of functions in the body and so has many mechanisms, not all of which have been fully described. Niacin can decrease lipids and apolipoprotein B (apo B)-containing lipoproteins by modulating triglyceride synthesis in the liver, which degrades apo B, or by modulating lipolysis in adipose tissue. Niacin inhibits hepatocyte diacylglycerol acyltransferase-2. This action prevents the final step of triglyceride synthesis in hepatocytes, limiting available triglycerides for very low density lipoproteins (VLDL). This activity also leads to intracellular degradation of apo B and decreased production of low density lipoproteins, the catabolic product of VLDL. Niacin also inhibits a high density lipoprotein (HDL) catabolism receptor, which increases the levels and half life of HDL. Prolonged niacin treatment elicits beneficial effects on the plasma lipid and lipoprotein profile that is associated with a protective CVD risk profile. Acute niacin treatment inhibits nonesterified fatty acid release from adipocytes and stimulates prostaglandin release from skin Langerhans cells, but the acute effects diminish upon prolonged treatment, while the beneficial effects remain. To gain insight in the prolonged effects of niacin on lipid metabolism in adipocytes, we used a mouse model with a human-like lipoprotein metabolism and drug response [female APOE*3-Leiden.CETP (apoE3 Leiden cholesteryl ester transfer protein) mice] treated with and without niacin for 15 weeks. The gene expression profile of gonadal white adipose tissue (gWAT) from niacin-treated mice showed an upregulation of the "biosynthesis of unsaturated fatty acids" pathway, which was corroborated by quantitative PCR and analysis of the FA ratios in gWAT. Also, adipocytes from niacin-treated mice secreted more of the PUFA DHA ex vivo. This resulted in an increased DHA/arachidonic acid (AA) ratio in the adipocyte FA secretion profile and in plasma of niacin-treated mice. Interestingly, the DHA metabolite 19,20-dihydroxy docosapentaenoic acid (19,20-diHDPA) was increased in plasma of niacin-treated mice. Both an increased DHA/AA ratio and increased 19,20-diHDPA are indicative for an anti-inflammatory profile and may indirectly contribute to the atheroprotective lipid and lipoprotein profile associated with prolonged niacin treatment. /The study objective was/ to determine the effects of niacin on adiponectin and markers of adipose tissue inflammation in a mouse model of obesity. Male C57BL/6 mice were placed on a control or high-fat diet (HFD) and were maintained on such diets for the duration of the study. After 6 weeks on the control or high fat diets, vehicle or niacin treatments were initiated and maintained for 5 weeks. Identical studies were conducted concurrently in HCA2 (-/-) (niacin receptor(-/-)) mice. Niacin increased serum concentrations of the anti-inflammatory adipokine, adiponectin by 21% in HFD-fed wild-type mice, but had no effect on lean wild-type or lean or HFD-fed HCA2 (-/-) mice. Niacin increased adiponectin gene and protein expression in the HFD-fed wild-type mice only. The increases in adiponectin serum concentrations, gene and protein expression occurred independently of changes in expression of PPARgamma C/EBPalpha or SREBP-1c (key transcription factors known to positively regulate adiponectin gene transcription) in the adipose tissue. Further, niacin had no effect on adipose tissue expression of ERp44, Ero1-Lalpha, or DsbA-L (key ER chaperones involved in adiponectin production and secretion). However, niacin treatment attenuated HFD-induced increases in adipose tissue gene expression of MCP-1 and IL-1beta in the wild-type HFD-fed mice. Niacin also reduced the expression of the pro-inflammatory M1 macrophage marker CD11c in HFD-fed wild-type mice. Niacin treatment attenuates obesity-induced adipose tissue inflammation through increased adiponectin and anti-inflammatory cytokine expression and reduced pro-inflammatory cytokine expressio

Pharmacodynamics

Niacin is a B vitamin used to treat vitamin deficiencies as well as hyperlipidemia, dyslipidemia, hypertriglyceridemia, and to reduce the risk of myocardial infarctions. Niacin acts to decrease levels of very low density lipoproteins and low density lipoproteins, while increasing levels of high density lipoproteins. Niacin has a wide therapeutic window with usual oral doses between 500mg and 2000mg. Patients with diabetes, renal failure, uncontrolled hypothyroidism, and elderly patients taking niacin with simvastatin or lovastatin are at increased risk of myopathy and rhabdomyolysis.