BASEVITA PLUS TABLETS

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

• Papulopustular rosacea
• Inflammatory acne vulgaris

Dosage

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

Adults: For papulopustular rosacea, apply daily for up to 4 months. The treatment course may be repeated; discontinue if no improvement is observed after 3 months. For inflammatory acne vulgaris, apply twice daily, reduced to once daily or alternate days if irritation occurs.

Mechanism of action

Nicotinamide exhibits anti-inflammatory effects by inhibiting the release of pro-inflammatory cytokines and enhancing the barrier function of the skin. It is also involved in the NAD salvage pathway, which is essential for maintaining cellular energy levels and promoting cell repair mechanisms. Additionally, nicotinamide contributes to the synthesis of coenzymes involved in metabolic processes, including the conversion of niacin into NAD+.

Pharmacodynamics

Nicotinamide is known for its ability to improve skin hydration and reduce transepidermal water loss. It has been shown to decrease the appearance of acne lesions and rosacea by modulating inflammatory responses and accelerating cell turnover. Its antioxidant properties also help to protect the skin from oxidative stress and UV damage.

Pharmacokinetics

When applied topically, nicotinamide is absorbed through the skin layers, with minimal systemic absorption. Its peak plasma concentrations are generally low, and the drug has a half-life that varies depending on the route of administration. The metabolism of nicotinamide occurs primarily in the liver, where it is converted into its active forms, including NAD+. The elimination route is via the kidneys, with metabolites excreted in urine.

Contra-indications

• Pregnancy
• Severe acne involving large areas
• Severe skin reactions

Adverse effects

• Sunburn
• Skin reactions (common or very common)
• Cheilitis
• Eyelid oedema
• Flushing
• Dry skin
• Eye irritation
• Photosensitivity reactions
• Transient skin pigmentation changes

Interactions

• Clindamycin
• Topical retinoids
• Abrasive cleaners
• Comedogenic cosmetics

Precautions

• Avoid exposure to UV light, including sunlight and sunlamps
• Wash hands immediately after use
• Avoid contact with eyes and mucous membranes
• Use moisturizers to reduce the risk of skin irritation
• Discontinue treatment if severe irritation occurs

Pregnancy

Avoid use during pregnancy due to potential risks, as limited information is available regarding toxicity.

Breast-feeding

Amount of drug in milk after topical application is probably too small to be harmful; ensure infant does not come in contact with treated areas.

Storage

Store at room temperature away from moisture and light.

Formulations

• Cream
• Gel

Indications

• Vitamin B2 deficiency
• Isoniazid-induced neuropathy (prophylaxis and treatment)
• Metabolic diseases
• Cystathioninuria
• Homocystinuria
• Wilson's disease
• Prevention of penicillamine-induced neuropathy

Mechanism of action

Riboflavin acts as a precursor to flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are essential coenzymes in various enzymatic reactions. It binds to riboflavin hydrogenase, riboflavin kinase, and riboflavin synthase, facilitating the production of FMN and FAD. These coenzymes are critical for normal tissue respiration and energy metabolism, influencing hydrogen transport in oxidative enzyme systems such as cytochrome C reductase and succinic dehydrogenase. Moreover, riboflavin contributes to the antioxidant activity by aiding in the production of reduced glutathione, a key antioxidant in the body.

Pharmacodynamics

Riboflavin is an easily absorbed, water-soluble micronutrient that supports energy production by assisting in the metabolism of fats, carbohydrates, and proteins. It is vital for red blood cell formation, antibody production, and regulating growth and reproduction. The vitamin plays a significant role in maintaining healthy skin, nails, and hair, as well as supporting thyroid activity. Riboflavin also has therapeutic implications in preventing or treating various eye disorders, including cataracts.

Pharmacokinetics

Riboflavin is rapidly absorbed in the gastrointestinal tract, with its bioavailability influenced by dietary intake. It is primarily excreted through urine, with excess intake leading to bright yellow urine, which is a harmless side effect. The vitamin does not accumulate in the body, necessitating regular dietary intake to maintain adequate levels.

Adverse effects

• Urine discolouration
• Peripheral neuritis

Precautions

• With intravenous use, risk of cardiovascular collapse; resuscitation facilities must be available and monitor closely.

Pregnancy

Crosses the placenta but no adverse effects reported; information at high doses limited.

Breast-feeding

Present in breast milk but no adverse effects reported; information at high doses limited.

Storage

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

Formulations

• 100 mg modified-release tablets
• 50 mg capsules
• 100 mg capsules
• 100 mg tablets
• Oral solution

Indications

• Vitamin B1 deficiency
• Wernicke-Korsakoff syndrome
• Beriberi
• Isoniazid-induced neuropathy (prophylaxis and treatment)
• Severe depletion or malabsorption of vitamins B and C

Dosage

Adults: For vitamin deficiency: 25–100 mg daily. For severe deficiency: 200–300 mg daily in divided doses. For

Mechanism of action

Thiamine functions primarily as a precursor for several phosphorylated active forms, which act as coenzymes in metabolic pathways. It reduces intracellular protein glycation by redirecting glycolytic flux and supports the synthesis of nucleic acids necessary for cell survival and proliferation. Additionally, thiamine has been shown to inhibit glucose-induced proliferation of endothelial cells, thus possibly playing a role in the modulation of vascular health.

Pharmacodynamics

Thiamine exhibits antioxidant properties and contributes to erythropoiesis, cognitive function, and mood regulation. It has protective effects against oxidative stress, particularly in neuronal tissues, where deficiency can lead to neuronal death due to increased free radical production. Thiamine also modulates glucose metabolism, influencing smooth muscle cell proliferation and potentially impacting the progression of atherosclerosis.

Pharmacokinetics

Thiamine is rapidly absorbed from the gastrointestinal tract, primarily in the jejunum, and is distributed throughout the body, with higher concentrations found in the liver, heart, and brain. It is excreted in urine, and its half-life is relatively short. The vitamin is converted into active forms within tissues, including thiamine diphosphate (TDP), which is the coenzyme form involved in carbohydrate metabolism. The body does not store significant amounts of thiamine, making regular dietary intake essential.

Adverse effects

• Allergic reactions
• Anaphylaxis (rare)
• Gastrointestinal disturbances

Precautions

• Facilities for treating anaphylaxis should be available when parenteral thiamine is administered
• Use with caution in patients with a history of hypersensitivity to thiamine

Pregnancy

Thiamine crosses the placenta but no adverse effects have been reported. Information regarding high doses is limited.

Breast-feeding

Severely thiamine-deficient mothers should avoid breast-feeding as thiamine is present in breast milk.

Storage

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

Formulations

• Thiamine hydrochloride 20 mg/ml oral solution
• Thiamine hydrochloride 50 mg tablets
• Thiamine hydrochloride 100 mg modified-release tablets
• Thiamine hydrochloride oral suspension

Indications

• Allergic conditions
• Hay fever
• Urticaria
• Pruritus
• Appetite stimulation

Dosage

Children: For children aged 6 months to 5 years, the dose is 5-15 mg daily in divided doses, adjusted according to weight, with a maximum of 2 mg/kg per day. For children aged 6-17 years weighing up to 40 kg, the initial dose is 15-25 mg daily in divided doses, adjusted as necessary to a maximum of 2 mg/kg per day. For those weighing 40 kg and above, the initial dose is 15-25 mg daily in divided doses, increased if necessary to 50-100 mg daily.

Adults: Initially, 25 mg daily, taken at night; may be increased if necessary to 25 mg 3-4 times a day. Maximum dose is 32 mg per day.

Mechanism of action

Cyproheptadine acts as a competitive antagonist at histamine H1 receptors, thereby inhibiting the action of histamine, which is responsible for allergic symptoms. Additionally, it may also block serotonin receptors, contributing to its appetite-stimulating effects.

Pharmacodynamics

The drug exhibits sedative effects by crossing the blood-brain barrier, leading to central nervous system depression. It can also produce anticholinergic effects, such as dry mouth and urinary retention, due to its action on muscarinic receptors. The sedative properties can impair the performance of skilled tasks and may be potentiated by alcohol consumption.

Pharmacokinetics

Cyproheptadine is well-absorbed from the gastrointestinal tract and undergoes hepatic metabolism. Its elimination half-life is approximately 8-12 hours, and it is excreted primarily in urine. The onset of action is typically within 1-2 hours, with effects lasting for several hours.

Contra-indications

• Acute porphyrias
• Prolonged QT-interval
• Risk factors for QT prolongation

Adverse effects

• Drowsiness
• Dizziness
• Dry mouth
• Nausea
• Constipation
• Headache
• Palpitations
• Tachycardia
• Fatigue
• Irritability
• Paradoxical excitability
• Tremor

Interactions

• Antihistamines
• Sedating agents
• Alcohol

Precautions

• Use with caution in the elderly
• Patients with epilepsy
• Prostatic hypertrophy
• Pyloroduodenal obstruction
• Susceptibility to angle-closure glaucoma
• Urinary retention

Pregnancy

Most manufacturers of antihistamines advise avoiding their use during pregnancy; however, there is no evidence of teratogenicity. Use in the latter part of the third trimester may cause adverse effects in neonates.

Breast-feeding

Most antihistamines are present in breast milk in varying amounts; although not known to be harmful, most manufacturers advise avoiding their use in mothers who are breastfeeding.

Storage

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

Formulations

• Oral suspension
• Tablets (4 mg)

Indications

• Vitamin D deficiency
• Rickets
• Osteomalacia
• Osteoporosis
• Hypoparathyroidism

Dosage

Adults: The usual adult dose for vitamin D deficiency is 800 to 2000 IU daily, depending on the severity of deficiency and clinical condition. Higher doses may be used under medical supervision.

Mechanism of action

Cholecalciferol is converted to its active forms, 25-hydroxyvitamin D in the liver and 1,25-dihydroxyvitamin D in the kidneys. These metabolites enhance the intestinal absorption of calcium and phosphorus, increase serum calcium levels, and mobilize these minerals from bone. This process is regulated by parathyroid hormone, which influences calcium and phosphate metabolism, particularly in the kidneys.

Pharmacodynamics

The pharmacodynamics of cholecalciferol involve its conversion to active metabolites that play a significant role in calcium and phosphorus homeostasis. The metabolites facilitate intestinal absorption of these minerals, promote bone mineralization, and influence renal reabsorption. The onset of action occurs within 10 to 24 hours following administration, as metabolic activation is required for its biological effects.

Pharmacokinetics

Cholecalciferol is absorbed in the gastrointestinal tract, and its absorption is enhanced by the presence of dietary fats. It is transported in the bloodstream bound to vitamin D-binding protein. Once in the liver, it undergoes hydroxylation to form 25-hydroxyvitamin D, which is further converted in the kidneys to the active form, 1,25-dihydroxyvitamin D. The elimination half-life of cholecalciferol varies, typically spanning several days, and it is primarily excreted in bile and urine.

Adverse effects

• Hypercalcemia
• Hypercalciuria
• Nausea
• Vomiting
• Constipation
• Weakness
• Fatigue

Interactions

• May enhance the effects of thiazide diuretics, leading to increased risk of hypercalcemia
• Anticonvulsants may increase metabolism of vitamin D, leading to reduced effectiveness
• Cholestyramine may reduce absorption of vitamin D

Precautions

• Monitor serum calcium levels in patients with renal impairment
• Caution in patients with a history of hypercalcemia or hyperparathyroidism
• Use with caution in patients taking other medications that affect calcium metabolism

Pregnancy

Cholecalciferol can be used during pregnancy if indicated, as vitamin D is essential for fetal bone development.

Breast-feeding

Cholecalciferol is excreted in breast milk, but is generally considered safe during breastfeeding.

Storage

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

Formulations

• Capsules
• Tablets
• Liquid formulations

Indications

• Allergic rhinitis
• Allergic conjunctivitis
• Urticaria
• Angioedema
• Anaphylaxis (as adjunct therapy)
• Appetite stimulation in certain conditions

Dosage

Children: Refer to BNF for Children for appropriate pediatric dosing, as it varies by age and condition. Generally, doses may start at 0.25 mg/kg for younger children, but specific guidelines should be

Adults: The usual adult dose for allergic conditions is 4 mg three times daily, which may be increased to a maximum of 12 mg per day as needed. For appetite stimulation, the starting dose is often 4 mg taken once or twice daily.

Mechanism of action

Cyproheptadine exerts its effects by competing with free histamine and serotonin for binding at their respective receptors. Its action as an H1 blocker is complemented by its antagonism of serotonin at 5-HT2A receptors, particularly influencing the appetite center in the hypothalamus. This dual action accounts for its appetite-stimulating properties and mitigates several pharmacodynamic effects of serotonin.

Pharmacodynamics

Cyproheptadine antagonizes several effects of serotonin and histamine, including bronchoconstriction and vasodepression. Its efficacy in combatting histamine-mediated effects has been established, although the details regarding its role in preventing anaphylactic shock remain unclear, likely linked to its anti-serotonergic activity. The drug's sedative properties arise from its central nervous system effects.

Pharmacokinetics

Cyproheptadine is well-absorbed after oral administration. It is metabolized in the liver, with a variable half-life and is primarily excreted in urine. The onset of action typically occurs within one to two hours, and the duration of action can last up to 12 hours. The pharmacokinetic profile may be influenced by individual metabolic variations.

Adverse effects

• Drowsiness
• Dizziness
• Dry mouth
• Constipation
• Blurred vision
• Increased appetite

Interactions

• cyproheptadine+metyrapone: Severe (decreases effects)
• cyproheptadine+fenfluramine: Unknown (decreases efficacy)

Precautions

• Caution in patients with glaucoma
• Caution in patients with prostate hypertrophy
• Use with caution in elderly patients due to increased sensitivity

Pregnancy

Cyproheptadine should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Limited data are available on its safety.

Breast-feeding

Cyproheptadine is excreted in breast milk. Caution is advised when administered to breastfeeding mothers.

Storage

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

Formulations

• Tablets
• Syrup

Indications

• Metabolic acidosis
• Lactic acidosis
• Energy substrate in critical illness
• Monitoring tissue perfusion and oxygenation

Dosage

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

Adults: Refer to specific guidelines based on clinical context as dosing is highly variable and situation-dependent.

Mechanism of action

Lactate acts as a signaling molecule and energy substrate in various physiological and pathological processes. It is involved in the modulation of several metabolic pathways, including the Cori cycle and Krebs cycle. Lactate also participates in metabolic reprogramming, especially in cancer cells, where it can promote tumor growth and survival by providing an alternative energy source and influencing cellular signaling pathways such as the PI3K/AKT/mTOR pathway.

Pharmacodynamics

Lactate plays a vital role in energy metabolism. It can be oxidized back to pyruvate by lactate dehydrogenase, entering the Krebs cycle for ATP production. In addition to serving as an energy substrate, lactate impacts pH regulation and can influence the function of various immune cells. Its levels can indicate the state of oxygen delivery and utilization in tissues, thus serving as a marker for metabolic stress.

Pharmacokinetics

Lactate is produced primarily in the cytoplasm during glycolysis, with its concentration in the blood reflecting the balance between production and clearance. It is metabolized predominantly in the liver, where it can be converted back to glucose or utilized in the Krebs cycle. Lactate levels can vary based on factors such as exercise, tissue hypoxia, and metabolic conditions.

Pregnancy

Lactate is generally regarded as safe during pregnancy as it is a naturally occurring metabolite in the body, but specific clinical advice should be sought.

Breast-feeding

Lactate is considered safe during breastfeeding as it is a normal component of human metabolism, but consult a healthcare provider for personalized advice.

Storage

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

Indications

• Pantothenate deficiency
• Support in energy metabolism
• Adjuvant therapy in chronic conditions requiring enhanced energy production

Dosage

Children: Refer to the BNF for Children for paediatric dosing recommendations.

Adults: Refer to the BNF for specific dosing information, generally 5-10 mg daily for adults.

Mechanism of action

Pantothenate functions primarily as a precursor to coenzyme A (CoA), which is vital for various biochemical reactions in the body. CoA is involved in the metabolism of fatty acids, the synthesis of cholesterol and steroid hormones, and the acetylation of various substrates, which is crucial for energy production and metabolic processes.

Pharmacodynamics

Pantothenate plays a significant role in energy metabolism, cellular respiration, and the biosynthesis of fatty acids. It facilitates the transfer of acyl groups, which is critical for the metabolism of carbohydrates and fats, thereby influencing the overall energy production in cells. Adequate levels of pantothenate are necessary for maintaining metabolic homeostasis and supporting growth and development.

Pharmacokinetics

Pantothenate is well absorbed from the gastrointestinal tract, with a bioavailability of approximately 70%. Once absorbed, it is widely distributed throughout the body, particularly in the liver, adrenal glands, and kidneys. The vitamin is metabolized primarily in the liver, where it is converted to coenzyme A. Excess pantothenate is excreted in the urine as pantothenic acid and its metabolites. The half-life of pantothenate in the body is not well-defined but is generally considered to be relatively short due to its water-soluble nature.

Pregnancy

Pantothenic acid (Vitamin B5) is generally regarded as safe during pregnancy. It is important to maintain adequate levels for fetal development.

Breast-feeding

Pantothenic acid is excreted in breast milk in small amounts. Adequate intake is important for breastfeeding mothers, but supplementation is typically not necessary.

Storage

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

Formulations

• Pantothenate tablets
• Pantothenic acid capsules
• Pantothenate injections

Indications

• Vitamin A deficiency
• Night blindness
• Impaired wound healing
• Epithelial disorders

Dosage

Children: Refer to BNF for Children for specific paediatric dosing information.

Adults: Refer to BNF for specific adult dosing information.

Mechanism of action

Retinol is converted in the retina to 11-cis-retinal, which is crucial for the conversion of light into neural signals necessary for vision. It binds to opsin in rhodopsin, facilitating the isomerization to all-trans-retinal upon exposure to light, thus triggering visual signaling. Additionally, retinol interacts with retinoic acid receptors (RARs) and retinoid-X receptors (RXRs) as transcription factors, modulating gene expression related to cellular differentiation and growth.

Pharmacodynamics

Vitamin A is effective in treating Vitamin A deficiency, which can lead to vision impairment and other health issues. It plays a critical role in various biological processes including vision, cellular differentiation, reproduction, and immune system function. Its deficiency can cause symptoms such as night blindness and impaired wound healing, while adequate levels support growth and development.

Pharmacokinetics

Retinol is absorbed from the gastrointestinal tract and stored in the liver, where it can be mobilized as needed. It undergoes metabolism primarily in the liver, where it is converted to retinal and retinoic acid, the active forms of Vitamin A. The elimination half-life varies, but retinol is generally excreted in urine and bile. The bioavailability can be affected by dietary fat intake.

Adverse effects

• Nausea
• Vomiting
• Headache
• Dizziness
• Fatigue
• Irritability
• Dry skin
• Peeling of skin
• Itching
• Blurred vision

Precautions

• Use with caution in patients with liver disease due to potential hepatotoxicity.
• Monitor for signs of vitamin A toxicity, especially in patients on high doses or prolonged therapy.
• Caution in patients with a history of alcohol abuse, as it may exacerbate liver conditions.

Pregnancy

Retinol should be used with caution during pregnancy due to the risk of teratogenic effects. High doses of vitamin A can lead to fetal malformations.

Breast-feeding

Retinol is generally considered safe during breastfeeding, but excessive intake should be avoided to prevent potential adverse effects on the infant.

Storage

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

Formulations

• Capsules
• Tablets
• Oral solutions
• Topical preparations

Indications

• Thiamine deficiency
• Wernicke's encephalopathy
• Beriberi
• Alcoholism-related complications
• Certain metabolic disorders

Dosage

Children: Refer to BNF for Children for appropriate dosing information.

Adults: Refer to established clinical guidelines or BNF for specific dosing recommendations.

Mechanism of action

Thiamine is a coenzyme for several important enzymatic reactions, including the pyruvate dehydrogenase complex and alpha-ketoglutarate dehydrogenase. It is essential for converting carbohydrates into energy, facilitating the metabolism of glucose, and maintaining normal nerve function.

Pharmacodynamics

Thiamine deficiency leads to impaired carbohydrate metabolism, which can result in neurological and cardiovascular dysfunction. Supplementation with thiamine helps restore normal metabolic function and can alleviate symptoms associated with deficiency, such as Wernicke's encephalopathy and Beriberi. It also plays a role in the synthesis of neurotransmitters and in maintaining myelin integrity.

Pharmacokinetics

Thiamine is readily absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1-2 hours after oral administration. It is distributed throughout the body, primarily in the liver, kidneys, and heart. Thiamine is metabolized in the liver to its active form, thiamine pyrophosphate. It has a biological half-life of about 9-18 days and is excreted primarily in the urine. Excess thiamine is excreted, making toxicity rare.

Adverse effects

• Allergic reactions
• Hypersensitivity reactions
• Gastrointestinal disturbances

Interactions

• May interact with certain diuretics, leading to altered thiamine levels

Precautions

• Use with caution in patients with renal impairment
• Monitor patients with a history of thiamine deficiency

Pregnancy

Thiamine is considered safe during pregnancy, as it is an essential nutrient.

Breast-feeding

Thiamine is excreted in breast milk, but supplementation is generally considered safe for breastfeeding mothers.

Storage

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

Formulations

• Thiamine hydrochloride injection
• Thiamine hydrochloride oral tablets
• Thiamine hydrochloride oral solution

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

Binds to riboflavin hydrogenase, riboflavin kinase, and riboflavin synthase. Riboflavin is the precursor of flavin mononucleotide (FMN, riboflavin monophosphate) and flavin adenine dinucleotide (FAD). The antioxidant activity of riboflavin is principally derived from its role as a precursor of FAD and the role of this cofactor in the production of the antioxidant reduced glutathione. Reduced glutathione is the cofactor of the selenium-containing glutathione peroxidases among other things. The glutathione peroxidases are major antioxidant enzymes. Reduced glutathione is generated by the FAD-containing enzyme glutathione reductase. Riboflavin is converted to 2 coenzymes, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are necessary for normal tissue respiration. Riboflavin is also required for activation of pyridoxine, conversion of tryptophan to niacin, and may be involved in maintaining erythrocyte integrity. Riboflavin functions as the coenzyme for flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), which primarily influence hydrogen transport in oxidative enzyme systems (eg, cytochrome C reductase, succinic dehydrogenase, xanthine oxidase). Two active forms of riboflavin exist ... coenzyme flavin mononucleotide (FMN) and coenzyme flavin adenine dinucleotide (FAD). They are formed by reaction of riboflavin with 1 and 2 molecules of ATP as follow: riboflavin + ATP = riboflavin-P (FMN) + ADP; FMN + ATP = riboflavin-ADP (FAD) + PP. Riboflavin is a water-soluble, yellow, fluorescent compound. The primary form of the vitamin is as an integral component of the coenzymes flavin mononucleotide (FMN) and flavin-adenine dinucleotide (FAD). It is in these bound coenzyme forms that riboflavin functions as a catalyst for redox reactions in numerous metabolic pathways and in energy production. ... The redox reactions in which flavocoenzymes participate include flavoprotein-catalyzed dehydrogenations that are both pyridine nucleotide (niacin) dependent and independent, reactions with sulfur-containing compounds, hydroxylations, oxidative decarboxylations (involving thiamin as its pyrophosphate), dioxygenations, and reduction of oxygen to hydrogen peroxide. There are obligatory roles of flavocoenzymes in the formation of some vitamins and their coenzymes. For example, the biosynthesis of two niacin-containing coenzymes from tryptophan occurs via FAD-dependent kynurenine hydroxylase, an FMN-dependent oxidase catalyzes the conversion of the 5'-phosphates of vitamin B6 to coenzymic pyridoxal 5'-phosphate, and an FAD-dependent dehydrogenase reduces 5,10-methylene-tetrahydrofolate to the 5'-methyl product that interfaces with the B12-dependent formation of methionine from homocysteine and thus with sulfur amino acid metabolism. For more Mechanism of Action (Complete) data for Riboflavin (7 total), please visit the HSDB record page.

Pharmacodynamics

Riboflavin or vitamin B2 is an easily absorbed, water-soluble micronutrient with a key role in maintaining human health. Like the other B vitamins, it supports energy production by aiding in the metabolising of fats, carbohydrates, and proteins. Vitamin B2 is also required for red blood cell formation and respiration, antibody production, and for regulating human growth and reproduction. It is essential for healthy skin, nails, hair growth and general good health, including regulating thyroid activity. Riboflavin also helps in the prevention or treatment of many types of eye disorders, including some cases of cataracts.

Mechanism of action

It is thought that the mechanism of action of thiamine on endothelial cells is related to a reduction in intracellular protein glycation by redirecting the glycolytic flux. Thiamine is mainly the transport form of the vitamin, while the active forms are phosphorylated thiamine derivatives. Natural derivatives of thiamine phosphate, such as thiamine monophosphate (ThMP), thiamine diphosphate (ThDP), also sometimes called thiamine pyrophosphate (TPP), thiamine triphosphate (ThTP), and thiamine triphosphate (AThTP), that act as coenzymes in addition to their each unique biological functions. Metabolic control analysis predicts that stimulators of transketolase enzyme synthesis such as thiamin (vitamin B-1) support a high rate of nucleic acid ribose synthesis necessary for tumor cell survival, chemotherapy resistance, and proliferation. Metabolic control analysis also predicts that transketolase inhibitor drugs will have the opposite effect on tumor cells. This may have important implications in the nutrition and future treatment of patients with cancer.

Pharmacodynamics

Thiamine is a vitamin with antioxidant, erythropoietic, cognition-and mood-modulatory, antiatherosclerotic, putative ergogenic, and detoxification activities. Thiamine has been found to protect against lead-induced lipid peroxidation in rat liver and kidney. Thiamine deficiency results in selective neuronal death in animal models. The neuronal death is associated with increased free radical production, suggesting that oxidative stress may play an important early role in brain damage associated with thiamine deficiency. Thiamine plays a key role in intracellular glucose metabolism and it is thought that thiamine inhibits the effect of glucose and insulin on arterial smooth muscle cell proliferation. Inhibition of endothelial cell proliferation may also promote atherosclerosis. Endothelial cells in culture have been found to have a decreased proliferative rate and delayed migration in response to hyperglycemic conditions. Thiamine has been shown to inhibit this effect of glucose on endothelial cells.

Mechanism of action

Most individuals naturally generate adequate amounts of vitamin D through ordinary dietary intake of vitamin D (in some foods like eggs, fish, and cheese) and natural photochemical conversion of the vitamin D3 precursor 7-dehydrocholesterol in the skin via exposure to sunlight. Conversely, vitamin D deficiency can often occur from a combination of insufficient exposure to sunlight, inadequate dietary intake of vitamin D, genetic defects with endogenous vitamin D receptor, or even severe liver or kidney disease. Such deficiency is known for resulting in conditions like rickets or osteomalacia, all of which reflect inadequate mineralization of bone, enhanced compensatory skeletal demineralization, resultant decreased calcium ion blood concentrations, and increases in the production and secretion of parathyroid hormone. Increases in parathyroid hormone stimulate the mobilization of skeletal calcium and the renal excretion of phosphorus. This enhanced mobilization of skeletal calcium leads towards porotic bone conditions. Ordinarily, while vitamin D3 is made naturally via photochemical processes in the skin, both itself and vitamin D2 can be found in various food and pharmaceutical sources as dietary supplements. The principal biological function of vitamin D is the maintenance of normal levels of serum calcium and phosphorus in the bloodstream by enhancing the efficacy of the small intestine to absorb these minerals from the diet. At the liver, vitamin D3 or D2 is hydroxylated to 25-hydroxyvitamin D and then finally to the primary active metabolite 1,25-dihydroxyvitamin D in the kidney via further hydroxylation. This final metabolite binds to endogenous vitamin d receptors, which results in a variety of regulatory roles - including maintaining calcium balance, the regulation of parathyroid hormone, the promotion of the renal reabsorption of calcium, increased intestinal absorption of calcium and phosphorus, and increased calcium and phosphorus mobilization of calcium and phosphorus from bone to plasma to maintain balanced levels of each in bone and the plasma. In particular, calcitriol interacts with vitamin D receptors in the small intestine to enhance the efficiency of intestinal calcium and phosphorous absorption from about 10-15% to 30-40% and 60% increased to 80%, respectively. Furthermore, calcitriol binds with vitamin D receptors in osteoblasts to stimulate a receptor activator of nuclear factor kB ligand (or RANKL) which subsequently interacts with receptor activator of nuclear factor kB (NFkB) on immature preosteoclasts, causing them to become mature bone-resorbing osteoclasts. Such mature osteoclasts ultimately function in removing calcium and phosphorus from bone to maintain blood calcium and phosphorus levels. Moreover, calcitriol also stimulates calcium reabsorption from the glomerular filtrate in the kidneys. Additionally, it is believed that when calcitriol binds with nuclear vitamin D receptors, that this bound complex itself binds to retinoic acid X receptor (RXR) to generate a heterodimeric complex that consequently binds to specific nucleotide sequences in the DNA called vitamin D response elements. When bound, various transcription factors attach to this complex, resulting in either up or down-regulation of the associated gene's activity. It is thought that there may be as much as 200 to 2000 genes that possess vitamin D response elements or that are influenced indirectly to control a multitude of genes across the genome. It is in this way that cholecalciferol is believed to function in regulating gene transcription associated with cancer risk, autoimmune disorders, and cardiovascular disease linked to vitamin D deficiency. In fact, there has been some research to suggest calcitriol may also be able to prevent malignancies by inducing cellular maturation and inducing apoptosis and inhibiting angiogenesis, exhibit anti-inflammatory effects by inhibiting foam cell formation and promoting angiogenesis in en

Pharmacodynamics

The in vivo synthesis of the predominant two biologically active metabolites of vitamin D occurs in two steps. The first hydroxylation of vitamin D3 cholecalciferol (or D2) occurs in the liver to yield 25-hydroxyvitamin D while the second hydroxylation happens in the kidneys to give 1, 25-dihydroxyvitamin D. These vitamin D metabolites subsequently facilitate the active absorption of calcium and phosphorus in the small intestine, serving to increase serum calcium and phosphate levels sufficiently to allow bone mineralization. Conversely, these vitamin D metabolites also assist in mobilizing calcium and phosphate from bone and likely increase the reabsorption of calcium and perhaps also of phosphate via the renal tubules. There exists a period of 10 to 24 hours between the administration of cholecalciferol and the initiation of its action in the body due to the necessity of synthesis of the active vitamin D metabolites in the liver and kidneys. It is parathyroid hormone that is responsible for the regulation of such metabolism at the level of the kidneys.

Mechanism of action

Cyproheptadine appears to exert its antihistamine and antiserotonin effects by competing with free histamine and serotonin for binding at their respective receptors. Antagonism of serotonin on the appetite center of the hypothalamus may account for cyproheptadine's ability to stimulate the appetite. CYPROHEPTADINE...IS A SEROTONIN & HISTAMINE ANTAGONIST... ... It is an effective H1 blocker. Cyproheptadine also has prominent 5-H blocking activity on smooth muscle by virtue of its binding to 5-HT2A receptors. ... It has weak anticholinergic activity and possess mild central depressant properties.

Pharmacodynamics

Cyproheptadine has been observed to antagonize several pharmacodynamic effects of serotonin in laboratory animals, including bronchoconstriction and vasodepression, and has demonstrated similar efficacy in antagonizing histamine-mediated effects. The reason for its efficacy in preventing anaphylactic shock has not been elucidated, but appears to be related to its anti-serotonergic effects.

Mechanism of action

Vision:Vitamin A (all-<i>trans</i> retinol) is converted in the retina to the 11-<i>cis</i>-isomer of retinaldehyde or 11-<i>cis</i>-retinal. 11-<i>cis</i>-retinal functions in the retina in the transduction of light into the neural signals necessary for vision. 11-<i>cis</i>-retinal, while attached to opsin in rhodopsin is isomerized to all-<i>trans</i>-retinal by light. This is the event that triggers the nerve impulse to the brain which allows for the perception of light. All-<i>trans</i>-retinal is then released from opsin and reduced to all-<i>trans</i>-retinol. All-<i>trans</i>-retinol is isomerized to 11-<i>cis</i>-retinol in the dark, and then oxidized to 11-<i>cis</i>-retinal. 11-<i>cis</i>-retinal recombines with opsin to re-form rhodopsin. Night blindness or defective vision at low illumination results from a failure to re-synthesize 11-<i>cis</i> retinal rapidly. Epithelial differentiation: The role of Vitamin A in epithelial differentiation, as well as in other physiological processes, involves the binding of Vitamin A to two families of nuclear retinoid receptors (retinoic acid receptors, RARs; and retinoid-X receptors, RXRs). These receptors function as ligand-activated transcription factors that modulate gene transcription. When there is not enough Vitamin A to bind these receptors, natural cell differentiation and growth are interrupted. Topical vitamin A can reverse the impairment of wound healing seen in patients receiving corticosteroids, perhaps by restoring the normal inflammatory reaction in the wound. The possibility has been suggested that systemic vitamin A could inhibit the anti-inflammatory effect of systemic corticosteroids. Retinol arrested proliferation of cultured neuroblastoma cells at concentrations of 50 um. A correlation existed between inhibition of growth and inhibition of ornithine decarboxylase in both neuroblastoma cells and glioma cells with retinol. In rats exptl-hypervitaminosis A has been shown ... to produce severe damage of the retina, mainly in the pigment epithelium according to electron microscopy. Alcohol dehydrogenase activity was shown to disappear in the pigment epithelium and visual cells ... . /The authors/ have shown that in an experimental cell culture system consisting of carcinogen-treated 10T1/2 cells, both retinoids and all dietary carotenoids examined can reversibly inhibit neoplastic transformation in the post-initiation phase of carcinogenesis. This activity strongly correlates with their ability to increase gap junctional intercellular communication by up-regulating the expression of the gene CX43 (connexin43). Connexins comprise the structural unit of gap junctions, organelles which allow direct transfer of signals, nutrients and waste products between contacting cells. CX43 is the most widely expressed member of the gap junction family of genes, and we have demonstrated that its expression is strongly down-regulated in human cancers and in several premalignant conditions. When several human tumour cell lines were genetically engineered to conditionally express CX43 under the influence of a tetracycline promoter, their neoplastic phenotype was strongly attenuated. Specifically, induced cells were inhibited from growing in an anchorage-independent manner and, additionally, growth as xenografts in immunocompromised animals was also strongly attenuated. Growth inhibition in suspension was associated both with increased G(1) cell-cycle arrest and with increased apoptosis. /The authors/ propose a model whereby junctional communication allows the transfer of growth inhibitory signals from normal to neoplastic cells and that retinoids and carotenoids, by increasing signal transfer, act to prevent cancer.

Pharmacodynamics

Vitamin A is effective for the treatment of Vitamin A deficiency. Vitamin A refers to a group of fat-soluble substances that are structurally related to and possess the biological activity of the parent substance of the group called all-<i>trans</i> retinol or retinol. Vitamin A plays vital roles in vision, epithelial differentiation, growth, reproduction, pattern formation during embryogenesis, bone development, hematopoiesis and brain development. It is also important for the maintenance of the proper functioning of the immune system.