SENSES SYRUP (Each 10ml contains Ginkgo biloba ext/Vitamin B1/Vitamin B3/Vitamin B5/Vitamin B6/Vitamin B12/Folic acid 100mg/2.5mg/2.5mg/6mg/2mg/30mcg/400mcg)

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

• Vitamin B6 deficiency
• Isoniazid-induced neuropathy (prophylaxis and treatment)
• Idiopathic sideroblastic anaemia
• Prevention of penicillamine-induced neuropathy in Wilson's disease
• Metabolic diseases such as cystathioninuria and homocystinuria
• Premenstrual syndrome

Mechanism of action

Pyridoxine hydrochloride is converted in the body to pyridoxal phosphate, which is the active form of vitamin B6. It serves as a cofactor for more than 100 enzymatic reactions, particularly those involved in the metabolism of amino acids, the synthesis of neurotransmitters (such as serotonin, dopamine, and gamma-aminobutyric acid), and the production of hemoglobin. Its role in neurotransmitter synthesis makes it crucial for normal brain function and mood regulation.

Pharmacodynamics

Pyridoxine hydrochloride exerts its effects by facilitating the conversion of amino acids into neurotransmitters and is involved in the synthesis of heme. It impacts the metabolism of tryptophan to serotonin and is essential for the production of norepinephrine and gamma-aminobutyric acid, which are vital for proper neurological function. Deficiency of vitamin B6 can lead to neurological symptoms, including peripheral neuropathy and cognitive disturbances.

Pharmacokinetics

Pyridoxine hydrochloride is readily absorbed from the gastrointestinal tract. It is primarily metabolized in the liver, where it is converted to its active form, pyridoxal phosphate. The elimination half-life of pyridoxine is approximately 15-20 days, and it is excreted primarily through the urine. Renal impairment may affect the metabolism and excretion of pyridoxine, necessitating dose adjustments.

Contra-indications

• Hyperkalaemia
• Severe liver damage

Adverse effects

• Peripheral neuritis
• Hepatitis
• Hypoglycaemia
• Urine discolouration

Interactions

• Potassium aminobenzoate
• Isoniazid

Precautions

• Caution in renal impairment (increased risk of hyperkalaemia)
• Interrupt treatment during periods of low food intake (such as fasting, anorexia, and nausea) to reduce risk of hypoglycaemia
• Monitor liver function tests monthly during high-dose therapy

Pregnancy

Manufacturer advises avoiding use in pregnancy due to potential risk of birth defects; however, no adverse effects have been reported at normal dietary levels.

Breast-feeding

Theoretical risk of toxicity in infants if mothers take large doses.

Storage

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

Formulations

• Pyridoxine hydrochloride 10 mg tablets
• Pyridoxine hydrochloride 20 mg tablets
• Pyridoxine hydrochloride 50 mg tablets
• Pyridoxine hydrochloride oral solution 20 mg per 1 ml

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

• Cognitive impairment
• Dementia
• Memory enhancement
• Anxiety
• Peripheral vascular disease

Dosage

Children: Safety and efficacy in children have not been established. Use is not generally recommended without professional guidance.

Adults: Refer to specific product guidelines, as Ginkgo biloba is available in various forms including tablets, extracts, and teas. Typical doses range from 120 to 240 mg per day, divided into two or three doses.

Mechanism of action

The exact mechanism of action of Ginkgo biloba is not fully understood, but it is believed to enhance cerebral blood flow and improve circulation by inhibiting platelet-activating factor (PAF) and promoting vasodilation through nitric oxide release. Additionally, the antioxidant properties of flavonoids and terpenoids may protect neurons from oxidative stress and free radical damage.

Pharmacodynamics

Ginkgo biloba exhibits several pharmacodynamic effects, including increased blood flow to the brain, improved oxygen utilization, and enhanced glucose metabolism. It may also modulate neurotransmitter systems, including serotonin and dopamine, which could contribute to its effects on mood and cognitive function. The anti-inflammatory properties may further aid in neuroprotection.

Pharmacokinetics

Ginkgo biloba extracts are well-absorbed after oral administration. The bioavailability of its active constituents varies, and peak plasma concentrations occur within 1 to 4 hours post-ingestion. The elimination half-life of ginkgo flavonoids is approximately 4 to 5 hours, and metabolites are primarily excreted in urine. Factors such as age, health status, and concurrent medications can affect its pharmacokinetics.

Adverse effects

• Headache
• Dizziness
• Gastrointestinal upset
• Allergic skin reactions
• Palpitations

Interactions

• Anticoagulants (e.g., warfarin)
• Antiplatelet agents (e.g., aspirin)
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Certain antidepressants (e.g., selective serotonin reuptake inhibitors)

Precautions

• Use with caution in patients with bleeding disorders
• Monitor for potential interactions with other medications
• Discontinue use prior to surgery to reduce bleeding risk

Pregnancy

Not recommended due to insufficient safety data.

Breast-feeding

Lack of sufficient data, caution is advised.

Storage

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

Formulations

• Tablets
• Capsules
• Liquid extracts

Indications

• Folate deficiency
• Megaloblastic anemia
• Prevention of neural tube defects in pregnancy
• Supplementation in patients on certain medications (e.g., methotrexate)

Dosage

Children: Refer to the BNF for Children for appropriate pa

Adults: Refer to specific guidelines or the BNF for appropriate adult dosing based on the indication.

Mechanism of action

Folate functions as a coenzyme in the conversion of homocysteine to methionine, a process that is vital for DNA synthesis and repair. It is involved in the one-carbon metabolism pathway, where it acts as a carrier of one-carbon units necessary for the synthesis of purines and thymidylate, thus supporting the production of nucleotides and DNA. This mechanism is particularly important in rapidly dividing cells.

Pharmacodynamics

Folate is critical for the formation of red blood cells and the proper functioning of the nervous system. It aids in the production of nucleic acids, which are essential for cell proliferation. Folate deficiency can lead to impaired DNA synthesis, resulting in megaloblastic anemia characterized by the presence of large, immature red blood cells in the bloodstream. Adequate folate levels are also associated with reduced risk of neural tube defects in developing fetuses.

Pharmacokinetics

Folate is absorbed in the proximal part of the small intestine, primarily in the jejunum, and is transported in the bloodstream bound to plasma proteins. It undergoes hepatic metabolism and is stored mainly in the liver. The elimination half-life varies, but dietary folate can be retained in the body for several weeks. Excess folate is excreted through the urine. The bioavailability of folate from food sources is lower compared to synthetic folic acid found in supplements.

Interactions

• folates+fluorouracil: Severe (increases risk of toxicity)
• folates+antiepileptics: Moderate (decreases concentration)
• folates+fosphenytoin: Moderate (decreases concentration)
• folates+phenobarbital: Moderate (decreases concentration)
• folates+phenytoin: Moderate (decreases concentration)
• folates+primidone: Moderate (decreases concentration)
• sulfasalazine+folates: Unknown (decreases absorption)

Pregnancy

Folate is essential for fetal development and is often recommended to prevent neural tube defects.

Breast-feeding

Folate is generally safe during breastfeeding, as it is important for both maternal and infant health.

Storage

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

Formulations

• Tablets
• Injection

Indications

• Cognitive enhancement
• Memory disorders
• Tinnitus
• Peripheral vascular disease
• Anxiety
• Age-related macular degeneration

Dosage

Children: Safety and efficacy have not been established in children, so refer to specific guidelines if considering use in paediatric populations.

Adults: Refer to specific product guidelines, typically ranging from 120 to 240 mg of standardized ginkgo extract per day, divided into two or three doses.

Mechanism of action

The exact mechanism of action of ginkgo is not fully understood, but it is thought to involve several pathways. Ginkgo extracts contain flavonoids and terpenoids, which are believed to contribute to its pharmacological effects. These compounds may enhance cerebral blood flow by dilating blood vessels and reducing blood viscosity. Ginkgo also has antioxidant properties that help protect against oxidative stress, and it may modulate neurotransmitter systems, particularly those involving serotonin and dopamine.

Pharmacodynamics

Ginkgo exhibits various pharmacodynamic effects, including vasodilation, increased blood flow, and improved neurotransmission. It is noted for its ability to enhance cognitive function, particularly in older adults with mild cognitive impairment. The antioxidant properties of ginkgo help mitigate damage caused by free radicals, potentially reducing the risk of neurodegenerative diseases. Its effects on blood circulation can also alleviate symptoms associated with peripheral vascular disease.

Pharmacokinetics

Ginkgo is rapidly absorbed after oral administration, with peak plasma concentrations typically occurring within 1-3 hours. It undergoes extensive metabolism in the liver, primarily via cytochrome P450 enzymes. The elimination half-life of ginkgo components can vary, generally ranging from 4 to 12 hours. The bioavailability of ginkgo extracts can be influenced by formulation and individual patient factors, including age and health status.

Contra-indications

• Hypersensitivity to ginkgo or any of its components
• Active bleeding disorders
• Concurrent use with anticoagulants or antiplatelet agents

Adverse effects

• Gastrointestinal upset
• Headache
• Dizziness
• Allergic skin reactions
• Palpitations

Interactions

• Increased risk of bleeding when used with warfarin, aspirin, or other anticoagulants
• Potential interaction with selective serotonin reuptake inhibitors (SSRIs) and other antidepressants
• May affect the metabolism of certain drugs metabolized by cytochrome P450 enzymes

Precautions

• Use with caution in patients with a history of seizures
• Monitor for bleeding complications in patients with bleeding disorders
• Discontinue use prior to surgical procedures to reduce bleeding risk

Pregnancy

Limited data available, caution advised; consult healthcare provider.

Breast-feeding

Insufficient reliable information available regarding safety; consult healthcare provider.

Storage

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

Formulations

• Ginkgo biloba extract (standardized)
• Ginkgo leaf tablets
• Ginkgo capsules
• Ginkgo tinctures

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 B6 deficiency
• Peripheral neuropathy associated with isoniazid therapy
• Supplementation in specific dietary deficiencies

Dosage

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

Adults: Refer to the BNF for specific dosing details, typically 10-50 mg daily for deficiency.

Mechanism of action

Pyridoxine, mainly in its active form pyridoxal 5'-phosphate, is involved in numerous biochemical reactions, including amino acid metabolism, glycogen breakdown, nucleic acid synthesis, and the production of key neurotransmitters. It aids in the synthesis of hemoglobin and sphingolipids, and its deficiency can impair several physiological processes, including immune response and vascular health.

Pharmacodynamics

Pyridoxine is utilized for the prevention and treatment of vitamin B6 deficiency, particularly in individuals undergoing treatment with isoniazid, which can deplete vitamin B6 levels. It may also have beneficial effects on blood pressure and lipid profiles, as studies have shown it can lower both systolic and diastolic blood pressure, inhibit platelet aggregation, and improve cholesterol levels. Additionally, it plays a role in enhancing immune function and protecting endothelial cells from injury.

Pharmacokinetics

Pyridoxine is rapidly absorbed from the gastrointestinal tract. It is transported to tissues where it is phosphorylated to its active form, pyridoxal 5'-phosphate. The vitamin is primarily excreted in urine as pyridoxine and its metabolites. Its half-life varies depending on the individual’s nutritional status and other factors. Adequate dietary intake is essential for maintaining optimal levels in the body.

Pregnancy

Pyridoxine is generally considered safe during pregnancy. However, high doses should be avoided unless specifically prescribed.

Breast-feeding

Pyridoxine is excreted in breast milk, but at normal dietary levels it is considered safe for breastfeeding mothers.

Storage

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

Formulations

• Tablets
• Oral solution
• Injectable form

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

Indications

• Vitamin deficiency syndromes (e.g., scurvy for vitamin C deficiency, rickets for vitamin D deficiency)
• Support for immune function
• Antioxidant support
• Bone health maintenance
• Vision health
• Energy metabolism support

Dosage

Children: Refer to the BNF for Children for specific vitamin dosing guidelines, which depend on age and nutritional requirements.

Adults: Refer to specific vitamin guidelines as dosage varies significantly depending on the type of vitamin and individual needs.

Mechanism of action

Vitamins function primarily as coenzymes or precursors for coenzymes in enzymatic reactions. For instance, B vitamins are involved in energy metabolism, while vitamins A, C, D, E, and K support various physiological functions including vision, antioxidant activity, calcium regulation, and blood clotting. Each vitamin has a unique mechanism of action based on its structure and role in the body.

Pharmacodynamics

Vitamins exert their effects at the cellular level, influencing metabolic pathways, gene expression, and immune responses. For example, vitamin D regulates calcium and phosphate homeostasis, while vitamin A is crucial for vision and immune function. Deficiencies in vitamins can lead to a range of disorders, highlighting their importance in maintaining health.

Pharmacokinetics

The pharmacokinetics of vitamins vary widely. Fat-soluble vitamins (A, D, E, and K) are stored in liver and adipose tissues and can be released into circulation as needed. Water-soluble vitamins (B-complex and C) are not stored and must be consumed regularly, with excess amounts excreted in urine. Absorption rates, half-lives, and distribution can also differ based on the specific vitamin and individual metabolic factors.

Interactions

• tretinoin+vitamin: Severe (increases risk of vitamin toxicity)
• retinoids+vitamin: Severe (increases risk of vitamin toxicity)
• retinoids+vitamin: Moderate (increases risk of toxicity)
• carbamazepine+vitamin: Unknown (decreases effects)
• cobicistat+vitamin: Unknown (increases exposure)
• vitamin D substances+digoxin: Unknown (increases risk of toxicity)
• idelalisib+vitamin: Unknown (increases exposure)
• clarithromycin+vitamin: Unknown (increases exposure)

Pregnancy

Consult healthcare professional before use. Vitamin supplementation during pregnancy should be carefully managed to avoid hypervitaminosis.

Breast-feeding

Consult healthcare professional before use. Some vitamins can pass into breast milk and may affect the infant.

Storage

Store in a cool, dry place, away from direct sunlight. Ensure it is kept out of reach of children.

Formulations

• {'name': 'Vitamin A', 'form': 'Capsule', 'strength': '10000 IU'}
• {'name': 'Vitamin D', 'form': 'Tablet', 'strength': '1000 IU'}
• {'name': 'Vitamin E', 'form': 'Softgel', 'strength': '400 IU'}

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

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

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.

Mechanism of action

Vitamin B6 is the collective term for a group of three related compounds, pyridoxine (PN), pyridoxal (PL) and pyridoxamine (PM), and their phosphorylated derivatives, pyridoxine 5'-phosphate (PNP), pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP). Although all six of these compounds should technically be referred to as vitamin B6, the term vitamin B6 is commonly used interchangeably with just one of them, pyridoxine. Vitamin B6, principally in its biologically active coenzyme form pyridoxal 5'-phosphate, is involved in a wide range of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemogloblin, sphingomyelin and other sphingolipids, and the synthesis of the neurotransmitters serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA).

Pharmacodynamics

Vitamin B6 (pyridoxine) is a water-soluble vitamin used in the prophylaxis and treatment of vitamin B6 deficiency and peripheral neuropathy in those receiving isoniazid (isonicotinic acid hydrazide, INH). Vitamin B6 has been found to lower systolic and diastolic blood pressure in a small group of subjects with essential hypertension. Hypertension is another risk factor for atherosclerosis and coronary heart disease. Another study showed pyridoxine hydrochloride to inhibit ADP- or epinephrine-induced platelet aggregation and to lower total cholesterol levels and increase HDL-cholesterol levels, again in a small group of subjects. Vitamin B6, in the form of pyridoxal 5'-phosphate, was found to protect vascular endothelial cells in culture from injury by activated platelets. Endothelial injury and dysfunction are critical initiating events in the pathogenesis of atherosclerosis. Human studies have demonstrated that vitamin B6 deficiency affects cellular and humoral responses of the immune system. Vitamin B6 deficiency results in altered lymphocyte differentiation and maturation, reduced delayed-type hypersensitivity (DTH) responses, impaired antibody production, decreased lymphocyte proliferation and decreased interleukin (IL)-2 production, among other immunologic activities.