VIKONON​ ​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

• 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

• Management of apnea of prematurity
• Enhancement of alertness and cognitive performance
• Relief of headaches, particularly when combined with analgesics
• Enhancement of physical performance in sports

Dosage

Children: For infants, particularly for apnea of prematurity

Adults: The usual adult dose for alertness enhancement is 100 to 200 mg, taken as needed. For the management of apnea of prematurity, doses may vary and should be determined by a healthcare professional.

Mechanism of action

Caffeine acts primarily as an antagonist of adenosine receptors, inhibiting the action of adenosine, which normally promotes sleep and relaxation. This antagonism leads to increased neuronal firing and the release of neurotransmitters such as dopamine and norepinephrine. Caffeine also inhibits phosphodiesterase enzymes, enhancing levels of cyclic AMP and cyclic GMP, which are important for various cellular functions. Additionally, in the context of respiratory function, caffeine stimulates the respiratory centers in the central nervous system, enhancing ventilation.

Pharmacodynamics

Caffeine stimulates the central nervous system, increasing alertness and reducing fatigue. It relaxes smooth muscles, increases cardiac muscle contraction, and can enhance physical performance. Caffeine also promotes gastric acid secretion and gastrointestinal motility, and it exhibits mild diuretic properties. Its effects can lead to restlessness and agitation in some individuals, particularly at higher doses.

Pharmacokinetics

Caffeine is rapidly absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 30 to 120 minutes after ingestion. It is distributed widely throughout body tissues, readily crossing the blood-brain barrier. Caffeine is metabolized primarily in the liver by cytochrome P450 1A2, producing three primary metabolites: paraxanthine, theobromine, and theophylline. The elimination half-life varies significantly among individuals, influenced by factors such as age, liver function, pregnancy, and the use of certain medications. It is primarily excreted in urine.

Adverse effects

• Restlessness
• Agitation
• Insomnia
• Increased heart rate
• Nausea
• Gastrointestinal discomfort
• Headaches

Interactions

• caffeinecitrate+adenosine: Unknown (decreases efficacy)
• caffeinecitrate+antiarrhythmics: Unknown (decreases efficacy)

Precautions

• Use cautiously in patients with a history of anxiety disorders, insomnia, or cardiac arrhythmias.
• Monitor caffeine intake in individuals with certain medical conditions, such as hypertension.

Pregnancy

Caffeine crosses the placenta; excessive intake during pregnancy may be associated with adverse outcomes. It is generally recommended to limit caffeine consumption.

Breast-feeding

Caffeine is excreted in breast milk; moderate consumption is considered safe, but excessive intake may affect the infant's sleep and behavior.

Storage

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

Formulations

• Tablets
• Oral solutions
• Injectable preparations
• Caffeine citrate

Indications

• Vitamin D deficiency
• Osteoporosis
• Rickets
• Hypoparathyroidism
• Renal osteodystrophy

Mechanism of action

For its activity, ergocalciferol must be transformed into its major active metabolite and transported to target organs to bind to the vitamin D receptor. This receptor activation, part of the vitamin D endocrine system, alters transcription rates of vitamin D receptor target genes. Ergocalciferol also has nongenomic effects such as stimulating intestinal calcium transport. The mechanism of calcitriol, the activated form of vitamin D, involves binding to cytosolic receptors, which then interact with DNA to modulate gene transcription, similar to steroid and thyroid hormones.

Pharmacodynamics

After activation of the vitamin D receptor, ergocalciferol induces several biological changes, including the mobilization and accretion of calcium and phosphorus in bone, intestinal absorption of these minerals, and renal reabsorption. It promotes osteoblast formation, fetal development, pancreatic function, neural function, immune response, cellular growth, and differentiation. Compared to cholecalciferol, ergocalciferol is less potent due to reduced induction of calcidiol. In patients with end-stage renal disease, ergocalciferol supplementation has shown significant benefits in bone and mineral metabolism, glycemic control, serum albumin levels, and inflammatory markers.

Pharmacokinetics

The pharmacokinetics of ergocalciferol involves its absorption in the gastrointestinal tract, conversion to active metabolites in the liver and kidneys, and subsequent distribution to various tissues. The bioavailability can be influenced by dietary fat and the presence of certain medical conditions. The half-life of ergocalciferol is approximately 15 days, and it is stored in fat tissues. Its elimination primarily occurs through hepatic metabolism and biliary excretion.

Adverse effects

• Nausea
• Vomiting
• Constipation
• Weakness
• Weight loss
• Bone pain
• Kidney stones
• Hypercalcemia

Interactions

• Anticonvulsants may reduce the effectiveness of ergocalciferol
• Thiazide diuretics may enhance the risk of hypercalcemia when used with ergocalciferol
• Magnesium-containing antacids may increase the risk of hypermagnesemia

Precautions

• Monitor calcium levels periodically during therapy
• Use with caution in patients with a history of kidney stones
• Caution in patients with hyperparathyroidism

Pregnancy

Ergocalciferol is generally considered safe during pregnancy when used as directed, but it should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Ergocalciferol is excreted in breast milk; however, the amounts are typically not expected to be harmful to the nursing infant.

Storage

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

Formulations

• Capsules
• Oral solution
• Tablets

Indications

• Calcium deficiency
• Osteoporosis prevention and treatment
• Rickets
• Hypoparathyroidism
• Postmenopausal bone loss
• Dietary supplement for bone health

Dosage

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

Adults: Refer to established guidelines or clinical protocols as no specific dose is provided.

Mechanism of action

Calcium glycerophosphate dissociates in the gastrointestinal tract to release calcium ions. The released calcium is essential for various physiological processes, including the maintenance of bone structure and function, neurotransmission, muscle contraction, and blood coagulation. Additionally, phosphorus plays a crucial role in energy metabolism and cellular function.

Pharmacodynamics

Calcium is vital for maintaining bone density and health. It acts by promoting the mineralization of bone and maintaining the structural integrity of bone tissue. Phosphorus, in conjunction with calcium, supports bone health and is involved in various metabolic pathways, including ATP formation and cellular signaling. The balance of calcium and phosphorus is critical for overall metabolic health.

Pharmacokinetics

After oral administration, calcium glycerophosphate is absorbed in the gastrointestinal tract, with calcium being absorbed primarily in the duodenum and jejunum. The absorption is influenced by dietary factors, such as the presence of vitamin D, which enhances calcium absorption. The peak plasma concentrations of calcium typically occur within a few hours after ingestion. Calcium is excreted primarily in the urine, while phosphorus is excreted in both urine and feces. The half-life of calcium in the body can vary, depending on factors such as age, dietary intake, and metabolic demand.

Contra-indications

• Hypercalcemia
• Severe renal impairment
• Hypersensitivity to calcium or any component of the formulation

Adverse effects

• Gastrointestinal disturbances such as nausea, vomiting, and constipation
• Hypercalcemia
• Kidney stones
• Dizziness
• Fatigue

Interactions

• Calcium may interfere with the absorption of certain oral medications, including bisphosphonates, tetracyclines, and levothyroxine
• Thiazide diuretics may increase the risk of hypercalcemia
• Calcium may reduce the effectiveness of certain medications such as quinolone antibiotics

Precautions

• Use with caution in patients with a history of kidney stones
• Monitor serum calcium levels in patients receiving high doses
• Consider adjusting dosage in patients with renal impairment
• Patients should be advised on dietary calcium intake

Pregnancy

Calcium glycerophosphate is generally considered safe during pregnancy, as calcium is essential for fetal development. However, it should be used under medical supervision.

Breast-feeding

Calcium glycerophosphate is excreted in breast milk but is not expected to cause adverse effects in nursing infants when taken at recommended doses.

Storage

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

Formulations

• Oral tablets
• Powder for oral solution
• Chewable tablets

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

• Prevention of vitamin E deficiency
• Antioxidant therapy
• Support in conditions related to oxidative stress

Dosage

Children: Refer to BNF for Children for specific dosage guidelines.

Adults: Refer to BNF for specific dosage guidelines.

Mechanism of action

Tocopherol acts as a radical scavenger, primarily functioning as an antioxidant for lipid bilayers. It donates hydrogen atoms to free radicals, trapping them and preventing cellular damage. Its effectiveness is influenced by its location within the membrane and its interaction with cytosolic reductants like ascorbate. Tocopherol can trap multiple radicals, including alkyl and peroxy radicals.

Pharmacodynamics

The antioxidant properties of tocopherol lead to significant pharmacodynamic effects, including the inhibition of cell death through modulation of protein kinase C (PKC). Tocopherol also exhibits anti-inflammatory effects, which can be attributed to its influence on cytokines, prostaglandins, prostanoids, and thromboxanes. These interactions may contribute to its protective effects in various pathological conditions.

Pharmacokinetics

Tocopherol is absorbed in the intestines and its bioavailability can be influenced by dietary fat intake. It is transported in the plasma primarily bound to lipoproteins. Tocopherol is stored in adipose tissue and the liver, and its elimination occurs through bile and urine. The half-life of tocopherol can vary depending on the individual's nutritional status and other factors.

Pregnancy

Tocopherol is generally considered safe during pregnancy, but it is advisable to consult a healthcare provider before use.

Breast-feeding

Tocopherol is excreted in breast milk, and while it is considered safe, a healthcare provider should be consulted for specific recommendations.

Storage

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

Dosage

Children: Refer to specific product guidelines for dosage, as this can vary widely depending on the active ingredient and intended use.

Adults: Refer to specific product guidelines for dosage, as this can vary widely depending on the active ingredient and intended use.

Mechanism of action

The mechanism of action of triturated drugs is primarily dependent on the active pharmaceutical ingredient (API) that has been triturated. Generally, the purpose of triturating is to facilitate faster dissolution and absorption of the drug in the body. Depending on the specific medication, the action may involve various biochemical pathways, receptor interactions, or inhibition of certain enzymes.

Pharmacodynamics

Pharmacodynamics of triturates varies widely based on the specific drug utilized. In general, the effects can include modulation of neurotransmitter levels, receptor activation or inhibition, and alteration of physiological functions. The finely powdered state can lead to a more rapid onset of action compared to larger particles, potentially enhancing therapeutic effects.

Pharmacokinetics

The pharmacokinetics of triturated drugs depend on the characteristics of the active ingredient. Typically, triturates are designed for rapid absorption through the mucosal membranes or gastrointestinal tract. The onset of action can be faster due to the increased surface area, leading to quicker dissolution in solution. The distribution, metabolism, and excretion profiles will also vary based on the specific drug and its formulation.

Pregnancy

Consult with a healthcare provider before use as safety during pregnancy has not been established.

Breast-feeding

Caution is advised when using during breastfeeding; consult a healthcare provider.

Storage

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

Indications

• Erectile dysfunction
• Impotence
• Sexual dysfunction

Dosage

Children: Yohimbine is not typically indicated for pediatric use; refer to the BNF for Children for specific guidance.

Adults: The usual dose for adults is 5.4 mg three times a day, taken before meals. Doses may be adjusted based on individual response and tolerance.

Mechanism of action

Yohimbine acts as a pre-synaptic alpha 2-adrenergic blocker. This blockade increases sympathetic drive, leading to enhanced norepinephrine release and increased firing rates of noradrenergic neurons in the brain. Additionally, it may influence other neurotransmitters such as dopamine and serotonin, playing a role in its effects on erectile function and mood.

Pharmacodynamics

Yohimbine is characterized as an indolalkylamine alkaloid with structural similarities to reserpine. Its pharmacological action includes the blockade of presynaptic alpha-2 adrenergic receptors, which modifies peripheral autonomic nervous system activity by stimulating parasympathetic (cholinergic) actions and inhibiting sympathetic (adrenergic) responses. Its effects on male sexual function are linked to increased cholinergic activity and alpha-2 blockade, potentially enhancing penile blood flow.

Pharmacokinetics

Yohimbine is absorbed following oral administration and exhibits a moderate half-life. It has a distribution pattern that allows it to cross the blood-brain barrier, contributing to its central nervous system effects. Metabolism primarily occurs in the liver, with excretion mainly through the kidneys. Its pharmacokinetic profile indicates variability based on individual factors such as age, health status, and concomitant medications.

Contra-indications

• Hypersensitivity to yohimbine or any of its components
• Severe renal impairment
• Severe cardiovascular disorders
• History of anxiety or panic disorders

Adverse effects

• Increased heart rate
• Hypertension
• Anxiety
• Nausea
• Dizziness
• Insomnia
• Headache
• Gastrointestinal disturbances

Interactions

• Monoamine oxidase inhibitors (MAOIs) may enhance the effects of yohimbine
• Other sympathomimetics may have additive effects
• Antihypertensives may have reduced effectiveness

Precautions

• Use with caution in patients with a history of cardiovascular disease
• Monitor blood pressure regularly during treatment
• Caution advised in patients with psychiatric disorders

Pregnancy

Yohimbine is not recommended during pregnancy due to lack of safety data.

Breast-feeding

Caution is advised as it is unknown if yohimbine is excreted in human milk.

Storage

Store at room temperature, in a dry place away from light.

Formulations

• Tablets
• Capsules
• Oral solutions

Indications

• Erectile dysfunction
• Aphrodisiac
• Orthostatic hypotension
• Veterinary medicine as a reversal agent for certain anesthetics

Dosage

Adults: The usual oral dose for erectile dysfunction is 5.4 to 6 mg three times daily, with a

Mechanism of action

Yohimbine hydrochloride exerts its pharmacological effects mainly through the selective blockade of alpha-2 adrenergic receptors, leading to increased release of norepinephrine. This results in enhanced sympathetic outflow, which may improve erectile function and libido. The increased norepinephrine also promotes vasodilation and increased blood flow to the genital area, contributing to its aphrodisiac effects.

Pharmacodynamics

The pharmacodynamic profile of yohimbine includes its ability to antagonize alpha-2 adrenergic receptors, leading to an increase in norepinephrine release. This results in a range of effects including increased heart rate, blood pressure, and improved blood flow. The anxiogenic and stimulant effects of yohimbine can also be attributed to its action on central nervous system receptors. The onset of action may vary, and the duration of effects can last several hours depending on the individual response.

Pharmacokinetics

Yohimbine hydrochloride is well-absorbed after oral administration, with peak plasma concentrations typically occurring within 1 to 2 hours. The bioavailability can be affected by food intake. It is extensively metabolized in the liver, and its metabolites are primarily excreted via the kidneys. The elimination half-life of yohimbine is approximately 5 hours, but this may vary among individuals due to differences in metabolism. Factors such as age, liver function, and concurrent medications can influence its pharmacokinetic profile.

Contra-indications

• Hypersensitivity to yohimbine or any component of the formulation
• Patients with a history of cardiovascular disease
• Patients with renal impairment
• Patients taking monoamine oxidase inhibitors (MAOIs)

Adverse effects

• Hypertension
• Tachycardia
• Anxiety
• Dizziness
• Nausea
• Headache

Interactions

• Caution when used with other antihypertensive medications
• May interact with antidepressants, particularly MAOIs
• Caution with sympathomimetic agents

Precautions

• Use with caution in patients with psychiatric disorders
• Monitor blood pressure regularly during treatment
• Consider potential for drug interactions
• Assess renal function before prescribing

Pregnancy

There is insufficient evidence regarding the safety of yohimbine in pregnancy, use only if potential benefit justifies the risk.

Breast-feeding

The excretion of yohimbine in human milk is not well studied, caution is advised.

Storage

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

Formulations

• Yohimbine hydrochloride tablets
• Yohimbine hydrochloride injectable 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

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

The mechanism of action of caffeine is complex, as it impacts several body systems, which are listed below. The effects as they relate to various body systems are described as follows: **General and cellular actions** Caffeine exerts several actions on cells, but the clinical relevance is poorly understood. One probable mechanism is the inhibition of nucleotide phosphodiesterase enzymes, adenosine receptors, regulation of calcium handling in cells, and participates in adenosine receptor antagonism. Phosphodiesterase enzymes regulate cell function via actions on second messengers cAMP and cGMP. This causes lipolysis through activation of hormone-sensitive lipases, releasing fatty acids and glycerol. **Respiratory** The exact mechanism of action of caffeine in treating apnea related to prematurity is unknown, however, there are several proposed mechanisms, including respiratory center stimulation in the central nervous system, a reduced threshold to hypercapnia with increased response, and increased consumption of oxygen, among others. The blocking of the adenosine receptors enhances respiratory drive via an increase in brain medullary response to carbon dioxide, stimulating ventilation and respiratory drive, while increasing contractility of the diaphragm. **Central nervous system** Caffeine demonstrates antagonism of all 4 adenosine receptor subtypes (A1, A2a, A2b, A3) in the central nervous system. Caffeine's effects on alertness and combatting drowsiness are specifically related to the antagonism of the A2a receptor. **Renal system** Caffeine has diuretic effects due to is stimulatory effects on renal blood flow, increase in glomerular filtration, and increase in sodium excretion. **Cardiovascular system** Adenosine receptor antagonism at the A1 receptor by caffeine stimulates inotropic effects in the heart. Blocking of adenosine receptors promotes catecholamine release, leading to stimulatory effects occurring in the heart and the rest of the body. In the blood vessels, caffeine exerts direct antagonism of adenosine receptors, causing vasodilation. It stimulates the endothelial cells in the blood vessel wall to release nitric oxide, potentiating blood vessel relaxation. Catecholamine release, however, antagonizes this and exerts inotropic and chronotropic effects on the heart, ultimately leading to vasoconstriction. Finally, caffeine is shown to raise systolic blood pressure measurements by 5 to 10 mmHg when it is not taken regularly, versus no effect in those who consume it regularly. The vasoconstricting effects of caffeine are beneficial in migraines and other types of headache, which are normally caused by vasodilation in the brain. Caffeine competitively inhibits phosphodiesterase, the enzyme that degrades cyclic 3',5'-adenosine monophosphate (AMP). Increased levels of intracellular cyclic AMP mediate most of caffeine's pharmacologic actions. Caffeine stimulates all levels of the CNS... Caffeine's cortical effects are milder and of shorter duration than those of amphetamines. In slightly larger doses, caffeine stimulates medullary, vagal, vasomotor, and respiratory centers, promoting bradycardia, vasoconstriction, and increased respiratory rate. Caffeine constricts cerebral vasculature. In contrast, the drug directly dilates peripheral blood vessels...

Pharmacodynamics

Caffeine stimulates the central nervous system (CNS), heightening alertness, and sometimes causing restlessness and agitation. It relaxes smooth muscle, stimulates the contraction of cardiac muscle, and enhances athletic performance. Caffeine promotes gastric acid secretion and increases gastrointestinal motility. It is often combined in products with analgesics and ergot alkaloids, relieving the symptoms of migraine and other types of headaches. Finally, caffeine acts as a mild diuretic.

Mechanism of action

For its activity, ergocalciferol is required to be transformed to its major active circulating hydroxylated metabolite and transported to the target organs in order to bind to its target, the vitamin D receptor. The activation of the vitamin D receptor is part of the vitamin D endocrine system and it is described by the production of a change in the transcription rates of the vitamin D receptor target genes. The target genes in the DNA affected by the presence of ergocalciferol are called vitamin D response elements which are dependent on co-modulators. The vitamin D receptor is a transcription factor and member of the steroid hormone nuclear receptor family. It presents a DNA binding domain (VDRE) that, when activated, recruits coregulatory complexes to regulate the genomic activity. Additionally, ergocalciferol presents nongenomic effects such as the stimulation of intestinal calcium transport via transcaltachia. The mechanism of action of calcitriol, the activated form of vitamin D, resembles that of the steroid and thyroid hormones. Thus, calcitriol binds to cytosolic receptors within target cells, and the receptor-hormone complex interacts with the DNA of certain genes to either enhance or inhibit their transcription. Structural analysis of the calcitriol receptor indicates that it belongs to the same supergene family as the steroid receptors. Calcitriol also appears to exert a few effects that occur too rapidly to be explained by genomic actions. /Calcitriol/ The mechanisms responsible for mobilization of bone salts have been only partially defined, and the interaction of multiple factors appears to be involved. Paradoxically, the cells responsible for bone resorption (osteoclasts) are not directly acted upon by calcitriol and do not appear to contain calcitriol receptors. Instead, calcitriol causes an increase in the number of osteoclasts available to resorb bone; this may result from an action upon myeloid hematopoietic precursor cells that are induced to differentiate toward functional osteoclasts. The cells responsible for bone formation (osteoblasts) do contain receptors, and calcitriol causes them to elaborate several proteins, including osteocalcin, a vitamin K-dependent protein that contains gamma-carboxyglutamic acid residues. The exact role of this protein is not known, but other unidentified substances are also elaborated that appear to stimulate the function of osteoclasts. In addition, calcitriol acts synergistically with gamma-interferon to increase the production of interleukin-1, a lymphokine that promotes bone resorption.

Pharmacodynamics

After the activation of the vitamin D receptor, some of the biological changes produced by ergocalciferol include mobilization and accretion of calcium and phosphorus in the bone, absorption of calcium and phosphorus in the intestine, and reabsorption of calcium and phosphorus in the kidney. Some other effects known to be produced due to the presence of vitamin D are osteoblast formation, fetus development, induction of pancreatic function, induction of neural function, improvement of immune function, cellular growth and cellular differentiation. When compared to its vitamin D counterpart [cholecalciferol], ergocalciferol has been shown to present a reduced induction of calcidiol and hence, it is less potent. Ergocalciferol supplementation in patients with end-stage renal disease has been shown to generate a significant benefit in lab parameters of bone and mineral metabolism as well as improvement in glycemic control, serum albumin levels and reduced levels of inflammatory markers.

Mechanism of action

Tocopherol acts as a radical scavenger. It mainly acts as an antioxidant for lipid bilayers. Tocopherol's functions depend on the H-atom donating ability, location, and movement within the membrane, as well as the efficiency in the radical recycling by some cytosolic reductants such as ascorbate. Tocopherol actions are related to the trap of radicals, and it has been shown that even in the absence of substituents in the ortho-positions, tocopherol can trap more than two radicals. The type of radicals available for tocopherol are alkyl and peroxy.

Pharmacodynamics

The antioxidant effects of tocopherol can be translated into different changes at the pharmacodynamic level. In vitro studies have shown that this antioxidant activity can produce modification in protein kinase C (PKC) which will later be translated into an inhibition of cell death. Some other derivate effects are the anti-inflammatory properties of tocopherol which can be related to the modulation of cytokines or prostaglandins, prostanoids and thromboxanes.

Mechanism of action

Yohimbine is a pre-synaptic alpha 2-adrenergic blocking agent. The exact mechanism for its use in impotence has not been fully elucidated. However, yohimbine may exert its beneficial effect on erectile ability through blockade of central alpha 2-adrenergic receptors producing an increase in sympathetic drive secondary to an increase in norepinephrine release and in firing rate of cells in the brain noradrenergic nuclei. Yohimbine-mediated norepinephrine release at the level of the corporeal tissues may also be involved. In addition, beneficial effects may involve other neurotransmitters such as dopamine and serotonin and cholinergic receptors.

Pharmacodynamics

Yohimbine is an indolalkylamine alkaloid with chemical similarity to reserpine. Yohimbine blocks presynaptic alpha-2 adrenergic receptors. Its action on peripheral blood vessels resembles that of reserpine, though it is weaker and of short duration. Yohimbine's peripheral autonomic nervous system effect is to increase parasympathetic (cholinergic) and decrease sympathetic (adrenergic) activity. It is to be noted that in male sexual performance, erection is linked to cholinergic activity and to alpha-2 adrenergic blockade which may theoretically result in increased penile inflow, decreased penile outflow or both. Yohimbine exerts a stimulating action on the mood and may increase anxiety. Such actions have not been adequately studied or related to dosage although they appear to require high doses of the drug. Yohimbine has a mild anti-diuretic action, probably via stimulation of hypothalmic center and release of posterior pituitary hormone. Reportedly Yohimbine exerts no significant influence on cardiac stimulation and other effects mediated by (beta)-adrenergic receptors. Its effect on blood pressure, if any, would be to lower it; however, no adequate studies are at hand to quantitate this effect in terms of Yohimbine dosage.