NAT B Forte

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

• Management of photosensitivity reactions
• Erythropoietic protoporphyria

Dosage

Children: Child 1–4 years: 60–90 mg daily, Child 5–8 years: 90–120 mg daily, Child 9–11 years: 120–150 mg daily, to be given as a single dose or in divided doses.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Betacarotene acts as an antioxidant and a precursor to vitamin A, which plays a critical role in cellular function, vision, growth, immune function, and skin health.

Pharmacodynamics

As a provitamin, betacarotene is converted to retinol (vitamin A) in the body, supporting various biological functions, including the maintenance of epithelial tissues and the modulation of immune responses.

Pharmacokinetics

Betacarotene is absorbed from the gastrointestinal tract and is stored in the liver. Its absorption can be influenced by dietary fat intake. It is primarily metabolized in the liver and has a relatively long half-life due to its storage in fat tissues.

Pregnancy

Safety in pregnancy has not been established; use only if clearly needed.

Breast-feeding

Excretion in breast milk is unknown; use with caution.

Storage

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

Formulations

• Oral preparations containing beta-carotene

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

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Bronchospasm associated with respiratory conditions

Dosage

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

Adults: Refer to the BNF for specific adult dosing guidelines.

Mechanism of action

Aminophylline works as a phosphodiesterase inhibitor, leading to an increase in intracellular cyclic AMP (cAMP). This action results in the relaxation of bronchial smooth muscle, bronchodilation, and reduced airway resistance. It may also exert anti-inflammatory effects by inhibiting the release of inflammatory mediators from mast cells.

Pharmacodynamics

The pharmacodynamics of aminophylline involve its ability to enhance respiratory function by decreasing airway resistance, improving mucociliary clearance, and increasing respiratory muscle strength. Its therapeutic effects typically begin within 30 minutes of administration, with a peak effect occurring within 2 hours.

Pharmacokinetics

Aminophylline is rapidly absorbed following intravenous administration, with a bioavailability of approximately 100%. Its volume of distribution is large, indicating extensive tissue binding. The drug is metabolized primarily in the liver via cytochrome P450 enzymes, with a half-life ranging from 3 to 10 hours depending on patient factors, including age, liver function, and concurrent medications.

Interactions

• aminoglycosides+agalsidasealfa: Severe (decreases effects)
• aminoglycosides+agalsidasebeta: Severe (decreases effects)
• betablockers,selective+aminophylline: Severe (increases risk of bronchospasm)
• aminophylline+phosphodiesterasetype-: Severe (increases exposure)
• stiripentol+aminophylline: Severe (increases exposure)
• deferasirox+aminophylline: Severe (increases exposure)
• aminophylline+roflumilast: Severe (increases exposure)
• aciclovir+aminophylline: Moderate (increases exposure)
• aminophylline+macrolides: Moderate (decreases exposure)
• aminophylline+erythromycin: Moderate (decreases exposure)

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

• Type 2 diabetes mellitus
• Insulin resistance
• Impaired glucose tolerance
• Metabolic syndrome
• Hyperlipidemia

Dosage

Children: Refer to the BNF for Children for specific dosage recommendations suitable for pediatric patients.

Adults: Refer to the BNF for specific dosage recommendations based on the condition being treated.

Mechanism of action

Chromium enhances insulin signaling by upregulating insulin receptor-mediated pathways. It affects downstream effector molecules after insulin binds to its receptor, leading to the activation of phosphatidylinositol 2-kinase (PI3K) and protein kinase B (Akt). This process promotes the translocation of glucose transporter-4 (Glut4) to the cell membrane, facilitating increased glucose uptake. Additionally, chromium can promote GLUT-4 transporter translocation independently of insulin receptor activity under insulin-resistant conditions and aids in cholesterol efflux by increasing membrane fluidity.

Pharmacodynamics

Trivalent chromium is essential for the glucose tolerance factor, which activates insulin-mediated pathways. It enhances insulin binding to cells, increases the density of insulin receptors, and activates insulin receptor kinase, all of which contribute to improved insulin sensitivity. Chromium deficiency can lead to impaired glucose metabolism, and supplementation can normalize glucose tolerance in individuals exhibiting diabetic-like characteristics due to deficiency.

Pharmacokinetics

Chromium absorption occurs primarily in the intestines, but its bioavailability is influenced by various dietary factors, such as the presence of other minerals and vitamins. The mineral is transported in the bloodstream bound to transferrin and is predominantly stored in the liver, spleen, and bone. The elimination of chromium occurs mainly through urine, with small amounts excreted in feces. The half-life and exact metabolic pathways for chromium can vary based on its form and the individual's nutritional status.

Pregnancy

Chromium is generally considered safe during pregnancy when taken in appropriate amounts, but it is advisable to consult a healthcare provider.

Breast-feeding

Chromium is excreted in breast milk, and while it is deemed safe in moderate amounts, consultation with a healthcare provider is recommended.

Storage

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

Indications

• Copper deficiency
• Occipital Horn Syndrome
• Menke's disease
• Contraception (via copper IUD)

Dosage

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

Adults: Refer to the relevant clinical guidelines and BNF for specific dosing information.

Mechanism of action

Copper is absorbed from the gastrointestinal tract via high affinity copper uptake proteins and low affinity copper uptake proteins, likely being reduced to the Cu1+ form prior to transport. Inside enterocytes, it binds to the copper transport protein ATOX1, which facilitates its transport to copper transporting ATPase-1 on the Golgi membrane for incorporation into the Golgi apparatus. Once in systemic circulation, copper binds primarily to ceruloplasmin, albumin, and alpha 2-macroglobulin. It acts as a cofactor in a variety of oxidase enzymes and also influences sperm motility when released from copper IUDs, contributing to its contraceptive effect.

Pharmacodynamics

Copper is essential for the activity of many enzymes and plays a vital role in processes such as iron metabolism, neurotransmitter synthesis, and antioxidant defense. Copper ions, particularly when released from intrauterine devices, have been shown to decrease sperm viability, thereby impacting fertility.

Pharmacokinetics

Copper is absorbed from the gut and is predominantly transported in the plasma bound to proteins such as ceruloplasmin and albumin. The absorption efficiency can vary; however, a significant portion of dietary copper is usually absorbed. The body regulates copper levels through hepatic excretion and storage mechanisms, ensuring homeostasis. Excess copper can lead to toxicity, while deficiency results in various health issues.

Pregnancy

Copper is considered essential during pregnancy, but excessive intake should be avoided due to potential toxicity.

Breast-feeding

Copper is excreted in breast milk, and adequate maternal intake is important for infant development.

Storage

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

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

• Vitamin B12 deficiency
• Megaloblastic anemia
• Peripheral neuropathy
• Neuropathic pain
• Multiple sclerosis

Dosage

Children: For paediatric patients, refer to the BNF for Children for appropriate dosing guidelines.

Adults: The typical adult dosage for methylcobalamin is 500 micrograms to 1,000 micrograms administered intramuscularly or subcutaneously, usually once daily for the initial treatment, followed by maintenance doses as needed.

Mechanism of action

Methylcobalamin serves as a cofactor for the enzyme methionine synthase, which catalyzes the conversion of homocysteine to methionine. This reaction is crucial in the synthesis of S-adenosylmethionine (SAMe), an important methyl donor in numerous methylation reactions within the body. Methylcobalamin also plays a role in myelin formation and the maintenance of nerve cells.

Pharmacodynamics

Methylcobalamin exhibits neuroprotective effects, promoting nerve regeneration and repair in peripheral neuropathy. It is believed to enhance nerve conduction and improve neurological function. The physiological effects are primarily attributed to its role in methylation processes and the synthesis of neurotransmitters.

Pharmacokinetics

Methylcobalamin is water-soluble and is absorbed in the intestine. The bioavailability can be affected by gastrointestinal health, and intrinsic factor is not required for its absorption. It is distributed throughout the body, with high concentrations in the liver, kidneys, and brain. The elimination half-life of methylcobalamin is approximately 6 hours, and it is excreted primarily in the urine.

Adverse effects

• Nausea
• Diarrhea
• Headache
• Dizziness
• Anxiety
• Rash
• Pruritus

Precautions

• Monitor patients with Leber's disease due to potential optic nerve damage.
• Caution in patients with allergies to cobalt or vitamin B12.
• Use with caution in patients with renal impairment.

Pregnancy

Methylcobalamin is classified as a category A drug. It is generally considered safe during pregnancy, but consultation with a healthcare provider is recommended.

Breast-feeding

Methylcobalamin is excreted in breast milk. It is generally considered safe during breastfeeding, but consultation with a healthcare provider is recommended.

Storage

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

Formulations

• Tablets
• Injections
• Sublingual tablets
• Oral solutions

Indications

• Cancer (various types)
• Rheumatoid arthritis
• Multiple sclerosis
• Inflammatory bowel disease
• Psoriasis
• Hypercholesterolemia
• Infectious diseases (e.g., COVID-19)

Dosage

Children: Refer to the BNF for Children for paediatric dosing information, as it varies based on the specific monoclonal antibody and the condition being treated.

Adults: Refer to the specific monoclonal antibody product information for adult dosage, as it varies based on indication and specific agent used.

Mechanism of action

Monoclonal antibodies work by binding to specific proteins on the surface of cells. This binding can block the activity of certain proteins, mark cells for destruction by the immune system, or deliver cytotoxic agents directly to target cells. The mechanism of action varies depending on the specific monoclonal antibody but often involves modulation of immune response, inhibition of cell proliferation, and induction of apoptotic pathways.

Pharmacodynamics

The pharmacodynamics of monoclonal antibodies is primarily characterized by their specificity and affinity for targeted antigens. This leads to a variety of effects, including neutralization of pathogens, blockade of receptor-ligand interactions, and antibody-dependent cellular cytotoxicity. The clinical effects depend on the disease being treated and the specific antibody's action, such as inducing tumor regression in cancer or reducing inflammation in autoimmune diseases.

Pharmacokinetics

Monoclonal antibodies typically have a long half-life, allowing for less frequent dosing. They are generally administered intravenously or subcutaneously, with absorption and distribution influenced by the antibody's size and charge. The elimination occurs primarily through proteolytic degradation and intracellular recycling. Factors such as patient-specific variables, including immunogenicity and the presence of antibodies against the monoclonal antibody, can impact pharmacokinetics.

Interactions

• abatacept+monoclonalantibodies: Severe (increases risk of generalised infection (possibly life-threatening))
• anakinra+monoclonalantibodies: Severe (increases risk of generalised infection (possibly life-threatening))
• anthracyclines+monoclonalantibodies: Severe (increases risk of cardiotoxicity)
• filgotinib+monoclonalantibodies: Severe (increases risk of immunosuppression)
• monoclonalantibodies+fingolimod: Severe (increases risk of generalised infection (possibly life-threatening))
• normal immunoglobulin+monoclonalantibodies: Severe (affects effects)
• monoclonalantibodies+ozanimod: Severe (increases risk of generalised infection (possibly life-threatening))
• monoclonalantibodies+siponimod: Severe (increases risk of generalised infection (possibly life-threatening))
• monoclonalantibodies+vemurafenib: Severe (increases risk of hepatotoxicity)
• monoclonalantibodies+aminophylline: Moderate (decreases exposure)

Indications

• Angina pectoris
• Chronic stable angina
• Angina due to coronary artery disease

Dosage

Children: Refer to the appropriate prescribing guidelines and consult clinical references for paediatric dosing recommendations.

Adults: Refer to the appropriate prescribing guidelines and consult clinical references for specific adult dosing recommendations.

Mechanism of action

Isosorbide mononitrate is converted to nitric oxide (NO) in the body, which activates guanylate cyclase. This leads to an increase in cyclic guanosine monophosphate (cGMP) levels in smooth muscle cells, resulting in smooth muscle relaxation and vasodilation. This vasodilatory effect decreases preload and afterload on the heart, reducing myocardial oxygen demand and relieving symptoms of angina.

Pharmacodynamics

Mononitrate demonstrates a dose-dependent reduction in myocardial oxygen consumption by decreasing both venous return (preload) and systemic vascular resistance (afterload). It also facilitates coronary artery dilation, improving blood flow to ischemic myocardial tissue. The onset of action can be within 30 minutes, with peak effects generally occurring 1-2 hours after administration. The effects can last for 6-8 hours, depending on the dosing schedule.

Pharmacokinetics

Isosorbide mononitrate is well absorbed from the gastrointestinal tract, with a bioavailability of approximately 100% due to its oral formulation. It undergoes minimal first-pass metabolism. The peak plasma concentration is reached within 1-2 hours post-ingestion. The drug has a half-life of approximately 5 hours, and it is primarily eliminated via the kidneys as unchanged drug and metabolites. Steady-state concentrations are typically achieved within 24 hours of regular dosing.

Contra-indications

• Hypersensitivity to mononitrate or any of its components
• Severe hypotension
• Cardiogenic shock
• Severe anemia
• Concurrent use with phosphodiesterase inhibitors (e.g. sildenafil) due to risk of severe hypotension

Adverse effects

• Headache
• Dizziness
• Hypotension
• Flushing
• Tachycardia
• Palpitations
• Nausea
• Vomiting

Interactions

• Nitrates may enhance the effects of other antihypertensive agents
• Use with caution with alcohol, as it may exacerbate hypotensive effects
• Interactions may occur with phosphodiesterase type 5 inhibitors (e.g. sildenafil) leading to severe hypotension

Precautions

• Caution in patients with recent myocardial infarction or congestive heart failure
• Use with caution in patients with hepatic or renal impairment
• Monitor blood pressure regularly during treatment
• Consider tolerance development with long-term use

Pregnancy

Limited data available on the use of mononitrate in pregnancy. It should only be used if clearly needed and the benefits outweigh the risks.

Breast-feeding

Limited data available. Consider the benefits of breastfeeding against the need for the medication.

Storage

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

Formulations

• Extended-release tablets
• Sustained-release capsules
• Oral tablets

Indications

• Pain relief
• Inflammatory conditions
• Dental applications
• Antifungal treatments
• Antioxidant support

Dosage

Children: Refer to specific product guidelines for pediatric dosing as it may vary based on formulation and intended use.

Adults: Refer to specific product guidelines as dosing may vary based on formulation and intended use.

Mechanism of action

The exact mechanism of action of eugenol is not fully understood. However, it has been shown to interrupt action potentials, contributing to its analgesic properties. Eugenol exhibits anti-inflammatory effects by modulating the activity of polymorphonuclear leukocytes, which release inflammatory mediators. Additionally, eugenol has demonstrated antioxidant activity, protecting cells from oxidative stress. It has been observed to inhibit the formation of malondialdehyde in irradiated thymocytes, suggesting a protective role against oxidative damage.

Pharmacodynamics

Eugenol exhibits several pharmacological properties, including analgesic, anti-inflammatory, antipyretic, neuroprotective, antifungal, and antioxidant effects. Its ability to inhibit reactive oxygen species generation and modulate inflammatory mediators contributes to its therapeutic potential in managing pain and inflammation. The dose-dependent effects of eugenol on respiratory inhibition of mitochondria highlight its impact on cellular energy metabolism, further extending its pharmacodynamic profile.

Pharmacokinetics

Eugenol is rapidly absorbed and distributed throughout the body following administration. It undergoes extensive metabolism in the liver, with various metabolic pathways including conjugation and oxidation. The elimination half-life and specific pharmacokinetic parameters can be influenced by the route of administration and individual patient factors. The exact pharmacokinetics of eugenol in humans require further elucidation through clinical studies.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Skin irritation
• Allergic reactions

Precautions

• Use with caution in individuals with liver disease or gastrointestinal disorders.
• Caution is advised in patients who are pregnant or breastfeeding.

Pregnancy

Eugenol should be used with caution during pregnancy due to insufficient data on safety.

Breast-feeding

Eugenol is excreted in breast milk; caution is advised when administering to breastfeeding mothers.

Storage

Store in a tightly closed container, in a cool, dry place away from light.

Formulations

• Essential oil
• Topical preparations

Dosage

Children: Refer to specific guidelines or consult a healthcare professional for appropriate dosing information, as current literature does not provide standardized dosing recommendations.

Adults: Refer to specific guidelines or consult a healthcare professional for appropriate dosing information, as current literature does not provide standardized dosing recommendations.

Mechanism of action

Picolinate acts as a metabolic intermediate, particularly in the catabolism of tryptophan. It participates in several biochemical pathways such as amino acid and derivative metabolism, and its presence is crucial for the degradation of tryptophan into various metabolites. This process includes its involvement in the production of important coenzymes and other bioactive compounds, thus influencing metabolic pathways and cellular functions.

Pharmacodynamics

Picolinate is involved in the metabolism of tryptophan, leading to the generation of kynurenine and other metabolites. The compound plays a role in the biosynthesis of NAD, which is essential for cellular respiration and energy production. Its effects may include modulation of metabolic pathways and potential influence on cognitive and metabolic health, although specific pharmacodynamic effects can vary based on the context of use.

Pharmacokinetics

The pharmacokinetics of picolinate, including absorption, distribution, metabolism, and excretion, are not extensively documented. It is generally understood that compounds involved in amino acid metabolism are absorbed and utilized by the body in a manner that supports metabolic functions. However, specific parameters such as bioavailability, half-life, and excretion pathways are not well-characterized.

Pregnancy

There is insufficient data on the safety of picolinate in pregnancy. Consult healthcare providers for advice.

Breast-feeding

Limited data is available on the excretion of picolinate in human milk. Caution is advised.

Storage

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

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

Beta-carotene is an antioxidant that presents significant efficacy against the reactive oxygen species singlet oxygen. Beta-carotene acts as a scavenger of lipophilic radicals within the membranes of every cell compartments. It also presents an oxidative modification of LDL. The presence of long chains of conjugated double bonds is responsible for its antioxidative properties by allowing beta-carotene to chelate oxygen-free radicals and dissipate their energy. The chelation of free radicals inhibits the peroxidation of lipids. The effect of beta-carotene in the immune response is thought to be related to the direct effect on the thymus which increases the production of immune cells. IN HEMATOPORPHYRIN PHOTOSENSITIZED MICE BETA-CAROTENE SHOWED PHOTOPROTECTION WAS DUE TO FREE RADICAL SCAVENGING OR SINGLET O QUENCHING BUT ALSO A POSSIBLE ROLE OF 400 NM LIGHT ABSORPTION, A PROPERTY OF BETA-CAROTENE. Beta carotene protects patients with erythropoietic protoporphyria against severe photosensitivity reactions (burning sensation, edema, erythema, pruritus, and/or cutaneous lesions). The drug has no effect on the basic biochemical abnormality of erythropoietic protoporphyria (eg, erythrocyte, plasma, and stool concentrations of protoporphyrins are not altered by the drug). The precise mechanism by which the drug exerts photoprotection has not been established. There is some evidence that photosensitizers may act through the formation of singlet excited oxygen and/or free radicals. Since in vitro studies indicate that beta carotene can quench free radicals and singlet excited oxygen, this may be the mechanism by which the drug acts. It is unlikely that beta carotene acts simply as a filter for the wavelengths of light that induce phototoxic effects. beta-Carotene inhibits UV-B carcinogenesis. beta-Carotene is an excellent quencher of singlet oxygen, and can quench free radicals. beta-Carotene has been shown to quench singlet oxygen/free radical reactions in the skin of porphyric mice, and has been found to quench excited species formed on irradiation of mouse skin by UV-B.

Pharmacodynamics

Oral administration of beta-carotene increases the serum concentration of beta-carotene by 60% but it does not change the concentration found in the heart, liver or kidneys. In vitro studies in hepatocytes have shown that beta-carotene ameliorates oxidative stress, enhances antioxidant activity and decreases apoptosis. Other than the antioxidant activities, some other actions have been correlated to beta-carotene. It is thought to have detoxifying properties, as well as to help increase resistance to inflammation and infection and increase immune response and enhance RNA production.

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

Chromium is an essential nutrient involved in the metabolism of glucose, insulin and blood lipids. Its role in potentiating insulin signalling cascades has been implicated in several studies. Chromium upregulates insulin-stimulated insulin signal transduction via affecting effector molecules downstream of the insulin receptor (IR). IR-mediated signalling pathway involves phoshorylation of multiple intracellular domains and protein kinases, and downstream effector molecules. Upon activation by ligands, intracellular β-subunit of IR autophosphorylates and activates tyrosine kinase domain of the IR, followed by activation and phosphorylation of regulatory proteins and downstream signalling effectors including phosphatidylinositol 2-kinase (PI3K). PI3K activates further downstream reaction cascades to activate protein kinase B (Akt) to ultimately promote translocation of glucose transporter-4 (Glut4)-vesicles from the cytoplasm to the cell surface and regulate glucose uptake. Chromium enhances the kinase activity of insulin receptor β and increases the activity of downstream effectors, pI3-kinase and Akt. Under insulin-resistant conditions, chromium also promotes GLUT-4 transporter translocation that is independent of activity of IR, IRS-1, PI3-kinase, or Akt; chromium mediates cholesterol efflux from the membranes via increasing fluidity of the membrane by decreasing the membrane cholesterol and upregulation of sterol regulatory element-binding protein. As a result, intracellular GLUT-4 transporters are stimulated to translocate from intracellular to the plasma membrane, leading to enhanced glucose uptake in muscle cells. Chromium attenuates the activity of PTP-1B _in vitro,_ which is a negative regulator of insulin signaling. It also alleviates ER stress that is observed to be elevated the suppression of insulin signaling. ER stress is thought to activate c-Jun N-terminal kinase (JNK), which subsequently induces serine phosphorylation of IRS and aberration of insulin signalling. Transient upregulation of AMPK by chromium also leads to increased glucose uptake. While the toxicity of metals and metalloids, like arsenic, cadmium, mercury, lead and chromium, is undisputed, the underlying molecular mechanisms are not entirely clear. General consensus holds that proteins are the prime targets; heavy metals interfere with the physiological activity of specific, particularly susceptible proteins, either by forming a complex with functional side chain groups or by displacing essential metal ions in metalloproteins. Recent studies have revealed an additional mode of metal action targeted at proteins in a non-native state; certain heavy metals and metalloids have been found to inhibit the in vitro refolding of chemically denatured proteins, to interfere with protein folding in vivo and to cause aggregation of nascent proteins in living cells. Apparently, unfolded proteins with motile backbone and side chains are considerably more prone to engage in stable, pluridentate metal complexes than native proteins with their well-defined 3D structure. By interfering with the folding process, heavy metal ions and metalloids profoundly affect protein homeostasis and cell viability. This review describes how heavy metals impede protein folding and promote protein aggregation, how cells regulate quality control systems to protect themselves from metal toxicity and how metals might contribute to protein misfolding disorders.

Pharmacodynamics

Trivalent chromium is part of glucose tolerance factor, an essential activator of insulin-mediated reactions. Chromium helps to maintain normal glucose metabolism and peripheral nerve function. Chromium increases insulin binding to cells, increases insulin receptor density and activates insulin receptor kinase leading to enhanced insulin sensitivity. In chromium deficiency, intravenous administration of chromium resulted in normalization of the glucose tolerance curve from the diabetic-like curve typical of chromium deficiency.

Mechanism of action

Copper is absorbed from the gut via high affinity copper uptake protein and likely through low affinity copper uptake protein and natural resistance-associated macrophage protein-2. It is believed that copper is reduced to the Cu1+ form prior to transport. Once inside the enterocyte, it is bound to copper transport protein ATOX1 which shuttles the ion to copper transporting ATPase-1 on the golgi membrane which take up copper into the golgi apparatus. Once copper has been secreted by enterocytes into the systemic circulation it remain largely bound by ceruloplasmin (65-90%), albumin (18%), and alpha 2-macroglobulin (12%). Copper is an essential element in the body and is incorporated into many oxidase enzymes as a cofactor. It is also a component of zinc/copper super oxide dismutase, giving it an anti-oxidant role. Copper defiency occurs in Occipital Horn Syndrome and Menke's disease both of which are associated with impaired development of connective tissue due to the lack of copper to act as a cofactor in protein-lysine-6-oxidase. Menke's disease is also associated with progressive neurological impairment leading to death in infancy. The precise mechanisms of the effects of copper deficiency are vague due to the wide range of enzymes which use the ion as a cofactor. Copper appears to reduce the viabilty and motility of spermatozoa. This reduces the likelihood of fertilization with a copper IUD, producing copper's contraceptive effect. The exact mechanism of copper's effect on sperm are unknown. The reason for the less severe reaction when the foreign body is at a distance from the retina has been proposed to be ... that near the retina & its blood vessels there is greater oxygen tension than at a distance, which causes metallic copper to oxidize to toxic copper compounds more rapidly close to or in contact with the retina than at a distance. Furthermore, the abscess formation that is characteristic of copper undergoing oxidation close to the retina & choroiod can be attributed to attraction of polymorphonuclear leukocytes from these nearby vascular tissues, which become heavily infiltrated. Liquefaction & disorganization of the vitreous body has been explained on the basis of copper catalysis of oxidation of ascorbic acid, leading to depolymerization of the hyaluronic acid of the vitreous humor. Changes in protein & hexosamine content have also been related to decrease in viscosity of the vitreous humor. Increased content of amino acids in the vitreous humor has been consistent with proteolysis of the vitreous body, but decreased concentration in the aqueous humor has suggested suppression of secretion of amino acids by the ciliary body under the influence of copper.

Pharmacodynamics

Copper is incorporated into many enzymes throughout the body as an essential part of their function. Copper ions are known to reduce fertility when released from copper-containing IUDs.

Mechanism of action

The exact mechanism of action of eugenol is unknown. However, eugenol has been shown to interrupt action potentials, which may be involved in its anti-pain activity. Research has also shown eugenol to have anti-inflammatory, neuroprotective, antipyretic, antioxidant, antifungal and analgesic properties. ... Thymocyte suspension was irradiated by gamma-rays, and the malondialdehyde (MDA) formation was measured with the thiobarbituric acid reactive species (TBARS) method. The results showed an increase in MDA in irradiated (2 Gy) thymocytes, which was inhibited in samples treated with increasing concentrations of eugenol (10-200 uM) prior to irradiation. The concentration of eugenol required to inhibit half of the MDA formation (IC(50)) in irradiated thymocytes was 100 uM. A dose-dependent increase in the generation of ROS was observed in irradiated thymocytes (0.5-200 cGy) as measured by 2,7-dichlorodihydro fluorescein diacetate (DCH-FDA), which was inhibited by eugenol administered before irradiation. Respiratory inhibition of isolated rat liver mitochondria by eugenol was dose related and uncoupled oxidative phosphorylation from electron transfer. Polymorphonuclear leukocytes (PMNL) play an important role in the modulation of inflammatory conditions in humans. PMNL cells recruited at the site of inflammation, release inflammatory mediators such as leukotrienes, proteolytic enzymes and reactive oxygen species. Among these, leukotrienes are implicated in pathophysiology of allergic and inflammatory disorders like asthma, allergic rhinitis, arthritis, inflammatory bowel disease and psoriasis. 5-lipoxygenase (5-LO) is the key enzyme in biosynthetic pathway of leukotrienes. Our earlier studies showed that spice phenolic active principles significantly inhibit 5-LO enzyme in human PMNLs. In this study we have further characterized the inhibitory mechanism of eugenol, the active principle of spice-clove on 5-LO enzyme and also its effect on leukotriene C((4)) (LTC(4)). Substrate dependent enzyme kinetics showed that the inhibitory effect of eugenol on 5-LO was of a non-competitive nature. Further, eugenol was found to significantly inhibit the formation of LTC(4) in calcium ionophore A23187 and arachidonic acid (AA) stimulated PMNL cells. These data clearly suggest that eugenol inhibits 5-LO by non-competitive mechanism and also inhibits formation of LTC(4) in human PMNL cells and thus may have beneficial role in modulating 5-LO pathway in human PMNL cells. The Ca(2+)-activated Cl(-) channel TMEM16A is involved in epithelial fluid secretion, smooth muscle contraction and neurosensory signaling. We identified a Thai herbal antidiarrheal formulation that inhibited TMEM16A Cl(-) conductance. C18-reversed-phase HPLC fractionation of the herbal formulation revealed >98% of TMEM16A inhibition activity in one out of approximately 20 distinct peaks. The purified, active compound was identified as eugenol (4-allyl-2-methoxyphenol), the major component of clove oil. Eugenol fully inhibited TMEM16A Cl(-) conductance with single-site IC(50)~150 uM. Eugenol inhibition of TMEM16A in interstitial cells of Cajal produced strong inhibition of intestinal contraction in mouse ileal segments. TMEM16A Cl(-) channel inhibition adds to the list of eugenol molecular targets and may account for some of its biological activities. For more Mechanism of Action (Complete) data for EUGENOL (21 total), please visit the HSDB record page.

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.