NISVEN (FORMERY NEURO NISSI) CAPSULES

Indications

• Hypertension
• Benign prostatic hyperplasia
• Urinary retention related to prostate enlargement

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations based on individual clinical scenarios.

Mechanism of action

Alpha acts by selectively blocking alpha-1 adrenergic receptors, which are responsible for mediating vasoconstriction in blood vessels. By inhibiting these receptors, alpha promotes vasodilation, leading to a decrease in peripheral vascular resistance and subsequently lowering blood pressure. Additionally, this action can help alleviate urinary symptoms associated with an enlarged prostate.

Pharmacodynamics

The pharmacodynamics of alpha involve its competitive antagonism at alpha-1 adrenergic receptors, resulting in decreased vasoconstriction and increased blood flow. This mechanism is beneficial in conditions characterized by high blood pressure and urinary retention due to prostatic enlargement. The onset of action typically occurs within hours, with peak effects observed within a few days of consistent dosing.

Pharmacokinetics

Alpha is absorbed well from the gastrointestinal tract, with peak plasma concentrations achieved within 1-3 hours post-administration. The drug undergoes hepatic metabolism, primarily via cytochrome P450 enzymes, resulting in active and inactive metabolites. The elimination half-life varies, but it generally is around 6-12 hours, allowing for once-daily dosing in many cases. Renal excretion is a significant route for its metabolites, necessitating caution in patients with renal impairment.

Interactions

• maois, irreversible + alpha blockers: Severe (increases effects)
• ribociclib + alpha blockers: Severe (increases exposure)
• cobicistat + alpha blockers: Moderate (increases exposure)
• idelalisib + alpha blockers: Moderate (increases exposure)
• dronedarone + alpha blockers: Unknown (increases exposure)
• antifungals, azoles + alpha blockers: Unknown (increases exposure)
• crizotinib + alpha blockers: Unknown (increases exposure)
• imatinib + alpha blockers: Unknown (increases exposure)
• letermovir + alpha blockers: Unknown (increases exposure)
• clarithromycin + alpha blockers: Unknown (increases exposure)

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

• 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

• Diabetic neuropathy
• Metabolic syndrome
• Weight management adjunct
• Antioxidant support
• General health and wellness

Dosage

Children: Refer to established guidelines for dosing.

Adults: Refer to established guidelines for dosing.

Mechanism of action

Alpha-lipoic acid functions as a coenzyme for mitochondrial oxidative decarboxylation of alpha-keto acids. It plays a critical role in energy metabolism by facilitating the conversion of carbohydrates into energy. Additionally, it possesses antioxidant properties, regenerating other antioxidants such as vitamin C and vitamin E. Its action includes chelation of metal ions and scavenge of free radicals, thereby reducing oxidative stress.

Pharmacodynamics

Liponoic exhibits both hydrophilic and lipophilic properties, allowing it to act in various cellular environments. Its antioxidant capability reduces oxidative damage, which is implicated in numerous chronic diseases. Furthermore, it enhances insulin sensitivity and may improve glucose uptake in peripheral tissues, making it beneficial in managing metabolic syndrome and diabetes.

Pharmacokinetics

After oral administration, alpha-lipoic acid is rapidly absorbed and reaches peak plasma concentrations within 30 to 60 minutes. It is distributed widely throughout the body, including the brain, where it exerts neuroprotective effects. The elimination half-life is approximately 30 minutes to 2 hours, and it is metabolized in the liver. Renal excretion of its metabolites occurs, indicating that dosage adjustments may be necessary in patients with renal impairment.

Adverse effects

• Nausea
• Vomiting
• Rash
• Headache
• Dizziness

Interactions

• May enhance the effects of insulin and other antidiabetic medications
• Potential interaction with chemotherapy agents due to antioxidant properties

Precautions

• Use with caution in patients with diabetes, as it may lower blood sugar levels
• Monitor for potential allergic reactions

Pregnancy

The safety of liponoic during pregnancy has not been established. Use only if clearly needed.

Breast-feeding

There is insufficient data on the excretion of liponoic in human milk. Caution is advised.

Storage

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

Formulations

• Oral capsules
• Tablets
• Injectable solutions

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

• Dietary supplementation
• Potential treatment for mood disorders
• Support for liver health
• Antioxidant support

Dosage

Children: Dosage for pediatric populations is not well established and should be

Adults: Dosage is variable and should be determined based on individual needs and clinical response. Refer to specific guidelines or product labeling for detailed dosing information.

Mechanism of action

Monomethionine functions by serving as a precursor to S-adenosylmethionine (SAMe), which is crucial for the methylation of DNA, proteins, and lipids. Through this methylation process, monomethionine can influence various metabolic pathways, including those involved in the synthesis of neurotransmitters and the detoxification of homocysteine. Additionally, it contributes to the reduction of oxidative stress by promoting the synthesis of glutathione, a key antioxidant in the body.

Pharmacodynamics

The pharmacodynamic effects of monomethionine are primarily mediated through its conversion to SAMe. This conversion leads to enhanced methylation reactions, impacting various physiological functions such as mood regulation, liver function, and the metabolism of lipids and neurotransmitters. Monomethionine may also exert neuroprotective effects due to its role in maintaining glutathione levels, thus protecting against oxidative damage in neuronal tissues.

Pharmacokinetics

Monomethionine is absorbed in the gastrointestinal tract after oral administration, although specific absorption rates have not been extensively studied. It is metabolized in the liver, contributing to the synthesis of SAMe. The elimination half-life and specific metabolic pathways of monomethionine are not well-characterized in the literature. Its effects may last longer due to the involvement of SAMe in several biochemical processes.

Adverse effects

• Gastrointestinal upset
• Nausea
• Diarrhea
• Allergic reactions

Interactions

• May interact with medications that affect liver enzymes
• Potential interactions with other amino acids or supplements

Precautions

• Use with caution in patients with liver disease
• Monitor for allergic reactions in sensitive individuals

Pregnancy

Safety during pregnancy has not been established, consult a healthcare provider.

Breast-feeding

Limited data available, consult a healthcare provider before use.

Storage

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

Formulations

• Capsules
• Powder for oral solution

Indications

• Polycystic ovary syndrome (PCOS)
• Insulin resistance
• Metabolic syndrome
• Mood disorders
• Neurodegenerative diseases

Dosage

Children: Dosage for paediatric patients is not established; refer to BNF for Children for specific guidance.

Adults: The typical adult dose of myo-inositol is 2 to 4 grams daily, usually divided into two doses.

Mechanism of action

Myo-inositol functions primarily as a precursor in the biosynthesis of inositol phosphates, which are critical for cell signaling. It contributes to the synthesis of 1D-myo-inositol hexakisphosphate and other inositol phosphates, facilitating the regulation of cellular functions such as insulin signaling and lipid metabolism. Myo-inositol also plays a role in the modulation of neurotransmitter signaling, particularly in the central nervous system.

Pharmacodynamics

Myo-inositol has been shown to influence insulin sensitivity and may help in restoring ovarian function in women with PCOS. It acts as a second messenger in various hormonal signaling pathways, particularly those involving insulin and follicle-stimulating hormone (FSH). The drug's action can lead to improved ovarian response and metabolic profiles in affected individuals.

Pharmacokinetics

Myo-inositol is well-absorbed when administered orally, with a bioavailability that may vary based on the formulation. It is distributed throughout the body and has a half-life that supports multiple dosing regimens. Myo-inositol is eliminated primarily through renal excretion, and its metabolism is closely linked to the pathways of inositol phosphate metabolism.

Pregnancy

The safety of myoinositol during pregnancy has not been established. Consultation with a healthcare professional is advised.

Breast-feeding

Myoinositol is generally considered safe during breastfeeding, but it is recommended to consult a healthcare provider for personalized advice.

Storage

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

Formulations

• Powder
• Tablet
• Capsule

Indications

• Hyperlipidemia
• Dyslipidemia
• Atherosclerosis
• Peripheral vascular disease

Dosage

Children: Refer to established clinical guidelines or pharmacology references for pediatric dosing, as specific pediatric doses may not be established.

Adults: Refer to established clinical guidelines or pharmacology references for specific dosing information, as dosing can vary based on the specific formulation and indication.

Mechanism of action

Polynicotinate exerts its effects primarily through the activation of nicotinic acid receptors, which leads to increased lipolysis in adipose tissue, resulting in the mobilization of free fatty acids. It also enhances the activity of lipoprotein lipase, aiding in the clearance of triglycerides from the bloodstream. This action contributes to a reduction in total cholesterol and low-density lipoprotein (LDL) levels while potentially increasing high-density lipoprotein (HDL) levels.

Pharmacodynamics

Polynicotinate influences lipid metabolism by modulating the synthesis and breakdown of lipoproteins. Its vasodilatory properties can lead to improved blood flow, which may contribute to its therapeutic effects in conditions related to poor circulation. Additionally, its modulation of lipid levels is beneficial in reducing the risk of cardiovascular diseases.

Pharmacokinetics

Polynicotinate is absorbed from the gastrointestinal tract, with the rate of absorption influenced by the presence of food. It undergoes extensive first-pass metabolism in the liver. The peak plasma concentration is typically reached within a few hours of administration. The elimination half-life is variable but generally ranges around 1 to 2 hours. Excretion primarily occurs via the kidneys, with metabolites being eliminated in urine.

Adverse effects

• Gastrointestinal disturbances
• Headache
• Dizziness
• Flushing
• Nausea

Precautions

• Use with caution in patients with liver or kidney impairment
• Monitor for allergic reactions

Pregnancy

There is limited data on the safety of polynicotinate during pregnancy. It should be used only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Limited information is available on the excretion of polynicotinate in human milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Tablets
• Capsules
• Oral solution

Indications

• Cancer chemoprevention
• Selenium deficiency

Dosage

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

Adults: Refer to the BNF for appropriate dosing information.

Mechanism of action

Selenomethionine exerts its anticancer effects primarily through metabolism into reactive metabolites that interact with cellular pathways. Specifically, when combined with methioninase, its anticancer activity is enhanced, leading to increased levels of superoxide and apoptosis in cancer cells expressing wild-type p53. This process involves translocation of p53 to mitochondria, activation of caspase pathways, and modulation of apoptosis-related proteins.

Pharmacodynamics

Selenomethionine has shown a capacity to induce apoptosis in certain cancer cell lines, particularly those with functional p53. The compound appears to increase superoxide production, mitochondrial dysfunction, and activation of apoptotic markers. While it has been investigated for its chemopreventive properties, its weaker efficacy compared to other selenium compounds limits its role as a primary agent in cancer therapy.

Pharmacokinetics

Upon administration, selenomethionine is absorbed and distributed throughout the body, where it participates in selenium metabolism and is incorporated into proteins in place of methionine. The metabolism involves conversion to various selenoamino acids and metabolites, which are then excreted primarily via renal pathways. The pharmacokinetics can be influenced by dietary selenium intake and individual metabolic variations.

Pregnancy

Selenomethionine should only be used in pregnancy if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution should be exercised when administering selenomethionine to nursing mothers.

Storage

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

Formulations

• Selenomethionine capsules
• Selenomethionine tablets

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

Selenomethionine (SeMet) is the chemical form or major component of selenium used for cancer chemoprevention in several clinical trials. However, evidence from experimental studies indicates that SeMet has weaker anticancer effects than most other forms of selenium. ... The anticancer activity of SeMet can be enhanced by methioninase (METase), indicating that SeMet metabolites are responsible for its anticancer activity. ... Wild-type p53-expressing LNCaP human prostate cancer cells were more sensitive to cotreatment with SeMet and METase than p53-null PC3 human prostate cancer cells. SeMet and METase cotreatment significantly increased levels of superoxide and apoptosis in LNCaP cells. Cotreatment with SeMet and METase resulted in increased levels of phosphorylated p53 (Ser15), total p53, Bax, and p21(Waf1) proteins. LNCaP cells treated with SeMet and METase also showed p53 translocation to mitochondria, decreased mitochondrial membrane potential, cytochrome c release into the cytosol, and activation of caspase-9. The effects of SeMet and METase were suppressed by pretreatment with a synthetic superoxide dismutase mimic or by knockdown of p53 via RNA interference. Reexpression of wild-type p53 in PC3 cells resulted in increases in superoxide production, apoptosis, and caspase-9 activity and a decrease in mitochondrial membrane potential following cotreatment with SeMet and METase. /The/ study shows that apoptosis induced by SeMet plus METase is superoxide mediated and p53 dependent via mitochondrial pathway(s). These results suggest that superoxide and p53 may play a role in cancer chemoprevention by selenium. ... The toxicity of Se is thought to arise from its ability to substitute for sulfur during the assembly of proteins. .../More/ recent studies also indicate that some forms of selenium are capable of generating oxidative stress in an in vitro test system that includes glutathione. L-Selenomethionine, the predominant form of selenium in the eggs of oviparous vertebrates, does not generate oxidative radicals in this system, but lesions consistent with oxidative stress have been identified in fish and birds with high concentrations of Se. /This study reports/ on the ability of rainbow trout embryos to transform L-selenomethionine to a form capable of producing a superoxide radical. Oxidative stress appears to be generated by methioninase enzyme activity in the embryos that liberates methylselenol from l-selenomethionine. Methylselenol redox cycles in the presence of glutathione producing superoxide and likely accounts for oxidative lesions present in fish and birds environmentally exposed to excessive loads of selenomethionine. /L-Selenomethionine/ Primary cultures of porcine aortic endothelial cells were used to test the potential protective effect ... against several types of oxidative stress. The stressors included exposure to hyperoxia, treatment with paraquat, and incubation in the presence of the hypoxanthine/xanthine oxidase system. This protective effect ... of selenomethionine ... is known to increase glutathione peroxidase activity. ... High-selenium containing yeast is being evaluated in clinical trials against colon polyp recurrence. However, the molecular targets for the anticancer effects of selenium remain unclear. Previous studies by our group demonstrated that selenomethionine-induced growth arrest appears to be mediated by activation of ERK and subsequent phosphorylation of RSK and histone H3. These results suggest that selenomethionine can alter gene expression. In the present study, we have used cDNA microarrays to determine whether gene expression differences exist in HCT116 colon cancer cells treated with selenomethionine. These experiments reveal statistically significant expression changes for 50 genes. Genes we found to increase with selenomethionine treatment include KLK6, ATOX1, SGK, GJB2, DAP-1, PLAU, VIM, DPYSL2, STC2 and PXN. Conversely, genes downregulated by selenomethionine include PRKACB,