CARDIOPAT CAPSULES Each Soft Gelatin capsule contains Omega-3 Fish oil/Eicosapentaenoic acid/Docosahexaenoic acid/Resveratrol/Grape Seed Extract/Zinc Sulphate monohydrate/Chromium Picolinate

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

• Support for cognitive function
• Cardiovascular health
• Anti-inflammatory effects
• Eye health
• Neuroprotection

Dosage

Children: Refer to specific product guidelines or clinical recommendations for dosage.

Adults: Refer to specific product guidelines or clinical recommendations for dosage.

Mechanism of action

DHA is incorporated into cell membranes, particularly in the brain and retina, where it contributes to membrane fluidity and function. It serves as a precursor for the synthesis of neuroprotective and anti-inflammatory mediators, including resolvins and protectins, which help to modulate inflammatory responses and promote neuronal health.

Pharmacodynamics

DHA influences various physiological processes, including lipid metabolism, inflammation, and neuronal signaling. It has been shown to enhance synaptic plasticity and cognitive functions, and it may exert cardioprotective effects by improving endothelial function and reducing triglyceride levels. DHA also plays a role in the modulation of gene expression related to inflammation and lipid metabolism.

Pharmacokinetics

DHA is absorbed from the gastrointestinal tract and distributed throughout the body, particularly to the brain and retina. Its bioavailability can be influenced by dietary factors and the presence of other fatty acids. Metabolism occurs primarily through beta-oxidation and incorporation into phospholipids, with elimination taking place via the bile and urine. The half-life of DHA varies, but its effects can be prolonged due to incorporation into tissue.

Adverse effects

• Nausea
• Diarrhea
• Gastrointestinal discomfort
• Increased bleeding tendency
• Allergic reactions

Interactions

• Anticoagulants (e.g., warfarin) - may increase the risk of bleeding
• Antiplatelet drugs - may enhance the effects of these medications

Precautions

• Use caution in patients with a known allergy to fish or shellfish
• Monitor bleeding in patients taking anticoagulants or antiplatelet medications
• Consult healthcare provider before use in patients with liver disease

Pregnancy

DHA is generally considered safe during pregnancy, but high doses should be avoided unless prescribed by a healthcare provider.

Breast-feeding

DHA is beneficial during breastfeeding, as it can support infant brain development, but consult a healthcare provider for dosage.

Storage

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

Formulations

• Softgel capsules
• Liquid fish oil
• Fortified foods and beverages

Indications

• Hyperlipidemia
• Cardiovascular disease prevention
• Rheumatoid arthritis
• Inflammatory bowel disease
• Major depressive disorder

Dosage

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

Adults: Refer to BNF for specific dosing guidelines, generally available in the form of supplements or prescription formulations.

Mechanism of action

Eicosapentaenoic acid works by influencing the production of eicosanoids, which are signaling molecules derived from fatty acids. It competes with arachidonic acid in the enzymatic pathways, leading to the production of less inflammatory eicosanoids. This shift in eicosanoid production is believed to contribute to reduced inflammation and improved cardiovascular outcomes.

Pharmacodynamics

The pharmacodynamic effects of EPA include the modulation of lipid levels, reduction of triglycerides, and anti-inflammatory effects. It has been shown to decrease platelet aggregation and may improve endothelial function, thus contributing to cardiovascular protection.

Pharmacokinetics

Eicosapentaenoic acid is readily absorbed from the gastrointestinal tract following oral administration. It undergoes metabolic processes in the liver and is incorporated into cell membranes, affecting cell signaling and inflammatory responses. The half-life of EPA is variable, influenced by dosage and individual metabolism, and it is primarily excreted in the urine and feces.

Adverse effects

• Nausea
• Diarrhea
• Abdominal pain
• Flatulence
• Rash

Precautions

• Use with caution in patients with known hypersensitivity to fish or shellfish.
• Monitor patients on anticoagulant therapy due to potential for increased bleeding risk.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Eicosapentaenoic acid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Eicosapentaenoic acid is excreted in breast 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

• Capsules
• Liquid formulations

Indications

• General wellness support
• Anti-inflammatory effects
• Antioxidant activity
• Digestive aid
• Support for immune function

Dosage

Children: Paediatric dosing should be determined based on the specific extract and its intended use. Consultation with a healthcare provider is recommended for accurate dosing.

Adults: Dosage varies widely depending on the specific extract and formulation. It is essential to follow the manufacturer's instructions or consult a healthcare professional for appropriate dosing.

Mechanism of action

The mechanism of action of herbal extracts can vary significantly based on their constituents. Commonly, they exert their effects through multiple pathways including modulation of neurotransmitter systems, interference with inflammatory processes, or direct antioxidant activity. Some extracts may activate certain receptors or inhibit enzymes related to disease processes.

Pharmacodynamics

The pharmacodynamics of extracts is complex due to the presence of multiple active compounds which can have synergistic or antagonistic effects. These compounds may influence cellular signaling pathways, alter gene expression, or modulate immune response. The overall pharmacological profile is determined by the specific composition of the extract, its concentration, and the biological target it interacts with.

Pharmacokinetics

The pharmacokinetics of extracts involves absorption, distribution, metabolism, and excretion of the active compounds. Generally, herbal extracts are absorbed in the gastrointestinal tract, with bioavailability influenced by factors such as formulation, the presence of food, and individual metabolic differences. Compounds may undergo hepatic metabolism, and elimination can occur through urine or feces, depending on their chemical nature.

Pregnancy

Consult a healthcare professional before use, as the safety of the extract during pregnancy has not been established.

Breast-feeding

Consult a healthcare professional before use, as the safety of the extract during breastfeeding has not been established.

Storage

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

Indications

• Cardiovascular disease prevention
• Hyperlipidemia
• Inflammatory conditions
• Cognitive decline and dementia
• Mood disorders

Dosage

Children: Refer to specific dietary guidelines or healthcare professional recommendations for fish intake in children as there is no established pharmacological dosage.

Adults: Refer to specific dietary guidelines or healthcare professional recommendations for fish intake as there is no established pharmacological dosage.

Mechanism of action

The beneficial effects of fish, particularly fatty fish, are primarily attributed to their high content of omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These omega-3 fatty acids modulate lipid metabolism and inflammatory pathways, leading to reduced levels of triglycerides, lower blood pressure, and improved endothelial function. They also influence the synthesis of eicosanoids, which are signaling molecules that play a role in inflammation and immune responses.

Pharmacodynamics

Omega-3 fatty acids from fish have anti-inflammatory properties and can help reduce the risk of chronic diseases. They are known to improve lipid profiles by lowering triglycerides and increasing HDL cholesterol. Additionally, they may enhance insulin sensitivity and have a positive effect on mood disorders, such as depression, through their impact on brain health and neuroprotection.

Pharmacokinetics

Omega-3 fatty acids are absorbed in the intestine and transported in the bloodstream in the form of triglycerides. They are incorporated into cell membranes and can influence cell signaling pathways. The half-life of omega-3 fatty acids can vary, but they tend to have sustained effects on the body due to their incorporation into cellular structures. Fish consumption leads to a gradual accumulation of these fatty acids in tissues, which can exert health benefits over time.

Adverse effects

• Allergic reactions
• Gastrointestinal upset
• Heavy metal accumulation
• Mercury poisoning

Interactions

• May interact with anticoagulants
• Potential interactions with certain antibiotics

Precautions

• Monitor for allergic reactions
• Consider heavy metal content in certain fish
• Use caution in patients with seafood allergies

Pregnancy

Generally considered safe; however, pregnant individuals should avoid high-mercury fish such as shark, swordfish, and king mackerel.

Breast-feeding

Safe to consume, but similar advice regarding mercury exposure applies.

Storage

Store in a cool, dry place. Refrigerate fresh fish and consume within a few days to maintain freshness.

Formulations

• Fresh fish
• Frozen fish
• Canned fish
• Fish oil supplements

Dosage

Children: Refer to specific medication guidelines for dosing adjustments due to grapefruit juice interactions.

Adults: Refer to specific medication guidelines for dosing adjustments due to grapefruit juice interactions.

Mechanism of action

Grapefruit juice contains compounds called furanocoumarins, which inhibit cytochrome P450 3A4 (CYP3A4) enzymes in the liver and intestines. This inhibition can lead to increased plasma concentrations of drugs that are metabolized by CYP3A4, resulting in enhanced pharmacological effects and potential toxicity.

Pharmacodynamics

The pharmacodynamic effects of grape juice are closely related to its antioxidant properties, primarily due to resveratrol and flavonoids. These compounds help in reducing oxidative stress and inflammation. However, the primary clinical concern is the modulation of drug metabolism, particularly affecting drugs with a narrow therapeutic index.

Pharmacokinetics

Grapefruit juice can significantly alter the pharmacokinetics of certain medications by affecting their absorption and metabolism. The inhibition of CYP3A4 can lead to increased bioavailability of drugs that are substrates of this enzyme, resulting in higher plasma concentrations. The effects of grapefruit juice can persist for up to 24 hours post-consumption, complicating timing and dosing of affected medications.

Interactions

• grapefruit juice + abemaciclib: Severe (increases exposure)
• grapefruit juice + aliskiren: Severe (decreases exposure)
• grapefruit juice + amiodarone: Severe (increases exposure)
• grapefruit juice + dronedarone: Severe (increases exposure)
• grapefruit juice + rupatadine: Severe (increases exposure)
• grapefruit juice + piperaquine: Severe (increases concentration)
• grapefruit juice + antipsychotics, second generation: Severe (increases exposure)
• grapefruit juice + lurasidone: Severe (increases exposure)
• grapefruit juice + quetiapine: Severe (increases exposure)
• grapefruit juice + cariprazine: Severe (increases exposure)

Pregnancy

Consult healthcare provider for guidance on use during pregnancy.

Breast-feeding

Consult healthcare provider for guidance on use during breastfeeding.

Storage

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

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

• Herpes simplex virus infections
• Potential cardiovascular benefits
• Anti-inflammatory conditions
• Cancer prevention

Dosage

Children: For paediatric dosing and recommendations, please refer to the BNF for Children.

Adults: For specific dosing recommendations, please refer to the BNF as they can vary based on indications and formulations.

Mechanism of action

Resveratrol suppresses NF-kappaB activation in HSV infected cells, which is essential for the replication of the virus. It acts as a mixed agonist/antagonist for estrogen receptors alpha and beta, binding both with lower affinity than estradiol. It decreases the expression of cell cycle regulatory proteins and anti-apoptotic proteins while increasing p21WAF1/CIP1. Additionally, resveratrol interferes with an ERalpha-associated PI3K pathway, contributing to its anti-proliferative effects.

Pharmacodynamics

As a phytoalexin, resveratrol inhibits the replication of herpes simplex virus types 1 and 2 in a dose-dependent manner. Its antioxidant properties help in scavenging free radicals, while its anti-inflammatory effects contribute to its therapeutic potential. Resveratrol's modulation of estrogen receptors and its ability to affect cell cycle regulation highlight its complex pharmacological profile, with implications for cancer prevention and cardiovascular health.

Pharmacokinetics

Resveratrol is absorbed in the gastrointestinal tract, but its bioavailability is relatively low due to extensive first-pass metabolism. It is metabolized primarily in the liver, with metabolites being excreted via urine. The pharmacokinetic profile can be influenced by factors such as food intake and the presence of other substances in the gastrointestinal tract.

Adverse effects

• Nausea
• Diarrhea
• Abdominal pain
• Headache
• Rash

Interactions

• May interact with anticoagulants and antiplatelet drugs, increasing the risk of bleeding
• Can interfere with the metabolism of certain medications due to its effects on cytochrome P450 enzymes

Precautions

• Use caution in patients with bleeding disorders
• Monitor patients on antidiabetic medications due to potential blood sugar-lowering effects

Pregnancy

Resveratrol is not recommended during pregnancy due to insufficient safety data.

Breast-feeding

Limited data is available; consult a healthcare provider before use.

Storage

Store in a cool, dry place, protected from light.

Formulations

• Capsules
• Tablets
• Powder

Indications

• Dietary supplement for heart health
• Source of essential fatty acids
• Antioxidant support
• Promotion of digestive health
• Management of cholesterol levels

Dosage

Children: Refer to specific seed type and formulation for dosing information, as it can vary widely based on type and intended use.

Adults: Refer to specific seed type and formulation for dosing information, as it can vary widely based on type and intended use.

Mechanism of action

The bioactive compounds in seeds, such as polyunsaturated fatty acids, phytosterols, and antioxidants, exert various effects in the body. For example, omega-3 fatty acids found in flaxseeds can influence lipid metabolism and reduce inflammation by modulating the production of eicosanoids. Antioxidants such as tocopherols and phenolic compounds can scavenge free radicals, reducing oxidative stress.

Pharmacodynamics

Seeds have shown potential benefits, including the modulation of lipid profiles, reduction in inflammatory markers, and improvement in glycemic control. The consumption of seeds may lead to decreased low-density lipoprotein (LDL) cholesterol levels and increased high-density lipoprotein (HDL) cholesterol levels, contributing to cardiovascular health. The dietary fiber in seeds can also aid in digestive health and promote satiety.

Pharmacokinetics

The pharmacokinetics of seeds can vary widely depending on the type of seed and the specific compounds being analyzed. Generally, the bioactive components are digested and absorbed in the gastrointestinal tract, with fatty acids being incorporated into chylomicrons and transported via the lymphatic system. Antioxidants are absorbed in the small intestine and may have systemic effects, while fiber can influence gastrointestinal motility and fermentation in the colon.

Pregnancy

Consult a healthcare provider before use, as safety during pregnancy is not well established.

Breast-feeding

Consult a healthcare provider before use, as safety during breastfeeding is not well established.

Storage

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

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

Resveratrol suppresses NF-kappaB (NF-kappaB) activation in HSV infected cells. Reports have indicated that HSV activates NF-kappaB during productive infection and this may be an essential aspect of its replication scheme [PMID: 9705914]. ... Resveratrol appears to act as a mixed agonist/antagonist for estrogen receptors alpha and beta. It has been found to bind estrogen receptor beta and estrogen receptor alpha with comparable affinity but with 7000-fold lower affinity than estradiol. Resveratrol differs from other phytoestrogens, which bind estrogen receptor beta with higher affinity than they bind estrogen receptor alpha. Resveratrol also shows estradiol antagonistic behavior for estrogen receptor alpha with some estrogen receptors. It does not show estradiol antagonistic activity with estrogen receptor beta ... The anti-proliferative effects of resveratrol were shown to be modulated by cell cycle regulatory proteins ... Resveratrol decreased the expression of cyclins D1 and D2, Cdk 2, 4 and 6, and proliferating cell nuclear antigen (PCNA) whereas p21WAF1/CIP1 was increased. Furthermore there was inhibited expression of anti-apoptotic proteins, such as survivin, and markers of tumor promotion, cyclooxygenase (COX)-2, and ornithine decarboxylase (ODC) were observed ... ... In addition to its antioxidant scavenging of free radicals and modulating estrogen receptor (ER) activity ... resveratrol can interfere with an ERalpha-associated PI3K pathway, following a process that could be independent of the nuclear functions of the ERalpha ... and acts as an agonist for the cAMP/kinase-A system ... It also promotes the accumulation of growth inhibitory/pro-apoptotic ceramide ... and induction of quinone reductase (QR, a phase II detoxification enzyme) ... and induces caspase-independent apoptosis through Bcl-2 downregulation ... It has been shown to suppress Src tyrosine kinase activity ... nitric oxide generation, and the NFkappaB pathway ...

Pharmacodynamics

Resveratrol, a phytoalexin, has been found to inhibit herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) replication in a dose-dependent, reversible manner, although this is only one of its many pharmaceutical properties. In some countries where there is higher consumption of red wine, there appears to be a lower incidence of heart disease. Other benefits of resveratrol include its anti-inflammatory and antioxidant effects. In preclinical studies, Resveratrol has been found to have potential anticancer properties.