RECARTIX FORTE TABLETS

Indications

• Symptomatic relief of mild to moderate osteoarthritis of the knee

Dosage

Children: Refer to the BNF for Children for

Adults: 200–400 mg daily, maximum 6.5 mg/kg per day, or 1250 mg once daily, or 1500 mg once daily dissolved in at least 250 mL of water; review treatment if no benefit after 2–3 months.

Mechanism of action

The mechanism of action of glucosamine in joint health is not entirely clear, but it is believed to involve several pathways. Glucosamine is a precursor for glycosaminoglycans, which are essential for cartilage integrity. It may also reduce inflammation by inhibiting interferon gamma and Nuclear factor kappa B subunit 65 (NF-κB p65), which could improve symptoms of arthritis and joint pain. Upon uptake by living cells, glucosamine reacts with ATP to form glucosamine-6-phosphate, further contributing to glycosaminoglycan synthesis.

Pharmacodynamics

Glucosamine is theorized to provide essential building blocks for the synthesis of glycosaminoglycans, potentially slowing the progression of osteoarthritis and alleviating joint pain. Although some studies have indicated modest improvements in joint pain and function among users, the overall evidence remains inconclusive. Glycosaminoglycans are critical for maintaining cartilage elasticity, strength, and flexibility, which are vital for joint health.

Pharmacokinetics

After oral administration, glucosamine is absorbed in the gastrointestinal tract and transported into the bloodstream, where it is metabolized into various forms, including glucosamine-6-phosphate. The exact pharmacokinetics, such as absorption rate and half-life, remain largely undefined, and much of the data is derived from animal studies. Further research is required to clarify its pharmacokinetic profiles in humans.

Adverse effects

• Constipation
• Diarrhoea
• Fatigue
• Gastrointestinal discomfort
• Headache
• Nausea
• Flushing
• Skin reactions

Interactions

• Glucosamine + warfarin: Severe (increases anticoagulant effect)
• Glucosamine + coumarins: Severe (increases anticoagulant effect)
• Glucosamine + acenocoumarol: Unknown (decreases anticoagulant effect)
• Glucosamine + coumarins: Unknown (decreases anticoagulant effect)

Precautions

• Asthma
• Impaired glucose tolerance
• Predisposition to cardiovascular disease

Pregnancy

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

Breast-feeding

Safety during breastfeeding has not been established; consult with a healthcare provider.

Storage

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

Formulations

• Alateris®
• Dolenio®
• Glusartel®

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

• Vitamin C deficiency
• Scurvy
• As an adjunct in the treatment of iron deficiency anemia
• Support for immune function
• Antioxidant therapy

Dosage

Adults: Refer to the BNF for specific

Mechanism of action

Ascorbic acid functions primarily as a reducing agent, donating electrons to various biochemical reactions. It is involved in the hydroxylation of proline and lysine residues in collagen synthesis, which is essential for maintaining connective tissue integrity. As an antioxidant, it also helps to regenerate other antioxidants, such as vitamin E, thereby protecting cells from oxidative damage. Furthermore, it enhances the absorption of non-heme iron from the gastrointestinal tract, promoting better iron utilization in the body.

Pharmacodynamics

Ascorbic acid is crucial for metabolic processes, including the synthesis of collagen and certain neurotransmitters. Its antioxidant properties help mitigate oxidative stress, which can lead to cellular damage and various diseases. The vitamin's role in iron absorption is particularly significant in preventing iron-deficiency anemia. The therapeutic effects of ascorbic acid are dose-dependent, with higher doses often resulting in more pronounced antioxidant effects.

Pharmacokinetics

Ascorbic acid is readily absorbed in the small intestine, with peak plasma concentrations occurring within 2 to 4 hours after oral administration. The bioavailability of ascorbic acid decreases at higher doses due to saturation of the transport mechanisms. It is distributed throughout bodily fluids and tissues, with highest concentrations found in the adrenal glands, pituitary gland, and leukocytes. The elimination half-life varies, typically ranging from 8 to 40 days, depending on the dose and the individual's renal function. Ascorbic acid is excreted primarily through the kidneys, with renal clearance being influenced by plasma concentration and renal health.

Interactions

• ascorbic acid + iron chelators: Unknown (increases risk of cardiovascular adverse effects)
• ascorbic acid + deferiprone: Unknown (increases risk of cardiovascular adverse effects)
• ascorbic acid + desferrioxamine: Unknown (increases risk of cardiovascular adverse effects)

Pregnancy

Ascorbic acid is generally considered safe during pregnancy but should be used with caution and only when necessary.

Breast-feeding

Ascorbic acid is excreted in breast milk and is generally considered safe during breastfeeding.

Storage

Store at room temperature, away from light and moisture.

Indications

• Osteoarthritis
• Joint pain
• Cartilage repair
• Joint health maintenance

Dosage

Children: Refer to healthcare professionals for guidance on dosing in children, as specific pediatric dosing information is not well established.

Adults: Refer to specific product labeling and consult healthcare professionals for guidance on dosing, as dosages can vary based on formulations and clinical guidelines.

Mechanism of action

Chondroitin works primarily by providing the building blocks necessary for the synthesis of glycosaminoglycans, which are critical components of cartilage. It is thought to inhibit the enzymes that break down cartilage, thereby promoting cartilage repair while also exhibiting anti-inflammatory properties. Additionally, chondroitin may enhance the retention of water in the cartilage, improving its elasticity and resilience.

Pharmacodynamics

Chondroitin has been shown to modulate inflammatory responses within the joints and may help to improve joint mobility and reduce pain associated with osteoarthritis. Its effects on cartilage metabolism are believed to contribute to its therapeutic benefits, although the clinical efficacy may vary among individuals. The anti-inflammatory properties may also contribute to a reduction in joint swelling and discomfort.

Pharmacokinetics

Chondroitin is poorly absorbed from the gastrointestinal tract, with bioavailability ranging from 12% to 36%. It is distributed in the extracellular matrix of cartilage and other connective tissues. Metabolism of chondroitin is not well understood, but it is believed to be metabolized in the liver. The elimination half-life in humans is not well defined, and it is primarily excreted via urine as metabolites. The effects of food on its absorption are still under investigation.

Adverse effects

• Nausea
• Diarrhea
• Constipation
• Abdominal pain
• Headache
• Skin reactions

Interactions

• Anticoagulants (e.g., warfarin) - may increase the risk of bleeding
• NSAIDs - may affect the efficacy of these medications

Precautions

• Use with caution in patients with a history of bleeding disorders
• Caution is advised in patients undergoing surgery due to potential bleeding risk
• Patients with shellfish allergies should consult a physician as some chondroitin supplements are derived from marine sources

Pregnancy

There is insufficient reliable information regarding the safety of chondroitin during pregnancy. It is advisable to avoid use unless prescribed by a healthcare professional.

Breast-feeding

It is not known if chondroitin is excreted in human milk. Caution is advised for nursing mothers considering its use.

Storage

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

Formulations

• Capsule
• Tablet
• Powder
• Liquid

Indications

• Manganese deficiency
• Bone health and development
• Antioxidant support
• Enzyme cofactor in metabolic processes

Dosage

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

Adults: Refer to specific clinical guidelines or the BNF for appropriate dosing recommendations.

Mechanism of action

Manganese serves as a cofactor for several enzymes, including manganese superoxide dismutase (MnSOD), which protects cells from oxidative stress by catalyzing the dismutation of superoxide radicals into oxygen and hydrogen peroxide. It also participates in the activation of enzymes involved in carbohydrate, fat, and protein metabolism.

Pharmacodynamics

Manganese plays a role in various biochemical pathways, particularly in the metabolism of amino acids, cholesterol, glucose, and carbohydrates. It is crucial for bone formation and the maintenance of cartilage. Manganese also aids in the synthesis of glycosyltransferases, which are important for the formation of glycoproteins and proteoglycans.

Pharmacokinetics

Manganese is absorbed primarily in the small intestine, with absorption efficiency influenced by dietary factors and the presence of competing minerals. It is transported in the bloodstream bound to proteins such as alpha-2-macroglobulin and transferrin. Manganese is stored in the liver, pancreas, and bones, and is excreted primarily through bile and to a lesser extent in urine. Its half-life in the human body is not well defined due to its trace nature and variable absorption.

Pregnancy

Manganese is classified as a dietary mineral that is essential for human health, but excessive intake should be avoided during pregnancy as it may affect fetal development.

Breast-feeding

Manganese is present in breast milk, and normal dietary intake is considered safe during breastfeeding. However, excessive supplementation should be avoided.

Storage

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

Dosage

Children: As with adult dosing, methane is not used therapeutically in paediatrics, and thus no specific paediatric doses are provided. Refer to clinical guidelines for any relevant applications.

Adults: Methane is not typically administered as a drug in therapeutic contexts. Therefore, specific dosage recommendations for adults do not apply. Consult relevant guidelines or literature for any potential applications.

Mechanism of action

Methane serves as a carbon source in various metabolic processes, particularly in methanogenic archaea and certain bacteria. It participates in biochemical pathways such as methylphosphonate degradation and the oxidation of methane to methanol, facilitating energy production and carbon cycling in anaerobic environments.

Pharmacodynamics

In the context of environmental and biological systems, methane acts as a substrate for methanogenic organisms. These organisms utilize methane to produce energy through anaerobic respiration. The dynamics of methane in the environment are influenced by factors such as temperature, pH, and the presence of other substrates or microorganisms.

Pharmacokinetics

Methane is generally not absorbed in a conventional pharmacokinetic sense as it is primarily a gas. Its distribution and metabolism occur in the environment rather than within a biological system. Methane's clearance from the atmosphere occurs through various processes, including oxidation to carbon dioxide and assimilation by methanotrophic bacteria.

Pregnancy

Methane is not recommended during pregnancy due to potential risks associated with exposure to flammable gases.

Breast-feeding

There is limited information regarding the effects of methane during breastfeeding, exercise caution.

Storage

Store in a cool, dry place away from sources of ignition and incompatible materials.

Indications

• Allergic reactions
• Asthma
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Multiple sclerosis exacerbations
• Inflammatory bowel disease
• Dermatologic conditions
• Certain types of cancer

Dosage

Children: For paediatric patients, the dosage is determined based on the specific condition and the child's weight or age. Refer to the BNF for Children for detailed dosing recommendations.

Adults: The usual oral dosage for adults varies by condition but typically ranges from 4 mg to 48 mg daily, depending on the severity of the condition being treated. For specific dosing, consult the BNF.

Mechanism of action

Methylprednisolone exerts its effects by binding to glucocorticoid receptors, which leads to the modulation of gene expression. This results in the inhibition of pro-inflammatory cytokines and chemokines, ultimately reducing inflammation and immune system activity. The drug's action also includes the stabilization of cell membranes and the inhibition of leukocyte infiltration at the site of inflammation.

Pharmacodynamics

Methylprednisolone has a high anti-inflammatory potency and is approximately 5 times more potent than hydrocortisone. It affects various pathways involved in inflammation and immune response, including the suppression of macrophage activity, reduction of capillary permeability, and inhibition of the release of inflammatory mediators such as prostaglandins and leukotrienes.

Pharmacokinetics

Methylprednisolone is well-absorbed after oral administration, with peak serum concentrations occurring within 1-2 hours. It has a bioavailability of approximately 70% when given orally. The drug is extensively metabolized in the liver, primarily by the cytochrome P450 system, and its metabolites are excreted in the urine. The elimination half-life ranges from 18 to 36 hours, depending on the route of administration and individual patient factors.

Interactions

• methylphenidate + apraclonidine: Severe (decreases effects)
• methylthioninium chloride + bupropion: Severe (increases risk of severe hypertension)
• methylphenidate + linezolid: Severe (increases risk of elevated blood pressure)
• rasagiline + methylphenidate: Severe (increases risk of a hypertensive crisis)
• monoamine oxidase inhibitors + methylphenidate: Severe (increases risk of a hypertensive crisis)
• dronedarone + methylprednisolone: Moderate (increases exposure)
• miconazole + methylprednisolone: Moderate (increases concentration)
• antifungals, azoles + methylprednisolone: Moderate (increases exposure)
• crizotinib + methylprednisolone: Moderate (increases exposure)

Pregnancy

Use with caution. Methylphenidate may be used if the benefits outweigh the risks.

Breast-feeding

Use with caution. Methylphenidate is excreted in breast milk; consider the benefits and risks.

Storage

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

Indications

• Type 2 diabetes mellitus
• Non-insulin dependent diabetes
• Secondary failure to monotherapy with metformin

Dosage

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

Adults: Refer to the BNF for specific dosing recommendations based on the individual drug within the sulphonylurea class.

Mechanism of action

Sulphonylureas work by binding to the ATP-sensitive potassium channels on the pancreatic beta cells, leading to the closure of these channels. This results in depolarization of the beta cell membrane and subsequent influx of calcium ions, which stimulates insulin secretion. Additionally, they may enhance the sensitivity of peripheral tissues to insulin, promoting glucose uptake.

Pharmacodynamics

The pharmacodynamic effects of sulphonylureas include a reduction in blood glucose levels through increased insulin secretion from the pancreas and improved insulin sensitivity in peripheral tissues. The onset of action typically occurs within hours, with the peak effects lasting several hours. The overall glucose-lowering effect is dose-dependent.

Pharmacokinetics

Sulphonylureas are usually well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1 to 4 hours after oral administration. They are extensively bound to plasma proteins, primarily albumin. The metabolism occurs primarily in the liver, involving cytochrome P450 enzymes, and they are excreted mainly via the urine. The half-life varies between different sulphonylureas but is generally around 3 to 5 hours.

Pregnancy

Refer to specific guidelines; data on safety in pregnancy is limited.

Breast-feeding

Consult relevant guidelines; limited data on excretion in breast milk.

Storage

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

Indications

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

Dosage

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

Adults: Refer to BNF for specific dosage guidelines.

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Pregnancy

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

Breast-feeding

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

Storage

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

Mechanism of action

The mechanism of action of glucosamine in joint health is unclear, however there are several possible mechanisms that contribute to its therapeutic effects. Because glucosamine is a precursor for glycosaminoglycans, and glycosaminoglycans are a major component of joint cartilage, glucosamine supplements may help to rebuild cartilage and treat the symptoms of arthritis. Some in vitro studies show evidence that glucosamine reduces inflammation via inhibition of interferon gamma and Nuclear factor kappa B subunit 65 (NF-κB p65), improving the symptoms of arthritis and joint pain. Clinical relevance is unknown at this time. When taken up by living cells, glucosamine reacts with ATP to form glucosamine-6-phosphate, the natural precursor of glycosaminoglycans (GAGs) that contain N-acetylglucosamine (keratan sulfate and Hyaluronan) and those that have N-acetylgalactosamine (heparan sulfate and chondroitin sulfate). These GAGs are polysaccharides composed of hexosamines and monosaccharides (e.g., galactose and glucuronic acid) arranged as a linear chain of repeating disaccharide units (such as the glucuronic acid and N-acetylgalactosamine-6-sulfate of chondroitin sulfate). With the exception of hyaluronan, GAGs do not exist alone in nature but are attached to specific "core" proteins, and the composite structures are called proteoglycans (protein-glycosaminoglycans). Both hyaluronan and many different kinds of proteoglycans (such as aggrecan, versican, and syndecan) are abundant throughout the body where they perform diverse functions.

Pharmacodynamics

The administration of glucosamine, in theory, provides a building block towards the synthesis of glycosaminoglycans, slowing the progression of osteoarthritis and relieving symptoms of joint pain. Studies to this date examining the efficacy of glucosamine sulfate have been inconclusive. Glycosaminoglycans contribute to joint cartilage elasticity, strength, and flexibility. A systematic review of various studies and guidelines determined that modest improvements were reported for joint pain and function in patients taking glucosamine. A consistent joint space narrowing was observed, but with an unclear clinical significance.

Mechanism of action

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

Pharmacodynamics

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