VAROSUN

Indications

• Prophylaxis of venous thromboembolism following knee replacement surgery
• Prophylaxis of venous thromboembolism following hip replacement surgery
• Treatment of deep vein thrombosis
• Treatment of pulmonary embolism

Dosage

Adults: For the prophylaxis of venous thromboembolism following knee replacement surgery: 10 mg once daily for 2 weeks, starting 6–10 hours

Mechanism of action

Rivaroxaban competitively inhibits both free and clot-bound factor Xa. Factor Xa is essential for the conversion of prothrombin to thrombin, which is necessary for fibrinogen to be activated into fibrin, leading to clot formation. By inhibiting factor Xa, rivaroxaban effectively terminates the amplification of thrombin generation, preventing thrombus formation. Its action is irreversible and does not require a cofactor, distinguishing it from other anticoagulants like heparin.

Pharmacodynamics

Rivaroxaban exhibits anticoagulant properties by directly binding to factor Xa. This binding prevents the activation of prothrombin, thereby blocking the coagulation cascade and thrombus formation. Unlike traditional anticoagulants, rivaroxaban does not utilize antithrombin III to exert its effects, and it is administered orally, making it more convenient compared to parenteral anticoagulants.

Pharmacokinetics

Rivaroxaban is rapidly absorbed and reaches peak plasma concentrations within 2-4 hours after oral administration. It is extensively metabolized in the liver, primarily by CYP3A4 and CYP2J2, and is also a substrate for P-glycoprotein. The half-life of rivaroxaban is approximately 5-9 hours in healthy individuals, and it is excreted via both renal and fecal routes, with about 66% excreted as metabolites and 28% as unchanged drug.

Contra-indications

• Active bleeding
• Bacterial endocarditis
• Active gastrointestinal ulcer

Adverse effects

• Anaemia
• Haemorrhage
• Chest pain
• Dyspnoea
• Fever
• Hepatic function abnormality
• Nausea
• Oedema
• Platelet abnormalities
• Thrombocytopenia
• Vomiting
• Wound secretion
• Anxiety
• Confusion
• Constipation
• Cough
• Diarrhoea
• Dizziness
• Drowsiness
• Fatigue
• Gastritis
• Gastrointestinal discomfort
• Genital oedema
• Headache
• Hyperbilirubinaemia
• Hypersensitivity
• Hypokalaemia
• Hypotension
• Leg pain
• Post procedural infection
• Syncope
• Vasodilation
• Vertigo

Interactions

• tucatinib+rivaroxaban: Moderate (increases exposure)
• vemurafenib+rivaroxaban: Moderate (increases exposure)
• antiarrhythmics+rivaroxaban: Unknown (increases exposure)
• antiepileptics (carbamazepine, phenobarbital, phenytoin, primidone)+rivaroxaban: Unknown (decreases exposure)
• ciclosporin+rivaroxaban: Unknown (increases exposure)
• mitotane+rivaroxaban: Unknown (decreases exposure)
• NNRTIs+rivaroxaban: Unknown (decreases exposure)
• St. John's Wort+rivaroxaban: Unknown (decreases exposure)

Precautions

• Elderly patients
• Low body weight
• Spinal or epidural anaesthesia (risk of spinal haematoma)
• Patients with a history of bleeding disorders
• Patients undergoing percutaneous coronary intervention
• Patients with renal impairment

Pregnancy

Manufacturer advises to avoid unless potential benefit outweighs possible risk-no information available.

Breast-feeding

Present in milk in animal

Dosage

Children: Refer to specific agent guidelines for paediatric dosing.

Adults: Refer to specific agent guidelines for dosing.

Mechanism of action

The mechanism of action varies significantly among different agents. For example, some agents may function by inhibiting specific enzymes or receptors, altering neurotransmitter levels, or modulating immune responses. Understanding the specific agent in question is crucial for determining its precise mechanism.

Pharmacodynamics

Pharmacodynamics pertains to the effects of the agent on the body and includes the relationship between drug concentration and effect. Agents may exhibit dose-dependent effects, with lower doses producing therapeutic effects and higher doses potentially leading to adverse reactions. The specific pharmacodynamic profile will depend on the class of the agent and its target pathways.

Pharmacokinetics

Pharmacokinetics encompasses the absorption, distribution, metabolism, and excretion of the agent. Agents may be absorbed through oral, intravenous, or other routes, with bioavailability varying based on formulation and administration. Distribution is influenced by factors such as protein binding and tissue permeability. Metabolism typically occurs in the liver, with cytochrome P450 enzymes playing a critical role, and excretion primarily happens through the kidneys.

Indications

• Constipation
• Dietary fiber supplementation
• Irritable bowel syndrome
• Diverticular disease
• Weight management

Dosage

Children: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Adults: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Mechanism of action

Cellulose acts primarily as a bulk-forming laxative. It absorbs water in the intestines, which increases stool bulk and stimulates peristalsis, thus facilitating bowel movements. Additionally, cellulose is not digestible by human enzymes, leading to fermentation by gut bacteria, which may enhance gut health and alter gut microbiota composition.

Pharmacodynamics

Cellulose increases stool weight and frequency of bowel movements. It works by retaining water in the intestines, leading to softer stools and improved passage through the gastrointestinal tract. The bulking effect of cellulose can help alleviate constipation and promote overall digestive health. It may also play a role in cholesterol reduction and glycemic control through its effects on digestion and absorption of nutrients.

Pharmacokinetics

Cellulose is not absorbed into the bloodstream due to its indigestible nature. Instead, it passes through the gastrointestinal tract, where it adds bulk to the stool. Its fermentation by colonic bacteria produces short-chain fatty acids, which may have beneficial effects on colon health. The onset of action for cellulose as a laxative can vary but is generally within 24 to 72 hours after ingestion.

Adverse effects

• Bloating
• Flatulence
• Diarrhea
• Abdominal discomfort

Precautions

• Use with caution in patients with a history of gastrointestinal disorders.
• Monitor for potential allergic reactions in sensitive individuals.

Pregnancy

Cellulose is generally considered safe during pregnancy as it is a non-toxic, indigestible fiber.

Breast-feeding

Cellulose is also considered safe during breastfeeding; it is excreted in breast milk in negligible amounts.

Storage

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

Formulations

• Powder
• Capsules
• Tablets
• Granules

Indications

• Protection of drugs from degradation
• Taste masking
• Controlled release of active ingredients
• Improvement of patient compliance
• Targeted delivery of medications

Dosage

Children: Refer to specific product labeling for dosing information, as this varies widely based on formulation and indication.

Adults: Refer to specific product labeling for dosing information, as this varies widely based on formulation and indication.

Mechanism of action

The mechanism of action of coatings primarily involves the modification of drug release profiles. By altering the solubility and permeability of the drug through the coating material, the release rate can be controlled. For example, enteric coatings prevent drug dissolution in the acidic environment of the stomach, allowing the drug to be released in the more neutral pH of the intestine.

Pharmacodynamics

Pharmacodynamics of coated formulations can vary significantly based on the type of coating used. Immediate-release coatings dissolve quickly, leading to rapid absorption and onset of action. Controlled-release coatings are designed to dissolve slowly over time, providing a sustained release of the drug, which can lead to prolonged therapeutic effects and reduced dosing frequency. The choice of coating material and thickness influences the overall pharmacodynamic profile of the drug.

Pharmacokinetics

The pharmacokinetics of coated drugs are influenced by the coating material and the drug itself. Factors such as the rate of dissolution, absorption site, and first-pass metabolism play critical roles. Coatings can alter the bioavailability and distribution of the drug. For example, enteric coatings can enhance the absorption of drugs that are unstable in acidic conditions, potentially increasing their bioavailability when the drug reaches the intestine.

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised as it is not known whether it passes into breast milk.

Storage

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

Indications

• Used as a disintegrant in tablet formulations
• Enhances the bioavailability of active pharmaceutical ingredients

Dosage

Children: Refer to the specific formulation guidelines, as dosage will vary based on the active ingredient and formulation type.

Adults: Refer to the specific formulation guidelines, as dosage will vary based on the active ingredient and formulation type.

Mechanism of action

Croscarmellose sodium works by swelling and absorbing water when it comes into contact with gastrointestinal fluids. This swelling leads to the rapid disintegration of the tablet or capsule matrix, facilitating the release and absorption of the active pharmaceutical ingredients.

Pharmacodynamics

Croscarmellose sodium is classified as a superdisintegrant. Its ability to rapidly disintegrate solid dosage forms can significantly enhance the dissolution rate of the active ingredient, which is crucial for achieving therapeutic effects in a timely manner.

Pharmacokinetics

Croscarmellose sodium is not absorbed in the gastrointestinal tract and does not exert pharmacological effects in the body. It is considered non-toxic and is excreted unchanged. Its main role is as an excipient, influencing the formulation's characteristics rather than the pharmacokinetics of the active ingredients.

Precautions

• Use with caution in patients with known hypersensitivity to croscarmellose or its components.

Pregnancy

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

Breast-feeding

Caution is advised when using during breastfeeding, as safety has not been established.

Storage

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

Formulations

• Powder
• Granules

Dosage

Children: Refer to specific BNF for Children guidelines for the medication contained within the film formulation, as dosing will depend on the active ingredient and the patient's age and weight.

Adults: Refer to specific BNF guidelines for the medication contained within the film formulation, as dosing will vary widely based on the active ingredient.

Mechanism of action

The mechanism of action for drugs delivered via film formulations varies depending on the active pharmaceutical ingredient contained within the film. Generally, the drug is absorbed through the mucosal membranes in the mouth or gastrointestinal tract, leading to systemic circulation. This can enhance the onset of action compared to traditional solid dosage forms.

Pharmacodynamics

Pharmacodynamics will vary based on the specific drug contained in the film formulation. In general, pharmacodynamics refers to the biochemical and physiological effects of the drug on the body, including its mechanism of action, therapeutic effects, and side effects. Film formulations may provide rapid onset of action due to faster dissolution and absorption of the drug.

Pharmacokinetics

Pharmacokinetics, which includes absorption, distribution, metabolism, and excretion (ADME), will also vary by the specific active ingredient in the film formulation. In general, films may exhibit faster absorption rates due to their design, leading to quicker peak plasma concentrations. The distribution will depend on the lipophilicity of the drug, while metabolism will occur primarily in the liver, and excretion can be renal or fecal, depending on the drug's characteristics.

Pregnancy

The safety of film in pregnancy has not been well established. Use only if clearly needed.

Breast-feeding

It is unknown if film is excreted in human milk. Use with caution while breastfeeding.

Storage

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

Indications

• Used as an excipient in pharmaceutical formulations
• Improves solubility and stability of active ingredients
• Facilitates drug absorption

Dosage

Children: Refer to specific product guidelines as hydroxypropyl is typically used as an excipient and not dosed independently.

Adults: Refer to specific product guidelines as hydroxypropyl is typically used as an excipient and not dosed independently.

Mechanism of action

Hydroxypropyl functions primarily as a solubilizing agent, which aids in the dissolution of poorly soluble drugs. It interacts with water and other solvents to improve the dispersion of pharmaceutical compounds, thereby enhancing their bioavailability. Hydroxypropyl may also facilitate the permeability of drug molecules through biological membranes, contributing to their overall efficacy.

Pharmacodynamics

The pharmacodynamics of hydroxypropyl relate to its role in improving the physicochemical properties of drug formulations. By increasing solubility and stability, hydroxypropyl can enhance the absorption of drugs administered via various routes, including oral and topical. Its non-toxic nature allows for safe incorporation into formulations, making it suitable for a wide range of applications.

Pharmacokinetics

The pharmacokinetics of hydroxypropyl have not been extensively studied as it primarily acts as an excipient rather than an active pharmaceutical ingredient. When used in formulations, it is typically not absorbed into systemic circulation in significant amounts, thereby minimizing potential systemic effects. Hydroxypropyl is generally regarded as safe when used in appropriate amounts in drug formulations.

Pregnancy

Hydroxypropyl is not classified for use during pregnancy, and its safety has not been established. Caution is advised.

Breast-feeding

There is limited information on the excretion of hydroxypropyl in human milk. Caution is advised when administering to breastfeeding women.

Storage

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

Indications

• Lactose intolerance
• As a filler or excipient in pharmaceutical formulations

Dosage

Children: Refer to the BNF for Children for specific dosing information based on age and clinical context.

Adults: Refer to the BNF for specific dosing information based on clinical context.

Mechanism of action

Lactose is metabolized in the intestine by the enzyme lactase into its constituent monosaccharides, glucose and galactose. In individuals with lactase deficiency, unabsorbed lactose passes into the colon, where it is fermented by bacteria, leading to gas production and osmotic effects that contribute to diarrhea.

Pharmacodynamics

The pharmacodynamics of lactose are primarily related to its effects on gastrointestinal function. In healthy individuals, lactose is effectively broken down into glucose and galactose, which are absorbed and utilized for energy. In individuals with lactose intolerance, the unabsorbed lactose can cause osmotic diarrhea and colonic fermentation, leading to discomfort and symptoms associated with lactose intolerance.

Pharmacokinetics

Lactose is not absorbed in the gastrointestinal tract until it is hydrolyzed into glucose and galactose by lactase. The absorption of glucose and galactose occurs in the small intestine. The half-life is not applicable as lactose is not typically administered as a medication but is rather ingested as a natural component of food. Its metabolism primarily occurs in the intestine.

Adverse effects

• Bloating
• Diarrhea
• Abdominal pain
• Flatulence

Precautions

• Use with caution in patients with lactose intolerance.
• Consider potential for gastrointestinal upset in sensitive individuals.

Pregnancy

Lactose is generally considered safe for use during pregnancy. However, consult a healthcare professional for individual advice.

Breast-feeding

Lactose is safe to use while breastfeeding, as it is a natural sugar present in breast milk.

Storage

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

Formulations

• Powder
• Granules
• Tablets
• Syrup

Indications

• Cleansing agent in topical formulations
• Emulsifying agent in cosmetic products
• Foaming agent in shampoos and body washes

Dosage

Children: Refer to specific product formulations for appropriate concentrations and application methods.

Adults: Refer to specific product formulations for appropriate concentrations and application methods.

Mechanism of action

Lauryl sulfate functions as an anionic surfactant. It reduces the surface tension between different substances, allowing for better spreading and wetting. In the context of cleansing, it facilitates the removal of dirt and oils from the skin and hair by emulsifying these substances, thus making them easier to rinse away with water.

Pharmacodynamics

As a surfactant, lauryl sulfate displays properties that can disrupt cellular membranes and alter permeability. This mechanism is beneficial in enhancing the penetration of other therapeutic agents in topical formulations. However, its irritant potential on skin and mucous membranes should be noted, as it can lead to dryness and irritation with prolonged exposure.

Pharmacokinetics

Lauryl sulfate is primarily applied topically and is not intended for systemic absorption. When used in formulations, it acts locally at the site of application. Its absorption through the skin is minimal, and any systemic exposure is limited. Metabolism and excretion pathways are not well-defined for topical applications, as it is largely washed away after use.

Pregnancy

Safety during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Unknown whether lauryl is excreted 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.

Indications

• Allergic conditions
• Autoimmune diseases
• Asthma and chronic obstructive pulmonary disease (COPD)
• Certain cancers (e.g., leukemia, lymphoma)
• Skin conditions (e.g., dermatitis)
• Inflammatory bowel disease
• Multiple sclerosis exacerbations
• Severe infections requiring immunosuppression

Dosage

Children: Refer to BNF for Children for specific dosing; doses vary significantly based on the child's age, weight, and condition being treated.

Adults: Refer to BNF for specific dosing; typically, initial doses range from 4 to 48 mg depending on the severity of the condition.

Mechanism of action

Methylprednisolone exerts its effects by binding to glucocorticoid receptors, leading to the modulation of gene expression. This interaction influences the transcription of anti-inflammatory proteins while suppressing the expression of pro-inflammatory genes, ultimately resulting in reduced inflammation and immune response.

Pharmacodynamics

The pharmacodynamic effects of methylprednisolone are characterized by its ability to decrease inflammation, suppress the immune response, and affect carbohydrate metabolism. Therapeutic doses lead to various systemic effects, including modification of leukocyte distribution and inhibition of cytokine production.

Pharmacokinetics

Methylprednisolone is well absorbed after oral administration, with a bioavailability of approximately 50%. It has a volume of distribution that reflects extensive tissue binding. The drug is metabolized primarily in the liver through conjugation and reduction, and its metabolites are excreted in urine. The half-life varies based on the route of administration but is generally around 18 to 36 hours.

Adverse effects

• Increased blood pressure
• Hyperglycemia
• Weight gain
• Mood changes
• Insomnia
• Gastrointestinal disturbances
• Increased susceptibility to infections

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)
• mao-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)

Precautions

• Use with caution in patients with hypertension
• Monitor blood glucose levels in diabetic patients
• Consider potential for infection risk due to immunosuppression
• Evaluate for psychiatric effects in susceptible individuals

Pregnancy

Corticosteroids may be used during pregnancy if the potential benefit justifies the risk to the fetus. Careful monitoring is advised.

Breast-feeding

Corticosteroids are excreted in breast milk; caution is advised. Monitor the infant for potential effects.

Storage

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

Formulations

• Tablets
• Injectable solutions
• Topical preparations

Mechanism of action

Methylsulphate functions as a methylating agent, transferring a methyl group to nucleophiles. This process involves the formation of a sulfonium ion, which is highly reactive and can readily react with nucleophilic sites on various substrates, leading to methylation reactions.

Pharmacodynamics

The pharmacodynamics of methylsulphate is primarily related to its role as a methylating agent in biochemical reactions. It can alter the structure and function of biological molecules, potentially affecting cellular processes and signaling pathways. However, detailed pharmacodynamic studies specific to therapeutic use are limited.

Pharmacokinetics

There is limited information on the pharmacokinetics of methylsulphate, given its typical use as a reagent in laboratory settings rather than a clinical drug. When used in chemical reactions, its reactivity and transformation into other compounds would dictate its pharmacokinetic profile, which could vary significantly based on the specific context of use.

Pregnancy

There is limited data on the use of methylsulphate in pregnancy. Consult relevant guidelines.

Breast-feeding

Data on the excretion of methylsulphate in human milk is not available. Caution is advised.

Storage

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

Indications

• Used as an excipient in tablet formulations
• Used as a bulking agent in capsule formulations
• Used in food products as a thickener or stabilizer

Dosage

Children: Refer to specific product guidelines as dosage will depend on the formulation and the active ingredients.

Adults: Refer to specific product guidelines as dosage will depend on the formulation and the active ingredients.

Mechanism of action

Microcrystalline cellulose acts as a non-digestible filler that enhances the flow properties of powders during the manufacturing of tablets and capsules. It does not have a direct pharmacological action on the body but ensures that the active ingredients are effectively delivered to the patient.

Pharmacodynamics

As a non-active ingredient, microcrystalline cellulose does not exert pharmacodynamic effects typical of active pharmaceutical ingredients. Its primary role is to provide a stable and consistent matrix for the drug, facilitating the release of the active compound once ingested.

Pharmacokinetics

Microcrystalline cellulose is not absorbed in the gastrointestinal tract; it passes through the digestive system largely unchanged. It adds bulk to the stool, which may aid in promoting regular bowel movements. The substance is excreted in feces, where it contributes to dietary fiber intake.

Pregnancy

Data regarding the use of microcrystalline cellulose during pregnancy is limited. It is advisable to consult with healthcare professionals before use.

Breast-feeding

Microcrystalline cellulose is considered safe during breastfeeding, as it is not absorbed systemically.

Storage

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

Indications

• Used in agriculture to regulate plant growth
• Commonly applied to cereal crops to prevent lodging
• Enhances crop yield and stability

Mechanism of action

Chlormequat chloride acts at the nicotinic receptor site of the neuromuscular junction, functioning as a depolarizing agent. This action leads to initial muscular excitation which is then followed by muscle weakness. The acute toxicity of chlormequat chloride may result in respiratory arrest, and its effects can vary by species due to differing sensitivities to depolarizing neuromuscular blockers.

Pharmacodynamics

Chlormequat chloride inhibits gibberellin biosynthesis, a key hormone in plant growth regulation, which leads to reduced cell elongation and overall dwarfing of plants. This mechanism helps enhance crop stability and yield by minimizing the risk of lodging in cereals, thus promoting a more efficient harvest.

Pharmacokinetics

The pharmacokinetics of chlormequat chloride in plants involves absorption, translocation, and metabolism within plant tissues. It is rapidly absorbed and translocated throughout the plant, with a relatively short half-life, leading to effective growth regulation while minimizing residues in harvested products.

Pregnancy

No adequate and well-controlled studies in pregnant women have been conducted. Use only if clearly needed.

Breast-feeding

It is not known whether chlormequat chloride is excreted in human milk. Caution should be exercised when administering to a nursing mother.

Storage

Store in a cool, dry place. Keep container tightly closed.

Dosage

Children: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Adults: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Mechanism of action

The mechanism of action for purified compounds varies widely depending on the specific substance. Generally, purified drugs exert their effects by interacting with specific biological targets, such as receptors, enzymes, or ion channels, leading to a desired therapeutic effect. This interaction can involve binding to receptors to activate or inhibit signaling pathways, modulating enzymatic activity, or altering physiological processes.

Pharmacodynamics

Pharmacodynamics describes the effects of a drug on the body and the relationship between drug concentration and effect. For purified drugs, this can involve dose-response relationships and the time course of their action. The purified form often enhances potency and reduces variability in response among patients, which can lead to more predictable therapeutic outcomes. The overall effect is determined by the drug's affinity for its target, the efficacy of the drug-receptor interaction, and the downstream signaling pathways activated as a result of this interaction.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of a drug. For purified substances, absorption can be more efficient due to the absence of impurities that may affect solubility or stability. Distribution may also be enhanced, leading to higher bioavailability. Metabolism can be influenced by the structure of the purified compound, as it may be metabolized more readily by liver enzymes. Excretion typically occurs through the kidneys or liver, depending on the molecular characteristics of the purified drug.

Pregnancy

Consult with a healthcare professional, as the safety of purified forms of medications during pregnancy may vary depending on the specific substance.

Breast-feeding

Consult with a healthcare professional, as the safety of purified forms of medications during breastfeeding may vary depending on the specific substance.

Storage

Store in a cool, dry place, away from light and moisture, and keep out of reach of children.

Mechanism of action

Rivaroxaban competitively inhibits free and clot bound factor Xa. Factor Xa is needed to activate prothrombin (factor II) to thrombin (factor IIa). Thrombin is a serine protease that is required to activate fibrinogen to fibrin, which is the loose meshwork that completes the clotting process. Since one molecule of factor Xa can generate more than 1000 molecules of thrombin, selective inhibitors of factor Xa are profoundly useful in terminating the amplification of thrombin generation. The action of rivaroxaban is irreversible. Rivaroxaban, an oral, direct activated factor X (Xa) inhibitor, is an anticoagulant. Factor Xa plays a central role in the blood coagulation cascade by serving as the convergence point for the intrinsic and extrinsic pathways; inhibition of coagulation factor Xa by rivaroxaban prevents conversion of prothrombin to thrombin and subsequent thrombus formation. Rivaroxaban inhibits both free and prothrombinase-bound factor Xa. Unlike fondaparinux, heparin, and the low molecular weight heparins, rivaroxaban binds directly to the active site of factor Xa without the need for a cofactor (e.g., antithrombin III). Rivaroxaban inhibits factor Xa with more than 100,000-fold greater selectivity than other biologically important serine proteases (e.g., thrombin, trypsin, plasmin, factor VIIa, factor IXa, urokinase, activated protein C). Xarelto is an orally bioavailable factor Xa inhibitor that selectively blocks the active site of factor Xa and does not require a cofactor (such as Anti-thrombin III) for activity. Activation of factor X to factor Xa (FXa) via the intrinsic and extrinsic pathways plays a central role in the cascade of blood coagulation.

Pharmacodynamics

Rivaroxaban is an anticoagulant which binds directly to factor Xa. Thereafter, it effectively blocks the amplification of the coagulation cascade, preventing the formation of thrombus. Rivaroxaban is a unqiue anticoagulant for two reasons. First of all, it is does not involve antithrombin III (ATIII) to exert its anticoagulant effects. Secondly, it is an oral agent whereas the widely used unfractionated heparin and low molecular weight heparins are for parenteral use only. Although the activated partial thromboplastin time (aPTT) and HepTest (a test developed to assay low molecular weight heparins) are prolonged in a dose-dependant manner, neither test is recommended for the assessment of the pharmacodynamic effects of rivaroxaban. Anti-Xa activity and inhibition of anti-Xa activity monitoring is also not recommended despite being influenced by rivaroxaban.

Mechanism of action

Chlormequat chloride has been reported in the literature to act at the nicotinic receptor site of the neuromuscular junction. The test material may act as a depolarizing agent at this site, leading to muscular excitation followed by muscle weakness. Acute toxicity may lead to respiratory arrest. Acute toxicity of chlormequat chloride has also been reported to differ by species, which is likely due to sensitivity to depolarizing neuromuscular blockers.