NIZACARD 500

Indications

• Dry eye conditions
• Tear deficiency
• Keratoconjunctivitis sicca

Dosage

Children: Apply as required, typically in the form of eye drops.

Adults: Apply as required, typically in the form of eye drops.

Mechanism of action

Hypromellose acts by forming a viscous gel upon contact with the ocular surface, which helps to retain moisture and protect against irritants. This gel-like property enhances the stability of the tear film and reduces evaporation, thereby alleviating symptoms associated with dry eye conditions.

Pharmacodynamics

The pharmacodynamic effects of hypromellose are primarily related to its ability to mimic natural tears, providing lubrication to the ocular surface. This lubrication reduces friction during blinking and maintains corneal hydration, which is critical for ocular comfort and health. Its high viscosity also contributes to prolonged retention time on the eye surface.

Pharmacokinetics

Hypromellose is administered topically as eye drops and is not significantly absorbed systemically. The retention time of hypromellose on the ocular surface is enhanced due to its viscosity, allowing for extended relief of dry eye symptoms. The elimination of hypromellose occurs primarily through drainage from the eye and dilution by the natural tear fluid.

Adverse effects

• Temporary visual disturbance
• Eye irritation

Precautions

• Should not be used during contact lens wear
• Use with caution in patients with known hypersensitivity to any component of the formulation

Pregnancy

Hypromellose is generally considered safe for use during pregnancy. However, it should be used only if clearly needed and after consulting a healthcare provider.

Breast-feeding

Hypromellose is unlikely to affect breastfed infants when used as directed, but consultation with a healthcare provider is advisable.

Storage

Store in a cool, dry place away from direct sunlight. Once opened, use within a specified period as indicated on the packaging.

Formulations

• {'name': 'Teardew', 'concentration': '0.3%', 'form': 'eye drops', 'volume': '10 ml'}
• {'name': 'Xailin Hydrate', 'concentration': '0.3%', 'form': 'eye drops', 'volume': '10 ml'}
• {'name': 'AacuLose', 'concentration': '0.3%', 'form': 'eye drops', 'volume': '10 ml'}
• {'name': 'Artelac', 'concentration': '0.32%', 'form': 'eye drops', 'volume': '10 ml'}
• {'name': 'Lacrilube', 'concentration': '2 mg/g', 'form': 'eye ointment', 'volume': '3.5 g'}
• {'name': 'Celluvisc', 'concentration': '1%', 'form': 'eye drops', 'volume': '0.4 ml unit dose'}

Indications

• Chronic stable angina pectoris
• Myocardial ischemia

Dosage

Adults: Initially, 375 mg twice daily for 2–4 weeks, then increased to 500 mg twice daily. Adjust based on response, maximum 750 mg twice daily, and reduce if not tolerated.

Mechanism of action

Ranolazine inhibits the late sodium current (I_Na) in cardiac myocytes, which helps restore the balance of sodium and potassium ions essential for normal heart function. This inhibition reduces intracellular calcium overload and improves myocardial energy metabolism, thereby alleviating symptoms of angina. Additionally, ranolazine has weak activity on L-type calcium channels and can exert minimal vasodilatory effects. It also antagonizes alpha 1 and beta 1 adrenergic receptors and inhibits fatty acid oxidation.

Pharmacodynamics

Ranolazine has antianginal and ischemic effects that are independent of its impact on heart rate or blood pressure. It blocks the rapid component of the delayed rectifier potassium current (I_Kr), which prolongs the QTc interval in a dose-dependent manner without causing negative chronotropic or inotropic effects during rest or exercise. This allows it to effectively manage angina symptoms without exacerbating heart failure or causing bradycardia.

Pharmacokinetics

Ranolazine is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 2 to 4 hours after administration. It undergoes extensive hepatic metabolism primarily via CYP3A4 and has a half-life of about 7 hours. The presence of food can increase the bioavailability of ranolazine. It is primarily excreted in the urine, with a significant portion of the drug metabolized to its active metabolites.

Contra-indications

• Severe hepatic impairment
• Concurrent use of strong CYP3A4 inhibitors (except diltiazem, erythromycin)
• Hypersensitivity to ranolazine or any of its components

Adverse effects

• Dizziness
• Nausea
• Constipation
• Headache
• QT interval prolongation
• Palpitations
• Abdominal pain
• Fatigue

Interactions

• Severe: fidaxomicin, grapefruit juice, clarithromycin, St. John's Wort
• Moderate: bictegravir, pramipexole, panobinostat, dopaminergic receptor agonists, ticagrelor, afatinib

Precautions

• Monitor heart rate and blood pressure
• Caution in patients with moderate to severe renal impairment
• Avoid in patients with body weight less than 60 kg
• Use with caution in elderly patients

Pregnancy

Manufacturer advises to avoid unless essential, no information available.

Breast-feeding

Manufacturer advises to avoid, no information available.

Storage

Store in a cool, dry place, away from light, at room temperature.

Formulations

• Modified-release tablet 375 mg
• Modified-release tablet 500 mg
• Modified-release tablet 750 mg
• Infusion 12.5 mg/250 ml
• Infusion 60 mg/250 ml

Indications

• Methemoglobinemia
• Urinary tract infections
• Surgical marking
• Treatment of certain types of cyanide poisoning

Dosage

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

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

Mechanism of action

Methylene blue acts as a reducing agent, converting methemoglobin back to its functional form, hemoglobin. This is primarily achieved through its action as an electron donor, facilitating the reduction of ferric iron (Fe3+) in hemoglobin to ferrous iron (Fe2+), thereby restoring its oxygen-carrying capacity. It also exhibits antimicrobial properties through its ability to generate reactive oxygen species when exposed to light, which can inhibit bacterial growth.

Pharmacodynamics

The pharmacodynamics of methylene blue involve its role in enhancing oxygen delivery in patients suffering from methemoglobinemia. By converting methemoglobin back to hemoglobin, it effectively increases the amount of hemoglobin available for oxygen transport. The drug also shows effects on the vascular system, where it can induce vasodilation and influence blood pressure.

Pharmacokinetics

Methylene blue is rapidly absorbed after intravenous administration, with peak plasma concentrations occurring within 1 to 3 hours. It is extensively distributed in body tissues and fluids, including the liver, kidneys, and lungs. The drug undergoes hepatic metabolism, primarily through the cytochrome P450 system, and is excreted mainly through urine. The half-life ranges from 5 to 24 hours, depending on the dosage and individual patient factors.

Pregnancy

Consult healthcare provider before use, as safety in pregnancy is not established.

Breast-feeding

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

Storage

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

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

• Drug delivery systems
• Biodegradable implants
• Controlled release formulations
• Tissue engineering
• Medical device coatings

Dosage

Children: As with adult dosing, paediatric dosing of copolymers is specific to the formulation and application. Consult relevant pediatric pharmacology resources for detailed dosing recommendations.

Adults: Dosing of copolymers is highly variable and dependent on the specific drug formulation and intended use. For precise dosing information, refer to established pharmacological guidelines or product-specific resources.

Mechanism of action

Copolymers can function as drug delivery vehicles, allowing for controlled release of therapeutic agents. They can encapsulate drugs and release them in a sustained manner, depending on environmental triggers such as pH or temperature. This mechanism enhances the efficacy of drugs while minimizing side effects.

Pharmacodynamics

The pharmacodynamic properties of copolymers depend on their composition and structure, influencing their interaction with biological systems. They can modify drug release profiles and enhance the therapeutic effects of co-administered agents, facilitating targeted delivery to specific tissues or cells.

Pharmacokinetics

The pharmacokinetics of copolymers vary based on their molecular weight, structure, and the drugs they carry. Factors such as absorption, distribution, metabolism, and excretion will depend on the formulation and the specific application. Generally, copolymers can improve drug stability and prolong circulation time in the body.

Pregnancy

The safety of copolymer use during pregnancy has not been established. Non-essential use should be avoided.

Breast-feeding

The excretion of copolymers in human milk is unknown. Caution is advised when administering to nursing mothers.

Storage

Store in a cool, dry place away from direct light. Check specific product storage requirements as they may vary.

Indications

• Controlled release formulations
• Enteric-coated tablets and capsules
• Stability enhancement of sensitive drugs

Dosage

Children: Refer to specific product guidelines for dosing, as formulations can vary.

Adults: Refer to specific product guidelines for dosing, as formulations can vary.

Mechanism of action

Eudragit polymers function through their ability to form a film that can encapsulate active pharmaceutical ingredients. This film can be designed to dissolve at specific pH levels, allowing for targeted drug release in the gastrointestinal tract. The polymers are often engineered to be soluble in alkaline conditions, making them ideal for enteric coatings that protect drugs from degradation in the acidic environment of the stomach.

Pharmacodynamics

The pharmacodynamic properties of Eudragit polymers are primarily linked to their physical and chemical characteristics, including solubility, permeability, and film-forming ability. By forming a barrier around the drug, Eudragit can modulate the release rate and protect the active ingredient from environmental factors, thus influencing its therapeutic efficacy and safety.

Pharmacokinetics

The pharmacokinetics of drugs formulated with Eudragit depends on the specific active ingredients and their interactions with the polymer matrix. Generally, the release of the drug is influenced by the dissolution of the Eudragit film, which occurs at specific pH levels in the gastrointestinal tract. The polymers themselves are not absorbed systemically, as they are designed to remain intact until reaching the targeted site of action.

Pregnancy

No adequate and well-controlled studies in pregnant women are available. Eudragit, a polymer used in enteric coating and controlled drug delivery, should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether Eudragit is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place, away from heat and moisture. Keep the container tightly closed.

Formulations

• Eudragit L
• Eudragit S
• Eudragit RL
• Eudragit RS

Dosage

Children: Refer to specific guidelines for pediatric dosing; consult the BNF for Children for accurate dosage information.

Adults: Refer to specific guidelines for use; dosage may vary based on the context of use.

Mechanism of action

Hydroxide ions act primarily as bases, neutralizing acids to form water and salts. They participate in various biochemical pathways, including selenium metabolism and the degradation of reactive oxygen species. Hydroxide can influence enzyme activity and stability by altering the pH of the environment, thereby affecting metabolic reactions.

Pharmacodynamics

Hydroxide ions can impact biological processes by changing the local pH, which influences enzyme activity, ion transport, and the solubility of other compounds. Their ability to neutralize acids can help regulate physiological pH, contributing to homeostasis in living organisms.

Pharmacokinetics

As an inorganic ion, hydroxide does not undergo traditional pharmacokinetic processes like absorption, distribution, metabolism, or excretion. Instead, it is rapidly equilibrated in biological fluids and participates in acid-base reactions, having immediate effects on the local environment.

Pregnancy

There is limited information regarding the use of hydroxide during pregnancy. Consult a healthcare professional for advice.

Breast-feeding

Limited data is available on the excretion of hydroxide in breast milk. Consult a healthcare professional before use.

Storage

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

Dosage

Children: Refer to product-specific guidelines or literature for dosing information, as methacrylic acid is primarily used in industrial and medical applications rather than as a direct therapeutic agent.

Adults: Refer to product-specific guidelines or literature for dosing information, as methacrylic acid is primarily used in industrial and medical applications rather than as a direct therapeutic agent.

Mechanism of action

Methacrylic acid functions primarily as a monomer that undergoes polymerization to form methacrylate-based polymers. The polymerization process can be initiated by thermal, chemical, or photoinitiated methods, resulting in the formation of cross-linked networks that provide structural integrity and durability to the final product. It interacts with radical initiators to form reactive free radicals that propagate the polymer chain growth.

Pharmacodynamics

Methacrylic acid and its derivatives exhibit good mechanical properties and biocompatibility, making them suitable for use in medical and dental applications. The polymers formed from methacrylic acid demonstrate resistance to wear, chemical degradation, and UV light, which enhances their stability and longevity in various environments. The biocompatibility of methacrylate polymers is essential for their application in medical devices, ensuring minimal adverse reactions upon implantation.

Pharmacokinetics

The pharmacokinetics of methacrylic acid is not extensively characterized due to its primary use as a polymer precursor rather than a therapeutic agent. However, when released in vivo, it is assumed to undergo rapid metabolism. The compound is likely to be absorbed through various routes, but specific absorption, distribution, metabolism, and excretion (ADME) data are limited. As a low molecular weight organic acid, it may be subject to conjugation and subsequent elimination through renal pathways.

Pregnancy

Methacrylic acid and its derivatives should be used with caution during pregnancy, as there is limited data on their safety. It is advisable to avoid use unless the potential benefits outweigh the risks.

Breast-feeding

There is insufficient information regarding the excretion of methacrylic acid into human milk. Caution is advised when administered to breastfeeding women.

Storage

Store in a cool, dry place away from direct sunlight. Keep containers tightly closed when not in use.

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

• Tablet coating
• Granule coating
• Improvement of drug stability
• Taste masking
• Aesthetic enhancement of pharmaceuticals

Dosage

Children: Dosage will depend on the specific formulation and active ingredients of the medication being coated. Refer to the specific product information for guidance.

Adults: Dosage will depend on the specific formulation and active ingredients of the medication being coated. Refer to the specific product information for guidance.

Mechanism of action

Opadry functions primarily as a coating polymer that adheres to the surface of tablets or granules, creating a protective layer. This layer can control the release of the active ingredient and protect it from environmental factors such as moisture and light. The specific composition of Opadry can vary, but it typically includes film-forming agents, plasticizers, and colorants that work together to achieve the desired coating characteristics.

Pharmacodynamics

The pharmacodynamics of Opadry is largely focused on its physical and chemical properties rather than specific biological interactions. The coating alters the dissolution characteristics of the drug, potentially leading to modified release profiles. This can enhance drug bioavailability or control the release rate of the active ingredient, thereby impacting the therapeutic effect.

Pharmacokinetics

As a coating agent, Opadry itself is not absorbed into the systemic circulation and does not have pharmacokinetic properties related to absorption, distribution, metabolism, or excretion of an active pharmaceutical ingredient. Its impact on pharmacokinetics is indirect, as it affects how the active drug is released and absorbed in the gastrointestinal tract.

Pregnancy

Opadry is a film-coating agent, and specific studies on its effects during pregnancy are not well-documented. Generally, it is advisable to use medications cautiously during pregnancy. Consult a healthcare provider for guidance.

Breast-feeding

Limited data are available regarding the safety of Opadry during breastfeeding. It is recommended to consult a healthcare provider before use.

Storage

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

Formulations

• Opadry OY - a coating system for oral solid dosage forms
• Opadry II - a polymer-based coating system for tablet and capsule applications

Mechanism of action

Myocardial ischemia exerts effects on adenosine triphosphate flux, leading to a decrease in the energy available for contraction and relaxation of the heart muscle. Electrolyte balance of sodium and potassium is necessary for maintaining normal cardiac contraction and relaxation. Disruption of adequate sodium and potassium electrolyte balance leads to excessively high concentrations of sodium and calcium, which likely interferes with oxygen supply to the heart muscle. This imbalance eventually leads to angina symptoms of chest pain or pressure, nausea, and dizziness, among others. The mechanism of action for ranolazine is not fully understood. At therapeutic concentrations, it can inhibit the cardiac late sodium 205 current (INa), which may affect the electrolyte balance in the myocardium, relieving angina symptoms. The clinical significance this inhibition in the treatment of angina symptoms is not yet confirmed. Ranolazine inhibits sodium and potassium ion channel currents. It has been shown to exert weak activity on L-type calcium channels making it a weak direct vasodilator and exerts minimal direct effects on atrioventricular nodal conduction. Some additional mechanisms have been elucidated. Ranolazine exerts antagonistic activity towards the alpha 1 and beta 1 adrenergic receptors and inhibition of fatty acid oxidation. Ranolazine, a piperazine derivative, is an antianginal agent. Although the exact mechanism of antianginal activity of ranolazine has not been fully elucidated, results of early studies suggested that ranolazine shifted adenosine triphosphate (ATP) production away from fatty acid oxidation (ie, partial inhibition of fatty acid oxidation) in favor of more oxygen-efficient glucose oxidation, especially when free fatty acid concentrations were elevated (eg, during ischemia), leading to reduced oxygen demand and symptoms of ischemia without affecting cardiac work. However, these pharmacologic effects generally were observed at concentrations exceeding therapeutic plasma concentrations in clinical studies. Recent data suggest that ranolazine may exert its antianginal and anti-ischemic effects through concentration-, voltage-, and frequency-dependent inhibition of the late (ie, sustained, persistent) sodium current and other cardiac ion channels and transporters. The late sodium current is created by inactivation of the sodium channel protein. However, angina (ie, ischemia, hypoxia) impairs sodium channel inactivation and increases the amount of sodium in cardiac cells, which facilitates calcium overload via the sodium-calcium exchange pump. Increased intracellular calcium may result in myocyte hyperexcitability and electrical instability, impaired diastolic relaxation, reduced coronary artery perfusion, impaired myocardial oxygen supply, increased oxygen demand, and ventricular dysfunction. Thus, ranolazine may decrease the magnitude of the late sodium current resulting in a net reduction in intracellular sodium concentrations, reversal of calcium overload, restoration of ventricular pump function, and prevention of ischemia-induced arrhythmias. Unlike other antianginal agents, the antianginal effects of ranolazine are not dependent upon reductions in heart rate or blood pressure. The QT prolongation effect of ranolazine on the surface electrocardiogram is the result of inhibition of IKr, which prolongs the ventricular action potential. /The authors/ investigated changes in Na(+) currents (I(Na)) in permanent (or chronic) atrial fibrillation (AF) and the effects of I(Na) inhibition using ranolazine (Ran) on arrhythmias and contractility in human atrial myocardium. Electrical remodeling during AF is typically associated with alterations in Ca(2+) and K(+) currents. It remains unclear whether I(Na) is also altered. Right atrial appendages from patients with AF (n = 23) and in sinus rhythm (SR) (n = 79) were studied. Patch-clamp experiments in isolated atrial myocytes showed significantly reduced peak I(Na) d

Pharmacodynamics

Ranolazine exerts both antianginal and ischemic effects independent from lowering heart rate or blood pressure. It blocks IKr, the rapid portion of the delayed rectifier potassium current, and prolongs the QTc interval in a dose-dependent fashion. The Ikr is important for cardiac repolarization. Ranolazine exerts its therapeutic effects without negative chronotropic, dromotropic, or inotropic actions neither at rest, nor during exercise.