WIMAL PLUS HS

Indications

• Malaria caused by Plasmodium species
• Toxoplasmosis, particularly in immunocompromised patients
• Adjunct treatment of autoimmunity-related conditions

Dosage

Adults: For the treatment of toxoplasmosis in adults, the recommended dosage is 50 mg once daily until delivery, usually in combination with sulfadiazine and

Mechanism of action

Pyrimethamine inhibits the dihydrofolate reductase enzyme in plasmodia, blocking the biosynthesis of purines and pyrimidines necessary for DNA synthesis and cell multiplication. This inhibition leads to failure in nuclear division during the formation of schizonts in erythrocytes and liver. Additionally, it has immunomodulatory effects by increasing oxidative stress, which may aid in the elimination of parasites.

Pharmacodynamics

As an antiparasitic compound, pyrimethamine is particularly effective against uncomplicated, chloroquine-resistant Plasmodium falciparum malaria and Toxoplasma gondii. It exhibits blood schizonticidal activity and some tissue schizonticidal effects, though it does not affect gametocytes. The selective toxicity towards parasites, contrasted with minimal effects on human cells, is due to differences in nucleic acid precursor requirements. Its effectiveness is notably enhanced when used in combination with sulfonamides.

Pharmacokinetics

Pyrimethamine is absorbed well after oral administration and undergoes hepatic metabolism. Its elimination half-life is variable but can be prolonged in cases of renal impairment. The drug is primarily excreted in urine, both as unchanged drug and metabolites. Caution is advised in patients with liver and renal impairment, and monitoring of blood counts is recommended during prolonged therapy due to the risk of haematological toxicity.

Contra-indications

• G6PD deficiency
• Severe renal impairment
• Severe hepatic impairment
• History of seizures
• Heart block (requires ECG monitoring during parenteral treatment)

Adverse effects

• Abdominal pain
• Agitation
• Agranulocytosis
• Anaemia
• Angioedema
• Asthma
• Diarrhoea
• Dizziness
• Fever
• Flushing
• Headache
• Hearing impairment
• Hypersensitivity reactions
• Loss of consciousness
• Muscle weakness
• Nausea
• Skin reactions
• Thrombocytopenia
• Tinnitus
• Vertigo
• Vomiting

Interactions

• Antiepileptics (increases risk of haematological toxicity)
• Fosphenytoin (increases risk of haematological toxicity)
• Phenytoin (increases risk of haematological toxicity)
• Phenobarbital (increases risk of haematological toxicity)
• Primidone (increases risk of haematological toxicity)
• Methotrexate (increases risk of adverse effects)
• Pemetrexed (increases risk of adverse effects)

Precautions

• Monitor blood counts during prolonged treatment
• Consider dose reduction in renal and hepatic impairment
• Caution in patients predisposed to folate deficiency
• Avoid large loading doses in patients with a history of seizures
• Use with caution in pregnancy (theoretical teratogenic risk in the first trimester)

Pregnancy

High doses are teratogenic in the first trimester; however, in malaria, the benefit of treatment may outweigh the risks.

Breast-feeding

Present in milk but not known to be harmful; adequate folate supplements should be given to the mother. Avoid breastfeeding during treatment of toxoplasmosis.

Storage

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

Formulations

• Daraprim 25 mg tablets
• Oral suspension

Indications

• Malaria caused by Plasmodium falciparum
• Rheumatoid arthritis
• Lupus erythematosus

Mechanism of action

The exact mechanism of action of amodiaquine is not completely understood. It is believed to inhibit heme polymerase activity, leading to an accumulation of free heme, which is toxic to malarial parasites. Amodiaquine binds to free heme, preventing its conversion to a less toxic form, and this drug-heme complex disrupts membrane function within the parasite. Additionally, it may interfere with protein synthesis by binding to nucleoproteins and intercalating into double-stranded DNA, inhibiting DNA and RNA polymerase. Furthermore, it is known to concentrate in the digestive vacuoles of the parasites, increasing vacuolar pH and impairing the parasite's ability to metabolize hemoglobin.

Pharmacodynamics

Amodiaquine is effective against malaria and exhibits anti-inflammatory properties. It can depress cardiac muscle function, impair conduction, and produce vasodilation, which may lead to hypotension. Other side effects include respiratory depression, diplopia, dizziness, and nausea. While its effectiveness is comparable to that of chloroquine, the development of resistance to amodiaquine has been documented. The drug's adverse effects and potential for toxicity necessitate monitoring during treatment.

Pharmacokinetics

Amodiaquine is well absorbed after oral administration. It undergoes hepatic metabolism, with its active metabolite contributing to its antimalarial effects. The pharmacokinetics can be influenced by factors such as hepatic function and concurrent medications. The elimination half-life of amodiaquine may vary, and it is important to consider individual patient factors when determining dosing regimens.

Contra-indications

• Hypersensitivity to amodiaquine or any of its components
• Severe liver impairment
• History of retinopathy related to 4-aminoquinoline derivatives
• Severe hematological disorders, including agranulocytosis and aplastic anemia

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Dizziness
• Diplopia
• Hypotension
• Cardiac arrhythmias
• Hepatotoxicity
• Skin rashes
• Agranulocytosis

Interactions

• May enhance effects of anticoagulants
• Concomitant use with other antimalarials may increase risk of toxicity
• Caution with drugs that can cause hepatotoxicity
• May affect the metabolism of drugs that are substrates for CYP450 enzymes

Precautions

• Monitor liver function during treatment
• Use with caution in patients with a history of cardiovascular disease
• Assess for signs of hematological disorders
• Consider potential for cross-resistance with other 4-aminoquinoline derivatives

Pregnancy

Amodiaquine should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. It is advised to refer to local guidelines.

Breast-feeding

Amodiaquine is excreted in breast milk. Caution is advised when administering to breastfeeding mothers.

Storage

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

Formulations

• Tablets
• Oral suspension

Indications

• Metabolic acidosis
• Acid-base imbalance
• Urinary alkalinization
• Treatment of certain poisonings
• Cardiac arrest in the context of metabolic acidosis

Dosage

Children: Refer to the BNF for Children for specific pediatric dosages, as they depend on the clinical condition

Adults: Refer to local guidelines and BNF for specific dosing recommendations as they may vary based on clinical condition and severity. General adult dosing for bicarbonate may range from 1 to 2 mEq/kg IV initially, followed by maintenance doses as needed.

Mechanism of action

Bicarbonate acts as a buffer that neutralizes excess acids in the body. It dissociates in solution to produce bicarbonate ions (HCO3-) which can react with hydrogen ions (H+) to form carbonic acid (H2CO3), subsequently leading to the production of carbon dioxide (CO2) and water (H2O). This process helps to raise the pH of the blood and other fluids, counteracting acidosis. Bicarbonate is involved in several metabolic pathways, including the urea cycle and various biosynthetic pathways.

Pharmacodynamics

Bicarbonate's primary pharmacodynamic effect is its ability to buffer hydrogen ions, thus increasing blood pH. This is essential in conditions such as metabolic acidosis, where the body accumulates excess acid. By raising blood pH, bicarbonate can help alleviate symptoms associated with acidemia, such as fatigue, confusion, and shortness of breath. Its effects can also influence the renal and respiratory systems to regulate acid-base homeostasis.

Pharmacokinetics

Bicarbonate is rapidly absorbed from the gastrointestinal tract. It is distributed throughout the body fluids, and its effects can be seen within minutes of administration. The kidneys play a significant role in bicarbonate homeostasis by reabsorbing bicarbonate from urine and excreting hydrogen ions. The elimination half-life can vary, depending on the patient's metabolic state and renal function.

Pregnancy

Use with caution. Consult with a healthcare provider before use.

Breast-feeding

Use with caution. Consult with a healthcare provider before use.

Storage

Store in a cool, dry place away from light.

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

• Hypovolemic shock
• Severe burns
• Postoperative fluid replacement
• Sepsis
• Trauma management

Dosage

Children: Refer to established guidelines for specific dosing, as it varies based on the type of colloidal solution used and the clinical condition being treated.

Adults: Refer to established guidelines for specific dosing, as it varies based on the type of colloidal solution used and the clinical condition being treated.

Mechanism of action

Colloidal solutions work by maintaining oncotic pressure in the blood, thus helping to retain fluid within the vascular system. This is primarily due to the large molecular weight of the colloidal particles, which cannot easily pass through capillary walls. The presence of colloids in the blood helps to draw water into the circulation, increasing blood volume and improving tissue perfusion.

Pharmacodynamics

The pharmacodynamics of colloidal solutions are centered on their ability to exert osmotic pressure, which helps maintain blood volume and pressure. This effect is particularly important in conditions such as hypovolemia and shock, where fluid replacement is necessary to restore hemodynamic stability. The efficacy of colloidal solutions can vary depending on the type of colloid used, as well as the underlying clinical condition being treated.

Pharmacokinetics

Colloidal solutions are typically administered intravenously and their pharmacokinetics can vary based on the specific formulation. Generally, colloids are distributed throughout the vascular compartment and have a longer duration of action compared to crystalloids, as they remain in circulation longer. The elimination of colloids is primarily through the reticuloendothelial system, where they are metabolized or eliminated by the liver and spleen. Factors such as particle size and composition can influence their distribution and clearance.

Adverse effects

• Allergic reactions
• Injection site reactions
• Nausea
• Vomiting
• Headache
• Fever

Precautions

• Use with caution in patients with known allergies to any component of the formulation
• Monitor for signs of hypersensitivity during administration
• Consider volume overload in patients with cardiac or renal impairment

Pregnancy

The safety of colloidal solutions during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether colloidal solutions are excreted in human milk. Caution should be exercised when administering to breastfeeding mothers.

Storage

Store at room temperature, protect from light, and do not freeze. Keep out of reach of children.

Formulations

• Colloidal silver
• Colloidal gold
• Colloidal iron
• Other metal colloids

Mechanism of action

The precise mechanism of action is not well-documented in the provided resources. However, compounds with similar molecular structures often interact with biological pathways through modulation of neurotransmitter systems or receptor activity.

Pharmacodynamics

Pharmacodynamics for compounds like Colour typically involve interactions at the cellular level, influencing physiological responses through receptor binding and modulation of signaling pathways. The specific effects and potency would depend on the context of use and formulation.

Pharmacokinetics

Information on the pharmacokinetics of Colour, including absorption, distribution, metabolism, and excretion, is not provided in the available resources. Generally, pharmacokinetic properties will vary significantly based on formulation and route of administration.

Pregnancy

Safety in pregnancy has not been established. Use only if the benefits outweigh the risks.

Breast-feeding

Caution is advised. There are no adequate studies in breastfeeding women.

Storage

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

Indications

• Used as a disintegrant in oral solid dosage forms
• Improves the bioavailability of poorly soluble drugs

Dosage

Children: Refer to specific formulation guidelines for dosage instructions, as croscarmellose sodium is used as an excipient.

Adults: Refer to specific formulation guidelines for dosage instructions, as croscarmellose sodium is used as an excipient.

Mechanism of action

Croscarmellose sodium acts by swelling and forming a gel-like consistency upon contact with moisture. This swelling property helps the disintegration of solid dosage forms, enhancing the release of the active pharmaceutical ingredient from the formulation, thereby promoting its absorption in the gastrointestinal tract.

Pharmacodynamics

Croscarmellose sodium enhances the rate of disintegration of solid dosage forms, which is crucial for the effective release of the active drug. The mechanism involves the rapid absorption of water, which leads to an increase in volume and pressure within the tablet matrix, ultimately causing it to break apart. This property improves the dissolution rate and bioavailability of the drug contained within the formulation.

Pharmacokinetics

Croscarmellose sodium is not absorbed in the gastrointestinal tract; therefore, it does not have systemic pharmacokinetics. It functions locally within the gastrointestinal lumen, facilitating the disintegration and dissolution of drugs. Its efficacy is dependent on the formulation composition, including the presence of other excipients and the physical characteristics of the dosage form.

Adverse effects

• Gastrointestinal disturbances
• Allergic reactions
• Bloating
• Abdominal pain

Precautions

• Use with caution in patients with known allergies to cellulose derivatives
• Monitor for gastrointestinal symptoms in predisposed individuals

Pregnancy

Croscarmellose is generally considered safe for use during pregnancy, but should be used under medical supervision.

Breast-feeding

Croscarmellose is not known to be excreted in breast milk and is considered safe during breastfeeding.

Storage

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

Formulations

• Tablets
• Capsules
• Powders

Indications

• Used as an excipient in solid dosage forms
• Facilitates drug disintegration and dissolution

Dosage

Children: Refer to specific product formulation guidelines as crospovidone is used as an excipient and does not have a direct dosage.

Adults: Refer to specific product formulation guidelines as crospovidone is used as an excipient and does not have a direct dosage.

Mechanism of action

Crospovidone acts by rapidly absorbing water and swelling upon contact with moisture. This action leads to the disintegration of solid dosage forms, thus increasing the surface area of the active ingredients and promoting their dissolution and subsequent absorption in the gastrointestinal tract. It does not affect the pH of the formulation, ensuring that the active ingredients remain stable.

Pharmacodynamics

Crospovidone exhibits properties that enhance the bioavailability of active ingredients in pharmaceutical formulations. Its ability to rapidly disintegrate tablets and capsules leads to quicker release and absorption of the drug into systemic circulation. As a disintegrant, it aids in the effective delivery of drugs that may otherwise be poorly soluble.

Pharmacokinetics

Crospovidone itself is not absorbed systemically when administered orally. It remains in the gastrointestinal tract, where it performs its function as a disintegrant. The pharmacokinetic profile of drugs formulated with crospovidone may be influenced by the enhanced dissolution and absorption rates provided by this excipient.

Pregnancy

Crospovidone is considered to have low toxicity and is generally regarded as safe for use during pregnancy, but specific studies are limited.

Breast-feeding

There is insufficient data on the excretion of crospovidone in human milk, but it is deemed safe for use during breastfeeding.

Storage

Store in a cool, dry place away from light and moisture, in tightly closed containers.

Formulations

• Powder
• Tablets

Indications

• Food coloring agent
• Pharmaceutical coloring agent
• Diagnostic agent in certain imaging procedures

Dosage

Children: Refer to specific preparations for paediatric dosing as it may vary widely depending on the formulation and intended use.

Adults: Refer to specific preparations for adult dosing as it may vary widely depending on the formulation and intended use.

Mechanism of action

Erythrosine acts as a fluorescent dye, absorbing light in the visible spectrum and emitting it at a different wavelength. It binds to proteins and nucleic acids, which can affect biological processes such as cell division and apoptosis. Erythrosine's mechanism also involves interaction with cellular membranes, potentially influencing membrane integrity and function.

Pharmacodynamics

Erythrosine exhibits properties as a photosensitizer, with its efficacy increasing under light exposure. It can impact cellular activity by generating reactive oxygen species when activated by light, leading to oxidative stress in cells. This mechanism is utilized in certain therapeutic applications, although it is primarily recognized for its colorant properties.

Pharmacokinetics

Erythrosine is absorbed from the gastrointestinal tract when ingested, with peak plasma concentrations occurring shortly after administration. It is distributed throughout the body and is known to cross biological membranes. The compound is primarily excreted via urine, with some metabolites detected, indicating hepatic metabolism. The elimination half-life of erythrosine is variable and influenced by individual physiology and dosage.

Contra-indications

• Hypersensitivity to erythrosine or any of its components
• Thyroid disorders
• Patients with iodine allergy

Adverse effects

• Hypersensitivity reactions
• Thyroid dysfunction
• Nausea
• Vomiting
• Diarrhea
• Skin rashes

Interactions

• May interact with thyroid function tests, leading to false results
• Potential for interactions with other iodine-containing compounds

Precautions

• Use with caution in patients with a history of thyroid disease
• Monitor thyroid function in patients receiving long-term therapy
• Assess for allergic reactions prior to administration

Pregnancy

Erythrosine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult healthcare professional for advice.

Breast-feeding

It is not known whether erythrosine is excreted in human milk. Use with caution, considering the benefits and risks.

Storage

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

Formulations

• Oral suspension
• Injectable solution

Indications

• To enhance the palatability of oral medications
• To improve compliance in pediatric patients
• To mask unpleasant tastes of active pharmaceutical ingredients

Dosage

Children: Refer to specific formulations for guidance, as flavoring agents are typically used in very small quantities and are not dosed independently.

Adults: Refer to specific formulations for guidance, as flavoring agents are typically used in very small quantities and are not dosed independently.

Mechanism of action

Flavor compounds act primarily by stimulating taste receptors on the tongue, which can enhance the overall sensory experience of ingesting a product. Certain flavor compounds may also interact with olfactory receptors, contributing to the perception of flavor through smell. The stimulation of these receptors can lead to increased salivation and improved swallowing.

Pharmacodynamics

The use of flavoring agents in pharmaceuticals can influence compliance, particularly in children and individuals who may have difficulty swallowing pills. By enhancing the taste of a medication, these agents can reduce gag reflex and aversion, potentially improving therapeutic outcomes. However, the pharmacodynamic effects are largely dependent on the individual's taste preferences and sensitivities.

Pharmacokinetics

The pharmacokinetics of flavoring agents vary widely depending on the specific compounds used. Generally, these compounds are rapidly absorbed through the gastrointestinal tract upon ingestion, with their effects occurring within minutes. Some flavoring agents may undergo metabolism in the liver, while others may be excreted unchanged. The specific absorption, distribution, metabolism, and excretion (ADME) profiles depend on the chemical structure of each flavor compound.

Pregnancy

Generally considered safe, but specific flavoring agents may need to be evaluated individually.

Breast-feeding

Generally considered safe, but specific flavoring agents may need to be evaluated individually.

Storage

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

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

• Nutritional support
• Source of carbohydrates
• Dietary fiber source
• Animal feed

Dosage

Children: As with adults, there are no specific dosing recommendations for maize for children. It can be introduced into the diet in age-appropriate forms and quantities, keeping in mind the overall dietary balance.

Adults: There are no specific dosing recommendations for maize as it is typically consumed as part of a balanced diet. It can be included in daily meals in various forms such as whole kernels, flour, or as part of dishes.

Mechanism of action

Maize primarily acts as a source of energy due to its high carbohydrate content. The complex carbohydrates in maize are broken down into glucose, which is then utilized by the body for energy production. It also contributes to dietary fiber intake, which can aid in digestive health and regulation of blood sugar levels.

Pharmacodynamics

The consumption of maize influences blood glucose and insulin levels due to its carbohydrate content. It has a relatively low glycemic index when consumed in whole form, which can help in managing blood sugar levels. The dietary fiber present in maize can also promote satiety and aid in weight management.

Pharmacokinetics

The digestion of maize begins in the mouth with salivary amylase breaking down starches into simpler sugars. In the stomach and small intestine, enzymes further break down these carbohydrates. The resultant glucose is absorbed into the bloodstream, where it is transported to cells for energy production. The absorption rate can vary based on the form of maize consumed (e.g., whole kernels versus processed forms).

Pregnancy

Maize is generally considered safe for consumption during pregnancy as it is a staple food and provides essential nutrients.

Breast-feeding

Maize is safe to consume while breastfeeding and can provide important nutrients to both the mother and the infant.

Storage

Store in a cool, dry place, away from moisture and pests. Properly sealed containers can help prolong shelf life.

Formulations

• Whole maize grains
• Maize flour (cornmeal)
• Maize starch
• Maize oil

Indications

• Used as an excipient in tablet formulations
• Used in dietary supplements as a bulking agent

Dosage

Children: Refer to specific product formulations for dosage guidance as microcrystalline cellulose is an excipient.

Adults: Refer to specific product formulations for dosage guidance as microcrystalline cellulose is an excipient.

Mechanism of action

Microcrystalline cellulose functions primarily as an inert filler and binder in pharmaceutical formulations. It does not have a direct pharmacological activity but aids in the formulation of drugs by improving their physical properties, such as enhancing tablet hardness and disintegration.

Pharmacodynamics

As an inert substance, microcrystalline cellulose does not exert any therapeutic effects. Its role in formulations is critical for the stability and delivery of the active pharmaceutical ingredients. It ensures uniformity in dosage forms and contributes to the bioavailability of the drugs it accompanies.

Pharmacokinetics

Microcrystalline cellulose is not absorbed in the gastrointestinal tract and is excreted unchanged. It acts as a bulking agent and is considered safe for consumption. Its presence in formulations does not affect the pharmacokinetics of the active ingredients significantly.

Pregnancy

Microcrystalline cellulose is generally considered safe for use during pregnancy, as it is a non-toxic compound. However, it is always advised to consult a healthcare provider before use.

Breast-feeding

Microcrystalline cellulose is not absorbed systemically and is considered safe for use while breastfeeding. Consultation with a healthcare provider is recommended for specific concerns.

Storage

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

Formulations

• Tablets
• Capsules
• Powders

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.

Dosage

Children: Refer to BNF for Children for specific recommendations regarding the consumption of orange juice in children.

Adults: There is no standard dosage for orange juice as it is typically consumed as a beverage. Moderation is advised, especially for individuals on certain medications.

Mechanism of action

The exact mechanism of action of orange juice is not fully understood, but it is known to contain compounds that can influence the metabolism of certain drugs. For instance, it may affect the activity of cytochrome P450 enzymes, particularly CYP3A4, which can alter the pharmacokinetics of medications.

Pharmacodynamics

Orange juice is known to enhance the bioavailability of certain nutrients and may influence the pharmacological effects of some drugs. Its high vitamin C content contributes to various physiological functions, including antioxidant activity, which may indirectly support overall health.

Pharmacokinetics

The pharmacokinetics of orange juice itself are not extensively studied, but it is generally absorbed well through the gastrointestinal tract. The compounds in orange juice can affect the absorption and metabolism of medications, leading to varied clinical effects depending on the drug in question.

Interactions

• orange juice + celiprolol: Unknown (decreases exposure)

Formulations

• juice
• whole fruit

Indications

• Topical antiseptic for skin disinfection
• Surgical scrubs and hand sanitizers
• Wound care management
• Pharmaceutical excipient in solid and liquid formulations

Dosage

Children: Refer to specific product guidelines for pediatric dosing recommendations, as doses can vary based on formulation and intended use.

Adults: Refer to specific product guidelines for dosing recommendations, as doses can vary based on the formulation and intended use.

Mechanism of action

Povidone acts by forming a complex with iodine when used as an antiseptic, which releases iodine slowly to exert its antimicrobial effect. The iodine disrupts microbial cell walls and interferes with protein synthesis, leading to cell death. Additionally, as a polymer, povidone can enhance drug solubility and stability by forming a hydrophilic matrix.

Pharmacodynamics

Povidone has a broad spectrum of antimicrobial activity against bacteria, viruses, and fungi. Its antiseptic properties are primarily due to the release of iodine, which is effective in reducing microbial load and preventing infection. The polymer's ability to bind to various substances allows it to be utilized in formulations that require improved stability and solubility.

Pharmacokinetics

Povidone is not absorbed systemically when applied topically, as it remains localized at the site of application. Its pharmacokinetics are largely dependent on the formulation and route of administration, with the polymer being metabolized by hydrolysis and excreted in urine as low-molecular-weight compounds. The release and activity of iodine are influenced by the concentration of povidone and the presence of organic matter.

Adverse effects

• Local irritation
• Allergic reactions
• Skin rashes
• Hypersensitivity reactions

Precautions

• Use with caution in patients with known allergies to iodine or povidone-iodine
• Avoid use in deep puncture wounds or serious burns

Pregnancy

Povidone is generally considered safe for use during pregnancy, but it is advisable to consult a healthcare professional before use.

Breast-feeding

Povidone is considered safe during breastfeeding, but it is recommended to consult a healthcare professional.

Storage

Store at room temperature, away from moisture and heat. Keep the container tightly closed.

Formulations

• Topical solution
• Ointment
• Surgical scrub
• Gauze impregnated with povidone-iodine

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.

Indications

• Silicosis
• Chronic obstructive pulmonary disease (COPD)
• Lung cancer associated with silica exposure

Dosage

Adults: Silica is not administered as a drug, but rather

Mechanism of action

Silica, particularly crystalline forms like quartz and cristobalite, can induce cytotoxicity and morphological transformation in cells. The cytotoxic effects are attributed to the presence of silanol groups and trace iron on the silica surface, which can generate reactive oxygen species. These interactions lead to cellular damage and transformation, suggesting multiple molecular mechanisms underlying silica's biological effects. The activity is sensitive to the silica's surface structure and composition, indicating that the biological response is a phenomenon originating from the silica's surface characteristics.

Pharmacodynamics

Silica's pharmacodynamic effects are largely related to its cytotoxic and transforming properties, particularly in lung tissue. The inhalation of crystalline silica can lead to the activation of inflammatory pathways, oxidative stress, and apoptosis in alveolar macrophages and epithelial cells. This can result in chronic inflammation, fibrosis, and ultimately, diseases such as silicosis and lung cancer. The degree of these effects varies based on the type of silica, its crystalline structure, and the presence of surface modifications.

Pharmacokinetics

The pharmacokinetics of silica is complex as it is not absorbed systemically when inhaled or ingested. Instead, inhaled silica particles can deposit in the alveolar region of the lungs, where they may persist for long periods. The body responds to silica exposure through inflammatory processes, and macrophages attempt to phagocytize silica particles. However, the persistence of these particles can lead to chronic lung conditions. Clearance mechanisms are inefficient, leading to prolonged retention in lung tissue.

Adverse effects

• Cytotoxicity
• Morphological transformation of cells
• Respiratory issues
• Silicosis
• Lung cancer

Precautions

• Use caution in occupational settings with silica dust exposure
• Regular monitoring of lung function in exposed individuals

Pregnancy

There is insufficient data on the effects of silica on pregnancy. It is advised to minimize exposure.

Breast-feeding

Limited data available; caution is advised due to potential respiratory effects.

Storage

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

Formulations

• Crystalline silica
• Amorphous silica (diatomaceous earth)
• Silica gel

Indications

• Administration of drugs requiring solubilization
• Intravenous fluid therapy
• Oral rehydration solutions

Dosage

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

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

The mechanism of action of soluble compounds typically involves their ability to dissociate in solution, allowing for increased bioavailability and enhanced pharmacological effects. In some cases, they may act as osmotic agents or facilitate the transport of drugs across biological membranes.

Pharmacodynamics

Pharmacodynamics of soluble compounds generally relates to their effects on the body, including their interaction with receptors, enzymes, or cellular pathways. The solubility enhances the distribution of the drug, leading to more predictable and effective therapeutic outcomes.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion of soluble compounds. Due to their solubility, these compounds are typically absorbed quickly into the bloodstream when administered orally or intravenously. They may undergo metabolism in the liver, and their elimination primarily occurs through renal pathways, depending on the specific compound and its formulation.

Indications

• Nutritional supplementation
• Energy source in enteral nutrition
• Excipient in pharmaceutical formulations

Dosage

Children: Refer to specific guidelines or product inserts for dosing information, as it can vary based on the context of use.

Adults: Refer to specific guidelines or product inserts for dosing information, as it can vary based on the context of use.

Mechanism of action

Starch is broken down into glucose units by enzymes such as amylase during digestion. The glucose is then absorbed in the intestines and utilized for energy production in the body's cells. This pathway involves hydrolysis of the glycosidic bonds, converting starch into simpler sugars.

Pharmacodynamics

Starch primarily serves as an energy source. Its digestion and absorption lead to an increase in blood glucose levels, which provides energy for metabolic processes. In this context, it plays a crucial role in maintaining energy homeostasis in the body.

Pharmacokinetics

Starch is not absorbed in its polymeric form; it must first be enzymatically hydrolyzed into simpler sugars such as maltose and glucose. The digestion and absorption of starch occur predominantly in the small intestine, with glucose being readily absorbed into the bloodstream. The rate of absorption can vary depending on the type of starch and its physical form.

Adverse effects

• Allergic reactions
• Gastrointestinal discomfort
• Diarrhea
• Constipation

Precautions

• Use with caution in individuals with known allergies to starch or starch derivatives
• Monitor for gastrointestinal symptoms in patients with a history of digestive disorders

Pregnancy

Starch is generally considered safe for use during pregnancy. However, it should be consumed in moderation as part of a balanced diet.

Breast-feeding

Starch is deemed safe for nursing mothers when used in moderation as part of a balanced diet.

Storage

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

Formulations

• Powder
• Granules
• Tablets
• Suspensions

Indications

• Caloric reduction in food and beverages
• Management of diabetes
• Weight management

Dosage

Children: Refer to the BNF for Children for specific guidelines on the use of sucralose in pediatric populations.

Adults: Sucralose is typically used in food and beverage products as a sweetener. There are no specific dosage recommendations for adults, as it is used according to taste preference and product formulation.

Mechanism of action

Sucralose acts as a positive allosteric modulator of the human sweet taste receptor. It interacts with the T1R taste receptor family, particularly enhancing the sweetness perception by binding to the hinge region of the receptor. This interaction induces a conformational change that stabilizes the active state of the receptor, increasing its responsiveness to sweet stimuli. This mechanism allows sucralose to mimic the taste of sugar without the associated caloric intake.

Pharmacodynamics

As a non-nutritive sweetener, sucralose does not undergo metabolic processing in the body, which means it does not contribute to energy intake. It provides intense sweetness at low concentrations, stimulating the sweetness receptors in the taste buds. The pharmacodynamic profile indicates minimal physiological effects beyond taste perception, making it suitable for dietary use without impacting blood glucose levels.

Pharmacokinetics

Sucralose is poorly absorbed in the gastrointestinal tract, with an estimated absorption rate of less than 15%. The majority of ingested sucralose is excreted unchanged in the urine. The elimination half-life is not well defined due to its minimal absorption, but it is generally considered to have a rapid clearance from the body. The pharmacokinetic properties support its use as a safe alternative to sugar for those managing caloric intake.

Pregnancy

Sucralose is generally considered safe during pregnancy, but it is recommended to consult a healthcare provider.

Breast-feeding

Sucralose is also considered safe during breastfeeding, although it is advisable to seek medical advice.

Storage

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

Formulations

• Granulated sucralose
• Liquid sucralose
• Tablets

Indications

• Treatment of malaria caused by Plasmodium falciparum
• Prevention of malaria in individuals traveling to endemic areas

Dosage

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

Adults: Refer to BNF for specific dosing information.

Mechanism of action

Sulfadoxine acts as an antimetabolite by competitively inhibiting the enzyme dihydropteroate synthase, which is crucial for the synthesis of folic acid from para-aminobenzoic acid (PABA). This inhibition disrupts the folic acid production necessary for DNA synthesis and cellular growth in the Plasmodium species, particularly P. falciparum, thereby impairing its ability to reproduce.

Pharmacodynamics

Sulfadoxine's inhibition of dihydropteroate synthetase leads to a decrease in folic acid levels within the parasite. Folic acid is essential for the synthesis, repair, and methylation of DNA, and its deficiency hampers the growth and replication of Plasmodium falciparum, thereby aiding in the treatment of malaria.

Pharmacokinetics

Sulfadoxine is well-absorbed after oral administration, with peak plasma concentrations typically reached within 4 to 6 hours. It has a long half-life, allowing for once-daily dosing in many cases. The drug is metabolized in the liver and excreted primarily via the kidneys. Its pharmacokinetic profile supports its use in combination therapies for malaria, as it maintains therapeutic levels over extended periods.

Contra-indications

• Hypersensitivity to sulfadoxine or other sulfonamides
• Severe liver or kidney impairment
• Pregnancy at term
• Infants under 2 months of age

Adverse effects

• Nausea
• Vomiting
• Rash
• Fever
• Anemia
• Leukopenia
• Thrombocytopenia
• Hepatotoxicity
• Stevens-Johnson syndrome

Interactions

• May enhance the effects of anticoagulants such as warfarin
• May interact with methotrexate, increasing its toxicity
• May reduce the effectiveness of certain oral contraceptives

Precautions

• Monitor for signs of hypersensitivity reactions
• Use cautiously in patients with G6PD deficiency
• Assess renal function prior to and during therapy

Pregnancy

Use is contraindicated at term due to the risk of kernicterus in the neonate. Caution is advised during the first and second trimesters.

Breast-feeding

Sulfadoxine is excreted in breast milk; caution is advised when administering to breastfeeding mothers.

Storage

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

Formulations

• Sulfadoxine 500 mg tablets
• Sulfadoxine/pyrimethamine combination tablets

Indications

• Used as an excipient in drug formulations
• Pleurodesis for the management of recurrent pleural effusions

Dosage

Children: Refer to specific guidelines for paediatric use, as dosing may differ based on age and clinical condition.

Adults: Refer to specific guidelines for the appropriate dosage in pleurodesis and other applications, as it may vary based on clinical context.

Mechanism of action

Talc exhibits very good absorptive properties, allowing it to absorb moisture and other substances effectively. This characteristic is particularly useful in pharmaceutical formulations, where it may enhance the stability and texture of the drug product.

Pharmacodynamics

Talc's primary pharmacodynamic effect is its ability to act as an inert filler and bulking agent in pharmaceutical preparations. It does not have any intrinsic pharmacological activity but serves to improve the physical properties of formulations, such as flowability and compressibility.

Pharmacokinetics

Talc is not absorbed systemically when used as an excipient or in medical procedures. Its effects are local, and it remains in the site of application, where it functions primarily as a mechanical agent. The pharmacokinetics of talc in the context of its use in pleurodesis involves its ability to promote adhesion of the pleural surfaces, thereby preventing fluid accumulation.

Pregnancy

Talc is classified as a substance with minimal systemic absorption, but safety during pregnancy has not been well established. Consult relevant guidelines.

Breast-feeding

Talc is not expected to be absorbed in significant amounts; however, caution is advised and consult guidelines.

Storage

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

Indications

• Flavoring agent in food and beverages
• Aromatherapy for stress relief
• Potential antioxidant supplementation

Dosage

Children: Refer to specific product guidelines for appropriate dosing, as pediatric doses can differ significantly based on age and formulation.

Adults: Refer to specific product guidelines for appropriate dosing as it may vary based on the form (e.g., extract, powder) and intended use.

Mechanism of action

The primary active component of vanilla, vanillin, acts as an antioxidant by scavenging free radicals, which helps to mitigate oxidative stress. It may also engage in various metabolic pathways including the degradation of vanillin and vanillate, contributing to its bioavailability and therapeutic effects.

Pharmacodynamics

Vanilla exhibits several pharmacodynamic properties, including its ability to enhance flavor perception and stimulate appetite. The antioxidant properties of vanillin can reduce cellular damage and support overall health. Additionally, it may influence mood and cognition through its aromatic compounds, which have been associated with improved psychological well-being.

Pharmacokinetics

Vanilla is typically consumed orally and is absorbed in the gastrointestinal tract. The bioavailability of vanillin can vary based on the formulation and method of consumption. Once absorbed, vanillin is metabolized in the liver and excreted primarily through urine. The half-life and exact pharmacokinetic parameters of vanilla compounds can differ based on individual metabolism and the presence of other substances.

Pregnancy

Vanilla is generally considered safe during pregnancy when used in food amounts. However, high concentrations or extracts should be used cautiously.

Breast-feeding

Vanilla is likely safe during breastfeeding when used in food amounts, but should be used cautiously in higher concentrations.

Storage

Store in a cool, dry place away from direct sunlight. Keep tightly closed to maintain flavor and prevent contamination.

Formulations

• Vanilla extract
• Vanilla powder
• Vanilla bean

Mechanism of action

Pyrimethamine inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which are essential for DNA synthesis and cell multiplication. This leads to failure of nuclear division at the time of schizont formation in erythrocytes and liver. Pyrimethamine is an antimalarial drug that has also been used successfully to treat autoimmune diseases such as lymphoproliferative syndrome. In this work, the effect of pyrimethamine (PYR) on the production of free radicals in malaria-infected mice was studied to better understand the drug's immunomodulatory properties. BALB/c and CBA/Ca mice were infected with Plasmodium yoelii 17XL. Seven days after infection, mice were treated with PYR or vehicle and sacrificed 24h later. Treatment with PYR increased superoxide dismutase and glutathione peroxidase activities in erythrocytes and the liver, augmented the levels of nitric oxide in the serum, and upregulated mRNA levels of superoxide dismutase, glutathione peroxidase, catalase, and iNOS in the spleen. In addition, PYR increased lipoperoxidation and protein carbonylation in infected mice. Our results indicate that P. yoelii 17XL reduces oxidative stress in infected cells, while PYR induces it, which is associated with increased parasite elimination. Thus, it is possible that oxidative stress generated by pyrimethamine is also involved in its immunomodulatory mechanism of action. Co-infection of human immunodeficiency virus (HIV) with malaria is one of the pandemic problems in Africa and parts of Asia. Here we investigated the impact of pyrimethamine (PYR) and two other clinical anti-malarial drugs (chloroquine [CQ] or artemisinin [ART]) on HIV-1 replication. Peripheral blood mononuclear cells (PBMCs) or MT-2 cells were infected with HIV(NL4.3) strain and treated with different concentrations of the anti-malarial drugs. HIV-1 replication was measured using p24 ELISA. We show that 10 uM CQ and ART inhibited HIV-1 replication by 76% and 60% in PBMCs, respectively, but not in MT-2 cells. In contrast, 10 uM PYR enhanced HIV-1 replication in MT-2 cells by >10-fold. A series of molecular mechanism studies revealed that PYR increased intracellular HIV gag proteins without affecting the promoter or the reverse transcriptase activity. The effect of PYR was independent of HTLV-1 produced by MT-2 cells. Of interest, PYR treatment led to S-phase accumulation and increased AZT and d4T antiviral activity by ~ 4-fold. Taken together, we show that PYR significantly enhances HIV-1 replication by affecting the cellular machinery. Our results could be relevant for the management of malaria and HIV particularly in regions where HIV-1 and malaria epidemics overlap. Autosomal dominant polycystic kidney disease (ADPKD) is a commonly inherited disorder mostly caused by mutations in PKD1, encoding polycystin-1 (PC1). The disease is characterized by development and growth of epithelium-lined cyst in both kidneys, often leading to renal failure. There is no specific treatment for this disease. Here, we report a sustained activation of the transcription factor signal transducer and activator of transcription 3 (STAT3) in ischemic injured and uninjured Pkd1 knockout polycystic kidneys and in human ADPKD kidneys. Through a chemical library screen, we identified the anti-parasitic compound pyrimethamine as an inhibitor of STAT3 function. Treatment with pyrimethamine decreases cell proliferation in human ADPKD cells and blocks renal cyst formation in an adult and a neonatal PKD mouse model. Moreover, we demonstrated that a specific STAT3 inhibitor, S3I-201, reduces cyst formation and growth in a neonatal PKD mouse model. Our results suggest that PC1 acts as a negative regulator of STAT3 and that blocking STAT3 signaling with pyrimethamine or similar drugs may be an attractive therapy for human ADPKD. The unresponsiveness of metastatic melanoma to conventional chemotherapeutic and biological agents is largely due to the de

Pharmacodynamics

Pyrimethamine is an antiparasitic compound commonly used as an adjunct in the treatment of uncomplicated, chloroquine resistant, P. falciparum malaria. Pyrimethamine is a folic acid antagonist and the rationale for its therapeutic action is based on the differential requirement between host and parasite for nucleic acid precursors involved in growth. This activity is highly selective against plasmodia and Toxoplasma gondii. Pyrimethamine possesses blood schizonticidal and some tissue schizonticidal activity against malaria parasites of humans. However, the 4-amino-quinoline compounds are more effective against the erythrocytic schizonts. It does not destroy gametocytes, but arrests sporogony in the mosquito. The action of pyrimethamine against Toxoplasma gondii is greatly enhanced when used in conjunction with sulfonamides.

Mechanism of action

The mechanism of plasmodicidal action of amodiaquine is not completely certain. Like other quinoline derivatives, it is thought to inhibit heme polymerase activity. This results in accumulation of free heme, which is toxic to the parasites. The drug binds the free heme preventing the parasite from converting it to a form less toxic. This drug-heme complex is toxic and disrupts membrane function. Amodiaquine is a Mannich base 4-aminoquinoline with a mode of action similar to that of chloroquine. It is effective against some chloroquine-resistant strains of P. falciparum, although there is cross-resistance. The 4-aminoquinoline derivatives appear to bind to nucleoproteins and interfere with protein synthesis in susceptible organisms; the drugs intercalate readily into double-stranded DNA and inhibit both DNA and RNA polymerase. In addition, the drugs apparently concentrate in parasite digestive vacuoles, increase the pH of the vacuoles, and interfere with the parasite's ability to metabolize and utilize erythrocyte hemoglobin. Plasmodial forms that do not have digestive vacuoles and do not utilize hemoglobin, such as exoerythrocytic forms, are not affected by /these medications/. The 4-aminoquinoline derivatives ... have anti-inflammatory activity; however, the mechanism(s) of action of the drugs in the treatment of rheumatoid arthritis and lupus erythematosus has not been determined. /4-aminoquinoline derivatives/ reportedly antagonizes histamine in vitro, has antiserotonin effects, and inhibits prostaglandin effects in mammalian cells presumably by inhibiting conversion of arachidonic acid to prostaglandin F2. The mode of action of amodiaquine has not yet been determined. 4-Aminoquinolines depress cardiac muscle, impair cardiac conductivity, and produce vasodilatation with resultant hypotension; they depress respiration and cause diplopia, dizziness and nausea.

Pharmacodynamics

Amodiaquine, a 4-aminoquinoline similar to chloroquine in structure and activity, has been used as both an antimalarial and an anti-inflammatory agent for more than 40 years. Amodiaquine is at least as effective as chloroquine, and is effective against some chloroquine-resistant strains, although resistance to amodiaquine has been reported. The mode of action of amodiaquine has not yet been determined. 4-Aminoquinolines depress cardiac muscle, impair cardiac conductivity, and produce vasodilatation with resultant hypotension. They depress respiration and cause diplopia, dizziness and nausea.

Mechanism of action

...Some quartz and cristobalite dusts (crystalline) as well as the diatomaceous earths (amorphous), but not the pyrogenic amorphous silica, were cytotoxic and induced morphological transformation of SHE cells in a concentration-dependent manner. The ranking in cytotoxicity was different from that in transforming potency, suggesting two separate molecular mechanisms for the two effects. The cytotoxic and transforming potencies were different from one dust to another, even among the same structural silicas. The type of crystalline structure (quartz vs cristobalite) and the crystalline vs biogenic amorphous form did not correlate with cytotoxic or transforming potency of silica dusts. Comparison of cellular effects induced by original and surface modified samples revealed that several surface functionalities modulate cytotoxic and transforming potencies. The cytotoxic effects appeared to be related to the distribution and abundance of silanol groups and to the presence of trace amounts of iron on the silica surface. Silica particles with fractured surfaces and/or iron-active sites, able to generate reactive oxygen species, induced SHE cell transformation. The results show that the activity of silica at the cellular level is sensitive to the composition and structure of surface functionalities and confirm that the biological response to silica is a surface originated phenomenon. In vivo exposure of rat lungs to crystalline silica either by intratracheal instillation or by inhalation results in an increase in mRNA levels for inducible nitric oxide synthase (iNOS) in bronchoalveolar lavage cells (BALC), elevated nitric oxide (.NO) production by BALC, and an increase in .NO-dependent chemiluminescence (CL) from alveolar macrophages (AM). Induction of iNOS message occurs in both AM and polymorphonuclear leukocytes (PMN) harvested from silica-exposed lungs but is not significantly elevated in lavaged lung tissue. This review presents characteristics of simple and complicated coal workers' pneumoconiosis (CWP) as well as pathologic indices of acute and chronic silicosis by summarizing results of in vitro, animal, and human investigations. These results support four basic mechanisms in the etiology of CWP and silicosis: a) direct cytotoxicity of coal dust or silica, resulting in lung cell damage, release of lipases and proteases, and eventual lung scarring; b) activation of oxidant production by pulmonary phagocytes, which overwhelms the antioxidant defenses and leads to lipid peroxidation, protein nitrosation, cell injury, and lung scarring; c) activation of mediator release from alveolar macrophages and epithelial cells, which leads to recruitment of polymorphonuclear leukocytes and macrophages, resulting in the production of proinflammatory cytokines and reactive species and in further lung injury and scarring; d) secretion of growth factors from alveolar macrophages and epithelial cells, stimulating fibroblast proliferation and eventual scarring. Results of in vitro and animal studies provide a basis for proposing these mechanisms for the initiation and progression of pneumoconiosis. Data obtained from exposed workers lend support to these mechanisms. /The authors/ reported previously that freshly fractured silica (FFSi) induces activator protein-1 (AP-1) activation through extracellular signal-regulated protein kinases (ERKs) and p38 kinase pathways. In the present study, the biologic activities of FFSi and aged silica (ASi) were compared by measuring their effects on the AP-1 activation and phosphorylation of ERKs and p38 kinase. The roles of reactive oxygen species (ROS) in this silica-induced AP-1 activation were also investigated. FFSi-induced AP-1 activation was four times higher than that of ASi in JB6 cells. FFSi also caused greater phosphorylation of ERKs and p38 kinase than ASi. FFSi generated more ROS than ASi when incubated with the cells as measured by electron spin resonance (ESR). Studies using ROS-sensitive dyes and

Mechanism of action

Positive allosteric modulators of the human sweet taste receptor ...developed as a new way of reducing dietary sugar intake .../can be used as/ ...valuable tool molecules to study the general mechanism of positive allosteric modulations of T1R taste receptors. Using chimeric receptors, mutagenesis, and molecular modeling, .../the study/ reveal how ...sweet enhancers follow a similar mechanism as the natural umami taste enhancer molecules. Whereas the sweeteners bind to the hinge region and induce the closure of the Venus flytrap domain of T1R2, the enhancers bind close to the opening and further stabilize the closed and active conformation of the receptor.

Mechanism of action

Sulfadoxine is a sulfa drug, often used in combination with pyrimethamine to treat malaria. This medicine may also be used to prevent malaria in people who are living in, or will be traveling to, an area where there is a chance of getting malaria. Sulfadoxine targets Plasmodium dihydropteroate synthase and dihydrofolate reductase. Sulfa drugs or Sulfonamides are antimetabolites. They compete with para-aminobenzoic acid (PABA) for incorporation into folic acid. The action of sulfonamides exploits the difference between mammal cells and other kinds of cells in their folic acid metabolism. All cells require folic acid for growth. Folic acid (as a vitamin) diffuses or is transported into human cells. However, folic acid cannot cross bacterial (and certain protozoan) cell walls by diffusion or active transport. For this reason bacteria must synthesize folic acid from p-aminobenzoic acid.

Pharmacodynamics

Sulfadoxine helps inhibit the enzyme dihydropteroate synthetase which is an enzyme necessary in the conversion of PABA to folic acid. As folic acid is vital to the synthesis, repair, and methylation of DNA which is vital to cell growth in Plasmodium falciparum. With this vital nutrient lacking, the parasite has difficulty in reproducing.

Mechanism of action

It has very good absorptive properties.