Artefan Dispersible

Indications

• Uncomplicated malaria caused by Plasmodium falciparum
• Malaria treatment in combination with lumefantrine

Dosage

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

Adults: Refer to specific guidelines; typically, artemether is administered in a combination therapy regimen with lumefantrine.

Mechanism of action

Artemether interacts with ferriprotoporphyrin IX (heme) in the acidic vacuole of malaria parasites, leading to the generation of cytotoxic radical species. This interaction involves the activation of the drug by reduced heme or ferrous iron, resulting in the formation of oxygen-centered radicals that subsequently convert into carbon-centered radicals. These radicals are toxic to the parasites, thereby inhibiting their growth and reproduction.

Pharmacodynamics

Artemether is rapidly metabolized to its active metabolite, dihydroartemisinin. It primarily targets the erythrocytic stages of Plasmodium falciparum by inhibiting nucleic acid and protein synthesis. The drug has a rapid onset of action, providing quick symptomatic relief by significantly reducing the number of circulating malarial parasites. In combination therapy with lumefantrine, artemether enhances overall treatment effectiveness and contributes to a higher clinical cure rate.

Pharmacokinetics

Artemether is absorbed quickly, with a rapid onset of action. It is metabolized in the liver to dihydroartemisinin, which is the active form responsible for its antimalarial effects. The drug is eliminated from the body relatively quickly, while lumefantrine, which has a longer half-life, aids in clearing any residual parasites. This pharmacokinetic profile supports the use of artemether in combination therapies for malaria.

Adverse effects

• nausea
• vomiting
• dizziness
• headache
• fatigue
• abdominal pain
• anemia
• QT prolongation

Interactions

• mitotane+artemether with lumefantrine: Severe (decreases exposure)
• mitotane+artemether: Severe (decreases exposure)
• rifampicin+artemether: Severe (decreases exposure)
• grapefruit juice+artemether: Unknown (increases exposure)
• efavirenz+artemether: Unknown (decreases concentration)
• etravirine+artemether: Unknown (decreases exposure)

Precautions

• Monitor for signs of hypersensitivity reactions
• Use with caution in patients with pre-existing QT prolongation
• Assess liver function before use, as hepatic impairment may alter drug metabolism

Pregnancy

Artemether is categorized as pregnancy category C. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Artemether is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Protect from light.

Formulations

• artemether/lumefantrine combination tablets
• artemether oral solution

Dosage

Children: Refer to the specific product guidelines for appropriate use, as dosages may vary depending on the product formulation.

Adults: Refer to the specific product guidelines for appropriate use, as dosages may vary depending on the product formulation.

Mechanism of action

Aspartame is metabolized into aspartic acid, phenylalanine, and methanol. These components are then absorbed into the bloodstream and utilized in normal physiological processes, similar to how these amino acids are used when derived from protein-rich foods.

Pharmacodynamics

Aspartame functions as a low-calorie sweetener, providing sweetness without significant caloric contribution. It is composed of naturally occurring amino acids, aspartic acid and phenylalanine, which are utilized by the body in the same way as those derived from dietary proteins. The sweetening effect of aspartame is primarily due to its high sweetness potency compared to sucrose.

Pharmacokinetics

Upon ingestion, aspartame is hydrolyzed in the gastrointestinal tract into its individual components: aspartic acid, phenylalanine, and methanol. These metabolites are then absorbed into the bloodstream. They do not accumulate in the body and are utilized in metabolic processes similar to those of their natural counterparts found in food.

Contra-indications

• Phenylketonuria (PKU)

Adverse effects

• Headaches
• Allergic reactions
• Gastrointestinal disturbances
• Mood changes

Precautions

• Use with caution in individuals with phenylketonuria due to phenylalanine content.

Pregnancy

Considered safe for use during pregnancy, but it is advisable to consult with a healthcare provider.

Breast-feeding

Considered safe for use during breastfeeding, but it is advisable to consult with a healthcare provider.

Storage

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

Formulations

• Tablets
• Powder
• Liquid sweeteners

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

Indications

• Used as a disintegrant in solid dosage forms
• Improves dissolution rate of active ingredients

Dosage

Children: Refer to specific product information or formulation guidelines as dosages can vary based on formulation and intended use.

Adults: Refer to specific product information or formulation guidelines as dosages can vary based on formulation and intended use.

Mechanism of action

Crospovidone acts by absorbing water and swelling, which leads to the disintegration of the tablet or capsule material. This process increases the surface area of the active ingredient, promoting faster dissolution and absorption in the gastrointestinal tract.

Pharmacodynamics

The pharmacodynamic properties of crospovidone are primarily related to its function as a disintegrant. By rapidly breaking down the dosage form upon contact with moisture, it allows for quicker release of the active ingredient. This mechanism is crucial for enhancing the bioavailability of poorly soluble drugs, thereby improving therapeutic efficacy.

Pharmacokinetics

Crospovidone is not absorbed systemically when administered orally, as it remains in the gastrointestinal tract. It is excreted unchanged in the feces. Due to its nature as an excipient, its pharmacokinetic profile is not typically characterized in the same manner as that of active pharmaceutical ingredients.

Adverse effects

• Allergic reactions
• Skin irritation
• Gastrointestinal disturbances

Precautions

• Use with caution in patients with known hypersensitivity to povidone or other related compounds
• Avoid contact with eyes, as it may cause irritation

Pregnancy

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

Breast-feeding

It is not known whether crospovidone is excreted in human milk. Use with caution.

Storage

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

Formulations

• Powder for oral solution
• Tablet

Indications

• Enhancement of taste in food and beverages
• Improvement of palatability in nutritional products
• Masking undesirable flavors in medications

Dosage

Children: There is no specific pediatric dosage for flavor agents as they are used as needed to improve the taste of food and beverages.

Adults: There is no specific dosage for flavor agents as they are used as needed to achieve the desired taste and aroma in food and beverages.

Mechanism of action

Flavor compounds interact with taste receptors on the tongue, stimulating the sensory neurons responsible for taste perception. This interaction influences the overall flavor profile of food and beverages, enhancing the eating experience. Some flavors may also have a psychological effect, stimulating appetite or evoking pleasant memories associated with certain tastes.

Pharmacodynamics

While flavor agents are primarily used for sensory enhancement in food, their pharmacodynamic effects are minimal as they are not designed to elicit a pharmacological response. However, certain flavors may influence digestion and metabolism indirectly by enhancing saliva production or affecting gut motility. The enjoyment of flavored products can also lead to increased food intake and satisfaction.

Pharmacokinetics

Flavour compounds are typically ingested and metabolized by the body. Their absorption rates can vary depending on their chemical structure and formulation. Once ingested, they may be rapidly metabolized in the liver and other tissues, with excretion primarily via urine. The specific pharmacokinetic profiles of flavor agents can vary significantly based on their source and chemical properties.

Pregnancy

Flavours are generally considered safe for use during pregnancy, but specific assessments should be made based on the type of flavouring agent.

Breast-feeding

Most flavouring agents are deemed safe during breastfeeding, although it's advisable to consult healthcare professionals regarding specific ingredients.

Storage

Store in a cool, dry place away from direct sunlight and heat sources. Ensure that the container is tightly sealed to prevent contamination.

Indications

• Uncomplicated malaria due to Plasmodium falciparum
• Coartem (lumefantrine and artemether) for rapid malaria treatment

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

The exact mechanism by which lumefantrine exerts its antimalarial effect is unknown. However, it is suggested that lumefantrine inhibits the formation of beta-hematin by forming a complex with hemin and inhibits nucleic acid and protein synthesis.

Pharmacodynamics

Lumefantrine is active against the erythrocytic stages of Plasmodium falciparum. When administered with artemether, it is believed to have cooperative antimalarial effects, with artemether providing rapid symptom relief and lumefantrine clearing residual parasites due to its longer half-life.

Pharmacokinetics

Lumefantrine has a long half-life, allowing for sustained effects after administration. It is absorbed from the gastrointestinal tract and is extensively metabolized in the liver. Its pharmacokinetic profile supports its use in combination therapy with rapidly acting agents like artemether.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Headache
• Fatigue
• Dizziness
• Palpitations

Interactions

• Drug interactions with artemether; co-administration may enhance antimalarial effects
• Potential interactions with drugs that affect liver enzymes, which may alter lumefantrine metabolism

Precautions

• Use with caution in patients with a history of cardiac arrhythmias
• Monitor for signs of hepatotoxicity in patients with pre-existing liver disease
• Consider potential for drug interactions in patients receiving multiple medications

Pregnancy

Lumefantrine should only be used in pregnancy if clearly needed; consult guidelines for specific considerations.

Breast-feeding

Use with caution while breastfeeding; consult healthcare provider for recommendations.

Storage

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

Formulations

• Tablets
• Oral suspension

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

• Irritable bowel syndrome
• Dyspepsia
• Nausea
• Headaches
• Respiratory congestion

Dosage

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

Adults: Refer to the relevant product-specific information for dosing recommendations, as peppermint formulations can vary widely.

Mechanism of action

The primary active component, menthol, works by activating the TRPM8 (transient receptor potential cation channel subfamily M member 8) ion channel, which is involved in the sensation of cold and cooling. This action can lead to a localized anesthetic effect, reducing pain and discomfort. Additionally, menthol can cause relaxation of smooth muscle in the gastrointestinal tract, aiding in the relief of digestive symptoms.

Pharmacodynamics

Peppermint exhibits antispasmodic effects, particularly in the gastrointestinal tract, by relaxing the smooth muscles. It also has a mild analgesic effect due to its cooling sensation, which can provide symptomatic relief in various conditions. Furthermore, peppermint oil may have antimicrobial properties, contributing to its use in treating certain infections.

Pharmacokinetics

Menthol is rapidly absorbed after oral administration and is metabolized in the liver. The peak plasma concentration typically occurs within a few hours. The elimination half-life of menthol is approximately 1.5 to 2 hours, and it is primarily excreted in the urine as metabolites. The pharmacokinetics of peppermint oil can vary based on the formulation and route of administration.

Interactions

• peppermint oil + lomitapide: Unknown (increases exposure)

Pregnancy

Peppermint is generally considered safe for use in pregnancy when used in culinary amounts. However, high doses should be avoided due to potential uterine stimulation.

Breast-feeding

Peppermint is considered safe during breastfeeding when used in culinary amounts. Caution is advised with high doses as effects on the infant are not well studied.

Storage

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

Formulations

• Peppermint oil
• Peppermint extract
• Peppermint tea

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

Dosage

Children: For paediatric dosing, consult the BNF for Children, as it provides essential dosing information tailored for children.

Adults: For dosing, refer to specific clinical guidelines or product information, as dosing can vary widely based on the specific drug and indication.

Mechanism of action

The mechanism of action for special drugs can vary significantly. Generally, these medications may work by modulating specific pathways involved in disease processes, such as inhibiting enzymes, blocking receptors, or altering neurotransmitter levels. For instance, some may act as agonists or antagonists at certain receptors, while others might influence cellular signaling pathways to achieve therapeutic effects.

Pharmacodynamics

Pharmacodynamics relates to the effects of special drugs on the body, including their therapeutic effects and side effects. The efficacy of these medications is often dose-dependent, and their action may involve a range of biological targets. The therapeutic window, which is the range between an effective dose and a toxic dose, is particularly crucial for special medications, necessitating precise dosing and monitoring.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion of special drugs. These parameters can significantly influence the drug's efficacy and safety profile. Factors such as bioavailability, half-life, volume of distribution, and clearance rates are critical in determining how the drug behaves in the body. Additionally, interactions with food and other medications can affect these pharmacokinetic profiles, requiring careful consideration in clinical practice.

Pregnancy

Consult healthcare provider, as risks may vary based on specific circumstances.

Breast-feeding

Consult healthcare provider, as risks and benefits should be evaluated.

Storage

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

Indications

• Thickening agent
• Stabilizer in pharmaceutical formulations
• Emulsifier in topical and oral medications

Dosage

Children: Refer to specific product guidelines, as dosing can vary based on formulation and indication.

Adults: Refer to specific product guidelines, as dosing can vary based on formulation and indication.

Mechanism of action

Substituted hydroxypropyl functions through the formation of hydrogen bonds within the polymeric structure, which increases viscosity and stabilizes emulsions. Its hydrophilic nature allows it to interact with water and other solvents, leading to improved formulation stability and bioavailability.

Pharmacodynamics

The pharmacodynamics of substituted hydroxypropyl relate primarily to its physical properties as a polysaccharide. It does not exert pharmacological effects in the traditional sense but influences the release profile of active pharmaceutical ingredients, thereby affecting their therapeutic outcomes.

Pharmacokinetics

Substituted hydroxypropyl is not absorbed systemically when used as an excipient, as it remains in the gastrointestinal tract or at the application site. It is metabolized minimally, if at all, and is excreted unchanged. Its action is predominantly local at the site of application or within the gastrointestinal lumen.

Pregnancy

Safety during pregnancy has not been established. Use only if clearly needed and potential benefits outweigh risks.

Breast-feeding

It is not known whether substituted hydroxypropyl is excreted in human milk. Caution is advised when administered to nursing women.

Storage

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

Indications

• Benign prostatic hyperplasia (BPH)

Dosage

Children: Not indicated for use in children; refer to appropriate pediatric guidelines for any related conditions.

Adults: Refer to the relevant prescribing information or guidelines for specific adult dosing recommendations.

Mechanism of action

Trusil acts by selectively inhibiting alpha-1A adrenergic receptors, which are predominantly located in the prostate and bladder neck. This inhibition leads to relaxation of the smooth muscle in these areas, thereby decreasing urinary obstruction and alleviating symptoms such as difficulty in urination, weak stream, and the sensation of incomplete bladder emptying.

Pharmacodynamics

Silodosin exerts its effects through selective antagonism of the alpha-1A adrenergic receptors, resulting in decreased smooth muscle tone in the prostate and bladder neck. This selective action minimizes cardiovascular side effects often associated with non-selective alpha blockers. The onset of action typically occurs within a few days, with peak effects observed within one to two weeks of continuous treatment.

Pharmacokinetics

Silodosin is well absorbed after oral administration, with a bioavailability of approximately 30%. It undergoes extensive hepatic metabolism, primarily by the cytochrome P450 enzyme system, particularly CYP3A4. The elimination half-life is around 13 hours, allowing for once-daily dosing. Silodosin is predominantly excreted via the feces, with a small percentage eliminated in the urine. Factors such as liver impairment can significantly affect its pharmacokinetics.

Contra-indications

• Hypersensitivity to trusil or any of its components
• Severe liver impairment
• Active peptic ulcer disease

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Dizziness
• Headache
• Fatigue
• Abdominal pain
• Rash
• Allergic reactions

Interactions

• May interact with anticoagulants, increasing the risk of bleeding
• Potential interactions with antiepileptic drugs
• May affect the metabolism of certain antiretrovirals
• Caution with other medications that affect liver enzymes

Precautions

• Use with caution in patients with liver disease
• Monitor for signs of gastrointestinal bleeding
• Assess renal function prior to use
• Consider potential for drug interactions

Pregnancy

Trusil should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Consult relevant guidelines for specific advice.

Breast-feeding

Trusil is excreted in breast milk. Caution is advised when administering to nursing mothers, weighing the benefits against potential risks.

Storage

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

Formulations

• Tablets
• Capsules
• Oral solution

Mechanism of action

Involves an interaction with ferriprotoporphyrin IX (“heme”), or ferrous ions, in the acidic parasite food vacuole, which results in the generation of cytotoxic radical species. The generally accepted mechanism of action of peroxide antimalarials involves interaction of the peroxide-containing drug with heme, a hemoglobin degradation byproduct, derived from proteolysis of hemoglobin. This interaction is believed to result in the formation of a range of potentially toxic oxygen and carbon-centered radicals. Artemether (AM) is an antimalarial drug derived from artemisinin (Qinghaosu), an extract of the herb Artemisia annua L., sweet wormwood. Its antiparasitic effect is that of a schizontocide and is explained by rapid uptake by parasitized erythrocytes and interaction with a component of hemoglobin degradation resulting in formation of free radicals. It has been shown to exhibit a high clinical cure rate. Two theories have been put forward for the mode of antimalarial action of the artemisinin antimalarials, in accodance with the known properties of peroxides with medicinal activity. The first assumes that the artemisinins must be activated by contact with either reduced haem (ferrous haem, Fe(ll)PPIX) or non-haem ferrous iron (exogenous iron), causing cleavage of the peroxide to generate oxygen-centered radicals (alkoxy radicals') which are then presumed to be converted into carbon-centered radicals by transfer of proximate hydrogen atoms from the periphery of the peroxide molecule. These carbon-centered radicals are then thought to alkylate sensitive, yet unspecified, biomolecules in the parasite. A second theory argues for a process in which the intact artemisinin binds to a site within a vital protein in the parasite. The act of binding causes the peroxide to be converted to hydroperoxide or similar open peroxide, which in accordance with known properties of such compounds, generates one or more active chemical entities, either oxidizing agents or oxygen transfer agents per se, or oxygen-centered free radicals. This would be associated with the binding process. In such a way, the artemisinins might act as (irreversibile) inhibitors. Iron may, or may not, be associated with the activation process. No specific biological target in the parasite has yet been identified in support of this theory, but it may be membrane-bound proteins. A 2025 systematic review notes Artemether's pharmacological activity is antimalarial.

Pharmacodynamics

In the body, artemether is metabolized into the active metabolite metabolite dihydroartemisinin. The drug works against the erythrocytic stages of <i>P. falciparum</i> by inhibiting nucleic acid and protein synthesis. Artemether is administered in combination with lumefantrine for improved efficacy. Artemether has a rapid onset of action and is rapidly cleared from the body. It is thought that artemether provides rapid symptomatic relief by reducing the number of malarial parasites. Lumefantrine has a much longer half life and is believed to clear residual parasites.

Mechanism of action

180 to 200 times sweeter than sucrose, it is metabolized as a protein and its subsequent amino-acids used up in there respective mechanisms.

Pharmacodynamics

Aspartame (L-alpha-aspartyl-L-phenylalanine methyl ester) is a low-calorie sweetener used to sweeten a wide variety of low- and reduced-calorie foods and beverages, including low-calorie tabletop sweeteners. Aspartame is composed of two amino acids, aspartic acid and phenylalanine, as the methyl ester. Aspartic acid and phenylalanine are also found naturally in protein containing foods, including meats, grains and dairy products. Methyl esters are also found naturally in many foods such as fruits and vegetable and their juices. Upon digestion, aspartame breaks down into three components (aspartic acid, phenylalanine and methanol), which are then absorbed into the blood and used in normal body processes. Neither aspartame nor its components accumulates in the body. These components are used in the body in the same ways as when they are derived from common foods.

Mechanism of action

The exact mechanism by which lumefantrine exerts its antimalarial effect is unknown. However, available data suggest that lumefantrine inhibits the formation of &beta;-hematin by forming a complex with hemin and inhibits nucleic acid and protein synthesis.

Pharmacodynamics

Lumefantrine is a blood schizonticide active against erythrocytic stages of <i>Plasmodium falciparum</i>. It is thought that administration of lumefantrine with artemether results in cooperate antimalarial clearing effects. Artemether has a rapid onset of action and is rapidly cleared from the body. It is thus thought to provide rapid symptomatic relief by reducing the number of malarial parasites. Lumefantrine has a much longer half life and is believed to clear residual parasites.

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