ATOP 250/100

Indications

• Adjunct in the treatment of non-falciparum malaria caused by Plasmodium vivax
• Adjunct in the treatment of non-falciparum malaria caused by Plasmodium ovale
• Treatment of mild to moderate Pneumocystis pneumonia in combination with clindamycin

Mechanism of action

Proguanil is a prodrug that is metabolized in the liver to its active form, cycloguanil. Cycloguanil inhibits dihydrofolate reductase, an enzyme required for the synthesis of tetrahydrofolate, which is necessary for the production of nucleic acids in the malaria parasite. This inhibition leads to the impairment of nucleic acid synthesis, ultimately resulting in the death of the parasite.

Pharmacodynamics

The pharmacodynamic effects of proguanil are primarily related to its antimalarial activity. The drug demonstrates a rapid onset of action against the malaria parasite, effectively reducing parasitemia and alleviating symptoms associated with malaria infection. Its effectiveness is enhanced when used in combination with other antimalarial agents, particularly those targeting different stages of the parasite's lifecycle.

Pharmacokinetics

Proguanil is well absorbed from the gastrointestinal tract, with peak plasma concentrations usually reached within 1 to 3 hours after oral administration. It undergoes extensive hepatic metabolism, mainly to cycloguanil, which has a longer half-life. The elimination half-life of proguanil itself is approximately 8 to 12 hours, while cycloguanil has a half-life of about 12 to 20 hours. The drug is predominantly eliminated through the urine, with both unchanged drug and metabolites present. In cases of renal impairment, caution is advised as elimination may be prolonged.

Contra-indications

• Hypersensitivity to proguanil or any component of the formulation
• Severe renal impairment
• Severe hepatic impairment
• Known G6PD deficiency (without expert advice)

Adverse effects

• Drowsiness
• Dizziness
• Nausea
• Vomiting
• Abdominal pain
• Rash
• Malaise
• Headache
• Psychosis
• Tremor
• Seizures
• Thrombocytopenia
• Neutropenia
• Pancreatitis
• Liver function abnormalities
• Haemolysis in G6PD-deficient patients

Interactions

• Antimalarials (refer to Appendix 1 in BNF)
• Warfarin (may enhance anticoagulant effect)
• Other nephrotoxic or hepatotoxic agents
• Potential interactions with drugs that induce or inhibit cytochrome P450 enzymes

Precautions

• Caution in patients with G6PD deficiency
• Caution in patients with history of psychiatric disorders
• Monitor renal and hepatic function
• Avoid in pregnancy unless benefits outweigh risks
• Screen for G6PD deficiency before treatment

Pregnancy

Manufacturer advises to avoid use, particularly in the first trimester, unless the potential benefit outweighs the risk due to teratogenicity observed in animal studies.

Breast-feeding

No specific information available; potential risk of haemolysis in G6PD-deficient infants.

Storage

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

Formulations

• {'form': 'Tablet', 'strength': '100 mg'}
• {'form': 'Tablet', 'strength': '200 mg'}
• {'form': 'Oral suspension', 'strength': None}

Indications

• Pneumocystis jirovecii pneumonia (in patients intolerant to co-trimoxazole)
• Prophylaxis of Pneumocystis jirovecii pneumonia

Dosage

Children: Child: 2 mg/kg once daily (max. per dose 100 mg).

Adults: 750 mg once daily with food.

Mechanism of action

Atovaquone is a selective inhibitor of the mitochondrial electron transport chain in protozoa, leading to a disruption in ATP production, which is crucial for their survival and replication.

Pharmacodynamics

Atovaquone exhibits antiprotozoal activity against Pneumocystis jirovecii by inhibiting its mitochondrial respiratory chain. The drug is effective in treating mild to moderate cases of Pneumocystis pneumonia.

Pharmacokinetics

Atovaquone is well absorbed when taken with food, particularly high-fat meals, which significantly enhance its bioavailability. It has a long half-life, allowing for once-daily dosing, and is primarily eliminated through feces. Its metabolism does not involve significant liver enzymes, thus reducing the risk of drug interactions.

Adverse effects

• Agranulocytosis
• Haemolytic anaemia
• Headache
• Hepatic disorders
• Hypoalbuminaemia
• Insomnia
• Nausea
• Photosensitivity reaction
• Psychosis
• Severe cutaneous adverse reactions (SCARs)
• Skin reactions
• Tachycardia
• Vomiting

Interactions

• efavirenz: Severe (decreases exposure)
• rifabutin: Severe (decreases exposure)
• rifampicin: Severe (decreases exposure)
• metoclopramide: Unknown (decreases concentration)
• nirmatrelvir boosted with ritonavir: Unknown (decreases concentration)
• tetracycline: Unknown (decreases concentration)

Precautions

• Use with caution in significant hepatic impairment
• Caution in renal impairment, monitor closely
• Monitor for blood disorders
• Dapsone syndrome: discontinue immediately if occurs

Pregnancy

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

Breast-feeding

Manufacturer advises avoid. Significant amount in milk, risk to infant very small unless infant is G6PD deficient.

Storage

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

Formulations

• Oral suspension
• Oral liquid formulations

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

Dosage

Children: Refer to specific clinical guidelines for dosing in children, as no standard paediatric dosage is specified in the provided resources.

Adults: Refer to specific clinical guidelines for dosing, as no standard adult dosage is specified in the provided resources.

Mechanism of action

Ethylene glycol toxicity results from its metabolism to glycolic acid and other toxic metabolites. Glycolate accumulates in the body and is eliminated more slowly than ethylene glycol itself. The renal excretion of both compounds plays a crucial role in their elimination, accounting for a significant portion of the administered dose.

Pharmacodynamics

The pharmacodynamics of glycolate are closely tied to its role as a metabolite of ethylene glycol. Its accumulation can lead to metabolic acidosis, although minimal clinical effects have been observed at low doses. The relationship between glycolate and ethylene glycol indicates that glycolate may contribute to the overall toxic effects of ethylene glycol ingestion.

Pharmacokinetics

The pharmacokinetics of glycolate indicate that it reaches peak plasma levels between 4-6 hours after the administration of ethylene glycol. The elimination half-life of ethylene glycol is approximately 1.7 hours in rats and 3.4 hours in dogs. Glycolate is predominantly eliminated through renal excretion, with about 5% of the dose being excreted unchanged.

Pregnancy

There is limited data on the safety of glycolate in pregnancy. Caution is advised.

Breast-feeding

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

Storage

Store at room temperature, away from light and moisture.

Mechanism of action

The hydroxyl group acts as a nucleophile, participating in various biochemical reactions, including the degradation of reactive oxygen species. It helps in the detoxification of oxidized guanosine triphosphate (GTP) and deoxyguanosine triphosphate (dGTP), which is critical for maintaining cellular integrity and function.

Pharmacodynamics

The presence of hydroxyl groups in compounds can significantly alter their pharmacological effects, enhancing solubility and reactivity. Hydroxyl groups can stabilize reactive intermediates, leading to increased efficacy in biochemical pathways, particularly in processes involving oxidative stress and cellular detoxification.

Pharmacokinetics

Hydroxyl-containing compounds typically exhibit variable absorption, distribution, metabolism, and excretion profiles depending on their specific structure. The pharmacokinetics of hydroxyl as a standalone entity is not well-defined, but its presence in larger molecules often influences their bioavailability and elimination.

Pregnancy

There is insufficient data to determine the safety of hydroxyl in pregnancy. Caution is advised.

Breast-feeding

There is no specific information available regarding the excretion of hydroxyl in human milk. Caution is advised.

Storage

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

Indications

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Pregnancy

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

Breast-feeding

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

Storage

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

Indications

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Pregnancy

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

Breast-feeding

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

Storage

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

Indications

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

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

Mechanism of action

The exact mechanism of action for Pink is not detailed in the provided information. However, compounds with similar structures often function as antagonists or inhibitors at certain receptors or enzymes, which modulates physiological processes.

Pharmacodynamics

Pharmacodynamics details for Pink are not specified. Typically, the pharmacodynamics of similar compounds involve interactions with neurotransmitter systems, influencing both central and peripheral nervous system functions. This can lead to varying therapeutic effects depending on the target receptors.

Pharmacokinetics

The pharmacokinetics of Pink, including absorption, distribution, metabolism, and excretion, are not explicitly stated. However, compounds of this nature generally exhibit moderate to high oral bioavailability, with metabolism primarily occurring in the liver, followed by renal excretion of metabolites.

Indications

• Topical formulations
• Injectable drug delivery systems
• Ophthalmic solutions
• Emulsions and suspensions
• Solubilization of hydrophobic drugs

Dosage

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

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

Mechanism of action

Poloxamers act primarily by reducing surface tension at the interface between different phases, such as oil and water. This property allows them to stabilize emulsions, enhance solubility of poorly soluble drugs, and facilitate the dispersion of active ingredients in topical formulations. The amphiphilic nature of poloxamers enables them to form micelles, which can encapsulate hydrophobic drugs, improving their bioavailability.

Pharmacodynamics

Poloxamers exhibit properties that influence drug release and absorption. By forming micelles, they can solubilize lipophilic drugs, enhancing their absorption through biological membranes. Their surfactant action can also improve the stability of emulsions and suspensions, impacting the pharmacokinetics of the drug formulations. The effectiveness of poloxamers can be influenced by their molecular weight and the ratio of ethylene oxide to propylene oxide in their structure.

Pharmacokinetics

The pharmacokinetics of poloxamers can vary depending on their molecular weight and formulation. Generally, they are not absorbed significantly through the gastrointestinal tract or skin when used as excipients. In the context of drug delivery systems, the release of the active ingredient from poloxamer-based formulations is influenced by the concentration of the poloxamer, the presence of other excipients, and the physicochemical properties of the drug. Poloxamers are typically considered safe for use in pharmaceutical formulations.

Adverse effects

• Allergic reactions
• Skin irritation
• Gastrointestinal disturbances

Precautions

• Use with caution in patients with known hypersensitivity to nonionic surfactants
• Monitor for allergic reactions in sensitive individuals

Pregnancy

Poloxamers are considered safe for use during pregnancy, but clinical data is limited. Always assess risks versus benefits.

Breast-feeding

Poloxamers are generally regarded as safe during breastfeeding, but consult healthcare providers for personalized advice.

Storage

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

Formulations

• Poloxamer 188
• Poloxamer 407

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

Indications

• Prevention of malaria
• Treatment of acute malaria
• Suppressive treatment of *P. vivax* malaria

Dosage

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

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Proguanil inhibits the dihydrofolate reductase of plasmodia, blocking the biosynthesis of purines and pyrimidines necessary for DNA synthesis and cell multiplication. This inhibition leads to failure of nuclear division during the schizont formation in both erythrocytes and liver.

Pharmacodynamics

Proguanil, as a biguanide derivative, is converted into cycloguanil, which exerts its antimalarial effects by inhibiting the parasitic dihydrofolate reductase enzyme. It possesses causal prophylactic and suppressive activity against *P. falciparum* and is effective in treating acute infections while also suppressing clinical attacks of *P. vivax* malaria. Its action, however, is comparatively slower than that of 4-aminoquinoline derivatives.

Pharmacokinetics

Proguanil is well absorbed from the gastrointestinal tract, with its absorption potentially affected by the presence of antacids. It is metabolized in the liver to the active metabolite cycloguanil, which has a longer half-life and is responsible for the drug's therapeutic effects. The pharmacokinetics of proguanil can be influenced by factors such as liver function and the presence of other medications.

Interactions

• oral antacids: Unknown (decreases absorption)
• efavirenz: Unknown (affects exposure)

Pregnancy

Proguanil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

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

Storage

Store at room temperature, away from light and moisture.

Formulations

• Proguanil hydrochloride tablets

Indications

• Hyperthyroidism
• Graves' disease
• Thyroid storm

Dosage

Children: Refer to the BNF

Adults: The usual initial dose of propylthiouracil in adults is 300 mg per day, divided into 3 doses. The maintenance dose is typically 100-150 mg per day, adjusted based on thyroid function tests.

Mechanism of action

Propylthiouracil acts by inhibiting the enzyme thyroid peroxidase, which is involved in the iodination of tyrosine residues in thyroglobulin, a precursor of thyroid hormones. By blocking this enzyme, PTU reduces the production of thyroxine (T4) and triiodothyronine (T3), leading to decreased thyroid hormone levels in circulation. Additionally, PTU inhibits the conversion of T4 to T3 in peripheral tissues, further contributing to its antithyroid effects.

Pharmacodynamics

The pharmacodynamic effects of propylthiouracil are primarily centered around its ability to lower thyroid hormone levels, which helps alleviate symptoms of hyperthyroidism such as increased heart rate, weight loss, and anxiety. The onset of action can vary, but therapeutic effects may be observed within several weeks of initiation. Monitoring thyroid function tests is essential to assess the efficacy and adjust dosing as needed.

Pharmacokinetics

Propylthiouracil is well absorbed from the gastrointestinal tract, though its bioavailability can be affected by factors such as food intake. The drug is extensively metabolized in the liver, and its elimination half-life averages around 1-2 hours. Most of the drug is excreted in urine as metabolites. It is important to note that due to its rapid metabolism, multiple daily doses may be required to maintain therapeutic levels.

Interactions

• propylthiouracil+metyrapone: Severe (decreases effects)

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

• 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

Mechanism of action

Ethylene glycol toxicity results from its metabolism to glycolic acid and other toxic metabolites. The accumulation of glycolate and the elimination kinetics of ethylene glycol and its metabolites are not well understood, so studies with male Sprague-Dawley rats and mixed breed dogs have been carried out. Ethylene glycol was administered by gavage to rats and dogs which were placed in metabolic cages for urine and blood sample collection at timed intervals. The peak plasma level of ethylene glycol occurred at 2 hr after dosing and that of glycolate between 4-6 hr. The rate of ethylene glycol elimination was somewhat faster in rats with a half-life of 1.7 hr compared to 3.4 hr in dogs. The maximum plasma level of glycolate was greater in rats although the pattern of accumulation was similar to that in dogs. Glycolate disappeared from the plasma at the same time as ethylene glycol, suggesting a slower rate of elimination of the metabolite than that of ethylene glycol. Renal excretion of ethylene glycol was an important route for its elimination accounting for 20-30% of the dose. Renal excretion of glycolate represented about 5% of the dose. Ethylene glycol induced an immediate, but short lived diuresis compared to that in control rats. Minimal clinical effects (mild acidosis with no sedation) were noted at these doses of ethylene glycol (1-2 g/kg) in both rats and dogs. The results indicate that the toxicokinetics of ethylene glycol and glycolate were similar in both species. The effect of 0.35 to 0.8 mmol/kg glycolic acid and 1.0 to 4.4 mmol/kg sodium glycolate on cyclopropane-epinephrine induced cardiac arrhythmias was examined using dogs. Doses of 0.35 to 0.5 mmol/kg glycolic acid increased the duration of arrhythmias in the 13 dogs tested, whereas doses >0.5 mmol/kg decreased or totally eliminated the arrhythmias in each of 11 dogs. Depression was observed for many of the dogs at higher doses. Sodium glycolate was much less effective in decreasing the arrhythmias, with 3 mmol/kg being required and its action being transient.

Mechanism of action

Proguanil 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.

Pharmacodynamics

Proguanil is a biguanide derivative that is converted to an active metabolite called cycloguanil. It exerts its antimalarial action by inhibiting parasitic dihydrofolate reductase enzyme. It has causal prophylactic and suppressive activity against <i>P. falciparum</i> and cures the acute infection. It is also effective in suppressing the clinical attacks of vivax malaria. However it is slower compared to 4-aminoquinolines.

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