Dapaone 10

Indications

• Type 2 diabetes mellitus as monotherapy or in combination with insulin or other antidiabetic drugs
• Chronic heart failure with reduced ejection fraction
• Chronic kidney disease

Dosage

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

Adults: 10 mg once daily, with caution advised in renal impairment (avoid initiation if eGFR less than 30 mL/min/1.73 m2).

Mechanism of action

Dapagliflozin inhibits the sodium-glucose cotransporter 2 (SGLT2) located in the proximal tubule of the nephron, leading to decreased glucose reabsorption and increased urinary glucose excretion. This mechanism contributes to better glycemic control in patients with type 2 diabetes mellitus.

Pharmacodynamics

Dapagliflozin reduces sodium reabsorption, increasing sodium delivery to the distal tubule, which may decrease both pre- and afterload on the heart. This results in downregulation of sympathetic activity and reduced intraglomerular pressure, mediated by increased tubuloglomerular feedback. Clinical studies have shown that doses of dapagliflozin lead to significant urinary glucose excretion, with near-maximum effects observed at higher doses.

Pharmacokinetics

Dapagliflozin is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 1 to 2 hours. It has a half-life of approximately 12.9 hours. The drug undergoes extensive metabolism primarily via UGT1A9 and UGT2B7, with renal excretion of metabolites. The pharmacokinetics may be affected by renal function, with caution advised if the estimated glomerular filtration rate (eGFR) is less than 60 mL/min/1.73 m2.

Contra-indications

• Severe renal impairment (eGFR less than 30 mL/minute/1.73 m2)
• Hypersensitivity to dapagliflozin or any excipients

Adverse effects

• Genital mycotic infections
• Urinary tract infections
• Dehydration
• Hypotension
• Diabetic ketoacidosis
• Acute kidney injury

Interactions

• Concomitant use with insulin or other antidiabetic agents may require dose adjustments to avoid hypoglycaemia
• Diuretics may enhance the risk of dehydration and hypotension
• Other drugs affecting renal function may require monitoring

Precautions

• Monitor renal function before initiation and periodically thereafter
• Consider risk of diabetic ketoacidosis in patients
• Use with caution in patients with a history of urinary tract infections or genital infections

Pregnancy

Avoid-toxicity in animal studies.

Breast-feeding

Avoid-present in milk in animal studies.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets: 5 mg, 10 mg

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 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

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Pregnancy

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

Breast-feeding

Unknown whether lauryl is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Dosage

Children: Paediatric fluid requirements should be calculated based on age, weight, and clinical condition. Refer to the guidelines in the BNF for Children for detailed recommendations.

Adults: Dosage in litres may vary depending on clinical circumstances, such as fluid resuscitation needs, maintenance fluid requirements, or medication delivery. Refer to clinical guidelines for specific scenarios.

Mechanism of action

Litres do not have a pharmacological mechanism of action as they are a unit of measurement rather than a drug. However, the administration of fluids measured in litres can influence various physiological processes, including hydration status, electrolyte balance, and overall fluid homeostasis in the body.

Pharmacodynamics

As a measurement unit, litres do not exhibit pharmacodynamics. However, the volume of fluid administered can impact the pharmacodynamics of medications that are diluted or delivered in fluid form, affecting the rate of absorption, distribution, metabolism, and excretion of drugs.

Pharmacokinetics

Litres as a unit of volume do not possess pharmacokinetic properties. The pharmacokinetics of a drug may be influenced by the volume of fluid in which it is administered, as this can affect the concentration of the drug in the bloodstream and its subsequent pharmacological effects.

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

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

Pregnancy

No specific data available, consult a healthcare professional.

Breast-feeding

No specific data available, consult a healthcare professional.

Storage

Store in a cool, dry place away from light.

Mechanism of action

Dapagliflozin inhibits the sodium-glucose cotransporter 2(SGLT2) which is primarily located in the proximal tubule of the nephron. SGLT2 facilitates 90% of glucose reabsorption in the kidneys and so its inhibition allows for glucose to be excreted in the urine. This excretion allows for better glycemic control and potentially weight loss in patients with type 2 diabetes mellitus.

Pharmacodynamics

Dapagliflozin also reduces sodium reabsorption and increases the delivery of sodium to the distal tubule. This may influence several physiological functions including, but not restricted to, lowering both pre- and afterload of the heart and downregulation of sympathetic activity, and decreased intraglomerular pressure which is believed to be mediated by increased tubuloglomerular feedback. Increases in the amount of glucose excreted in the urine were observed in healthy subjects and in patients with type 2 diabetes mellitus following the administration of dapagliflozin. Dapagliflozin doses of 5 or 10 mg per day in patients with type 2 diabetes mellitus for 12 weeks resulted in excretion of approximately 70 grams of glucose in the urine per day at Week 12. A near-maximum glucose excretion was observed at the dapagliflozin daily dose of 20 mg. This urinary glucose excretion with dapagliflozin also results in increases in urinary volume. After discontinuation of dapagliflozin, on average, the elevation in urinary glucose excretion approaches baseline by about 3 days for the 10 mg dose. Dapagliflozin was not associated with clinically meaningful prolongation of QTc interval at daily doses up to 150 mg (15 times the recommended maximum dose) in a study of healthy subjects. In addition, no clinically meaningful effect on QTc interval was observed following single doses of up to 500 mg (50 times the recommended maximum dose) of dapagliflozin in healthy subjects.

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