DAPIFLOZIN-M 10/500

Indications

• Dry eye conditions
• Tear deficiency
• Keratoconjunctivitis sicca

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Adverse effects

• Temporary visual disturbance
• Eye irritation

Precautions

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

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

Indications

• Type 2 diabetes mellitus
• Gestational diabetes
• Management of pre-existing diabetes in pregnant women

Dosage

Children: For children aged 10 years and older, the usual starting dose is 500 mg taken with food, with gradual increases based on clinical response. Refer to the BNF for Children for specific dosing recommendations.

Adults: The initial dose is usually 500 mg to 1,000 mg taken orally with food, and the dosage may be gradually increased based on glycemic control and tolerance, with a maximum daily dose typically not exceeding 2,000 mg.

Mechanism of action

Metformin decreases hepatic glucose production and increases peripheral glucose utilization. It does not stimulate insulin release from the pancreas, making it antihyperglycemic rather than hypoglycemic. The drug also interacts with SIRT1, a protein involved in bile acid metabolism, contributing to its effects on glucose homeostasis.

Pharmacodynamics

Metformin improves glycemic control in patients with type 2 diabetes by reducing fasting and postprandial plasma glucose levels. It acts by decreasing intestinal absorption of glucose, increasing insulin sensitivity, and enhancing peripheral glucose uptake and utilization, without causing hypoglycemia.

Pharmacokinetics

Metformin is absorbed from the gastrointestinal tract and is excreted unchanged in the urine. It has a half-life of about 6 hours and does not undergo significant metabolism. The drug's pharmacokinetics can be affected by renal function, and caution is advised in patients with renal impairment.

Contra-indications

• Severe renal impairment (creatinine clearance less than 25 mL/minute)
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis
• Hypersensitivity to metformin or any of its components

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Lactic acidosis (rare)
• Hepatic disorders (rare)
• Oedema (rare)
• Acute generalised exanthematous pustulosis (very rare)
• Thrombocytopenia (very rare)

Interactions

• Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists may require monitoring and adjustments
• Antacids containing magnesium and aluminium salts may reduce the absorption of metformin
• Concomitant use with other antihyperglycemic agents requires careful monitoring for hypoglycemia

Precautions

• Caution in patients with hepatic impairment
• Monitor liver function regularly during treatment
• Patients should be advised to discontinue use in the event of significant illness, especially dehydration or infections

Pregnancy

Avoid use during pregnancy. Women planning to become pregnant should discontinue metformin and consult a healthcare provider for safer alternatives.

Breast-feeding

Avoid use during breastfeeding. Metformin is excreted in breast milk, and its effects on a nursing infant are unknown.

Storage

Store in a cool, dry place, below 25°C. Protect from light.

Formulations

• Metformin hydrochloride 500 mg tablets
• Metformin hydrochloride 850 mg tablets
• Metformin hydrochloride 1000 mg tablets

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

Mechanism of action

Acetone acts as a solvent and is utilized in various biochemical pathways. It participates in the biosynthesis of isopropanol and is involved in the degradation pathways where it converts into other metabolites such as methylglyoxal and acetoacetate. It also plays a role in pyruvate fermentation and is integral to the fermentation processes in Clostridium acetobutylicum.

Pharmacodynamics

Acetone has a low molecular weight and is highly volatile, which allows it to penetrate biological membranes easily. Its pharmacological effects are primarily due to its role as a solvent and its ability to influence metabolic processes. Acetone can affect lipid metabolism and may impact energy homeostasis by influencing the balance between fat and carbohydrate utilization.

Pharmacokinetics

Acetone is rapidly absorbed through inhalation and dermal exposure. It is distributed throughout the body and can cross the blood-brain barrier. Metabolism occurs primarily in the liver where acetone is converted into acetoacetate and other metabolites. The elimination of acetone occurs mainly through renal excretion, with a half-life varying based on the route of exposure and individual metabolism.

Pregnancy

Acetone is classified as a pregnancy category C drug. Its effects during pregnancy are not well-studied, and caution should be exercised.

Breast-feeding

There is limited information on the excretion of acetone in breast milk. Caution is advised when using acetone during breastfeeding.

Storage

Store in a cool, dry place, away from heat and direct sunlight. Keep tightly closed in original container.

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 tablet formulations
• Enhances the bioavailability of active pharmaceutical ingredients

Dosage

Children: Refer to the specific formulation guidelines, as dosage will vary based on the active ingredient and formulation type.

Adults: Refer to the specific formulation guidelines, as dosage will vary based on the active ingredient and formulation type.

Mechanism of action

Croscarmellose sodium works by swelling and absorbing water when it comes into contact with gastrointestinal fluids. This swelling leads to the rapid disintegration of the tablet or capsule matrix, facilitating the release and absorption of the active pharmaceutical ingredients.

Pharmacodynamics

Croscarmellose sodium is classified as a superdisintegrant. Its ability to rapidly disintegrate solid dosage forms can significantly enhance the dissolution rate of the active ingredient, which is crucial for achieving therapeutic effects in a timely manner.

Pharmacokinetics

Croscarmellose sodium is not absorbed in the gastrointestinal tract and does not exert pharmacological effects in the body. It is considered non-toxic and is excreted unchanged. Its main role is as an excipient, influencing the formulation's characteristics rather than the pharmacokinetics of the active ingredients.

Precautions

• Use with caution in patients with known hypersensitivity to croscarmellose or its components.

Pregnancy

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

Breast-feeding

Caution is advised when using during breastfeeding, as safety has not been established.

Storage

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

Formulations

• Powder
• Granules

Indications

• Monitoring respiratory function
• Assessment of metabolic status
• Management of respiratory acidosis
• Management of respiratory alkalosis

Dosage

Children: Dosing for interventions related to carbon dioxide levels in pediatric patients should be guided by clinical protocols and the BNF for Children.

Adults: Dosing for interventions related to carbon dioxide levels is typically based on clinical assessment and individual patient needs. Refer to clinical guidelines for specific scenarios.

Mechanism of action

Carbon dioxide acts primarily as a signaling molecule in the body, influencing respiratory drive and blood pH. It is produced during cellular respiration and is a critical component of the bicarbonate buffering system, which helps maintain acid-base homeostasis. Elevated levels of CO2 in the blood stimulate ventilation in the lungs, increasing the rate of gas exchange and facilitating the removal of excess CO2.

Pharmacodynamics

The pharmacodynamic effects of dioxides, particularly carbon dioxide, are closely related to its concentration in the blood. As CO2 levels increase, it leads to respiratory acidosis, which can stimulate the respiratory centers in the brain to increase ventilation. Conversely, low levels of CO2 can cause respiratory alkalosis, potentially leading to decreased respiratory drive. CO2 also plays a role in vasodilation and can affect blood flow and pressure through its influence on smooth muscle tone.

Pharmacokinetics

Carbon dioxide is produced endogenously during metabolic processes and is transported in the bloodstream primarily in three forms: dissolved in plasma, as bicarbonate ions (HCO3-), and bound to hemoglobin. The half-life of CO2 in the bloodstream is very short due to its rapid exchange with alveolar gas in the lungs. The elimination of CO2 occurs through exhalation, making it a dynamic component of respiratory physiology.

Pregnancy

Data on the effects of dioxide during pregnancy are limited. Caution is advised due to potential risks associated with exposure.

Breast-feeding

Limited data are available regarding the excretion of dioxide in human milk. Caution is recommended.

Storage

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

Indications

• Iron deficiency anemia
• Chronic blood loss
• Nutritional iron deficiency
• Pregnancy-related anemia

Dosage

Children: Refer to the BNF for Children for specific dosing information as it may vary based on the formulation and clinical context.

Adults: Refer to the BNF for specific dosing information as it may vary based on the formulation and clinical context.

Mechanism of action

Ferric ions participate in various biological processes, including oxygen transport and electron transfer. They facilitate the formation of hemoglobin in red blood cells, allowing for efficient oxygen delivery throughout the body. Ferric compounds can also promote the absorption of iron from the gastrointestinal tract by providing a more bioavailable form of iron.

Pharmacodynamics

Ferric compounds exhibit their effects primarily through the restoration of iron levels in the body. This leads to improved synthesis of hemoglobin and overall enhancement of oxygen-carrying capacity. The pharmacological action is dose-dependent, with higher doses leading to more pronounced effects on hemoglobin levels and erythropoiesis. Additionally, ferric ions can influence various metabolic pathways involved in cellular respiration and energy production.

Pharmacokinetics

Ferric is absorbed in the gastrointestinal tract, with absorption rates influenced by dietary factors and the presence of other substances in the gut. Once absorbed, ferric ions are transported in the bloodstream bound to transferrin, a transport protein. The body regulates iron levels primarily through absorption rather than excretion, and excess iron can be stored in the liver, spleen, and bone marrow. The elimination of ferric compounds is generally slow, as they are incorporated into various biological systems or stored for future use.

Contra-indications

• Hypersensitivity to ferric compounds
• Iron overload conditions such as haemochromatosis or haemosiderosis
• Chronic liver disease
• Active peptic ulcer disease

Adverse effects

• Gastrointestinal disturbances including nausea, vomiting, and constipation
• Diarrhea
• Abdominal pain
• Black stools
• Allergic reactions including rashes and anaphylaxis
• Staining of teeth (with oral formulations)

Interactions

• Antacids may reduce the absorption of oral ferric preparations
• Tetracyclines and quinolone antibiotics may have reduced absorption when taken with iron
• Ascorbic acid may enhance the absorption of iron

Precautions

• Caution in patients with a history of gastrointestinal disease
• Monitor for signs of iron overload in patients receiving repeated doses
• Use with caution in patients with renal impairment

Pregnancy

Ferric compounds are generally considered safe in pregnancy when used as directed to treat iron deficiency, but should be used under medical supervision.

Breast-feeding

Ferric compounds are excreted in breast milk in small amounts, usually considered safe but should be used under medical supervision.

Storage

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

Formulations

• Oral tablets
• Oral solution
• Intravenous injection

Indications

• Lactose intolerance
• As a filler or excipient in pharmaceutical formulations

Dosage

Children: Refer to the BNF for Children for specific dosing information based on age and clinical context.

Adults: Refer to the BNF for specific dosing information based on clinical context.

Mechanism of action

Lactose is metabolized in the intestine by the enzyme lactase into its constituent monosaccharides, glucose and galactose. In individuals with lactase deficiency, unabsorbed lactose passes into the colon, where it is fermented by bacteria, leading to gas production and osmotic effects that contribute to diarrhea.

Pharmacodynamics

The pharmacodynamics of lactose are primarily related to its effects on gastrointestinal function. In healthy individuals, lactose is effectively broken down into glucose and galactose, which are absorbed and utilized for energy. In individuals with lactose intolerance, the unabsorbed lactose can cause osmotic diarrhea and colonic fermentation, leading to discomfort and symptoms associated with lactose intolerance.

Pharmacokinetics

Lactose is not absorbed in the gastrointestinal tract until it is hydrolyzed into glucose and galactose by lactase. The absorption of glucose and galactose occurs in the small intestine. The half-life is not applicable as lactose is not typically administered as a medication but is rather ingested as a natural component of food. Its metabolism primarily occurs in the intestine.

Adverse effects

• Bloating
• Diarrhea
• Abdominal pain
• Flatulence

Precautions

• Use with caution in patients with lactose intolerance.
• Consider potential for gastrointestinal upset in sensitive individuals.

Pregnancy

Lactose is generally considered safe for use during pregnancy. However, consult a healthcare professional for individual advice.

Breast-feeding

Lactose is safe to use while breastfeeding, as it is a natural sugar present in breast milk.

Storage

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

Formulations

• Powder
• Granules
• Tablets
• Syrup

Indications

• Type 2 diabetes mellitus
• Polycystic ovary syndrome (PCOS)

Dosage

Children: The

Adults: The usual starting dose of metformin for adults is 500 mg taken orally twice a day or 850 mg once daily, with gradual increases based on tolerance and blood glucose levels. The maximum recommended daily dose is 2000-3000 mg, depending on the formulation used.

Mechanism of action

Metformin decreases blood glucose levels by decreasing hepatic glucose production (gluconeogenesis), decreasing intestinal absorption of glucose, and increasing insulin sensitivity, which enhances peripheral glucose uptake and utilization. It is known to inhibit mitochondrial complex I activity, leading to increased AMP:ATP ratios that activate AMP-activated protein kinase (AMPK), a key regulator of glucose metabolism. This activation results in reduced hepatic glucose output and improved cellular glucose uptake.

Pharmacodynamics

Metformin exerts its effects primarily by enhancing insulin sensitivity and reducing glucose production by the liver. Unlike sulfonylureas, which increase insulin secretion, metformin does not cause hyperinsulinemia. Its ability to lower fasting plasma glucose and glycosylated hemoglobin (HbA1c) levels makes it a cornerstone in the management of type 2 diabetes. Clinical studies have shown significant reductions in fasting plasma glucose and HbA1c levels in patients treated with metformin.

Pharmacokinetics

Metformin is absorbed from the gastrointestinal tract, with peak plasma concentrations typically occurring 2-3 hours after ingestion. It has a bioavailability of approximately 50-60% when administered orally. The drug is primarily eliminated unchanged by the kidneys, and its clearance is proportional to renal function. The half-life of metformin is about 6.5 hours. Accumulation may occur in cases of renal impairment, necessitating caution in patients with reduced renal function.

Adverse effects

• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Lactic acidosis
• Vitamin B12 deficiency

Interactions

• dolutegravir+metformin: Moderate (increases exposure)
• cimetidine+metformin: Moderate (increases exposure)
• risdiplam+metformin: Moderate (increases concentration)
• vandetanib+metformin: Moderate (increases exposure)
• bictegravir+metformin: Unknown (increases exposure)
• guanfacine+metformin: Unknown (increases concentration)
• mexiletine+metformin: Unknown (affects exposure)
• pitolisant+metformin: Unknown (increases exposure)
• ribociclib+metformin: Unknown (increases exposure)

Precautions

• Renal impairment
• Dehydration
• Excessive alcohol intake

Pregnancy

Metformin is classified as a Category B medication. It is often used during pregnancy for managing gestational diabetes but should be administered under medical supervision.

Breast-feeding

Metformin is excreted in breast milk, but is generally considered safe for use during breastfeeding. Consult with a healthcare provider for specific guidance.

Storage

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

Formulations

• Tablets
• Extended-release tablets
• Oral solution

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.

Mechanism of action

Oxides do not have a single mechanism of action as they are a broad category of compounds. However, in general, metal oxides can exhibit catalytic properties, while non-metal oxides may participate in biochemical reactions by forming acids or bases upon dissolution in water.

Pharmacodynamics

The pharmacodynamics of oxides depend on the specific type of oxide and its interaction with biological systems. For instance, metal oxides may have antimicrobial properties, while certain non-metal oxides can influence metabolic pathways through their acid-base chemistry. The effects vary widely, necessitating specific studies for each oxide's role in therapeutic contexts.

Pharmacokinetics

The pharmacokinetics of oxides are also variable. Many metal oxides are poorly soluble and thus have limited absorption when ingested. Non-metal oxides, such as carbon dioxide, can be readily absorbed and utilized in metabolic processes. The distribution, metabolism, and excretion of oxides depend on their chemical form and the biological system in which they are involved.

Pregnancy

Not applicable as oxide is not a drug but a class of chemical compounds.

Breast-feeding

Not applicable as oxide is not a drug but a class of chemical compounds.

Storage

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

Dosage

Children: Refer to product-specific guidelines for dosing information.

Adults: Refer to product-specific guidelines for dosing information.

Pregnancy

Consult healthcare provider for risk assessment.

Breast-feeding

Consult healthcare provider before use.

Storage

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

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

• Bacterial infections
• Pneumonia
• Urinary tract infections
• Skin and soft tissue infections
• Sepsis

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations based on the child's age, weight, and condition.

Adults: Refer to the specific dosage guidelines based on the condition being treated and the patient's renal function.

Mechanism of action

Sepitrap works by inhibiting bacterial cell wall synthesis through binding to penicillin-binding proteins (PBPs), which are critical for the cross-linking of peptidoglycan layers in bacterial cell walls. This disruption leads to cell lysis and death, particularly in actively dividing bacteria.

Pharmacodynamics

The pharmacodynamics of sepitrap involve its concentration-dependent bactericidal activity. It is effective against a wide range of gram-positive and some gram-negative bacteria. The drug's activity is influenced by the bacterial growth phase, showing higher efficacy against actively dividing organisms. Resistance mechanisms may include the production of beta-lactamases, alterations in PBPs, and decreased permeability of the bacterial cell membrane.

Pharmacokinetics

Sepitrap is typically administered parenterally, leading to rapid distribution throughout the body. It is metabolized to some extent in the liver and excreted primarily via the kidneys. The half-life of sepitrap varies depending on renal function, necessitating dosage adjustments in patients with impaired renal clearance. Its volume of distribution suggests good tissue penetration, making it effective for treating infections in various body compartments.

Pregnancy

Sepitrap should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Caution is advised.

Breast-feeding

It is unknown whether sepitrap is excreted in human milk. Caution is recommended when administering to nursing mothers.

Storage

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

Indications

• Potential role in bone health
• Support for connective tissue formation
• May aid in mineral metabolism

Dosage

Children: There is no established clinical dosage for silicon in paediatric populations, as it is not classified as an essential nutrient.

Adults: There is no established clinical dosage for silicon in adults, as it is not classified as an essential nutrient.

Mechanism of action

Silicon is believed to enhance the synthesis of glycosaminoglycans and collagen, which are important for the structural integrity of connective tissues. It may also influence the activity of certain enzymes involved in bone mineralization, thus playing a role in maintaining bone density and health.

Pharmacodynamics

The pharmacodynamics of silicon is not fully elucidated; however, it is thought to involve the modulation of bone metabolism and the promotion of connective tissue health. Silicon may have a synergistic effect with other minerals, such as calcium and magnesium, aiding in their utilization and metabolism in the body.

Pharmacokinetics

The pharmacokinetics of silicon is complex, as it is not absorbed through typical gastrointestinal pathways. Instead, silicon is thought to be taken up in the form of silicates and then distributed throughout the body, particularly in connective tissues. The elimination of silicon occurs primarily through renal excretion, with some variations depending on dietary intake and individual metabolism.

Pregnancy

Silicon is generally considered safe during pregnancy, as it is a naturally occurring element in the human body. However, specific recommendations regarding supplementation should be followed based on the advice of a healthcare provider.

Breast-feeding

Silicon is present in breast milk in small amounts. Its safety during breastfeeding is generally regarded as acceptable, although supplementation should be approached with caution and under medical advice.

Storage

Silicon should be stored in a cool, dry place, protected from light and moisture. Follow specific storage recommendations provided by the manufacturer if available.

Indications

• Dry skin conditions
• Cosmetic formulations
• Emollient in topical creams and lotions
• Emulsifying agent in pharmaceutical preparations

Dosage

Children: For pediatric use, refer to specific product formulations and guidelines, as dosing may vary based on the formulation and concentration.

Adults: Stearyl alcohol is used topically in various formulations. Specific dosing is typically determined by the formulation and intended use, refer to product guidelines for detailed instructions.

Mechanism of action

Stearyl alcohol functions primarily as an emollient and emulsifier. It aids in the formation of stable emulsions by reducing the surface tension between oil and water phases, allowing for the creation of creams and lotions. Its hydrophobic tail interacts with lipids, while the hydroxyl group can form hydrogen bonds with water, enhancing moisture retention in the skin.

Pharmacodynamics

Stearyl alcohol acts by providing a protective barrier on the skin, reducing transepidermal water loss and enhancing hydration. Its emollient properties make it effective in softening and smoothing the skin, which can alleviate dryness and improve the overall appearance of the skin. Additionally, it can enhance the delivery of other active ingredients in topical formulations.

Pharmacokinetics

Stearyl alcohol is not significantly absorbed systemically when applied topically. Its primary action is local to the site of application, where it exerts its emollient effects. The compound is metabolized in the body to various fatty acids and alcohols, and it is excreted primarily through the skin and gastrointestinal tract, with minimal systemic exposure.

Pregnancy

Stearyl is generally considered safe for use during pregnancy; however, specific formulations should be evaluated for their ingredients.

Breast-feeding

Stearyl can be used while breastfeeding, but it's recommended to consult a healthcare provider for specific concerns regarding topical applications.

Storage

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

Formulations

• Cream
• Ointment
• Lotion

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

Metformin is widely used to treat hyperglycemia. However, metformin treatment may induce intrahepatic cholestasis and liver injury in a few patients with type II diabetes through an unknown mechanism. Here we show that metformin decreases SIRT1 protein levels in primary hepatocytes and liver. Both metformin-treated wild-type C57 mice and hepatic SIRT1-mutant mice had increased hepatic and serum bile acid levels. However, metformin failed to change systemic bile acid levels in hepatic SIRT1-mutant mice. Molecular mechanism study indicates that SIRT1 directly interacts with and deacetylates Foxa2 to inhibit its transcriptional activity on expression of genes involved in bile acids synthesis and transport. Hepatic SIRT1 mutation elevates Foxa2 acetylation levels, which promotes Foxa2 binding to and activating genes involved in bile acids metabolism, impairing hepatic and systemic bile acid homeostasis. Our data clearly suggest that hepatic SIRT1 mediates metformin effects on systemic bile acid metabolism and modulation of SIRT1 activity in liver may be an attractive approach for treatment of bile acid-related diseases such as cholestasis. Metformin is antihyperglycemic, not hypoglycemic. It does not cause insulin release from the pancreas and does not cause hypoglycemia, even in large doses. Metformin has no significant effects on the secretion of glucagon, cortisol, growth hormone or somatostatin. Metformin reduces glucose levels primarily by decreasing hepatic glucose production and by increasing insulin action in muscle and fat. ... May decrease plasma glucose by reducing the absorption of glucose from the intestine. /Salt not specified/ Metformin potentiates the effect of insulin by mechanisms not fully understood. Metformin does not stimulate pancreatic beta cells to increase secretion of insulin; insulin secretion must be present for metformin to work properly. It is postulated that metformin decreases hepatic glucose production and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. /Salt not specified/ People with Type 2 diabetes mellitus (T2DM) have reduced bone mineral density and an increased risk of fractures due to altered mesenchymal stem cell (MSC) differentiation in the bone marrow. This leads to a shift in the balance of differentiation away from bone formation (osteogenesis) in favour of fat cell development (adipogenesis). The commonly used anti-diabetic drug, metformin, activates the osteogenic transcription factor Runt-related transcription factor 2 (Runx2), which may suppress adipogenesis, leading to improved bone health. Here we investigate the involvement of the metabolic enzyme, AMP-activated protein kinase (AMPK), in these protective actions of metformin. The anti-adipogenic actions of metformin were observed in multipotent C3H10T1/2 MSCs, in which metformin exerted reciprocal control over the activities of Runx2 and the adipogenic transcription factor, PPARgamma, leading to suppression of adipogenesis. These effects appeared to be independent of AMPK activation but rather through the suppression of the mTOR/p70S6K signalling pathway. Basal AMPK and mTOR/p70S6K activity did appear to be required for adipogenesis, as demonstrated by the use of the AMPK inhibitor, compound C. This observation was further supported by using AMPK knockout mouse embryo fibroblasts (MEFs) where adipogenesis, as assessed by reduced lipid accumulation and expression of the adipogeneic transcription factor, C/EBPbeta, was found to display an absolute requirement for AMPK. Further activation of AMPK in wild type MEFS, with either metformin or the AMPK-specific activator, A769662, was also associated with suppression of adipogenesis. It appears, therefore, that basal AMPK activity is required for adipogenesis and that metformin can inhibit adipogenesis through AMPK-dependent or -independent mechanisms, depending on the cellular context.

Mechanism of action

Metformin's mechanisms of action are unique from other classes of oral antihyperglycemic drugs. Metformin decreases blood glucose levels by decreasing hepatic glucose production (also called gluconeogenesis), decreasing the intestinal absorption of glucose, and increasing insulin sensitivity by increasing peripheral glucose uptake and utilization. It is well established that metformin inhibits mitochondrial complex I activity, and it has since been generally postulated that its potent antidiabetic effects occur through this mechanism. The above processes lead to a decrease in blood glucose, managing type II diabetes and exerting positive effects on glycemic control. After ingestion, the organic cation transporter-1 (OCT1) is responsible for the uptake of metformin into hepatocytes (liver cells). As this drug is positively charged, it accumulates in cells and in the mitochondria because of the membrane potentials across the plasma membrane as well as the mitochondrial inner membrane. Metformin inhibits mitochondrial complex I, preventing the production of mitochondrial ATP leading to increased cytoplasmic ADP:ATP and AMP:ATP ratios. These changes activate AMP-activated protein kinase (AMPK), an enzyme that plays an important role in the regulation of glucose metabolism. Aside from this mechanism, AMPK can be activated by a lysosomal mechanism involving other activators. Following this process, increases in AMP:ATP ratio also inhibit _fructose-1,6-bisphosphatase_ enzyme, resulting in the inhibition of gluconeogenesis, while also inhibiting _adenylate cyclase_ and decreasing the production of cyclic adenosine monophosphate (cAMP), a derivative of ATP used for cell signaling. Activated AMPK phosphorylates two isoforms of acetyl-CoA carboxylase enzyme, thereby inhibiting fat synthesis and leading to fat oxidation, reducing hepatic lipid stores and increasing liver sensitivity to insulin. In the intestines, metformin increases anaerobic glucose metabolism in enterocytes (intestinal cells), leading to reduced net glucose uptake and increased delivery of lactate to the liver. Recent studies have also implicated the gut as a primary site of action of metformin and suggest that the liver may not be as important for metformin action in patients with type 2 diabetes. Some of the ways metformin may play a role on the intestines is by promoting the metabolism of glucose by increasing glucagon-like peptide I (GLP-1) as well as increasing gut utilization of glucose. In addition to the above pathway, the mechanism of action of metformin may be explained by other ways, and its exact mechanism of action has been under extensive study in recent years. Metformin is widely used to treat hyperglycemia. However, metformin treatment may induce intrahepatic cholestasis and liver injury in a few patients with type II diabetes through an unknown mechanism. Here we show that metformin decreases SIRT1 protein levels in primary hepatocytes and liver. Both metformin-treated wild-type C57 mice and hepatic SIRT1-mutant mice had increased hepatic and serum bile acid levels. However, metformin failed to change systemic bile acid levels in hepatic SIRT1-mutant mice. Molecular mechanism study indicates that SIRT1 directly interacts with and deacetylates Foxa2 to inhibit its transcriptional activity on expression of genes involved in bile acids synthesis and transport. Hepatic SIRT1 mutation elevates Foxa2 acetylation levels, which promotes Foxa2 binding to and activating genes involved in bile acids metabolism, impairing hepatic and systemic bile acid homeostasis. Our data clearly suggest that hepatic SIRT1 mediates metformin effects on systemic bile acid metabolism and modulation of SIRT1 activity in liver may be an attractive approach for treatment of bile acid-related diseases such as cholestasis. Metformin is antihyperglycemic, not hypoglycemic. It does not cause insulin release from the pancreas and does not cause hypoglycemia, even in large doses. Me

Pharmacodynamics

**General effects** Insulin is an important hormone that regulates blood glucose levels. Type II diabetes is characterized by a decrease in sensitivity to insulin, resulting in elevations in blood glucose when the pancreas can no longer compensate. In patients diagnosed with type 2 diabetes, insulin is unable to exert adequate effects on tissues and cells (i.e. insulin resistance) and insulin deficiency may also be present. Metformin reduces hepatic production of glucose, decreases the intestinal absorption of glucose, and enhances insulin sensitivity by increasing both peripheral glucose uptake and utilization. In contrast with drugs of the sulfonylurea class, which lead to hyperinsulinemia, the secretion of insulin is unchanged with metformin use. **Effect on fasting plasma glucose (FPG) and Glycosylated hemoglobin (HbA1c)** HbA1c is an important periodic measure of glycemic control used to monitor diabetic patients. Fasting plasma glucose is also a useful and important measure of glycemic control. In a 29-week clinical trial of subjects diagnosed with type II diabetes, metformin decreased the fasting plasma glucose levels by an average of 59 mg/dL from baseline, compared to an average increase of 6.3 mg/dL from baseline in subjects taking a placebo. Glycosylated hemoglobin (HbA1c) was decreased by about 1.4% in subjects receiving metformin, and increased by 0.4% in subjects receiving placebo only.