DOLUTEGRAVIR

Indications

• HIV infection without resistance to other inhibitors of HIV integrase
• HIV infection in patients with resistance to other inhibitors of HIV integrase (specialist use only)

Dosage

Children: Refer to BNF for Children for appropriate dosing.

Adults: 50 mg once daily.

Mechanism of action

Dolutegravir inhibits the HIV integrase enzyme by binding to its active site, blocking the strand transfer step of retroviral DNA integration into the host cell genome. This step is essential for the replication of HIV, and by preventing this integration, dolutegravir effectively inhibits viral activity and replication.

Pharmacodynamics

Clinical trials have demonstrated that dolutegravir leads to a rapid and dose-dependent reduction of HIV-1 RNA in infected subjects. The antiviral response can be sustained for several days following the last dose, indicating its long half-life and strong binding affinity. This characteristic contributes to a high barrier to the development of resistance, making dolutegravir a potent option in combination therapy regimens.

Pharmacokinetics

Dolutegravir exhibits favorable pharmacokinetics, with a mean elimination half-life of approximately 14 hours. It is well absorbed following oral administration, with food enhancing its bioavailability. The drug is metabolized primarily by UGT1A1 and UGT1A9 enzymatic pathways, and it is excreted mainly via feces. Drug interactions may occur, particularly with medications that induce or inhibit UGT enzymes.

Contra-indications

• Hypersensitivity to dolutegravir or any of its excipients

Adverse effects

• Nausea
• Vomiting
• Drowsiness
• Increased weight
• Skin reactions
• Sleep disorders
• Hepatotoxicity
• Pancreatitis
• Osteonecrosis

Interactions

• Moderate increase in exposure with dopaminergic receptor agonists
• Moderate increase in exposure with pramipexole
• Moderate increase in exposure with metformin
• Moderate increase in exposure with atazanavir
• Unknown decrease in exposure with carbamazepine
• Unknown decrease in exposure with oxcarbazepine
• Unknown decrease in exposure with phenytoin
• Unknown decrease in exposure with primidone
• Unknown increase in exposure with encorafenib
• Unknown increase in concentration with fampridine

Precautions

• Use with caution in patients with HIV-1 subtype A6/A1, or BMI of 30 kg/m2 or more
• Caution in severe hepatic impairment
• Patients or carers should be advised on how to recognize signs of hypersensitivity

Pregnancy

Avoid unless potential benefit outweighs risk, no information available.

Breast-feeding

Avoid; may be present in milk for up to 12 months or longer after last prolonged-release injection.

Storage

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

Formulations

• Tablets: 50 mg and 30 mg
• Powder and solvent for solution for injection

Indications

• Cerebral edema
• Elevated intracranial pressure
• Acute kidney injury
• Oliguria
• Glaucoma
• Renal function diagnostic aid

Dosage

Adults: For cerebral edema, administer 0

Mechanism of action

Mannitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma. This action reduces cerebral edema and intracranial pressure. As a diuretic, it increases the osmolality of glomerular filtrate, leading to increased urinary excretion of water and preventing sodium and chloride reabsorption in the renal tubules. Mannitol also facilitates the urinary excretion of toxic substances and can help in assessing renal function by measuring glomerular filtration rate (GFR).

Pharmacodynamics

Mannitol is classified as an osmotic diuretic. It is chemically similar to other sugar alcohols but has a unique ability to promote diuresis by remaining unabsorbed in the renal tubules. Its use is indicated for conditions associated with increased body fluids, such as cerebral edema and glaucoma. Mannitol may be combined with other diuretics to enhance diuretic efficacy. Inhaled formulations are used in cystic fibrosis, though they may cause bronchospasm and hemoptysis.

Pharmacokinetics

Mannitol is freely filtered by the glomeruli with less than 10% tubular reabsorption, which allows for its urinary excretion rate to serve as a measurement of GFR. It does not undergo significant metabolism and is eliminated primarily through the kidneys. The onset of action occurs within 30 to 60 minutes after intravenous administration, with effects lasting for several hours. Administration may require monitoring of renal function and fluid balance.

Contra-indications

• Anuria
• Severe dehydration
• Severe renal impairment
• Intracranial bleeding

Adverse effects

• Asthenia
• Gastrointestinal disturbances
• Dry mouth
• Confusion
• Visual impairment
• Hypotension
• Electrolyte imbalances
• Pulmonary edema
• Hemoptysis (with inhalation use)
• Bronchospasm (with inhalation use)

Interactions

• Potassium-sparing diuretics may increase the risk of hyperkalemia
• Other diuretics may have additive effects
• Caution with nephrotoxic agents

Precautions

• Caution in patients with diabetes mellitus
• Caution in the elderly
• Caution in patients with gout
• Caution in patients with hepatic impairment
• Monitor renal function and electrolytes regularly
• May cause blue fluorescence of urine

Pregnancy

Manufacturer advises avoid due to potential toxicity in animal studies.

Breast-feeding

Manufacturer advises avoid due to lack of information available.

Storage

Store in a cool, dry place, away from light. Do not freeze.

Formulations

• Solution for injection
• Inhalation powder
• Oral solution

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

• Protection of drugs from degradation
• Taste masking
• Controlled release of active ingredients
• Improvement of patient compliance
• Targeted delivery of medications

Dosage

Children: Refer to specific product labeling for dosing information, as this varies widely based on formulation and indication.

Adults: Refer to specific product labeling for dosing information, as this varies widely based on formulation and indication.

Mechanism of action

The mechanism of action of coatings primarily involves the modification of drug release profiles. By altering the solubility and permeability of the drug through the coating material, the release rate can be controlled. For example, enteric coatings prevent drug dissolution in the acidic environment of the stomach, allowing the drug to be released in the more neutral pH of the intestine.

Pharmacodynamics

Pharmacodynamics of coated formulations can vary significantly based on the type of coating used. Immediate-release coatings dissolve quickly, leading to rapid absorption and onset of action. Controlled-release coatings are designed to dissolve slowly over time, providing a sustained release of the drug, which can lead to prolonged therapeutic effects and reduced dosing frequency. The choice of coating material and thickness influences the overall pharmacodynamic profile of the drug.

Pharmacokinetics

The pharmacokinetics of coated drugs are influenced by the coating material and the drug itself. Factors such as the rate of dissolution, absorption site, and first-pass metabolism play critical roles. Coatings can alter the bioavailability and distribution of the drug. For example, enteric coatings can enhance the absorption of drugs that are unstable in acidic conditions, potentially increasing their bioavailability when the drug reaches the intestine.

Pregnancy

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

Breast-feeding

Caution is advised as it is not known whether it passes into breast milk.

Storage

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

Indications

• Malnutrition
• Post-operative recovery
• Chronic illnesses requiring nutritional support
• Increased caloric needs due to illness or injury
• Weight gain in undernourished patients

Dosage

Children: Refer to the specific product guidelines for paediatric dosing as it varies by formulation and patient needs.

Adults: Refer to the specific product guidelines for adult dosing as it varies by formulation and patient needs.

Mechanism of action

The mechanism of action of Complete primarily revolves around the provision of essential nutrients that support metabolic processes. Proteins are broken down into amino acids, which are used for tissue repair and synthesis. Carbohydrates serve as a primary energy source, while fats provide essential fatty acids. The vitamins and minerals included help in various biochemical pathways, including enzyme function and antioxidant defense.

Pharmacodynamics

Complete works by supplying macronutrients and micronutrients required for various physiological functions. The carbohydrates are metabolized to glucose, providing immediate energy. Proteins enhance muscle protein synthesis, aiding in recovery and growth. The fats contribute to energy reserves and are vital for the absorption of fat-soluble vitamins. The vitamins and minerals support metabolic reactions, maintain immune function, and contribute to overall health.

Pharmacokinetics

Complete is typically absorbed in the gastrointestinal tract. The components are metabolized in the liver and utilized by various tissues throughout the body. The rate of absorption and metabolism can vary based on the individual's digestive health, metabolic rate, and specific nutrient requirements. The elimination of by-products occurs mainly through urine and feces, depending on the nutrient type.

Contra-indications

• Hypersensitivity to the active substance or to any of the excipients
• Severe liver impairment
• Severe renal impairment

Adverse effects

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

Interactions

• Increased risk of bleeding with anticoagulants
• May reduce the effectiveness of certain antihypertensives
• Potential interactions with drugs that are substrates of cytochrome P450 enzymes

Precautions

• Monitor liver function tests during prolonged therapy
• Use with caution in patients with a history of gastrointestinal disorders
• Caution in elderly patients or those with comorbidities

Pregnancy

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult healthcare providers for individualized assessment.

Breast-feeding

Caution is advised when using this drug while breastfeeding. Consider the importance of the drug to the mother against the potential risks to the infant.

Storage

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

Formulations

• Tablets
• Oral suspension
• Injectable solution

Dosage

Children: Refer to specific BNF for Children guidelines for the medication contained within the film formulation, as dosing will depend on the active ingredient and the patient's age and weight.

Adults: Refer to specific BNF guidelines for the medication contained within the film formulation, as dosing will vary widely based on the active ingredient.

Mechanism of action

The mechanism of action for drugs delivered via film formulations varies depending on the active pharmaceutical ingredient contained within the film. Generally, the drug is absorbed through the mucosal membranes in the mouth or gastrointestinal tract, leading to systemic circulation. This can enhance the onset of action compared to traditional solid dosage forms.

Pharmacodynamics

Pharmacodynamics will vary based on the specific drug contained in the film formulation. In general, pharmacodynamics refers to the biochemical and physiological effects of the drug on the body, including its mechanism of action, therapeutic effects, and side effects. Film formulations may provide rapid onset of action due to faster dissolution and absorption of the drug.

Pharmacokinetics

Pharmacokinetics, which includes absorption, distribution, metabolism, and excretion (ADME), will also vary by the specific active ingredient in the film formulation. In general, films may exhibit faster absorption rates due to their design, leading to quicker peak plasma concentrations. The distribution will depend on the lipophilicity of the drug, while metabolism will occur primarily in the liver, and excretion can be renal or fecal, depending on the drug's characteristics.

Pregnancy

The safety of film in pregnancy has not been well established. Use only if clearly needed.

Breast-feeding

It is unknown if film is excreted in human milk. Use with caution while breastfeeding.

Storage

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

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.

Indications

• Wound healing
• Skin ulceration
• Burns
• Psoriasis
• Dermatitis

Dosage

Children: Refer to the BNF for Children for appropriate dosing information based on the child's age and condition.

Adults: Refer to the BNF for specific formulations and dosing guidelines, as dosages may vary based on the condition being treated and the formulation used.

Mechanism of action

While there is no well-controlled data to formally substantiate the method of action, ongoing studies suggest that allantoin may induce a histological wound healing profile in animal models, leading to improved reestablishment of normal skin. This includes increased vasodilation, inflammatory cell presence, angiogenesis, fibroblast proliferation, and collagen deposition in treated wounds compared to untreated ones.

Pharmacodynamics

There is limited controlled data regarding the pharmacodynamic properties of allantoin. However, studies indicate that allantoin may possess moisturizing and keratolytic effects, increasing the extracellular matrix's water content and enhancing the desquamation of dead skin cells. These activities can promote cell proliferation and facilitate wound healing.

Pharmacokinetics

Specific pharmacokinetic data for allantoin in humans is limited. However, it is known to be applied topically, which suggests local absorption at the site of application. Systemic absorption is considered minimal due to its low molecular weight and hydrophilicity.

Pregnancy

There is limited data on the safety of allantoin in pregnancy. It is advisable to consult a healthcare professional before use.

Breast-feeding

Allantoin is generally considered safe during breastfeeding, but caution is recommended. Consult a healthcare professional before use.

Storage

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

Formulations

• Topical cream
• Gel
• Ointment

Indications

• Used as an excipient in tablet and capsule formulations
• Used as a bulking agent in food products
• Used in cosmetic formulations

Dosage

Children: Dosage depends on the specific formulation and intended use. Refer to the specific product information for guidance.

Adults: Dosage depends on the specific formulation and intended use. Refer to the specific product information for guidance.

Mechanism of action

Microcrystalline cellulose acts primarily as a bulking agent and binder in tablet formulations. It enhances the physical properties of the drug, allowing for better tablet formation and stability. Its porous structure aids in the disintegration of tablets, facilitating the release of the active pharmaceutical ingredients.

Pharmacodynamics

Microcrystalline cellulose is not an active pharmaceutical ingredient and does not exhibit pharmacological effects on its own. Its primary role in drug formulations is to improve the physical characteristics of the formulation, which may influence the bioavailability of the active ingredients.

Pharmacokinetics

Microcrystalline cellulose is not absorbed in the gastrointestinal tract as it is a form of cellulose, which is a non-digestible fiber. It passes through the digestive system largely unchanged. Due to its non-absorbable nature, it does not have systemic pharmacokinetic properties.

Adverse effects

• Gastrointestinal discomfort
• Nausea
• Diarrhea
• Constipation
• Flatulence

Precautions

• Use with caution in patients with gastrointestinal disorders
• Ensure adequate hydration
• Monitor for signs of intestinal obstruction

Pregnancy

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

Breast-feeding

Use with caution, as it is unknown if microcrystalline cellulose is excreted in breast milk.

Storage

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

Formulations

• Tablets
• Capsules
• Powder for suspension

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

Indications

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Adverse effects

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

Precautions

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

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

Dosage

Children: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Adults: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Mechanism of action

The mechanism of action for purified compounds varies widely depending on the specific substance. Generally, purified drugs exert their effects by interacting with specific biological targets, such as receptors, enzymes, or ion channels, leading to a desired therapeutic effect. This interaction can involve binding to receptors to activate or inhibit signaling pathways, modulating enzymatic activity, or altering physiological processes.

Pharmacodynamics

Pharmacodynamics describes the effects of a drug on the body and the relationship between drug concentration and effect. For purified drugs, this can involve dose-response relationships and the time course of their action. The purified form often enhances potency and reduces variability in response among patients, which can lead to more predictable therapeutic outcomes. The overall effect is determined by the drug's affinity for its target, the efficacy of the drug-receptor interaction, and the downstream signaling pathways activated as a result of this interaction.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of a drug. For purified substances, absorption can be more efficient due to the absence of impurities that may affect solubility or stability. Distribution may also be enhanced, leading to higher bioavailability. Metabolism can be influenced by the structure of the purified compound, as it may be metabolized more readily by liver enzymes. Excretion typically occurs through the kidneys or liver, depending on the molecular characteristics of the purified drug.

Pregnancy

Consult with a healthcare professional, as the safety of purified forms of medications during pregnancy may vary depending on the specific substance.

Breast-feeding

Consult with a healthcare professional, as the safety of purified forms of medications during breastfeeding may vary depending on the specific substance.

Storage

Store in a cool, dry place, away from light and moisture, and keep out of reach of children.

Indications

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Adverse effects

• Allergic reactions
• Gastrointestinal discomfort
• Diarrhea
• Constipation

Precautions

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

• Powder
• Granules
• Tablets
• Suspensions

Indications

• 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

Dosage

Children: Refer to specific drug information for appropriate dosing.

Adults: Refer to specific drug information for appropriate dosing.

Mechanism of action

Systemic medications typically work by entering the bloodstream and interacting with specific receptors or enzymes in various tissues, leading to a therapeutic effect. For example, antibiotics may inhibit bacterial cell wall synthesis, while analgesics may block pain receptors in the central nervous system.

Pharmacodynamics

The pharmacodynamics of systemic drugs depend on their specific class and mechanism of action. Generally, systemic drugs are intended to provide widespread effects across the body, which can lead to both therapeutic effects and potential side effects. The efficacy of these drugs is often measured by their ability to achieve desired plasma concentrations that correlate with clinical outcomes.

Pharmacokinetics

Pharmacokinetics of systemic medications involves absorption, distribution, metabolism, and excretion (ADME). After administration, systemic drugs are absorbed into the bloodstream, distributed to various tissues, metabolized by the liver or other organs, and then excreted, primarily through the kidneys. The half-life and clearance rates can vary significantly depending on the drug's chemical properties and the patient's physiology.

Pregnancy

Consult with a healthcare professional before use, as safety in pregnancy has not been established for all drugs.

Breast-feeding

Consult with a healthcare professional before use, as some drugs may pass into breast milk.

Storage

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

Mechanism of action

Dolutegravir is an HIV-1 antiviral agent. It inhibits HIV integrase by binding to the active site and blocking the strand transfer step of retroviral DNA integration in the host cell. The strand transfer step is essential in the HIV replication cycle and results in the inhibition of viral activity. Dolutegravir has a mean EC50 value of 0.5 nM (0.21 ng/mL) to 2.1 nM (0.85 ng/mL) in peripheral blood mononuclear cells (PBMCs) and MT-4 cells. Dolutegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration which is essential for the HIV replication cycle. Strand transfer biochemical assays using purified HIV-1 integrase and pre-processed substrate DNA resulted in IC50 values of 2.7 nM and 12.6 nM.

Pharmacodynamics

HIV-1 infected subjects on dolutegravir monotherapy demonstrated rapid and dose-dependent reduction of antiviral activity with declines of HIV-1 RNA copies per ml. The antiviral response was maintained for 3 to 4 days after the last dose. The sustained response obtained in clinical trials indicates that dolutegravir has a tight binding and longer dissociative half-life providing it a high barrier to resistance. The combination therapy (ripivirine and dolutegravir) presented the same viral suppression found in previous three-drug therapies without integrase strand transfer inhibitor mutations or rilpivirine resistance.

Mechanism of action

Mannitol is an osmotic diuretic that is metabolically inert in humans and occurs naturally, as a sugar or sugar alcohol, in fruits and vegetables. Mannitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma. As a result, cerebral edema, elevated intracranial pressure, and cerebrospinal fluid volume and pressure may be reduced. As a diurectic mannitol induces diuresis because it is not reabsorbed in the renal tubule, thereby increasing the osmolality of the glomerular filtrate, facilitating excretion of water, and inhibiting the renal tubular reabsorption of sodium, chloride, and other solutes. Mannitol promotes the urinary excretion of toxic materials and protects against nephrotoxicity by preventing the concentration of toxic substances in the tubular fluid. As an Antiglaucoma agent mannitol levates blood plasma osmolarity, resulting in enhanced flow of water from the eye into plasma and a consequent reduction in intraocular pressure. As a renal function diagnostic aid mannitol is freely filtered by the glomeruli with less than 10% tubular reabsorption. Therefore, its urinary excretion rate may serve as a measurement of glomerular filtration rate (GFR). The exact mechanism of action of inhaled mannitol in the symptomatic maintenance treatment of cystic fibrosis remains unclear. It is hypothesized that mannitol produces an osmotic gradient across the airway epithelium that draws fluid into the extracellular space and alters the properties of the airway surface mucus layer, allowing easier mucociliary clearance. MANNITOL IS.../USED/ IN PROPHYLAXIS OF ACUTE RENAL FAILURE. IT IS USED FOR THIS PURPOSE IN CONDITIONS AS DIVERSE AS CARDIOVASCULAR OPERATIONS, SEVERE TRAUMATIC INJURY, OPERATIONS IN THE PRESENCE OF SEVERE JAUNDICE, AND MGMNT OF HEMOLYTIC TRANSFUSION REACTIONS. IN EACH OF THESE CONDITIONS, A PRECIPITOUS FALL IN THE FLOW OF URINE MAY BE ANTICIPATED EITHER AS THE RESULT OF AN ACUTELY REDUCED FILTRATION RATE OR FROM ACUTE CHANGES IN TUBULAR PERMEABILITY. THE LATTER MAY BE CONSEQUENCE OF THE PRESENCE OF NOXIOUS AGENT WITHIN THE TUBULAR FLUID IN EXCESSIVELY HIGH CONCN, IN SOME INSTANCES SUFFICIENT TO RESULT IN ACTUAL PRECIPITATION. IN THESE SITUATIONS, MANNITOL EXERTS OSMOTIC EFFECT WITHIN THE TUBULAR FLUID, INHIBITS WATER REABSORPTION, & MAINTAINS THE RATE OF URINE FLOW. ...CONCN OF TOXIC AGENT WITHIN TUBULAR FLUID DOES NOT REACH EXCESSIVELY HIGH LEVELS THAT OTHERWISE WOULD HAVE BEEN ACHIEVED BY MORE COMPLETE REABSORPTION OF WATER. ...EVEN THOUGH /GLOMERULAR/ FILTRATION RATE IS REDUCED, MANNITOL IS STILL FILTERED @ GLOMERULUS. THE TUBULAR IMPERMEABILITY TO MANNITOL IS NOT ALTERED BY ACUTE RENAL ISCHEMIA OF SHORT DURATION. HENCE, THE MANNITOL THAT IS FILTERED IS ALSO EXCRETED IN THE VOIDED URINE. UNREABSORBED SOLUTE LIMITS BACK DIFFUSION OF WATER. ...URINE VOL CAN BE MAINTAINED EVEN IN PRESENCE OF DECR GLOMERULAR FILTRATION.

Pharmacodynamics

Chemically, mannitol is an alcohol and a sugar, or a polyol; it is similar to xylitol or sorbitol. However, mannitol has a tendency to lose a hydrogen ion in aqueous solutions, which causes the solution to become acidic. For this reason, it is not uncommon to add a substance to adjust its pH, such as sodium bicarbonate. Mannitol is commonly used to increase urine production (diuretic). It is also used to treat or prevent medical conditions that are caused by an increase in body fluids/water (e.g., cerebral edema, glaucoma, kidney failure). Mannitol is frequently given along with other diuretics (e.g., furosemide, chlorothiazide) and/or IV fluid replacement. Inhaled mannitol has the possibility to cause bronchospasm and hemoptysis; the occurrence of either should lead to discontinuation of inhaled mannitol.

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

There is no well controlled data that can formally substantiate the method of action. However, ongoing studies suggest that there may exist a histological wound healing profile induced by allantoin in rats that leads to the amelioration and fastening of the reestablishment of normal skin. This facilitation of wound healing is supported by observations that wounds inflicted to rat subjects to which topical allantoin preparations were applied histologically demonstrated increased vasodilation, presence of inflammatory exudates, number of inflammatory cells, angiogenesis, fibroblast proliferation, and increased collagen deposition when compared to rat subjects with wounds that did not receive any allantoin administration.

Pharmacodynamics

There is no well controlled and appropriate data that can formally substantiate the pharmacodynamic properties of allantoin. Nevertheless, ongoing studies suggest that allantoin possesses moisturizing and keratolytic effects, as well as abilities to increase the water content of the extracellular matrix and enhance the desquamation of upper layers of dead skin cells, all of which are activities that can promote cell proliferation and facilitate wound healing.