Abacavir, Dolutegravir and Lamivudine Dispersible Tablets (60 mg/5 mg/30 mg)

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

• HIV infection in combination with other antiretroviral drugs
• Chronic hepatitis B infection with evidence of viral replication and active liver inflammation or fibrosis

Dosage

Children: For children aged 3 months to

Adults: For HIV infection, the adult dose is 150 mg every 12 hours or alternatively 300 mg once daily. For chronic hepatitis B, the recommended dose is 300 mg once daily.

Mechanism of action

Lamivudine is phosphorylated intracellularly to its active form, lamivudine triphosphate (L-TP). This active metabolite is incorporated into viral DNA by HIV reverse transcriptase and HBV polymerase, leading to DNA chain termination. Lamivudine competes with deoxycytidine triphosphate for binding to reverse transcriptase, and its incorporation into DNA results in the disruption of DNA synthesis due to the absence of a 3'-OH group necessary for chain elongation.

Pharmacodynamics

As a nucleoside reverse transcriptase inhibitor (NRTI), lamivudine disrupts the viral DNA synthesis pathway, particularly for HIV-1 and HBV. The active metabolite formed competes with natural nucleotides and incorporates into the growing viral DNA chain, ultimately leading to chain termination. This action inhibits the replication of the virus, thereby reducing viral load in infected individuals.

Pharmacokinetics

Lamivudine is absorbed via passive diffusion and is rapidly phosphorylated to its active triphosphate form within cells. Its bioavailability is approximately 80-85% when taken orally. The drug has a half-life of about 5-7 hours in plasma and is primarily eliminated via the kidneys through glomerular filtration and active tubular secretion. Renal impairment necessitates dose adjustments, particularly in patients with creatinine clearance below 50 mL/min.

Contra-indications

• Severe hypersensitivity to lamivudine or any of its excipients
• Patients with decompensated liver disease when used for chronic hepatitis B

Adverse effects

• Peripheral neuropathy
• Headache
• Nausea
• Diarrhea
• Fatigue
• Insomnia
• Malaise
• Cough
• Pharyngitis
• Respiratory tract infections
• Alopecia
• Arthralgia

Interactions

• Trimethoprim may increase exposure to lamivudine
• Concomitant use with other antiretroviral drugs should be evaluated for cross-resistance

Precautions

• Monitor liver function tests every 3 months in patients with chronic hepatitis B
• Recurrent hepatitis may occur upon discontinuation in chronic hepatitis B patients
• Use with caution in renal impairment; dose adjustments may be necessary if creatinine clearance is less than 50 mL/min

Pregnancy

Lamivudine is classified as category B, indicating that there are no known risks in humans, but caution should be exercised. It may be used during pregnancy if deemed necessary by the healthcare provider.

Breast-feeding

Lamivudine can be used with caution while breastfeeding, provided adequate measures are taken to prevent hepatitis B infection in infants.

Storage

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

Formulations

• Lamivudine 150 mg tablets
• Lamivudine 300 mg tablets
• Epivir oral solution

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

• HIV infection
• HIV-1 infection

Dosage

Children: For children aged 12–17 years, the recommended dose is 25 mg once daily.

Adults: The usual adult dosage of abacavir is 600 mg once daily or 300 mg twice daily.

Mechanism of action

Abacavir inhibits the reverse transcriptase enzyme, which is essential for the replication of HIV. By incorporating itself into the viral DNA, it prevents the synthesis of viral RNA and DNA, thereby halting viral replication.

Pharmacodynamics

The pharmacodynamic effects of abacavir include a reduction in the viral load of HIV in plasma, leading to improved immune function and a decrease in the risk of HIV-related complications.

Pharmacokinetics

Abacavir is rapidly absorbed after oral administration and reaches peak plasma concentrations within 1-2 hours. It is primarily metabolized in the liver through glucuronidation and has a half-life of about 1.5 hours. It is excreted mainly in urine as metabolites.

Contra-indications

• Hypersensitivity to abacavir or any component of the formulation
• Severe hepatic impairment

Adverse effects

• Hypersensitivity reactions
• Abdominal pain
• Anaemia
• Decreased appetite
• Dizziness
• Fatigue
• Headache
• Nausea
• Rash
• Vomiting
• Immune reconstitution inflammatory syndrome
• Mitochondrial dysfunction

Interactions

• Increased exposure when used with riociguat

Precautions

• Caution in patients with chronic hepatitis B or C (increased risk of hepatic side-effects)
• Monitoring of liver function required in patients with hepatic disease
• Patients should be monitored for signs of hypersensitivity reactions

Pregnancy

Manufacturer advises to avoid unless essential-no information available.

Breast-feeding

Use with caution; limited information on the excretion in breast milk.

Storage

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

Formulations

• Tablet
• Oral suspension

Indications

• HIV infection
• HIV-1 infection
• HIV/AIDS treatment

Dosage

Children: For children aged 3 months to 16 years, the dosage of abacavir sulfate should be determined based on body weight. Refer to the B

Adults: The usual adult dose of abacavir sulfate is 300 mg twice daily or 600 mg once daily, taken with or without food.

Mechanism of action

Abacavir is converted intracellularly to its active form, carbovir triphosphate, which competes with the natural nucleotides for incorporation into viral DNA. This incorporation leads to termination of the DNA chain, thereby inhibiting viral replication. The conversion process involves several steps and enzymes, primarily adenosine phosphotransferase and cellular kinases, which phosphorylate abacavir to its active metabolite. Importantly, this activation occurs in both infected and uninfected cells.

Pharmacodynamics

As an NRTI, abacavir exhibits dose-dependent antiviral activity against HIV-1. The drug is effective in reducing viral load and increasing CD4 cell counts in patients with HIV. Resistance may develop through mutations in the reverse transcriptase enzyme, reducing the efficacy of abacavir. Adverse effects can include hypersensitivity reactions, which are significant and require immediate discontinuation of the drug.

Pharmacokinetics

Abacavir is well absorbed following oral administration, with peak plasma concentrations occurring approximately 1.5 hours post-dose. The drug has a half-life of about 1.5 hours, and its elimination is primarily hepatic, with metabolites excreted in the urine. It has good tissue distribution, including penetration into the central nervous system. The pharmacokinetics can be influenced by genetic factors, particularly the presence of the HLA-B*5701 allele, which is associated with an increased risk of hypersensitivity reactions.

Contra-indications

• Hypersensitivity to abacavir or any component of the formulation
• Severe hepatic impairment
• History of hypersensitivity reaction to abacavir

Adverse effects

• Hypersensitivity reactions
• Nausea
• Vomiting
• Diarrhea
• Fatigue
• Headache
• Rash
• Liver enzyme abnormalities
• Lactic acidosis
• Fat redistribution

Interactions

• May interact with other antiretroviral agents
• Alcohol may increase the risk of hypersensitivity reactions
• Other medications metabolized by the liver may influence abacavir levels

Precautions

• Monitor for signs of hypersensitivity reactions
• Assess liver function prior to initiation and during therapy
• Consider HLA-B*5701 testing before starting treatment to reduce the risk of hypersensitivity
• Use caution in patients with cardiovascular disease

Pregnancy

Abacavir is categorized as a Category C drug. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Abacavir is excreted in breast milk. A decision should be made whether to discontinue nursing or to discontinue the drug, considering the importance of the drug to the mother.

Storage

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

Formulations

• Abacavir sulfate 300 mg film-coated tablets
• Abacavir sulfate 20 mg/ml oral solution

Indications

• Use as a non-nutritive sweetener in food and beverages
• Sugar substitute for individuals with diabetes
• Caloric reduction in dietetic products

Dosage

Children: The use of acesulfame in children should follow dietary guidelines and recommendations. For specific dosing, refer to the BNF for Children.

Adults: Acesulfame is used in varying amounts depending on the product formulation. Consult specific product guidelines for usage.

Mechanism of action

Acesulfame works by stimulating the sweet taste receptors on the tongue, specifically the T1R2 and T1R3 receptors, leading to the perception of sweetness without contributing calories. It is not metabolized by the body, allowing it to provide sweetness without energy.

Pharmacodynamics

As a sweetener, acesulfame does not have traditional pharmacodynamic effects associated with therapeutic drugs. Its primary action is to activate sweet taste receptors, leading to a sweet taste sensation. It does not elicit insulin secretion or affect blood glucose levels, making it suitable for individuals with diabetes.

Pharmacokinetics

Acesulfame is rapidly absorbed following oral administration, but it is not metabolized and is excreted unchanged in urine. This results in a rapid onset of action for sweetness perception. The half-life and specific metabolic pathways are not extensively documented, but its elimination through the kidneys is well established.

Pregnancy

Acesulfame is generally regarded as safe for use during pregnancy. However, it is advisable to consult a healthcare professional before consumption.

Breast-feeding

Acesulfame is considered safe during breastfeeding, but consultation with a healthcare provider is recommended.

Storage

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Contra-indications

• Phenylketonuria (PKU)

Adverse effects

• Headaches
• Allergic reactions
• Gastrointestinal disturbances
• Mood changes

Precautions

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

• Tablets
• Powder
• Liquid sweeteners

Indications

• Constipation
• Dietary fiber supplementation
• Irritable bowel syndrome
• Diverticular disease
• Weight management

Dosage

Children: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Adults: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Mechanism of action

Cellulose acts primarily as a bulk-forming laxative. It absorbs water in the intestines, which increases stool bulk and stimulates peristalsis, thus facilitating bowel movements. Additionally, cellulose is not digestible by human enzymes, leading to fermentation by gut bacteria, which may enhance gut health and alter gut microbiota composition.

Pharmacodynamics

Cellulose increases stool weight and frequency of bowel movements. It works by retaining water in the intestines, leading to softer stools and improved passage through the gastrointestinal tract. The bulking effect of cellulose can help alleviate constipation and promote overall digestive health. It may also play a role in cholesterol reduction and glycemic control through its effects on digestion and absorption of nutrients.

Pharmacokinetics

Cellulose is not absorbed into the bloodstream due to its indigestible nature. Instead, it passes through the gastrointestinal tract, where it adds bulk to the stool. Its fermentation by colonic bacteria produces short-chain fatty acids, which may have beneficial effects on colon health. The onset of action for cellulose as a laxative can vary but is generally within 24 to 72 hours after ingestion.

Adverse effects

• Bloating
• Flatulence
• Diarrhea
• Abdominal discomfort

Precautions

• Use with caution in patients with a history of gastrointestinal disorders.
• Monitor for potential allergic reactions in sensitive individuals.

Pregnancy

Cellulose is generally considered safe during pregnancy as it is a non-toxic, indigestible fiber.

Breast-feeding

Cellulose is also considered safe during breastfeeding; it is excreted in breast milk in negligible amounts.

Storage

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

Formulations

• Powder
• Capsules
• Tablets
• Granules

Indications

• Hypovolemic shock
• Severe burns
• Postoperative fluid replacement
• Sepsis
• Trauma management

Dosage

Children: Refer to established guidelines for specific dosing, as it varies based on the type of colloidal solution used and the clinical condition being treated.

Adults: Refer to established guidelines for specific dosing, as it varies based on the type of colloidal solution used and the clinical condition being treated.

Mechanism of action

Colloidal solutions work by maintaining oncotic pressure in the blood, thus helping to retain fluid within the vascular system. This is primarily due to the large molecular weight of the colloidal particles, which cannot easily pass through capillary walls. The presence of colloids in the blood helps to draw water into the circulation, increasing blood volume and improving tissue perfusion.

Pharmacodynamics

The pharmacodynamics of colloidal solutions are centered on their ability to exert osmotic pressure, which helps maintain blood volume and pressure. This effect is particularly important in conditions such as hypovolemia and shock, where fluid replacement is necessary to restore hemodynamic stability. The efficacy of colloidal solutions can vary depending on the type of colloid used, as well as the underlying clinical condition being treated.

Pharmacokinetics

Colloidal solutions are typically administered intravenously and their pharmacokinetics can vary based on the specific formulation. Generally, colloids are distributed throughout the vascular compartment and have a longer duration of action compared to crystalloids, as they remain in circulation longer. The elimination of colloids is primarily through the reticuloendothelial system, where they are metabolized or eliminated by the liver and spleen. Factors such as particle size and composition can influence their distribution and clearance.

Adverse effects

• Allergic reactions
• Injection site reactions
• Nausea
• Vomiting
• Headache
• Fever

Precautions

• Use with caution in patients with known allergies to any component of the formulation
• Monitor for signs of hypersensitivity during administration
• Consider volume overload in patients with cardiac or renal impairment

Pregnancy

The safety of colloidal solutions during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether colloidal solutions are excreted in human milk. Caution should be exercised when administering to breastfeeding mothers.

Storage

Store at room temperature, protect from light, and do not freeze. Keep out of reach of children.

Formulations

• Colloidal silver
• Colloidal gold
• Colloidal iron
• Other metal colloids

Indications

• Used as an excipient in solid dosage forms
• Facilitates drug disintegration and dissolution

Dosage

Children: Refer to specific product formulation guidelines as crospovidone is used as an excipient and does not have a direct dosage.

Adults: Refer to specific product formulation guidelines as crospovidone is used as an excipient and does not have a direct dosage.

Mechanism of action

Crospovidone acts by rapidly absorbing water and swelling upon contact with moisture. This action leads to the disintegration of solid dosage forms, thus increasing the surface area of the active ingredients and promoting their dissolution and subsequent absorption in the gastrointestinal tract. It does not affect the pH of the formulation, ensuring that the active ingredients remain stable.

Pharmacodynamics

Crospovidone exhibits properties that enhance the bioavailability of active ingredients in pharmaceutical formulations. Its ability to rapidly disintegrate tablets and capsules leads to quicker release and absorption of the drug into systemic circulation. As a disintegrant, it aids in the effective delivery of drugs that may otherwise be poorly soluble.

Pharmacokinetics

Crospovidone itself is not absorbed systemically when administered orally. It remains in the gastrointestinal tract, where it performs its function as a disintegrant. The pharmacokinetic profile of drugs formulated with crospovidone may be influenced by the enhanced dissolution and absorption rates provided by this excipient.

Pregnancy

Crospovidone is considered to have low toxicity and is generally regarded as safe for use during pregnancy, but specific studies are limited.

Breast-feeding

There is insufficient data on the excretion of crospovidone in human milk, but it is deemed safe for use during breastfeeding.

Storage

Store in a cool, dry place away from light and moisture, in tightly closed containers.

Formulations

• Powder
• Tablets

Indications

• 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

• To enhance the palatability of oral medications
• To improve compliance in pediatric patients
• To mask unpleasant tastes of active pharmaceutical ingredients

Dosage

Children: Refer to specific formulations for guidance, as flavoring agents are typically used in very small quantities and are not dosed independently.

Adults: Refer to specific formulations for guidance, as flavoring agents are typically used in very small quantities and are not dosed independently.

Mechanism of action

Flavor compounds act primarily by stimulating taste receptors on the tongue, which can enhance the overall sensory experience of ingesting a product. Certain flavor compounds may also interact with olfactory receptors, contributing to the perception of flavor through smell. The stimulation of these receptors can lead to increased salivation and improved swallowing.

Pharmacodynamics

The use of flavoring agents in pharmaceuticals can influence compliance, particularly in children and individuals who may have difficulty swallowing pills. By enhancing the taste of a medication, these agents can reduce gag reflex and aversion, potentially improving therapeutic outcomes. However, the pharmacodynamic effects are largely dependent on the individual's taste preferences and sensitivities.

Pharmacokinetics

The pharmacokinetics of flavoring agents vary widely depending on the specific compounds used. Generally, these compounds are rapidly absorbed through the gastrointestinal tract upon ingestion, with their effects occurring within minutes. Some flavoring agents may undergo metabolism in the liver, while others may be excreted unchanged. The specific absorption, distribution, metabolism, and excretion (ADME) profiles depend on the chemical structure of each flavor compound.

Pregnancy

Generally considered safe, but specific flavoring agents may need to be evaluated individually.

Breast-feeding

Generally considered safe, but specific flavoring agents may need to be evaluated individually.

Storage

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

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

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Pregnancy

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

Breast-feeding

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

Storage

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

Indications

• 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

• 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

• 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

Indications

• Nutritional supplementation
• Antioxidant support
• Heart health
• Anti-inflammatory properties
• Skin health
• Digestive health

Dosage

Children: As strawberries are generally safe and nutritious, they can be introduced to children as part of a healthy diet. Portion sizes should be age-appropriate, and whole strawberries should be cut to prevent choking hazards in younger children.

Adults: Strawberries can be consumed as part of a balanced diet. Recommended servings vary, but a common suggestion is about one cup of fresh strawberries daily to obtain health benefits.

Mechanism of action

The health benefits of strawberries can be attributed to their high content of polyphenols, particularly anthocyanins, which have antioxidant properties. These compounds may help reduce oxidative stress and inflammation in the body, potentially lowering the risk of chronic diseases. The vitamins and minerals present in strawberries, such as vitamin C and manganese, also play essential roles in various metabolic processes.

Pharmacodynamics

Strawberries exhibit multiple pharmacodynamic effects. The antioxidants in strawberries help neutralize free radicals, which can prevent cellular damage and reduce the risk of chronic diseases. Additionally, the fiber content aids in digestive health and may help regulate blood sugar levels, while the anti-inflammatory properties can support cardiovascular health and contribute to overall wellness.

Pharmacokinetics

The bioavailability of nutrients from strawberries can vary based on factors like preparation and individual metabolism. Vitamins such as vitamin C are readily absorbed in the gastrointestinal tract. The various phytonutrients, including flavonoids, are metabolized in the liver, where they can exert their beneficial effects on health. The absorption and metabolism of these compounds can be influenced by factors such as the presence of other foods and individual digestive health.

Adverse effects

• Allergic reactions (e.g., skin rash, itching)
• Gastrointestinal upset (e.g., diarrhea, nausea)

Precautions

• Monitor for allergic reactions in individuals with known sensitivities to strawberries
• Use with caution in individuals with oxalate kidney stones due to high oxalate content

Pregnancy

Strawberries are generally considered safe to consume during pregnancy as they provide essential nutrients and hydration.

Breast-feeding

Strawberries can be consumed during breastfeeding. However, monitor for any signs of allergy in the infant, especially if there is a family history of food allergies.

Storage

Store strawberries in a cool, dry place. Refrigeration can help extend freshness, ideally in a breathable container to prevent mold.

Formulations

• Fresh strawberries
• Frozen strawberries
• Strawberry puree
• Strawberry juice
• Strawberry jams and preserves

Mechanism of action

Abacavir is a carbocyclic synthetic nucleoside analogue and an antiviral agent. Intracellularly, abacavir is converted by cellular enzymes to the active metabolite carbovir triphosphate, an analogue of deoxyguanosine-5'-triphosphate (dGTP). Carbovir triphosphate inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. Viral DNA growth is terminated because the incorporated nucleotide lacks a 3'-OH group, which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation.

Pharmacodynamics

Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Abacavir is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The concentration of drug necessary to effect viral replication by 50 percent (EC50) ranged from 3.7 to 5.8 μM (1 μM = 0.28 mcg/mL) and 0.07 to 1.0 μM against HIV-1IIIB and HIV-1BaL, respectively, and was 0.26 ± 0.18 μM against 8 clinical isolates. Abacavir had synergistic activity in cell culture in combination with the nucleoside reverse transcriptase inhibitor (NRTI) zidovudine, the non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine, and the protease inhibitor (PI) amprenavir; and additive activity in combination with the NRTIs didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zalcitabine.

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

Lamivudine is a synthetic nucleoside analogue and is phosphorylated intracellularly to its active 5'-triphosphate metabolite, lamivudine triphosphate (L-TP). This nucleoside analogue is incorporated into viral DNA by HIV reverse transcriptase and HBV polymerase, resulting in DNA chain termination. Lamivudine enters cells by passive diffusion and is phosphorylated to its active metabolite, lamivudine triphosphate. Lamivudine triphosphate competes with deoxycytidine triphosphate for binding to reverse transcriptase, and incorporation into DNA results in chain termination. Lamivudine has very low affinity for human alpha and omega DNA polymerases, moderate affinity for beta DNA polymerase, and higher affinity for gamma DNA polymerase.

Pharmacodynamics

Lamivudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1) and hepatitis B (HBV) to disrupt viral DNA synthesis. When phosphorylated, lamivudine can form active metabolites that compete for incorporation into viral DNA. Via DNA incorporation, lamivudine metabolites competitively inhibit the activity of the HIV reverse transcriptase enzyme and act as a chain terminator of DNA synthesis. Due to the lack of a 3'-OH group, incorporated nucleoside analogues prevent the formation of a 5' to 3' phosphodiester linkage that is essential for DNA chain elongation.

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

Like dideoxynucleoside reverse transcriptase inhibitors (e.g., didanosine, lamivudine, stavudine, zalcitabine, zidovudine), the antiviral activity of abacavir appears to depend on intracellular conversion of the drug to a 5-triphosphate metabolite; thus, carbovir triphosphate (carbocyclic guanosine triphosphate) and not unchanged abacavir appears to be the pharmacologically active form of the drug. Substantial differences exist in the rates at which human cells phosphorylate various nucleoside antiviral agents and in the enzymatic pathways involved. Enzymatic conversion of abacavir to carbovir triphosphate appears to be complex and involves certain steps and enzymes that differ from those involved in the enzymatic conversion of dideoxynucleoside reverse transcriptase inhibitors. Abacavir is phosphorylated by adenosine phosphotransferase to abacavir monophosphate, which is converted to carbovir monophosphate by a cytosolic enzyme. Subsequently, carbovir monophosphate is phosphorylated by cellular kinases to carbovir triphosphate. Abacavir is not a substrate for enzymes (i.e., thymidine kinase, deoxycytidine kinase, adenosine kinase, mitochondrial deoxyguanosine kinase) known to phosphorylate other nucleoside analogs. Because phosphorylation of abacavir depends on cellular rather than viral enzymes, conversion of the drug to the active triphosphate derivative occurs in both virus-infected and uninfected cells. Carbovir triphosphate is a structural analog of deoxyguanosine-5-triphosphate (dGTP), the usual substrate for viral RNA-directed DNA polymerase. Although other mechanisms may be involved in the antiretroviral activity of the drug, carbovir triphosphate appears to compete with deoxyguanosine-5-triphosphate for viral RNA-directed DNA polymerase and incorporation into viral DNA. Following incorporation of carbovir triphosphate into the viral DNA chain instead of deoxyguanosine-5-triphosphate, DNA synthesis is prematurely terminated because the absence of the 3-hydroxy group on the drug prevents further 5 to 3 phosphodiester linkages. The complete mechanism(s) of antiviral activity of abacavir has not been fully elucidated. Following conversion to a pharmacologically active metabolite, abacavir apparently inhibits replication of retroviruses, including human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2), by interfering with viral RNA-directed DNA polymerase (reverse transcriptase). The drug, therefore, exerts a virustatic effect against retroviruses by acting as a reverse transcriptase inhibitor.

Mechanism of action

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

Pharmacodynamics

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

Mechanism of action

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.