NITAFIN 500

Indications

• Dry eye conditions
• Tear deficiency
• Keratoconjunctivitis sicca

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Adverse effects

• Temporary visual disturbance
• Eye irritation

Precautions

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

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

Indications

• Energy source
• Dietary fiber supplement
• Source of vitamins and minerals
• Antioxidant support

Dosage

Children: Corn can be introduced to children as part of a balanced diet. There is no specific paediatric dosage; it should be given according to age-appropriate dietary guidelines.

Adults: Corn can be consumed in various forms as part of a balanced diet. There is no specific adult dosage; intake should be based on dietary preferences and nutritional needs.

Mechanism of action

The primary component of corn is starch, which is a polysaccharide composed of glucose units. Upon ingestion, starch is broken down into glucose by enzymes such as amylase in the digestive system. The glucose is then absorbed into the bloodstream, providing energy to cells throughout the body. Corn also contains antioxidants such as lutein and zeaxanthin, which may help protect against oxidative stress and support eye health.

Pharmacodynamics

Corn is mainly metabolized for energy due to its high carbohydrate content. The dietary fiber in corn aids in digestion and promotes satiety. Additionally, the presence of vitamins and minerals contributes to overall health, supporting various bodily functions including immune response and bone health. The antioxidants in corn may help reduce inflammation and lower the risk of chronic diseases.

Pharmacokinetics

The digestion and absorption of corn depend on its form (whole kernel, cornmeal, corn syrup, etc.). Generally, carbohydrates are digested and absorbed relatively quickly, with glucose appearing in the bloodstream shortly after consumption. The fiber content can slow digestion and help maintain stable blood sugar levels. The bioavailability of nutrients from corn can vary based on processing methods, such as cooking or milling.

Pregnancy

Corn is generally considered safe during pregnancy. It provides essential nutrients such as fiber, vitamins, and minerals, but should be consumed in moderation as part of a balanced diet.

Breast-feeding

Corn is safe for consumption while breastfeeding. It can provide important nutrients, but it's advisable to monitor for any allergic reactions in infants.

Storage

Store corn in a cool, dry place. Fresh corn should be kept in the refrigerator and consumed within a few days for optimal freshness.

Formulations

• Fresh corn
• Canned corn
• Frozen corn
• Cornmeal
• Corn syrup
• Corn oil

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

• Obesity management
• Weight loss in overweight individuals
• Adjunct to lifestyle modifications such as diet and exercise

Dosage

Children: There is insufficient data to establish a safe and effective dose in the pediatric population. Refer to clinical guidelines or consult a healthcare provider for specific recommendations.

Adults: Dosage should be individualized based on the patient's response and tolerability. Refer to product labeling for specific dosing recommendations.

Mechanism of action

Ligamed works by inhibiting gastric and pancreatic lipases, the enzymes responsible for breaking down dietary fats into absorbable free fatty acids. By inhibiting these enzymes, Ligamed prevents the digestion and absorption of approximately 30% of dietary fats, leading to a decrease in caloric intake and promoting weight loss.

Pharmacodynamics

The pharmacodynamics of Ligamed are characterized by its ability to reduce fat absorption from the gastrointestinal tract. This mechanism leads to decreased body weight and fat mass in patients adhering to a calorie-restricted diet. Additionally, the medication may help improve metabolic parameters associated with obesity, such as insulin sensitivity and lipid profiles.

Pharmacokinetics

Ligamed is minimally absorbed systemically, with its primary action localized within the gastrointestinal tract. The onset of action typically occurs within 24 to 48 hours after ingestion. The drug has a half-life that allows for once or twice daily dosing, depending on the formulation. Ligamed is excreted primarily in the feces in unabsorbed form, with minimal renal excretion.

Pregnancy

Safety 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 ligamed is excreted in human milk. Caution should be exercised when administered to nursing women.

Storage

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

Indications

• Type 2 diabetes mellitus
• Impaired glucose tolerance

Dosage

Children: Safety and efficacy in children have not been established. Refer to specific pediatric guidelines for management of diabetes.

Adults: The usual starting dose is 50 mg three times daily taken with the first bite of each meal. The dose may be increased to a maximum of 100 mg three times daily based on tolerance and glycemic control.

Mechanism of action

Luzenac inhibits alpha-glucosidase enzymes in the brush border of the small intestine. This inhibition leads to a reduction in the digestion and absorption of carbohydrates, resulting in a decreased rate of glucose absorption and lower postprandial blood glucose levels. The action of Luzenac is site-specific and primarily affects carbohydrate metabolism.

Pharmacodynamics

The pharmacodynamics of Luzenac is characterized by its ability to lower postprandial blood glucose levels without causing significant hypoglycemia when used alone. By slowing the absorption of carbohydrates, it helps to prevent spikes in glucose levels after meals. The drug is not absorbed systemically, which minimizes the risk of systemic side effects.

Pharmacokinetics

Luzenac is not absorbed from the gastrointestinal tract and, therefore, does not have a systemic circulation. It acts locally within the gut. The onset of action occurs within 30 minutes to 2 hours after a meal, and its effects can last for several hours. The drug is eliminated from the body through feces, primarily in its unchanged form.

Pregnancy

There is limited data on the use of luzenac during pregnancy. Caution is advised, and it should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is unknown if luzenac is excreted in human milk. Caution is advised when administering to breastfeeding women.

Storage

Store at room temperature, away from moisture and heat. Protect from light.

Mechanism of action

The most widely accepted mechanism of nitazoxanide is the disruption of energy metabolism in anaerobic microbes by inhibition of the pyruvate:ferredoxin/flavodoxin oxidoreductase (PFOR) cycle. It induces lesions in cell membranes and depolarizes the mitochondrial membrane, inhibiting enzymes such as quinone oxidoreductase NQO1, nitroreductase-1, and protein disulfide isomerase. Additionally, it inhibits glutathione-S-transferase, modulates the Avr-14 gene in nematodes, and exhibits various antibacterial mechanisms, including inhibition of pyruvate dehydrogenase in E. coli and disruption of Mycobacterium tuberculosis membrane potential. Nitazoxanide also suppresses viral replication by inhibiting maturation of viral hemagglutinin and activating antiviral intracellular proteins.

Pharmacodynamics

Nitazoxanide prevents microbial activity by disrupting essential energy pathways necessary for survival and proliferation. It exhibits antiprotozoal activity by interfering with the PFOR-dependent electron transfer reaction, crucial for anaerobic energy metabolism. This interference inhibits the sporozoites of Cryptosporidium parvum and trophozoites of Giardia lamblia, relieving diarrhea symptoms. The disruption of the PFOR enzyme-dependent reaction is one of several pathways through which nitazoxanide exerts its antiprotozoal effects.

Pharmacokinetics

Nitazoxanide is rapidly absorbed and extensively metabolized in the liver to its active metabolite, tizoxanide. The drug is excreted primarily in the urine and feces. The pharmacokinetics of nitazoxanide can be influenced by factors such as age, liver function, and co-administration of other medications. The half-life of nitazoxanide is approximately 1 to 3 hours, while tizoxanide has a longer half-life, allowing for

Adverse effects

• Abdominal pain
• Diarrhea
• Nausea
• Headache
• Dizziness

Precautions

• Use with caution in patients with hepatic impairment
• Monitor for gastrointestinal side effects

Pregnancy

Nitazoxanide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Data on the use of nitazoxanide in pregnant women is limited.

Breast-feeding

It is not known whether nitazoxanide is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

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

Formulations

• Oral suspension
• Tablet

Indications

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Pregnancy

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

Breast-feeding

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

Storage

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

Formulations

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

Dosage

Children: For specific paediatric dosing, refer to the BNF for Children.

Adults: For specific dosing, refer to the BNF or relevant drug-specific guidelines.

Mechanism of action

Pharmaceuticals work through a variety of mechanisms depending on the specific drug. Common mechanisms include receptor modulation, enzyme inhibition, ion channel blockade, and alteration of neurotransmitter levels. For example, many analgesics act by inhibiting cyclooxygenase enzymes, leading to decreased production of pro-inflammatory compounds.

Pharmacodynamics

Pharmacodynamics involves how drugs exert their effects on the body. This includes the relationship between drug concentration and effect, the duration of action, and the therapeutic window. The efficacy and safety of a drug are determined by its pharmacodynamic properties, including its potency, selectivity for its target, and the biochemical pathways it influences.

Pharmacokinetics

Pharmacokinetics refers to the absorption, distribution, metabolism, and excretion (ADME) of drugs. This includes how a drug is absorbed into the bloodstream, its distribution throughout the body, how it is metabolized by enzymes (often in the liver), and its route of excretion (usually via urine or feces). These processes determine the onset, intensity, and duration of a drug's action.

Pregnancy

Consult a healthcare professional before use. Safety during pregnancy has not been established.

Breast-feeding

Consult a healthcare professional before use. Safety during breastfeeding has not been established.

Storage

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

Indications

• Used as a binder in tablet formulations
• Serves as a disintegrant to enhance drug release
• Utilized in the formulation of granules and powders

Dosage

Children: Refer to specific formulation guidelines as doses vary based on the formulation and active ingredients.

Adults: Refer to specific formulation guidelines as doses vary based on the formulation and active ingredients.

Mechanism of action

Pregelatinized starch acts primarily as a binder and disintegrant in tablet formulations. When exposed to moisture, it swells and rapidly absorbs water, leading to the disintegration of the tablet and facilitating the release of the active pharmaceutical ingredients.

Pharmacodynamics

The pharmacodynamic properties of pregelatinized starch are closely related to its physicochemical characteristics. It enhances the dissolution rate of poorly soluble drugs and helps in achieving a uniform distribution of the active ingredients within a formulation. Its ability to form a gel-like consistency in the presence of water aids in the controlled release of the drug.

Pharmacokinetics

As an excipient, pregelatinized starch is not intended to exert pharmacological effects on its own. It is generally regarded as safe and is not absorbed systemically. Its role is primarily mechanical, aiding in the formulation process of pharmaceutical products. The pharmacokinetics of any drug formulated with pregelatinized starch will depend on the active ingredients present in the formulation.

Pregnancy

Pregelatinized starch is generally considered safe for use during pregnancy as it is a food grade ingredient, but it is advisable to consult with a healthcare professional.

Breast-feeding

Pregelatinized starch is also considered safe during breastfeeding as it is unlikely to affect milk production or quality.

Storage

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

Formulations

• Powder
• Granules

Indications

• Used as a binding agent in tablet formulations
• Serves as a disintegrant to facilitate drug release
• Functions as a thickening agent in various pharmaceutical preparations

Dosage

Children: Refer to specific product formulations and guidelines, as dosing will depend on the active ingredients and intended use of the formulated product.

Adults: Refer to specific product formulations and guidelines, as dosing will depend on the active ingredients and intended use of the formulated product.

Mechanism of action

Pregelatinized starch acts primarily as a binding and disintegrating agent in tablet formulations. Upon contact with water, it swells and allows for the disintegration of the tablet, facilitating the release of the active pharmaceutical ingredient. Its gelatinized form enables rapid absorption of water, promoting effective dispersion and dissolution of the formulation components.

Pharmacodynamics

The pharmacodynamics of pregelatinized starch are primarily related to its physical properties rather than pharmacological activity. It aids in the formation and stability of tablets and capsules, influencing the release profile of the active ingredient. Its ability to disintegrate tablets quickly ensures that the drug is available for absorption in the gastrointestinal tract.

Pharmacokinetics

As an excipient, pregelatinized starch does not exhibit pharmacokinetic properties typical of active drugs. It is not absorbed into the systemic circulation, as it primarily functions within the formulation to aid in the delivery of the active drug. The pharmacokinetic behavior of the final dosage form will depend on the active pharmaceutical ingredient rather than the excipient itself.

Pregnancy

Consult a healthcare professional before use during pregnancy.

Breast-feeding

Consult a healthcare professional before use while breastfeeding.

Storage

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

Dosage

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

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

Mechanism of action

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

Pharmacodynamics

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

Pharmacokinetics

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

Pregnancy

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

Breast-feeding

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

Storage

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

Indications

• 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

• Used as an excipient in drug formulations
• Pleurodesis for the management of recurrent pleural effusions

Dosage

Children: Refer to specific guidelines for paediatric use, as dosing may differ based on age and clinical condition.

Adults: Refer to specific guidelines for the appropriate dosage in pleurodesis and other applications, as it may vary based on clinical context.

Mechanism of action

Talc exhibits very good absorptive properties, allowing it to absorb moisture and other substances effectively. This characteristic is particularly useful in pharmaceutical formulations, where it may enhance the stability and texture of the drug product.

Pharmacodynamics

Talc's primary pharmacodynamic effect is its ability to act as an inert filler and bulking agent in pharmaceutical preparations. It does not have any intrinsic pharmacological activity but serves to improve the physical properties of formulations, such as flowability and compressibility.

Pharmacokinetics

Talc is not absorbed systemically when used as an excipient or in medical procedures. Its effects are local, and it remains in the site of application, where it functions primarily as a mechanical agent. The pharmacokinetics of talc in the context of its use in pleurodesis involves its ability to promote adhesion of the pleural surfaces, thereby preventing fluid accumulation.

Pregnancy

Talc is classified as a substance with minimal systemic absorption, but safety during pregnancy has not been well established. Consult relevant guidelines.

Breast-feeding

Talc is not expected to be absorbed in significant amounts; however, caution is advised and consult guidelines.

Storage

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

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.

Mechanism of action

The most widely accepted mechanism of NTZ is believed to be the disruption of the energy metabolism in anaerobic microbes by inhibition of the pyruvate: ferredoxin/flavodoxin oxidoreductase (PFOR) cycle. In parasitic-protozoa, Nitazoxanide also induces lesions in the cell membranes and depolarizes the mitochondrial membrane while inhibiting quinone oxidoreductase NQO1, nitroreductase-1 and protein disulphide isomerase enzymes. In addition, this drug also inhibits the glutathione-S-transferase (a major detoxifying enzyme) and modulates the Avr-14 gene, encoding for the alpha-type subunit of glutamate-gated chloride ion channel present in nematodes. Aside from its well understood non-competitive inhibition of the PFOR in anaerobic bacteria, NTZ also demonstrates various other antibacterial mechanisms. It inhibits pyruvate dehydrogenase in E Coli, disrupts the membrane potential and pH homeostasis in the Mycobacterium tuberculosis, suppresses the chaperone/usher (CU) pathway of the gram-negative bacteria, and stimulates host macrophage autophagy in tuberculosis patients. NTZ also suppresses viral replication by inhibiting the maturation of the viral hemagglutinin and the viral transcription factor immediate early 2 (IE2) as well as by activating the eukaryotic translation initiation factor 2α (an antiviral intracellular protein). Lastly, NTZ exhibits an inhibitory effect on tumor cell progression by altering drug detoxification (glutathione-S-transferase P1), unfolded protein response, autophagy, anti-cytokines activity, and c-Myc inhibition.

Pharmacodynamics

The general effect of this medication is the prevention of microbe activity through disruption of important energy pathways for survival and proliferation. Nitazoxanide exhibits antiprotozoal activity by interfering with the pyruvate ferredoxin/flavodoxin oxidoreductase dependent electron transfer reaction, an essential reaction need for anaerobic energy metabolism of various microorganisms. Sporozoites of Cryptosporidium parvum and trophozoites of Giardia lamblia are therefore inhibited, relieving symptoms of diahrrea. Interference with the PFOR enzyme-dependent electron transfer reaction may only be one of the many pathways by which nitazoxanide exhibits antiprotozoal activity.

Mechanism of action

It has very good absorptive properties.