AMIDIOSTAT -PLUS WATER SOLUBLE POWDER

Indications

• Coccidiosis in poultry
• Coccidiosis in livestock
• Prevention of coccidial infections in animals

Dosage

Children: Refer to veterinary guidelines for specific dosing for younger animals, as it may vary according to weight and age.

Adults: Refer to veterinary guidelines for specific dosing based on the type of animal and severity of infection.

Mechanism of action

Amprolium acts as a thiamine antagonist, inhibiting the uptake of thiamine in the protozoa. This leads to depletion of thiamine within the parasites, which is essential for their energy metabolism and growth. The lack of thiamine disrupts several metabolic pathways, ultimately resulting in the death of the parasitic organisms.

Pharmacodynamics

Amprolium exhibits selective toxicity towards protozoa by exploiting the differences in thiamine metabolism between the host and the parasite. The drug's action is primarily coccidiostatic, preventing the development and reproduction of Eimeria species. The effectiveness of amprolium is influenced by factors such as the specific strain of Eimeria, the dosage administered, and the duration of treatment.

Pharmacokinetics

Amprolium is well absorbed after oral administration, with peak plasma concentrations occurring within a few hours. It is primarily metabolized in the liver, and its metabolites are excreted mainly through the urine. The drug has a relatively short half-life, necessitating multiple doses for effective treatment. The pharmacokinetic profile may vary between species, and veterinary guidelines should be followed for specific dosing regimens.

Adverse effects

• Anorexia
• Weight loss
• Neurological signs including ataxia
• Thiamine deficiency symptoms

Precautions

• Use with caution in animals with pre-existing neurological conditions
• Monitor for signs of thiamine deficiency

Pregnancy

There are no adequate and well-controlled studies in pregnant animals. Use with caution.

Breast-feeding

Not established. Caution is advised.

Storage

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

Formulations

• Oral powder
• Oral solution

Indications

• Vitamin A deficiency
• Night blindness
• Impaired wound healing
• Epithelial disorders

Dosage

Children: Refer to BNF for Children for specific paediatric dosing information.

Adults: Refer to BNF for specific adult dosing information.

Mechanism of action

Retinol is converted in the retina to 11-cis-retinal, which is crucial for the conversion of light into neural signals necessary for vision. It binds to opsin in rhodopsin, facilitating the isomerization to all-trans-retinal upon exposure to light, thus triggering visual signaling. Additionally, retinol interacts with retinoic acid receptors (RARs) and retinoid-X receptors (RXRs) as transcription factors, modulating gene expression related to cellular differentiation and growth.

Pharmacodynamics

Vitamin A is effective in treating Vitamin A deficiency, which can lead to vision impairment and other health issues. It plays a critical role in various biological processes including vision, cellular differentiation, reproduction, and immune system function. Its deficiency can cause symptoms such as night blindness and impaired wound healing, while adequate levels support growth and development.

Pharmacokinetics

Retinol is absorbed from the gastrointestinal tract and stored in the liver, where it can be mobilized as needed. It undergoes metabolism primarily in the liver, where it is converted to retinal and retinoic acid, the active forms of Vitamin A. The elimination half-life varies, but retinol is generally excreted in urine and bile. The bioavailability can be affected by dietary fat intake.

Adverse effects

• Nausea
• Vomiting
• Headache
• Dizziness
• Fatigue
• Irritability
• Dry skin
• Peeling of skin
• Itching
• Blurred vision

Precautions

• Use with caution in patients with liver disease due to potential hepatotoxicity.
• Monitor for signs of vitamin A toxicity, especially in patients on high doses or prolonged therapy.
• Caution in patients with a history of alcohol abuse, as it may exacerbate liver conditions.

Pregnancy

Retinol should be used with caution during pregnancy due to the risk of teratogenic effects. High doses of vitamin A can lead to fetal malformations.

Breast-feeding

Retinol is generally considered safe during breastfeeding, but excessive intake should be avoided to prevent potential adverse effects on the infant.

Storage

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

Formulations

• Capsules
• Tablets
• Oral solutions
• Topical preparations

Indications

• Bacterial infections in veterinary medicine
• Coccidiosis in poultry
• Treatment of certain protozoal infections

Dosage

Children: Refer to the relevant prescribing information for specific dosing guidelines as per clinical condition.

Adults: Refer to the relevant prescribing information for specific dosing guidelines as per clinical condition.

Mechanism of action

Sulfaquinoxaline acts as a competitive antagonist of para-aminobenzoic acid (PABA), a key substrate in the bacterial synthesis of folic acid. By inhibiting the enzyme dihydropteroate synthase, sulfaquinoxaline prevents the incorporation of PABA into dihydropteroic acid, which is the precursor of folic acid. This inhibition disrupts the formation of folic acid necessary for DNA synthesis, thus hindering bacterial cell multiplication. Mammalian cells, which utilize preformed folic acid, are not affected by this mechanism.

Pharmacodynamics

The pharmacodynamics of sulfaquinoxaline are characterized by its ability to inhibit bacterial growth through the blockade of folic acid synthesis. It demonstrates a bacteriostatic effect, meaning it stops bacteria from multiplying rather than killing them directly. The efficacy of sulfaquinoxaline depends on the susceptibility of the bacteria involved and is influenced by the presence of PABA in the environment, which can compete with the drug.

Pharmacokinetics

Sulfaquinoxaline is well absorbed from the gastrointestinal tract and achieves therapeutic levels in the serum. It has a distribution that allows it to penetrate tissues and body fluids. The drug is metabolized in the liver and excreted primarily through the kidneys. The pharmacokinetic profile can be influenced by factors such as the presence of other substances that may compete for absorption or metabolism.

Contra-indications

• Hypersensitivity to sulfonamides
• Severe hepatic or renal impairment
• Porphyria

Adverse effects

• Allergic reactions including rash, itching, and fever
• Gastrointestinal disturbances such as nausea and vomiting
• Hematological effects including leukopenia, thrombocytopenia, and aplastic anemia
• Kernicterus in newborns
• Crystalluria

Interactions

• May enhance the effects of anticoagulants such as warfarin
• Potentially decreases the effectiveness of oral contraceptives
• Can increase the toxicity of methotrexate
• May interact with other drugs that affect renal function

Precautions

• Use with caution in patients with renal impairment
• Monitor for signs of blood dyscrasias
• Adequate hydration is important to prevent crystalluria
• Caution in patients with a history of asthma or allergic reactions

Pregnancy

Use during pregnancy only if clearly needed, as sulfonamides can cross the placenta and may cause harm to the fetus.

Breast-feeding

Breastfeeding is not recommended while taking sulfaquinoxaline due to potential adverse effects on the infant.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets
• Suspensions
• Injectable forms

Indications

• Vitamin deficiency syndromes (e.g., scurvy for vitamin C deficiency, rickets for vitamin D deficiency)
• Support for immune function
• Antioxidant support
• Bone health maintenance
• Vision health
• Energy metabolism support

Dosage

Children: Refer to the BNF for Children for specific vitamin dosing guidelines, which depend on age and nutritional requirements.

Adults: Refer to specific vitamin guidelines as dosage varies significantly depending on the type of vitamin and individual needs.

Mechanism of action

Vitamins function primarily as coenzymes or precursors for coenzymes in enzymatic reactions. For instance, B vitamins are involved in energy metabolism, while vitamins A, C, D, E, and K support various physiological functions including vision, antioxidant activity, calcium regulation, and blood clotting. Each vitamin has a unique mechanism of action based on its structure and role in the body.

Pharmacodynamics

Vitamins exert their effects at the cellular level, influencing metabolic pathways, gene expression, and immune responses. For example, vitamin D regulates calcium and phosphate homeostasis, while vitamin A is crucial for vision and immune function. Deficiencies in vitamins can lead to a range of disorders, highlighting their importance in maintaining health.

Pharmacokinetics

The pharmacokinetics of vitamins vary widely. Fat-soluble vitamins (A, D, E, and K) are stored in liver and adipose tissues and can be released into circulation as needed. Water-soluble vitamins (B-complex and C) are not stored and must be consumed regularly, with excess amounts excreted in urine. Absorption rates, half-lives, and distribution can also differ based on the specific vitamin and individual metabolic factors.

Interactions

• tretinoin+vitamin: Severe (increases risk of vitamin toxicity)
• retinoids+vitamin: Severe (increases risk of vitamin toxicity)
• retinoids+vitamin: Moderate (increases risk of toxicity)
• carbamazepine+vitamin: Unknown (decreases effects)
• cobicistat+vitamin: Unknown (increases exposure)
• vitamin D substances+digoxin: Unknown (increases risk of toxicity)
• idelalisib+vitamin: Unknown (increases exposure)
• clarithromycin+vitamin: Unknown (increases exposure)

Pregnancy

Consult healthcare professional before use. Vitamin supplementation during pregnancy should be carefully managed to avoid hypervitaminosis.

Breast-feeding

Consult healthcare professional before use. Some vitamins can pass into breast milk and may affect the infant.

Storage

Store in a cool, dry place, away from direct sunlight. Ensure it is kept out of reach of children.

Formulations

• {'name': 'Vitamin A', 'form': 'Capsule', 'strength': '10000 IU'}
• {'name': 'Vitamin D', 'form': 'Tablet', 'strength': '1000 IU'}
• {'name': 'Vitamin E', 'form': 'Softgel', 'strength': '400 IU'}

Mechanism of action

Vision:Vitamin A (all-<i>trans</i> retinol) is converted in the retina to the 11-<i>cis</i>-isomer of retinaldehyde or 11-<i>cis</i>-retinal. 11-<i>cis</i>-retinal functions in the retina in the transduction of light into the neural signals necessary for vision. 11-<i>cis</i>-retinal, while attached to opsin in rhodopsin is isomerized to all-<i>trans</i>-retinal by light. This is the event that triggers the nerve impulse to the brain which allows for the perception of light. All-<i>trans</i>-retinal is then released from opsin and reduced to all-<i>trans</i>-retinol. All-<i>trans</i>-retinol is isomerized to 11-<i>cis</i>-retinol in the dark, and then oxidized to 11-<i>cis</i>-retinal. 11-<i>cis</i>-retinal recombines with opsin to re-form rhodopsin. Night blindness or defective vision at low illumination results from a failure to re-synthesize 11-<i>cis</i> retinal rapidly. Epithelial differentiation: The role of Vitamin A in epithelial differentiation, as well as in other physiological processes, involves the binding of Vitamin A to two families of nuclear retinoid receptors (retinoic acid receptors, RARs; and retinoid-X receptors, RXRs). These receptors function as ligand-activated transcription factors that modulate gene transcription. When there is not enough Vitamin A to bind these receptors, natural cell differentiation and growth are interrupted. Topical vitamin A can reverse the impairment of wound healing seen in patients receiving corticosteroids, perhaps by restoring the normal inflammatory reaction in the wound. The possibility has been suggested that systemic vitamin A could inhibit the anti-inflammatory effect of systemic corticosteroids. Retinol arrested proliferation of cultured neuroblastoma cells at concentrations of 50 um. A correlation existed between inhibition of growth and inhibition of ornithine decarboxylase in both neuroblastoma cells and glioma cells with retinol. In rats exptl-hypervitaminosis A has been shown ... to produce severe damage of the retina, mainly in the pigment epithelium according to electron microscopy. Alcohol dehydrogenase activity was shown to disappear in the pigment epithelium and visual cells ... . /The authors/ have shown that in an experimental cell culture system consisting of carcinogen-treated 10T1/2 cells, both retinoids and all dietary carotenoids examined can reversibly inhibit neoplastic transformation in the post-initiation phase of carcinogenesis. This activity strongly correlates with their ability to increase gap junctional intercellular communication by up-regulating the expression of the gene CX43 (connexin43). Connexins comprise the structural unit of gap junctions, organelles which allow direct transfer of signals, nutrients and waste products between contacting cells. CX43 is the most widely expressed member of the gap junction family of genes, and we have demonstrated that its expression is strongly down-regulated in human cancers and in several premalignant conditions. When several human tumour cell lines were genetically engineered to conditionally express CX43 under the influence of a tetracycline promoter, their neoplastic phenotype was strongly attenuated. Specifically, induced cells were inhibited from growing in an anchorage-independent manner and, additionally, growth as xenografts in immunocompromised animals was also strongly attenuated. Growth inhibition in suspension was associated both with increased G(1) cell-cycle arrest and with increased apoptosis. /The authors/ propose a model whereby junctional communication allows the transfer of growth inhibitory signals from normal to neoplastic cells and that retinoids and carotenoids, by increasing signal transfer, act to prevent cancer.

Pharmacodynamics

Vitamin A is effective for the treatment of Vitamin A deficiency. Vitamin A refers to a group of fat-soluble substances that are structurally related to and possess the biological activity of the parent substance of the group called all-<i>trans</i> retinol or retinol. Vitamin A plays vital roles in vision, epithelial differentiation, growth, reproduction, pattern formation during embryogenesis, bone development, hematopoiesis and brain development. It is also important for the maintenance of the proper functioning of the immune system.

Mechanism of action

Bacteriostatic. Sulfonamides interfere with the biosynthesis of folic acid in bacterial cells; they compete with paraaminobenzoic acid (PABA) for incorporation in the folic acid molecule. By replacing the PABA molecule and preventing the folic acid formation required for DNA synthesis, the sulfonamides prevent multiplication of the bacterial cell. Susceptible organisms must synthesize their own folic acid; mammalian cells use preformed folic acid and, therefore, are not susceptible. Cells that produce excess PABA or environments with PABA, such as necrotic tissues, allow for resistance by competition with the sulfonamide. /Sulfonamides/ Sulfonamides are structural analogs and competitive antagonists of para-aminobenzoic acid (PABA) and thus prevent normal bacterial utilization of PABA for the synthesis of folic acid (pteroylglutamic acid). More specifically, sulfonamides are competitive inhibitors of dihydropteroate synthase,the bacterial enzyme responsible for the incorporation of PABA into dihydropteroic acid, the immediate precursor of folic acid. Sensitive microorganisms are those that must synthesize their own folic acid; bacteria that can utilize preformed folate are not affected. Bacteriostasis induced by sulfonamides is counteracted by PABA competitively. Sulfonamides do not affect mammalian cells by this mechanism, since they require preformed folic acid and cannot synthesize it. /Sulfonamides/