TINILOX-MPS TABLETS

Indications

• Intestinal amoebiasis
• Urogenital trichomoniasis
• Giardiasis

Dosage

Children: For children aged 1 month to 11 years, the dosage is 50–75 mg/kg once, with a maximum of 2 g per dose. For children aged 12 to 17 years, the dosage is 2 g for a single dose, which may be repeated once if necessary.

Adults: The usual adult dosage is 2 g taken orally as a single dose for urogenital trichomoniasis or giardiasis, and 1.5 g to 2 g once daily for 3 to 6 days for intestinal amoebiasis.

Mechanism of action

Tinidazole acts as a prodrug and antiprotozoal agent. Its nitro group is reduced in Trichomonas by a ferredoxin-mediated electron transport system, generating free nitro radicals that covalently bind to DNA, causing DNA damage and cell death. The exact mechanism of action against Giardia and Entamoeba species is not fully understood but is believed to be similar to that of Trichomonas.

Pharmacodynamics

Tinidazole demonstrates in vitro and clinical activity against Trichomonas vaginalis, Giardia duodenalis (also known as G. lamblia), and Entamoeba histolytica. It does not exhibit significant activity against most strains of vaginal lactobacilli, which are beneficial bacteria in the vaginal flora.

Pharmacokinetics

Tinidazole is well absorbed following oral administration, with peak plasma concentrations occurring within 0.5 to 3 hours. It is extensively distributed throughout body tissues and fluids. The drug undergoes hepatic metabolism and is eliminated primarily through the urine, with a half-life of approximately 12 to 14 hours. Clinical and laboratory monitoring is advised if treatment extends beyond 10 days.

Adverse effects

• Abdominal pain
• Decreased appetite
• Diarrhoea
• Headache
• Nausea
• Skin reactions
• Vertigo
• Vomiting

Precautions

• Clinical and laboratory monitoring is advised if treatment exceeds 10 days

Pregnancy

Manufacturer advises avoiding use in the first trimester.

Breast-feeding

Present in milk; the manufacturer advises avoiding breastfeeding during and for 3 days after stopping treatment.

Storage

Store below 25°C, protect from moisture.

Formulations

• Tinidazole 500 mg tablets
• Tinidazole oral suspension

Indications

• Head lice
• Scabies
• Other parasitic skin infections

Dosage

Children: For head lice, apply once weekly for 2 doses, rub preparation into dry hair and scalp, allow to dry naturally, and wash off after 12 hours or overnight. For scabies, children can also apply the treatment over the whole body, allowing it to dry naturally and washing off after 12 hours or overnight.

Adults: Apply twice daily for a minimum of 8 hours (or overnight) for head lice treatment. For scabies, apply over the whole body and wash off after 24 hours. Dosage may vary depending on the specific formulation and clinical guidelines.

Mechanism of action

Dimeticone acts by forming a protective barrier on the skin, which can interfere with the respiration of lice and other parasites. This suffocation mechanism helps to eliminate these pests effectively. Additionally, it reduces surface tension, minimizing foaming and aiding in the smooth application of topical formulations.

Pharmacodynamics

Dimeticone exhibits emollient properties, providing a protective layer on the skin. It is largely inert and does not significantly penetrate the skin, which limits systemic absorption. The primary action of Dimeticone is mechanical rather than chemical, as it acts to physically block or suffocate ectoparasites.

Pharmacokinetics

Dimeticone is poorly absorbed through the skin and is not expected to enter systemic circulation to any significant extent. Its effects are localized to the site of application, where it remains on the skin's surface to provide a physical barrier. The compound is metabolically stable and is excreted unchanged.

Adverse effects

• Skin irritation
• Eye irritation
• Mucosal irritation
• Hypersensitivity reactions

Precautions

• Avoid contact with eyes
• Avoid contact with mucous membranes
• Avoid application on broken or inflamed skin

Pregnancy

Use with caution; consult healthcare provider.

Breast-feeding

Suspend feeding until product has been washed off.

Storage

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

Formulations

• Cream
• Ointment
• Liquid

Indications

• Dry eye conditions
• Anterior uveitis
• Cycloplegia

Dosage

Children: For children aged 3 months to 1 year, apply 1 drop once daily or on alternate days, adjusted according to response. For children aged 2 to 17 years

Adults: Apply 1 drop to the affected eye 3–4 times daily as directed, adjusting frequency based on clinical response.

Mechanism of action

Homatropine hydrobromide works by blocking the action of acetylcholine at muscarinic receptors in the iris sphincter and ciliary body. This antagonism leads to dilation of the pupil (mydriasis) and paralysis of the ciliary muscle (cycloplegia), resulting in decreased eye accommodation. It also reduces secretions from mucous membranes, which can help alleviate symptoms associated with dry eye.

Pharmacodynamics

The pharmacodynamic effects of homatropine hydrobromide are characterized by its ability to induce mydriasis and cycloplegia, which are crucial for diagnostic procedures in ophthalmology. Its anti-secretory properties also contribute to its therapeutic effects in treating dry eye conditions. The onset of action occurs within 30 to 60 minutes after administration, with peak effects typically lasting up to 24 hours.

Pharmacokinetics

Homatropine hydrobromide is administered topically as eye drops, leading to localized effects with minimal systemic absorption. Its bioavailability through the ocular route is influenced by factors such as corneal permeability and the formulation of the eye drops. The metabolism and excretion pathways are not extensively documented, but the drug is expected to undergo hepatic metabolism, with metabolites likely excreted renally. Systemic absorption may lead to side effects, particularly in sensitive populations such as children and the elderly.

Adverse effects

• Eye discomfort
• Eye redness
• Abdominal distension (in children)
• Behavioural abnormalities (in children)
• Cardiac arrhythmias
• Respiratory distress (in children)
• Conjunctivitis
• Constipation
• Dry mouth
• Oedema (on prolonged administration)
• Flushing
• Gastrointestinal disorders
• Hyperaemia (on prolonged administration)
• Mydriasis
• Palpitations
• Psychotic disorders (in children)
• Staggering
• Urinary disorders
• Vomiting

Precautions

• Use caution in children and the elderly due to potential for systemic side effects.
• Preservative-free formulations are preferred for frequent and chronic application.

Pregnancy

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

Breast-feeding

Use with caution. The effects on a nursing infant are unknown.

Storage

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

Formulations

• Homatropine hydrobromide 0.5% eye drops
• Homatropine hydrobromide 1% eye drops

Indications

• Asymptomatic intestinal amebiasis
• Amebic dysentery (as part of combination therapy)

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing guidelines.

Adults: Refer to the BNF for specific adult dosing guidelines.

Mechanism of action

The exact mechanism of action of diloxanide is unknown. It may inhibit protein synthesis, which contributes to its efficacy against the trophozoites of E. histolytica.

Pharmacodynamics

Diloxanide acts as a luminal amebicide, effectively destroying the trophozoites of Entamoeba histolytica. The drug's action helps in reducing the load of the organism in the intestinal lumen, thereby preventing the formation of cysts and subsequent transmission of the infection.

Pharmacokinetics

Diloxanide is administered orally and is hydrolyzed in the gastrointestinal tract to release the active ingredient. The pharmacokinetics, including absorption, distribution, metabolism, and excretion specifics, are not well-documented, indicating a need for further research in these areas.

Pregnancy

There is limited data on the use of diloxanide during pregnancy. It should only be used if clearly needed.

Breast-feeding

Diloxanide is excreted in breast milk, caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• tablets

Indications

• Asymptomatic intestinal amebiasis
• Amoebic dysentery (mild cases)

Dosage

Children: Refer to the relevant prescribing information or guidelines.

Adults: Refer to the relevant prescribing information or guidelines.

Mechanism of action

Diloxanide furoate works by inhibiting the growth of the Entamoeba histolytica trophozoites in the intestines. The active metabolite, diloxanide, disrupts the cellular function of the protozoa, leading to cell lysis and death. It is thought to interfere with the protozoan's ability to utilize glucose and other nutrients, thereby inhibiting their metabolic processes.

Pharmacodynamics

Diloxanide furoate's effectiveness against Entamoeba histolytica is due to its ability to alter the protozoan's metabolic pathways, particularly affecting glucose metabolism. This results in a reduction of the organism's viability and ability to replicate. The drug's action is primarily localized to the intestinal lumen, minimizing systemic exposure and associated side effects.

Pharmacokinetics

After oral administration, diloxanide furoate is rapidly absorbed and metabolized to its active form, diloxanide. The drug is extensively metabolized in the liver, with a half-life of approximately 12 hours. It is excreted mainly in the feces, with minimal renal excretion. The bioavailability of diloxanide is enhanced when taken with food, leading to improved therapeutic outcomes.

Adverse effects

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

Precautions

• Use with caution in patients with a history of gastrointestinal disorders.
• Monitor liver function tests in patients with pre-existing liver conditions.

Pregnancy

There is limited data on the use of diloxanide furoate in pregnancy. It should be used only if clearly needed and the potential benefits justify the potential risks to the fetus.

Breast-feeding

It is not known whether diloxanide furoate is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Oral tablet
• Oral suspension

Indications

• Mydriasis for ophthalmic examination
• Cycloplegia for refractive error assessment
• Treatment of uveitis and iritis

Dosage

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

Adults: For mydriasis, 1-2 drops of 2% or 5% solution may be instilled in the affected eye(s) as needed, up to 3 times a day.

Mechanism of action

Homatropine works by blocking the action of acetylcholine on muscarinic receptors in the iris sphincter muscle and the ciliary body. This results in dilation of the pupil (mydriasis) and paralysis of the ciliary muscle (cycloplegia), leading to reduced accommodation and facilitating diagnostic procedures in the eye.

Pharmacodynamics

The anticholinergic effects of homatropine lead to increased intraocular pressure due to the relaxation of the ciliary muscle and the dilation of the pupil. This can be particularly useful in certain ocular conditions but may also pose risks in patients with narrow-angle glaucoma. The onset of mydriatic effect typically occurs within 30 minutes and can last for several hours.

Pharmacokinetics

Homatropine is rapidly absorbed following ocular administration. Its effects can be prolonged due to its binding to ocular tissues. The drug is metabolized in the liver and excreted in the urine. The half-life of homatropine is variable but generally, its effects persist for a few hours after administration.

Interactions

• clozapine+homatropine: Unknown (additive effect)
• antipsychotics, second generation+homatropine: Unknown (additive effect)

Pregnancy

The safety of homatropine during pregnancy has not been established. Use with caution and only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Homatropine is excreted in breast milk. Caution is recommended when administering to nursing mothers.

Storage

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

Indications

• Allergic conditions
• Autoimmune diseases
• Asthma and chronic obstructive pulmonary disease (COPD)
• Certain cancers (e.g., leukemia, lymphoma)
• Skin conditions (e.g., dermatitis)
• Inflammatory bowel disease
• Multiple sclerosis exacerbations
• Severe infections requiring immunosuppression

Dosage

Children: Refer to BNF for Children for specific dosing; doses vary significantly based on the child's age, weight, and condition being treated.

Adults: Refer to BNF for specific dosing; typically, initial doses range from 4 to 48 mg depending on the severity of the condition.

Mechanism of action

Methylprednisolone exerts its effects by binding to glucocorticoid receptors, leading to the modulation of gene expression. This interaction influences the transcription of anti-inflammatory proteins while suppressing the expression of pro-inflammatory genes, ultimately resulting in reduced inflammation and immune response.

Pharmacodynamics

The pharmacodynamic effects of methylprednisolone are characterized by its ability to decrease inflammation, suppress the immune response, and affect carbohydrate metabolism. Therapeutic doses lead to various systemic effects, including modification of leukocyte distribution and inhibition of cytokine production.

Pharmacokinetics

Methylprednisolone is well absorbed after oral administration, with a bioavailability of approximately 50%. It has a volume of distribution that reflects extensive tissue binding. The drug is metabolized primarily in the liver through conjugation and reduction, and its metabolites are excreted in urine. The half-life varies based on the route of administration but is generally around 18 to 36 hours.

Adverse effects

• Increased blood pressure
• Hyperglycemia
• Weight gain
• Mood changes
• Insomnia
• Gastrointestinal disturbances
• Increased susceptibility to infections

Interactions

• methylphenidate+apraclonidine: Severe (decreases effects)
• methylthioninium chloride+bupropion: Severe (increases risk of severe hypertension)
• methylphenidate+linezolid: Severe (increases risk of elevated blood pressure)
• rasagiline+methylphenidate: Severe (increases risk of a hypertensive crisis)
• mao-inhibitors+methylphenidate: Severe (increases risk of a hypertensive crisis)
• dronedarone+methylprednisolone: Moderate (increases exposure)
• miconazole+methylprednisolone: Moderate (increases concentration)
• antifungals, azoles+methylprednisolone: Moderate (increases exposure)
• crizotinib+methylprednisolone: Moderate (increases exposure)

Precautions

• Use with caution in patients with hypertension
• Monitor blood glucose levels in diabetic patients
• Consider potential for infection risk due to immunosuppression
• Evaluate for psychiatric effects in susceptible individuals

Pregnancy

Corticosteroids may be used during pregnancy if the potential benefit justifies the risk to the fetus. Careful monitoring is advised.

Breast-feeding

Corticosteroids are excreted in breast milk; caution is advised. Monitor the infant for potential effects.

Storage

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

Formulations

• Tablets
• Injectable solutions
• Topical preparations

Indications

• Pest control in agriculture
• Fumigation of stored products
• Soil treatment

Dosage

Children: Refer to specific guidelines for application and exposure limits, as methylbromide is not generally administered therapeutically.

Adults: Refer to specific guidelines for application and exposure limits as methylbromide is used mainly in agricultural settings.

Mechanism of action

Methylbromide acts as a methylating agent, affecting the biological pathways of pest organisms. It disrupts cellular processes by alkylating nucleophilic sites in DNA and proteins, leading to cell death. The compound is absorbed through the respiratory system in pests, where it interferes with their metabolic functions.

Pharmacodynamics

Methylbromide is a potent neurotoxin for insects and other pests. Its ability to disrupt normal cellular function and induce apoptosis makes it highly effective for pest control. The compound's efficacy is influenced by environmental factors such as temperature, concentration, and exposure time.

Pharmacokinetics

Methylbromide is rapidly absorbed through inhalation and can be metabolized in the body to various products, though specific metabolic pathways in humans are not well characterized. The gas is primarily excreted through exhalation, and its distribution in the body is influenced by lipid solubility. Due to its physical properties, it can accumulate in adipose tissue.

Pregnancy

There is limited information on the safety of methylbromide during pregnancy. Use only if clearly needed and the potential benefits justify the risks.

Breast-feeding

There is no available information on the excretion of methylbromide in human milk. Caution should be exercised when administering to nursing women.

Storage

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

Mechanism of action

Methylsulphate functions as a methylating agent, transferring a methyl group to nucleophiles. This process involves the formation of a sulfonium ion, which is highly reactive and can readily react with nucleophilic sites on various substrates, leading to methylation reactions.

Pharmacodynamics

The pharmacodynamics of methylsulphate is primarily related to its role as a methylating agent in biochemical reactions. It can alter the structure and function of biological molecules, potentially affecting cellular processes and signaling pathways. However, detailed pharmacodynamic studies specific to therapeutic use are limited.

Pharmacokinetics

There is limited information on the pharmacokinetics of methylsulphate, given its typical use as a reagent in laboratory settings rather than a clinical drug. When used in chemical reactions, its reactivity and transformation into other compounds would dictate its pharmacokinetic profile, which could vary significantly based on the specific context of use.

Pregnancy

There is limited data on the use of methylsulphate in pregnancy. Consult relevant guidelines.

Breast-feeding

Data on the excretion of methylsulphate in human milk is not available. Caution is advised.

Storage

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

Mechanism of action

Tinidazole is a prodrug and antiprotozoal agent. The nitro group of tinidazole is reduced in <i>Trichomonas</i> by a ferredoxin-mediated electron transport system. The free nitro radical generated as a result of this reduction is believed to be responsible for the antiprotozoal activity. It is suggested that the toxic free radicals covalently bind to DNA, causing DNA damage and leading to cell death. The mechanism by which tinidazole exhibits activity against <i>Giardia</i> and <i>Entamoeba</i> species is not known, though it is probably similar. The nitro group of tinidazole is reduced by cell extracts of Trichomonas. As a result of this reduction a free nitro radical is generated which may be responsible for the antiprotozoal activity. The mechanism by which tinidazole exhibits activity against Giardia and Entamoeba species is not known.

Pharmacodynamics

Tinidazole is a synthetic antiprotozoal agent. Tinidazole demonstrates activity both in vitro and in clinical infections against the following protozoa: <i>Trichomonas vaginalis</i>, <i>Giardia duodenalis</i> (also termed <i>G. lamblia</i>), and <i>Entamoeba histolytica</i>. Tinidazole does not appear to have activity against most strains of vaginal lactobacilli.

Mechanism of action

Unknown. Diloxanide may inhibit protein synthesis.

Pharmacodynamics

Diloxanide is a luminal amebicide, however the mechanism of action of diloxanide is unknown. Diloxanide destroys the trophozoites of E. histolytica that eventually form into cysts. The cysts are then excreted by persons infected with asymptomatic amebiasis. Diloxanide furoate is a prodrug, and is hydrolyzed in the gastrointestinal tract to produce diloxanide, the active ingredient.