CENTRE-TIAMDOX WATER SOLUBLE POWDER

Indications

• Bacterial infections
• Acne
• Destructive (refractory) periodontal disease
• Exacerbations of chronic bronchitis
• Leptospirosis
• Chlamydia infections
• Rickettsial infections
• Mycoplasma infections
• Acute necrotising ulcerative gingivitis

Dosage

Children: For children aged 12–17 years, initially 200 mg daily in 1–2 divided doses for the

Adults: Initially 200 mg daily in 1–2 divided doses for the first day, then maintenance 100 mg daily.

Mechanism of action

Doxycycline exerts its antibacterial effects by binding to the 30S ribosomal subunit of bacterial ribosomes, inhibiting the binding of aminoacyl-tRNA to the mRNA-ribosome complex. This inhibition of protein synthesis is crucial for bacterial growth and is the primary mechanism by which doxycycline exhibits its antimicrobial activity. It also impacts cellular metabolism and has been associated with non-genotoxic carcinogenic effects.

Pharmacodynamics

Doxycycline has a broad spectrum of activity against Gram-positive, Gram-negative bacteria, and some protozoa. Its bacteriostatic action is particularly effective against certain resistant strains, including MRSA. The drug's efficacy may vary based on the sensitivity of the bacteria, and resistance can develop through various mechanisms, such as efflux pumps and ribosomal protection.

Pharmacokinetics

Doxycycline is well absorbed from the gastrointestinal tract, with peak plasma concentrations typically reached within 2 hours after oral administration. It has a high volume of distribution and is approximately 90% protein-bound. The drug is metabolized in the liver and excreted primarily in feces, with a smaller fraction eliminated in urine. The half-life of doxycycline is approximately 18 to 22 hours, allowing for once or twice daily dosing in most cases.

Contra-indications

• Pregnancy
• Breastfeeding
• Hypersensitivity to doxycycline or other tetracyclines
• Myasthenia gravis
• Severe hepatic impairment

Adverse effects

• Photosensitivity
• Dizziness
• Headache
• Nausea
• Vomiting
• Diarrhoea
• Angioedema
• Skin reactions
• Pseudomembranous enterocolitis
• Tooth discolouration
• Intracranial hypertension
• Thrombocytopenia
• Stevens-Johnson syndrome
• Pancreatitis

Interactions

• Fosphenytoin (decreases concentration)
• Rifampicin (decreases exposure)
• Ciclosporin (unknown effect on concentration)
• Antacids containing aluminium or magnesium (reduce absorption)
• Iron supplements (reduce absorption)
• Warfarin (may enhance anticoagulant effect)

Precautions

• Use with caution in renal impairment
• May cause increased intracranial pressure
• Risk of superinfection (e.g., fungal infections)
• Avoid exposure to sunlight or sun lamps
• Monitor liver function in patients receiving prolonged therapy

Pregnancy

Should not be given to pregnant women; effects on skeletal development have been documented in the first trimester in animal studies. Administration during the second or third trimester may cause discoloration of the child's teeth, and maternal hepatotoxicity has been reported with large parenteral doses.

Breast-feeding

Should not be given to women who are breastfeeding; absorption may lead to discoloration of teeth in the infant.

Storage

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

Formulations

• Tablets
• Capsules
• Oral suspension
• Oral solution

Dosage

Children: Refer to official dosing guidelines for paediatric indications and dosages.

Adults: Refer to official dosing guidelines for specific indications and dosages.

Mechanism of action

Fumarate acts primarily as an intermediate in the TCA cycle, where it is converted to malate by the enzyme fumarase. This process is essential for the continuation of aerobic respiration, facilitating the conversion of carbohydrates, fats, and proteins into energy. Additionally, fumarate can participate in redox reactions, influencing cellular metabolism and signaling pathways.

Pharmacodynamics

Fumarate influences various metabolic pathways, including the urea cycle and glycolysis, by participating in electron transfer processes. Its role in the TCA cycle is vital for ATP production, and its interaction with other metabolic pathways helps regulate energy homeostasis and the balance of nitrogen in the body.

Pharmacokinetics

The pharmacokinetics of fumarate involve its absorption, distribution, metabolism, and excretion. Fumarate is readily absorbed when introduced into the body and is distributed to various tissues where it participates in metabolic processes. The metabolic conversion of fumarate occurs primarily in the mitochondria through the TCA cycle, and its elimination from the body is facilitated by renal pathways.

Pregnancy

There are no established guidelines regarding the use of fumerate during pregnancy. Consult healthcare professionals for individual risk assessment.

Breast-feeding

The safety of fumerate during breastfeeding has not been established. Caution is advised and consultation with healthcare professionals is recommended.

Storage

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

Indications

• Bacterial infections in livestock
• Respiratory diseases in pigs
• Enteritis in poultry

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines in pediatric patients.

Adults: Refer to the BNF for specific dosing regimens based on the indication and patient characteristics.

Mechanism of action

Tiamulin functions by inhibiting the activity of cytochrome P-450 enzymes, particularly CYP3A4, thereby affecting drug metabolism. This inhibition occurs through the formation of a metabolic intermediate complex that stabilizes CYP3A4 protein, ultimately reducing the mutation frequency associated with aflatoxin B1 in CYP3A4-expressing cells.

Pharmacodynamics

Tiamulin exhibits antibacterial activity by targeting the bacterial protein synthesis process, specifically binding to the 50S ribosomal subunit. This action disrupts the translation process, thereby inhibiting the growth of susceptible bacteria. Its effectiveness against anaerobic bacteria and certain gram-positive organisms makes it a valuable treatment option in veterinary medicine.

Pharmacokinetics

Tiamulin is absorbed following oral administration, with its pharmacokinetic profile characterized by variable bioavailability. It is extensively metabolized in the liver, primarily via cytochrome P-450 pathways. The drug has a relatively short half-life, necessitating multiple doses for effective therapeutic outcomes. It is excreted mainly through urine and feces, and its distribution in tissues is influenced by its lipophilic nature.

Pregnancy

Tiamulin should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Tiamulin is not recommended during breastfeeding due to the potential for serious adverse reactions in nursing infants.

Storage

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

Mechanism of action

The mutation frequency of aflatoxin B1 could be completely inhibited by tiamulin in CYP3A4-expressing cells, but no effect was observed on the mutation frequency of the direct mutagen ethylmethanesulphonate. Western blotting of homogenates of the CYP3A4-expressing cell line showed stabilization of CYP3A4 protein after incubation with tiamulin, supporting the hypothesis that the mechanism of inhibition is by binding of tiamulin to the cytochrome. Tiamulin is a semisynthetic diterpene antibiotic frequently used in farm animals. The drug has been shown to produce clinically important--often lethal--interactions with other compounds. It has been suggested that this is caused by a selective inhibition of oxidative drug metabolism via the formation of a cytochrome P-450 metabolic intermediate complex. In the present study, rats were treated orally for 6 days with tiamulin at two different doses: 40 & 226 mg/kg of body weight. For comparison, another group received 300 mg of triacetyloleandomycin (TAO) per kg, which is equivalent to the 226-mg/kg tiamulin group. Subsequently, microsomal P-450 contents, P-450 enzyme activities, metabolic intermediate complex spectra, & P-450 apoprotein concentrations were assessed. In addition, effects on individual microsomal P-450 activities were studied in control microsomes at different tiamulin & substrate concentrations. In the rats treated with tiamulin, a dose-dependent complex formation as evidenced by its absorption spectrum & an increase in cytochrome P-4503A1/2 contents as assessed by Western blotting (immunoblotting) were found. The effects were comparable to those of TAO. Tiamulin induced microsomal P-450 content, testosterone 6 beta-hydroxylation rate, erythromycin N-demethylation rate, & the ethoxyresorufin O-deethylation activity. Other activities were not affected or decreased. When tiamulin was added to microsomes of control rats, the testosterone 6 beta-hydroxylation rate & the erythromycin N-demethylation were strongly inhibited. It is concluded that tiamulin is a potent & selective inducer-inhibitor of cytochrome P-450. Though not belonging to the macrolides, the compound produces an effect on P-450 similar to those of TAO & related compounds.