DOXYLIN WSP

Indications

• Bacterial infections
• Respiratory tract infections
• Urinary tract infections
• Acne
• Malaria prophylaxis
• Periodontal disease

Dosage

Children: For children aged 8 years and older, the usual dose for most infections is 2 mg/kg body weight as a loading dose on the first day, followed by 1 mg/kg daily. For children under 8 years, doxycycline is generally not recommended.

Adults: The usual adult dose for most infections is 100 mg to 200 mg daily, administered in one or two divided doses.

Mechanism of action

Doxycycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit. This binding prevents the attachment of aminoacyl-tRNA to the acceptor site on the mRNA-ribosome complex, thereby inhibiting the elongation of the peptide chain and ultimately leading to bacteriostatic effects.

Pharmacodynamics

Doxycycline exhibits a time-dependent killing effect, with its efficacy being related to the duration of exposure above the minimum inhibitory concentration (MIC). It has a longer half-life compared to other tetracyclines, allowing for once or twice daily dosing. It also possesses anti-inflammatory properties, which can contribute to its effectiveness in treating acne and other inflammatory conditions.

Pharmacokinetics

Doxycycline is well absorbed from the gastrointestinal tract, with an oral bioavailability of approximately 90%. It is widely distributed throughout body tissues and fluids, including the central nervous system. The drug is primarily excreted in the bile and undergoes enterohepatic recirculation, with minimal renal excretion. Its half-life is approximately 18-22 hours, allowing for convenient dosing schedules.

Contra-indications

• Hypersensitivity to doxycycline or any of the tetracycline antibiotics.
• Severe renal impairment (creatinine clearance < 50 mL/min).
• Pregnancy, particularly during the second and third trimesters.

Adverse effects

• Gastrointestinal disturbances (nausea, vomiting, diarrhea).
• Photosensitivity reactions.
• Esophageal irritation or ulceration.
• Skin rashes.
• Alterations in liver function tests.
• Intracranial hypertension.

Interactions

• Antacids containing aluminum, calcium, or magnesium can reduce the absorption of doxycycline.
• Iron preparations may also interfere with absorption.
• Oral contraceptives may be less effective when used concurrently with doxycycline.
• Warfarin and other anticoagulants may have increased effects.

Precautions

• Use with caution in patients with a history of esophageal disorders.
• Monitor liver function in patients with pre-existing liver disease.
• Caution in renal impairment, as dosage adjustments may be necessary.
• Avoid use in children under 12 years of age due to potential effects on bone growth and teeth.

Pregnancy

Doxycycline is contraindicated in pregnancy, especially during the second and third trimesters due to the risk of harm to the developing fetus, including effects on bone and teeth.

Breast-feeding

Doxycycline is excreted in breast milk. Caution is advised when administering to nursing mothers, as it may affect the infant's teeth and bone development.

Storage

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

Formulations

• Capsules
• Tablets
• Oral suspension
• Injectable solution

Indications

• Motion sickness
• Nausea and vomiting
• Gastrointestinal spasms
• Preoperative sedation

Dosage

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

Adults: Refer to the appropriate clinical guidelines or BNF for specific dosing recommendations based on the condition being treated and patient factors.

Mechanism of action

Hyclate exerts its effects by antagonizing muscarinic acetylcholine receptors, which are found throughout the central and peripheral nervous systems. This inhibition leads to a decrease in acetylcholine-induced effects, particularly in the gastrointestinal system and vestibular apparatus, thus alleviating symptoms of nausea and motion sickness.

Pharmacodynamics

The pharmacodynamic effects of hyoscine include reduced gastrointestinal motility, decreased secretions, and a sedative effect on the central nervous system. Its antimuscarinic activity can result in side effects such as dry mouth, blurred vision, constipation, and drowsiness, depending on the dose and individual patient response.

Pharmacokinetics

Hyclate is well-absorbed from the gastrointestinal tract, and its peak plasma concentrations are typically reached within 2 hours after oral administration. The drug is widely distributed throughout the body, including the central nervous system where it crosses the blood-brain barrier. Hyoscine is metabolized in the liver and excreted primarily through the urine. The half-life of hyoscine is approximately 3 to 5 hours, but this can vary based on the formulation and route of administration.

Contra-indications

• Hypersensitivity to hyoscyamine or any of the excipients
• Glaucoma
• Myasthenia gravis
• Severe ulcerative colitis
• Tachycardia

Adverse effects

• Dry mouth
• Blurred vision
• Constipation
• Urinary retention
• Dizziness
• Confusion
• Nausea
• Vomiting

Interactions

• Anticholinergic agents may enhance effects
• Opioids may increase risk of constipation
• Antidepressants may increase anticholinergic effects
• Antihistamines may have additive sedative effects

Precautions

• Use with caution in patients with prostate enlargement
• May exacerbate conditions like heart disease or hypertension
• Caution in elderly patients due to increased sensitivity

Pregnancy

Consult the prescribing information; safety during pregnancy is not established.

Breast-feeding

Consult a healthcare provider; may inhibit lactation.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Oral tablets
• Injection solution
• Extended-release capsules

Indications

• Bacterial infections in livestock
• Respiratory infections
• Enteritis caused by various pathogens
• Mycoplasma infections

Dosage

Children: For paediatric dosing, refer to the BNF for Children for appropriate dosing information based on age and weight.

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated, as doses may vary.

Mechanism of action

Tylosin inhibits peptide bond formation by binding to the 50S ribosomal subunit of bacteria, blocking the aminoacyl-tRNA from entering the ribosome and thus halting protein synthesis. This inhibition acts as a slow-binding, slowly reversible process, and the interaction with the ribosome is characterized by a significant degree of irreversibility, which is crucial for its antibiotic properties.

Pharmacodynamics

Tylosin exhibits bacteriostatic activity, meaning it inhibits bacterial growth rather than directly killing bacteria. Its effectiveness is particularly notable against certain strains of bacteria that are resistant to other antibiotic classes. The irreversibility of its action on the ribosome contributes to its long-lasting effects against bacterial infections.

Pharmacokinetics

After administration, tylosin is absorbed and distributed throughout the body. It is metabolized in the liver and excreted primarily in the bile, with some renal excretion. The half-life of tylosin can vary based on the route of administration and the species being treated. It is important to monitor for potential accumulation in cases of renal impairment.

Pregnancy

There is insufficient data on the use of tylosin during pregnancy. It should only be used if the potential benefits outweigh the risks.

Breast-feeding

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

Storage

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

Formulations

• Tylosin tartrate tablets
• Tylosin injectable solution
• Tylosin oral suspension

Mechanism of action

The inhibition of peptide bond formation by tylosin, a 16-membered ring macrolide, was studied in a model system derived from Escherichia coli. In this cell-free system, a peptide bond is formed between puromycin (acceptor substrate) and AcPhe-tRNA (donor substrate) bound at the P-site of poly(U)-programmed ribosomes. It is shown that tylosin inhibits puromycin reaction as a slow-binding, slowly reversible inhibitor. Detailed kinetic analysis reveals that tylosin (I) reacts rapidly with complex C, i.e., the AcPhe-tRNA. poly(U).70S ribosome complex, to form the encounter complex CI, which then undergoes a slow isomerization and is converted to a tight complex, CI, inactive toward puromycin. These events are described by the scheme C + I <==> (K(i)) CI <==> (k(4), k(5)) CI. The K(i), k(4), and k(5) values are equal to 3 microM, 1.5 min(-1), and 2.5 x 10(-3) min(-1), respectively. The extremely low value of k(5) implies that the inactivation of complex C by tylosin is almost irreversible. The irreversibility of the tylosin effect on peptide bond formation is significant for the interpretation of this antibiotic's therapeutic properties; it also renders the tylosin reaction a useful tool in the study of other macrolides failing to inhibit the puromycin reaction but competing with tylosin for common binding sites on the ribosome. Thus, the tylosin reaction, in conjunction with the puromycin reaction, was applied to investigate the erythromycin mode of action. It is shown that erythromycin (Er), like tylosin, interacts with complex C according to the kinetic scheme C + Er <==> (K(er)) CEr <==> (k(6), k(7)) C*Er and forms a tight complex, CEr, which remains active toward puromycin. The determination of K(er), k(6), and k(7) enables us to classify erythromycin as a slow-binding ligand of ribosomes