COLIDOX FORTE

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

Indications

• Treatment of multidrug-resistant gram-negative bacterial infections
• Pneumonia caused by Pseudomonas aeruginosa
• Complicated urinary tract infections
• Infections in cystic fibrosis patients

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing information.

Adults: Refer to the BNF for specific dosing guidelines, as doses may vary based on infection severity and renal function.

Mechanism of action

Colistin interacts with the bacterial cytoplasmic membrane, disrupting its integrity and altering permeability. It binds to the membrane through its cationic properties, leading to leakage of essential intracellular components, which results in bactericidal effects.

Pharmacodynamics

Colistin functions as a cationic polypeptide that disrupts bacterial cell membranes via a detergent-like mechanism. It is effective against certain multidrug-resistant organisms, including Pseudomonas aeruginosa and Acinetobacter baumannii. Its use has increased due to the rise of antibiotic-resistant infections, particularly in patients with cystic fibrosis and other serious infections.

Pharmacokinetics

Colistin is administered parenterally and has variable pharmacokinetics depending on the route of administration. It is not well-absorbed orally and is primarily eliminated by the kidneys. The pharmacokinetic profile may vary based on renal function and dosage regimen, necessitating careful monitoring in patients with renal impairment.

Adverse effects

• Nephrotoxicity
• Neurotoxicity
• Allergic reactions
• Rash
• Fever

Interactions

• Increased risk of nephrotoxicity with other nephrotoxic agents
• Potential interactions with neuromuscular blockers

Precautions

• Monitor renal function during treatment
• Use with caution in patients with renal impairment
• Consider monitoring neuromuscular function in patients receiving concomitant neuromuscular blockers

Pregnancy

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

Breast-feeding

It is not known whether colistin is excreted in human milk. Caution should be exercised when administering to a nursing mother.

Storage

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

Formulations

• Colistin sulfate for injection
• Colistin methanesulfonate for injection

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

Mechanism of action

Colistin is a surface active agent which penetrates into and disrupts the bacterial cell membrane. Colistin is polycationic and has both hydrophobic and lipophilic moieties. It interacts with the bacterial cytoplasmic membrane, changing its permeability. This effect is bactericidal. There is also evidence that polymyxins enter the cell and precipitate cytoplasmic components, primarily ribosomes. POLYMYXIN B IS SURFACE-ACTIVE AGENT... CONTAINING LIPOPHILIC & LIPOPHOBIC GROUPS SEPARATED WITHIN MOLECULE. /POLYMYXIN B/ PERMEABILITY OF THE BACTERIAL MEMBRANE CHANGES IMMEDIATELY ON CONTACT WITH DRUG. SENSITIVITY TO POLYMYXIN B APPARENTLY IS RELATED TO THE PHOSPHOLIPID CONTENT OF THE CELL WALL-MEMBRANE COMPLEX. /POLYMYXIN B/ Colistin acts like a cationic detergent and binds to and damages the bacterial cytoplasmic membrane of susceptible bacteria. Damage to the bacterial cytoplasmic membrane alters the osmotic barrier of the membrane and causes leakage of essential intracellular metabolites and nucleosides.

Pharmacodynamics

Colistin is a polymyxin antibiotic agent. Polymyxins are cationic polypeptides that disrupt the bacterial cell membrane through a detergentlike mechanism. With the development of less toxic agents, such as extended-spectrum penicillins and cephalosporins, parenteral polymyxin use was largely abandoned, except for the treatment of multidrug-resistant pulmonary infections in patients with cystic fibrosis. More recently, however, the emergence of multidrug-resistant gram-negative bacteria, such as <i>Pseudomonas aeruginosa</i> and <i>Acinetobacter baumannii</i>, and the lack of new antimicrobial agents have led to the revived use of the polymyxins.