Gentadox WS

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

• Bacterial infections
• Sepsis
• Pneumonia
• Meningitis
• Endocarditis
• Biliary tract infections
• Prostatitis
• Surgical prophylaxis
• Acute diverticulitis
• Leg ulcer infections

Dosage

Adults: 3–5 mg/kg daily in 3 divided doses, or a single daily dose of 5–7 mg/kg adjusted according to serum-gentamicin concentration. For surgical prophylaxis, 1.5 mg/kg administered intraven

Mechanism of action

Gentamicin exerts its antibacterial effects through a multi-phase mechanism. Initially, it binds to negatively charged components of bacterial cell membranes, increasing membrane permeability. Following this, it enters the bacterial cell via energy-dependent transport mechanisms, where it binds to the 30S ribosomal subunit. This binding causes mistranslation of proteins and disrupts membrane integrity, resulting in bacterial cell death. The action is concentration-dependent, leading to rapid bactericidal effects.

Pharmacodynamics

Gentamicin has a rapid onset of action due to its mechanism of disrupting the bacterial cell membrane and inhibiting protein synthesis. Its effectiveness is enhanced by higher concentrations, and it demonstrates a post-antibiotic effect where bacteria remain suppressed even after drug levels fall below the minimum inhibitory concentration. The drug's efficacy is influenced by factors like the bacterial strain and its susceptibility patterns.

Pharmacokinetics

Gentamicin is usually administered intravenously or intramuscularly. It has a volume of distribution of approximately 0.25 L/kg and is not significantly protein-bound. The drug is primarily eliminated via renal excretion, with a half-life of 2 to 3 hours in individuals with normal renal function. Dosing adjustments are necessary in patients with renal impairment to avoid toxicity. Serum levels should be monitored to optimize therapeutic efficacy while minimizing toxicity.

Contra-indications

• Hypersensitivity to gentamicin or any aminoglycoside
• Severe renal impairment
• Pre-existing auditory or vestibular dysfunction

Adverse effects

• Ototoxicity (hearing loss, vertigo, tinnitus)
• Nephrotoxicity
• Neuromuscular blockade
• Allergic reactions (rash, pruritus)
• Injection site reactions

Interactions

• Gentamicin + relugolix: Unknown (increases exposure)
• Gentamicin + other nephrotoxic drugs (e.g., vancomycin, cisplatin): Increased risk of nephrotoxicity
• Gentamicin + neuromuscular blocking agents: Enhanced neuromuscular blockade

Precautions

• Monitor renal function during therapy, especially in patients with pre-existing renal impairment
• Caution in patients with pre-existing hearing loss or vestibular disorders
• Use with caution in pregnant women and during breastfeeding

Pregnancy

Use only if clearly needed and the benefit justifies the risk to the fetus. Limited data on use in pregnancy.

Breast-feeding

Gentamicin is excreted in breast milk, exercise caution when administering to breastfeeding mothers. Monitor infant for possible side effects.

Storage

Store below 25°C. Protect from light. Do not freeze.

Formulations

• Injection solution (various concentrations)
• Ophthalmic solution (0.3% w/v)
• Topical ointment (0.1% w/v)

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

There are 3 key phases of aminoglycoside entry into cells. The first “ionic binding phase” occurs when polycationic aminoglycosides bind electrostatically to negatively charged components of bacterial cell membranes including with lipopolysaccharides and phospholipids within the outer membrane of Gram-negative bacteria and to teichoic acids and phospholipids within the cell membrane of Gram-positive bacteria. This binding results in displacement of divalent cations and increased membrane permeability, allowing for aminoglycoside entry. The second “energy-dependent phase I” of aminoglycoside entry into the cytoplasm relies on the proton-motive force and allows a limited amount of aminoglycoside access to its primary intracellular target - the bacterial 30S ribosome. This ultimately results in the mistranslation of proteins and disruption of the cytoplasmic membrane. Finally, in the “energy-dependent phase II” stage, concentration-dependent bacterial killing is observed. Aminoglycoside rapidly accumulates in the cell due to the damaged cytoplasmic membrane, and protein mistranslation and synthesis inhibition is amplified. The necessity of oxygen-dependent active transport explains why aminoglycosides are ineffective against anaerobic bacteria. Hence, aminoglycosides have both immediate bactericidal effects through membrane disruption and delayed bactericidal effects through impaired protein synthesis; observed experimental data and mathematical modeling support this two-mechanism model. Inhibition of protein synthesis is a key component of aminoglycoside efficacy. Structural and cell biological studies suggest that aminoglycosides bind to the 16S rRNA in helix 44 (h44), near the A site of the 30S ribosomal subunit, altering interactions between h44 and h45. This binding also displaces two important residues, A1492 and A1493, from h44, mimicking normal conformational changes that occur with successful codon-anticodon pairing in the A site. Overall, aminoglycoside binding has several negative effects including inhibition of translation, initiation, elongation, and ribosome recycling. Recent evidence suggests that the latter effect is due to a cryptic second binding site situated in h69 of the 23S rRNA of the 50S ribosomal subunit. Also, by stabilizing a conformation that mimics correct codon-anticodon pairing, aminoglycosides promote error-prone translation. Mistranslated proteins can incorporate into the cell membrane, inducing the damage discussed above. Aminoglycosides are usually bactericidal in action. Although the exact mechanism of action has not been fully elucidated, the drugs appear to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits. /Aminoglycosides/ ... Aminoglycosides are aminocyclitols that kill bacteria by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane. Aminoglycoside resistance mechanisms include: (a) the deactivation of aminoglycosides by N-acetylation, adenylylation or O-phosphorylation, (b) the reduction of the intracellular concentration of aminoglycosides by changes in outer membrane permeability, decreased inner membrane transport, active efflux, and drug trapping, (c) the alteration of the 30S ribosomal subunit target by mutation, and (d) methylation of the aminoglycoside binding site. ... /Aminoglycosides/