Usage
Metronidazole + Nalidixic Acid is a combination antibiotic used to treat various bacterial and parasitic infections, particularly those affecting the gastrointestinal and genitourinary tracts. Specifically, it is prescribed for:
- Bacterial Infections: Urinary tract infections, stomach infections, brain infections, skin infections, reproductive system infections, endocarditis, peritonitis, pneumonia, and dysentery.
- Parasitic Infections: Amebiasis, giardiasis, trichomoniasis, and intestinal worms.
- Other Conditions: Peptic ulcers, rosacea, H. pylori infection, bacterial vaginosis, blood in stool, toothache, and bleeding gums.
Pharmacological Classification: Antibiotic (combination of a nitroimidazole and a quinolone).
Mechanism of Action: Metronidazole disrupts DNA synthesis and causes DNA strand breakage in susceptible anaerobic bacteria and protozoa. Nalidixic acid inhibits bacterial DNA gyrase, thereby hindering DNA replication and repair in susceptible gram-negative bacteria.
Alternate Names
There are no widely recognized alternate names for this specific combination. Brand names may vary regionally; an example is Gramoneg M.
How It Works
Pharmacodynamics: Metronidazole exerts its bactericidal and parasiticidal effects by damaging DNA and inhibiting DNA synthesis. Nalidixic acid, a bactericidal agent, inhibits DNA gyrase (topoisomerase II) and topoisomerase IV, essential enzymes for bacterial DNA replication and repair.
Pharmacokinetics:
- Absorption: Metronidazole is well-absorbed orally. Nalidixic acid’s absorption is also good, though slightly reduced by food.
- Metabolism: Metronidazole is primarily metabolized in the liver. Nalidixic acid undergoes hepatic metabolism, forming active and inactive metabolites.
- Elimination: Metronidazole and its metabolites are mainly excreted in urine, with some fecal excretion. Nalidixic acid is primarily excreted renally, both as the parent compound and its metabolites.
Mode of Action: Metronidazole enters anaerobic bacterial and protozoal cells and forms toxic metabolites that damage DNA, leading to cell death. Nalidixic acid inhibits bacterial topoisomerases, blocking DNA replication and repair, ultimately causing bacterial death.
Receptor Binding, Enzyme Inhibition, Neurotransmitter Modulation: Metronidazole’s mechanism does not involve receptor binding or neurotransmitter modulation. It disrupts DNA through intracellular reduction of its nitro group and subsequent DNA adduct formation. Nalidixic acid specifically inhibits bacterial DNA gyrase and topoisomerase IV.
Elimination Pathways: Metronidazole is eliminated via hepatic metabolism and renal excretion. Nalidixic acid undergoes both renal and hepatic elimination.
Dosage
Dosage is determined by patient factors (age, weight, kidney/liver function) and infection severity. Always consult medical resources for precise dosing recommendations.
Standard Dosage
Adults: The typical adult dosage for urinary tract infections is 1 g four times daily for one to two weeks for initial therapy, and it can be reduced to 2g/day for prolonged therapy.
Children: Dosage in children is based on weight. Consult pediatric dosing guidelines, particularly those based on weight or age.
Special Cases:
- Elderly Patients: Close monitoring is required due to potential age-related changes in drug clearance.
- Patients with Renal Impairment: Dosage adjustment is needed to prevent drug accumulation and potential toxicity.
- Patients with Hepatic Dysfunction: Caution is advised, and dosage modification might be required.
- Patients with Comorbid Conditions: Carefully assess each patient’s specific conditions and adjust medication as needed.
Clinical Use Cases Dosage in specific clinical situations requires careful consideration of patient status and potential complications.
Dosage Adjustments Dosage modifications are necessary based on individual patient factors, including renal and hepatic function.
Side Effects
Common Side Effects: Nausea, vomiting, abdominal pain or cramps, headache, dark-colored urine, skin redness, skin burning, skin irritation, agitation, blurred vision, fever, constipation, loss of appetite, and vaginal irritation.
Rare but Serious Side Effects: Convulsions, severe abdominal pain, blistering or peeling skin, fever, chills, hallucinations, severe headaches, difficulty breathing.
Long-Term Effects: Peripheral neuropathy (with prolonged use of metronidazole), resistance development (with prolonged antibiotic use).
Adverse Drug Reactions (ADR): Stevens-Johnson Syndrome (rare), toxic epidermal necrolysis (rare), anaphylaxis (rare), seizures (rare), encephalopathy (rare).
Contraindications
- Hypersensitivity to metronidazole or nalidixic acid.
- History of blood disorders (nalidixic acid).
- Severe liver or kidney disease (nalidixic acid).
- Neurological conditions such as epilepsy or seizures (nalidixic acid).
- First trimester of pregnancy.
Drug Interactions
- Anticoagulants (e.g., warfarin): Metronidazole may enhance anticoagulant effects.
- Antiepileptics (e.g., phenytoin): Metronidazole may affect the metabolism of these drugs.
- Lithium: Metronidazole may increase lithium levels.
- Cyclosporine: Metronidazole may increase cyclosporine levels.
- Alcohol: Disulfiram-like reaction (flushing, nausea, vomiting) with metronidazole.
Pregnancy and Breastfeeding
- Pregnancy: Contraindicated in the first trimester. Use with caution in later trimesters only if clearly needed.
- Breastfeeding: Short courses are generally considered safe, but monitor the infant. High single doses may require temporary interruption of breastfeeding.
Drug Profile Summary
- Mechanism of Action: Metronidazole disrupts DNA; nalidixic acid inhibits DNA gyrase.
- Side Effects: Nausea, vomiting, abdominal pain, headache, dark urine; rarely seizures, severe skin reactions.
- Contraindications: Hypersensitivity, first trimester pregnancy, specific conditions (see Contraindications section).
- Drug Interactions: Anticoagulants, antiepileptics, lithium, alcohol.
- Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks.
- Dosage: Varies depending on indication and patient. See Dosage section.
- Monitoring Parameters: Renal and hepatic function, complete blood count (CBC), signs of superinfection.
Popular Combinations (Not applicable, this is already a combination drug)
Precautions
- Assess renal and hepatic function before and during treatment.
- Monitor for signs of superinfection (e.g., Candida overgrowth).
- Patients should avoid alcohol during and for several days after treatment.
- Caution in patients with CNS disorders.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Metronidazole + Nalidixic Acid?
A: The dosage varies depending on the infection being treated and patient-specific factors. Refer to the Dosage section above and always consult up-to-date medical resources for precise recommendations.
Q2: What are the most common side effects?
A: Nausea, vomiting, headache, and dark urine.
Q3: Can this medication be used during pregnancy?
A: It’s contraindicated in the first trimester. Use with caution in later trimesters only if essential, and under careful medical supervision.
Q4: Are there any drug interactions I should be aware of?
A: Yes, it interacts with anticoagulants, antiepileptics, lithium, and alcohol.
Q5: What should I do if a dose is missed?
A: Take the missed dose as soon as you remember unless it is almost time for the next dose. Do not double the dose.
Q6: How long does the treatment typically last?
A: The treatment duration varies depending on the infection. Consult a healthcare professional for guidance.
Q7: Can this combination treat parasitic infections?
A: Yes, it’s effective against certain parasites, including those causing amebiasis, giardiasis, and trichomoniasis.
Q8: Is it safe to drink alcohol while taking this medicine?
A: No, alcohol should be avoided during and for at least three days after treatment due to the risk of a disulfiram-like reaction.
Q9: What should patients be advised regarding potential side effects?
A: Advise patients to report any unusual or bothersome side effects promptly to their doctor, especially neurological symptoms or severe skin reactions.
Q10: Should this combination be used as a first-line treatment for all urinary tract infections?
A: No, antibiotic selection should be based on the suspected pathogen and local resistance patterns. Other options may be more appropriate in some cases.
