Anti-Tubercular Drugs: Considerations for Nurses

• It is important to be aware of the initial anti-tubercular drugs that are used as a first line of treatment – Isoniazid, Rifampin, Pyrazinamide, and Ethambutol.
• Drug interactions are inevitable and must be considered with anti-tubercular drugs.  Adverse reactions are also inevitable and must be acknowledged.
• Patient education regarding anti-tubercular drug therapy must be presented to the patient and/or caregiver.   

Anti-tubercular drugs are those given to treat tuberculosis infection caused by Mycobacterium tuberculosis.  These drugs also are effective against less common mycobacterial infections caused by M. kansasii, M. avium-intracellulare, M. fortuitum, and other related organisms. These drugs might not cure all cases but can halt the infection’s progress.  

Unlike other antibacterial drugs, anti-tubercular drugs need to be administered over a long period of time spreading over several months; therefore, patient compliance remains an issue in tuberculosis treatment, along with drug resistance and adverse drug reactions. 

It is important to modify the anti-tubercular regimen if the local drug test shows drug resistance as one may need to start a five or six-drug regimen for drug-resistant tuberculosis.  

Anti-tubercular drugs are used specifically against mycobacteria.  At usual dosages, ethambutol and isoniazid are tuberculostatic, which means they inhibit the growth of M. tuberculosis; however, rifampicin is tuberculocidal, which means it kills the mycobacterial cell. 

Isoniazid and rifampicin can develop antibiotic resistance and should always be used with other anti-tubercular drugs.  

Mechanism of Action of Anti-Tubercular Drugs

Ethambutol affects lipid synthesis, thereby resulting in the inhibition of mycolic acid incorporation into the cell wall that inhibits bacterial protein synthesis.  However, it only acts against replicating cells.  

Isoniazid inhibits cell wall protein synthesis by interfering with mycolic acid incorporation.  

Rifampicin inhibits RNA synthesis in susceptible organisms and it is mostly effective against active bacteria; however, it might be active against the resting bacterial cell.  

The exact mechanism of action of pyrazinamide is unknown.  It converts into pyrazinoic acid, which creates an acidic environment for the bacteria in which mycobacteria cannot replicate.  

Isoniazid is often combined with other drugs, such as ethambutol, rifampin, or streptomycin because the combination therapy can help prevent antibiotic resistance.  

Drug Interactions With Anti-Tubercular Drugs

The typical drug interactions that can occur with anti-tubercular drugs are: 

• The levels of phenytoin, carbamazepine, diazepam, ethosuximide, primidone, theophylline, and warfarin may be increased when given with isoniazid.  
• Rifampicin might interact with oral contraceptives.  It is important to tell the patient to have another contraception method while on rifampin therapy, as it can result in an unplanned pregnancy. 
• Corticosteroids and isoniazid, when given together, can result in reduced effectiveness of isoniazid and increased effects of corticosteroids.  
• Isoniazid may reduce the plasma concentration of ketoconazole, itraconazole, and oral antidiabetic drugs.  
• The combination of rifampin, isoniazid, ethionamide, and pyrazinamide increases the risk of hepatotoxicity. Due to this, one needs to adjust the dose and monitor the patient closely with hepatitis.  
• Pyrazinamide and phenytoin, when given together, can result in increased phenytoin levels.  

Adverse Reactions of Anti-Tubercular Drugs

Ethambutol may cause:  

• Itching 
• Joint pain 
• GI distress 
• Malaise  
• Retrobulbar neuritis and blindness 
• Leukopenia 
• Headache 
• Dizziness 
• Numbness and tingling of the extremities 
• Confusion 

The most common adverse reaction of isoniazid is peripheral neuropathy.   

Occasionally, it might cause fatal hepatitis.  It can even occur after months of stopping the isoniazid therapy; therefore one must monitor the patient for hepatitis even after the therapy has been stopped.  

Rifampin can cause:

• Epigastric pain 
• Nausea and vomiting 
• Abdominal cramps 
• Flatulence 
• Anorexia 
• Diarrhea 
• Red-orange-brown discoloration of urine, tears, sweat, and sputum.  One must tell the patient to not panic if the bodily secretions become orangish brown.  

The major side effect of pyrazinamide is liver toxicity. Other gastrointestinal effects are nausea, vomiting, and anorexia.  

Patient Education

With anti-tubercular drug therapy, the following tips should be reviewed with the patient and caregiver: 

• Take the drug therapy as the healthcare provider has prescribed.  Do not stop drug therapy without his/her consent.  If any adverse drug reactions are experienced, report these to the doctor soon.  
• Use any back-up birth control methods.  
• If gastrointestinal irritation occurs, take the medicines with food.  
• Avoid alcohol consumption during drug therapy.    
• Avoid certain foods such as fish and tuna.  Avoid products containing tyramine such as aged cheese, beer, and chocolate because the drug has some monoamine oxidase inhibitor activity that can lead to adverse effects.  
• If one exhibits any signs and symptoms of liver impairment, such as loss of appetite, fatigue, malaise, jaundice, or dark urine, report to the healthcare provider soon. 

The Bottom Line

Anti-tubercular drugs are typically needed for a long time.  Patients often stop taking them due to adverse drug reactions and lack of compliance, which can lead to antibiotic resistance. Encourage the patient to take the therapy as prescribed by the healthcare provider even if symptoms get better.  

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