Chapter 43 Drugs Treating Mycobacterial Infections

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Question
Mycobacteria are slow-growing microbes that require short treatment. A. True

B. False

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Rationale
B. False
This chapter discusses pharmacologic management of mycobacterial infections. Mycobacteria are slow-growing microbes that require prolonged treatment, generally with multiple medications. Many of the antimycobacterial drugs may be used for more than one type of infection. Table 43.1 presents a summary of antimycobacterial drugs. Although many Mycobacterium species exist, this chapter focuses on three species: M. tuberculosis, M. leprae, and M. avium. The prototype drug for treating M. tuberculosis is isoniazid (INH), and the prototype for treating M. leprae infection is rifampin. The drugs of choice for M. avium are clarithromycin and azithromycin; both of these macrolide drugs are discussed in Chapter 40.

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Pathophysiology
Tuberculosis (TB) is a mycobacterial infection that is found most frequently in the lungs. Human TB is an airborne disease spread by droplet nuclei. Symptoms of active TB include night sweats, cough, low-grade fever, fatigue, weight loss, and anorexia. Leprosy A chronic infectious disease caused by M. leprae. The disease mainly affects the skin, the peripheral nerves, the mucosa of the upper respiratory tract, and the eyes. Mycobacterium avium complex The term used to describe an opportunistic infection.

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Drug Treatment for TB

Copyright 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

 Chemoprophylaxis single drug therapy with isoniazid to prevent active TB is given if Patient is:

Definitions

asymptomatic , < 35 yrs. with + PPD

are / or have been in close contact with a person with active TB no active S & S of TB.

patients with a chest X-ray that shows TB lesions; but

patients with special risk factors

Active TB therapy - Induction phase Continuation phase

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Drugs for Treating Mycobacterium tuberculosis Infection

Antitubercular drugs are divided into two major categories: first- and second-line drugs. First-line drugs are those that are effective for treatment and have manageable toxicities. First-line drugs include isoniazid, rifampin, rifapentine, rifabutin, ethambutol, and pyrazinamide. Because TB can easily become drug resistant, combination therapy with three to four drugs is common. Prototype drug: isoniazid( INH)

Copyright 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

Isoniazid (INH): Core Drug Knowledge

Pharmacotherapeutics

Used to treat or prevent TB.

Pharmacokinetics Administered: oral or IM.

Metabolism: liver.
Excreted: urine and feces. Peak: 12 hours. Pharmacodynamics Disrupts the synthesis of the bacterial cell wall.
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Isoniazid: Core Drug Knowledge (cont.)

Contraindications- Acute hepatic disease Precautions chronic hepatic disease, alcoholism, renal impairment ( all elimination of the drug)

Pregnancy Category C- ( effects on the fetus is hard to ascertain since it is given as part of a multidrug regiment
Adverse effects Hepatotoxicity,( Black Box Warning)

peripheral neuropathy, and encephalopathy

Can cause hyperglycemia Drug interactions- Antiseizure drugs, alcohol, aluminum-based antacids, benzodiazepines, Copyright 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

Isoniazid: Core Patient Variables

Health status Assess for hepatic disease. Treatment for active TB may need to be given for 24 mos.

Prophylaxis with INH may need to be given for 9 mos.

Life span and gender Pregnancy category C. Those > 35 yrs. likely to develop drug induced hepatitis Lifestyle, diet, and habits Assess alcohol consumption. Limit amount of consumption of foods with tyramine . Environment- drug usually given to pt. at home Culture and inherited traits- assess ethnic background metabolized in the body by a process called acetylation.
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Isoniazid: Nursing Diagnoses and Outcomes

Altered Protection related to drug-induced hepatitis Desired outcome: the patient will call the prescriber immediately if signs or symptoms of hepatitis occur. Risk for Infection related to drug-induced blood dyscrasias Desired outcome: the patient will monitor for signs of infection and contact the prescriber if any occur. Risk for Peripheral Neurovascular Dysfunction related to druginduced neuropathy Desired outcome: the patient will take pyridoxine throughout INH therapy to decrease potential for peripheral neuropathy.
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Isoniazid: Planning & Interventions

Maximizing therapeutic effects Administer INH to the patient with an empty stomach 1 hour before or 2 hours after meals to increase absorption. Minimizing adverse effects Advise patients to report any of the prodromal symptoms of hepatitis, including anorexia, malaise, fatigue, jaundice, or nausea.

Copyright 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

Isoniazid: Teaching, Assessment & Evaluations

Patient and family education Advise patients to take the drug on an empty stomach every day as prescribed

If pt. starts and stops therapy ; will be at greater risk to develop MDR -TB
Explain diet and alcohol restrictions. Teach S & S of hepatotxicity & peripheral neuropathy Ongoing assessment and evaluation Monitor for signs of adverse effects, especially hepatitis.
Copyright 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

Question
INH is contraindicated in what patient? A. Patient with coronary artery disease B. Patient with renal impairment C. Patient with acute hepatitis C D. Patient with chronic obstructive pulmonary disease

Copyright 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

Rationale
INH is contraindicated in what patient? C. Patient with acute hepatitis C INH is contraindicated in patients with acute hepatic disease and in patients with a history of INH-induced hepatic disease.

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Drugs for Treating Mycobacterium leprae Infection

Multidrug therapy, the standard approach for other mycobacterial infections, is also recommended for treating leprosy. Rifampin is the drug of choice for both types of leprosy.

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Rifampin: Core Drug Knowledge

Pharmacotherapeutics Treating TB in conjunction with other therapy

TB prophylaxis in conjunction with other therapy

Meningococcal infections; prosthetic valve endocardiits Treating leprosy.

Pharmacokinetics
Administered: parenterally or orally. Metabolism: liver. Excreted: feces.
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Rifampin: Core Drug Knowledge (cont.)

Pharmacodynamics blocks initiation of RNA transcription Contraindications and precautions

Hypersensitivity
Adverse effects Discolor bodily fluids,( turns them red-orange) GI disturbances, fever, chills, headache, and fatigue Drug interactions Inducer of the P-450 enzyme system
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Rifampin: Core Patient Variables

Health status Assess for contraindications to therapy. Life span and gender Pregnancy category C. Increases the metabolism of oral contraceptives Lifestyle, diet, and habits Assess alcohol consumption.

Environment
Assess environment where drug will be given.

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Rifampin: Nursing Diagnoses and Outcomes

Risk for Injury related to hepatic injury Desired outcome: the patient will remain free of injury and contact the prescriber if signs such as yellow skin, itching, or fatigue occur.

Imbalanced Nutrition: Less than Body Requirements related to potential nausea, vomiting, anorexia, and diarrhea
Desired outcome: the patient will have balanced nutrition throughout therapy. Ineffective Protection related to potential leukopenia or hemolysis with anemia Desired outcome: the patient will remain without superinfection throughout therapy.
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Rifampin: Planning & Interventions

Maximizing therapeutic effects Administer IV rifampin by slow infusion over 3 hours. Oral formulation should be given on an empty stomach. Minimizing adverse effects Assess patients taking other hepatotoxic drugs.

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Rifampin: Teaching, Assessment & Evaluations

Patient and family education Explain the potential effect of rifampin on the liver. Advise patients with soft contact lenses to consult their ophthalmologist for an alternate form of contacts or glasses. ( cant use soft contact lenses) Ongoing assessment and evaluation Periodic testing of hematopoietic, renal, and hepatic function should also be arranged.

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Question
Rifampin is metabolized by which of the following ? A. By C-121 enzyme B. By cytochrome P-450 enzyme C. By conjugation D. By acetylating hepatic enzyme
Answer : B

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