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Antitubercular Agents
Tuberculosis <ul><li>Agent: Mycobacterium tuberculosis ALSO: M. africanum & M. bovis </li></ul><ul><li>Route of Infection:...
Tb Infection may not cause disease <ul><li>A good example of difference between infection and infectious disease </li></ul...
Tuberculosis: Types <ul><li>Sites: </li></ul><ul><ul><li>Pulmonary (most common) </li></ul></ul><ul><ul><li>Bone </li></ul...
Tuberculosis: Risk Factors <ul><li>HIV infection </li></ul><ul><li>Close contacts of persons with infectious Tb </li></ul>...
Antitubercular Agents Trecator Ethionamide Seromycin Cycloserine Streptomycin (SM) Myambutol Ethambutol HCl (EMB) Pyrazina...
Indications for drug therapy <ul><li>Prevention & treatment of tuberculosis </li></ul><ul><li>No prototype – each drug dif...
Patient Variables <ul><li>Geriatrics </li></ul><ul><ul><li>Increased risk for toxic effects, esp. liver & CNS </li></ul></...
Prophylaxis <ul><li>Recent skin test converters </li></ul><ul><ul><li>Positive PPD, nL CXR & no evidence of active Tb </li...
Treatment of active disease <ul><li>Direct Observed Treatment (DOT) </li></ul><ul><ul><li>Standard of care in MD & NYC </l...
Tuberculosis: Resistance <ul><li>Reasons for development </li></ul><ul><ul><li>Inadequate treatment </li></ul></ul><ul><ul...
Patient Monitoring <ul><li>INH Prophylaxis </li></ul><ul><ul><li>Seen Q month & assess for </li></ul></ul><ul><ul><ul><li>...
Patient Monitoring <ul><li>Active Tb Treatment </li></ul><ul><ul><li>CXR at baseline & 6 mo </li></ul></ul><ul><ul><li>Spu...
Isoniazid (INH) <ul><li>Mechanism of Action </li></ul><ul><ul><li>Bacteriostatic for resting organisms </li></ul></ul><ul>...
INH Pharmacokinetics <ul><li>Half-life </li></ul><ul><ul><li>Variable  </li></ul></ul><ul><li>Distribution </li></ul><ul><...
Isoniazid (INH) <ul><li>Adverse Effects </li></ul><ul><ul><li>Most frequent: liver & nervous system effects </li></ul></ul...
Isoniazid (INH) <ul><li>Drug Interactions </li></ul><ul><ul><li>P450 1A2 inhibitor & 2C inhibitor </li></ul></ul><ul><ul><...
INH: Patient Education <ul><li>Take on empty stomach 1 hr before or 2 hrs after meal </li></ul><ul><li>Minimize alcohol co...
Pharmacokinetics Renal: active drug & metabolites Hepatic 80% & rapid Ethionamide Renal Hepatic Well absorbed Cycloserine ...
Pharmacokinetics Wide Wide Well distributed Most tissues Most tissues Wide distribution 80% protein bound Diffuses to all ...
Tuberculosis: Symptoms <ul><li>Sx: </li></ul><ul><ul><li>Cough, pain in chest when breathing or coughing, cough productive...
Tuberculosis: Exposure Testing <ul><li>Purified Protein Derivative (PPD) or Mantoux Test </li></ul><ul><ul><li>Mantoux – p...
Criteria for Positive Tb Skin Test <ul><li>Negative does NOT r/o </li></ul><ul><ul><li>Person may be anergic </li></ul></u...
Testing for Tb Exposure <ul><li>Skin testing for person with history of BCG vaccine </li></ul><ul><ul><li>WAS: never give ...
Testing for Tb Exposure <ul><li>Chest X-ray  </li></ul><ul><ul><li>AP & LAT for all persons with positive PPD </li></ul></...
Diagnosis of Active Tb <ul><li>PRESUMPTIVE (report w/in 24 hr to HD): </li></ul><ul><ul><li>Recent conversion to positive ...
Rifampin <ul><li>Mechanism of Action </li></ul><ul><ul><li>Inhibits DNA-dependent RNA polymerase activity    suppressing ...
Rifampin <ul><li>Warnings / Precautions </li></ul><ul><ul><li>Hepatotoxicity with fatality – monitor LFTs & adjust dose wi...
Rifampin <ul><li>Adverse Effects </li></ul><ul><ul><li>Common: GI Sx’s & rash </li></ul></ul><ul><ul><li>High doses    fl...
Rifampin: Patient Education <ul><li>Take on an empty stomach, 1 hr before or 2 hrs after meals </li></ul><ul><li>Avoid mis...
Pyrazinamide (PZA) <ul><li>Mechanism of Action </li></ul><ul><ul><li>Unknown </li></ul></ul><ul><ul><li>Bacteriostatic vs....
Pyrazinamide (PZA) <ul><li>Warning / Precautions </li></ul><ul><ul><li>Inhibits renal excretion of urates – may cause hype...
Pyrazinamide (PZA) <ul><li>Adverse Effects </li></ul><ul><ul><li>Frequent: mild arthralgia & myalgia </li></ul></ul><ul><u...
PZA: Patient Education <ul><li>Report: </li></ul><ul><ul><li>Fever, loss of appetite, malaise, N/V, darkened urine, yellow...
Ethambutol HCl <ul><li>Mechanism of Action </li></ul><ul><ul><li>Impairs cellular metabolism    stops cell multiplication...
Ethambutol HCl <ul><li>Warnings / Precautions </li></ul><ul><ul><li>Visual testing (on each eye individually & both togeth...
Ethambutol HCl <ul><li>Adverse Effects </li></ul><ul><ul><li>Fever, malaise, dizziness, headache </li></ul></ul><ul><ul><l...
EMB: Patient Education <ul><li>May cause GI upset – take with food </li></ul><ul><li>Aluminum-containing antacids may inte...
Cycloserine <ul><li>Mechanism of Action </li></ul><ul><ul><li>Inhibits cell wall synthesis </li></ul></ul><ul><ul><li>May ...
Cycloserine <ul><li>Adverse Effects </li></ul><ul><ul><li>CNS Sx’s: convulsions, psychosis, somnolence, depression, confus...
Cycloserine: Pt Education <ul><li>Notify provider of: </li></ul><ul><ul><li>Dizziness, mental confusion, skin rash, tremor...
Ethionamide (when 1st line Tx has failed) <ul><li>Mechanism of Action </li></ul><ul><ul><li>Inhibits peptide synthesis </l...
Ethionamide: Pt Education <ul><li>May cause stomach upset, metallic taste, or loss of appetite </li></ul><ul><li>Take with...
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Antitubercular Agents

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Antitubercular Agents

  1. 1. Antitubercular Agents
  2. 2. Tuberculosis <ul><li>Agent: Mycobacterium tuberculosis ALSO: M. africanum & M. bovis </li></ul><ul><li>Route of Infection: </li></ul><ul><ul><li>Primary: inhalation of infectious particles (droplet nuclei) ALSO: spread by lymphatics </li></ul></ul><ul><li>Incubation: 2-10 weeks; risk of progressive disease greatest in first 2 years (HIV decreases both) </li></ul><ul><li>Cell-mediated immune response  tubercle formation </li></ul><ul><li>Culture takes 6 weeks </li></ul><ul><li>Dx relies on AFB smear (Acid-Fast Bacillus) </li></ul><ul><ul><li>BUT threshold of detection 5-10,000 organisms/mL </li></ul></ul>
  3. 3. Tb Infection may not cause disease <ul><li>A good example of difference between infection and infectious disease </li></ul><ul><li>Tb skin test converters have been infected, </li></ul><ul><li>but are not sick. They are at risk of developing disease </li></ul>
  4. 4. Tuberculosis: Types <ul><li>Sites: </li></ul><ul><ul><li>Pulmonary (most common) </li></ul></ul><ul><ul><li>Bone </li></ul></ul><ul><ul><li>Urinary tract </li></ul></ul><ul><li>Primary </li></ul><ul><ul><li>Initial infection with the disease </li></ul></ul><ul><li>Reactivation </li></ul><ul><ul><li>Patient infected in past has reactivation of disease </li></ul></ul>
  5. 5. Tuberculosis: Risk Factors <ul><li>HIV infection </li></ul><ul><li>Close contacts of persons with infectious Tb </li></ul><ul><li>Persons with medical conditions that decrease resistance to infection </li></ul><ul><li>Persons who inject drugs </li></ul><ul><li>Foreign-born persons where Tb is endemic </li></ul><ul><li>Medically underserved, low-income populations </li></ul><ul><li>Residents & employees of LTC facilities </li></ul><ul><li>Local high prevalence groups (e.g., migrants) </li></ul><ul><li>Healthcare workers at risk of exposure in workplace </li></ul>
  6. 6. Antitubercular Agents Trecator Ethionamide Seromycin Cycloserine Streptomycin (SM) Myambutol Ethambutol HCl (EMB) Pyrazinamide (PZA) Rifandin, Rimactane Rifampin (RIF) Laniazid Isoniazid (INH) TRADE GENERIC
  7. 7. Indications for drug therapy <ul><li>Prevention & treatment of tuberculosis </li></ul><ul><li>No prototype – each drug differs from the others </li></ul><ul><li>TB: </li></ul><ul><ul><li>Highly contagious </li></ul></ul><ul><ul><li>Reportable disease </li></ul></ul><ul><ul><li>Treatment initiated by specialist </li></ul></ul><ul><ul><li>Refer for initial work-up & treatment </li></ul></ul><ul><li>PCP ROLE: </li></ul><ul><ul><li>Follow patient while on therapy </li></ul></ul><ul><ul><li>Prophylaxis </li></ul></ul>
  8. 8. Patient Variables <ul><li>Geriatrics </li></ul><ul><ul><li>Increased risk for toxic effects, esp. liver & CNS </li></ul></ul><ul><li>Pediatrics </li></ul><ul><ul><li>INH, RIF, PZA commonly used </li></ul></ul><ul><ul><li>EMB NOT recommended for children < 13 </li></ul></ul><ul><ul><li>Streptomycin NOT recommended for use in children </li></ul></ul><ul><ul><li>Cycloserine & ethionamide: safety NOT established </li></ul></ul><ul><li>Pregnancy </li></ul><ul><ul><li>Category C: prescribe only when necessary </li></ul></ul><ul><ul><li>Category D: Aminoglycosides (SM) & Ethionamide (teratogenicity in animals) </li></ul></ul><ul><li>Lactation </li></ul><ul><ul><li>INH, RIF, PZA, EMB, cycloserine all appear in breast milk </li></ul></ul>
  9. 9. Prophylaxis <ul><li>Recent skin test converters </li></ul><ul><ul><li>Positive PPD, nL CXR & no evidence of active Tb </li></ul></ul><ul><li>Close contacts of individuals with infectious, clinically active Tb </li></ul><ul><li>Evaluate to r/o active Tb </li></ul><ul><li>Assess for Hx hepatitis, heavy alcohol ingestion, liver disease, age > 35 </li></ul><ul><ul><li>If Hx positive  obtain LFTs to evaluate any contraindications to therapy </li></ul></ul><ul><li>Must weigh risk vs. benefit </li></ul><ul><li>Prophylaxis: INH 300mg PO QD </li></ul><ul><li>Length of Tx: </li></ul><ul><ul><li>Children < 18: 9 mo </li></ul></ul><ul><ul><li>Adults: 6 mo </li></ul></ul><ul><ul><li>Immunocompromised or abnL CXR(NOT active Tb): 12 mo </li></ul></ul><ul><li>Dispense: 1 mo supply – monitor Qmo </li></ul>
  10. 10. Treatment of active disease <ul><li>Direct Observed Treatment (DOT) </li></ul><ul><ul><li>Standard of care in MD & NYC </li></ul></ul><ul><ul><li>Every dose of anti-Tb medication observed and supervised by a h/c worker </li></ul></ul><ul><ul><li>Compliance is KEY </li></ul></ul><ul><ul><li>Noncompliant may be sent to prison to assure compliance (has been shown to reduce prevalence of multidrug resistance </li></ul></ul><ul><li>Increased prevalence of resistance  4 drug regimen </li></ul><ul><ul><li>INH, RIF, PZA & (EMB OR SM) </li></ul></ul>
  11. 11. Tuberculosis: Resistance <ul><li>Reasons for development </li></ul><ul><ul><li>Inadequate treatment </li></ul></ul><ul><ul><li>Discontinuance of treatment prematurely </li></ul></ul><ul><li>Many organisms resistant to standard Tx </li></ul><ul><ul><li>INH, RIF, & EMB </li></ul></ul><ul><li>Some strains resistant to all known Tb drugs </li></ul><ul><li>Patterns of resistance determine local treatment </li></ul>
  12. 12. Patient Monitoring <ul><li>INH Prophylaxis </li></ul><ul><ul><li>Seen Q month & assess for </li></ul></ul><ul><ul><ul><li>s/s of liver damage or other toxic effects, anorexia, n/v, fatigue, weakness, paresthesias of hands/feet, persistent dark urine, icterus, rash, elevated temp </li></ul></ul></ul><ul><ul><li>Routine LFTs (Q mo) for patients at high risk for developing INH hepatitis (age >35, daily drinkers, concomitant medications toxic to liver, hx of liver disease) </li></ul></ul><ul><ul><li>D/C INH immediately if s/s of toxicity </li></ul></ul>
  13. 13. Patient Monitoring <ul><li>Active Tb Treatment </li></ul><ul><ul><li>CXR at baseline & 6 mo </li></ul></ul><ul><ul><li>Sputum smear & culture at baseline and monthly until negative </li></ul></ul><ul><ul><li>Measure: liver enzymes, bilirubin, serum creatinine, CBC, PLTs, serum uric acid at baseline & monthly </li></ul></ul><ul><ul><ul><li>INH  periodic ophthalmologic exam </li></ul></ul></ul><ul><ul><ul><li>PZA  blood glucose levels </li></ul></ul></ul><ul><ul><ul><li>EMB  color vision for red/green at baseline & 2-3 months </li></ul></ul></ul><ul><ul><ul><li>SM  audiogram prior to Tx & 2-3 months; serum SM levels </li></ul></ul></ul><ul><ul><ul><li>Cycloserine  weekly blood levels in reduced renal function </li></ul></ul></ul>
  14. 14. Isoniazid (INH) <ul><li>Mechanism of Action </li></ul><ul><ul><li>Bacteriostatic for resting organisms </li></ul></ul><ul><ul><li>Bactericidal for dividing organisms </li></ul></ul><ul><ul><li>Interferes with lipid and nucleic acid biosynthesis </li></ul></ul><ul><li>Contraindications </li></ul><ul><ul><li>Known contact with INH-resistant Tb case </li></ul></ul><ul><ul><li>Previous INH-associated adverse effect </li></ul></ul><ul><ul><li>Acute liver disease, severe chronic liver disease </li></ul></ul>
  15. 15. INH Pharmacokinetics <ul><li>Half-life </li></ul><ul><ul><li>Variable </li></ul></ul><ul><li>Distribution </li></ul><ul><ul><li>Widely distributed to all body tissues </li></ul></ul><ul><li>Metabolism </li></ul><ul><ul><li>Acetylation & dehydrazination </li></ul></ul><ul><ul><li>Rate of acetylation genetically determined 50% of blacks & whites are “slow acetylators” majority of Eskimos & Asians are “rapid acetylators” </li></ul></ul><ul><li>Excretion </li></ul><ul><ul><li>Renal </li></ul></ul>
  16. 16. Isoniazid (INH) <ul><li>Adverse Effects </li></ul><ul><ul><li>Most frequent: liver & nervous system effects </li></ul></ul><ul><ul><li>Stains urine orange-red </li></ul></ul><ul><ul><li>Fever, rash, vasculitis </li></ul></ul><ul><ul><li>N/V </li></ul></ul><ul><ul><li>Agranulocytosis, thrombocytopenia </li></ul></ul><ul><ul><li>Peripheral neuropathy, numbness & tingling of extremities </li></ul></ul><ul><ul><li>Jaundice, abnormal LFTs </li></ul></ul>
  17. 17. Isoniazid (INH) <ul><li>Drug Interactions </li></ul><ul><ul><li>P450 1A2 inhibitor & 2C inhibitor </li></ul></ul><ul><ul><li>Concomitant use of alcohol associated with higher incidence of hepatitis </li></ul></ul><ul><ul><li>Higher rate of hepatotoxicity with RIF </li></ul></ul><ul><ul><li>Aluminum containing antacids decrease absorption </li></ul></ul><ul><ul><li>Some MAOI activity (tyramine containing foods) </li></ul></ul><ul><li>Overdose </li></ul><ul><ul><li>EARLY: N/V, dizziness, slurring of speech, blurring of vision, visual hallucination </li></ul></ul><ul><ul><li>LATE: respiratory distress, CNS depression (may be fatal) </li></ul></ul>
  18. 18. INH: Patient Education <ul><li>Take on empty stomach 1 hr before or 2 hrs after meal </li></ul><ul><li>Minimize alcohol consumption </li></ul><ul><li>Avoid foods containing tyramine (wine, hard cheese, liver) and histamine (tuna, sauerkraut) </li></ul><ul><li>Notify provider if fatigue, weakness, n/v, loss of appetite, yellowing of skin or eyes, darkening of urine, numbness/tingling of hands / feet </li></ul>
  19. 19. Pharmacokinetics Renal: active drug & metabolites Hepatic 80% & rapid Ethionamide Renal Hepatic Well absorbed Cycloserine Renal: Glomerular Filtration Hepatic PO: poor IM: rapid SM Renal: 80% Feces: 20% Hepatic-oxidation 75-80% EMB Renal Hepatic Well absorbed PZA Bile: 70% Urine: 30% Hepatic Readily RIF Renal Hepatic-acetylation genetic Interference with food INH EXCRETION METABOLISM ABSORPTION DRUG
  20. 20. Pharmacokinetics Wide Wide Well distributed Most tissues Most tissues Wide distribution 80% protein bound Diffuses to all body tissue DISTRIBUTION & PROTEIN-BINDING 3 hr Ethionamide 25-30 mcg/ml 12 hr 4-8 hr Cycloserine 25-50 mcg/ml 5-6 hr 1 hr SM Requires special assay 24 hr 2-4 hr EMB 9-12 mcg/ml 9-10 hr 2 hr PZA 4-32 mcg/ml 2-3 hr varies RIF 24 hr 1-2 hr varies INH THERAPEUTIC SERUM LEVEL ½-LIFE PEAK DRUG
  21. 21. Tuberculosis: Symptoms <ul><li>Sx: </li></ul><ul><ul><li>Cough, pain in chest when breathing or coughing, cough productive of sputum or blood </li></ul></ul><ul><ul><li>Weight loss, fatigue, malaise, fever, & night sweats </li></ul></ul><ul><li>Assume contagious if: </li></ul><ul><ul><li>Cough is present </li></ul></ul><ul><ul><li>Undergoing cough inducing procedures </li></ul></ul><ul><ul><li>Sputum smear is positive until 3 negative </li></ul></ul><ul><ul><li>Until patient on Tx at least 1 week </li></ul></ul><ul><ul><li>Showing poor response to Tx </li></ul></ul>
  22. 22. Tuberculosis: Exposure Testing <ul><li>Purified Protein Derivative (PPD) or Mantoux Test </li></ul><ul><ul><li>Mantoux – preferred, more accurate </li></ul></ul><ul><ul><li>Tine test – no longer used </li></ul></ul><ul><li>0.1 mL of PPD with 5 TU injected intradermally – pale elevation 6-10 mm read 48-72 hours after injection </li></ul><ul><li>Only induration (hardness) is measured </li></ul>
  23. 23. Criteria for Positive Tb Skin Test <ul><li>Negative does NOT r/o </li></ul><ul><ul><li>Person may be anergic </li></ul></ul><ul><li>> 5 mm induration </li></ul><ul><ul><li>Children <1 year of age </li></ul></ul><ul><ul><li>X-ray or clinical evidence of disease </li></ul></ul><ul><ul><li>Close contact of person with active disease </li></ul></ul><ul><ul><li>Evidence of old healed Tb </li></ul></ul><ul><ul><li>Persons with risk factors for HIV infection </li></ul></ul><ul><ul><li>Persons who inject drugs </li></ul></ul><ul><li>> 10 mm induration </li></ul><ul><ul><li>Children between 1 & 4 years old </li></ul></ul><ul><ul><li>Foreign-born persons from high prevalence countries </li></ul></ul><ul><ul><li>HIV seronegative IV drug users </li></ul></ul><ul><ul><li>Persons with medical risk factors (DM, ETOH, drug abuse) </li></ul></ul><ul><ul><li>Employees / residents of LTC facilities </li></ul></ul><ul><li>> 15 mm induration </li></ul><ul><ul><li>All others </li></ul></ul>
  24. 24. Testing for Tb Exposure <ul><li>Skin testing for person with history of BCG vaccine </li></ul><ul><ul><li>WAS: never give PPD to person who had received BCG </li></ul></ul><ul><ul><li>NOW: BCG status should NOT influence need for Tb skin testing – may see boosted reaction </li></ul></ul><ul><li>Two-step Tb skin testing (PPD  2nd PPD in 1-3 wks) </li></ul><ul><ul><li>Distinguishes boosted reaction (b/c hypersensitivity reaction wanes with time) vs. reaction d/t new infection </li></ul></ul><ul><ul><li>Recommended for elderly patients and high-risk employees </li></ul></ul>
  25. 25. Testing for Tb Exposure <ul><li>Chest X-ray </li></ul><ul><ul><li>AP & LAT for all persons with positive PPD </li></ul></ul><ul><ul><li>Very sensitive (not a lot of false negatives): nL CXR  Tb unlikely </li></ul></ul><ul><ul><li>Detected abnormalities  biopsy showing caseation granulomas to confirm diagnosis </li></ul></ul><ul><ul><li>Policies on annual CXR vary for positive skin test most are considered cleared of Tb if CXR clear & F/U CXR only required if s/s of Tb </li></ul></ul><ul><li>Sputum </li></ul><ul><ul><li>Direct examination shows presence of AFB </li></ul></ul><ul><ul><li>Positive smear  considered contagious </li></ul></ul><ul><ul><li>Classic Dx made by culture (takes 6 weeks) </li></ul></ul><ul><ul><li>Mycobacterium tuberculosis Direct Test results in 4-5 hours BUT misses 5% of cases (requires culture) </li></ul></ul>
  26. 26. Diagnosis of Active Tb <ul><li>PRESUMPTIVE (report w/in 24 hr to HD): </li></ul><ul><ul><li>Recent conversion to positive PPD associated with characteristic s/s </li></ul></ul><ul><ul><li>Positive sputum (or other body fluid) smear </li></ul></ul><ul><ul><li>Characteristic CXR </li></ul></ul><ul><ul><li>Bx showing caseating granulomas </li></ul></ul><ul><ul><li>HIV/AIDS (d/t high rate of concurrent infection) </li></ul></ul><ul><li>CONFIRMED (report w/in 24 hr to HD): </li></ul><ul><ul><li>Positive culture (any body fluid or Bx specimen) </li></ul></ul><ul><ul><li>Also tests for drug susceptibility </li></ul></ul>
  27. 27. Rifampin <ul><li>Mechanism of Action </li></ul><ul><ul><li>Inhibits DNA-dependent RNA polymerase activity  suppressing RNA synthesis </li></ul></ul><ul><ul><li>May be bacteriostatic or bactericidal </li></ul></ul><ul><ul><li>Most active against bacteria undergoing cell division </li></ul></ul><ul><li>Contraindications </li></ul><ul><ul><li>Hypersensitivity </li></ul></ul>
  28. 28. Rifampin <ul><li>Warnings / Precautions </li></ul><ul><ul><li>Hepatotoxicity with fatality – monitor LFTs & adjust dose with impaired liver fxn </li></ul></ul><ul><ul><li>Hyperbilirubinemia </li></ul></ul><ul><ul><li>Porphyria exacerbation </li></ul></ul><ul><ul><li>Meningococci resistance may emerge </li></ul></ul><ul><ul><li>Hypersensitivity reaction if intermittent or interrupted therapy </li></ul></ul><ul><ul><li>May be associated with carcinogenesis </li></ul></ul><ul><ul><li>Monitor CBC & LFTs </li></ul></ul><ul><ul><li>Urine, feces, saliva, sputum, sweat, & tears may be colored red-orange. Soft contact lenses may be permanently stained </li></ul></ul><ul><ul><li>Thrombocytopenia – usu. reversible but may be fatal </li></ul></ul>
  29. 29. Rifampin <ul><li>Adverse Effects </li></ul><ul><ul><li>Common: GI Sx’s & rash </li></ul></ul><ul><ul><li>High doses  flulike syndrome, hematopoietic reactions </li></ul></ul><ul><li>Drug Interactions </li></ul><ul><ul><li>P450 1A2 substrate, 2C inducer, 2D6 inducer, 3A4 inducer and substrate </li></ul></ul><ul><ul><li>Decreases effectiveness of many drugs including oral anticoagulants & oral contraceptives </li></ul></ul><ul><ul><li>Decreases serum digoxin concentrations </li></ul></ul><ul><li>Overdose – requires hospitalization </li></ul><ul><ul><li>N/V, lethargy </li></ul></ul><ul><ul><li>Liver toxicity </li></ul></ul>
  30. 30. Rifampin: Patient Education <ul><li>Take on an empty stomach, 1 hr before or 2 hrs after meals </li></ul><ul><li>Avoid missing doses </li></ul><ul><li>May cause red-orange discoloration of body fluids </li></ul><ul><li>Notify provider if “flulike” Sx’s, yellow discoloration of skin or eyes, skin rash or itching </li></ul>
  31. 31. Pyrazinamide (PZA) <ul><li>Mechanism of Action </li></ul><ul><ul><li>Unknown </li></ul></ul><ul><ul><li>Bacteriostatic vs. bactericidal activity dose-dependent </li></ul></ul><ul><li>Contraindications </li></ul><ul><ul><li>Hypersensitivity, liver damage, acute gout </li></ul></ul>
  32. 32. Pyrazinamide (PZA) <ul><li>Warning / Precautions </li></ul><ul><ul><li>Inhibits renal excretion of urates – may cause hyperuricemia and gout </li></ul></ul><ul><ul><li>Use with caution in patient with renal function impairment – reduced dose usually not necessary </li></ul></ul><ul><ul><li>Monitor patients with hepatic impairment closely </li></ul></ul><ul><ul><li>In patients with DM, BG control may be more difficult </li></ul></ul>
  33. 33. Pyrazinamide (PZA) <ul><li>Adverse Effects </li></ul><ul><ul><li>Frequent: mild arthralgia & myalgia </li></ul></ul><ul><ul><li>Most common serious: gout & hepatic toxicity </li></ul></ul><ul><li>Drug Interactions </li></ul><ul><ul><li>No known P450 </li></ul></ul><ul><li>Overdose </li></ul><ul><ul><li>Liver toxicity </li></ul></ul>
  34. 34. PZA: Patient Education <ul><li>Report: </li></ul><ul><ul><li>Fever, loss of appetite, malaise, N/V, darkened urine, yellowish discoloration of skin or eyes, pain or swelling or joints </li></ul></ul>
  35. 35. Ethambutol HCl <ul><li>Mechanism of Action </li></ul><ul><ul><li>Impairs cellular metabolism  stops cell multiplication & causes cell death </li></ul></ul><ul><ul><li>Bactericidal & active only against mycobacteria </li></ul></ul><ul><li>Contraindications </li></ul><ul><ul><li>Hypersensitivity </li></ul></ul><ul><ul><li>Known optic neuritis </li></ul></ul>
  36. 36. Ethambutol HCl <ul><li>Warnings / Precautions </li></ul><ul><ul><li>Visual testing (on each eye individually & both together) before initiating Tx and periodically including visual acuity, ophthalmoscopy, peripheral fields, & color discrimination </li></ul></ul><ul><ul><li>Renal impairment requires dose adjustment </li></ul></ul>
  37. 37. Ethambutol HCl <ul><li>Adverse Effects </li></ul><ul><ul><li>Fever, malaise, dizziness, headache </li></ul></ul><ul><ul><li>Dermatitis, pruritis </li></ul></ul><ul><ul><li>Thrombocytopenia </li></ul></ul><ul><ul><li>Common: N/V, anorexia, abdominal pain </li></ul></ul><ul><ul><li>SEVERE: Optic neuritis, loss of acuity, loss of red-green discrimination </li></ul></ul><ul><li>Drug Interactions </li></ul><ul><ul><li>Aluminum salts may delay/reduce absorption </li></ul></ul>
  38. 38. EMB: Patient Education <ul><li>May cause GI upset – take with food </li></ul><ul><li>Aluminum-containing antacids may interfere with absorption  separate administration by several hours </li></ul><ul><li>Notify provider of </li></ul><ul><ul><li>Changes in vision: blurring, red-green color blindness </li></ul></ul><ul><ul><li>Rash </li></ul></ul>
  39. 39. Cycloserine <ul><li>Mechanism of Action </li></ul><ul><ul><li>Inhibits cell wall synthesis </li></ul></ul><ul><ul><li>May be bacteriostatic or bactericidal </li></ul></ul><ul><li>Warnings / Precautions </li></ul><ul><ul><li>D/C if: CNS toxicity, dysarthria, allergic dermatitis </li></ul></ul><ul><ul><li>Small Therapeutic Index: Toxicity r/t to high blood levels </li></ul></ul><ul><ul><li>Renal Function Impairment: accumulation & toxicity </li></ul></ul><ul><ul><li>Anticonvulsants or sedatives may be effective in controlling Sx’s. ALSO, pyridoxine may be helpful in ameliorating neurotoxicity </li></ul></ul><ul><ul><li>Associated with B12, folic acid deficiency, megaloblastic & sideroblastic anemia </li></ul></ul>
  40. 40. Cycloserine <ul><li>Adverse Effects </li></ul><ul><ul><li>CNS Sx’s: convulsions, psychosis, somnolence, depression, confusion, hyperreflexia, headache, tremor, vertigo, paresis </li></ul></ul><ul><li>Drug Interactions </li></ul><ul><ul><li>INH: increase in dizziness </li></ul></ul><ul><ul><li>Alcohol: increased risk of epileptic episodes </li></ul></ul><ul><li>Overdose </li></ul><ul><ul><li>CNS depression </li></ul></ul>
  41. 41. Cycloserine: Pt Education <ul><li>Notify provider of: </li></ul><ul><ul><li>Dizziness, mental confusion, skin rash, tremor </li></ul></ul><ul><li>Avoid alcohol </li></ul><ul><li>May cause drowsiness, use caution when operating heavy machinery </li></ul>
  42. 42. Ethionamide (when 1st line Tx has failed) <ul><li>Mechanism of Action </li></ul><ul><ul><li>Inhibits peptide synthesis </li></ul></ul><ul><ul><li>Bacteriostatic or bactericidal depending on concentration & susceptibility of organism </li></ul></ul><ul><ul><li>Highly specific for Mycobacterium </li></ul></ul><ul><ul><li>NOT a first line agent </li></ul></ul><ul><li>Contraindications </li></ul><ul><ul><li>Hepatic damage or hypersensitivity </li></ul></ul><ul><li>Warnings / Precautions </li></ul><ul><ul><li>Hepatitis occurs more frequently  monitor LFTs </li></ul></ul><ul><ul><li>Management of DM may be more difficult </li></ul></ul><ul><li>Drug Interactions </li></ul><ul><ul><li>Raises serum concentrations of INH </li></ul></ul><ul><ul><li>May potentiate adverse effects of other antitubercular drugs, esp. cycloserine </li></ul></ul><ul><ul><li>Avoid alcohol ingestion (may produce psychotic reaction) </li></ul></ul>
  43. 43. Ethionamide: Pt Education <ul><li>May cause stomach upset, metallic taste, or loss of appetite </li></ul><ul><li>Take with food to minimize GI upset </li></ul><ul><li>Notify provider if effects persist </li></ul>

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