Tuberculosis www.freelivedoctor.com
<ul><li>Tuberculosis (TB) remains the leading cause of death worldwide from a single infectious disease agent. Indeed up t...
<ul><li>It is estimated that between 2000 and 2020, nearly  one billion  people will be newly infected, 200 million people...
<ul><li>TB is an ancient infectious disease caused by  Mycobacterium tuberculosis . It has been known since 1000 B.C., so ...
<ul><li>With the increased incidence of AIDS, TB has become more a problem in the U.S., and the world. </li></ul><ul><li>I...
Transmission <ul><li>Pulmonary tuberculosis is a disease of respiratory transmission, Patients with the active disease (ba...
<ul><li>Once inhaled by a tuberculin free person, the bacilli multiply 4 -6 weeks and spreads throughout the body. The bac...
<ul><li>This is known as the  primary infection.  The patient will heal and a scar will appear in the infected loci. There...
www.freelivedoctor.com
Classification of Drugs   <ul><li>3 Groups depending upon the degree of effectiveness and potential side effects   </li></...
Isoniazid <ul><li>Considered the drug of choice for the chemotherapy of TB.  discovered in 1945   a hydrazide of isonicoto...
Mechanism of action   <ul><li>Unknown, but the hypothesis include effects on lipids, nucleic acid and biosynthesis.  </li>...
www.freelivedoctor.com
Resistance   <ul><li>Organism eventually develops resistance.  </li></ul><ul><li>The mechanism of resistance is related   ...
Pharmacokinetics   <ul><li>Absorption : INH rapidly absorbed either oral or parenteral route. Peak [plasma] of 3-5 microgr...
Excretion   <ul><li>75-95% of a dose excreted in the urine in 24 hr. </li></ul><ul><li>- Mostly as a metabolite. </li></ul...
Excretion cont. <ul><li>Those that have slow acetyl transferase activity are  slow acetylators , may produce more of the t...
Adverse Effects   <ul><li>Induced Hepatitis (2% of Population) due to the buildup of toxic metabolic products of acetyliso...
Age dependency www.freelivedoctor.com % incidence age   0.13 25 .59 35 1.09 45 1.75 55 2.5 >60
<ul><li>Patients with renal failure, the normal dose can be given, because it is secreted in the inactive form. </li></ul>...
Drug Interaction <ul><li>Competition between Isoniazid and Phenytoin (anticonvulsant). They both compete for drug metaboli...
Rifampin  <ul><li>Mechanism of Action </li></ul><ul><li>Rifampin inhibits DNA dependent RNA polymerase of the bacilli. </l...
Resistance:   <ul><li>Due to alteration of the target (DNA dependent RNA polymerase) of the   drug,   prevents further ini...
Pharmacokinetics <ul><li>Absorption </li></ul><ul><li>peak levels reached 2-4 hrs. after oral dose </li></ul><ul><li>rapid...
<ul><li>Distribution: </li></ul><ul><li>Throughout the total body water </li></ul><ul><li>Present in effective concentrati...
Adverse Effects:   <ul><li>Does not cause many side effects in any great frequency. </li></ul><ul><li>G.I. reactions:  Ano...
<ul><li>Allergic Reactions  </li></ul><ul><li>Fever </li></ul><ul><li>Skin Eruptions </li></ul><ul><li>Rash </li></ul><ul>...
WARNING! Rifampin and Isoniazid are the most effective drugs for the treatment of TB, The drug enjoys high patient complia...
2nd Line Drugs:   Not as effective and have more toxicity   <ul><li>Streptomycin   </li></ul><ul><li>The first drug used c...
<ul><li>Adverse Effects: </li></ul><ul><li>affects C. Nerve 8: auditory and vestibular functions. - this drug is now 2nd '...
para- Aminosalicylic Acid <ul><li>a structural analog of PABA (p-aminobenzoic acid)   is bacteriostatic   inhibits de novo...
Adverse effects <ul><li>GI irritation   due to the amount of drug given (high doses)   nausea, vomiting, bleeding, occurs ...
Third Line Drug s -  least effective and most toxic   <ul><li>Third line drugs are used when resistance is developed to 1s...
Adverse effects <ul><li>These drugs are:  Nephrotoxic  - will cause  Proteinuria,   Hematuria,   Nitrogen metabolism, and ...
<ul><li>Ototoxic   will result in deafness and some loss of vestibular function, leads to cranial nerve 8 damage.  The ner...
Cycloserine <ul><li>can cause CNS disturbances  </li></ul><ul><li>Therapeutic State s    Cycloserine  should be used when ...
<ul><li>Pharmacokinetics:   Rapidly absorbed   Peak [plasma] occurs in 3-4 hours   Distributed throughout all body fluids,...
<ul><li>Toxicity: </li></ul><ul><li>Most common in the CNS:  Headache,   Tremor,   Vertigo,   Confusion,   Nervousness,   ...
Chemoprophylaxis of TB Used only in high risk groups <ul><li>Household members and other close contacts of a patient with ...
<ul><li>The drug of choice for chemoprophylaxis is  isoniazid.  Prophylaxis uses only one drug. In patients who are HIV+ a...
Chemotherapy of TB   <ul><li>Most patients are treated in an ambulatory setting - admitted to the hospital  - diagnosis is...
Treatment <ul><li>Isoniazid, Ethambutol, & Rifampin are given for 2 months. </li></ul><ul><li>Isoniazid & Rifampin are giv...
Antitubercular Agents <ul><li>Tuberculosis, “TB” </li></ul><ul><li>Caused by Mycobacterium tuberculosis </li></ul><ul><li>...
Mycobacterium Infections <ul><li>Common Infection Sites </li></ul><ul><li>lung (primary site) </li></ul><ul><li>brain </li...
Mycobacterium Infections <ul><li>Aerobic bacillus </li></ul><ul><li>Passed from infected: </li></ul><ul><ul><li>Humans </l...
Mycobacterium Infections <ul><li>Tubercle bacilli are conveyed by droplets. </li></ul><ul><li>Droplets are expelled by cou...
Antitubercular Agents <ul><li>Primary Agents Secondary Agents </li></ul><ul><li>isoniazid* capreomycin </li></ul><ul><li>e...
Antitubercular Agents:  Mechanism of Action <ul><li>Three Groups </li></ul><ul><li>Protein wall synthesis inhibitors strep...
Antitubercular Agents: Mechanism of Action isoniazid (INH) <ul><li>Drug of choice for TB </li></ul><ul><li>Resistant strai...
Used for the prophylaxis or treatment of TB Antitubercular Agents: Therapeutic Uses
Antitubercular Therapy <ul><li>Effectiveness depends upon: </li></ul><ul><li>Type of infection </li></ul><ul><li>Adequate ...
Antitubercular Agents: Side Effects <ul><li>INH peripheral neuritis, hepatotoxicity </li></ul><ul><li>ethambutol retrobulb...
Antitubercular Agents:  Nursing Implications <ul><li>Obtain a thorough medical history and assessment. </li></ul><ul><li>P...
Antitubercular Agents:  Nursing Implications <ul><li>Patient education is CRITICAL: </li></ul><ul><li>Therapy may last for...
Antitubercular Agents:  Nursing Implications <ul><li>Patient education is CRITICAL: </li></ul><ul><li>Remind patients that...
Antitubercular Agents:  Nursing Implications <ul><li>Patients should not consume alcohol while on these medications nor ta...
Antitubercular Agents:  Nursing Implications <ul><li>Patients who are taking rifampin should be told that their urine, sto...
Antitubercular Agents: Nursing Implications <ul><li>Monitor for side effects </li></ul><ul><li>Instruct patients on the si...
Antitubercular Agents: Nursing Implications <ul><li>Monitor for therapeutic effects: </li></ul><ul><li>Decrease in symptom...
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Tuberculosis& its management

  1. 1. Tuberculosis www.freelivedoctor.com
  2. 2. <ul><li>Tuberculosis (TB) remains the leading cause of death worldwide from a single infectious disease agent. Indeed up to 1/2 of the world's population is infected with TB.  The registered number of new cases of TB worldwide roughly correlates with economic conditions: the highest incidences are seen in those countries of Africa, Asia, and Latin America with the lowest gross national products. WHO estimates that eight million people get TB every year, of whom 95% live in developing countries. An estimated 2 million people die from TB every year.  </li></ul>www.freelivedoctor.com
  3. 3. <ul><li>It is estimated that between 2000 and 2020, nearly one billion people will be newly infected, 200 million people will get sick, and 35 million will die from TB - if control is not further strengthened. The mechanisms, pathogenesis, and prophylaxis knowledge is minimal. After a century of decline TB is increasing and there are strains emerging which are resistant to antibiotics. This excess of cases is attributable to the changes in the social structure in cities, the human immunodeficiency virus epidemic, and failure of most cities to improve public health programs, and the economic cost of treating. </li></ul>www.freelivedoctor.com
  4. 4. <ul><li>TB is an ancient infectious disease caused by Mycobacterium tuberculosis . It has been known since 1000 B.C., so it not a new disease. Since TB is a disease of respiratory transmission, optimal conditions for transmission include: </li></ul><ul><ul><li>overcrowding </li></ul></ul><ul><ul><li>poor personal hygiene </li></ul></ul><ul><ul><li>poor public hygiene </li></ul></ul>www.freelivedoctor.com
  5. 5. <ul><li>With the increased incidence of AIDS, TB has become more a problem in the U.S., and the world. </li></ul><ul><li>It is currently estimated that 1/2 of the world's population (3.1 billion) is infected with Mycobacterium tuberculosis. Mycobacterium avium complex is associated with AIDS related TB. </li></ul>www.freelivedoctor.com
  6. 6. Transmission <ul><li>Pulmonary tuberculosis is a disease of respiratory transmission, Patients with the active disease (bacilli) expel them into the air by: </li></ul><ul><ul><li>coughing, </li></ul></ul><ul><ul><li>sneezing, </li></ul></ul><ul><ul><li>shouting, </li></ul></ul><ul><ul><li>or any other way that will expel bacilli into the air </li></ul></ul>www.freelivedoctor.com
  7. 7. <ul><li>Once inhaled by a tuberculin free person, the bacilli multiply 4 -6 weeks and spreads throughout the body. The bacilli implant in areas of high partial pressure of oxygen: </li></ul><ul><li>lung </li></ul><ul><li>renal cortex </li></ul><ul><li>reticuloendothelial system </li></ul>www.freelivedoctor.com
  8. 8. <ul><li>This is known as the primary infection. The patient will heal and a scar will appear in the infected loci. There will also be a few viable bacilli/spores may remain in these areas (particularly in the lung). The bacteria at this time goes into a dormant state, as long as the person's immune system remains active and functions normally this person isn't bothered by the dormant bacillus. </li></ul><ul><li>When a person's immune system is depressed., a secondary reactivation occurs. 85-90% of the cases seen which are of secondary reactivation type occurs in the lungs. </li></ul>www.freelivedoctor.com
  9. 9. www.freelivedoctor.com
  10. 10. Classification of Drugs <ul><li>3 Groups depending upon the degree of effectiveness and potential side effects </li></ul><ul><ul><li>First Line: (Primary agents) </li></ul></ul><ul><ul><ul><li>are the most effective and have lowest toxicity. Isoniazid Rifampin </li></ul></ul></ul><ul><ul><li>Second Line: </li></ul></ul><ul><ul><ul><li>Less effective and more toxic effects </li></ul></ul></ul><ul><ul><ul><li>include (in no particular order): p-amino salicylic acid, Streptomycin, Ethambutol </li></ul></ul></ul><ul><ul><li>Third Line </li></ul></ul><ul><ul><ul><li>are least effective and most toxic. Amikacin, Kanamycin, Capreomycin, Viomycin, Kanamycin, Cycloserine </li></ul></ul></ul>www.freelivedoctor.com
  11. 11. Isoniazid <ul><li>Considered the drug of choice for the chemotherapy of TB. discovered in 1945 a hydrazide of isonicotonic acid </li></ul><ul><ul><li>is bacteriostatic for resting bacilli, </li></ul></ul><ul><ul><li>bactericidal for growing bacilli. </li></ul></ul>www.freelivedoctor.com
  12. 12. Mechanism of action <ul><li>Unknown, but the hypothesis include effects on lipids, nucleic acid and biosynthesis. </li></ul><ul><li>Primary action seems to inhibit the biosynthesis of mycolic acids which are part of cell wall structure. </li></ul>www.freelivedoctor.com
  13. 13. www.freelivedoctor.com
  14. 14. Resistance <ul><li>Organism eventually develops resistance. </li></ul><ul><li>The mechanism of resistance is related to the failure of the drug to penetrate or be taken up by the micro-organism (by active transport system), </li></ul><ul><li>Remember treatment is up to 2 years. </li></ul>www.freelivedoctor.com
  15. 15. Pharmacokinetics <ul><li>Absorption : INH rapidly absorbed either oral or parenteral route. Peak [plasma] of 3-5 micrograms/milliliter after oral administration. </li></ul><ul><li>Distribution: </li></ul><ul><ul><li>Diffuses readily into all bodily fluids does not bind to plasma proteins </li></ul></ul><ul><ul><li>In the CSF the [conc] is about 20% of [plasma], </li></ul></ul><ul><ul><li>t1/2 =1-3 hrs. </li></ul></ul>www.freelivedoctor.com
  16. 16. Excretion <ul><li>75-95% of a dose excreted in the urine in 24 hr. </li></ul><ul><li>- Mostly as a metabolite. </li></ul><ul><li>- The main excretory product- acetylisoniazid. This is a result of enzymatic acetylation, Very important in terms of metabolism, Isoniazid is under genetic control, There are 2 groups of people. Fast and slow acetylators </li></ul>www.freelivedoctor.com
  17. 17. Excretion cont. <ul><li>Those that have slow acetyl transferase activity are slow acetylators , may produce more of the toxic intermediate. </li></ul><ul><li>This is an inherited trait ==> Autosomal Dominant </li></ul><ul><li>The average [plasma] will be (1/3) to (1/2) of the slow acetylators Average t1/2, is less than 90 minutes, in the slow acetylators, t1/2 will be about 3 hours. </li></ul><ul><li>Ethnicity- Eskimos,Native American Indians, and Asians are fast aceytlators, </li></ul>www.freelivedoctor.com
  18. 18. Adverse Effects <ul><li>Induced Hepatitis (2% of Population) due to the buildup of toxic metabolic products of acetylisoniazid --> acetylhydrazine. This is more frequent in slow acetylators . </li></ul><ul><li>Hepatic reactions to Isoniazid are also age dependent </li></ul><ul><ul><li>There is a 250X increase in the incidence of hepatitis over age. More frequent in the fast acetylators when measured intragroup, (Compare elderly fast acetylators patients with elderly slow patients,) Ranges from mild hepatitis to serious tissue necrosis. </li></ul></ul>www.freelivedoctor.com
  19. 19. Age dependency www.freelivedoctor.com % incidence age   0.13 25 .59 35 1.09 45 1.75 55 2.5 >60
  20. 20. <ul><li>Patients with renal failure, the normal dose can be given, because it is secreted in the inactive form. </li></ul><ul><li>Patients with hepatic insufficiency - give a reduced dose of the drug. </li></ul><ul><li>ETOH causes induction of drug metabolizing enzymes, Isoniazid is broken down faster. Leads to lsoniazid hepatotoxicity. </li></ul><ul><li>Glucose 6- Phosphate deficiency. People with a deficiency of Glucose-6-phosphate cannot adequately process the drug. </li></ul>www.freelivedoctor.com
  21. 21. Drug Interaction <ul><li>Competition between Isoniazid and Phenytoin (anticonvulsant). They both compete for drug metabolism enzymes. Phenytoin interferes with metabolism of isoniazid by reduction in excretion or enhancement of effect of isoniazid </li></ul>www.freelivedoctor.com
  22. 22. Rifampin <ul><li>Mechanism of Action </li></ul><ul><li>Rifampin inhibits DNA dependent RNA polymerase of the bacilli. </li></ul>www.freelivedoctor.com
  23. 23. Resistance: <ul><li>Due to alteration of the target (DNA dependent RNA polymerase) of the drug, prevents further initiation but not elongation. The micro-organism can change the structure of the enzyme so that the drug no longer has an effect. </li></ul>www.freelivedoctor.com
  24. 24. Pharmacokinetics <ul><li>Absorption </li></ul><ul><li>peak levels reached 2-4 hrs. after oral dose </li></ul><ul><li>rapidly eliminated in the bile and reabsorbed (enterohepatic circulation) It can be delayed with use of aminosalicylic acid. </li></ul><ul><li>during this time there is a progressive deacylation of the drug; </li></ul><ul><li>the metabolites maintain full effect </li></ul><ul><li>Half life is 6 hours. </li></ul>www.freelivedoctor.com
  25. 25. <ul><li>Distribution: </li></ul><ul><li>Throughout the total body water </li></ul><ul><li>Present in effective concentrations in many organs and body fluids including CSF, </li></ul><ul><li>With Rifampin you must warn patients: The drug has an orange red color in body excretions, This color will be imparted to all body fluids. </li></ul>www.freelivedoctor.com
  26. 26. Adverse Effects: <ul><li>Does not cause many side effects in any great frequency. </li></ul><ul><li>G.I. reactions: Anorexia, Nausea , Vomiting Mild abdominal pain, Hepatic Reactions in children, pregnant women and alcoholics, can result in minor elevations in serum transaminase as some jaundice </li></ul>www.freelivedoctor.com
  27. 27. <ul><li>Allergic Reactions </li></ul><ul><li>Fever </li></ul><ul><li>Skin Eruptions </li></ul><ul><li>Rash </li></ul><ul><li>Pruritis </li></ul><ul><li>Rifampin does induce microsomal drug metabolizing enzymes. This will decrease the half-life of some other drugs. (ie. phenytoin, digitoxin) </li></ul>www.freelivedoctor.com
  28. 28. WARNING! Rifampin and Isoniazid are the most effective drugs for the treatment of TB, The drug enjoys high patient compliance and acceptability. But these 2 drugs should never be given alone! They are always used in combination because resistance occurs to one drug alone very rapidly. They are used in combination with each other initially as well as other drugs. Bacilli must become resistant to two drugs in order to remain viable. Statistically, the chances are verv small of the bacilli becoming resistant to both. . Prophylaxis is with one drug usually isoniazid. www.freelivedoctor.com
  29. 29. 2nd Line Drugs: Not as effective and have more toxicity <ul><li>Streptomycin </li></ul><ul><li>The first drug used clinically for treatment of TB 1947-1952; was the only drug available at that time. </li></ul><ul><li>is an aminoglycoside antibiotic </li></ul><ul><li>acts by protein synthesis inhibitor and decreases the fidelity mRNA and garbles the message, leads to nonsense proteins. </li></ul><ul><li>Streptomycin only binds to the 30s subunit. </li></ul>www.freelivedoctor.com
  30. 30. <ul><li>Adverse Effects: </li></ul><ul><li>affects C. Nerve 8: auditory and vestibular functions. - this drug is now 2nd 'line because of its toxicity.  </li></ul>www.freelivedoctor.com
  31. 31. para- Aminosalicylic Acid <ul><li>a structural analog of PABA (p-aminobenzoic acid) is bacteriostatic inhibits de novo folate synthesis </li></ul><ul><li>half life = 1 hour after 4 g. dose </li></ul><ul><li>you can give this drug up to 12 grams per day. 80% of the drug is excreted in the urine and 50% of that is as an acetylated metabolite which is insoluble. You must make sure the patient's urine is normal or alkaline. </li></ul>www.freelivedoctor.com
  32. 32. Adverse effects <ul><li>GI irritation due to the amount of drug given (high doses) nausea, vomiting, bleeding, occurs in 30-40% of the patients. be careful with those who have peptic ulcers </li></ul><ul><li>Hypersensitivity reactions Rash, Fever some hepatotoxicity </li></ul><ul><li>All will disappear when the drug is stopped </li></ul><ul><li>This drug has poor patient acceptability and compliance:   </li></ul>www.freelivedoctor.com
  33. 33. Third Line Drug s - least effective and most toxic <ul><li>Third line drugs are used when resistance is developed to 1st and 2nd line drugs; these drugs are also used in combination. </li></ul><ul><li>A minoglycosides </li></ul><ul><li>Capreomycin - Viomycin - Kanamycin </li></ul>www.freelivedoctor.com
  34. 34. Adverse effects <ul><li>These drugs are: Nephrotoxic - will cause Proteinuria, Hematuria, Nitrogen metabolism, and Electrolyte disturbances However effect is reversible when drug is stopped. </li></ul>www.freelivedoctor.com
  35. 35. <ul><li>Ototoxic will result in deafness and some loss of vestibular function, leads to cranial nerve 8 damage. The nerve damage is permanent. </li></ul><ul><li>Capreomycin has replaced viomycin because of less toxic effects, but all three drugs have the same effects. </li></ul>www.freelivedoctor.com
  36. 36. Cycloserine <ul><li>can cause CNS disturbances </li></ul><ul><li>Therapeutic State s Cycloserine should be used when re-treatment is necessary or when the micro-organism is resistant to the other drugs. </li></ul><ul><li>It must be given in combination with other anti-tuberculosis drugs. </li></ul><ul><li>Mechanism of Action: </li></ul><ul><li> An analog of D-alanine synthetase, will block bacterial cell wall synthesis. </li></ul>www.freelivedoctor.com
  37. 37. <ul><li>Pharmacokinetics: Rapidly absorbed Peak [plasma] occurs in 3-4 hours Distributed throughout all body fluids, including CSF About 50% is excreted in unchanged form in the urine during the first 12 hours. Only about 35% of the drug metabolized This drug can accumulate to toxic conc in patients with renal insufficiency </li></ul>www.freelivedoctor.com
  38. 38. <ul><li>Toxicity: </li></ul><ul><li>Most common in the CNS: Headache, Tremor, Vertigo, Confusion, Nervousness, Psychotic states with suicidal tendencies , Paranoid reactions, Catatonic and depressed reactions </li></ul>www.freelivedoctor.com
  39. 39. Chemoprophylaxis of TB Used only in high risk groups <ul><li>Household members and other close contacts of a patient with active TB. </li></ul><ul><li>A positive skin test in persons less than 35 years. </li></ul><ul><li>A positive skin test reactive in the immunosuppressed, persons with leukemia, and Hodgkin's Disease, </li></ul><ul><li>HIV + patients with a positive TB test, </li></ul>www.freelivedoctor.com
  40. 40. <ul><li>The drug of choice for chemoprophylaxis is isoniazid. Prophylaxis uses only one drug. In patients who are HIV+ and TB+ and have the disease; they are treated for a minimum of 9 months, The first 2 months using isoniazid and rifampin and for the next 7 months or longer, use only 2 or 3 of the 2nd/3rd line drugs and Isoniazid/Rifampin. </li></ul>www.freelivedoctor.com
  41. 41. Chemotherapy of TB <ul><li>Most patients are treated in an ambulatory setting - admitted to the hospital - diagnosis is established - initiate and stabilize therapy - send patient home , usually after 2 or 3 weeks </li></ul><ul><li>First and second line agents are usually given orally. Third line drugs are given parenterally. </li></ul>www.freelivedoctor.com
  42. 42. Treatment <ul><li>Isoniazid, Ethambutol, & Rifampin are given for 2 months. </li></ul><ul><li>Isoniazid & Rifampin are given for 4 months. </li></ul><ul><li>If you suspect resistance to isoniazid use Isoniazid, Ethambutol, Rifampin & Parazinamide. Incidence of drug resistance is 2-5% in the U.S. </li></ul><ul><li>Prolonged bed rest is not necessary or helpful in obtaining a speedy recovery. The patient must be seen at regular and frequent intervals to follow the course of the disease and treatment. Look for toxic effects </li></ul>www.freelivedoctor.com
  43. 43. Antitubercular Agents <ul><li>Tuberculosis, “TB” </li></ul><ul><li>Caused by Mycobacterium tuberculosis </li></ul><ul><li>Antitubercular agents treat all forms of mycobacterium </li></ul>
  44. 44. Mycobacterium Infections <ul><li>Common Infection Sites </li></ul><ul><li>lung (primary site) </li></ul><ul><li>brain </li></ul><ul><li>bone </li></ul><ul><li>liver </li></ul><ul><li>kidney </li></ul>
  45. 45. Mycobacterium Infections <ul><li>Aerobic bacillus </li></ul><ul><li>Passed from infected: </li></ul><ul><ul><li>Humans </li></ul></ul><ul><ul><li>Cows (bovine) </li></ul></ul><ul><ul><li>Birds (avian) </li></ul></ul>
  46. 46. Mycobacterium Infections <ul><li>Tubercle bacilli are conveyed by droplets. </li></ul><ul><li>Droplets are expelled by coughing or sneezing, then gain entry into the body by inhalation. </li></ul><ul><li>Tubercle bacilli then spread to other body organs via blood and lymphatic systems. </li></ul><ul><li>Tubercle bacilli may become dormant, or walled off by calcified or fibrous tissue. </li></ul>
  47. 47. Antitubercular Agents <ul><li>Primary Agents Secondary Agents </li></ul><ul><li>isoniazid* capreomycin </li></ul><ul><li>ethambutol cycloserine </li></ul><ul><li>pyrazinamide (PZA) ethionamide </li></ul><ul><li>rifampin kanamycin </li></ul><ul><li>streptomycin para-aminosalicyclic acid (PSA) </li></ul><ul><li>*most frequently used </li></ul>
  48. 48. Antitubercular Agents: Mechanism of Action <ul><li>Three Groups </li></ul><ul><li>Protein wall synthesis inhibitors streptomycin, kanamycin, capreomycin, rifampin, rifabutin </li></ul><ul><li>Cell wall synthesis inhibitors cycloserine, ethionamide, isoniazid </li></ul><ul><li>Other mechanisms of action </li></ul>
  49. 49. Antitubercular Agents: Mechanism of Action isoniazid (INH) <ul><li>Drug of choice for TB </li></ul><ul><li>Resistant strains of mycobacterium emerging </li></ul><ul><li>Metabolized in the liver through acetylation—watch for “slow acetylators” </li></ul>
  50. 50. Used for the prophylaxis or treatment of TB Antitubercular Agents: Therapeutic Uses
  51. 51. Antitubercular Therapy <ul><li>Effectiveness depends upon: </li></ul><ul><li>Type of infection </li></ul><ul><li>Adequate dosing </li></ul><ul><li>Sufficient duration of treatment </li></ul><ul><li>Drug compliance </li></ul><ul><li>Selection of an effective drug combination </li></ul>
  52. 52. Antitubercular Agents: Side Effects <ul><li>INH peripheral neuritis, hepatotoxicity </li></ul><ul><li>ethambutol retrobulbar neuritis, blindness </li></ul><ul><li>rifampin hepatitis, discoloration of urine, stools </li></ul>
  53. 53. Antitubercular Agents: Nursing Implications <ul><li>Obtain a thorough medical history and assessment. </li></ul><ul><li>Perform liver function studies in patients who are to receive isoniazid or rifampin (especially in elderly patients or those who use alcohol daily). </li></ul><ul><li>Assess for contraindications to the various agents, conditions for cautious use, and potential drug interactions. </li></ul>
  54. 54. Antitubercular Agents: Nursing Implications <ul><li>Patient education is CRITICAL: </li></ul><ul><li>Therapy may last for up to 24 months. </li></ul><ul><li>Take medications exactly as ordered, at the same time every day. </li></ul><ul><li>Emphasize the importance of strict compliance to regimen for improvement of condition or cure. </li></ul>
  55. 55. Antitubercular Agents: Nursing Implications <ul><li>Patient education is CRITICAL: </li></ul><ul><li>Remind patients that they are contagious during the initial period of their illness—instruct in proper hygiene and prevention of the spread of infected droplets. </li></ul><ul><li>Emphasize to patients to take care of themselves, including adequate nutrition and rest. </li></ul>
  56. 56. Antitubercular Agents: Nursing Implications <ul><li>Patients should not consume alcohol while on these medications nor take other medications, including OTC, unless they check with their physician. </li></ul><ul><li>Diabetic patients taking INH should monitor their blood glucose levels because hyperglycemia may occur. </li></ul><ul><li>INH and rifampin cause oral contraceptives to become ineffective; another form of birth control will be needed. </li></ul>
  57. 57. Antitubercular Agents: Nursing Implications <ul><li>Patients who are taking rifampin should be told that their urine, stool, saliva, sputum, sweat, or tears may become reddish-orange; even contact lenses may be stained. </li></ul><ul><li>Vitamin B 6 may is needed to combat peripheral neuritis associated with INH therapy. </li></ul>
  58. 58. Antitubercular Agents: Nursing Implications <ul><li>Monitor for side effects </li></ul><ul><li>Instruct patients on the side effects that should be reported to the physician immediately. </li></ul><ul><li>These include fatigue, nausea, vomiting, numbness and tingling of the extremities, fever, loss of appetite, depression, jaundice. </li></ul>
  59. 59. Antitubercular Agents: Nursing Implications <ul><li>Monitor for therapeutic effects: </li></ul><ul><li>Decrease in symptoms of TB, such as cough and fever </li></ul><ul><li>Lab studies (culture and sensitivity tests) and CXR should confirm clinical findings </li></ul><ul><li>Watch for lack of clinical response to therapy, indicating possible drug resistance </li></ul>
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