Download - 47 ANTIMYCOBACTERIAL DRUGS
![Page 1: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/1.jpg)
Lourdes T. M. Dominguez, M.D.
University of Santo Tomas
Faculty of Pharmacy
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
![Page 2: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/2.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
• Mycobacterium tuberculosis• Mycobacterium leprae• Mycobacterium avium
![Page 3: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/3.jpg)
HOW IS TB SPREAD?
• Spread through the air from one person to another
• Most likely to spread to people who are close contacts (people they spend time with every day, family, friends, co-workers, schoolmates)
• Transmitted through airborne droplets when person with active TB of the lungs (PTB) or throat (laryngeal TB) coughs, sneezes, speaks or sings
• TB of the lung or throat can be infectious
![Page 4: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/4.jpg)
HOW IS TB SPREAD?
![Page 5: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/5.jpg)
HOW IS TB SPREAD?
• TB of the lungs or throat can be infectious• Extra-pulmonary TB is usually not infectious
![Page 6: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/6.jpg)
CLINICAL MANIFESTATIONS
• Fever• Weight loss • Weakness• Night sweats• Malaise• Hematologic abnormalities
![Page 7: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/7.jpg)
HISTORY AND PHYSICAL EXAMINATION
• Lungs: 71% Extrapulmonary: 20% Both: 9%• Cough (for 2-3 weeks is the most common)• Pleuritic pain• Pneumothorax• Dyspnea• Hemoptysis
![Page 8: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/8.jpg)
DIAGNOSTIC EXAMS
Chest radiograph• Usually the first diagnostic study done• May be negative in some patients with positive sputum
cultures• Cannot provide a definitive diagnosis of TB• Activity cannot be determined from a single radiographic
examination
![Page 9: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/9.jpg)
DIAGNOSTIC EXAMS
Bacteriologic Evaluation• Sputum examination• Sampling of gastric contents• Broncho-alveolar lavage, Transbronchial lung
biopsy• Needle aspiration biopsy
![Page 10: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/10.jpg)
SPUTUM AFB SMEAR•Sputum is initial specimen of choice•3 specimens, early morning specimen
![Page 11: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/11.jpg)
MTB CULTURE
• More sensitive than microscopy• Sensitivity of 80-85%; specificity of 98%• Growth of organisms is necessary for precise
species identification• Required for drug susceptibility testing
![Page 12: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/12.jpg)
DRUG SUSCEPTIBILITY TESTING
• Performed on initial isolates from all patients in order to identify what should be an effective regimen
• Repeated if patient continues to produce culture-positive sputum after 3 months of treatment or becomes positive after a negative culture
![Page 13: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/13.jpg)
PPD
![Page 14: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/14.jpg)
Types of TB Cases
Definition of Terms
New A patient who has never had treatment for TB or who has taken anti-tuberculosis drugs for less than one month.
Relapse A patient previously treated for tuberculosis who has been declared cured or treatment completed, and is diagnosed with bacteriologically positive (smear or culture) tuberculosis.
Failure A patient who, while on treatment, is sputum smear positive at five months or later during the course of treatment.
Return after Default (RAD)
A patient who returns to treatment with positive bacteriology (smear or culture), following interruption of treatment of treatment for two months or more.
Transfer-In A patient who has been transferred from another facility with proper referral slip to continue treatment.
Other All cases that do not fit into any of the above definitionsThis group includes:1. A patient who is starting treatment again after interrupting
treatment for more than two months and has remained or become smear-negative.
2. A sputum smear negative patient initially before starting treatment and became sputum smear—positive during the treatment.
3. Chronic case: a patient who is sputum positive at the end of a re-treatment regimen.
![Page 15: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/15.jpg)
![Page 16: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/16.jpg)
Location of Lesion
Definition of Terms
Extra-Pulmonary
TB
1. A patient with at least one mycobacterial smear/culture positive from an extra-pulmonary site (organs other than the lungs: pleura, lymph nodes, genito-urinary tract, skin, joints and bones, meninges, intestines, peritoneum and pericardium, among others), or
2. A patient with histological and/or clinical evidence consistent with active TB and there is a decision by a Medicla Officer to treat the patient with anti-TB drugs.
![Page 17: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/17.jpg)
LATENT TB
• Not infectious; cannot transmit the organism
• Approximately 10% who acquire TB infection and not treated will develop active TB
• Risk is highest in the first 2 year of infection
![Page 18: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/18.jpg)
A person with latent TB infection
A person with Active TB disease
Usually has a skin test or blood test result indicating TB infection
Usually has a skin test or blood test result indicating TB infection
Has a normal chest x-ray and a negative sputum test
May have an abnormal chest x-ray, or positive sputum smear or culture
Has TB bacteria in his/her body that are alive, but inactive
Has active TB bacteria in his/her body
Does not feel sick Usually feels sick and may have symptoms such as coughing, fever, and weight loss
Cannot spread the TB bacteria to others
May spread TB bacteria to others
Needs treatment for latent TB infection to prevent TB disease
Needs treatment to treat active TB disease
![Page 19: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/19.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
USE OF DRUG COMBINATIONS • To delay emergence of resistance • To enhance antimycobacterial efficacy
![Page 20: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/20.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
COMPLICATIONS OF CHEMOTHERAPY• Limited information about the MOA• Development of resistance• Intracellular location of mycobacteria• Chronic nature of the disease
(protracted therapy and drug toxicities)• Patient compliance
![Page 21: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/21.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
ANTIMYCOBACTERIAL DRUGS
Drugs used in Drugs used Drugs used for tuberculosis in leprosy atypical
mycobacteria
First-line Alternative Drugs for Drugs for drugs drugs major infections minor
infections
![Page 22: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/22.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSIS• Isoniazid (INH)• Rifampin• Pyrazinamide (PZA)• Ethambutol• Streptomycin
![Page 23: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/23.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSIS• Bactericidal or bacteriostatic
o Drug concentrationo Strain susceptibility
![Page 24: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/24.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSIS• Initial treatment
o 3-or 4 drug combination regimens o Known or anticipated rate of resistance
to INH
![Page 25: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/25.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISA. ISONIAZID1. MOA• Structural congener of pyridoxine• Inhibition of enzymes required for the
synthesis of mycolic acid and mycobacterial cell walls
• Resistance can emerge rapidly if used alone
![Page 26: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/26.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISA. ISONIAZID2. PHARMACOKINETICS• Well absorbed orally• Acts on intracellular mycobacteria• Liver metabolism is by acetylation
and is under genetic control
![Page 27: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/27.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISA. ISONIAZID2. PHARMACOKINETICS• Patients maybe fast (Asians) or slow
inactivators of the drug• Fast acetylators may require higher
dosage
![Page 28: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/28.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISA. ISONIAZID3. CLINICAL USE• Single most important drug in TB• Component of most drug regimen
combinations• Latent infection (“prophylaxis”)
![Page 29: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/29.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISA. ISONIAZID3. CLINICAL USE• Sole drug treatment
o Latent infection (“prophylaxis”)o Skin test converterso Close contacts of patients with
active disease
![Page 30: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/30.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISA. ISONIAZID4. TOXICITY AND DRUG INTERACTIONS• Neurotoxic effects
o Peripheral neuritis, restlessness, muscle twitching, and insomnia
o Pyridoxine (25-50 mg/day)
![Page 31: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/31.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISA. ISONIAZID4. TOXICITY AND DRUG INTERACTIONS• Hepatotoxic
o Abnormal liver function testso Jaundice, hepatitiso Rare in children
![Page 32: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/32.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISA. ISONIAZID4. TOXICITY AND DRUG INTERACTIONS• Inhibits the metabolism of other drugs
(eg, phenytoin)• Hemolysis in patients with G-6PD
(Glucose 6-phosphate deficiency)• Lupus-like syndrome
![Page 33: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/33.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISB. RIFAMPIN1. MOA• Derivative of rifamycin• Bactericidal against M. tuberculosis• Inhibits DNA-dependent RNA polymerase• Resistance emerges rapidly if used alone
![Page 34: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/34.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISB. RIFAMPIN2. PHARMACOKINETICS• Well absorbed orally• Distributed to most body tissues, including CNS• Enterohepatic cycling, partly metabolized by
the liver• Free drug and metabolites (orange colored)
are excreted in the feces
![Page 35: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/35.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISB. RIFAMPIN3. CLINICAL USES• Used in combination with other drugs• Leprosy
o Given monthly to delay the emergence of resistance to dapsone
![Page 36: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/36.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISB. RIFAMPIN3. CLINICAL USES• Sole drug therapy
o Latent TB in INH-intolerant patientso Close contacts of patients with INH-
resistant strains• Meningococcal and staphylococcal
carrier states
![Page 37: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/37.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISB. RIFAMPIN4. TOXICITY AND INTERACTIONS• Light chain proteinuria• May impair antibody immune responses• Skin rashes, thrombocytopenia, nephritis,
and liver dysfunction
![Page 38: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/38.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISB. RIFAMPIN4. TOXICITY AND INTERACTIONS• If given less often than twice weekly
o Flu-like syndrome and anemia
• Induces liver drug-metabolizing enzymes
![Page 39: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/39.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISB. RIFAMPIN4. TOXICITY AND INTERACTIONS• Enhances elimination
Anticonvulsants Contraceptive steroidsCyclosporine KetoconazoleMethadone TerbinafineWarfarin
![Page 40: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/40.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISB. RIFAMPIN4. TOXICITY AND INTERACTIONS• Rifabutin
o Less likely to cause drug interaction than rifampin o Equally as effective as antimycobacterial agent
![Page 41: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/41.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISB. RIFAMPIN4. TOXICITY AND INTERACTIONS• Rifabutin
o Another rifamycin o Preferred for TB in HIV patients
![Page 42: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/42.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISC. ETHAMBUTOL1. MOA• Inhibits arabinoyl transferases
Synthesis of arabinogalactanComponent of mycobacterial cell walls
• Resistance emerges rapidly when used alone
![Page 43: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/43.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISC. ETHAMBUTOL2. PHARMACOKINETICS• Well absorbed orally• Distributed to most tissues, including CNS• Large fraction is excreted unchanged in urine• Dose reduction necessary in renal failure
![Page 44: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/44.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISC. ETHAMBUTOL3. CLINICAL USE• Main use in TB• Used in combination with other
drugs
![Page 45: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/45.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISC. ETHAMBUTOL4. TOXICITY• Dose-dependent visual disturbances
o Increased visual acuityo Red-green color blindnesso Optic neuritiso Possible retinal damage (prolonged use at high
doses)
![Page 46: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/46.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISC. ETHAMBUTOL4. TOXICITY• Neurotoxic
o Headacheo Confusiono Peripheral neuropathy
![Page 47: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/47.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISD. PYRAZINAMIDE1. MOA• Not known• Bacteriostatic
o Require metabolic conversion via pyrazinamidases present in M. tuberculosis
![Page 48: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/48.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISD. PYRAZINAMIDE1. MOA• Resistance emerges rapidly when
used alone• Minimal cross-tolerance with other
antimycobacterial drugs
![Page 49: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/49.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISD. PYRAZINAMIDE2. PHARMACOKINETICS• Well absorbed orally• Distributed to most tissues, including CNS• Partly metabolized to pyrazinoic acid
![Page 50: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/50.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISD. PYRAZINAMIDE2. PHARMACOKINETICS• Parent molecule and metabolite are
excreted in urine• Half-life is increased in hepatic or renal failure
![Page 51: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/51.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISD. PYRAZINAMIDE3. CLINICAL USE• Combined use with other drugs
o “Short-course” regimens
![Page 52: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/52.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISD. PYRAZINAMIDE4. TOXICITY• 40% develop nongouty polyarthralgia• Asymptomatic hypeuricemia• Myalgia GI irritation• Porphyria Hepatic dysfunction• Maculopapular rash• Photosensitivity reactions
![Page 53: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/53.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISE. STREPTOMYCIN• Used more frequently than before
o Prevalence of drug-resistance strains of M. tuberculosis
• Administered intramuscularly
![Page 54: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/54.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISE. STREPTOMYCIN• Used in drug combinations for treatment
of life-threatening TB diseaseo Meningitiso Miliary disseminationo Severe organ TB
![Page 55: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/55.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISE. STREPTOMYCIN• Pharmacodynamics and kinetics
similar to other aminoglycosides• Kills mainly extracellular tubercle
bacilli
![Page 56: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/56.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISF. ALTERNATIVE DRUGS• Cases that are resistant to first-line drugs• Second-line drugs• Not more effective than first-line drugs• Toxicities are more serious
![Page 57: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/57.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISF. ALTERNATIVE DRUGS
AMIKACIN• Streptomycin-resistant or multi-drug
resistant mycobacterial strains• Used in combination with other drugs
![Page 58: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/58.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISF. ALTERNATIVE DRUGS
CIPROFLOXACIN and OFLOXACIN• Fluoroquinolones• Mycobacterial strains resistant to
first-line drugs• Used in combination with other drugs
![Page 59: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/59.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISF. ALTERNATIVE DRUGS
p-AMINOSALICYLIC ACID (PAS)• Rarely used because of primary resistance• GI irritation• Peptic ulceration• Hypersensitivity reactions• Effects on kidney, liver and thyroid function
![Page 60: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/60.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISF. ALTERNATIVE DRUGS
ETHIONAMIDE• Congener of INH, cross-resistance does
not occur• Severe GI irritation and adverse neurologic
effects at doses needed to achieve effective plasma levels
![Page 61: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/61.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISF. ALTERNATIVE DRUGS
CAPREOMYCIN• Limited use because of toxicity• Ototoxicity and renal dysfunction
![Page 62: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/62.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR TUBERCULOSISF. ALTERNATIVE DRUGS
CYCLOSERINE• Limited use because of toxicity• Peripheral neuropathy and CNS
dysfunction
![Page 63: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/63.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR LEPROSYA. SULFONES
DAPSONE1. MOA• Diaminodiphenylsulfone• Inhibition of folic acid synthesis• Resistance can develop if low doses
are given
![Page 64: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/64.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR LEPROSYA. SULFONES
DAPSONE2. PHARMACOKINETICS• Well absorbed orally• Penetrates tissues well• Enterohepatic cycling• Eliminated in the urine,
Partly as acetylated metabolites
![Page 65: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/65.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR LEPROSYA. SULFONES
DAPSONE3. CLINICAL USES• Most active drug against M. leprae• Rarely used alone
![Page 66: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/66.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR LEPROSYA. SULFONES
DAPSONE4. TOXICITY• GI irritation Fever• Skin rashes Methemoglobinemia• Hemolysis in patients with G-6PD
![Page 67: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/67.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR LEPROSYA. SULFONES
ACEDAPSONE• Repository form of dapsone• Provides inhibitory plasma concentrations
for several months• Alternative drug for P. carinii pneumonia
in HIV patients
![Page 68: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/68.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR LEPROSYA. OTHER AGENTS• Combination of dapsone with rifampin
(or rifabutin) plus or minus clofazimine• Clofazimine
GI irritation Pinkish-brown discoloration of urine
![Page 69: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/69.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR ATYPICAL MYCOBACTERIALINFECTIONS• M. marinum• M. avium-intracellulare• M. ulcerans
![Page 70: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/70.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR ATYPICAL MYCOBACTERIALINFECTIONS• Sometimes asymptomatic• Antimycobacterial drugs
Ethambutol Rifampin
• Other antibiotics Erythromycin Amikacin
![Page 71: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/71.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DRUGS FOR ATYPICAL MYCOBACTERIAL INFECTIONSM. avium complex (MAC)• Disseminated infection in HIV patients• Combination of drugs
Clarithromycin or azithromycin With ethambutol and rifabutin
![Page 72: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/72.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DIRECTLY OBSERVED TREATMENT (DOT)• Noncompliant patients • Drug-resistant tuberculosis
![Page 73: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/73.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DIRECTLY OBSERVED TREATMENT (DOT)• Direct sputum smear microscopy
o Primary diagnostic toolo Definitive diagnosis of active TBo Simple and economicalo Microscopy center would be organized
even in remote areas
![Page 74: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/74.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DIRECTLY OBSERVED TREATMENT (DOT)• All tb symptomatics must undergo sputum
examination prior to initiation of treatment, with or without x-ray results
![Page 75: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/75.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DIRECTLY OBSERVED TREATMENT (DOT)• Contraindication to examination is massive
hemoptysis• No diagnosis of TB shall be made based
on the result of x-ray examinations alone
![Page 76: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/76.jpg)
ANTIMYCOBACTERIAL DRUGSANTIMYCOBACTERIAL DRUGS
DIRECTLY OBSERVED TREATMENT (DOT) H = ISONIAZID R = RIFAMPICIN Z = PYRAZINAMIDE E = ETHAMBUTOL S = STREPTOMYCIN
![Page 77: 47 ANTIMYCOBACTERIAL DRUGS](https://reader035.vdocument.in/reader035/viewer/2022081418/55179d48497959a1248b4646/html5/thumbnails/77.jpg)
TB Diagnostic Category
TB Patients To Be Given Treatment
Tuberculosis Treatment Regimen & Duration of
Treatment
Category I • New pulmonary smear (+) cases• New pulmonary smear (-) cases with extensive parenchymal involvement and as assessed by the TBDC• Extra-pulmonary TB cases
2HRZE / 4 HR:HRZE for two months during
the intensive phase
HR for 4 months during the maintenance phase
Category II • Failure cases• Relapse cases• RAD• Other (smear +)• Other (smear -)
2HRZES / 1HRZE / 5HRE:HRZES for the first two
months, then HRZE for the third month during intensive
phase
HRE for the next five months during the maintenance
phase
Category III • New smear (-) but with minimal pulmonary TB on radiography and as assessed by the TBDC
2HRZE / 4HR:HRZE for 2 months during the
intensive phase
HR for 4 months during the maintenance phase