Antitubercular Agents

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Information about Antitubercular Agents

Published on November 15, 2007

Author: girlie

Source: slideshare.net

Antitubercular Agents

Tuberculosis Agent: Mycobacterium tuberculosis ALSO: M. africanum & M. bovis Route of Infection: Primary: inhalation of infectious particles (droplet nuclei) ALSO: spread by lymphatics Incubation: 2-10 weeks; risk of progressive disease greatest in first 2 years (HIV decreases both) Cell-mediated immune response  tubercle formation Culture takes 6 weeks Dx relies on AFB smear (Acid-Fast Bacillus) BUT threshold of detection 5-10,000 organisms/mL

Agent: Mycobacterium tuberculosis ALSO: M. africanum & M. bovis

Route of Infection:

Primary: inhalation of infectious particles (droplet nuclei) ALSO: spread by lymphatics

Incubation: 2-10 weeks; risk of progressive disease greatest in first 2 years (HIV decreases both)

Cell-mediated immune response  tubercle formation

Culture takes 6 weeks

Dx relies on AFB smear (Acid-Fast Bacillus)

BUT threshold of detection 5-10,000 organisms/mL

Tb Infection may not cause disease A good example of difference between infection and infectious disease Tb skin test converters have been infected, but are not sick. They are at risk of developing disease

A good example of difference between infection and infectious disease

Tb skin test converters have been infected,

but are not sick. They are at risk of developing disease

Tuberculosis: Types Sites: Pulmonary (most common) Bone Urinary tract Primary Initial infection with the disease Reactivation Patient infected in past has reactivation of disease

Sites:

Pulmonary (most common)

Bone

Urinary tract

Primary

Initial infection with the disease

Reactivation

Patient infected in past has reactivation of disease

Tuberculosis: Risk Factors HIV infection Close contacts of persons with infectious Tb Persons with medical conditions that decrease resistance to infection Persons who inject drugs Foreign-born persons where Tb is endemic Medically underserved, low-income populations Residents & employees of LTC facilities Local high prevalence groups (e.g., migrants) Healthcare workers at risk of exposure in workplace

HIV infection

Close contacts of persons with infectious Tb

Persons with medical conditions that decrease resistance to infection

Persons who inject drugs

Foreign-born persons where Tb is endemic

Medically underserved, low-income populations

Residents & employees of LTC facilities

Local high prevalence groups (e.g., migrants)

Healthcare workers at risk of exposure in workplace

Antitubercular Agents Trecator Ethionamide Seromycin Cycloserine Streptomycin (SM) Myambutol Ethambutol HCl (EMB) Pyrazinamide (PZA) Rifandin, Rimactane Rifampin (RIF) Laniazid Isoniazid (INH) TRADE GENERIC

Indications for drug therapy Prevention & treatment of tuberculosis No prototype – each drug differs from the others TB: Highly contagious Reportable disease Treatment initiated by specialist Refer for initial work-up & treatment PCP ROLE: Follow patient while on therapy Prophylaxis

Prevention & treatment of tuberculosis

No prototype – each drug differs from the others

TB:

Highly contagious

Reportable disease

Treatment initiated by specialist

Refer for initial work-up & treatment

PCP ROLE:

Follow patient while on therapy

Prophylaxis

Patient Variables Geriatrics Increased risk for toxic effects, esp. liver & CNS Pediatrics INH, RIF, PZA commonly used EMB NOT recommended for children < 13 Streptomycin NOT recommended for use in children Cycloserine & ethionamide: safety NOT established Pregnancy Category C: prescribe only when necessary Category D: Aminoglycosides (SM) & Ethionamide (teratogenicity in animals) Lactation INH, RIF, PZA, EMB, cycloserine all appear in breast milk

Geriatrics

Increased risk for toxic effects, esp. liver & CNS

Pediatrics

INH, RIF, PZA commonly used

EMB NOT recommended for children < 13

Streptomycin NOT recommended for use in children

Cycloserine & ethionamide: safety NOT established

Pregnancy

Category C: prescribe only when necessary

Category D: Aminoglycosides (SM) & Ethionamide (teratogenicity in animals)

Lactation

INH, RIF, PZA, EMB, cycloserine all appear in breast milk

Prophylaxis Recent skin test converters Positive PPD, nL CXR & no evidence of active Tb Close contacts of individuals with infectious, clinically active Tb Evaluate to r/o active Tb Assess for Hx hepatitis, heavy alcohol ingestion, liver disease, age > 35 If Hx positive  obtain LFTs to evaluate any contraindications to therapy Must weigh risk vs. benefit Prophylaxis: INH 300mg PO QD Length of Tx: Children < 18: 9 mo Adults: 6 mo Immunocompromised or abnL CXR(NOT active Tb): 12 mo Dispense: 1 mo supply – monitor Qmo

Recent skin test converters

Positive PPD, nL CXR & no evidence of active Tb

Close contacts of individuals with infectious, clinically active Tb

Evaluate to r/o active Tb

Assess for Hx hepatitis, heavy alcohol ingestion, liver disease, age > 35

If Hx positive  obtain LFTs to evaluate any contraindications to therapy

Must weigh risk vs. benefit

Prophylaxis: INH 300mg PO QD

Length of Tx:

Children < 18: 9 mo

Adults: 6 mo

Immunocompromised or abnL CXR(NOT active Tb): 12 mo

Dispense: 1 mo supply – monitor Qmo

Treatment of active disease Direct Observed Treatment (DOT) Standard of care in MD & NYC Every dose of anti-Tb medication observed and supervised by a h/c worker Compliance is KEY Noncompliant may be sent to prison to assure compliance (has been shown to reduce prevalence of multidrug resistance Increased prevalence of resistance  4 drug regimen INH, RIF, PZA & (EMB OR SM)

Direct Observed Treatment (DOT)

Standard of care in MD & NYC

Every dose of anti-Tb medication observed and supervised by a h/c worker

Compliance is KEY

Noncompliant may be sent to prison to assure compliance (has been shown to reduce prevalence of multidrug resistance

Increased prevalence of resistance  4 drug regimen

INH, RIF, PZA & (EMB OR SM)

Tuberculosis: Resistance Reasons for development Inadequate treatment Discontinuance of treatment prematurely Many organisms resistant to standard Tx INH, RIF, & EMB Some strains resistant to all known Tb drugs Patterns of resistance determine local treatment

Reasons for development

Inadequate treatment

Discontinuance of treatment prematurely

Many organisms resistant to standard Tx

INH, RIF, & EMB

Some strains resistant to all known Tb drugs

Patterns of resistance determine local treatment

Patient Monitoring INH Prophylaxis Seen Q month & assess for 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 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) D/C INH immediately if s/s of toxicity

INH Prophylaxis

Seen Q month & assess for

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

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)

D/C INH immediately if s/s of toxicity

Patient Monitoring Active Tb Treatment CXR at baseline & 6 mo Sputum smear & culture at baseline and monthly until negative Measure: liver enzymes, bilirubin, serum creatinine, CBC, PLTs, serum uric acid at baseline & monthly INH  periodic ophthalmologic exam PZA  blood glucose levels EMB  color vision for red/green at baseline & 2-3 months SM  audiogram prior to Tx & 2-3 months; serum SM levels Cycloserine  weekly blood levels in reduced renal function

Active Tb Treatment

CXR at baseline & 6 mo

Sputum smear & culture at baseline and monthly until negative

Measure: liver enzymes, bilirubin, serum creatinine, CBC, PLTs, serum uric acid at baseline & monthly

INH  periodic ophthalmologic exam

PZA  blood glucose levels

EMB  color vision for red/green at baseline & 2-3 months

SM  audiogram prior to Tx & 2-3 months; serum SM levels

Cycloserine  weekly blood levels in reduced renal function

Isoniazid (INH) Mechanism of Action Bacteriostatic for resting organisms Bactericidal for dividing organisms Interferes with lipid and nucleic acid biosynthesis Contraindications Known contact with INH-resistant Tb case Previous INH-associated adverse effect Acute liver disease, severe chronic liver disease

Mechanism of Action

Bacteriostatic for resting organisms

Bactericidal for dividing organisms

Interferes with lipid and nucleic acid biosynthesis

Contraindications

Known contact with INH-resistant Tb case

Previous INH-associated adverse effect

Acute liver disease, severe chronic liver disease

INH Pharmacokinetics Half-life Variable Distribution Widely distributed to all body tissues Metabolism Acetylation & dehydrazination Rate of acetylation genetically determined 50% of blacks & whites are “slow acetylators” majority of Eskimos & Asians are “rapid acetylators” Excretion Renal

Half-life

Variable

Distribution

Widely distributed to all body tissues

Metabolism

Acetylation & dehydrazination

Rate of acetylation genetically determined 50% of blacks & whites are “slow acetylators” majority of Eskimos & Asians are “rapid acetylators”

Excretion

Renal

Isoniazid (INH) Adverse Effects Most frequent: liver & nervous system effects Stains urine orange-red Fever, rash, vasculitis N/V Agranulocytosis, thrombocytopenia Peripheral neuropathy, numbness & tingling of extremities Jaundice, abnormal LFTs

Adverse Effects

Most frequent: liver & nervous system effects

Stains urine orange-red

Fever, rash, vasculitis

N/V

Agranulocytosis, thrombocytopenia

Peripheral neuropathy, numbness & tingling of extremities

Jaundice, abnormal LFTs

Isoniazid (INH) Drug Interactions P450 1A2 inhibitor & 2C inhibitor Concomitant use of alcohol associated with higher incidence of hepatitis Higher rate of hepatotoxicity with RIF Aluminum containing antacids decrease absorption Some MAOI activity (tyramine containing foods) Overdose EARLY: N/V, dizziness, slurring of speech, blurring of vision, visual hallucination LATE: respiratory distress, CNS depression (may be fatal)

Drug Interactions

P450 1A2 inhibitor & 2C inhibitor

Concomitant use of alcohol associated with higher incidence of hepatitis

Higher rate of hepatotoxicity with RIF

Aluminum containing antacids decrease absorption

Some MAOI activity (tyramine containing foods)

Overdose

EARLY: N/V, dizziness, slurring of speech, blurring of vision, visual hallucination

LATE: respiratory distress, CNS depression (may be fatal)

INH: Patient Education Take on empty stomach 1 hr before or 2 hrs after meal Minimize alcohol consumption Avoid foods containing tyramine (wine, hard cheese, liver) and histamine (tuna, sauerkraut) Notify provider if fatigue, weakness, n/v, loss of appetite, yellowing of skin or eyes, darkening of urine, numbness/tingling of hands / feet

Take on empty stomach 1 hr before or 2 hrs after meal

Minimize alcohol consumption

Avoid foods containing tyramine (wine, hard cheese, liver) and histamine (tuna, sauerkraut)

Notify provider if fatigue, weakness, n/v, loss of appetite, yellowing of skin or eyes, darkening of urine, numbness/tingling of hands / feet

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

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

Tuberculosis: Symptoms Sx: Cough, pain in chest when breathing or coughing, cough productive of sputum or blood Weight loss, fatigue, malaise, fever, & night sweats Assume contagious if: Cough is present Undergoing cough inducing procedures Sputum smear is positive until 3 negative Until patient on Tx at least 1 week Showing poor response to Tx

Sx:

Cough, pain in chest when breathing or coughing, cough productive of sputum or blood

Weight loss, fatigue, malaise, fever, & night sweats

Assume contagious if:

Cough is present

Undergoing cough inducing procedures

Sputum smear is positive until 3 negative

Until patient on Tx at least 1 week

Showing poor response to Tx

Tuberculosis: Exposure Testing Purified Protein Derivative (PPD) or Mantoux Test Mantoux – preferred, more accurate Tine test – no longer used 0.1 mL of PPD with 5 TU injected intradermally – pale elevation 6-10 mm read 48-72 hours after injection Only induration (hardness) is measured

Purified Protein Derivative (PPD) or Mantoux Test

Mantoux – preferred, more accurate

Tine test – no longer used

0.1 mL of PPD with 5 TU injected intradermally – pale elevation 6-10 mm read 48-72 hours after injection

Only induration (hardness) is measured

Criteria for Positive Tb Skin Test Negative does NOT r/o Person may be anergic > 5 mm induration Children <1 year of age X-ray or clinical evidence of disease Close contact of person with active disease Evidence of old healed Tb Persons with risk factors for HIV infection Persons who inject drugs > 10 mm induration Children between 1 & 4 years old Foreign-born persons from high prevalence countries HIV seronegative IV drug users Persons with medical risk factors (DM, ETOH, drug abuse) Employees / residents of LTC facilities > 15 mm induration All others

Negative does NOT r/o

Person may be anergic

> 5 mm induration

Children <1 year of age

X-ray or clinical evidence of disease

Close contact of person with active disease

Evidence of old healed Tb

Persons with risk factors for HIV infection

Persons who inject drugs

> 10 mm induration

Children between 1 & 4 years old

Foreign-born persons from high prevalence countries

HIV seronegative IV drug users

Persons with medical risk factors (DM, ETOH, drug abuse)

Employees / residents of LTC facilities

> 15 mm induration

All others

Testing for Tb Exposure Skin testing for person with history of BCG vaccine WAS: never give PPD to person who had received BCG NOW: BCG status should NOT influence need for Tb skin testing – may see boosted reaction Two-step Tb skin testing (PPD  2nd PPD in 1-3 wks) Distinguishes boosted reaction (b/c hypersensitivity reaction wanes with time) vs. reaction d/t new infection Recommended for elderly patients and high-risk employees

Skin testing for person with history of BCG vaccine

WAS: never give PPD to person who had received BCG

NOW: BCG status should NOT influence need for Tb skin testing – may see boosted reaction

Two-step Tb skin testing (PPD  2nd PPD in 1-3 wks)

Distinguishes boosted reaction (b/c hypersensitivity reaction wanes with time) vs. reaction d/t new infection

Recommended for elderly patients and high-risk employees

Testing for Tb Exposure Chest X-ray AP & LAT for all persons with positive PPD Very sensitive (not a lot of false negatives): nL CXR  Tb unlikely Detected abnormalities  biopsy showing caseation granulomas to confirm diagnosis 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 Sputum Direct examination shows presence of AFB Positive smear  considered contagious Classic Dx made by culture (takes 6 weeks) Mycobacterium tuberculosis Direct Test results in 4-5 hours BUT misses 5% of cases (requires culture)

Chest X-ray

AP & LAT for all persons with positive PPD

Very sensitive (not a lot of false negatives): nL CXR  Tb unlikely

Detected abnormalities  biopsy showing caseation granulomas to confirm diagnosis

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

Sputum

Direct examination shows presence of AFB

Positive smear  considered contagious

Classic Dx made by culture (takes 6 weeks)

Mycobacterium tuberculosis Direct Test results in 4-5 hours BUT misses 5% of cases (requires culture)

Diagnosis of Active Tb PRESUMPTIVE (report w/in 24 hr to HD): Recent conversion to positive PPD associated with characteristic s/s Positive sputum (or other body fluid) smear Characteristic CXR Bx showing caseating granulomas HIV/AIDS (d/t high rate of concurrent infection) CONFIRMED (report w/in 24 hr to HD): Positive culture (any body fluid or Bx specimen) Also tests for drug susceptibility

PRESUMPTIVE (report w/in 24 hr to HD):

Recent conversion to positive PPD associated with characteristic s/s

Positive sputum (or other body fluid) smear

Characteristic CXR

Bx showing caseating granulomas

HIV/AIDS (d/t high rate of concurrent infection)

CONFIRMED (report w/in 24 hr to HD):

Positive culture (any body fluid or Bx specimen)

Also tests for drug susceptibility

Rifampin Mechanism of Action Inhibits DNA-dependent RNA polymerase activity  suppressing RNA synthesis May be bacteriostatic or bactericidal Most active against bacteria undergoing cell division Contraindications Hypersensitivity

Mechanism of Action

Inhibits DNA-dependent RNA polymerase activity  suppressing RNA synthesis

May be bacteriostatic or bactericidal

Most active against bacteria undergoing cell division

Contraindications

Hypersensitivity

Rifampin Warnings / Precautions Hepatotoxicity with fatality – monitor LFTs & adjust dose with impaired liver fxn Hyperbilirubinemia Porphyria exacerbation Meningococci resistance may emerge Hypersensitivity reaction if intermittent or interrupted therapy May be associated with carcinogenesis Monitor CBC & LFTs Urine, feces, saliva, sputum, sweat, & tears may be colored red-orange. Soft contact lenses may be permanently stained Thrombocytopenia – usu. reversible but may be fatal

Warnings / Precautions

Hepatotoxicity with fatality – monitor LFTs & adjust dose with impaired liver fxn

Hyperbilirubinemia

Porphyria exacerbation

Meningococci resistance may emerge

Hypersensitivity reaction if intermittent or interrupted therapy

May be associated with carcinogenesis

Monitor CBC & LFTs

Urine, feces, saliva, sputum, sweat, & tears may be colored red-orange. Soft contact lenses may be permanently stained

Thrombocytopenia – usu. reversible but may be fatal

Rifampin Adverse Effects Common: GI Sx’s & rash High doses  flulike syndrome, hematopoietic reactions Drug Interactions P450 1A2 substrate, 2C inducer, 2D6 inducer, 3A4 inducer and substrate Decreases effectiveness of many drugs including oral anticoagulants & oral contraceptives Decreases serum digoxin concentrations Overdose – requires hospitalization N/V, lethargy Liver toxicity

Adverse Effects

Common: GI Sx’s & rash

High doses  flulike syndrome, hematopoietic reactions

Drug Interactions

P450 1A2 substrate, 2C inducer, 2D6 inducer, 3A4 inducer and substrate

Decreases effectiveness of many drugs including oral anticoagulants & oral contraceptives

Decreases serum digoxin concentrations

Overdose – requires hospitalization

N/V, lethargy

Liver toxicity

Rifampin: Patient Education Take on an empty stomach, 1 hr before or 2 hrs after meals Avoid missing doses May cause red-orange discoloration of body fluids Notify provider if “flulike” Sx’s, yellow discoloration of skin or eyes, skin rash or itching

Take on an empty stomach, 1 hr before or 2 hrs after meals

Avoid missing doses

May cause red-orange discoloration of body fluids

Notify provider if “flulike” Sx’s, yellow discoloration of skin or eyes, skin rash or itching

Pyrazinamide (PZA) Mechanism of Action Unknown Bacteriostatic vs. bactericidal activity dose-dependent Contraindications Hypersensitivity, liver damage, acute gout

Mechanism of Action

Unknown

Bacteriostatic vs. bactericidal activity dose-dependent

Contraindications

Hypersensitivity, liver damage, acute gout

Pyrazinamide (PZA) Warning / Precautions Inhibits renal excretion of urates – may cause hyperuricemia and gout Use with caution in patient with renal function impairment – reduced dose usually not necessary Monitor patients with hepatic impairment closely In patients with DM, BG control may be more difficult

Warning / Precautions

Inhibits renal excretion of urates – may cause hyperuricemia and gout

Use with caution in patient with renal function impairment – reduced dose usually not necessary

Monitor patients with hepatic impairment closely

In patients with DM, BG control may be more difficult

Pyrazinamide (PZA) Adverse Effects Frequent: mild arthralgia & myalgia Most common serious: gout & hepatic toxicity Drug Interactions No known P450 Overdose Liver toxicity

Adverse Effects

Frequent: mild arthralgia & myalgia

Most common serious: gout & hepatic toxicity

Drug Interactions

No known P450

Overdose

Liver toxicity

PZA: Patient Education Report: Fever, loss of appetite, malaise, N/V, darkened urine, yellowish discoloration of skin or eyes, pain or swelling or joints

Report:

Fever, loss of appetite, malaise, N/V, darkened urine, yellowish discoloration of skin or eyes, pain or swelling or joints

Ethambutol HCl Mechanism of Action Impairs cellular metabolism  stops cell multiplication & causes cell death Bactericidal & active only against mycobacteria Contraindications Hypersensitivity Known optic neuritis

Mechanism of Action

Impairs cellular metabolism  stops cell multiplication & causes cell death

Bactericidal & active only against mycobacteria

Contraindications

Hypersensitivity

Known optic neuritis

Ethambutol HCl Warnings / Precautions Visual testing (on each eye individually & both together) before initiating Tx and periodically including visual acuity, ophthalmoscopy, peripheral fields, & color discrimination Renal impairment requires dose adjustment

Warnings / Precautions

Visual testing (on each eye individually & both together) before initiating Tx and periodically including visual acuity, ophthalmoscopy, peripheral fields, & color discrimination

Renal impairment requires dose adjustment

Ethambutol HCl Adverse Effects Fever, malaise, dizziness, headache Dermatitis, pruritis Thrombocytopenia Common: N/V, anorexia, abdominal pain SEVERE: Optic neuritis, loss of acuity, loss of red-green discrimination Drug Interactions Aluminum salts may delay/reduce absorption

Adverse Effects

Fever, malaise, dizziness, headache

Dermatitis, pruritis

Thrombocytopenia

Common: N/V, anorexia, abdominal pain

SEVERE: Optic neuritis, loss of acuity, loss of red-green discrimination

Drug Interactions

Aluminum salts may delay/reduce absorption

EMB: Patient Education May cause GI upset – take with food Aluminum-containing antacids may interfere with absorption  separate administration by several hours Notify provider of Changes in vision: blurring, red-green color blindness Rash

May cause GI upset – take with food

Aluminum-containing antacids may interfere with absorption  separate administration by several hours

Notify provider of

Changes in vision: blurring, red-green color blindness

Rash

Cycloserine Mechanism of Action Inhibits cell wall synthesis May be bacteriostatic or bactericidal Warnings / Precautions D/C if: CNS toxicity, dysarthria, allergic dermatitis Small Therapeutic Index: Toxicity r/t to high blood levels Renal Function Impairment: accumulation & toxicity Anticonvulsants or sedatives may be effective in controlling Sx’s. ALSO, pyridoxine may be helpful in ameliorating neurotoxicity Associated with B12, folic acid deficiency, megaloblastic & sideroblastic anemia

Mechanism of Action

Inhibits cell wall synthesis

May be bacteriostatic or bactericidal

Warnings / Precautions

D/C if: CNS toxicity, dysarthria, allergic dermatitis

Small Therapeutic Index: Toxicity r/t to high blood levels

Renal Function Impairment: accumulation & toxicity

Anticonvulsants or sedatives may be effective in controlling Sx’s. ALSO, pyridoxine may be helpful in ameliorating neurotoxicity

Associated with B12, folic acid deficiency, megaloblastic & sideroblastic anemia

Cycloserine Adverse Effects CNS Sx’s: convulsions, psychosis, somnolence, depression, confusion, hyperreflexia, headache, tremor, vertigo, paresis Drug Interactions INH: increase in dizziness Alcohol: increased risk of epileptic episodes Overdose CNS depression

Adverse Effects

CNS Sx’s: convulsions, psychosis, somnolence, depression, confusion, hyperreflexia, headache, tremor, vertigo, paresis

Drug Interactions

INH: increase in dizziness

Alcohol: increased risk of epileptic episodes

Overdose

CNS depression

Cycloserine: Pt Education Notify provider of: Dizziness, mental confusion, skin rash, tremor Avoid alcohol May cause drowsiness, use caution when operating heavy machinery

Notify provider of:

Dizziness, mental confusion, skin rash, tremor

Avoid alcohol

May cause drowsiness, use caution when operating heavy machinery

Ethionamide (when 1st line Tx has failed) Mechanism of Action Inhibits peptide synthesis Bacteriostatic or bactericidal depending on concentration & susceptibility of organism Highly specific for Mycobacterium NOT a first line agent Contraindications Hepatic damage or hypersensitivity Warnings / Precautions Hepatitis occurs more frequently  monitor LFTs Management of DM may be more difficult Drug Interactions Raises serum concentrations of INH May potentiate adverse effects of other antitubercular drugs, esp. cycloserine Avoid alcohol ingestion (may produce psychotic reaction)

Mechanism of Action

Inhibits peptide synthesis

Bacteriostatic or bactericidal depending on concentration & susceptibility of organism

Highly specific for Mycobacterium

NOT a first line agent

Contraindications

Hepatic damage or hypersensitivity

Warnings / Precautions

Hepatitis occurs more frequently  monitor LFTs

Management of DM may be more difficult

Drug Interactions

Raises serum concentrations of INH

May potentiate adverse effects of other antitubercular drugs, esp. cycloserine

Avoid alcohol ingestion (may produce psychotic reaction)

Ethionamide: Pt Education May cause stomach upset, metallic taste, or loss of appetite Take with food to minimize GI upset Notify provider if effects persist

May cause stomach upset, metallic taste, or loss of appetite

Take with food to minimize GI upset

Notify provider if effects persist

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