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17 Cards in this Set
- Front
- Back
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Therapy of Tuberculosis
-Difficulties |
-immunosuppressed patientshave increased incidence of TB
-long duration of therapy (6-24 months) -intracellular pathogen grows slowly -lesions within lung get walled off -resistance to drugs developes readily -all useful drugs possess toxicity problems |
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First Line Drugs for TB
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Isoniazid
-primary drug in all regimens, also prophylaxis Rifampin -excellent tuberculcidal drug, most rapid acting useful for other bacterial infections -Ethambutol very effective with isoniazid -Pyrazinamide and Streptomycin used when resistance to above agents |
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Clinical Problems
of drugs |
Isoniazid (peripheral neuritis, hepatitis)
Rifampin (hepatic toxicity and GI effects) Ethambutol (altered visual acuity and and ability to peceive green) Pyrazinamide (hepatic necrosis) Streptomycin (ototoxicity, vestibular toxicity, and nephrotoxicity |
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Isoniazid
-Mechansm of Action |
inhibit synthesis of mycolic acid & DNA synthesis
static (resting bacilli), cidal (growing bacilli) |
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Isoniazid;
Toxicities |
peripheral neurtitis due to inactivation and depletion of pyridoxine by reaction with isoniazid
hepatitis (especially above age 35)(covalent binding of reactive metabolite in liver) hypersensitivity reactions |
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Rifampin
-Mechanism -Spectrum -Pharmacokinetics -1/2 -Toxicities |
inhibit RNA polymerase)
-(sev. gram-pos. & gram-neg.) -oral admin, excellent distribution , metabolized -1-5 hrs -**jaundice colors secretions (urine & tears) red-orange -induces hepatic metabolism of other drugs -GI distress, diarrhea, -influenzae-like syndrome |
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rifampin
considerations, why it is good |
more rapid action in eliminating infectious state
-used in combination with isoniazid in uncomplicated cases, add other drugs if resistance |
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Rifampin Therapy
Non-tuberculosis therapy 3 things |
-asymptomatic carriers and prophylaxis of N. meningitidis
-erythromycin-resistant Legionella -combination with vancomycin for endocarditis or osteomyelitis due to methicillin-resistant staph. |
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Ethambutol
-characteristic feature -Pharmacokinetics -Toxicity - |
-tuberulostatic so resistance if used alone
-good oral absorption and mainly eliminated by renal excretion -decreased visual acuity impaired ability to perceive green -optic neuritis -may precipitate gout |
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Streptomycin
-General Features -Toxicity |
aminoglycoside (same mechanism, limited distribution and toxicities
-ototoxicity -vestibular toxicity -nephrotoxicity |
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Pyrazinamide
-General Features |
bactericidal
-added if resistance problems or require three effective agents -partially metabolized and excreted by renal glomerular filtration |
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pyrazinamide Toxicity
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-liver necrosis
-hyperuricemia -nausea and vomiting |
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Chemoprophylaxis of TB
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-Isoniazid is only TB drug proven effective for prophylaxis
-Rifampin being studied for prophylaxis when isoniazid cannot be used -BCG vaccination recommended for infants and children with negative PPD |
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6 Candidates for Prophylaxis
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-Individuals definitely infected (positive PPD) but no apparent disease
-History of disease that presently inactive -Persons infected with HIV -Drug users (esp. if IV admin.) -Others at high risk (immunosuppressed) -Individuals exposed to active TB but without evidence of infection |
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6 General Principles of TB Therapy
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-Always use more than one agent
-Use agents to which bacteria are sensitive -Isoniazid is usually primary agent, ethambutol or rifampin second if organism sensitive to all -(may use 4 drugs initially until susceptibility determined, esp. in patients likely to have resistant organisms) -Two drug regimens usually adequate if bacteria sensitive to both drugs which must be tuberculocidal -Very serious as well as retreatment cases require 3 or 4 drugs -3rd drug can be sensitive if any of first line drugs if organism is sensitive - |
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4 Potentially effective TB drugs
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1.Amikacin
2. Fluoroquinolones Ciprofloxacin, Levofloxacin, newer drugs tested 3. Rifamycin derivatives Rifabutin and Rifapentine 4. Clofazimine |
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Summary of Clinical Problems of the 5 first line drugs
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-Isoniazid (peripheral neuritis, hepatitis)
-Rifampin (hepatic toxicity and GI effects) -Ethambutol (altered visual acuity and and ability to peceive green) -Pyrazinamide (hepatic necrosis) -Streptomycin (ototoxicity, vestibular toxicity, and nephrotoxicity |
