Antimycobacterial Drugs Flashcards
Nicotinic acid derivative (isonicotinic acid hydrazide)
Isoniazid
Isoniazid - MoA
Inhibition of mycolic acid synthesis (needed for cell wall)
katG gene
Isoniazid - Clinical use
1st line TB.
Bactericidal: M.tuberculosis and M.kansaii
Little activity: M.avium-intracellulare.
Not active: M. leprae.
Given to prevent TB in neonates and children who have had close contact with persons in whom active TB was recently diagnosed
Active and latent TB
Isoniazid - Adverse effects
Hepatotoxicity (from metabolite acetylhydrazine)
Peripheral neuritis (paresthesias, numbness of fingers and toes, in vit B6 deficiency, effect individuals with slow acetylator phenotype)
Toxic encephalopathy
Seizures
Hematologic abnormalities (granulocytosis, anemia, thrombocytopenia)
Hepatitis (highest prevalence for persons over 50 years, elevated serum transaminase)
Isoniazid - Interactions
Alcohol + rifampin: increased risk of hepatotoxicity.
Increases carbamazepine and phenytoin levels.
Aluminum salts: inhibits absorption
Isoniazid - Special considerations
Genetically different rate of acetylation of drug causes different plasma concentrations.
Synthetic butanol derivative
Ethambutol
Ethambutol - MoA
Bacteriostatic for mycobacteria
Inhihits arabinosyl transferase and the synthesis of arabinogalactam required for mycobacterial cell wall formation
Ethambutol - Clinical use
1st line TB.
Bacteriostatic activity
M. avium-intracellulare infections
Ethambutol - Adverse effects
Dose dependent optic neuritis and impaired red-green color discrimination
Hyperuricemia
Gout
Hepatitis
Thrombocytopenia
Ethambutol - Special consideration
Monitor visual color discrimination regularly
Ethambutol - Contraindications
Children too young to permit assessment of visual acuity and red-green discrimination
Synthetic Nicotinamide derivatie
Pyrazinamide
Pyrazinamide - MoA
disrupts mycobacterial cell membrane metabolism and transport functions
M. tuberculosis: inhibits the growth by inhibiting fatty acid synthesis required for cell membrane function.
Inhibits also RNA
Pyrazinamide - Clinical use
1st line TB.
Rapid bactericidal action
Pyrazinamide - Adverse effects
Hepatits Hyperuricemia and gout Arthalgia Hematologic toxicity Fever Increase in Fe serum concentration
Rifamycin derivatives
Rifampin
Rifapentine
Rifabutin
Rifampin - MoA
Binds to DNA-dependent RNA polymerase, preventing DNA transcription and RNA synthesis
Rifampin - Clinical use
Broad-spectum, gram (+), (-) and acid fast bacilli
1st line TB.
Combined with isoniazid, ethambutol, pyrazinamide to treat TB.
Combined with sulfone or clofazimine to treat leprosy.
Alternative to INH if resistance.
Meningitis prophylaxis
H. influenzae B inf
Prevent meningococcal disease
Tubercular meningtiis
Eliminate staph.coccal carriage,
Staph endocarditis (in comb. with vancomycin and gentamicin)
Legionella pneumphila (in comb with macrolide/fluoroquinolone)
Rifampin - Special considerations
Penetrates inflamed meninges
Liver function tests must be done evere 2-4 weeks of treatment.
Never use alone in active infection
Rifampin - Adverse effects
Impaired liver function
Elevate serum bilirubin and transaminase levels
Hepatitis
Hypersensitivity: chills, fever, fatigue, headache (50 % of patients!)
High dose: renal disease, leukopenia, thrombocytopenia, purpura
Reddish-orange to brown discoloration of saliva, tears, and urine
Light-chain proteinuria
If administered less often than twice weekly: flu-like syndrome (fever, chills, myalgias, anemia, thrombocytopenia)
Rifampin - Interactions
Alcohol consumption appears to increase the risk of hepatitis and should be avoided in persons being treated for TB.
Rifampin induces cytochrome p450 isozymes, CYP1A2, CYP2C9 and CYP3A4, and can thereby accelerate the metabolism of other drugs and reduce their serum concentrations and therapeutic effectiveness
These drugs include: macrolides, benzodiazepines, Ca channel blockers, digoxin, estrogens, sulfonylureas, theophylline, warfarin.
Rifapentine - Clinical use
Pulmonary TB by M. tuberculosis
Twice-weekly combined with isoniazid, ethambutol, and pyrazinamide for 2 months, and once-weekly with isoniazid for an additional 4 months.
Rifabutin - Clinical use
Preferred for treating TB in HIV patients (protease inhibitors can be used).
M. avium intracellulare
M. fortuitum
Rifabutin - Interactions and Adverse effects
Cytochrome P450 and GI irritation
Streptomycin (antimycobacterial) - Clinical use
TB: Resistance to other TB drugs
Active against M. avium complex, M. kansasii
Streptomycin (antimycobacterial) - Adverse effects
Nephrotoxicity, ototoxicity
Amikacin (antimycobacterial) - Clinical use
2nd line TB
Multidrug resistant tuberculosis strains, atypical mycobacteria. Combined with at least one other drug
Dapsone - MoA
Inhibits folic acid synthesis
Dapsone - Clinical use
Leprosy (both types)
Bacteriostatic
Dapsone - Adverse effects
GI disturbances Peripheral neuropathy Optic neuritis and blurred vision Proteinuria Nephrotic syndrome SLE-like syndrome Hematologic toxicity G6PD-def: hemolytic anemia
Clofazimine - Clinical use
Bactericidal: M. tuberculosis
Bacteriostatic: M. leprae + avium-intracellulare.
Erythema nodosum leprosum (in lepromatous leprosy)
Dapsone - Contraindications
Glucose 6 phosphate dehydrogenase deficiency
Clofazimine - Adverse effects
GI distress Photosensitivity Skin discolorations Discoloration of body fluids Elevation of hepatic enzyme levels Hepatitis
Clofazimine - Contraindications
Hepatic disease
Thalidomide - Clinical use
TB
Leprosy
Erythema nodosum leprosum
Antimycobacterial drugs - Administration
Generally Oral
Isoniazid: + IM
Rifampim: + IV
Streptomycin: Only IM
Bedaquiline - MoA
Blocks the proton pump for ATP synthase in M. tuberculosis
Bedaquiline - Clinical use
MDR-TB in adults and children when another effective treatment cannot be provided.
Adm. Once daily for 2 weeks, then 3 times per week for 22 weeks.
Bedaquiline - Advers effects
Prolonged QT - arrhythmias, sudden death
Liver reactions; nausea, headache
Bedaquiline - Special considerations
Used with at least 3 other drugs
Patients must have an electrocardiogram before treatment is begun, and at regular intervals thereafter
Patients should be monitored for adverse liver reactions
Bedaquiline - Interactions
Cytochrome P450
Isoniazid - Contraindications
Vitamin B6 deficiency
