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52 Cards in this Set
- Front
- Back
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How do mycobacteria differ from other bacteria?
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Their cell wall contains murein. Also enclosed by an inner cytoplasmic membrane.
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Why are mycobacteria permeable to both hydrophilic and hydrophobic substances?
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Due to the prescence of mycolic acids.
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First line agents for TB
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Isoniazid-primary agent
Rifampin Ethambutol Pyrazinamide Streptomycin |
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Isoniazid (INH) MA
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(-) synthesis of mycolic acids
Bacteriostatic |
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Isoniazid PK
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Readily absorbed from GI-diffuses to all tissues and fluids
CNS levels can reach 20-100% of serum concentration []=concentration |
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How is INH inactivated? How may this affect sensitivity?
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Acetylation
Rate of acetylation may influence individual sensitivity |
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Clinical usese of INH?
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Treatment of clinically manifest dz (in combo w/ethambutol, rifampin, and streptomycin) and for prophylaxis of those whose TB test went from (-) ---> (+)
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Adverse Rxns to INH
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Peripheral and central neurotoxicity (peripheral neuritis, insomnia, restlessness, muscle twitching)
Hepatotoxicity-hepatitis in 1% Allergic rxns |
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HOw do you prevent neurotoxicity from INH?
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Coadmin. of B6 (pyridoxine)
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Drug interxns of INH?
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(-) prahydroxylation of phenytoin
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Bacterial resistance (BR) of INH
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- 1 in 10^6 - 10^7 (this is high)
No cross resistance between INH and other anti-TB agents |
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What enzymes activates INH? Why should we know this?
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Kat G enzyme
Mutation can confer resistance (Don't you feel better w/this knowledge) |
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How is rifampin usually given?
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In combo w/INH as a first-line agent
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MA of rifampin
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(-) bacterial DNA dependent RNA polymerase
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PK of rifampin
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Well absorbed from GI tract
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An alarming side effect of rifampin?
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Orange-red pee, poop, and spit. :-0
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Clinical use of rifampin
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Used in combo w/INH, ethambutol, or others
Prophalaxis of meningococcal dz and menigitis due to H.flu and Staph infections (endocarditis, osteomyelitis, nasopharyngeal infection) |
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Adverse Rxn of rifampin
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Jaundice, rashes, thrombocytopenia, nephritis
*When administered less than 2X/wk. get flu-like symptoms (so don't do this) |
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Drug interxns of rifampin
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Reduces t1/2 life of many drugs: anticoagulants, contraceptives, cyclosporine, chloramphenicol, clofibrate, and methadone
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What should you do when you prescribe rifampin?
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Check other meds-many interactions
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Bacterial resistance of rifampin
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Similar to INH, no cross resistance
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Rifapentine
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First new TB drug in 25 years, essentially long acting rifampin
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Ethambutol
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TB drug
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MA of ethambutol
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(-) the synthesis of arabinogalactan
Bacteriostatic |
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PK of ethambutol
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Readily absorbed in GI and excreted in urine
Does not cross BBB except in cases of meningitis |
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Clinical use of ethambutol
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First line treatment w/INH for TB
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Adverse Rxns of ethambutol
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Notable for few side effects. Can cause optical neuritis--> decreased visual acuity and ability to tell red from green
*Avoid in kids |
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BR of ethambutol
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Develops fairly rapidly when admin. alone--> so don't do it!
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Streptomycin and MA, and Adverse Rxns
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First effective mycobacterial drug
Note doesn't enter cells--bacteriostatic Ototoxicity and Nephrotoxicity |
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Pyramizinamide MA
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TB drug that (-) mycolic acid synthesis
ENTERS CELLS |
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PK of Pyrazinamide
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Readily absorbed from GI and mainly excreted in urine
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Clinical use of Pyrazinamide
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Important for short term (6 mo) multiple therapy for TB
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Adverse Rxns of Pyrazinamide
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Hepatotoxicity
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BR of Pyrazinamide
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Mutation in activation enzyme can confer resistance when administered alone--> that's right so don't do it.
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Activation enzyme of Pyrazinamide
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Pyrazinamidase (hard right?)
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When do we use 2nd line TB drugs?
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1. Resistance to 1st line
2. Clincal response to 1st line fails 3. Avoid SE of 1st line |
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What are the 2nd line TB drugs/
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1. Ethionamide
2. Aminosalicylic acid (PAS) 3. Cycloserine 4. Capreomycin, viomycin, kanamycin, amikan, tetracyclines, fluoroquinolones |
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MA and PK of Ethionamide
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Like INH
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Adverse rxns to Ethionamide
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Poorly tolerated b.c. of GI irritation, metallic taste, and neurologic symptoms (olfactory disturbances, blurred vision)
*Note this is the only drug I found that gives you problems with smelling |
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BR to Ethiomide
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Rapid resistance
No cross resistance w/INH |
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PAS MA
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Similar to sulfonamides
Bacteriostatic |
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PK of PAS
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Readily absorbed in GI, excreted in urine
High [] can be reached in urine |
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How do we prevent the formation of crystalluria in pts. taking PAS
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Alkanalize the urine
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Adverse Rxns of PAS
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GI(anorexia, nausea, diarrhea)
Drug fever Joint pain Rashes Granulocytopenia |
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Cycloserine MA
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Irreversible (-) of alanine racemase and D-ALA D-ALA syntetase
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PK of Cycloserine
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Absorbed from GI tract, excreted in urine
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Adverse Rxns of Cycloserine
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CNS dysfxn (somonolence, headache, tremor) and psychotic rxns (suicidal tendencies, paranoia) (25% of pts)
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BR of Cycloserine
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No cross-resistance
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Capreomycin, Viomycin, Kanamycin, Amikacin
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All given parenterally- some cross resistance
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Major SE of Tetracyclines and Fluroquinolones
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Ototoxicity and Nephrotoxicity
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5 guidelines of TB treatment
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1. At least 2 drugs
2. At least 6mo: INH, rifampin, and pyrazinamide for 2 mo followed by INH and rifampin for 4 mo. 3. Length depends on combo, more drugs --> less time 4. HIV pts need more intense therapy. Intiate treatment w/4 drugs. INH, rifampin, pyrizinamide, and ethambutol or streptomycin 5. Never use single agent |
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What kind of therapy do we employ for TB treatment?
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Direct observed therapy
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