Antimycobacterial Drug Med class- Quiz 2 Flashcards
TB Overview
Rod shaped aerobic bacilli that multiply slowly
-These infections cause slow-growing granulomatous lesions—and can occur anywhere in the body
-Are classified as “acid-fast bacilli”
-M. tuberculosis is slow growing and
requires treatment for months –years
-LTBI can be treated for 9 months with INH or 12 months once a week higher doses of INH + Rifapentine
-Active TB has to be treated with several drugs for several months
-Multi-drug resistant TB is typically
treated for 2 years
What are the first line agents for TB?
-Ethambutol
-Isoniazid [INH]—PROTOTYPE drug
-Pyrazinamide
-Rifampin (Rifabutin or Rifapentine may replace under certain circumstances)
What is considered extremely drug resistant (XDR) tuberculosis?
-A bacilli that is resistant to INH and
Rifampin, is resistant to any
fluoroquinolone and at least 1 of 3 injectable 2nd line agents
-Resistance occurs when only one med is used, therefore several meds are often used in combo
-Clinical improvement occurs quickly—weeks, but therapy is continued much longer to kill persistent organisms and prevent relapse
-Tx: Standard therapy is INH, Rifampin, Ethambutol and Pyrazinamide for 8 weeks, then INH and Rifampin for 16 more weeks (Clofazimine and Linezolid may be used)
-NOTE* Active disease ALWAYS requires multiple drugs—3 or more w proven activity against the isolate
Isoniazid
-PROTOTYPE Drug for TB
-MOA: They inhibit mycolic acid which leads to destruction of the tubercular cell wall
-Specific for the treatment of TB
-Drug levels in CSF is the same as in the serum
-Readily absorbed orally (absorption is impaired if taken with food)
-ADE: Hepatitis is most serious, Peripheral neuropathy—due to a relative Pyridoxine deficiency—daily
supplementation w B6 is mandatory, convulsions, rash, fever
-NOTE* take baseline hepatic enzyme labs*
Rifamycins
(Rifampin, Rifabutin, Rifapentine)
-First line oral agents for TB
Rifampin:
-Has broader antimicrobial coverage than INH
-MOA: Blocks RNA transcription
-Adequate absorption orally
-Lot of drug-drug interactions (CYP450 inducer) (May necessitate higher dose of other drugs)
-Elimination through feces
-ADE: n,v, rash, Urine/feces/other secretions will become orange-red in color; contact lens will be
stained, use with caution in alcoholics
Rifabutin (derivative of Rifampin):
-Preferred for TB patiens who also have HIV
-Less potent CYP450 inducer
-ADE’s similar w hyperpigmentation, neutropenia
Rifapentine:
-Longer half life than Rifampin so may be dosed once weekly
-NOTE* baseline hepatic enzymes & CBC*
Pyrazinamide
-Synthetic, oral agent used short-term with INH, Rifampin and Ethambutol
-MOA is unknown
-Distributes throughout body, penetrates CSF
-Can contribute to liver dysfunction
-Most benefit occurs early in treatment— so is only used 8 weeks in a 24 week regimen
-NOTE* baseline hepatic enzymes & CBC*
Ethambutol
-Bacteriostatic and first line for mycobacteria
-MOA: Inhibits an enzyme important for the synthesis of mycobacterial cell wall
-Used with INH, Pyrazinamide and Rifampin pending cultures and
susceptibility
-ADEs—optic neuritis—which affects vision/ ability to see red and green
-NOTE* Baseline visual acuity and color vision*
Second line TB drugs
-Less effective and more toxic
-Para-aminosalicylic acid
-Cycloserine
-Ethionamide
-Fluoroquinolones
-Macrolides
-Bedaquiline
-Linezolid
-Pretomanid
Leprosy Overview
-AKA “Hansen’s disease”
-Skin infection with M. leprae
-Uncommon in US—but still a
major problem world wide
Drugs to treat Leprosy
- Dapsone:
-MOA: inhibits enzyme in the folate synthesis pathway
-Bacteriostatic for M. leprae
-Well absorbed from the GI tract
-Distributed throughout the body, with high concentrations in the skin
-ADEs: hemolysis, methemoglobulinemia, and peripheral neuropathy
2.Clofazamine:
-Phenazine dye
-MOA: involves binding to DNA
-Given orally; accumulates in the tissues, allowing intermittent therapy—does not enter the CNS
-Pink to brownish-black discoloration of the skin occurs—tell patient in advance
