Antimicrobials Flashcards
what composes mycobacterias cell wall
lipid-rich
mycolic acids
how do you treat active TB
4 drugs for 2 months
continuation phase for 18 weeks - reduce to 2 drugs
INH, Rif, PZA, EMB
how do you treat latent TB
Isoniazid - 9 months
Rifampin - 4 motnhs
INH and Rifapentne for 3 months
what is the most active drug used in the treatment of acute and latent TB
Isoniazid
Isoniazid:
1 (bacterostatic/cidal) for actively growing bacilli
Penetrates into 2. Active against both extracellular and intracellular organisms
Less effective against treating 3
Structural similarity to 4
- bacteriocidal
- macrophages
- atypical mycobacterial infections (M. avium complex)
- pyridoxine (vit. B6)
MOA of isoniazid
inhibits synthesis of mycolic acid
delivered as prodrug, activated by a mycobacterial catalase-peroxidase enzyme (Kat G)
activated INH forms a covalent bond with at least 2 proteins involved in mycolic acid synthesis and impedes function
how is resistance developed against INH
mutation in Kat G gene - lack of prodrug activation
overexpression of Inh A protein - enzyme involved in mycolic acid synthesis
what is necessary when treating TB to prevent emergence of drug resistance during therapy
at least 2 antituberculosis agents are used
INH is readily absorbed from the 1
Achieves peak plasma concentration in 2 hours - diffuses into all body fluids and tissues (including CNS)
INH is acetylated to acetyl-INH in the 2. Slow acetylators are prone to develop 3. (peripheral neuropathy)
- GI tract
- liver, bowel, kidney
- toxicity
Adverse rxns to INH
Hepatitis - risk increases with age and greater in individuals with alcohol dependence
peripheral neuropathy - results from structural similairty to pyridoxine; slow metabolism of drug; malnourished, alcoholic, diabetic, or suffers AIDs
- reverse with low doses of pyridoxine
first line tx for active TB
alternative to INH tx of latent TB
rifampin
MOA of rifampin
inhibits RNA synthesis
binds to bacteria DNA dependent RNA polymerase
bactericidal
penetrates most tissues as well as phagocytic cells - kill intracellular
resistance to rifampin
point mutation in bacterial RNA polymerase gene (target)
Rifampin is well absorbed from ___ and is widely distributed to all tissues/fluids
GI tract
Adverse rxns to rifampin
GI
Nervous system: HA, dizziness, fatigue
hepatitis - most common in those with underlying liver condition, INH slow acetylators (combo therapy)
harmless red-orange color in urine, feces, sweat, tears, and saliva
Rifampin drug interactions
strong inducer of cytochrome p450
increase elimination of many drugs
In HIV patients what drug is used instead of rifampinfor treated TB
rifabutin
essential component of multidrug regimens used in treating active TB
synthetic analogue of nicotinamide
Pyrazinamide
MOA of pyrazinamide
inhibit mycolic acid synthesis
activity is dependent on an acidic environemtn
prodrug - pyrazinamidase enzyme –> active form
resistance to pyrazinamide
mutation in pyrazinamidase enzyme
Pyrazinamide
Well absorbed from the 1
Widely distributed throughout the body, can enter 2 and 3
- GI tract
- macrophages
- TB cavities
Adverse reactions to pyrazinamide
Hepatoxicity
hyperuricemia - nearly all patients
___ is essential component in tx of combo therapy used to treat active TB and infections caused by M. avium
Ethambutol
MOA of ethambutol
inhibits arabinosyl transferases (involved in mycobacterial cellw all synthesis)
resistance to ethambutol
point mutations in genes encoding arabinosyl transferases
should always be given in combo with other drugs
Adverse reactions to ethambutol
retrobulbar neuritis - reversible following discontinuation
hyperuicemia - less than pyradinazole
aminoglycoside antibiotic used in tx of TB caused by strains resistant to first line drugs - used in combo with other drugs to prevent resistance
Streptomycin
MOA of streptomycin
interferes with bacterial protein synthesis
streptomycin effective against intracellular, extracellular or both?
extracellular - penetrates cells poorly
what does streptomycin have antimicrobial activity against
M. tuberculosis
M. avium
resistance to streptomycin
point mutations in ribosomal proteins
Streptomycin:
delivered as a 1
distributed in most 2
penetrates 3 poorly
- injectable
- body fluids
- cells and tissues
adverse reactions to streptomycin
- ototoxic - vertigo, hearing loss
2. nephrotic
what is rifabutin active against?
M. tuberculosis and M. avium complex
MAC organisms more that rifampin
Rifabutin is a less potent induced of _____
cytochrome p450
how do you treat M. avium complex (MAC)
combination therapy
- macrolide (clarithromycin or azithromycin) - protein synthesis inhibitor
- rifampin
- ethambutol
- (+/-) streptomycin
drugs used for prophylaxis of MAC in HIV pts (CD4<50)
Clarithromycin or azithromycin
tx of leprosy
multidrug regimen:
- dapsone
- clofazimine
- rifampin
therapy last for years:
1-2 years for tuberculoid
5 years for lepromatous
Dapsone is a competitive inhibitor of what
folic acid synthesis
Adverse effects of Dapsone
non-hemolytic anemia
acute hemolytic anemia in pts with G6P deficiency
what drug for leprosy can cuase skin to turn red-brown to black
Clofazimine
