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75 Cards in this Set
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- 3rd side (hint)
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why mycobacterial infections are difficult to treat
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- slow growing compared to other bacteria
- dormant and resistant to several drugs - lipid rich mycobacterial cell wall is impermeable to many agents - intracellular pathogens and are inaccessible to drugs (macrophages) |
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what bacteria is this?
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Mycobacterium tuberculosis; acid-fast stain Ziehl-Neelsen stain
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Describe gross morphology
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TB cavity with caseous content. Cavity contains central core with many bacilli lined by caseous material containing fewer bacteria
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Drugs used in TB first line
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- isoniazid
- rifampin - pyrazinamide - ethambutol |
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bactericidal first-line anti-tb drugs
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- isoniazid
- rifampin - pyrazinamide |
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first-line anti-tb drugs characteristics
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- bactericidal (not ethambutol)
- relatively less toxic - effective in combination |
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second-line anti-tb drugs
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- cycloserine
- ethionadmide - kanamycin - capreomycin - para-amino salicylic acid - streptomycin |
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second line anti-tb drugs characteristics
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- more toxic
- less tolerated - reserved for txn of drug resistant tb |
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Isoniazid (INH)
mode of action |
- bioactivated by katG (catalase)
- inhibits enzymes for mycolic acid synthesis - resistance associated with deletion in katG gene |
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Isoniazid (INH)
pharmacokinetics |
- oral, absorbs well, distributes in all tissues, high intracellular concentrations
- metabolized mainly in liver and excreted in urine |
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Izoniazid (INH)
adverse effects |
- hepatitis
- neuropathy - vitamin b6 deficiency |
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Izoniazid (INH)
precautions |
- pyridoxine may be given to pts to prevent neuropathy
- inhibits metabolism of phenytoin (potentiates side effects (ataxia) of this drug |
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Rifampin (RIF)
mode of action |
- blocks transcription
- inhibits bacterial DNA- dependent RNA polymerase by binding to beta subunit and inhibit RNA synthesis - bactericidal |
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Rifampin (RIF)
pharmacology |
- orally well absorbed
- well distributed in tissues - metabolized in liver - excreted in feces and in urine (tears and urine rosy) |
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Rifampin (RIF)
adverse effects |
- skin eruptions
- hepatitis - increases elimination of other drugs such as contraceptive steroids - urine has reddish color |
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Rifampin (RIF)
precautions |
- watch for levels of other drugs
- HIV infected individuals should be given Rifabutin (does not increase metabolism of protease |
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Rifampin induces:
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:cytochrome P450
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Drugs affected by Rifampin
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- oral contraceptives
- protease inhibitors |
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Pyrazinamide (PZA)
mode of action |
- converted to pyrazinoic acid (pncA)
- resistance may be due to mutations in pncA that impairs conversion of pyrazianamide to active form - active at pH of 5.5 affects mycobacteria residing in acidic envt of lysosomes - bactericidal |
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Pyrazinamide (PZA)
pharmokinetics |
- absorbed orally
- well distributed in tissues - concentrates inside the cells - metabolized in liver - excreted in urine |
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Pyrazinamide (PZA)
adverse effects |
- hepatitis
- hyperuricemia and gout - arthralgia, fever, rash |
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Pyrazinamide (PZA)
precautions |
- monitor serum glutamic oxaloacetic transaminase (SGOT) and uric acid levels
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Ethambutol
mode of action |
- inhibits arabinosyl transferase involved in bacterial cell wall synthesis
- bacteriostatic |
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Ethambutol
pharmokinetics |
- well absorbed orally
- well distributed in most tissues - tuberculous meningitis txn - excreted mostly unchanged in urine |
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txn for tuberculous meningitis
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ethambutol
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Ethambutol
adverse effects |
- OPTIC NEURITIS resulting in red-green blindness
- peripheral neuritis |
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Ethambutol
precautions |
- monthly tests for visual acuity
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second line therapy used in case of:
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- resistance to first-line agents
- failure of clinical response to conventional therapy - seriously txn-limiting adverse drug rxns |
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Streptomycin (SM)
mode of action |
- inhibits bacterial protein synthesis
- interferes w/ initiation complex of peptide formation - causes misreading of mRNA |
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Streptomycin (SM)
pharmokinetics |
- given IV or IM
- distributed in most of the tissues - very low intracellular concentrations effective against extracellular bacilli - excreted unchanged |
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Streptomycin (SM)
adverse effedcts |
- ototoxicity
- vestibulr dysfunction (pts fall in dark room), irreversible |
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Streptomycin (SM)
precautions |
routine audiometry
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Ethambutol
adverse effects |
optic neuritis with blurred vision, red-green color blindness
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Ethambutol
watch for |
establish baseline visual acuity and color vision, test monthly
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Isoniazid
adverse effects |
- hepatic enzyme elevation
- hepatitis - peripheral neuropathy |
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Isoniazid
watch for |
take baseline hepatic enzyme measurements; significant interaction with phenytoin and antifungal agents
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Pyrazinamide
adverse effects |
- hepatitis
- nausea - hyperuricemia - rash - joint ache - gout |
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Pyrazinamide
watch for |
take baseline hepatic enzymes and uric acid measurement
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Rifampin
adverse effects |
- hepatitis
- flu-like syndrome - significant interaction with several drugs |
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Rifampin
watch for |
take baseline hepatic enzyme measurements and CBC count; warn pt urine and tears may turn red-orange in color
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Streptomycin
adverse effects |
- ototoxicity
- nephrotoxicity |
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Streptomycin
watch for |
baseline audiography and renal fxn tests
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Paramino salicylic acid (PAS)
mode of action |
- competes with PABA for mycobacterial dihydropteroate synthetase
- bacteriostatic |
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Paramino salicylic acid (PAS)
pharmokinetics |
- readily absorbed orally, give w/ food
- metabolized in liver - excreted in urine |
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Paramino salicylic acid (PAS)
adverse effects |
- nausea
- ab pain - diarrhea - hypersensitivity - hepatitis |
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Paramino salicylic acid (PAS)
precautions |
- GI symptoms common but give with food
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Ethionamide
mode of action |
- related to INH
- blocks synthesis of mycolic acids |
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Ethionamide
pharmokinetics |
- well absorbed orally
- widely distributed in body - metabolized in liver to ethionamide sulphoxide - excreted in urine |
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Ethionamide
adverse effects |
- nausea
- diarrhea - gastic irritation - hepatotoxicity - neurological symptoms |
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can lessen neurological side effects of ethionamide
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Pyridoxine
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Clofazimine
mode of action |
- inhibits bacterial DNA synthesis
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Clofazimine
pharmacology |
- absorbed fairly by oral route
- distributed widely - concentrates in reticuloendothelial system and slowly released from deposits - metabolized into several inactive metabolites - excreted mainly in feces |
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Clofazimine
adverse effects |
- GI disturbances
- Red-brown skin color - discoloration of skin, urine, and feces |
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Cycloserine
acts by: |
- inhibiting cell wall synthesis
(rarely used - poor efficacy and adverse effects) |
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Fluoroquinolones
act by: |
- inhibiting topoisomerase II
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Fluoroquinolones
list |
- cirpofloxacin
- moxifloxacin - levofloxacin |
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most active drug against M tuberculosis and is useful for drug resistant TB
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moxifloxacin (a fluoroquinolones)
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Standard txn regiments for pulmonary tuberculosis
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- initial phase (2 mnths daily)
- INH, RIF, PZA or - INH, RIF, PZA, EMB - sterilizing phase (4 mnths daily or 3x/wk) - INH, RIF |
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Preventive chemotherapy for tb
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- individuals w/ + tuberculin test
- contacts of infectious cases of tb - INH monotherapy for 6 mnths |
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Leprosy (hansen's disease) caused by:
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Mycobacterium leprae (hansen's bacillus)
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Mycobacterium leprae
characteristics |
- gram-positive
- rod shaped - surrounded by waxy coating - stains with carbol-fuchsin |
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why M leprae will not grow in artificial culture conditions
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it is an obligate intracellular parasite that lacks many necessary genes for independent survival
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Tuberculoid (paucibacillary)
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form of leprosy characterized by one or more hypopigmented skin macules and anaesthetic patches
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Common features of tuberculoid leprosy
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- skin sensations lost due to damaged peripheral nerves
- thickening of auricular nerve on neck of pts |
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Lepromatous (multibacillary)
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form of leprosy associated w/ symmetric skin lesions, nodules, plaques, thickened dermis, frequent involvement of nasal mucosa resulting in nasal congestion, gynaecomastia; detectable nerve damage is late
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leonine faces
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sign of lepromatous leprosy; loss of eyebrows and partial collapse of nose with heavy bacterial load
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types of leprosy
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- tuberculoid (paucibacilary)
- lepromatous (multibacillary) |
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Treatment for leprosy
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- Dapson (diamino diphenyl sulfone)
- recommended for MB: rifampin, clofazamine, dapsone - recommended for PB: rifampin, dapsone |
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Type of therapy treatment for leprosy
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multidrug therapy
(monotherapy is considered unethical) |
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Dapson
mode of action |
- inhibits folate synthesis
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Dapson
pharmacokinetics |
- oral well absorbed from gut
- excreted into bile - reabsorbed from intestine - excreted into urine |
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Dapson
adverse side effects |
- well-tolerated
- fever - gastrointestinal intolerance - skin rash - exfoliative dermatitis |
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Dapsone should not be given to:
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:pts allergic to any of sulpha drugs
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atypical mycobacteria seen in late stages of AIDS
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Mycobacterium avium
(nontuberculous, noncommunicable) |
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Mycobacterium avium
treatment |
- azithromycin
- ethambutol - rifabutin - moxifloxacin (a fluoroquinolones) |
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