antimycobacterials Flashcards by David Gordon

First Line antimycobaterials

Isoniazid, Rifampacin, Pyrinizinamide, Ethambutol

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INH- MOA

Inhibits mycolic acid synthesis

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INH activation

KatG- only in Mb

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INH & liver enzymes

p450 inhibitor, metabolized in liver, various rates of acetylation

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INH distribution

All tissues- w/ high intracellular concentrations

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INH MOR

katG mutation

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INH- AE

Hepatitis, B6 deficiency- peripheral neuropathy, give pyridoxine, Inhibition of Phenytoin metabolism- ataxia

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INH method of admin

Oral

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INH Tmax

1-2 hr

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INH 1/2 life

.75-5h

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INH excretion

Kidney

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Rifampin- MOA

binds to beta subunit of Mb RNA pol –> inhibits transcription

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RIF method of admin

Oral- well absorbed

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RIF T1/2

2.5-5hr

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RIF- distribution

all tissues

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RIF & liver enzymes

CYP450 inducer

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RIF excretion

mostly feces, some urine

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RIF AE

Reddish/ brown Urine, Hepatitis, Abdominal discomfort, fever, skin eruptions

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RIF drug interactions

inc elimination of other drugs esp Birth control and HIV proteases- monitor the level

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RIfabutin

doesn’t affect CYP450 so use in AIDs patients so don’t inc elimination of PI

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Rifampimicin

Used for leprosy

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Pyrizinamide (PZA)- MOA

Pyrizinamidase converts it to pyrizinmatoic acid –> unknown MOA

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PZA method of admin

Oral

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PZA 1/2 life

9 hr

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PZA- distribution

well distributed in tissues but concentrates in cells

PZA activity

active in acidic environments ie lysozomes inside of macropahges

PZA metabolism

Liver

PZA excretion

Kidney

PZA AE

Hyperuricemia- Pyrazinoic acid inhibits renal secretion of Uric acid --> Gout monitor SGOT (liver enzyme) and uric acid, Heptatitis, Arthralgia, fever, skin rashes

Ethambutol MOA

inhibits arabinosyl tranferase --> inhibits bac wall synthesis. Bacerial static

Ethambutol admin

Oral

Ethambutol 1/2 life

10 -15 h

Ethambutol distribution

most tissues, including CNS --> used for TB meningitis

Ethambutol excretion

Unchanged in urine

Ethambutol AE

Retrobulbar neuritis- Optic neuritis w/o swelling of optic disc. R/G color blindness- Monthly tests for visual acuity. Peripheral neuritis, HA, Rash

Streptomycin (SM)- use

occasionally used in conjunction with first line tax

SM- admin

IV/ IM

SM- tissue distribution

distributes to tissues, but doesn't concentrate in cells

SM- excretion

Excreted unchanged in urine, no liver metabolism

SM- AE

Ototoxicity- vistibular and auditory, renal injury, hypersensitivity

SM- MOA

binds 30s subunit of bac ribosome- prevents initiation complex formation. Inhibits translation

Paraminosalicylic Acid- PSA- MOA

competes with PABA for Mb dihyropterase synthase, interferes with folic acid and thus DNA synthesis. bacteriastatic

PSA- admin

oral, well absorbed, always with food

PSA- T1/2

2 hr

PSA metabolism

Liver

PSA excretion

Kidney

PSA toxicity

GI- nausea, abdominal pain, diarrhea, nausea if not given w/ food. Goiter, hypothyroidism. Anemia

Ethionamide- MOA

Inhibits mycolic acid synthesis

Ethionamide- admin

Oral- well absorbed

Ethionamide- distribution

wide

Ethionamide- metabolism

Liver metabolizes it to ethionamide sulphoxide

Ethionamide excretion

ethionamide sulphoxide- kidney excretion

Ethionamide - AE

pyridoxine deficiency , GI- N/D/ pain, hepatotoxicity, allergic reactions

Clofazamine- uses

Leprosy and Tb

Clofazoamine- MOA

inhibits DNA synthesis

Clofazamine- Admin

Oral

Clofazamine T1/2

10 days

Clofazamine distribution

widely. Concentrates in reticuloendothelil system and is slowly let out, partially accounts for long half life

Clofazamine- excretion

metabolized to several inactive metabolites and excreted in the feces and urine

Clofazamine - AE

Drug accumulation in tissues turns- skin, urine, and feces a red brown color, so people with leprosy don't like it b/c it marks them. GI disturbances

Cycloserine/ kanamycin- MOA

inhibits cell wall synthesis

Cycloserine/ Kanmycin- use

rarely used due to poor efficacy and adverse eventes

Fluroquinolones-

Ciprofloxacin, Moxifloxacin, Levofloxacin

Fluroquinolones- MOA

inhibit topoisomerase II

Fluroquinolones- disrtibution

Low intracellular concentration

Dapsone- use

Tx leprosy

Dapsone- MOA

inhibits folate synthesis

Dapsone- excretion

excreted into bile, reabsorbed, excreted in urine

Dapsone- AE

well tolerated. Fever, GI, rash, exoliative dermatitis

Dapsone Contratindications

Don't give to someone with sulfa drug allergies

Second line Tb tx

Streptomyocin, Paramino Salacylic Acid, Ethionamide, Clofazamine, Cyloserine/ Kanomycin, Fluroquinolones, capreomycin

Paucibacillary Tb- Tx

Rifampin& Dapsone for 6 months. Single lesion- Rifampin, ofloxacin, Minocycline

Lepromatous MB- Tx

Rifampin, Dapsone, Clofazamine- 12 mos

M. avium Tx

Azithromycin, Ethambutol, Rifabutin, Fluroquinolones