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Pharm Final > Antituberculotics > Flashcards

Antituberculotics Flashcards

1
Q

Latent TB infection

A

TB bacilli dormant in lungs, don’t cause destruction
No s/sx
Not infectious

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2
Q

TB disease

A

TB bacilli invade and damage parts of body
S/sx of disease disappear
can be infectious

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3
Q

TB sx

A 
Cough x 3 weeks
tired
weight loss
sweating at night
fever
no appetite
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4
Q

Transmission of TB

A

droplet nuclei; expelled when a person with INFECTIOUS TB sneezes, speaks, sings, or coughs

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5
Q

Other names for mycobacterium tuberculosis

A 
Captain of death
white death
white plague
consumption
tuberculosis
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6
Q

Mycobacterium tuberculosis (Mtb)

A

acid-fast
slow generation time, 15-20 hours (drug resistance - time to mutate)
facultative intracellular parasite, usually of macrophages

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7
Q

Mtb structure

A

acid fast cell wall: mycolic acid + arabinogalactan + peptidoglycan

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8
Q

Tx path for TB

A

always use first-line drugs IN COMBO; then result to second-line (not as good, more toxic)

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9
Q

1st line TB drugs

A

Isoniazid, rifampin, pyrazinamide, ethambutol; (streptomycin, rifabutin) - alternates

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10
Q

MDR TB tx

A

INH, Rif

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11
Q

XDR TB tx

A

INH, Rif, any fluoroquinolone, and one injectable

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12
Q

Tx TB

A

Initial: INH, Rif, Pyrazinamide (PZA), Ethambutol (EMB) x 2 months

Continuation: INH, Rif x 4 months

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13
Q

Tx for latent TB

A

INH or Rif as monotherapy daily

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14
Q

Isoniazid (INH) MOA

A

Inhibits biosynthesis of mycolic acid; produg that required KatG

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15
Q

Spectrum of INH

A

MOST NARROW DRUG (inhibits only mycolic acid)

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16
Q

Resistance to INH

A

mutated KatG (required to activate INH

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17
Q

Prodrugs

A

INH (KatG), PZA

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18
Q

INH use

A

prophylaxis (alone) - liver damage esp. >35 yo

Active TB (give with Rif, EMB, PXA)
Latent TB- monotherapy

can reach intracellular bacilli, advantage
static; INH and Rif is cidal

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19
Q

INH Pharmacokinetics

A

Oral
Good GI absorption
Metabolism by acetylation (liver) inactivates drug (fast vs. slow)
Excreted through urine

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20
Q

Who are slow metabolizers of INH

A

whites and blacks

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21
Q

Who are fast metabolizers of INH

A

Eskimos, Native Am, Asians

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22
Q

INH toxicities

A

HEPATITIS (abnormal LFT, jaundice, hep in older people, more common in fast acetyltors)
PERIPHERAL NEURITIS (slow acetylators, antagonized by pyridoxine)
HEMOLYSIS (in G6PD- not contra)
LUPUS LIKE SYNDROME (HIP drugs)
CNS stimulations
Others: H/A, vertigo, constipation, micturition, orthostatic HTN, eosinophilia, albuminuria, skin rashes, allergy, bone marrow depression

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23
Q

Rifampin MOA

A

inhibits DNA dependent RNA polymerase (rpoB subunit)- prevents transcription; oral

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24
Q

Rifamycins

A

group of structurally similar complex macrocyclic abx (rifabutin, rifapentine)

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25
Q

Resistance to Rifampin

A

rpoB mutation

26
Q

Rifampin use

A

Active TB - combo (RIPE)
Latent TB- monotherapy
similar to INH

Additional: leprosy

27
Q

Rifampin toxicities

A 
not serious (no hepatotoxicity)
GI 
Hypersensitivity
HEPATIC ENZYME INDUCTION (P450s) - not recommended for HIV-treated individuals
ORANGE urine, sweat, tears, contacts
DECREASES BC EFFECTIVENESS
28
Q

Rifampin drug interactions

A

induces adrenal, thyroid hormones, vitamin D and HAART (HIV)

29
Q

Ethambutol MOA

A

inhibits arabinosyl transferase (embCAB) (involved in AG synthesis; STATIC; just as narrow as INH

30
Q

Kinetics of Ethambutol

A 
Combo therapy (RIPE)
oral, well absorbed, GETS INTO CNS!!!
renal elimination, excreted in feces and urine, dose adjustment needed in renal failure
31
Q

Ethambutol Toxicities

A

decrease visual acuity and loss of green-red percention*** (usually reversible); no recommended <13 but not contra (opthamology exam)

Allergy, GI, numbness, joint pain, peripheral neuritis
Renal insufficiency- give smaller dose

32
Q

Pyrazinamide

A

prodrug; MOA
active at acidic pH**
greatest activity against DORMANT organisms
oral; well absorbed, good tissue penetration (Meninges)
combo tx (RIPE)

33
Q

Responsible for reducing tx for TB to 6 months

A

Pyrazinamide

34
Q

CNS penetration

A

Ethambutol, Pyrazinamide

35
Q

Toxicity of PZA

A

hepatic dysfunction, hyperuricemia, non gouty polyarthralgia, myalgia, GI, porphyria, photosensitivity

36
Q

Hepatic effecting TB drugs

A

INH - hepatitis
Rif - hepatic enzyme induction (P450s)
Ethambutol - none
PZA- hepatic dysfunction

37
Q

Streptomycin

A

30s inhibitor of protein synthesis; cidal

parenteral, limited tissue penetration, cell penetration poor thereforebest for extracellular Mtb

38
Q

Renal excretion TB drugs

A

Ethambutol, Streptomycin (dose adjustment)

39
Q

Toxicity of Streptomycin

A

ototoxicity, nephrotoxicity

40
Q

Rifabutin

A

inhibits DNA dependent RNA polymerase (rpoB)

oral, well absorbed, enterohepatic cycling, metabolies ORANGE COLORED

41
Q

Rifabutin use

A

replaces Rifampin in HIV-TB co-infected individuals to avoid drug interactions; less potent inducer of P450 enzymes

42
Q

2nd line TB tx

A

lower potency and/or greater toxicity

43
Q

Mycobacterium avium complex (MAC) cause

A

M. avium, M. intracellulare

44
Q

What is MAC

A

common environmental pathogen; infection following inhalation (similar to TB) or swallowing (GI, diarrhea)

45
Q

Sx of MAC

A

hair loss, ulcers, kidney destruction

46
Q

MAC resistance

A

resistant to anti-TB and antimicrobials

47
Q

Tx for MAC

A

2-3 Antimicrobials x 12 months

  1. Clarithromycin or azithromycin
  2. ethambutol
  3. Add third oral (rifabutin, rifampin, ciprofloxacin)

IV amikacin in certain cases (resistance to clarithromycin)

48
Q

Coinfectious HIV

A

Mtb, MAC

49
Q

Mycobacterium leprae tx (WHO-MDT) vague

A

multi-drug therapy (tx w/ one with always confer resistance

50
Q

PB leprosy sx

A

1-5 patches

51
Q

Posi leproxy tx

A

rifampin and dapsone, 6 mo

52
Q

Multi leproxy sx

A

> 5 patches

53
Q

MB leproxy tx

A

rifampin, dapsone, 6-12 months

54
Q

Most widely used and least expensive drug

A

Dapson

55
Q

Dapsone MOA

A

similar to sulfa (PABA antagonist); oral, GI absorption complete and rapid; slow excretion

56
Q

Dapsone toxicity

A 
N/V, H/A, Dizziness
dose-related hemolysis
Methemolgobinemia, leukopenia, agranulocytosis, allergic derm, exfoliative derm with concurrent liver damage
peripheral neuritis
NASAL OBSTRUCTION (IMPROVES 3-6 MONTHS)
57
Q

Peripheral neuritis

A

INH
Ethambutol
Dapson

58
Q

Most heavily regulated drug in US

A

Thalidomide (STEP) program

59
Q

Thalidomide toxicity

A

teratogenic; not be given any time in pregnancy

60
Q

Thalidomide use

A

DOC for moderate to severe ENL (erythema nodosum leprosum) in non-childbearing people

Orphan drug status: lepromatous leprosy, tx of mycobacterium infections;

61
Q

Lupus like syndrom drugs

A

“HIP”

Hydrazaline, INH, Procainamide

62
Q

What drug is used in both leprosy and TB

A

Rifampin

Pharm Final (6 decks)

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