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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
Resistance to Rifampin
rpoB mutation
26
Rifampin use
Active TB - combo (RIPE) Latent TB- monotherapy similar to INH Additional: leprosy
27
Rifampin toxicities
``` 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
Rifampin drug interactions
induces adrenal, thyroid hormones, vitamin D and HAART (HIV)
29
Ethambutol MOA
inhibits arabinosyl transferase (embCAB) (involved in AG synthesis; STATIC; just as narrow as INH
30
Kinetics of Ethambutol
``` Combo therapy (RIPE) oral, well absorbed, GETS INTO CNS!!! renal elimination, excreted in feces and urine, dose adjustment needed in renal failure ```
31
Ethambutol Toxicities
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
Pyrazinamide
prodrug; MOA active at acidic pH** greatest activity against DORMANT organisms oral; well absorbed, good tissue penetration (Meninges) combo tx (RIPE)
33
Responsible for reducing tx for TB to 6 months
Pyrazinamide
34
CNS penetration
Ethambutol, Pyrazinamide
35
Toxicity of PZA
hepatic dysfunction, hyperuricemia, non gouty polyarthralgia, myalgia, GI, porphyria, photosensitivity
36
Hepatic effecting TB drugs
INH - hepatitis Rif - hepatic enzyme induction (P450s) Ethambutol - none PZA- hepatic dysfunction
37
Streptomycin
30s inhibitor of protein synthesis; cidal | parenteral, limited tissue penetration, cell penetration poor thereforebest for extracellular Mtb
38
Renal excretion TB drugs
Ethambutol, Streptomycin (dose adjustment)
39
Toxicity of Streptomycin
ototoxicity, nephrotoxicity
40
Rifabutin
inhibits DNA dependent RNA polymerase (rpoB) | oral, well absorbed, enterohepatic cycling, metabolies ORANGE COLORED
41
Rifabutin use
replaces Rifampin in HIV-TB co-infected individuals to avoid drug interactions; less potent inducer of P450 enzymes
42
2nd line TB tx
lower potency and/or greater toxicity
43
Mycobacterium avium complex (MAC) cause
M. avium, M. intracellulare
44
What is MAC
common environmental pathogen; infection following inhalation (similar to TB) or swallowing (GI, diarrhea)
45
Sx of MAC
hair loss, ulcers, kidney destruction
46
MAC resistance
resistant to anti-TB and antimicrobials
47
Tx for MAC
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
Coinfectious HIV
Mtb, MAC
49
Mycobacterium leprae tx (WHO-MDT) vague
multi-drug therapy (tx w/ one with always confer resistance
50
PB leprosy sx
1-5 patches
51
Posi leproxy tx
rifampin and dapsone, 6 mo
52
Multi leproxy sx
>5 patches
53
MB leproxy tx
rifampin, dapsone, 6-12 months
54
Most widely used and least expensive drug
Dapson
55
Dapsone MOA
similar to sulfa (PABA antagonist); oral, GI absorption complete and rapid; slow excretion
56
Dapsone toxicity
``` 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
Peripheral neuritis
INH Ethambutol Dapson
58
Most heavily regulated drug in US
Thalidomide (STEP) program
59
Thalidomide toxicity
teratogenic; not be given any time in pregnancy
60
Thalidomide use
DOC for moderate to severe ENL (erythema nodosum leprosum) in non-childbearing people Orphan drug status: lepromatous leprosy, tx of mycobacterium infections;
61
Lupus like syndrom drugs
"HIP" | Hydrazaline, INH, Procainamide
62
What drug is used in both leprosy and TB
Rifampin

Pharm Final (6 decks)

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