Shared Flashcard Set

Details

Resp - Exam 2 - AntiTb Pharm
Pharm directed against Tb
69
Pharmacology
Post-Graduate
12/09/2011

Additional Pharmacology Flashcards

 


 

Cards

Term
Min. # of drugs Tb pts should be on?
Definition
2
Term
Types of therapy that cause/prevent resistance?
Definition
Cause: monotherapy
Prevent: combo therapy
Term
Development of resistance indicates what?
Definition
worse prognosis AND more severe disease
Term
How do you handle a failing regimen?
Definition
Put pt on at least 2 drugs they have NEVER had.
DO NOT add a single drug to the failing regimen
Term
2 categories of therapy you must have in order to effectively treat Tb?
Definition
1) Early bactericidal therapy (stop the bugs from growing) AND 2) sterilizing activity (kill off the remaining bugs)
Term
Reasoning behind giving BACTERICIDAL and STERILIZING therapy at the same time during the first 2 months?
Definition
Shortens treatment time (6 instead of 9 mo) AND dec chance of relapse
Term
Why does relapse usually occur?
Definition
Tissues were not properly STERILIZED
Term
Most common drug combo for the first 2 months (bactericidal)?

Why do we use this combo?
Definition
RIPE -- we don't know the sensitivity of the Tb so we use all 4 and hope the drug is sensitive to 2 or 3 of them
Rifampin (RIF)
Isoniazid (INH)
Pyrazinamide (PZA)
Ethambutol (EMB)
Term
What do you if during the first 2 months, your pt is on RIPE, and the Tb comes back being INH sensitive?
Definition
Stop the EMB (dec chances of SE - vision)! Continue the other 3

You only start them on EMB just in case the Tb is INH resistant.
Term
Of RIPE, which 2 are the best sterilizers?
Definition
RIF and PZA

(both are cidal)
Term
If you were not able to use PZA during the first 2 months, how long does your pt have to be on Tb drugs?
Definition
9

Pts can only do 6 months of treatment if they have been able to be on PZA the entire first 2 months b/c PZA is a really good STERILIZER, so if you couldn’t sterilize for the first 2 months, must inc the sterilization period (7 months)
Term
Why wouldn't someone be able to be on PZA?
Definition
Liver problems, gout, pregnant
Term
After 2 months of therapy w/ RIP (the bug was INH sensitive, so we dropped the EMB) -- what do you do next?
Definition
Drop the PZA and continue the RIF and INH for 4 more months

Pts will either take it daily, twice weekly, or three times weekly (depending on HIV+/immunocompromised)

If HIV-negative, absence of cavitary disease at presentation, and negative sputum smears at 2 months of therapy then: 1x/week INH-rifapentine
Term
What do you do if the pt can't take RIF?
Definition
Use PZA throughout the course instead

[I'm not sure how long it would have to be.. my guess is probably the longer (9 mo) but I'm not sure]
Term
Most active of all the Tb drugs?
Definition
INH

(one 1 that is both static AND cidal)
Term
Quick and dirty summary of Tb treatment
Definition
1) 2 months: RIPE
--drop the EMB if INH sensitive
2) 4 (or 7) months: RIF & INH

***use PZA throughout treatment if can’t use RIF
Term
What types of bacteria is RIF effective against?
Definition
mycobacteria, most Gram-positive and many gram negative bacteria
Term
Which one is more selective: INH or RIF?
Definition
INH
Term
MOA of RIF?
Definition
inhibition of DNA-dependent RNA polymerase → inhibits the synthesis of RNA
***must be in high concentrations to do this!
Term
Which Tb drugs have intracellular AND extraceullar activity?
Definition
INH and RIF
Term
Why do you need to give RIF 2x/wk?
Definition
to avoid a flu-like syndrome of fever, chills and myalgia
Term
Which Tb drug has the SE of: red-orange color to the urine, feces, saliva, sweat and tears?
Definition
RIF
Term
SE of RIF?
Definition
rash, fever, nausea and vomiting

Also: induces several P450 isoforms
Term
How is RIF self destructive?
Definition
when administered over longer periods could cause CYP3A auto induction reducing its own systemic exposure
Term
Why do you have monitor RIF in ppl with liver problems?

What other Tb drug do you need to monitor for liver function?
Definition
excreted mainly in bile and is subject to enterohepatic recirculation

Other drug: EMB -- 1/2 is excreted in urine and 1/2 in the bile so renal and hepatic function must be monitored
Term
How is RIF administered?
Definition
oral and IV
Term
Which Tb drug(s) is a pro drug?
Definition
INH & PZA

INH: activated by catalase-peroxidase (KatG gene)
Deletions or mutations in this gene --> resistance to INH

PZA: metabolized by mycobacteria (nicotinamidase) to pyrazinoic acid (active form)
**only active in acidic places (the edge of necrotic TB where lactic is b/c of inflamm. cells)
Term
MOA of INH?
Definition
disrupts cell wall synthesis

by inhibiting the enzymes
--enoyl acyl carrier protein reductase --β-ketoacyl-ACP synthase
Term
Is INH cidal or static?
Definition
BOTH!
cidal - growing bacteria
static - resting bacteria
Term
How does renal/hepatic impairment affect the toxicity of INH?
Definition
metabolized partly by acetylation b/c it's a hydrazine

If pt is a slow acetylator, then renal/hepatic impairment → inc toxicity

(***PAS also metabolized by acetylation)
Term
SE of INH?
Definition
hepatitis (inc during pregnancy), lupus like syndrome, convulsions, peripheral neuritis

***Also: inhibits cytochrome P450
Term
True or False
INH and RIF inhibit cytochrome P450
Definition
FALSE
INH inhibits but RIF INDUCES

Yeah.. I just Parsaed you :)
Term
PZA = cidal or static?
Definition
cidal
Term
MOA of PZA?
Definition
They can't decide:

either by
1)inhibiting transcription of the mycobacterial fatty acid synthase I (FASI) gene or
2)inhibiting FAS1 itself
Term
If FAS1 isn't allowed to do it's job, what happens?
Definition
interference with
(a) mycolic acid synthesis,
(b) reduction of intracellular pH and (c) disruption of membrane transport by POAH (the protonated form of POA- (pyrazinoic acid))
Term
SE of PZA?

What SE does EMB share with PZA?
Definition
hepatotoxicity, hyperuricemia (can't excrete uric acid) --> acute gout

arthralgias, nausea, vomiting and fever

EMB also has hyperuricemia
Term
EMB: static or cidal?
Definition
static
Term
EMB MOA?
Definition
inhibits arabinosyltransferase --> disrupts cell wall synthesis
Term
How does EMB work with the other Tb drugs?
Definition
disrupts the cell wall thus increasing the penetration of other antiTb drugs
Term
Main SE of EMB?
Definition
retrobulbar neuritis

causing red-green color blindness and loss of visual acuity
Term
How is Rifabutin like RIF? Different?
Definition
Derivative of RIF w/ same mechanism of action

Diff: less potent inducer of cytochrome P450, has SE: polymyalgia, pseudojaundice and anterior uveitis
Term
How does Rifapentine compare to RIF and Rifabutin?

(1/2 life? P450?)
Definition
--Longer 1/2 life than other 2
--In between the 2 for inducing cytochrome P450
Term
MOA of Cycloserine?
Definition
interferes with cell wall synthesis 2 ways:

1) inhibits alanine racemase
2) inhibits D-ala-D-ala synthetase
Term
SE of Cycloserine?
Definition
serious CNS toxicity, headache, tremors, psychoses and convulsions
Term
ETHIONAMIDE has MOA like which of the 4 big Tb drugs?
Definition
INH
Term
SE of ETHIONAMIDE?
Definition
gastric irritation, hepatotoxicity, peripheral neuropathies and optic neuritis
Term
3 aminoglycosides that are also antiTb?
Definition
Streptomycin, Kanamycin, and Amikacin

**Capreomycin is not an AG (it's amixture of four active cyclic peptides)
Term
Streptomycin: cidal or static?

Extracellular or intracellular?
Definition
Cidal in vivo (some evidence suggests static in vivo too..)

Extracellular
Term
How does Streptomycin compare to other Tb drugs?
Definition
less effective and more toxic than other drugs
Term
Streptomycin MOA?
Definition
inhibits initiation of protein synthesis, causes misreading of mRNA → synthesis of faulty proteins and it causes premature termination of protein synthesis by breaking polysomes into nonfunctional monosomes
Term
Streptomycin SE?
Definition
nephrotoxicity (reversible) and ototoxicity
Term
How do Amikacin/kanamycin compare to streptomycin?
Definition
less toxic
similar MOA
same SEs as streptomycin
Term
3 FQ's that are antiTB?
Definition
Levofloxacin, Moxifloxacin, Gatifloxacin

..no CIPRO
Term
FQ: static or cidal?
Definition
static
Term
FQ MOA?
Definition
inhibits bacterial DNA gyrase (bacterial eq. of mammallian topoisomerase II which prevents supercoiling)
Term
FQ SE?
Definition
SE: nausea, headache, dizziness, rash and pseudomembranous colitis (C. difficile)
Term
How is CAPREOMYCIN administered?
Definition
IM -- painful
Term
CAPREOMYCIN MOA?
Definition
inhibits protein synthesis but how is unclear
Term
CAPREOMYCIN: static or cidal?
Definition
static
Term
Why can't you give CAPREOMYCIN w/ streptomycin?
Definition
B/c both are nephrotoxic and ototoxic

**Same rule goes for the other AGs kanamycin and amikacin
Term
SE of CAPREOMYCIN?
Definition
nephrotoxic and ototoxi
eosinophilia, which is common, hearing loss and tinnitus.
Term
Which 2 drugs are given when the first line agents (RIPE and other 2 Rif's) can't be used?
Definition
CAPREOMYCIN, PARA-AMINOSALICYLIC ACID (PAS)
Term
MOA of PARA-AMINOSALICYLIC ACID (PAS)?
Definition
PAS competes with p-aminobenzoic acid in the synthesis of folic acid
Term
PAS: static or cidal?
Definition
static

Think about MOA: competes with p-aminobenzoic acid in the synthesis of folic acid.. this prevents growth/reproduction but doesn't kill the bugs that are already there
Term
How does PAS affect INH levels?
Definition
Both metabolized by acetylation --> PAS competes with INH for the metabolizing enzymes thus increasing the levels of INH
Term
SE PAS?
Definition
nausea, vomiting, diarrhea, anorexia, epigastric pain, abdominal distress, fever, malaise or joint pain. High drug concentrations in urine can cause crystalluria
Term
Difference b/t cidal and static?
Definition
Static -- the drug simply STOPS growth/reproduction.. it does not harm the bugs that are already there (1000 bugs will stay at 1000 bugs, can not increase but also, will not go down to 0)

Cidal -- Drugs actually KILLS the bugs that currently exist (1000 bugs will eventually go to 0 bugs)
Term
Drugs that are static?
Definition
INH (both static and cidal)
EMB
FQ
CAPREOMYCIN
PAS
Term
Drugs that are cidal?
Definition
INH (both static and cidal)
RIF
PZA
Streptomycin (in vivo)
Supporting users have an ad free experience!