Drug Induced Disease Flashcards
QTc prolongation is a QTc of
> =500 ms
or
=60 ms from baseline
what are 6 classes that can cause QT prolongation
antiarrhythmics
antibiotics
antipsychotics
antidepressants
antiemetics
antifungals
nonmodifiable risks for QT prolongation
> 65, female, genetics, CV disease
which 3 antiarrhythmics cause QT prolong
sotalol, amiodarone, dofetilide
which 2 antibiotic classes cause QT prolong
fluoroquinolones
macrolides
main antidepressant that prolongs QT
citalopram
after d/c the offending drug, what is done to treat TORSADES
magnesium push or infusion
transcutaneous pacing
isoproterenol infusion
avoid prolonging agents in pt with pretreatment QTc of
> 450
reduce dose or d/c prolonging agent if QTc increases
> 60 from pretreatment
d/c QT prolonging agent if QTc increases to
> 500
which 2 electrolytes should be maintained when treating QT PROLONGATION
K>4
Mg>2
which 3 classes contribute to Na and volume retention HF
NSAIDs, steroids, TZDs
class with BBW to avoid in HF class III and IV
TZDs
2 chemo anthracyclines that cause direct cardiotoxicity and HF
doxorubicin, daunorubicin
the max lifetime anthracycline dose is
500 mg/m2
is cardiomyopathy from anthracyclines reversible?
irreversible
agent that causes reversible cardiomyopathy through inhibition at HER2 receptors
trastuzumab
agent with BBW for reductions in LVEF and development of HF
trastuzumab
2 classes that can cause HF due to negative inotropy
non-DHP CCBs
beta-blockers
agent that causes MI due to vasospasm and vasoconstriction of coronary arteries
cocaine
main treatment for chest pain and HTN in cocaine induced MI
benzos
agent with BBW for increased risk of thrombotic CV events, MI, or stroke
NSAIDs
3 main roles of the liver are
metabolism
synthesis
detoxification
what are the 2 aminotransferases? what are their normal ranges?
AST & ALT
normal 5-40 U/L
LFT used to confirm elevated ALP is due to liver injurt
GGT
which LFT is found most exclusively in hepatocytes
ALT
LFT found in liver and bone?
what is its normal range?
ALP
normal 30-140 U/L
2 labs that measure synthetic function of the liver
albumin, PT/INR
lab involved in jaundice, and its normal range?
bilirubin
~1 mg/dL
hepatocellular injury is characterized by elevation in?
what R?
AST & ALT elevation
R >= 5
cholestatic injury is characterized by elevation in?
what R?
ALP elevation
R <= 2
mixed injury is a R of
2.5
how do you calculate R for liver injury?
R = [ALT/ULN] / [ALP/ULN]
top drug CLASS associated with DILI
antimicrobials
top med that causes DILI
amox/clav
should someone who had DILI be rechallenged with the med?
no unless no alternative
top 10 meds causing DILI
- amox/clav
- isoniazid
- nitrofurantoin
- Bactrim
- minocycline
- cefazolin
- azithromycin
- ciprofloxacin
- levofloxacin
- diclofenac
general metabolism of APAP causing overdose?
saturated conjugation, 2E1 forms more NAPQI, NAPQI attacks hepatocytes
when can activated charcoal be used for APAP overdose
within 1-2 hours of ingestion
AEs of PO vs IV NAC?
PO- bad tase, NV
IV- anaphylactoid rxn
how to prepare and administer PO NAC? when should be repeated?
dilute solution to 5% with a soft drink and lid to cover smell
repeat dose if vomited within 1 hour
when should IV NAC be used over PO?
liver failure, pregnancy, inability to tolerate PO
what are the situations where statins should NOT be used in relation to DILI
decompensated cirrhosis
acute liver failure
risk factors for DIKI
age>65, CKD, concomitant nephrotoxins, renin-dependent state, allergy to drug, duration of therapy, DM, HTN
what is preferred for hydration in DIKI
balanced crystalloids (lactated ringers)
5 main classes of med that can cause pre-renal or hemodynamic injury
ACE, ARB, NSAIDs, diuretics, calcineurin inhibitors
mechanism of hemodynamic injury
loss of autoregulation – inc risk of low intraglomerular pressure – reduce GFR
NSAID & ACE/ARB combos should NOT BE USED TOGETHER in patients with
CKD, HF, and liver disease
3 meds that cause acute tubular necrosis (ATN)
aminoglycosides, amphotericin B, IV contrast
hallmark sign of ATN
muddy brown casts
nephrotoxicity with aminoglycosides correlates with
trough
how should aminoglycosides be dosed to reduce risks?
what should trough be?
extended interval dosing
want undetectable trough concentrations
2 contrast media that cause ATN
iohexol
iodixanol
risks for contrast media AKI
DM, large dose, high osmolol, ionic contrast, short interval between 2 admins
gold standard treatment for contrast media ATN
saline hydration 12 before and after to flush kidneys
alternative to saline for contrast media ATN for high risk patients
NAC
4 classes that cause acute interstitial nephritis (AIN)
beta lactams, NSAIDs, sulfa drugs, PPIs
what can be used to treat DIKI with AIN if quickly
steroids aggressive within 2 weeks
mechanism of vancomycin kidney injury
not known
TDM factors that contribute to injury with vancomycin
trough >20
AUC >600
TDD >4g
>7 day treatment
weight >101.4 kg
concomitant nephrotoxins
severity of illness
3 meds that may cause nephrolithiasis (post renal injury)
topiramate, sulfonamide, furosemide
how to treat nephrolithiasis?
hydration to induce diuresis
meds that cause rhabdomyolysis (post-renal)
statin, statin-fibrate combos
treatment for rhabdomyolysis
aggressive IV fluids
CKD can be caused by which med
lithium
main mechanism causing lithium CKD
nephrogenic diabetes insipidus
main risk factor for CKD from lithium
cumulative lithium exposure
possible DDI with lithium that may cause kidney injury
HCTZ
med that can be used for symptoms of DI in CKD from lithium
amiloride for polydipsia & polyuria
can lithium be restarted after injury to the kidney is resolved?
NO!! NOW HAVE CKD! want to prevent further progression/decline
