drug dosing in the critically ill patients Flashcards
what are the 4 phases of critical illness
rescue (fluid resuscitation, vasoactive drugs)
optimization (preserve organ & tissue function)
stabilization (clinical improvement)
de-escalation (weaning of support)
what are the ideal characteristics of a medication in the ICU
predictable bioavailability
fast onset
rapid titratability
wide therapeutic window
which route is most common in the ICU
IV (100% bioavailability)
which routes have high/low bioavailability?
IV has 100%
IM, SQ, transdermal, sublingual, enteral have lower bioavailability
what are some patient factors in the critically ill that will affect ABSORPTION
gastric pH
GI motility
regional blood flow
peripheral or gut edema
what things DECREASE absorption
perfusion abnormalities
GI motility
altered gastric pH
bowel wall edema
drug- nutrient interactions
what are some examples of commonly used ICU drugs that are affected by changes in ABSORPTION
itraconazole- needs an acidic medium
phenytoin- drug/nutrient interactions
enoxaparin- incompletely absorbed in the setting of pressors and edema
a drug’s distribution depends on both ___ and ___
the patient’s physiology (blood flow, protein, body composition)
AND
the properties of the drug (protein binding affinity, solubility, molecular weight, etc)
what are some contributors to changes in Vd?
fluid shifts, tissue perfusion, changes in plasma protein binding
hydrophilic drugs have a ______ Vd and are thus dependent on ______
smaller
tissue perfusion & blood volume
(reduced tissue perfusion will decrease the distribution of hydrophilic drug)
what are some factors that can INCREASE Vd
large volume resuscitation
capillary leak syndrome
ascites
mechanical ventilation
hypoalbuminemia
what are some drugs affected by hypoalbuminemia
albumin-bound drugs
amiodarone
ceftriaxone
midazolam
morphine
phenytoin
propofol
valproic acid
warfarin
what are some drugs affected by: large volume resuscitation, capillary leak, ascites, mechanical ventilation
hydrophilic drugs
aminoglycosides
beta lactams
daptomycin
hydromorphone
morphine
vanco
what would DECREASE Vd
decreased alpha l-acid glycoprotein
drugs affected by decreased alpha l-acid glycoprotein
medications bound to alpha l-acid glycoprotein
azithromycin
carvedilol
fentanyl
lidocaine
olanzapine
phenobarbital
_____ is the primary site for drug metabolim
LIVER
why might hepatic drug elimination be altered during critical illness?
changes in blood flow & intrinsic enzyme activity
(liver is highly perfused, 30% of cardiac output, when CO decreases it will impact drug clearance)
what are some factors that may INCREASE metabolism
hepatic enzyme induction
augmented hepatic blood flow
drugs affected by increased metabolism?
flow dependent drugs (high extraction drugs)
propofol
midazolam
morphine
metoprolol
what are some factors that may DECREASE metabolism
hepatic enzyme inhibition
decreased hepatic blood flow
drugs affected by decreased metabolism?
flow-independent medications (low extraction drugs)
warfarin
diazepam
phenytoin
______ are the primary organ responsible for drug elimination
kidneys
what are some factors that can INCREASE clearance
augmented renal clearance
extracorporeal removal
drugs affected by INCREASED clearance
renally eliminated medications
beta lactams
vancomycin
enoxaparin
gabapentin
levetiracetam
what are some factors that can DECREASE clearance
AKI
drugs affected by AKI
nephrotoxic meds
aminoglycosides
NSAIDs
antivirals
contrast
creatinine lags by ___ from the onset of kidney damage
48 hours
(as much as 50% of kidney function is lost before detectable changes in SCr occur)
____% of critically ill patients experience AKI
20-50%
affects on drugs in CKD
decreased clearance
increased half life
accumulation of active metabolites (morphine)
decreased kidney drug metabolism
altered drug distribution (protein binding)
dosing considerations for hemodialysis
give dose after hemodialysis
supplemental doses after hemodialysis
consider the dialyzer
dialysis times
dosing considerations for peritoneal dialysis
timing of dose (random compared to hemodialysis recommendations, look up specific drug)
route of admin: IV vs peritoneal
residual urine output
drug removal in dialysis depends on?
size of drug molecule
other factors like protein binding, Vd, solubility, flow rates, etc
