Variability Flashcards
what drug has higher plasma concentrations in Asians
rosuvastatin
which race is more sensitive to propranolol
Chinese
which CYP has a lot of genetic variability
CYP2D6
what drug has higher concentrations with less functional CYP2D6 genes
nortriptyline
renal clearance of which two drugs rise from birth before peaking and declining with age
ceftriaxone
theophylline
this drug has a half life and Vd that increases and CL that decreases with age
diazepam
this drug shows higher Cp and lower CL in the elderly
EC50 is also at a lower concentration, so they have reduced metabolism and greater sensitivity
midazolam
what is generally expected of metabolism and clearance with age
decreased drug metabolism and renal clearance
neonates haw low clearance, long half lives, and high Vd for this drug
theophylline
which gender has increased CYP3A4 activity (ex. lovastatin)
females
which gender has increased CYP2D6 activity (ex. metoprolol) and CYP1A2 (ex. theophylline)
males
males and females have the same activity in which CYP
CYP2C19 (ex. omeprazole)
with methylprednisolone, females show
higher sensitivity and clearance (CYP3A4)
which class of drugs have higher AUCs in women, so they are more likely to have toxic concentrations
antiretrovirals (ritonavir, atazanavir, CYP3A4 and 2D6)
metoprolol shows what in females
higher concentrations and lower CL
females are more sensitive to what AE when taking quinidine (CYP3A4)
ECG changes
which drug showed a DDI with antifungals (-azoles) leading to QT interval changes in females
terfenadine (seldane)
aspirin showed __ reduction in CV events in women than men
less reduction
drugs show reduced renal clearance at what time of day
night
theophylline shows less AEs when administered with or without food?
without
with food increases incidence of AE
effects of food on drug absorption
delayed gastric emptying
increases dissolving poorly soluble drugs
changed GI pH
stimulated bile flow
etc
which 2 drugs showed higher peak concentrations when given with food
tizanidine
desvenlafaxine
GFJ inactivates GI CYP3A4, increasing the AUC of which drug
simvastatin
vitamins should always be taken ___ food
with
are there absorption changes with obesity
no
drug distribution may be affected in obesity and depends on
water, fat, logP
what effect does obesity have on CL
increase in CrCl, partial increase in renal Cl
which drug shows increased ddrug clearance in obesity
lithium
what metabolism changes occur in obesity
variable, CLm can increase, decrease, or not change
which drug shows lower CLm in obesity and why
methylprednisolone
liver is larger, but behaves as though it is impaired
which drug has higher EC50 in the obese, so they are less sensitive to drug effects
atracarium
enzyme induction of CYP1A2 in smoking leads to what ADME change?
increased CL or elimination
enhanced disposition
which drugs show increases CL with smoking
propranolol, tizanidine
which drugs induce CYP3A4
anticonvulsants, St Johns Wort
which drug induces CYP1A2
omeprazole
which drug induces CYP2E1
ethanol
OCs induce which metabolic pathway
conjugation
chronic liver disease –> reduce liver cell mass and enzyme activity due to alteration –> what effect on metabolism?
impaired drug metabolism
sinusoidal capillarization –> uptake of certain drugs in liver cells may be impaired –> what effect on metabolism (chronic liver disease)?
reduced metabolism
how does liver disease affect CL
reduced bile formation –> decreased CL
cirrhosis causes reduced plasma blood flow and GFR –> decreased renal Cl
hepatic CL of high CL drugs if limited by what
blood flow
hepatic CL of low CL drugs is influenced by
blood binding and CLint
do high and low CL drugs have low or high bioavailability
high CL – low F
low CL – high F
cirrhosis reduced pre-systemic hepatic metabolism which affects oral bioavailability how
increases oral bioavailability
cockcroft gault equation
CrCl = [140-age]IBW / 72Scr
IBW =
M = 50 + 2.3 (ht over 5 ft)
F = 45.5 + 2.3 (ht over 5 ft)
for cockcroft gault, if ABW < IBW use what in the equation
ABW
for cockcroft gault if patient is >65 and Cr concentration is <1 use what to calculate CrCl
1
what effect might renal disease have on absorption
Tmax may slightly increase- negligible consequences
Impaired metabolism may increase oral bioavailability
plasma protein biding of ACIDIC drugs is ___ in renal dysfunction
decreased
plasma protein binding of basic drugs is ___ in renal dysfunction
unaffected
Vd of drugs is ___ in renal dysfunction
increased
is non-renal CL affected by renal dysfunction
can be altered, impaired drug metabolism
is renal metabolism impaired in renal dysfunction
yes
is renal excretion impaired in renal dysfunction?
what is the effect
yes
excessive drug accumulation
which rule says elimination rate constant (ke) depends linearly on GFR
dose is adjusted to renal function proportional to ke, and interval stays the same
Dettli RUle 1
CKD
which rule says half the starting dose is given every 1 half life
Kunin RUle
CKD
which rule says a normal dose is given at longer intervals, which is prolonged proportional to the CL ration
Dettli RUle 2
CKD
distribution is affected in diabetes due to altered what?
albumin and reduced binding
is metabolism affected in diabetes
may be if liver dysfunction develops
which model shows how a disease progresses over time
disease progression model
phenytoin is effective at ___ plasma concentrations in T2DM
lower
ADME changes in CHF
reduced metabolism
reduced renal function/CL
decreased hepatic BF
increased IL6
which drug shows impaired metabolism in HF
lidocaine
which drug has reduced CL in CHF
vancomycin
which ADME changes are seen in thyroid disease
CLm and CLr increase in hyperthyroidism and decrease in hypothyroidism
which ADME change is seen in cystic fibrosis
which drugs are an example
increased renal clearance
dicloxacillin, prednisolone, lorazepam
which mediator is increased in inflammatory states, and how does it affect CL
IL6 increases which reduces drug CL
