Exam 1 Flashcards
(157 cards)
1
Q
Lecture 1: Genetics
Goals of product label
A
ensure consistency
provide clarity
general information framework
emphasizes variability measures
2
Q
Lecture 1: Genetics
Forest plot
A
the greater the confidence length, the more significant the factor i sin terms of disturbing the drug
3
Q
Lecture 1: Genetics
cmax and Auc higher in males or females?
A
females
4
Q
Lecture 1: Genetics
most important eq. in pk
A
Css= FxDose/ (Cltot x tau)
5
Q
Lecture 1: Genetics
most major clearance mechanisms in order
A
- metabolism
- renal
- bile1
6
Q
Lecture 1: Genetics
most major metabolic mechanisms for clearance
A
- CYP
- UGT
- esterase
- other
7
Q
Lecture 1: Genetics
most major cyp mechanisms
A
- cyp3a
- CYP2C9
- CYP2D6
- CYP2C19
- CYP1A
- CYP2E1
- CYP2B6
8
Q
Lecture 1: Genetics
What is central tendency and variation
A
central tendency measure (mean exposure ) btw 2 specific populations (ex: w. and w.o hepatic impairment)
variability: variability in oboe measures
PKPK values should be reported as mean(arithmic or geometric) or median with measure of dispersion (standard of deviation and/or max and min values)
9
Q
Lecture 1: Genetics
Box and whisper plot
A
bar in the middle is the median
t
10
Q
Lecture 1: Genetics
variance
A
measures of the deviation of observers from the mean
11
Q
Lecture 1: Genetics
standard deviation
A
average deviation of observations from the mean
12
Q
Lecture 1: Genetics
coefficient variation
A
the standard deviation normalized to the mean.
CV= SD/mean
13
Q
Lecture 1: Genetics
intersubject variation
A
btw 2 patients
high is above 30% cv
14
Q
Lecture 1: Genetics
intrasubject variation
A
in one pt
low is below 30%
medium is 30-60%
high is above 60%
15
Q
Lecture 1: Genetics
which drugs tend to have higher variability?
ones with low bioavailability (F) or high F?
A
low bioavailability
16
Q
Lecture 1: Genetics
Pristiq (DEsvenlafaxine) variability
A
has low variability
Coefficient variant (CV)<30 % means there is low variability
17
Q
Lecture 1: Genetics
For central tendency, does tmax use mean or median?
A
median
18
Q
Lecture 1: Genetics
spaghetti plot
A
shows variability in lines of all pts
19
Q
Lecture 1: Genetics
histogram
A
emphasizes skewed distribution
20
Q
Lecture 1: Genetics
crestor (rosuvastatin) genetic varibaility
A
asian subjects have higher plasma concentrations after standard doses of the drug.
recommend lower dose in asians
21
Q
Lecture 1: Genetics
propanolol
A
white ppl needed twice as high conc. to recieve the same amount of beta blockade as asians .
22
Q
Lecture 1: Genetics
which enzyme causes for greatest variability
A
CYP2D6
23
Q
Lecture 1: Genetics
how is pristiq (desvenlafaxine) primarily metabolized
A
primarily by conjugation budgeted by UGT and to a minor extent by CYP3A4 (basically primarily eliminated by metabolism)
not metabolized by
24
Q
Lecture 1: Genetics
metabolic ratio equation.
what does it mean?
Is it a true pk parameter
A
metabolic ration=Drug/OHD metabolite
high ratio: … more drug, less metabolite
not a true pk parameter
25
Lecture 1: Genetics
examples of drugs subject to genetic variability in pk because od cyp2d6
DEBRISOQUINE, METOPROLO, ENCAINAMIDE, IMIPRAMINE, NORTRIPTYLINE, MAPROTILINE, ETC.
26
Lecture 2: Age and Weight
as age increases, percentage of no prescription drug use increases or decreases?
decreases
27
Lecture 2: Age and Weight
what sex weighs more
males weigh more than female
28
Lecture 2: Age and Weight
clearance values corrected for body size
look at the units of clearance to see if it has been adjusted for body size.
gives a better understanding of the pk parameter
29
Lecture 2: Age and Weight
what age does CL peak
around 2-3 years old, at max capability.
then, it decreases 1% per year
30
Lecture 2: Age and Weight
what is the average adult weight
male: 70 kg-1.73 m^2
female ~ 60 kg
31
Lecture 2: Age and Weight
allometric scaling
body functions change in proportion to body weight by a power function,
CL: ax BW^0.75 (can range depending on drug)
vd: A X BW^ 1.0
32
Lecture 2: Age and Weight
Calculation of BSA
approximation EQUATION
SA=0.1 BW^2/3 (kg)
33
Lecture 2: Age and Weight
diazepam changes in t 1/2
as age increased, t 1/2 increases, lower CL
males have higher t 1/2 then females
CL higher in older females than older males
34
Lecture 2: Age and Weight
effect of Vd and CL with age
with age, Vd increased because fat increases, and Cl decreases because kidney function decreases,, there for that joint effect creates longer t 1/2
t 1/2= (0.693 x V)/CL
35
Lecture 2: Age and Weight
age on Vd
as you get oder , gain more fat, so Vd increases, especially with drugs with higher lipophilicity. not so much in hydrophilic drugs
36
Lecture 2: Age and Weight
concentrations and EC50
aging patients are more sensitive to lower blood concentrations, which means they would not require as high as a dose as younger pts to reach the same effect.
37
Lecture 2: Age and Weight
aging and PD
aging effects on PD have been reported with increases and decreases in drug sensitivity. no clear trend may be anticipated
38
Lecture 2: Age and Weight
percent of total body weight of baby
water accounts for 80% in babies'TBW.
39
Lecture 2: Age and Weight
changes in metabolic activity
newborns have very limited metabolic activity. don't metabolize drugs well
40
Lecture 2: Age and Weight
Cl and ec50 in neonates
neonates have lower CL, and therefor have lower ec50's. means they are more sensitive to the drug
41
Lecture 2: Age and Weight
dosing of drugs for children < 2 year sold
dosing must be individualized for drugs at ages <2 years old.
42
Lecture 2: Age and Weight
equation for childs maintenance dose
1.5 x ((wt. (kg)child)/70)^0/75 x adult maintenance dose
43
Lecture 2: Age and Weight
pk pid of d- tubocurarine
neonates showed lower Cl, and thus had lower EC50's then infants, children, and adults
44
Lecture 3: Role of Sex (gender) and chronobiology
difference in metabolism tendencies btw M and F..
CYP3A4
CYP2C19
CYP2D6
CYP1A2
cyp3a4: F>M
cyp2c19: F=M
Cyp2d6: F
45
Lecture 3: Role of Sex (gender) and chronobiology
methylprednisolone is met. by cyp3a4. which sex metabolizes faster?
F>M
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Lecture 3: Role of Sex (gender) and chronobiology
cortisol circadian rhythms
women had a lower IC50, meaning they are more sensitive to adrenal suppression.
net response is the same
47
Lecture 3: Role of Sex (gender) and chronobiology
metoprolol and cyp2d6 metabolism
men have higher clearances, so would require more drug.
no differences in PD
48
Lecture 3: Role of Sex (gender) and chronobiology
quinidine and cyp3a4
women were faster metabolizers
women had greater qt elongation (an AE of the drug)
49
Lecture 3: Role of Sex (gender) and chronobiology
seldane (terfenadine)
was toxic to women because seldane has an interaction with ketoconazole. cause huge qt prolongation. causing tornadoes des pointes. leading to death
50
Lecture 3: Role of Sex (gender) and chronobiology
aspirin
women have less stroke prevention, even though decrease of platelet aggregation was the same
51
Lecture 3: Role of Sex (gender) and chronobiology
effect of pregnancy on pK
increased cL: heparin, nifedipine
decreased cL: theophylline, caffeine (both cyp1a substrates)
some no effect: overall, unpredicatable PK differences in pregnancy
52
Lecture 3: Role of Sex (gender) and chronobiology
heparin in pregnancy
increase cL, decreased response
53
Lecture 3: Role of Sex (gender) and chronobiology
COC users and theophylline
drugs that are cyp metabolized have reduced clearance in women taking COC's
cons cause metabolic inhibition. (or decreased clearance)
54
Lecture 3: Role of Sex (gender) and chronobiology
COC users and tizanidine
greater conc. because of cyp1a2 inhibition od coc's
55
Lecture 3: Role of Sex (gender) and chronobiology
COC users and most conjugation enzymes
ex: lorazepam
increased clearance due to induced conjugation by coc
56
Lecture 3: Role of Sex (gender) and chronobiology
circadian rhythm
over 24 hours
| ADME can change depending on the time of day
57
Lecture 3: Role of Sex (gender) and chronobiology
circadian rhythm and renal function
GFR is 20-30% higher during the day than at night.
| many drugs show reduced Clr at night
58
Lecture 3: Role of Sex (gender) and chronobiology
circadian rhythm and 5FU
plasma conc were higher at night because of reduced decreased enzyme activity at night
59
Lecture 3: Role of Sex (gender) and chronobiology
propanolol
plasma conc during the day were high, produced in a good % decreased heart rate, however, when given propranolol at night, the conc were very low, but the response was the same as propranolol given in the day
60
Lecture 3: Role of Sex (gender) and chronobiology
diastolic bp with valsartan
if valsartan is dosed during the day, higher drops of diastolic bp occur than if the valsartan is dosed at night
61
Lecture 3: Role of Sex (gender) and chronobiology
diseased and circadian rhthms
some diseases are exacerbated at certain times of the day.
62
Lecture 3: Role of Sex (gender) and chronobiology
bio markers and circadian rhythms
cortisol: peaks in morning
melatonin: peaks at night
serum IL-6: go up during early morning.
63
Lecture 3: Role of Sex (gender) and chronobiology
acrophase
the peak
64
Lecture 3: Role of Sex (gender) and chronobiology
circatrigintan rhythm
female menstruation rhythm
over a 28 day period
65
Lecture 4: Role of food and Obesity
Theo-24 (theophylline 1500 mg) single dose
theophylline dose usually 500 mg tid. however when theo-24 was used, after r breakfast, it caused a drug release during the food regimen (dose dumping) pt got nausea, repeated vomiting, or severe throbbing headache
66
Lecture 4: Role of food and Obesity
what is a food effect study
give drug with empty stomach and then with food (high fat) and look at pk
67
Lecture 4: Role of food and Obesity
food effect with tizanidine
food decreased plasma concentrations of tizanidine when taken in a capsule dosage form
68
Lecture 4: Role of food and Obesity
FDA and food effect study requirements
no food effect if 90% of Cl of fed/fasted Cmax and AUC rations within 80-125%
69
Lecture 4: Role of food and Obesity
desvenlafaxine
food study showed that there is no food effect
70
Lecture 4: Role of food and Obesity
possible food effects on drug absorption
delayed gastric emptying
stimulated bile flor
changed gi pH
increased splanchnic (GI) blood flow
altered luminal metabolism/ transport of drugs
physically or chemically interact with the dosage form or drug substance (degradation in acidic stomach)
71
Lecture 4: Role of food and Obesity
food effect on gastric emptying
food decreases gastric emptying
72
Lecture 4: Role of food and Obesity
grapefruit
grapefruit contains furanocoumarins, which inactivate GI cyp3a4. loss of first pass effect in the intestine, causing higher concentrations
ex: grapefruitt and simvastatin
how long does it take: ~3 days, but completely about a week
73
Lecture 4: Role of food and Obesity
vitamins
vitamins should always be taken with food. absorbed better
74
Lecture 4: Role of food and Obesity
are drug studies required for obese ppl by the FDA ?
no
75
Lecture 4: Role of food and Obesity
causes of obesity
primary causes: genetic, monogenic, syndromes
76
Lecture 4: Role of food and Obesity
BMI
BMI equation: weight (kg)/Ht (m^2)
```
normal bmi= 19-24
pre obesity: 25-29.9
obesity class I. 30-34.9obesity class II: 35-39.9
obesity class III: 40+
```
77
Lecture 4: Role of food and Obesity
body adiposity index (bai)
measure body fat
78
Lecture 4: Role of food and Obesity
CCl in obesity
CrCl equations for weight
slightly greater in obesity than in ppl with normal weights. kidneys work better because they are struggling to get water out of obese subject, so they work harder
Salazaar equations:
male: [137-age]x[0.285xwt)+(12.1xht^2)]/ (51x Scr)
female: [146-age]x[0.287xwt)+(9.74xht^2)]/ (60x Scr)
79
Lecture 4: Role of food and Obesity
methods of measurementt of %fat or ibw
skin fold calipers
bioimpedence: electric shock through body that can measure % body weight (like a bathroom scale)
estimation of IBW by equations
80
Lecture 4: Role of food and Obesity
drug absorption
no change in drug absorption in obese
81
Lecture 4: Role of food and Obesity
total clearances of compounds eliminated primarily by renal excretion
obesity is accompanied by partial increases in renal function.
account for partial increase is using adjusted body weight
ABW= IBW +0.4 (tbw-ibw)
82
Lecture 4: Role of food and Obesity
volume of distribution
VD depends on lipophilicity Fat and degree of obesity (vfat)
83
Lecture 4: Role of food and Obesity
thiopental in obese pts
cl is difference, but when adjusted for body weight, cl is the same
t 1/2 is larger due to larger Vd and larger log p
thiopental has a logp=3.52, which means it is lipophyllic
84
Lecture 4: Role of food and Obesity
volume of distribution for hydrophilic drugs
vd is about the same
85
Lecture 4: Role of food and Obesity
metabolic cl in obese
unpredicatable. anything can happen. (increase, decrease, constant, enhanced)
reduced cl can happen with some drugs due to obese liver
86
Lecture 4: Role of food and Obesity
methylprednisolone conc. in obese
steroid con. increases
however ic50 for cortisol suppression is not different
87
Lecture 4: Role of food and Obesity
conjugation in obesity
enhanced glucuronide conjugation in obesity. cl most likely to increase for jugs which are conjugated
88
Lecture 4: Role of food and Obesity
lithium Cl in obese
lithium is hydrophilic and mainly excreted by kidneys.
lithium may need larger doses due to increase CrCl in obese ppl
89
Lecture 4: Role of food and Obesity
verapamil and atracurium in obesity
both show increased ec50 with obesity, meaning less sensitivity
90
Lecture 5: smoking
primary effect of tobacco on drugs
induction of hepatic microsomal enzymes
91
Lecture 5: smoking
theophylline and smoking
smokers had exaggerated increase in cL
92
Lecture 5: smoking
thiocyanate
metabolic product of cyanide which is found in tolerance
93
Lecture 5: smoking
2nd hand smoking
passive exposure was to environmental cigarette smoke for atleast 4 hours a day .
saw increases in plasma cotinine (metabolite of nicotine) as well increased Cl
94
Lecture 5: smoking
probable causative compounds for enzyme induction
carcinogenic polycyclic hydrocarbons
95
Lecture 5: smoking
propanolol
metabolized by 2d6. marked decrease in plasma concentration.
enzyme induction more prominent in younger ppl than older ppl
96
Lecture 5: smoking
tizanidine
the effects of tizanidine on bp pressure were weaker in smokers
97
Lecture 5: smoking
trends
mostly unpredictable, but cyp1a substrates are more predictable, but no really
98
Lecture 5: smoking
coc and smoking
cigarettes increase risk of serious cv effects and potential death
99
Lecture 5: smoking
impotence
smoking increases impotence in men
100
Lecture 5: smoking
vitamin use
smokers need more vitamins to have the same serum conc. of non smokers
101
Lecture 5: smoking
OTCs drug use
smokers need and use more OTCs
102
Lecture 5: smoking
smokers face
lines or wrinkles
giantess
atrophic grey appearance
plethoric blue, bloated appearance
103
Lecture 5: smoking
time of enzyme induction in smoking
enzyme induction is slow (3 days to a week).
| also a slow process to return back to normal
104
Lecture 5: enzyme induction
compounds concerned for enzyme induction and what enzymes they induce
```
tobacco
rifampin
COC
anticonvulsants
st johns wort
ompeprazole
ethanol
hiv protease inhibitors
```
a. various
b. various
c. conjugation
d. cyp3a4
e. cyp3a4
f. cyp1a2
g. cyp2e1
h. various
105
Lecture 5: smoking
st johns wort and alprazolam
st johns wort lowers concentration
chronically increases drug metabolism
106
Lecture 5: enzyme induction
| pkpd model for enzyme induction
ksyn->CYP3A4-> kdeg
107
Lecture 5: smoking/ inducers
fda guidance on inducer
what are condiered strong inducers
moderate
weak
all new drugs should undergo cell structuree screening for causation of enzyme induction
strong: >80%
moderate: 50-80%
weak: 20-50%
108
Lecture 5: smoking/ induction
fda guidance which enzymes sensitive to enzyme induction
```
cyp1a2
cyp2b6
cyp2c8
cyp2c9
cyp3a4
```
CYP2D6 NOT SHOWN TO BE SENSITIVE TO ENZYME INDUCTION
109
Lecture 6: Hepatic disease
hepatic diseases
liver cirrhosis:
characterized by over of fibrosis, reduced blood flor, reduced number of active hepatocytes, and impaired albumin ptoduction
Liver cholestasis: below flow from liver to duodenum is hindered, retention of substances normally excreted by bile
hepatitis and primary liver cancer:
110
Lecture 6: Hepatic disease
child pugh score criterias
and score categories
encephalopathy:
ascites
bilirubin
albumin
prothrombin time
class a=5-6 points (least sever liver disease)
class b= 7-9 (moderately sever liver disease)
class c =10-15(most sever liver disease)
111
Lecture 6: Hepatic disease
effect of liver disease on metabolism
radiation in absolute liver cell mass, decrease in enzyme activity
drug uptake in certain cells is impaired
decrease metabolism
112
Lecture 6: Hepatic disease
hepatic enzymes effects from liver disease
cyp2e1: heavily influenced by liver disease
113
Lecture 6: Hepatic disease
biliary nd renal excretion
in pts with chronic liver disease, dosage modification is not only necessary for drugs predominantly cleared by liver, but may also be indicated for renal cleared drugs
drugs and metabolites excreted by bile can accumulate
also cirrhotics have reduced renal plasma flow and GFR
114
Lecture 6: Hepatic disease
general guidelines for optimization of dosing regimen for hepatic diseasepts.
reduction in dose or increase in dosing interval
115
Lecture 6: Hepatic disease
High vs low Cl (extraction ) drug
high Cl drugs: Cl=Qh (he fastest the ever can metabolize is = to blood flow).
high cl drugs are relative insensitive to changes in drug binding or enzyme transporter activity
Low cl drugs: fu x Clint.
116
Lecture 6: Hepatic disease
hepatic drug cl and bioavailability
h cl drug: lower f, which is very sensitive to changes in drug binding and intrinsic clearance
low cl drug: have higher f, which is less sensitive to changes in fu and intrinsic clearance
117
Lecture 6: Hepatic disease
oral clearance vs iv clearance
if drug has high cl and given iv, cl=qh
all other situations ( low cl given iv, or high or low cl given orally ), cl= fu x clint
118
Lecture 6: Hepatic disease
extent of absorption
F, bioavailability
oral bioavailability increases in absorption
ex: chlormethiazole
because you have decreased cl, you increase the bioavailability
119
Lecture 6: Hepatic disease
effect on absorption rate
rate of absorption gets slowed down.
ex: furosemide, due to impaired gastric motility. cirrhosis pts are affected by gastritis and upper git ulcers, which may lead to delayed and unpredictable onset of action
120
Lecture 6: Hepatic disease
protein binding and vd
decreased albumin production by liver in cirrhosis, as well as increased accumulation of endogenous compounds inhibiting plasma protein binding, and qualitative changes in albumin.
drugs that are highly protein bound have higher fu in cirrhosis and higher vd.
if dealing with a drug that has low vd, it does not matter how fu is changed,
if dealing with high vd drug, fu can significantly change the vd
121
Lecture 6: Hepatic disease
total vs unbound concentration
cirrhosis can increase unbound concentrations,
however, it may not change total drug concentrations, because in the equation
css=dose/ (tau x fu x clint) , fu is going up, but clint is going down, keeping the total css appearing the same.
but b/c unbound conc drives pharmacologic effect, the increase in unbound conc can change the effects of the drug significantly without even realizing b/c the total conc is staying the same.
therefor, drug dosages still need to be changed.
Css u equations for oral and iv
oral: cuss= dose/ tau x clint
iv cuss: fu x dose/ q x tau
122
Lecture 6: hepatic disease
css and cssu equations for oral and iv
oral:
css= dose/(tau x fu x clint)
cssu=dose /(tau x clint
iv: css= dose/ tau x Q
cssu= fu x dose/ tau x q
123
Lecture 7: renal disease
how many L of filtrate does the kidney generate a day
how much urine does it generate a day
180 L
2L of urine a day
124
Lecture 7: renal disease
assessment of renal function
Crcl: creatinine a by product of muscle metabolism that is primarily eliminated by glomerular filtration
eGFR
125
Lecture 7: renal disease
Crcl units
overall Crcl would be in ml/min
make sure the SCr is in mg/dl
126
common unit prefix conversions
10^-1: deci : (10)
10^-2: centi (100)
10^-3: milli (1000
10^-6: micro (1000000)
10^-9: nano (1000000000)
127
Lecture 7: renal disease
when to use abw OR IBW
if the abw is less than the ibw, use abw in CRcl equation
if the pt is >65 yo ND SCR IS <1.0, USE 1 TO CALCULATE THE CRCL
if
128
Lecture 7: renal disease
Crcl for obese patients
in obese pts, use actual weight. and the height in meters
1 METER=3.28 FT
if TBW is 30% more than ibw, then they are obese
129
Lecture 7: renal disease
Crcl in children
independent weight formula
schwartz equation
130
Lecture 7: renal disease
non steady state
to estimate Crclin non steady state situation, must measure Scr at 2 different points in time
131
Lecture 7: renal disease
effect on absorption
small effects:
tmax can slightly increase
bioavailability can slightly increase
132
Lecture 7: renal disease
| effect and distribution
acidic drugs ( drugs that bind to albumin, are effected because increase in endogenous substances can decrease albumin, alter albumin, and displace drugs that bind to albumin. obverall increasing fu
basic drugs that bind to AAG protein may not be effected, however they might have a slightly lower fu because aaa is cleared through the kidney. high binding, lower fu.
133
Lecture 7: renal disease
protein binding and vd
vd of a few drugs such as digoxin etc. can increase because of fluid overload in esrd due to increase in fluid overload
134
Lecture 7: renal disease
effect on metabolism
non renal metabolism is effected by esrd because uremic toxins that accumulate can reduce drug metabolizing enzyme activity
however esrd can also effect phase II metabolism
135
Lecture 7: renal disease
renal drug elmination
if renal function goes down, all cl mechanisms through the kidney will go down.
136
Lecture 7: renal disease
fe: fraction excrete unchanged in urine and t 1/2
higher the value of fe, more pronounce the effect of renal failure on drug pk
137
Lecture 7: renal disease
optimization of dosing regimens for renal disease
Detli rule 1:
kunin rule
Detli rule 2:
1. rule 1: if keldepends linearly on gfr. if eel reduces by 1/2, reduces dose by 1/2, but keep the dosing interval
kunin rule 2:
start w. loading dose. then with every half life, give half the dose
Detli rule 2:
do not change dose level, instead, double the dosing interval.
138
c0 equation
c0= dos/vd
139
Lecture 8: endo/exo and other diseases
lidocaine and chi
increased conc due to decreased hepatic perfusion , decreasing liver metabolism of lidocaine
140
Lecture 8: endo/exo and other diseases
pittsburg cocktail and chf
increase in pro inflammatory cytokines like tif a and il-6 can reduce metabolism of drugs
141
Lecture 8: endo/exo and other diseases
vancomycin in chf
low clearance in chf
142
Lecture 8: endo/exo and other diseases
thyroid diseases
hypo and hyper on ADME
HYPO
decrease ADME for the most part except increase serum albumin and agp
HYPER increase ADME for the most part except decrease serum albumin and agp
143
Lecture 8: endo/exo and other diseases
prednisolone in hypethyroidism
decreased bioavailability due to increased gastric emptying
144
Lecture 8: endo/exo and other diseases
antipyrine nd t1/2
hypo t, caused longer t1/2
145
Lecture 8: endo/exo and other diseases
thyroid and renal cl
hyper increases grr and hypo decreases gfr
146
Lecture 8: endo/exo and other diseases
cystic fibrosis ADME
A: absorption not impaired
D: reduced binding
M:many drugs exhibit enhanced clearances
e: many abx exhibit increased cl
147
Lecture 8: endo/exo and other diseases
dicloxacillin in cystic fibrosis
has increased cl also decreased protein binding
148
Lecture 8: endo/exo and other diseases
abx in cf
marked increase in cl, primarily cleared by kidneys
149
Lecture 8: endo/exo and other diseases
eryhtromycin breath test
given radioactive erythrmoycin. metabolized by cyp3a4, and breathed out.
the more breathed out, the more it was metabolized
150
Lecture 8: endo/exo and other diseases
surgery and proinfammatory cytokines
antiancer drugs and chemo
surgery ad inflammation showed decreased metabolism. presented by the erythromycin breathiest.
chemo drugs were metabolized less with increase degree of inflammation
151
Lecture 8: endo/exo and other diseases
naproxen and RA
reduced metabolic cl and decreased protein binding
152
Lecture 9: PKPD models and diabetes
ADME
A: not altered
D: altered albumin, reduced binding
M: liver dysfunction may develop
e: INCREASED GFR, THEN DECREASED GFR
153
Lecture 9: PKPD models and diabetes
EFFECTS OF DIABETES ON PHENYTOIN PK
REDUCED PHENYTOIN PROTEIN BINDING, more free drug available, so they need less drug
154
Lecture 9: PKPD models and diabetes
biologic turnovers
heart rate: fast msec
hormones, mrna: about an hour/hrs
cells: days tissue organs years
155
Lecture 9: PKPD models and diabetes
direct effect models
biophase mpdela
de: rsponses follow along with plasma or biophase conc.
turnover models: responses controlled by turnover
156
Lecture 9: PKPD models and diabetes
cox enzyme turnover after aspirin
aspirin inhibits platelets, and have to wait for turnover to get function again
157
Lecture 9: PKPD models and diabetes
indirect response models
1. inhibit k in (u)
2. inhibit k out (n)
3. stimulate kin (n)
4. stimulation k out
