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IPCS > PK Exam > Flashcards

PK Exam Flashcards

1
Q

What is applied pharmacokinetics

A

the process of optimizing drug therapy in individual patients

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2
Q

What are the variables of drugs usually monitored serum concentration measurement

A

correlation btw serum concentration and efficacy and toxicity
low therapeutic index
variable pharmacokinetics and pharmacodynamics

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3
Q

What are the pharmacokinetics principles

A

variability (drug to drug, pt to pt)
prospective vs retrospective assessment
ADME

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4
Q

What are the pharmacodynamic principles: assumptions

A

dose response curve
receptor theory
free drug concentration at site of action vs total drug concentration in plasma/serum

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5
Q

What are the pharmacodynamic principles: variability

A

physiologic agonist/antagonist
genetic factors
severity of disease
distribution to site of action
protein binding
tolerance
active metabolites

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6
Q

What is the overall goal of serum concentration monitoring

A

utilize serum concentration as an aid in optimizing drug therapy in individual pts to max probability of desired effect and min toxicity

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7
Q

What is the key point of applied pharmacokinetics

A

the patients response is more important than the absolute serum concentration

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8
Q

What are the common misconceptions of therapeutic ranges

A

efficacy (always have even in range)
toxicity (always have even in range)
therapeutic range never changes (it can)
***ranges need to be individualized, everyone is different

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9
Q

What is bioavailability (F)

A

the percentage or fraction of the administered dose that reaches the systemic circulation of the patient

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10
Q

Bioavailability estimates only the extent of absorption; not the _____ of absorption

A

rate

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11
Q

What is chemical form (S)

A

drugs administered as a salt form of the active compound: must multiple by factor that represents percentage of active compound

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12
Q

What does the first pass effect describe

A

hepatic metabolism of drug before reaching the ststemic circulation

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13
Q

What is the first pass effect on bioavailability

A

end result on dose and administration

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14
Q

What is administration rate (RA)

A

average rate at which absorbed drug reaches the systemic circulation

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15
Q

What is volume of distribution (Vd)

A

the size of a compartment necessary to account for the total amount of drug in the body if it were present throughout the body at the same concentration found in plasma

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16
Q

What does low lipid solubility have to do with volume of distribution

A

smaller

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17
Q

What does high lipid solubility have to do with volume of distribution

A

larger

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18
Q

What does low protein binding have to do with volume of distribution (plasma)

A

larger

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19
Q

What does high protein binding have to do with volume of distribution (plasma)

A

smaller

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20
Q

What does low tissue binding have to do with volume of distribution

A

smaller

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21
Q

What does low tissue binding have to do with volume of distribution

A

larger

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22
Q

Factors that alter Vd and dosing: decreased tissue binding

A

mat occur in uremic patients with drugs like digoxin, decreases Vd, higher plasma concentrations, and decrease loading doses in uremic patient

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23
Q

Factors that alter Vd and dosing: decreased plasma protein binding

A

increase Vd which decreases plasma concentrations, fraction of free drug will increase, no adjustment needed

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24
Q

What is Vi

A

the initial compartment, rapid equilibrating compartment - blood and organs/tissues with high blood flow

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25
Q

What is Vt

A

tissue compartment, slowly equilibrating

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26
Q

The initial half life for drugs is the _____ half-life. The terminal half-life is the ______ half-life

A

alpha
beta

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27
Q

During a loading dose if the loading dose is calculated based on Vd, the initial observed plasma concentration may be higher than predicted, as Vi is smaller than ___

A

Vd

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28
Q

If the target organ during loading doses is in Vi what can occur

A

toxic events

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29
Q

Target organs appear to be in Vi: drugs of lidocaine, quinidine, procainamide what do you do when altering the loading dose

A

decrease the dose
-administer full dose at slow rate
-administer in repeated incremental bolus doses

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30
Q

Target organs appear to be in Vt: drugs of digoxin and lithium what do you do when altering the loading dose

A

no empiric dose adjustment
must wait for complete distribution to occur to make clinical assessment

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31
Q

Drug concentration

A

in the plasma (Cp) refers to a total amount of drug in the plasma, consisting of drug that is protein-bound and free

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32
Q

What does protein binding refer to

A

drug that is bound to plasma protein

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33
Q

What does free or unbound drug refer to

A

drug that is not bound by plasma protein, drug that is able to interact at the receptor site, and is therefore pharmacologically active (alpha or Fu)

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34
Q

How do we assess protein status

A

albumin
other proteins
-albumin
-prealbumin
-total protein

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35
Q

What are the factors that determine alpha in protein-binding sites not saturable

A

plasma-protein concentration
binding affinity
exception: (salicylates, valproic acid)

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36
Q

Low plasma protein concentration effect on bound drug, effect on Vd, effect on total drug concentration, effect on fraction of free drug,
net effect on free drug

A

effect on bound drug: decrease
effect on Vd: increase
effect on total drug concentration: decrease
effect on fraction of free drug: increase
net effect on free drug: no effect

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37
Q

What does normal levels of Cp total, Fu, and Cp free change to during low plasma protein when albumin decreases from 5 g/dL to 2.5 g/dL

A

Cp total: 10 mg/L to 5
Fu: 0.1 to 0.2
Cp free: 1 mg/L to 1

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38
Q

What are the components of elevated plasma protein concentration

A

acute phase reactive proteins
cirrhosis
alpha1-acid glycoproteins (AAG)
(follow patients clinical response)

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39
Q

What does uremia and phenytoin do to binding affinity

A

decrease binding affinity
net-effect (drug levels and patient response)

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40
Q

Monitoring free concentration are uncommon why

A

limited availability
increased cost
most patients have normal binding characteristics
little data to show better correlation with free than with total

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41
Q

As general rule is as alpha increases one should ________ Cp desired by the same proportion

A

decrease

42
Q

Clearance

A

represents a theoretical volume of blood or plasma which is totally cleared of drug in a given period of time

43
Q

In body size of a larger individual what is the effect of clearance adjusted on body weight, clearance adjusted on body surface area, effect on clearance, effect on drug concentration, effect on amount of drug removed at steady state, effect on patient response at steady state

A

effect of clearance adjusted on body weight: increase
clearance adjusted on body surface area: increase
effect on clearance: increase
effect on drug concentration: decrease
effect on amount of drug removed at steady state: equal
effect on patient response at steady state: decrease

44
Q

During diminished protein binding (with a highly protein-bound drug what is the effect on clearance, effect on drug concentration, effect on amount of drug removed, effect on patient response

A

effect on clearance: increase
effect on drug concentration: decrease
effect on amount of drug removed: increase
effect on patient response: no change

44
Q

What is extraction ratio

A

less than alpha
extr ratio > free drug ratio = less drug available for removal
proteins act as carrier to facilitate for removal

45
Q

Drugs that effect renal function

A

digoxin
vancomycin
gentamycin

46
Q

Drugs that effect hepatic function

A

lidocaine

47
Q

Drugs that effect cardiac output

A

decrease in this causes a decrease in CL
blood flow dependent CL drugs

48
Q

Is Cl(renal) and Cl(non-renal) independent of each other

A

yes

49
Q

What Cl(non-reanl) a metabolite of

A

hepatic metabolism (but not always)

50
Q

What is first order kinetics

A

a process in which drug amounts or concentration diminish logarithmically (amount of drug eliminated per unit of time changes, but fraction of eliminated drug stays the same)

51
Q

What is elimination rate constant (Ke)

A

fraction or percentage of drug eliminated per unit of time

52
Q

If Cl increase what happens to Ke

A

increases

53
Q

If Vd increases what happens to Ke

A

decreases (half-life prolonged)

54
Q

If Cl and Vd change proportionally then Ke does what

A

stays the same

55
Q

If Cl and Vd change disproportionately then Ke does what

A

changes

56
Q

Half-life (t1/2)

A

the time it takes for the total amount of drug in the body or the plasma concentration to decrease by 1/2

57
Q

During steady state and time for drug elimination how many half-lives does it take to complete

A

4-5

58
Q

What is first order decay represented by

A

e^-kt

59
Q

At average steady state tao is significantly less than what

A

t1/2
(helpful for infusion model and intermittent dosing model)

60
Q

What are the 2 assumptions in calculating C(ssmax)

A

Immediate and complete absorption and distribution

61
Q

What is CrCL

A

the volume of plasma cleared of creatinine per unit of time

62
Q

What age is elderly classified as

A

65 yo

63
Q

Age range for young-old, middle-old, old-old

A

young-old: 54-74
middle-old: 75-84
old-old: 85 and older

64
Q

What are age related factors that affect absorption (elderly)

A

gastric fluid pH and rate
GI blood flow and age related GI disease
nutrition

65
Q

Effects of absorption (elderly)

A

dissolution
first pass effect (may be decreased which increase bioavailability)

66
Q

Net effect and clinical significance on absorption (elderly)

A

rate
extent
non-oral dosage forms

67
Q

Potential age related factors that may affect distribution (elderly)

A

body comp (decrease in water, increase in fat)
change in multi-compartment model
altered protein-binding
age-related disease
bed rest

68
Q

Net effect and clinical significance on distribution (elderly)

A

protein-binding
hydro-lipo philicity
single vs multi compartment

69
Q

Factors that may affect metabolism (elderly)

A

increase comorbidities, drug use, environment exposure
poor nutrition
decrease liver mass, hepatic blood flow

70
Q

Effect of age on metabolism

A

deceased blood flow and liver mass
intrinsic metabolic function

71
Q

Net effect and clinical significance of metabolism (elderly)

A

extraction ratio (high ER drugs will show decreased Cl due to decreased hepatic blood flow)
route of elimination

72
Q

Potential age related factor that may affect excretion (elderly)

A

decreased renal blood flow, kidney mass, intrinsic function

73
Q

Net effect and clinical significance of excretion (elderly)

A

renal clearance decrease
route of elimination
dose regimen
active metabolite

74
Q

When is there an exception for start low and go slow for elderly

A

septic shock

75
Q

What are the major reasons a patient will receive dialysis

A

acidosis
electrolyte imbalance
ingestion of overdose
overload
uremia

76
Q

What are the two types of dialysis for CKD

A

intermittent hemodialysis (IHD)
peritoneal dialysis (PD)

77
Q

What are the two types of dialysis for acute kidney injury patients

A

continuous renal replacement therapy
IHD

78
Q

Common PK changes in AKI/Renal/CKD

A

decreased renal CL and metabolism
Increase Vd
altered protein binding to uremia

79
Q

How to decrease dose in renal insufficiency

A

lower Cssmax, higher Cssmin, same Cssave

80
Q

How to extend the interval for renal insufficiency

A

net result of same Css max/min/ave
mimic normal serum concentration

81
Q

Do you have the change the loading dose in renal insufficiency

A

no except when there is fluid overload and first dose needs to be increased

82
Q

What does dialysis do

A

removes toxins and waste products from the blood

83
Q

IHD influences on Cl*

A

Molecular weight (<500 daltons)
Protein binding (too large to cross membrane)
Flow rate
Filter type (high vs low flux)

84
Q

Components of dialysis drug removal*

A

Vd (unbound fraction)
Estimate patients CL
Dosing Interval (compare to 1/2 life)
Molecular Weight

85
Q

What is standard hemodialysis

A

maintenance dose (between sessions)
Drug removed during dialysis then dose drug post-dialysis and calc replacement dose

86
Q

True or False: IHD and CRRT have significantly different effects on drug clearance

A

True

87
Q

What is the optimal bacterial killing peak/MIC

A

> 10

88
Q

What is PAE (post-antibiotic effect)

A

continual suppression of bacterial growth after limied exposure

89
Q

How is Vd effected in aminoglycosides

A

malnourishment
obesity
pregnancy
ascites
ill

90
Q

Tissue compartments in aminoglycosides are generally lower than serum concentration except for what parts of the body

A

kidney
perilymph
inner ear
urine

91
Q

How to estimate Vd based on weight (aminoglycosides)

A

use IBW
if actual BW < IBW use actual BW
morbidly obese use adjusted BW

92
Q

If significant fluid retention has occurred in aminoglycosides how to estimate Vd

A

use actual BW and Vd (0.25-0.3 L/kg)
use IBW and Vd of 0.35 L/kg

93
Q

What is essentially responsible for all drug removal in aminoglycosides

A

glomerular filtration

94
Q

Normal elimination t1/2 in adults and children for aminoglycosides is how long

A

2-3 hours

95
Q

What is the conventional method of dosing for gent/tobra

A

1-2mg/kg q8-12h

96
Q

Principles for extended interval dosing for aminoglycosides

A

high peak/MIC ratio improve efficacy and resistance
PAE increases with increasing concentration
longer dosing interval allows for drug-free period

97
Q

What are the limitations not accounted for on the monogram for aminoglycosides

A

no indication for infection
nothing about MIC
nothing about severity
no pharmaodynamics
no synergy

98
Q

How to dose nomogram ER (hartfort) for CrCL 60 and above, 40-59, 30-39, less than 30

A

DOSE: 7mg/kg
INTERVAL:
>60: 24h
40-59: 36h
30-39: 48h
<30: traditional dosing method

99
Q

Hartford nomogram limitations

A

one-compartment from traditional dosing methods
aminoglycosides at high doses differ significantly
similar kinetics are invalid

IPCS (9 decks)

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