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x F2: IPCS > PK Exam > Flashcards

PK Exam Flashcards

(100 cards)

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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
What is Vt
tissue compartment, slowly equilibrating
26
The initial half life for drugs is the _____ half-life. The terminal half-life is the ______ half-life
alpha beta
27
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 ___
Vd
28
If the target organ during loading doses is in Vi what can occur
toxic events
29
Target organs appear to be in Vi: drugs of lidocaine, quinidine, procainamide what do you do when altering the loading dose
decrease the dose -administer full dose at slow rate -administer in repeated incremental bolus doses
30
Target organs appear to be in Vt: drugs of digoxin and lithium what do you do when altering the loading dose
no empiric dose adjustment must wait for complete distribution to occur to make clinical assessment
31
Drug concentration
in the plasma (Cp) refers to a total amount of drug in the plasma, consisting of drug that is protein-bound and free
32
What does protein binding refer to
drug that is bound to plasma protein
33
What does free or unbound drug refer to
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)
34
How do we assess protein status
albumin other proteins -albumin -prealbumin -total protein
35
What are the factors that determine alpha in protein-binding sites not saturable
plasma-protein concentration binding affinity exception: (salicylates, valproic acid)
36
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
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
37
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
Cp total: 10 mg/L to 5 Fu: 0.1 to 0.2 Cp free: 1 mg/L to 1
38
What are the components of elevated plasma protein concentration
acute phase reactive proteins cirrhosis alpha1-acid glycoproteins (AAG) (follow patients clinical response)
39
What does uremia and phenytoin do to binding affinity
decrease binding affinity net-effect (drug levels and patient response)
40
Monitoring free concentration are uncommon why
limited availability increased cost most patients have normal binding characteristics little data to show better correlation with free than with total
41
As general rule is as alpha increases one should ________ Cp desired by the same proportion
decrease
42
Clearance
represents a theoretical volume of blood or plasma which is totally cleared of drug in a given period of time
43
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
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
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
effect on clearance: increase effect on drug concentration: decrease effect on amount of drug removed: increase effect on patient response: no change
44
What is extraction ratio
less than alpha extr ratio > free drug ratio = less drug available for removal proteins act as carrier to facilitate for removal
45
Drugs that effect renal function
digoxin vancomycin gentamycin
46
Drugs that effect hepatic function
lidocaine
47
Drugs that effect cardiac output
decrease in this causes a decrease in CL blood flow dependent CL drugs
48
Is Cl(renal) and Cl(non-renal) independent of each other
yes
49
What Cl(non-reanl) a metabolite of
hepatic metabolism (but not always)
50
What is first order kinetics
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
What is elimination rate constant (Ke)
fraction or percentage of drug eliminated per unit of time
52
If Cl increase what happens to Ke
increases
53
If Vd increases what happens to Ke
decreases (half-life prolonged)
54
If Cl and Vd change proportionally then Ke does what
stays the same
55
If Cl and Vd change disproportionately then Ke does what
changes
56
Half-life (t1/2)
the time it takes for the total amount of drug in the body or the plasma concentration to decrease by 1/2
57
During steady state and time for drug elimination how many half-lives does it take to complete
4-5
58
What is first order decay represented by
e^-kt
59
At average steady state tao is significantly less than what
t1/2 (helpful for infusion model and intermittent dosing model)
60
What are the 2 assumptions in calculating C(ssmax)
Immediate and complete absorption and distribution
61
What is CrCL
the volume of plasma cleared of creatinine per unit of time
62
What age is elderly classified as
65 yo
63
Age range for young-old, middle-old, old-old
young-old: 54-74 middle-old: 75-84 old-old: 85 and older
64
What are age related factors that affect absorption (elderly)
gastric fluid pH and rate GI blood flow and age related GI disease nutrition
65
Effects of absorption (elderly)
dissolution first pass effect (may be decreased which increase bioavailability)
66
Net effect and clinical significance on absorption (elderly)
rate extent non-oral dosage forms
67
Potential age related factors that may affect distribution (elderly)
body comp (decrease in water, increase in fat) change in multi-compartment model altered protein-binding age-related disease bed rest
68
Net effect and clinical significance on distribution (elderly)
protein-binding hydro-lipo philicity single vs multi compartment
69
Factors that may affect metabolism (elderly)
increase comorbidities, drug use, environment exposure poor nutrition decrease liver mass, hepatic blood flow
70
Effect of age on metabolism
deceased blood flow and liver mass intrinsic metabolic function
71
Net effect and clinical significance of metabolism (elderly)
extraction ratio (high ER drugs will show decreased Cl due to decreased hepatic blood flow) route of elimination
72
Potential age related factor that may affect excretion (elderly)
decreased renal blood flow, kidney mass, intrinsic function
73
Net effect and clinical significance of excretion (elderly)
renal clearance decrease route of elimination dose regimen active metabolite
74
When is there an exception for start low and go slow for elderly
septic shock
75
What are the major reasons a patient will receive dialysis
acidosis electrolyte imbalance ingestion of overdose overload uremia
76
What are the two types of dialysis for CKD
intermittent hemodialysis (IHD) peritoneal dialysis (PD)
77
What are the two types of dialysis for acute kidney injury patients
continuous renal replacement therapy IHD
78
Common PK changes in AKI/Renal/CKD
decreased renal CL and metabolism Increase Vd altered protein binding to uremia
79
How to decrease dose in renal insufficiency
lower Cssmax, higher Cssmin, same Cssave
80
How to extend the interval for renal insufficiency
net result of same Css max/min/ave mimic normal serum concentration
81
Do you have the change the loading dose in renal insufficiency
no except when there is fluid overload and first dose needs to be increased
82
What does dialysis do
removes toxins and waste products from the blood
83
IHD influences on Cl*
Molecular weight (<500 daltons) Protein binding (too large to cross membrane) Flow rate Filter type (high vs low flux)
84
Components of dialysis drug removal*
Vd (unbound fraction) Estimate patients CL Dosing Interval (compare to 1/2 life) Molecular Weight
85
What is standard hemodialysis
maintenance dose (between sessions) Drug removed during dialysis then dose drug post-dialysis and calc replacement dose
86
True or False: IHD and CRRT have significantly different effects on drug clearance
True
87
What is the optimal bacterial killing peak/MIC
>10
88
What is PAE (post-antibiotic effect)
continual suppression of bacterial growth after limied exposure
89
How is Vd effected in aminoglycosides
malnourishment obesity pregnancy ascites ill
90
Tissue compartments in aminoglycosides are generally lower than serum concentration except for what parts of the body
kidney perilymph inner ear urine
91
How to estimate Vd based on weight (aminoglycosides)
use IBW if actual BW < IBW use actual BW morbidly obese use adjusted BW
92
If significant fluid retention has occurred in aminoglycosides how to estimate Vd
use actual BW and Vd (0.25-0.3 L/kg) use IBW and Vd of 0.35 L/kg
93
What is essentially responsible for all drug removal in aminoglycosides
glomerular filtration
94
Normal elimination t1/2 in adults and children for aminoglycosides is how long
2-3 hours
95
What is the conventional method of dosing for gent/tobra
1-2mg/kg q8-12h
96
Principles for extended interval dosing for aminoglycosides
high peak/MIC ratio improve efficacy and resistance PAE increases with increasing concentration longer dosing interval allows for drug-free period
97
What are the limitations not accounted for on the monogram for aminoglycosides
no indication for infection nothing about MIC nothing about severity no pharmaodynamics no synergy
98
How to dose nomogram ER (hartfort) for CrCL 60 and above, 40-59, 30-39, less than 30
DOSE: 7mg/kg INTERVAL: >60: 24h 40-59: 36h 30-39: 48h <30: traditional dosing method
99
Hartford nomogram limitations
one-compartment from traditional dosing methods aminoglycosides at high doses differ significantly similar kinetics are invalid

x F2: IPCS (10 decks)

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