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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

26
Q

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

A

alpha
beta

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

28
Q

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

A

toxic events

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

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

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

32
Q

What does protein binding refer to

A

drug that is bound to plasma protein

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)

34
Q

How do we assess protein status

A

albumin
other proteins
-albumin
-prealbumin
-total protein

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)

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

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

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)

39
Q

What does uremia and phenytoin do to binding affinity

A

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

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

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

IPCS (5 decks)

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