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SBL > Pharmacokinetics > Flashcards

Pharmacokinetics Flashcards

1
Q

Factors that determine the intensity of a drug response

A

prescribed dose, administered dose, concentration at sites of action

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2
Q

four key factors of pharmacokinetics

A

absorption, distribution, metabolism, excretion

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3
Q

Ways physicians can promote compliance

A

simplified regimen, clear and concise instructions, daily reminders, support system, pay attention to cost

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4
Q

Types of medication errors

A

wrong patient, drug, route, dose, etc; wrong technique; wrong dosage form; use of expired drug

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5
Q

Factors that affect drug absorption

A

rate of dissolution, surface area, blood flow, lipid solubility and pH partitioning

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6
Q

Enteral route examples

A

oral, rectal, buccal or sublingual

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7
Q

Parenteral route examples

A

IV, IM, subcutaneous

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8
Q

Three common ways for drugs to cross the cell membrane

A

facilitated diffusion, active transport, direct penetration (simple diffusion)

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9
Q

Polar drug characteristics

A

fixed charge or separation of charge, cannot readily cross cell membranes, readily dissolve in polar solvents

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10
Q

Nonpolar drug characteristics

A

readily dissolve in nonpolar solvents, readily cross cell membranes

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11
Q

pKa

A

equivalent to the pH when one half of weak acid is ionized

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12
Q

How can weak acids and bases cross membranes?

A

in their unionized form (HA)

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13
Q

Ka

A

rate constant for absorption

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14
Q

S

A

salt factor

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15
Q

F

A

bioavailability, fraction of drug that reaches the blood stream; measured as AUCrout/AUCiv

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16
Q

amount absorbed =

A

SxFxDose

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17
Q

Concentration in plasma (Cp) =

A

(SxFxDose)/Vd

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18
Q

Volume of distribution (Vd) =

A

amount of drug in body / Cp

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19
Q

Male TBW approx

A

60% body weight in kg

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20
Q

Female TBW approx

A

55% body weight in kg

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21
Q

ECV approx

A

1/3 x TBW

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22
Q

Plasma volume approx

A

25% x ECV

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23
Q

Sites of peripheral drug concentration

A

fat, tissue, bone, transcellular reservoirs

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24
Q

Factors affecting drug distribution

A

ability of drugs to enter cells, blood flow tissues, ability of drugs to exit the vascular system

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25
Q

Primary site of drug metabolism

A

liver

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26
Q

Secondary areas of drug metabolism

A

kidney proximal tubules, lungs, intestines, testes, skin epithelial cells, brain, plasma

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27
Q

Reactions in phase I drug metabolism

A

oxidation, reduction, hydrolysis

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28
Q

Reactions in phase II drug metabolism

A

conjugation

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29
Q

Enzymes and products involved in phase I reactions

A

products are usually more polar, oxidative processes involve CYPs or esterases, dehydrogenases, deaminases, decarboxylases

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30
Q

Action of CYP Inducers

A

increases enzyme levels to speed up metabolism, quickly lowers plasma levels

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31
Q

Action of CYP Inhibitors

A

inhibit enzyme, slow metabolism of drug which can leac to toxic levels

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32
Q

CYP relationship with grapefruit juice

A

inhibitor of CYP3A4, increases bioavailability of other drugs in intestinal epithelial cells

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33
Q

What occurs in phase II, biotransformation reactions?

A

synthesis reaction, something is added to the molecule; conjugation, acetylation, methylation

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34
Q

Action of conjugation in phase II drug metabolism

A

makes drugs more water soluble and more excretable; glucuronidation (occurs in ER) and sulfation (cytoplasm)

35
Q

Action of acetylation and methylation in phase II drug metabolism

A

makes drugs less water soluble, tends to reduce drug activity

36
Q

Drug elimination routes

A

renal (major), nonrenal (bile, sweat, breath, breast milk)

37
Q

Steps in renal drug excretion

A

glomerular filtration, PASSIVE tubular reabsorption, ACTIVE tubular secretion

38
Q

What drugs can be filtered via glomerular filtration?

A

small molecule drugs

39
Q

What drugs can be excreted via passive tubular reabsorption

A

lipid soluble drugs, unionized weak acids and bases

40
Q

How can protein0bound drugs be eliminated?

A

active tubular secretion

41
Q

Key factors that modify renal drug excretion?

A

pH-dependent ionization, competition for active tubular transport, age

42
Q

Definition of excretion rate

A

mass eliminated per unit time; directly related to changes in plasma concentration

43
Q

Definition of clearance

A

plasma volume from which all solute is removed per time, flow rate; remains constant as plasma concentration changes

44
Q

eGFR equation

A

{[(140-age) x BW kgs] / (72 x Scr) } (x 0.85 if female)

45
Q

Toxicity definition

A

extension of therapeutic mechanism of action due to excess drug

46
Q

Side-effect definition

A

adverse effect seen as doses similar to therapeutic effect, unrelated to therapeutic effect

47
Q

Tolerance definition

A

reduced response to a drug with continued treatment

48
Q

Tachyphylaxis

A

rapid tolerance

49
Q

Drug physical dependence

A

characteristic of chronic tx with some drugs characterized by tolerance and withdrawal sxs

50
Q

Drug-drug interaction definition

A

phenomenon of one drug increasing or decreasing the effect of another drug

51
Q

Idiosyncrasy definition

A

unusual response to a drug due to inherited alteration

52
Q

Teratogenic effect

A

abnormal fetal development due to a drug

53
Q

Two potential consequences of drug-drug interactions

A

potentiation, antagonism

54
Q

Common AE of drugs

A

constipation, rash, diarrhea, dizziness, drowsiness, dry mouth, HA, insomnia

55
Q

Are drug allergies related to drug dose?

56
Q

How does food impact drug interaction?

A

can change absorption, metabolism, toxicity, action, or timing of drug administration

57
Q

Examples of organ-specific drug toxicity

A

liver damage leading to failure, QT prolongation leading to torsades de pointes

58
Q

Requirements for labeling a drug as teratogenic

A

characteristic malformation, must act during a specific window of vulnerability, incidence should increase with dose and duration of exposure

59
Q

Why is drug-induced carcinogenesis difficult to identify?

A

may be >20 years before cancer appears

60
Q

Carcinogenic effects of diethylstilbestrol (DES)

A

originally used to prevent spontaneous abortion in high risk pregnancies, daughters exposed in utero had a high incidence of vaginal and uterine cancers

61
Q

Drug response variation in infants

A

Varied ADME; low albumin gives rise to higher free levels of protein bound drug, blood-brain barrier not fully developed, low hepatic metabolism and renal excretion

62
Q

Drug response variation in children

A

ADE similar to adults, metabolism occurs much faster

63
Q

Drug response variation in geriatrics

A

changes based on water and fat distribution, plasma albumin levels fall, metabolism and GFR decrease

64
Q

Definition of placebo effect

A

measurable, observable, or felt improvement in health not attributable to an actual treatment

65
Q

Drug response variation as a result of physiologic changes during pregnancy

A

decreased bowel tone and motility, increase in absorption; increased hepatic metabolism; increased GFR

66
Q

What drugs can most easily cross the placenta?

A

lipid soluble drugs

67
Q

Potential adverse reactions during pregnancy

A

teratogenesis, dependence-producing drugs, drugs that change uterine tone

68
Q

Zero order kinetics occur when…

A

drug elimination process is saturated; amount of drug related is independent of concentration

69
Q

Equation for zero order kinetics

A

dCp/dt = k

70
Q

First order kinetics

A

constant fraction is eliminated over time, drug process is not saturated; mass eliminated is directly related to drug concentration

71
Q

Equation for first order kinetics

A

dCp/dt = kCp

72
Q

-kel =

A

(lnCpt2 - Ln Cpt1) / t2 - t1

73
Q

kt1/2 =

74
Q

Cpt =

A

Cp0 x e^(-kt)

75
Q

Kel =

76
Q

Cl =

A

(S x F x (Dose/dosing interval)) / Cp

77
Q

What kind of kinetics are displayed in capacity-limited reactions?

A

zero order initially, first order as drug concentration falls

78
Q

Rate of elimination =

A

(Vmax x C) / (Km + C)

79
Q

Mean plasma concentration at steady state =

A

Dosing rate / Cl

80
Q

What is a loading dose?

A

dose needed to rapidly achieve therapeutic drug concentrations for drugs with long half-life

81
Q

loading dose =

A

(Cpss x Vd) / (S x F)

82
Q

How does peak concentration change as absorption increases?

A

higher peak concentration

83
Q

How does peak concentration change with varying doses?

A

proportionally changes

84
Q

How does peak concentration change as elimination increases?

A

lower peak concentration

SBL (21 decks)

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