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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
Primary site of drug metabolism
liver
26
Secondary areas of drug metabolism
kidney proximal tubules, lungs, intestines, testes, skin epithelial cells, brain, plasma
27
Reactions in phase I drug metabolism
oxidation, reduction, hydrolysis
28
Reactions in phase II drug metabolism
conjugation
29
Enzymes and products involved in phase I reactions
products are usually more polar, oxidative processes involve CYPs or esterases, dehydrogenases, deaminases, decarboxylases
30
Action of CYP Inducers
increases enzyme levels to speed up metabolism, quickly lowers plasma levels
31
Action of CYP Inhibitors
inhibit enzyme, slow metabolism of drug which can leac to toxic levels
32
CYP relationship with grapefruit juice
inhibitor of CYP3A4, increases bioavailability of other drugs in intestinal epithelial cells
33
What occurs in phase II, biotransformation reactions?
synthesis reaction, something is added to the molecule; conjugation, acetylation, methylation
34
Action of conjugation in phase II drug metabolism
makes drugs more water soluble and more excretable; glucuronidation (occurs in ER) and sulfation (cytoplasm)
35
Action of acetylation and methylation in phase II drug metabolism
makes drugs less water soluble, tends to reduce drug activity
36
Drug elimination routes
renal (major), nonrenal (bile, sweat, breath, breast milk)
37
Steps in renal drug excretion
glomerular filtration, PASSIVE tubular reabsorption, ACTIVE tubular secretion
38
What drugs can be filtered via glomerular filtration?
small molecule drugs
39
What drugs can be excreted via passive tubular reabsorption
lipid soluble drugs, unionized weak acids and bases
40
How can protein0bound drugs be eliminated?
active tubular secretion
41
Key factors that modify renal drug excretion?
pH-dependent ionization, competition for active tubular transport, age
42
Definition of excretion rate
mass eliminated per unit time; directly related to changes in plasma concentration
43
Definition of clearance
plasma volume from which all solute is removed per time, flow rate; remains constant as plasma concentration changes
44
eGFR equation
{[(140-age) x BW kgs] / (72 x Scr) } (x 0.85 if female)
45
Toxicity definition
extension of therapeutic mechanism of action due to excess drug
46
Side-effect definition
adverse effect seen as doses similar to therapeutic effect, unrelated to therapeutic effect
47
Tolerance definition
reduced response to a drug with continued treatment
48
Tachyphylaxis
rapid tolerance
49
Drug physical dependence
characteristic of chronic tx with some drugs characterized by tolerance and withdrawal sxs
50
Drug-drug interaction definition
phenomenon of one drug increasing or decreasing the effect of another drug
51
Idiosyncrasy definition
unusual response to a drug due to inherited alteration
52
Teratogenic effect
abnormal fetal development due to a drug
53
Two potential consequences of drug-drug interactions
potentiation, antagonism
54
Common AE of drugs
constipation, rash, diarrhea, dizziness, drowsiness, dry mouth, HA, insomnia
55
Are drug allergies related to drug dose?
No
56
How does food impact drug interaction?
can change absorption, metabolism, toxicity, action, or timing of drug administration
57
Examples of organ-specific drug toxicity
liver damage leading to failure, QT prolongation leading to torsades de pointes
58
Requirements for labeling a drug as teratogenic
characteristic malformation, must act during a specific window of vulnerability, incidence should increase with dose and duration of exposure
59
Why is drug-induced carcinogenesis difficult to identify?
may be >20 years before cancer appears
60
Carcinogenic effects of diethylstilbestrol (DES)
originally used to prevent spontaneous abortion in high risk pregnancies, daughters exposed in utero had a high incidence of vaginal and uterine cancers
61
Drug response variation in infants
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
Drug response variation in children
ADE similar to adults, metabolism occurs much faster
63
Drug response variation in geriatrics
changes based on water and fat distribution, plasma albumin levels fall, metabolism and GFR decrease
64
Definition of placebo effect
measurable, observable, or felt improvement in health not attributable to an actual treatment
65
Drug response variation as a result of physiologic changes during pregnancy
decreased bowel tone and motility, increase in absorption; increased hepatic metabolism; increased GFR
66
What drugs can most easily cross the placenta?
lipid soluble drugs
67
Potential adverse reactions during pregnancy
teratogenesis, dependence-producing drugs, drugs that change uterine tone
68
Zero order kinetics occur when...
drug elimination process is saturated; amount of drug related is independent of concentration
69
Equation for zero order kinetics
dCp/dt = k
70
First order kinetics
constant fraction is eliminated over time, drug process is not saturated; mass eliminated is directly related to drug concentration
71
Equation for first order kinetics
dCp/dt = kCp
72
-kel =
(lnCpt2 - Ln Cpt1) / t2 - t1
73
kt1/2 =
0.693
74
Cpt =
Cp0 x e^(-kt)
75
Kel =
Cl/Vd
76
Cl =
(S x F x (Dose/dosing interval)) / Cp
77
What kind of kinetics are displayed in capacity-limited reactions?
zero order initially, first order as drug concentration falls
78
Rate of elimination =
(Vmax x C) / (Km + C)
79
Mean plasma concentration at steady state =
Dosing rate / Cl
80
What is a loading dose?
dose needed to rapidly achieve therapeutic drug concentrations for drugs with long half-life
81
loading dose =
(Cpss x Vd) / (S x F)
82
How does peak concentration change as absorption increases?
higher peak concentration
83
How does peak concentration change with varying doses?
proportionally changes
84
How does peak concentration change as elimination increases?
lower peak concentration

SBL (21 decks)

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