Pharmacokinetics Flashcards
1
Q
What relationship does pharmacokinetics describe?
A
dose - concentration
2
Q
What relationship does pharmacodynamics describe?
A
concentration - effect
3
Q
What is pharmacokinetics?
A
What the BODY does to the DRUG
4
Q
What are the 4 components of pharmacokinetics?
A
Absorption, Distribution, Metabolism, Excretion
5
Q
What is Fick’s Law of Diffusion?
A
Rate of Diffusion = Concentration Gradient * Surface Area * Diffusion Coefficient / Membrane Thickness
6
Q
The rate of diffusion is directly proportional to what?
A
Concentration Gradient, Surface Area, and Diffusion Coefficient
7
Q
The rate of diffusion is inversely proportional to what?
A
Membrane Thickness
8
Q
What is bioavailability?
A
The fraction of unchanged drug that reaches systemic circulation aka the free drug available to a receptor
9
Q
What is the equation for determining bioavailability (F)?
A
F = Bioavailable dose / Administered dose * 100
10
Q
What is the bioavailability of medications given via the oral route?
A
5-100%
11
Q
What is First Pass Hepatic Metabolism?
A
Medications are first distributed through the portal vein to the liver where they are then secreted in the bile leading to low bioavailability
12
Q
What is the bioavailability of medications given via sublingual/buccal routes?
A
60-100%
13
Q
What is the bioavailability of medications given via intranasal route?
A
up to 95%
14
Q
What is the bioavailability of medications given via the rectal route?
A
30-100%
15
Q
What routes of administration are subject to First Pass Hepatic Metabolism?
A
Oral, proximal rectal
16
Q
What is the bioavailability of medications given via SQ/IM routes?
A
75-100%
17
Q
What is the bioavailability of medications given via the IV route?
A
100%
18
Q
What are the molecule requirements for a medication to be given transdermally?
A
lipid & water soluble, MW <1000, dose <10 mg over 24 hours, pH 7-9
19
Q
Where do the veins in the mouth drain?
A
SVC
20
Q
What body type has the highest percentage of BW as water?
A
Infants 70%
21
Q
What is the volume of total body water?
A
42 liters
22
Q
What is the volume of plasma?
A
4 liters
23
Q
What is K12?
A
movement from the central to the peripheral compartment
24
Q
What is K21?
A
movement from the peripheral to the central compartment
25
What drug properties affect the volume of distribution?
plasma protein binding, ionization, lipid solubility
26
What is the equation for the volume of distribution?
amount of drug / desired plasma concentration
27
Do lipid or water soluble meds require higher doses to distribute?
lipid soluble meds
28
What is aqueous diffusion?
driven by concentration gradient across membrane for lipid insoluble meds
29
What is lipid diffusion?
driven by concentration gradient across phospholipid bilayers
30
What is active transport?
driven by sodium pump using ATP
31
What is facilitated diffusion?
passive action without using ATP using special carriers
32
What is endocytosis?
the wall of a membrane engulfs the molecule within the cell (phago-solids, pino-liquids)
33
What can protein binding affect?
distribution of the drug, potency, elimination
34
What are the 3 main proteins for plasma protein binding?
albumin, alpha1-acidglycoprotein (AAG), beta-globulins
35
Does albumin bind to acidic or basic drugs?
acidic (Thiopental)
36
Does AAG bind to acidic or basic drugs?
basic (local anesthetics)
37
Factors that decrease albumin will INCREASE or DECREASE the amount of free drug.
INCREASE
38
Factors that increase AAG will INCREASE or DECREASE bioavailability and require a SMALLER or LARGER dose.
DECREASE, LARGER
39
Vd is DIRECTLY or INVERSELY proportionate to the amount of protein binding?
INVERSELY
40
Do polar molecules have GOOD or POOR lipid solubility?
POOR
41
Drugs that are more ionized are LIPID/WATER soluble and POLAR/NONPOLAR.
water-soluble and polarized
42
True/False: Ionized molecules have a positive or negative charge.
True
43
True/False: Ionized molecules readily cross membranes.
False
44
True/False: Ionized molecules repel cells with similar charges.
True
45
Ionized/Nonionized: Pharmacologically active.
nonionized
46
Ionized/Nonionized: Easily cross lipid barriers
nonionized
47
Ionized/Nonionized: Easily metabolized.
nonionized
48
Ionized/Nonionized: Excreted by the kidneys.
ionized
49
What type of molecule is reabsorbed into the body through the nephron?
lipid soluble
50
What is pKa?
the pH when 50% of the drug is ionized and 50% of the drug is nonionized
51
Weak acids form salts with POSITIVE or NEGATIVE ions?
positive
52
What ions are positive?
sodium (Na+), magnesium (Mg++), and calcium (Ca++)
53
Weak bases form salts with POSITIVE or NEGATIVE ions?
negative
54
What ions are negative?
sulfate (SO--), chloride (Cl-)
55
Do acids donate or accept protons?
donate
56
If an acidic drug is put into a basic solution, does it become more ionized or nonionized?
ionized
57
If an acidic drug is put into an acidic solution, does it become more ionized or nonionized?
nonionized
58
If an acid has a higher pKa, is there more ionized or nonionized form of the drug?
nonionized
59
If a basic drug is put into an acidic solution, does it become more ionized or nonionized?
ionized
60
If a basic drug is put into a basic solution, does it become more ionized or nonionized?
nonionized
61
If a base has a lower pKa, is there more ionized or nonionized form of the drug?
nonionized
62
What two things affect biotransformation?
intrinisic rate and concentration of the drug
63
What is phase 1 of biotransformation?
Modification via oxidation, reduction, or hydroloysis
64
What is phase 2 of biotransformation?
Conjugation
65
In what way does oxidation work?
via the loss of an electron using the P450 system
66
In what way does reduction work?
via the addition of an electron using the P450 system
67
In what way does hydrolysis work?
by breaking a compound into 2 parts by adding water
68
Where in the body does hydrolysis work?
plasma (most common), stomach
69
What medications are metabolized through hydrolysis?
remifentanil, succinylcholine, esmolol, ester local anesthetics
70
In premature infants, is conjugation DECREASED or INCREASED leading to DECREASED or INCREASED frequency of administration?
decreased, decreased
71
Phase II reactions use what enzymes?
glucuronosyl transferases, sulftransferases, N-acetyltransferases (NAT)
72
What hepatic microsomal enzyme is responsible for >50% of anesthesia medications?
3A4
73
What is a medication that its active metabolites continue to work in the body?
morphine
74
What is a prodrug?
A drug that is inactive in its parent form and becomes active once going through phase 1 metabolism
75
What are 2 examples of a prodrug?
fospropofol and codeine
76
How does an inducer affect the P450 system?
speeds up function of the enzyme leading to increased clearance and decreased half-life
77
If a P450 enzyme is induced, does the frequency of drug need to be INCREASED or DECREASED?
increased
78
If a P450 enzyme is inhibited, does the frequency of drug need to be INCREASED or DECREASED?
decreased
79
How does an inhibitor affect the P450 system?
decreases function of the enzyme leading to decreased clearance and increased half-life
80
What are some CPY 3A4 inducers?
Ethanol (chronic), Carbamazepine, Rifampin, St John's Wart, Tamoxifen, Barbituates
81
What are some CPY 3A4 inhibitors?
Azole antifungals, Erythromycin, Grapefruit juice, SSRIs
82
What are some CYP 2D6 inducers?
Phenytoin, Carbamazepine, Dexamethasone
83
What are some CYP 2D6 inhibitors?
Isoniazid, SSRIs, Quinidine
84
Is the genetic variability of having red hair an inducer or inhibitor of the P450 system?
inducer - needs higher dosages
85
Drugs that are water soluble tend to be MORE or LESS POLAR and MORE or LESS ionized?
MORE, MORE
86
Drugs that are lipid soluble tend to be MORE or LESS polar and MORE or LESS ionized?
LESS, LESS
87
What type of molecule is the most common type in anesthesia to cross a lipid membrane?
lipophilic molecule
88
True/False: Highly lipophilic drugs have a higher Vd requiring a decreased dosage.
False, requires an increased dosage
89
True/False: Plasma protein binding is non-competitive.
False
90
True/False: Intranasal cocaine given in the OR is subject to First Pass Hepatic Metabolism.
False, goes directly into vasculature
90
True/False: Intranasal cocaine given in the OR is subject to First Pass Hepatic Metabolism.
False, goes directly into vasculature
91
Besides pain control, what other reason is Fentanyl given during RSI?
blunts laryngeal spasms
92
Besides preventing pain during the administration of Propofol, what other reason is Lidocaine given during RSI?
blunts laryngeal spasms
93
Why is Midazolam a better choice than Diazepam for RSI?
Diazepam lasts longer due to active metabolites
94
Why is a higher first dose or bolus dose needed with Propofol?
highly lipid soluble, distributes out to fat
95
Why is Succynylcholine still used despite better NMBD?
quicker onset, shorter duration for learners
96
Which NMBD is depolarizing?
Succinylcholine
97
What does having atypical cholinesterase cause?
unable to metabolize succinylcholine, increased time paralyzed
98
A drug with a Vd that is less than total body water is assumed to be...
hydrophilic
99
A drug with a Vd that exceeds total body water is assumed to be...
lipophilic
100
Clearance of a drug is directly proportional to...
drug dose, extraction ratio, and blood flow to target organ
101
Clearance of a drug is inversely proportional to...
half-life and drug concentration
102
After how many half-times is steady-state achieved?
5
103
What is elimination half-life?
The time it takes for 50% of the drug to be eliminated from the body
104
What is elimination half-time?
The time it takes for 50% of the drug to be removed from the plasma
105
What conditions decrease protein concentrations leading to higher bioavailability?
liver disease, renal disease, old age, malnutrition, and pregnancy
106
What is zero order kinetics?
A constant AMOUNT of a drug is metabolized per unit of time; more drug than enzyme
107
What is first order kinetics?
A constant FRACTION of the drug is metabolized per unit of time; less drug than enzyme
108
What are some drugs that follow zero order kinetics?
aspirin, phenytoin, alcohol, warfarin, heparin, theophylline
109
The purpose of metabolism is to change a WATER or LIPID SOLUBLE, pharmacologically ACTIVE or INACTIVE compound into a WATER or LIPID SOLUBLE, pharmacologically ACTIVE or INACTIVE byproduct.
Lipid, active: water, inactive
110
A drug with a high hepatic extraction ration (>0.7), clearance is dependent on...
liver blood flow
111
A drug with a low hepatic extraction ratio (<0.3), clearance is dependent on...
the ability of the liver to extract the drug from the blood
112
What is the equation for creatinine clearance?
(140-age) * weight / 72 * SCr
(* 0.85 if female)
113
A drug with a Vd that exceeds total body water is assumed to be lipophilic OR hydrophilic?
Lipophilic
114
A drug with a Vd that is less than total body water is assumed to be lipophilic OR hydrophilic?
Hydrophilic
115
Hydrophilic drugs need a lower OR higher dose to achieve the desired plasma concentration?
Lower
116
Lipophilic drugs need a lower OR higher drug dose to achieve the desired plasma concentration?
Higher
Distributes out to the fat as well as the rest of the body
117
What drugs have a low hepatic extraction ratio?
Rocuronium
Diazepam
Lorazepam
Methadone
Thiopental
Theophylline
Phenytoin
118
What drugs have a high hepatic extraction ratio?
Fentanyl
Sufentanil
Morphine
Meperidine
Naloxone
Ketamine
Propofol
Lidocaine
Bupivacaine
Metoprolol
Propranolol
Alprenolol
Nifedipine
Diltiazem
Verapamil
