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Pharmacology Exam 1 > Pharmacokinetics > Flashcards

Pharmacokinetics Flashcards

1
Q

What relationship does pharmacokinetics describe?

A

dose - concentration

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2
Q

What relationship does pharmacodynamics describe?

A

concentration - effect

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3
Q

What is pharmacokinetics?

A

What the BODY does to the DRUG

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4
Q

What are the 4 components of pharmacokinetics?

A

Absorption, Distribution, Metabolism, Excretion

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5
Q

What is Fick’s Law of Diffusion?

A

Rate of Diffusion = Concentration Gradient * Surface Area * Diffusion Coefficient / Membrane Thickness

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6
Q

The rate of diffusion is directly proportional to what?

A

Concentration Gradient, Surface Area, and Diffusion Coefficient

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7
Q

The rate of diffusion is inversely proportional to what?

A

Membrane Thickness

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8
Q

What is bioavailability?

A

The fraction of unchanged drug that reaches systemic circulation aka the free drug available to a receptor

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9
Q

What is the equation for determining bioavailability (F)?

A

F = Bioavailable dose / Administered dose * 100

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10
Q

What is the bioavailability of medications given via the oral route?

A

5-100%

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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

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12
Q

What is the bioavailability of medications given via sublingual/buccal routes?

A

60-100%

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13
Q

What is the bioavailability of medications given via intranasal route?

A

up to 95%

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14
Q

What is the bioavailability of medications given via the rectal route?

A

30-100%

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15
Q

What routes of administration are subject to First Pass Hepatic Metabolism?

A

Oral, proximal rectal

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16
Q

What is the bioavailability of medications given via SQ/IM routes?

A

75-100%

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17
Q

What is the bioavailability of medications given via the IV route?

A

100%

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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

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19
Q

Where do the veins in the mouth drain?

A

SVC

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20
Q

What body type has the highest percentage of BW as water?

A

Infants 70%

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21
Q

What is the volume of total body water?

A

42 liters

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22
Q

What is the volume of plasma?

A

4 liters

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23
Q

What is K12?

A

movement from the central to the peripheral compartment

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24
Q

What is K21?

A

movement from the peripheral to the central compartment

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25
Q

What drug properties affect the volume of distribution?

A

plasma protein binding, ionization, lipid solubility

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26
Q

What is the equation for the volume of distribution?

A

amount of drug / desired plasma concentration

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27
Q

Do lipid or water soluble meds require higher doses to distribute?

A

lipid soluble meds

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28
Q

What is aqueous diffusion?

A

driven by concentration gradient across membrane for lipid insoluble meds

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29
Q

What is lipid diffusion?

A

driven by concentration gradient across phospholipid bilayers

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30
Q

What is active transport?

A

driven by sodium pump using ATP

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31
Q

What is facilitated diffusion?

A

passive action without using ATP using special carriers

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32
Q

What is endocytosis?

A

the wall of a membrane engulfs the molecule within the cell (phago-solids, pino-liquids)

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33
Q

What can protein binding affect?

A

distribution of the drug, potency, elimination

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34
Q

What are the 3 main proteins for plasma protein binding?

A

albumin, alpha1-acidglycoprotein (AAG), beta-globulins

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35
Q

Does albumin bind to acidic or basic drugs?

A

acidic (Thiopental)

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36
Q

Does AAG bind to acidic or basic drugs?

A

basic (local anesthetics)

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37
Q

Factors that decrease albumin will INCREASE or DECREASE the amount of free drug.

A

INCREASE

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38
Q

Factors that increase AAG will INCREASE or DECREASE bioavailability and require a SMALLER or LARGER dose.

A

DECREASE, LARGER

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39
Q

Vd is DIRECTLY or INVERSELY proportionate to the amount of protein binding?

A

INVERSELY

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40
Q

Do polar molecules have GOOD or POOR lipid solubility?

A

POOR

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41
Q

Drugs that are more ionized are LIPID/WATER soluble and POLAR/NONPOLAR.

A

water-soluble and polarized

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42
Q

True/False: Ionized molecules have a positive or negative charge.

A

True

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43
Q

True/False: Ionized molecules readily cross membranes.

A

False

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44
Q

True/False: Ionized molecules repel cells with similar charges.

A

True

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45
Q

Ionized/Nonionized: Pharmacologically active.

A

nonionized

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46
Q

Ionized/Nonionized: Easily cross lipid barriers

A

nonionized

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47
Q

Ionized/Nonionized: Easily metabolized.

A

nonionized

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48
Q

Ionized/Nonionized: Excreted by the kidneys.

49
Q

What type of molecule is reabsorbed into the body through the nephron?

A

lipid soluble

50
Q

What is pKa?

A

the pH when 50% of the drug is ionized and 50% of the drug is nonionized

51
Q

Weak acids form salts with POSITIVE or NEGATIVE ions?

52
Q

What ions are positive?

A

sodium (Na+), magnesium (Mg++), and calcium (Ca++)

53
Q

Weak bases form salts with POSITIVE or NEGATIVE ions?

54
Q

What ions are negative?

A

sulfate (SO–), chloride (Cl-)

55
Q

Do acids donate or accept protons?

56
Q

If an acidic drug is put into a basic solution, does it become more ionized or nonionized?

57
Q

If an acidic drug is put into an acidic solution, does it become more ionized or nonionized?

A

nonionized

58
Q

If an acid has a higher pKa, is there more ionized or nonionized form of the drug?

A

nonionized

59
Q

If a basic drug is put into an acidic solution, does it become more ionized or nonionized?

60
Q

If a basic drug is put into a basic solution, does it become more ionized or nonionized?

A

nonionized

61
Q

If a base has a lower pKa, is there more ionized or nonionized form of the drug?

A

nonionized

62
Q

What two things affect biotransformation?

A

intrinisic rate and concentration of the drug

63
Q

What is phase 1 of biotransformation?

A

Modification via oxidation, reduction, or hydroloysis

64
Q

What is phase 2 of biotransformation?

A

Conjugation

65
Q

In what way does oxidation work?

A

via the loss of an electron using the P450 system

66
Q

In what way does reduction work?

A

via the addition of an electron using the P450 system

67
Q

In what way does hydrolysis work?

A

by breaking a compound into 2 parts by adding water

68
Q

Where in the body does hydrolysis work?

A

plasma (most common), stomach

69
Q

What medications are metabolized through hydrolysis?

A

remifentanil, succinylcholine, esmolol, ester local anesthetics

70
Q

In premature infants, is conjugation DECREASED or INCREASED leading to DECREASED or INCREASED frequency of administration?

A

decreased, decreased

71
Q

Phase II reactions use what enzymes?

A

glucuronosyl transferases, sulftransferases, N-acetyltransferases (NAT)

72
Q

What hepatic microsomal enzyme is responsible for >50% of anesthesia medications?

73
Q

What is a medication that its active metabolites continue to work in the body?

74
Q

What is a prodrug?

A

A drug that is inactive in its parent form and becomes active once going through phase 1 metabolism

75
Q

What are 2 examples of a prodrug?

A

fospropofol and codeine

76
Q

How does an inducer affect the P450 system?

A

speeds up function of the enzyme leading to increased clearance and decreased half-life

77
Q

If a P450 enzyme is induced, does the frequency of drug need to be INCREASED or DECREASED?

78
Q

If a P450 enzyme is inhibited, does the frequency of drug need to be INCREASED or DECREASED?

79
Q

How does an inhibitor affect the P450 system?

A

decreases function of the enzyme leading to decreased clearance and increased half-life

80
Q

What are some CPY 3A4 inducers?

A

Ethanol (chronic), Carbamazepine, Rifampin, St John’s Wart, Tamoxifen, Barbituates

81
Q

What are some CPY 3A4 inhibitors?

A

Azole antifungals, Erythromycin, Grapefruit juice, SSRIs

82
Q

What are some CYP 2D6 inducers?

A

Phenytoin, Carbamazepine, Dexamethasone

83
Q

What are some CYP 2D6 inhibitors?

A

Isoniazid, SSRIs, Quinidine

84
Q

Is the genetic variability of having red hair an inducer or inhibitor of the P450 system?

A

inducer - needs higher dosages

85
Q

Drugs that are water soluble tend to be MORE or LESS POLAR and MORE or LESS ionized?

A

MORE, MORE

86
Q

Drugs that are lipid soluble tend to be MORE or LESS polar and MORE or LESS ionized?

A

LESS, LESS

87
Q

What type of molecule is the most common type in anesthesia to cross a lipid membrane?

A

lipophilic molecule

88
Q

True/False: Highly lipophilic drugs have a higher Vd requiring a decreased dosage.

A

False, requires an increased dosage

89
Q

True/False: Plasma protein binding is non-competitive.

90
Q

True/False: Intranasal cocaine given in the OR is subject to First Pass Hepatic Metabolism.

A

False, goes directly into vasculature

90
Q

True/False: Intranasal cocaine given in the OR is subject to First Pass Hepatic Metabolism.

A

False, goes directly into vasculature

91
Q

Besides pain control, what other reason is Fentanyl given during RSI?

A

blunts laryngeal spasms

92
Q

Besides preventing pain during the administration of Propofol, what other reason is Lidocaine given during RSI?

A

blunts laryngeal spasms

93
Q

Why is Midazolam a better choice than Diazepam for RSI?

A

Diazepam lasts longer due to active metabolites

94
Q

Why is a higher first dose or bolus dose needed with Propofol?

A

highly lipid soluble, distributes out to fat

95
Q

Why is Succynylcholine still used despite better NMBD?

A

quicker onset, shorter duration for learners

96
Q

Which NMBD is depolarizing?

A

Succinylcholine

97
Q

What does having atypical cholinesterase cause?

A

unable to metabolize succinylcholine, increased time paralyzed

98
Q

A drug with a Vd that is less than total body water is assumed to be…

A

hydrophilic

99
Q

A drug with a Vd that exceeds total body water is assumed to be…

A

lipophilic

100
Q

Clearance of a drug is directly proportional to…

A

drug dose, extraction ratio, and blood flow to target organ

101
Q

Clearance of a drug is inversely proportional to…

A

half-life and drug concentration

102
Q

After how many half-times is steady-state achieved?

103
Q

What is elimination half-life?

A

The time it takes for 50% of the drug to be eliminated from the body

104
Q

What is elimination half-time?

A

The time it takes for 50% of the drug to be removed from the plasma

105
Q

What conditions decrease protein concentrations leading to higher bioavailability?

A

liver disease, renal disease, old age, malnutrition, and pregnancy

106
Q

What is zero order kinetics?

A

A constant AMOUNT of a drug is metabolized per unit of time; more drug than enzyme

107
Q

What is first order kinetics?

A

A constant FRACTION of the drug is metabolized per unit of time; less drug than enzyme

108
Q

What are some drugs that follow zero order kinetics?

A

aspirin, phenytoin, alcohol, warfarin, heparin, theophylline

109
Q

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.

A

Lipid, active: water, inactive

110
Q

A drug with a high hepatic extraction ration (>0.7), clearance is dependent on…

A

liver blood flow

111
Q

A drug with a low hepatic extraction ratio (<0.3), clearance is dependent on…

A

the ability of the liver to extract the drug from the blood

112
Q

What is the equation for creatinine clearance?

A

(140-age) * weight / 72 * SCr
(* 0.85 if female)

113
Q

A drug with a Vd that exceeds total body water is assumed to be lipophilic OR hydrophilic?

A

Lipophilic

114
Q

A drug with a Vd that is less than total body water is assumed to be lipophilic OR hydrophilic?

A

Hydrophilic

115
Q

Hydrophilic drugs need a lower OR higher dose to achieve the desired plasma concentration?

116
Q

Lipophilic drugs need a lower OR higher drug dose to achieve the desired plasma concentration?

A

Higher
Distributes out to the fat as well as the rest of the body

117
Q

What drugs have a low hepatic extraction ratio?

A

Rocuronium
Diazepam
Lorazepam
Methadone
Thiopental
Theophylline
Phenytoin

118
Q

What drugs have a high hepatic extraction ratio?

A

Fentanyl
Sufentanil
Morphine
Meperidine
Naloxone
Ketamine
Propofol
Lidocaine
Bupivacaine
Metoprolol
Propranolol
Alprenolol
Nifedipine
Diltiazem
Verapamil

Pharmacology Exam 1 (5 decks)

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