Inflammation - Pharmacology - Basic Principles; Disposition & Metabolism; Pharmacokinetics Flashcards

1
Q

Pharmacodynamics is the study of what ________ do(es) to ________.

Pharmacokinetics is the study of what ________ do(es) to ________.

A

Pharmacodynamics is the study of what drugs do to the body.

Pharmacokinetics is the study of what the body does to drugs.

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2
Q

_______________ is the study of what the body does to drugs.

_______________ is the study of what drugs do to the body.

A

Pharmacokinetics;

pharmacodynamics

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3
Q

Most drugs are in what molecular weight range?

A

rarely selective < 100 — 1000 > not well absorbed / distributed

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4
Q

While some drugs don’t have a specific ‘site of action’ (e.g. a binding site), most drugs are ____________ that bind a specific site.

A

Ligands

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5
Q

While both can bind drugs/substances, what is the difference between a receptor (e.g. the TSH receptor) and a binding site (e.g. albumin)?

A

Receptors transduce a signal to produce a biological effect;

binding sites don’t

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6
Q

Which of the following is the most common type of drug ligand binding?

Covalent bonds

Electrostatic interactions

H+ , Van der Waals, & hydrophobic interactions

A

Electrostatic interactions

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7
Q

Which of the following is the most common type of ligand binding seen in lipophilic drugs?

Covalent bonds

Electrostatic interactions

H+ , Van der Waals, & hydrophobic interactions

A

H+ , Van der Waals, & hydrophobic interactions

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8
Q

Which of the following is the least common type of drug ligand binding?

Covalent bonds

Electrostatic interactions

H+ , Van der Waals, & hydrophobic interactions

A

Covalent bonds

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9
Q

True/False.

Stererospecificity matters to proper drug ligand function.

A

True.

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10
Q

What is the difference between ligand affinity and efficacy in pharmacodynamics?

A

Affinity — binding attractiveness

Efficacy — strength of effect

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11
Q

How are ligand antagonists different from agonists in terms of affinity and efficacy?

A

Antagonists possess affinity only

(no efficacy)

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12
Q

A high KA indicates ________ affinity.

A high KD indicates ________ affinity.

A

High;

low

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13
Q

What are K1 and K-1 in terms of ligand-receptor binding?

A
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14
Q

The __ is the amount of drug required to saturate 50% of receptors.

A

KD

(ratio of K-1 to K1)

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15
Q

The Law of Mass Action: the number of receptors [R] occupied by a drug depends on:

________ concentration

L-R association [__] rate constant

L-R dissociation [__] rate constant

A

Ligand;

K1;

K-1

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16
Q

The KD is the amount of drug required to saturate ________________.

A

50% of receptors

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17
Q

Where can KD and binding max (Bmax) be identified on a graph of [drug] on the X-axis and percent of receptors bound on the Y-axis?

A
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18
Q

True/False.

Drugs with high affinity are usually better structural fits with the receptors they bind.

A

True.

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19
Q

What is a dose-response curve?

A

A curve comparing drug dosages (X axis) and physiological responses (Y axis)

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20
Q

What is this type of graph called?

A

A dose-response curve

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21
Q

On a dose-response curve, what is EMax?

What is EC50?

A

The maximal effect (Y axis)

the drug concentration (X axis) at 50% of Emax

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22
Q

Why are drug dosages on dose-response curves given on log scales?

A

Easier visualization and math on the sigmoidal curve

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23
Q

What is indicated if the dose-response and the ligand-binding curves don’t line up so that EffectMax is obtained at less than 100% of Bmax?

A

Spare receptors are present

(maximal effect is obtained at less than 100% binding)

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24
Q

For a certain drug, EC50 = Kd.

Are spare receptors present?

A

No.

(Only if EC50 < Kd; as shown below)

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25
Q

If spare receptors ____ (are / are not) present, then the duration of the biological effect will be longer than the duration of drug-receptor interactions.

A

If spare receptors are present, then the duration of the biological effect will be longer than the duration of drug-receptor interactions.

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26
Q

True/False.

We are typically more sensitive to agonists with fewer receptors than agonists with spare receptors.

A

False.

We are typically more sensitive to agonists with spare receptors.

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27
Q

The drug with the _______ (lowest / highest) EC50 is the most potent.

A

The drug with the lowest EC50 is the most potent.

(Less drug for more effect)

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28
Q
A

A. Drug X

(Lower EC50)

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29
Q

Would any of the drugs in this image qualify as partial agonists?

Or antagonists?

A

B and C;

D

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30
Q

Describe how increasing drug efficacies changes a dose-response curve.

A
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31
Q
A

Drug X

(higher Emax)

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32
Q

What is inverse pharmacological agonism?

A

Decreasing a consititutively active receptor

(i.e. decreasing basal tone / intrinsic activity)

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33
Q

True/False.

Inverse agonism is just another term for antagonism.

A

False.

(Inverse a. refers to a drug that decreases the activity of receptor’s constitutively active basal tone)

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34
Q

________ drugs increase receptor activity to levels above basal tone.

________ ________ drugs decrease receptor activity to levels below below basal tone.

A

Agonist drugs increase receptor activity to levels above basal tone.

Inverse agonist drugs decrease receptor activity to levels below below basal tone.

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35
Q

Drugs are often compared against what to determine their levels of agonism?

A

The endogenous agonist

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36
Q

True/False.

By definition, partial agonists have both agonistic and antagonistic activity.

A

True.

By definition, partial agonists have both agonistic and antagonistic activity.

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37
Q

__________ic antagonists bind the same receptor as the agonist drug in question.

__________ic antagonists bind a different receptor as the agonist drug in question.

A

Pharmacologic antagonists bind the same receptor as the agonist drug in question.

Physiologic antagonists bind a different receptor as the agonist drug in question.

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38
Q

__________ antagonists bind or alter the agonist drug in question, not a receptor.

A

Chemical antagonists bind or alter the agonist drug in question, not a receptor.

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39
Q
A

D. Pharmacologic antagonist

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40
Q
A

C.

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41
Q

The _____ is the drug concentration at which 50% of the population manifests the desired effect.

A

The ED50 is the drug concentration at which 50% of the population manifests the desired effect.

(Effective Dose)

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42
Q

The _____ is the drug concentration at which 50% of the population is killed by the drug.

A

The LD50 is the drug concentration at which 50% of the population is killed by the drug.

(Lethal Dose)

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43
Q

The _____ is the drug concentration at which 50% of the population manifests a given toxic effect.

A

The TD50 is the drug concentration at which 50% of the population manifests a given toxic effect.

(Toxic Dose)

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44
Q

The ED50 is the drug concentration at which 50% of the population manifests a given ______ effect.

The TD50 is the drug concentration at which 50% of the population manifests a given ______ effect.

The LD50 is the drug concentration at which 50% of the population is ______ by the effects of the drug.

A

The ED50 (effective dose) is the drug concentration at which 50% of the population manifests a given desired effect.

The TD50 (toxic dose) is the drug concentration at which 50% of the population manifests a given toxic effect.

The LD50 (lethal dose) is the drug concentration at which 50% of the population is killed by the effects of the drug.

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45
Q

How is the therapeutic index of a drug calculated?

A

*LD50 / ED50

*(or TD50)

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46
Q

The median effective dose (ED50) for a certain medication is 3 mg, and the median lethal dose (LD50) is 150 mg.

What is the therapeutic index?

A

150/3 = 50

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47
Q

Which is preferable, a high therapeutic index or a low therapeutic index?

A

High!

(LD50 / ED50)

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48
Q
A

Drug B

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49
Q

Agonists typically ______-regulate receptors on target tissues.

Antagonists typically ______-regulate receptors on target tissues.

A

Agonists typically down-regulate receptors on target tissues.

Antagonists typically up-regulate receptors on target tissues.

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50
Q
A

B.

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51
Q
A

E. Partial agonist

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52
Q

Gα<strong>s</strong> is a(n) _______ subunit.

Gαi is a(n) _______ subunit.

Gαq increases intracellular _______.

A

Gs is a stimulatory subunit.

Gi is an inhibitory subunit.

Gq increases intracellular calcium.

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53
Q
A

D. Activation of adenylate cyclase

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54
Q
A

C. RTKs

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55
Q

What are two methods via which agonists might cause receptor down-regulation?

A
  1. Increased synthesis of receptor-blocking proteins
  2. Increased degradation of receptors
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56
Q

True/False.

Differing drugs will have various and complex methods of transport and metabolism in the body.

A

True.

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57
Q

Describe some of the different forms of drug intake and distribution in the body.

A
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58
Q

True/False.

All drugs undergo this basic mechanism:

Administration –> Absorption –> Distribution –> Metabolism –> Excretion

A

False.

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59
Q

True/False.

The GI tract is highly permeable to many medications (given they are lipophilic).

A

True.

The GI tract is highly permeable to many medications (given they are lipophilic).

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60
Q

P-__________ is an outward transporter found in several areas of the body and acts to __crease drug absorption.

A

P-glycoprotein is an outward transporter found in several areas of the body and acts to decrease drug absorption.

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61
Q

Lipo_____ drugs are more easily absorbed.

A

Lipophilic drugs are more easily absorbed.

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62
Q

What type of drug is readily absorbed in the stomach?

A

Weak acids

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63
Q

True/False.

Weak bases are well-absorbed in the stomach.

A

False.

Weak acids are well-absorbed in the stomach.

(Weak bases are almost not absorbed at all)

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64
Q

Both weak acids and weak bases are decently well absorbed in the ______________.

A

Both weak acids and weak bases are decently well absorbed in the small intestine (~70% for WAs and ~50% for WBs).

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65
Q

Will decreasing the ionization of a drug increase or decrease its reabsorption?

A

Increase

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66
Q

What is pharmacologic ion trapping?

A

Drugs are ionized after being taken up

(and thus trapped)

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67
Q

What do the pharmacologic abbreviations qd, bid, tid & qid mean?

A

qd : every day
bid : twice a day
tid : three times a day
qid: four times a day

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68
Q

With most drugs, why is only a small amount of the absorbed drug is in contact with body receptors at any particular point in time?

A

The majority of the drug is often localized in areas removed from the site of action (e.g. bound to plasma proteins).

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69
Q

Drugs in the plasma are often ____ly bound to ______.

A

Drugs in the plasma are often weakly bound to albumin.

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70
Q

Which three organs receive the majority of cardiac output and, thus, the majority of drugs in the plasma passing through (especially for fat-soluble medications)?

A

Liver, kidney, brain

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71
Q

What are some potential storage tissues for many types of drug (especially for fat-soluble ones)?

A

Fat, muscle, and bone

(many drugs are tissue-specific)

72
Q

Drug excretion mainly happens via what organs?

(the most important one is bolded)

A

Kidneys (urine);

liver (bile)

73
Q

How can ion trapping be used to increase drug excretion?

A

Alkalinization or acidification of the urine

74
Q

Besides the kidneys and liver, what are some other organs that might provide some drug excretion?

A

Sweat glands;

mammary glands;

lungs

75
Q

Drugs typically become more easily excreted and less toxic the more __________ they become.

A

Drugs typically become more easily excreted and less toxic the more hydrophilic they become.

76
Q

Lots of CP450 metabolism of drugs revolves around what type of reaction?

A

Making substances more hydrophilic

(hydroxylations, removal of aryl groups, etc.)

77
Q

Name if each of the following is a type I or type II reaction performed by the CP450 system:

Oxidation

Conjugation

Reduction

Hydrolysis

A

Oxidation (Type I)

Conjugation (Type II)

Reduction (Type I​)

Hydrolysis (Type I​)

78
Q

The following are all part of what system?

Alcohol dehydrogenase

Xanthine oxidase

Monoamine oxidases

Diamine oxidases

Reductases (azo- or nitro-)

Hydroxylases

A

Type I cytochrome P450

79
Q

What type of drug induces the P450 system?

A

Drugs that challenge the system

(often have lots of side chains)

80
Q

What are some example of the reaction types of type II CP450 action?

A

Conjugation;

acetylation;

methylation;

glucoronidation

81
Q

The cytochrome P450 system occurs mainly inside of cellular ___________ in the liver, _______ glands, intestines, and _______ (although it is found in other organs as well).

A

The cytochrome P450 system occurs mainly inside of cellular microsomes in the liver, adrenal glands, intestines, and kidneys (although it is found in other organs as well).

82
Q

The CP450 system is made of mixed-function oxidases in that the enzymes require both a ________ agent and ____.

A

The CP450 system is made of mixed-function oxidases in that the enzymes require both a reducing agent and O2.

83
Q

The _____ system is the rate-limiting step in drug metabolism.

A

The P450 system is the rate-limiting step in drug metabolism.

84
Q

True/False.

Some foods such as grapefruit and kale can interfere with normal CP450 function (either inducing or decreasing activity).

A

True.

Some foods such as grapefruit and kale can interfere with normal CP450 function (either inducing or decreasing activity).

85
Q

Beside its role in drug metabolism, does CP450 have other normal functions in the body?

A

Yes!

(Wikipedia: In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown.)

86
Q

Is CP450 induction typically reversible?

A

Yes

87
Q

Which CP450 isozyme is induced by cigarette smoking?

A

CYP1A

88
Q

Which CP450 isozyme is involved in metabolism of SSRIs, propranolol and morphine?

A

P-450 2D6

89
Q

Which CP450 isozyme is involved in ethanol metabolism and is inhibited by disulfiram?

A

CYP2E1

90
Q

Which CP450 isozyme is the most abundant in the liver microsomes and the most important for drug metabolism?

A

CYP3A4

91
Q

What type of drug blocks the CYP3A4 isozyme of the CP450 system (the most abundant of the liver isozymes and the most important for drug metabolism)?

(NOTE: some of the relevant substrates are listed below.)

A

Drugs that end in ‘-azole’

(flucanazole; ketoconazole; clotrimazole; etc.)

(NOTE: some of the relevant substrates are listed below.)

92
Q

Aspirin is an example of a weak ______.

Quinidine is an example of a weak ______.

A

Aspirin is an example of a weak acid.

Quinidine is an example of a weak base.

93
Q

What are some examples of substances that increase P-glycoproteins (an outward transporter that acts to decrease drug absorption) in the body?

A

Rifampin;

St. John’s wort

94
Q

What are some examples of substances that decrease P-glycoproteins (an outward transporter that acts to decrease drug absorption) in the body?

A

Cimetidine;

grapefruit juice

95
Q

What is the ‘first pass effect’ of pharmacodynamics?

What are some example drugs where this occurs?

A

A phenomenon where the concentration of a drug (often PO) is greatly reduced before it reaches the systemic circulation;

propranolol, morphine, nitroglycerin

96
Q

What are some example substances that induce the CP450 system?

A

Rifampin, barbiturates, St. John’s Wort

97
Q

What are some example substances that suppress the CP450 system?

A

Cimetidine, grapefruit juice, ketoconazole

98
Q

~___% of all drugs are metabolized by the CP450 system.

A

~50% of all drugs are metabolized by the CP450 system.

99
Q

True/False.

All medications have a similar volume of distribution (Vd) of about 40 L.

A

False.

Medications have many varying volumes of distribution (Vd). They may be be in plasma alone, in the ECF, in total body water, in fat, or any other number of locations.

100
Q

Define volume of distribution (Vd).

Define clearance (Cl).

A

The body volume (L) that the drug dose (mg) occupies;

the volume per unit time that is filtered completely free of drug

101
Q

Vd = Loading ____ / ___

A

Vd = Loading dose / [Drugintiital]

Vd — volume of distribution;

Loading dose — initial dosage given

C0 — initial [drug]

102
Q

If you want to achieve an initial therapeutic plasma drug level (C0) of 5 ug/ml (5 mg/L) and the Vd for the drug is 30 L, then the loading dose you need to give is:

A

Loading Dose = C0 x Vd = 5 mg/L x 30 L = 150 mg

103
Q

t1/2 = 0.___ Vd / ___

A

t1/2 = 0.69 Vd / Cl

104
Q

In order to maintain plasma drug concentrations, maintenance dose must _______ the clearance rate.

A

In order to maintain plasma drug concentrations, maintenance dose must equal the clearance rate.

105
Q

How many half-lives does it take for a drug concentration to reach 90% of steady state concentration?

A

3.3

(t(0.90) = 3.3 t1/2)

106
Q

What is CSS?

(Pharmacokinetics)

A

Steady-state [drug]

(e.g. the concentration measured from a blood sample once steady-state conditions have been achieved after continuous drug dosing)

107
Q

CSS = _________ / Clearance.

CSS — steady state [drug]

A

CSS = Dosing Rate / Clearance.

CSS — steady state [drug]

108
Q

If you know the desired therapeutic plasma concentration (CSS) that you want to achieve (e.g. 5 mg/L), and you know the elimination clearance (Cl) for the drug (e.g. 0.5 L/hr), then how would you calculate the dosing rate?

A

Dosing Rate = CSS x Cl = 5 mg/L x 0.5 L/hr = 2.5 mg/hr.

109
Q

Name a few medications metabolized under zero-order conditions.

A

Ethanol (above 2-ish beers), phenytoin, aspirin (high dose)

110
Q

What is bioavailability?

A

The amount making it to circulation from PO meds / Amount making it to circulation from IV meds * 100

(IV meds have 100% bioavailability)

111
Q

________________ is the amount of medication (mg) being put into the body.

__________________ is the volume (L) into which the medication is being distributed.

_____________ is the rate at which the volume (and accompanying medication) is excreted.

A

Drug dose is the amount of medication (mg) being put into the body.

Volume of distribution is the volume (L) into which the medication is being distributed.

Clearance is the rate at which the volume (and accompanying medication) is excreted.

112
Q

If you know the plasma drug steady state you wish to achieve, how can you calculate the dosing rate?

A

Dosing rate = clearance * CSS

113
Q

A decrease in drug clearance will have what effect on steady state concentration?

A

Increase

(Dosing rate = clearance * CSS)

114
Q

What is first pass metabolism?

A

Per oral drugs absorbed through the GI tract are first metabolized by the liver before reaching general circulation

115
Q

True/False.

The three components of pharmacokinetics are absorption, distribution, and elimination.

A

True.

The three components of pharmacokinetics are absorption, distribution, and elimination.

116
Q
A

C.

A drug with the highest efficacy will produce the largest maximal response.

117
Q
A

A.

118
Q
A

B. EC50

119
Q
A

C. 10

(TD50/ED50)

120
Q

Digoxin is a drug that has been used to treat systolic heart failure for over 200 years. It has a therapeutic index value of 2. How many daily doses of digoxin will the average patient have to take at one time to have a 50:50 chance of developing toxic side effects?

A

2

(TD50)

121
Q
A

D. Drug D

122
Q
A

B. Drug B

123
Q
A

B. Competitive antagonist

124
Q
A

C. Noncompetitive antagonist

125
Q
A

C. Signal transduction

(only true receptors cause signal transduction)

126
Q

Treatment of pediatric patients sometimes requires considering age-appropriate dosage forms. For example, when treating an 8 year old boy with an inner ear infection, the antibiotic dosage formulation most acceptable to them would likely be a(an):

IM injection

Per rectum

Oral suspension

Oral tablet

A

Oral suspension

127
Q

Some drugs have a low oral bioavailability due to extensive metabolism in the GI tract or liver. Which dosage form can be used to best avoid this complication?

A. Controlled release tablet

B. Enteric coated tablet

C. Soft capsule

D. Transdermal patch

A

D. Transdermal patch

128
Q

In a medical emergency, a rapid onset of drug effect is often desired. A route of administration that would best achieve this for a centrally acting pain reliever is:

A. i.v. injection

B. oral suspension

C. s.c. injection

D. transdermal patch

A

A. i.v. injection

129
Q

Your 65 year old grandfather who has a history of heart disease begins to have an attack of exertional angina while working beside you in his garden. He gestures towards a dark glass vial in his pocket that has a prescription label indicating it contains nitroglycerin triturate. How would you help him administer this dosage form?

A. Dissolve it in water like an alka-selzer, then have him swallow it

B. Place it under his tongue

C. Rub it on his chest above the heart

D. Place it in a nebulizer and have him inhale it

A

B. Place it under his tongue

(no significant pre-clearance)

130
Q
A

E. 50 L

8 ug/ml = 8 mg/L
C0 (mg/L) = Dose/Vd
Vd = (400 mg)/(8 mg/L) = 50L

131
Q

A 70 kg man with severe burns arrives in the Emergency Department and requires i.v. morphine to treat his pain. The Vd for morphine is 200 L. What i.v. loading dose do you need to give to rapidly achieve a therapeutic level of 60 ng/ml and relieve his pain?

A. 3 ug

B. 30 ug

C. 120 ug

D. 12 mg

E. 30 mg

A

D. 12 mg

C0 (mg/L) = Dose/Vd, or Dose = C0 x Vd.

Therefore, the Loading Dose = 60 ug/L x 200 L = 12,000 ug or

12 mg.

132
Q

Brian is a 40 kg teen who has been admitted to the hospital with a severe case of septicemia caused by a Gram-negative bacteria that has been determined to be sensitive to gentamicin. Gentamicin’s Vd = 0.5 L/kg. What i.v. loading dose would you give Brian to rapidly achieve a therapeutic plasma level of 5 ug/ml?

A. 20 mg

B. 25 mg

C. 50 mg

D. 100 mg

E. 500 mg

A

D. 100 mg

Vd = 0.5 L/kg x 40 kg = 20 L. 5 ug/ml = 5 mg/L. Dose = 5 mg/L x 20 L =

100 mg.

133
Q

After being given a loading dose, treatment of Brian’s bacterial infection requires maintenance dosing with gentamicin for 48 hours. Gentamicin’s elimination clearance is 5.0 L/hr. What i.v. maintenance dose should you give every 8 hours to maintain an average plasma level of 5 ug/ml?

A. 20 mg

B. 25 mg

C. 50 mg

D. 100 mg

E. 200 mg

F. 500 mg

A

E. 200 mg

Dosage Rate = CSS x Cl = (5 mg/L) x (5L/hr) x (8 hrs) = 25 mg/hr x 8 hrs =

200 mg.

134
Q
A

1.75 L/hr

Vd = (320 mg)/(32 mg/L )= 10 L
t1/2 = 0.7 Vd/Cl or Cl = 0.7Vd/t1/2
Cl = 0.7 x 10 L/4 hr = 1/75 L/hr

135
Q

You start an i.v. infusion of a drug to a patient at a rate of 500 mg/hr. The drug is known to be cleared by first-order kinetics. Which single variable will allow you to determine how long it will take to reach a steady-state drug level?

A. Bioavailability

B. Dosage rate (mg/hr)

C. Elimination half life

D. infusion rate

E. Volume of distribution

A

C. Elimination half life

136
Q

Bob is a 65 year old man on amiodarone therapy for chronic atrial fibrillation. He arrives in your clinic complaining of symptoms of hyperthyroidism, one of the many forms of amiodarone toxicity. A blood sample confirms a drug level of 4 ug/ml, well above his normal range of 1-2 ug/ml. The half life of amiodarone is 25 days. If you discontinue his medication, how long will you have to wait for Bob’s amiodarone level to fall to a normal level of 1 ug/ml?

A. 25 days

B. 50 days

C. 75 days

D. 82.5 days

E. 100 days

A

B. 50 days

137
Q

You initiate a patient on oral ibuprofen (400 mg bid) to treat a case of painful rheumatoid arthritis. Ibuprofen has an elimination half life of 2 hours. How long will it take for the ibuprofen plasma level to reach 90% of its eventual steady state, assuming a one compartment model?

A. 2 hrs

B. 3.6 hrs

C. 6.6 hrs

D. 8 hrs

E. 12 hrs

A

C. 6.6 hrs

(It takes 3.3t1/2 to reach 90% of steady state during a continued maintenance dosage regimen.)

138
Q

You decide to switch a hospitalized patient’s medication from a continuous intravenous drip to a t.i.d. oral tablet dosage equivalent prior to discharge. The i.v. dosage regimen he was receiving was 10 mg/hr. What tablet dose should he be given t.i.d. (‘ter in die’ — 3x per day) to maintain the same dosing rate, assuming 100% bioavailability?

A. 20 mg

B. 40 mg

C. 60 mg

D. 80 mg

E. 120 mg

A

D. 80 mg

139
Q

You are treating a 100 kg hospitalized patient suffering from fibromyalgia with a new experimental pain reliever taken p.o.. Because its analgesic efficacy has not been well established, you wish to assess the extent of its pain relief once it has approached steady-state plasma levels. To estimate how long this may take, you need to first calculate its half-life.

According to the information provided by the manufacturer, the drug has a Vd of 0.2 L/kg and an elimination clearance of 7 L/hr. Therefore its half life should be:

A. 0.2 hr

B. 1 hr

C. 1.5 hr

D. 2 hr

E. 4 hr

A

D. 2 hr

V<sub>d</sub> = 0. 2L/kg x 100 kg = 20 L
t<sub>1/2</sub> = 0.69(V<sub>d</sub>/Cl) = 0.69(20 L / 7 L/hr) = 2 hr.
140
Q

Carbamazepine is a lipid soluble antiepileptic drug that has a larger volume of distribution in obese patients. As a result, the elimination half-life in very heavy patients (compared to anorexic patients) is expected to be:

A. Decreased (shorter)

B. Increased (longer)

C. Unchanged

A

B. Increased (longer)

(t1/2 = 0.7 Vd/Cl)

141
Q

Your cardiac patient is being given 1 gram of procainamide sustained release tablets every 6 hours to control a ventricular arrhythmia. Procainamide’s Cl = 33 L/hr. With regular dosing, its steady-state plasma level will be approximately:

A. 0.3 ug/L

B. 0.5 ug/ml

C. 5 ug/ml

D. 33 ug/ml

E. 50 ug/ml

A

C. 5 ug/ml

CSS = Dosing Rate ÷ Cl = (1000 mg/6 hr) ÷ (33 L/hr) = (166.7 mg/hr) ÷ (33 L/hr) = 5.05 mg/L.

142
Q

Boudreaux is a 70 year-old man with systolic heart failure and chronic atrial fibrillation that requires therapy with digoxin. You start him on 250 ug digoxin tablets q.d. (one per day). Based upon assessment of his kidney function (serum creatinine levels), his digoxin renal clearance is estimated to be 250 L/day. Assuming 100% bioavailability, the steady-state concentration of digoxin is expected to be:

A. 0.1 ug/L

B. 1.0 ug/L

C. 10 ug/L

D. 100 ug/L

A

B. 1.0 ug/L

Dosing Rate (ug/day) = CSS (ug/L) x Cl (L/day)

or CSS (ug/L) = Dosing Rate (ug/day)/Cl (L/day) = (250 ug/day)/250 (L/day)= 1 ug/L

143
Q

Thibidoux is a 72 year old man hospitalized after a recent MI that requires lidocaine therapy to suppress post-MI ventricular arrhythmias. Assuming a single compartment model, Vd = 50 L and CL = 0.5 L/min, what infusion rate would you need to use to achieve a therapeutic plasma level of 4 ug/ml lidocaine?

A. 0.2 mg/min

B. 0.8 mg/min

C. 1 mg/min

D. 2 mg/min

E. 25 mg/ml

A

D. 2 mg/min

4 ug/ml = 4 mg/L

Dosing Rate = Css (ug/L) x Cl (L/day) = 4 mg/L x 0.5 L/min = 2 mg/min

144
Q

Digoxin is a drug that can be used to control the ventricular rate in patients suffering from both systolic heart failure and atrial fibrillation. However, when a loading dose of digoxin is administered i.v. or orally, there is a ~6 hour delay before a maximal reduction in ventricular rate is observed in patients with AFib. The reason for this delay is attributed to:

A. A long digoxin elimination half-life

B. Distribution time for a one-compartment model

C. Rapid renal elimination of digoxin

D. The time it takes for digoxin distribution into a peripheral compartment

A

D. The time it takes for digoxin distribution into a peripheral compartment

145
Q

GD is an 84 year-old man with severe congestive heart failure that has been taking digoxin orally for several years at a typical dose of 0.25 mg/day. His digoxin plasma levels have historically averaged around ~1.2 ng/ml (therapeutic range is 0.5-1.5 ng/ml). However, his most recent series of lab tests have indicated a slow decline in renal function, and his creatine clearance is now stable at 50% of its previous normal value. Since digoxin undergoes renal clearance with a normal half life of 1.5 days, what would you recommend be done?

A. continue the same daily dose and recheck levels in a month

B. give 0.25 mg every 72 hours and recheck levels in 10 days.

C. reduce the daily dose by 25% and recheck levels in 10 days.

D. reduce the daily dose to 0.125 mg, recheck levels in 10 days.

E. stop digoxin

A

D. reduce the daily dose to 0.125 mg, recheck levels in 10 days.

146
Q

A patient with chronic obstructive pulmonary disease (COPD) is being treated with theophylline by i.v. infusion. What fraction of the eventual steady-state theophylline level will be achieved after a time equal to two elimination half-lives following the start of the infusion?

A. 25%

B. 50%

C. 75%

D. >90%

A

C. 75%

(In one half-life, you get to 50% of steady state.)

147
Q

Some drugs such as amiodarone and digoxin have apparent volumes of distribution of hundreds of liters in an average 70 kg patient. This is because such drugs have a:

A. high degree of binding to plasma proteins

B. high affinity for tissue proteins or high fat solubility

C. large first-pass effect

D. long half life

E. short half-life

A

B. high affinity for tissue proteins or high fat solubility

148
Q

Amiodarone is an antiarrhythmic drug that is sometimes given to patients who are also taking digoxin for systolic heart failure. In such patients, amiodarone can interfere with the renal tubular secretion of digoxin by inhibiting renal p-glycoprotein. When this pharmacokinetic drug interaction occurs, which of the following would you expect to observe?

A. decreased digoxin plasma levels, and decreased digoxin t1/2

B. decreased digoxin plasma levels, and increased digoxin t1/2

C. increased digoxin plasma levels, and decreased digoxin t1/2

D. increased digoxin plasma levels, and increased digoxin t1/2

A

D. increased digoxin plasma levels, and increased digoxin t1/2

149
Q

Axl Ant is a 70-year-old aging rock musician with a long history of alcohol and heroin abuse who recently developed a form of epilepsy resistant to drug therapy. Despite being treated with high doses of both valproate and phenytoin for several weeks, Axl has continued to suffer from periodic seizures. To determine a possible cause for Axl’s drug resistance, blood & urine samples were collected at repeated time intervals after stopping drug therapy for several days and then giving a loading dose of both drugs. Axl’s lab results indicate the half-life for valproate was signficantly shorter than normal (8) (vs a normal 16 hrs). Which of the following is the most likely cause for the abnormal elimination half-life?

A. Coadministration of cimetidine for peptic ulcer

B. Cirrhosis of the liver

C. Renal failure

D. P450-induction by phenytoin

E. Viral hepatitis

A

D. P450-induction by phenytoin

150
Q

Drugs that are taken orally must first cross several biological membranes (diffusion barriers) before they reach their target receptors inside the body. Which of the following drug characteristics would best facilitate this process?

A. Glucuronidated form

B. Ionized form

C. Protein bound

D. Quaternary charge

E. Unionized form

A

E. Unionized form

151
Q

Enzymatic modification of drugs by hepatic enzymes can commonly:

1) decrease a drug’s ability to interact with receptors (reduce their pharmacodynamic efficacy), as well as
2) structurally modify a drug to increase its water solubilty, which enhances its renal clearance.

Enzymatic addition of which side group would most likely accomplish both goals?

A. alkyl (CH3)

B. aryl (phenyl group)

C. bromine (Br)

D. hydroxyl (OH)

E. sulfur (S)

A

D. hydroxyl (OH)

152
Q

A patient with cancer is being evaluated for treatment with Protokil®, a potentially life-saving “prodrug” that requires first pass metabolism by hepatic CYP1A2. The patient’s recent lab results indicate elevated serum levels of liver enzymes related to tissue damage caused by hepatitis C infection. What effect would this patient’s liver status likely have on drug therapy with Protokil®?

A. an increased rate of drug metabolism

B. less than normal therapeutic response to drug therapy

C. increased sensitivity to drug therapy

D. a lower oral dosage should be used

A

B. less than normal therapeutic response to drug therapy

Prodrugs need to be converted to their active form, in this case by hepatic CYP1A2. Liver damage would reduce hepatic function

153
Q

A drug that is a weak organic acid (pK=3) would be least ionized in the:

A. large intestine (pH=8)

B. pulmonary alveoli (pH=7.4)

C. small intestine (pH=6)

D. stomach (pH=2)

A

D. stomach (pH=2)

154
Q

Your 69 year-old patient who has been taking warfarin for chronic atrial fibrillation appears in your office looking pale and complaining of weakness. You check his blood pressure and find it much lower than during his three most recent clinic visits. He mentions having had a dark tarry stool for the past three days, and his lab test indicates a high INR and low hematocrit. When questioned about his recent history he mentions taking OTC cimetidine for an upset stomach for the past few days. The most likely explanation for your patient’s symptoms is:

A. cimetidine induction of warfarin metabolism

B. cimetidine inhibition of warfarin metabolism

C. cimetidine induced synthesis of clotting factors

D. cimetidine interfering with warfarin absorption

E. cimetidine reducing the anticoagulant effect of warfarin

A

B. cimetidine inhibition of warfarin metabolism

155
Q

An antibiotic (rifampin) and an anticoagulant (warfarin) were administered daily together to a hospitalized patient for a week following a heart valve replacement. During this time the warfarin dosage was adjusted to get an INR of 2-3 and an increase in prothrombin time. On day 8, the rifampin was discontinued, and the patient was discharged. The same dosage of warfarin was continued for the next two weeks after discharge. What change would be expected at the end of the two weeks post-discharge?

A. prothrombin time would be decreased

B. warfarin plasma levels would remain unchanged

C. warfarin plasma levels would be increased

D. the patients INR would be below normal (<1.0)

E. the patients INR would be normal (1-1.3)

A

C. warfarin plasma levels would be increased

156
Q

Describe some of the potential differences in bioavailability between forms of medication administration (e.g. IV, PO, PR, IM, etc.).

A
157
Q
A

Both A and B

A. Cimetidine

B. Grapefruit juice

158
Q

How is ethanol distributed in the body?

A

In total body water

159
Q

A drug stored in tissues (e.g. fats) will have an artificially __________ volume of distribution.

A

A drug stored in tissues (e.g. fats) will have an artificially elevated volume of distribution.

(I.e. the apparent Vd is high because the plasma concentration is relatively low)

160
Q

________ binds medications in the bloodstream.

Liver damage leads to decreased ________ and a wider distribution of medications through body water and tissues.

A

Albumin binds medications in the bloodstream.

Liver damage leads to decreased albumin and a wider distribution of medications through body water and tissues.

161
Q
A

B. 15 L

162
Q
A

B. 250 mg

163
Q
A

C. The elimination clearance

164
Q

Liver metabolism depends on what?

(1) How much _______ is free
(2) _______ flow rates
(3) Internal _______ clearance

A

(1) How much medication is free*
(2) Blood flow rates
(3) Internal hepatic clearance
* *Only free (not protein-bound) medications can make it into the liver.*

165
Q
A

Small effect

166
Q

Via what organ systems can medications be cleared from the body?

A

Kidneys;

liver;

lungs;

secretions

167
Q

What happens before an administered drug starts being eliminated from the body?

A

It is distributed

168
Q

Describe the relationship between number of half-lives during maintenance dosing and eventual steady state concentration.

A
169
Q
A

C. 13 hours (half-life * 3.3)

170
Q
A

C. 3 days (2 half-lives)

2* dosing rate = 2 * steady state concentration

171
Q

True/False.

Clearance determines steady state concentration.

A

True.

Clearance determines steady state concentration.

172
Q

________, ______ frequent dosing has less likelihood of reaching toxic thresholds than ________, ______ frequent dosing (also, more likely to drop below effective threshold).

A

Smaller, less frequent dosing has less likelihood of reaching toxic thresholds than larger, more frequent dosing (also, more likely to drop below effective threshold).

173
Q

Describe the relationship between zero- and first-order kinetics and the rate of medication elimination.

A
174
Q

_______ _______ = same amount of medication coming in (via maintenance dosing) as is going out (via clearance).

A

Steady state = same amount of medication coming in (via maintenance dosing) as is going out (via clearance).

175
Q

Infusion rate = _________ rate * desired _______ _______

(multiply by bioavailability if an oral dose)

A

Infusion rate = clearance rate * desired steady state

(multiply by bioavailability if an oral dose)

176
Q

Describe the general relationship between time and drug effects in the body.

A