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

Question 1

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

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

Answer 1

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

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

Question 2

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

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

Answer 2

Pharmacokinetics;

pharmacodynamics

Question 3

Most drugs are in what molecular weight range?

Answer 3

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

Question 4

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

Answer 4

Ligands

Question 5

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)?

Answer 5

Receptors transduce a signal to produce a biological effect;

binding sites don’t

Question 6

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

Covalent bonds

Electrostatic interactions

H⁺ , Van der Waals, & hydrophobic interactions

Answer 6

Electrostatic interactions

Question 7

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

Answer 7

H+ , Van der Waals, & hydrophobic interactions

Question 8

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

Covalent bonds

Electrostatic interactions

H+ , Van der Waals, & hydrophobic interactions

Answer 8

Covalent bonds

Question 9

True/False.

Stererospecificity matters to proper drug ligand function.

Answer 9

True.

Question 10

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

Answer 10

Affinity — binding attractiveness

Efficacy — strength of effect

Question 11

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

Answer 11

Antagonists possess affinity only

(no efficacy)

Question 12

A high K_A indicates ________ affinity.

A high K_D indicates ________ affinity.

Answer 12

High;

low

Question 13

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

Answer 13

Question 14

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

Answer 14

K_D

(ratio of K_-1 to K₁)

Question 15

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

Answer 15

Ligand;

K₁;

K_-1

Question 16

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

Answer 16

50% of receptors

Question 17

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

Answer 17

Question 18

True/False.

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

Answer 18

True.

Question 19

What is a dose-response curve?

Answer 19

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

Question 20

What is this type of graph called?

Answer 20

A dose-response curve

Question 21

On a dose-response curve, what is E_Max?

What is EC₅₀?

Answer 21

The maximal effect (Y axis)

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

Question 22

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

Answer 22

Easier visualization and math on the sigmoidal curve

Question 23

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

Answer 23

Spare receptors are present

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

Question 24

For a certain drug, EC₅₀ = K_d.

Are spare receptors present?

Answer 24

No.

(Only if EC₅₀ < K_d; as shown below)

Question 25

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

Answer 25

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

Question 26

**True/False**. We are typically more sensitive to agonists with fewer receptors than agonists with spare receptors.

Answer 26

**False**. We are typically more sensitive to agonists ***with spare receptors.***

Question 27

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

Answer 27

The drug with the ***_lowest_*** **EC₅₀** is the most potent. (Less drug for more effect)

Question 28

Answer 28

A. Drug X (Lower EC₅₀)

Question 29

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

Answer 29

B and C; D

Question 30

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

Answer 30

Question 31

Answer 31

Drug X (higher E_max)

Question 32

What is inverse pharmacological agonism?

Answer 32

Decreasing a consititutively active receptor (i.e. decreasing basal tone / intrinsic activity)

Question 33

**True/False**. Inverse agonism is just another term for antagonism.

Answer 33

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

Question 34

\_\_\_\_\_\_\_\_ drugs increase receptor activity to levels above basal tone. \_\_\_\_\_\_\_\_ ________ drugs decrease receptor activity to levels below below basal tone.

Answer 34

**Agonist** drugs increase receptor activity to levels above basal tone. **Inverse** **agonist** drugs decrease receptor activity to levels below below basal tone.

Question 35

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

Answer 35

The endogenous agonist

Question 36

**True/False**. By definition, partial agonists have both agonistic and antagonistic activity.

Answer 36

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

Question 37

\_\_\_\_\_\_\_\_\_\_ic antagonists bind the *_same_* receptor as the agonist drug in question. \_\_\_\_\_\_\_\_\_\_ic antagonists bind a *_different_* receptor as the agonist drug in question.

Answer 37

**Pharmacolog**ic antagonists bind the *_same_* receptor as the agonist drug in question. **Physiolog**ic antagonists bind a *_different_* receptor as the agonist drug in question.

Question 38

\_\_\_\_\_\_\_\_\_\_ antagonists bind or alter the agonist drug in question, *_not_* a receptor.

Answer 38

**Chemical** antagonists bind or alter the agonist drug in question, *_not_* a receptor.

Question 39

Answer 39

D. Pharmacologic antagonist

Question 40

Answer 40

C.

Question 41

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

Answer 41

The **ED₅₀** is the drug concentration at which 50% of the population manifests the desired effect. (**E**ffective **D**ose)

Question 42

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

Answer 42

The **LD₅₀** is the drug concentration at which 50% of the population is killed by the drug. (**L**ethal **D**ose)

Question 43

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

Answer 43

The **TD₅₀** is the drug concentration at which 50% of the population manifests a given toxic effect. (**T**oxic **D**ose)

Question 44

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.

Answer 44

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.

Question 45

How is the therapeutic index of a drug calculated?

Answer 45

\***LD₅₀ / ED₅₀** \**(or TD₅₀)*

Question 46

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?

Answer 46

150/3 = **50**

Question 47

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

Answer 47

**High**! (LD₅₀ / ED₅₀)

Question 48

Answer 48

Drug B

Question 49

Agonists typically \_\_\_\_\_\_-regulate receptors on target tissues. Antagonists typically \_\_\_\_\_\_-regulate receptors on target tissues.

Answer 49

Agonists typically **down**-regulate receptors on target tissues. Antagonists typically **up**-regulate receptors on target tissues.

Question 50

Answer 50

B.

Question 51

Answer 51

E. Partial agonist

Question 52

G_αs is a(n) _______ subunit. G_α**i** is a(n) _______ subunit. G_α**_q** increases intracellular \_\_\_\_\_\_\_.

Answer 52

G_s is a **stimulatory** subunit. Gi is an **inhibitory** subunit. G_q increases intracellular **calcium**.

Question 53

Answer 53

D. Activation of adenylate cyclase

Question 54

Answer 54

C. RTKs

Question 55

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

Answer 55

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

Question 56

**True/False**. Differing drugs will have various and complex methods of transport and metabolism in the body.

Answer 56

True.

Question 57

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

Answer 57

Question 58

**True/False**. All drugs undergo this basic mechanism: Administration --\> Absorption --\> Distribution --\> Metabolism --\> Excretion

Answer 58

**False**.

Question 59

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

Answer 59

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

Question 60

P-\_\_\_\_\_\_\_\_\_\_ is an outward transporter found in several areas of the body and acts to _\_\_crease_ drug absorption.

Answer 60

P-**_glycoprotein_** is an outward transporter found in several areas of the body and acts to **_decrease_** drug absorption.

Question 61

Lipo\_\_\_\_\_ drugs are more easily absorbed.

Answer 61

Lipo**philic** drugs are more easily absorbed.

Question 62

What type of drug is readily absorbed in the stomach?

Answer 62

Weak acids

Question 63

**True/False**. Weak bases are well-absorbed in the stomach.

Answer 63

**False**. Weak ***acids*** are well-absorbed in the stomach. (Weak bases are almost not absorbed at all)

Question 64

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

Answer 64

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

Question 65

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

Answer 65

Increase

Question 66

What is pharmacologic ion trapping?

Answer 66

Drugs are ionized *after* being taken up | (and thus trapped)

Question 67

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

Answer 67

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

Question 68

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?

Answer 68

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

Question 69

Drugs in the plasma are often \_\_\_\_ly bound to \_\_\_\_\_\_.

Answer 69

Drugs in the plasma are often **weak**ly bound to **albumin**.

Question 70

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)?

Answer 70

Liver, kidney, brain

Question 71

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

Answer 71

Fat, muscle, and bone (many drugs are tissue-specific)

Question 72

Drug excretion mainly happens via what organs? (the most important one is bolded)

Answer 72

**Kidneys** (urine); liver (bile)

Question 73

How can ion trapping be used to increase drug excretion?

Answer 73

Alkalinization or acidification of the urine

Question 74

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

Answer 74

Sweat glands; mammary glands; lungs

Question 75

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

Answer 75

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

Question 76

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

Answer 76

Making substances more hydrophilic (hydroxylations, removal of aryl groups, etc.)

Question 77

Name if each of the following is a type I or type II reaction performed by the CP450 system: ## Footnote **Oxidation** **Conjugation** **Reduction** **Hydrolysis**

Answer 77

Oxidation (**Type I**) Conjugation (**Type I**​**I**) Reduction (**Type I**​) Hydrolysis (**Type I**​)

Question 78

The following are all part of what system? **Alcohol dehydrogenase** **Xanthine oxidase** **Monoamine oxidases** **Diamine oxidases** **Reductases** (azo- or nitro-) **Hydroxylases**

Answer 78

Type I cytochrome P450

Question 79

What type of drug induces the P450 system?

Answer 79

Drugs that challenge the system | (often have lots of side chains)

Question 80

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

Answer 80

Conjugation; acetylation; methylation; glucoronidation

Question 81

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

Answer 81

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).

Question 82

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

Answer 82

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

Question 83

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

Answer 83

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

Question 84

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

Answer 84

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

Question 85

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

Answer 85

Yes! ## Footnote *(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.)*

Question 86

Is CP450 induction typically reversible?

Answer 86

Yes

Question 87

Which CP450 isozyme is induced by cigarette smoking?

Answer 87

CYP1A

Question 88

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

Answer 88

P-450 **2D6**

Question 89

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

Answer 89

CYP2E1

Question 90

Which CP450 isozyme is the **_most abundant_** in the liver microsomes and the **_most important_ for drug metabolism**?

Answer 90

CYP3A4

Question 91

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)? ## Footnote *(NOTE: some of the relevant substrates are listed below.)*

Answer 91

Drugs that end in '-azole' (flucanazole; ketoconazole; clotrimazole; etc.) *(NOTE: some of the relevant substrates are listed below.)*

Question 92

Aspirin is an example of a weak \_\_\_\_\_\_. Quinidine is an example of a weak \_\_\_\_\_\_.

Answer 92

Aspirin is an example of a weak **acid**. Quinidine is an example of a weak **base**.

Question 93

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

Answer 93

Rifampin; St. John's wort

Question 94

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

Answer 94

Cimetidine; grapefruit juice

Question 95

What is the 'first pass effect' of pharmacodynamics? What are some example drugs where this occurs?

Answer 95

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

Question 96

What are some example substances that induce the CP450 system?

Answer 96

Rifampin, barbiturates, St. John’s Wort

Question 97

What are some example substances that suppress the CP450 system?

Answer 97

Cimetidine, grapefruit juice, ketoconazole

Question 98

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

Answer 98

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

Question 99

**True/False**. All medications have a similar volume of distribution (Vd) of about 40 L.

Answer 99

**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.

Question 100

# Define volume of distribution (Vd). Define clearance (Cl).

Answer 100

The body volume (**L**) that the drug dose (mg) occupies; the volume per unit time that is filtered completely free of drug

Question 101

**V_d = Loading ____ / \_\_\_**

Answer 101

V_d = Loading **dose** / **[Drug_intiital]** **V_d** --- volume of distribution; Loading dose --- initial dosage given **C₀** --- initial [drug]

Question 102

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

Answer 102

Loading Dose = **C₀ x V_d** = 5 mg/L x 30 L = **150 mg**

Question 103

t_1/2 = 0.\_\_\_ V_d / \_\_\_

Answer 103

t_1/2 = 0.**69** V_d / **Cl**

Question 104

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

Answer 104

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

Question 105

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

Answer 105

**3.3** (t(0.90) = 3.3 t_1/2)

Question 106

What is C_SS? | (Pharmacokinetics)

Answer 106

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

Question 107

**C_SS = _________ / Clearance.** C_SS --- steady state [drug]

Answer 107

C_SS = **_Dosing Rate_** / Clearance. C_SS --- steady state [drug]

Question 108

If you know the desired therapeutic plasma concentration (C_SS) 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?

Answer 108

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

Question 109

Name a few medications metabolized under zero-order conditions.

Answer 109

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

Question 110

What is bioavailability?

Answer 110

The amount making it to circulation from PO meds / Amount making it to circulation from IV meds \* 100 (IV meds have 100% bioavailability)

Question 111

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ 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.

Answer 111

**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.

Question 112

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

Answer 112

**Dosing rate** = **clearance** \* **C_SS**

Question 113

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

Answer 113

**Increase** *(Dosing rate = clearance \* C_SS)*

Question 114

What is first pass metabolism?

Answer 114

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

Question 115

**True/False**. The three components of pharmacokinetics are absorption, distribution, and elimination.

Answer 115

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

Question 116

Answer 116

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

Question 117

Answer 117

A.

Question 118

Answer 118

B. EC₅₀

Question 119

Answer 119

C. 10 (TD₅₀/ED₅₀)

Question 120

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?

Answer 120

**2** (TD₅₀)

Question 121

Answer 121

D. Drug D

Question 122

Answer 122

B. Drug B

Question 123

Answer 123

B. Competitive antagonist

Question 124

Answer 124

C. Noncompetitive antagonist

Question 125

Answer 125

C. Signal transduction (only true receptors cause signal transduction)

Question 126

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): ## Footnote **IM injection** **Per rectum** **Oral suspension** **Oral tablet**

Answer 126

**Oral suspension**

Question 127

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

Answer 127

D. Transdermal patch

Question 128

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

Answer 128

A. i.v. injection

Question 129

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

Answer 129

B. Place it under his tongue (no significant pre-clearance)

Question 130

Answer 130

**E. 50 L** 8 ug/ml = 8 mg/L C₀ (mg/L) = Dose/Vd V_d = (400 mg)/(8 mg/L) = 50L

Question 131

A 70 kg man with severe burns arrives in the Emergency Department and requires i.v. morphine to treat his pain. The V_d 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

Answer 131

**D. 12 mg** C₀ (mg/L) = Dose/V_d, or Dose = C₀ x V_d. Therefore, the Loading Dose = 60 ug/L x 200 L = 12,000 ug or 12 mg.

Question 132

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 V_d = 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

Answer 132

**D. 100 mg** V_d = 0.5 L/kg x 40 kg = 20 L. 5 ug/ml = 5 mg/L. Dose = 5 mg/L x 20 L = 100 mg.

Question 133

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

Answer 133

**E. 200 mg** Dosage Rate = C_SS x Cl = (5 mg/L) x (5L/hr) x (8 hrs) = 25 mg/hr x 8 hrs = 200 mg.

Question 134

Answer 134

**1.75 L/hr** V_d = (320 mg)/(32 mg/L )= **_10 L_** t_1/2 = 0.7 V_d/Cl or Cl = 0.7V_d/t_1/2 Cl = 0.7 x 10 L/4 hr = 1/75 L/hr

Question 135

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

Answer 135

C. Elimination half life

Question 136

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

Answer 136

B. 50 days

Question 137

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

Answer 137

C. 6.6 hrs (It takes 3.3t_1/2 to reach 90% of steady state during a continued maintenance dosage regimen.)

Question 138

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

Answer 138

D. 80 mg

Question 139

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 V_d 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

Answer 139

**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. ```

Question 140

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

Answer 140

**B. Increased (longer)** (t_1/2 = 0.7 Vd/Cl)

Question 141

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

Answer 141

**C. 5 ug/ml** C_SS = Dosing Rate ÷ Cl = (1000 mg/6 hr) ÷ (33 L/hr) = (166.7 mg/hr) ÷ (33 L/hr) = 5.05 mg/L.

Question 142

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

Answer 142

**B. 1.0 ug/L** Dosing Rate (ug/day) = C_SS (ug/L) x Cl (L/day) or C_SS (ug/L) = Dosing Rate (ug/day)/Cl (L/day) = (250 ug/day)/250 (L/day)= 1 ug/L

Question 143

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, V_d = 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

Answer 143

**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

Question 144

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

Answer 144

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

Question 145

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

Answer 145

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

Question 146

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%

Answer 146

C. 75% (In one half-life, you get to 50% of steady state.)

Question 147

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

Answer 147

B. high affinity for tissue proteins or high fat solubility

Question 148

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 t_1/2 B. decreased digoxin plasma levels, and increased digoxin t_1/2 C. increased digoxin plasma levels, and decreased digoxin t_1/2 D. increased digoxin plasma levels, and increased digoxin t_1/2

Answer 148

D. increased digoxin plasma levels, and increased digoxin t_1/2

Question 149

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

Answer 149

D. P450-induction by phenytoin

Question 150

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

Answer 150

E. Unionized form

Question 151

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)

Answer 151

D. hydroxyl (OH)

Question 152

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

Answer 152

**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

Question 153

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)

Answer 153

D. stomach (pH=2)

Question 154

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

Answer 154

B. cimetidine inhibition of warfarin metabolism

Question 155

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)

Answer 155

C. warfarin plasma levels would be increased

Question 156

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

Answer 156

Question 157

Answer 157

**Both A and B** A. Cimetidine B. Grapefruit juice

Question 158

How is ethanol distributed in the body?

Answer 158

In total body water

Question 159

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

Answer 159

A drug stored in tissues (e.g. fats) will have an artificially **elevated** volume of distribution. ## Footnote *(I.e. the apparent V_d is high because the plasma concentration is relatively low)*

Question 160

\_\_\_\_\_\_\_\_ binds medications in the bloodstream. Liver damage leads to decreased ________ and a wider distribution of medications through body water and tissues.

Answer 160

**Albumin** binds medications in the bloodstream. Liver damage leads to decreased **albumin** and a wider distribution of medications through body water and tissues.

Question 161

Answer 161

**B. 15 L**

Question 162

Answer 162

**B. 250 mg**

Question 163

Answer 163

**C. The elimination clearance**

Question 164

Liver metabolism depends on what? (1) How much _______ is free (2) _______ flow rates (3) Internal _______ clearance

Answer 164

(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.*

Question 165

Answer 165

Small effect

Question 166

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

Answer 166

**Kidneys**; **liver**; lungs; secretions

Question 167

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

Answer 167

It is distributed

Question 168

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

Answer 168

Question 169

Answer 169

C. 13 hours (half-life \* 3.3)

Question 170

Answer 170

C. 3 days (2 half-lives) 2\* dosing rate = 2 \* steady state concentration

Question 171

**True/False**. Clearance determines steady state concentration.

Answer 171

**True**. Clearance determines steady state concentration.

Question 172

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

Answer 172

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

Question 173

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

Answer 173

Question 174

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

Answer 174

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

Question 175

Infusion rate = _________ rate \* desired _______ \_\_\_\_\_\_\_ (multiply by bioavailability if an oral dose)

Answer 175

Infusion rate = **clearance** rate \* desired **steady** **state** (multiply by bioavailability if an oral dose)

Question 176

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

Answer 176