Intro To Pharmacology Exam 1

Front 1

Pharmacodynamics

Back 1

actions of drug on the body
(what the drug does to the body)

Front 2

Pharmacokinetics

Back 2

actions of the body on the drug
(ADME)

Front 3

What is needed for pharmacodynamics to occur?

Back 3

drug binding to receptor

Front 4

drug product

Back 4

preparations and formulations of drugs
(pills, tablets, capsules)

Front 5

drug substance

Back 5

active ingredient

Front 6

excipients

Back 6

inactive substances used as a carrier for the active ingredient
-accurate dosage
-stabilize the drug

Front 7

3 Names of a drug

Back 7

chemical, generic, trade

Front 8

Name of drug assigned by the FDA and is public property

Back 8

generic name
-first letter lower case with same endings in same pharmacological class

Front 9

Name of drug assigned by company, aka brand name

Back 9

trade name
-first letter is capitalized
-able to have a lot of trade names for one generic

Front 10

Prescription Drugs

Back 10

deemed unsafe without medical supervision

Front 11

Orphan Drugs

Back 11

target rare disease or conditions affecting fewer than 200,000 people

Front 12

Controlled Drugs

Back 12

classification depends on schedule

Front 13

Drugs scheduled according to:

Back 13

-medical use
-abuse liability
-tendency to develop physical and psychological dependence

Front 14

Dietary Supplement

Back 14

NOT intended to diagnose, treat, prevent, or cure disease

Front 15

Investigational New Drug (IND) Application

Back 15

FDA has 30 days to review

Front 16

Duties of the Institutional Review Board (IRB)

Back 16

-scientific merit
-ethical acceptabiltiy
-protection of patient rights
-proper consent process

Front 17

Basic Elements of Informed Consent

Back 17

-explanation of purpose and procedures of the research
-description of foreseeable risks and expected benifits
-statement of available alternative procedures or course treatment
-statement on confidentiality of records
-explanation of compenstaion and available medical treatments if injury occurs
-Participation is voluntary
-who to contact

Front 18

4 Phases of Clinical Trials

Back 18

Phase I - safety and pharmacokinetics
Phase II - safety and efficacy
Phase III - safety and efficacy
Phase IV - postmarketing studies

Front 19

Describe Phase I Clinical Trials

Back 19

-1st time in patients
-6 mo to 1 yr
-20 to 100 HEALTHY volunteers
-evaluating: safety and tolerability; pharmacokinetics and dose range

Front 20

Describe Phase II Clinical Trials

Back 20

-assess efficacy and safety
(optimal dose selection and dose schedule)
-100-200 pts with disease or condition

Front 21

Describe Phase II Clinical Trials

Back 21

-1000 - 6000 patients
-PROVE safety and efficacy

Front 22

Describe Phase IV Clinical Trials

Back 22

-detect rare or long term adverse effects
-larger pt population and longer timescales

Front 23

Receptors are responsible for drug _________

Back 23

selectivity

Front 24

Receptor determine relationship between drug dose and ________ _______

Back 24

pharmacological effect

Front 25

What do receptors mediate?

Back 25

action of agonist and antagonist

Front 26

Main affect of antagonist binding

Back 26

prevent agonist from binding and activating

Front 27

How does the degree of inhibition increase with competitive antagonist?

Back 27

increase the concentration of competitive antagonist

[Increase conc. of agonist can overcome effect of antagonist]

Front 28

What does a non-competitive antagonist do to receptor efficacy?

Back 28

decreases efficacy

-its potency is independent of the agonist dose

Front 29

Action of an irreversible antagonist

Back 29

covalently (irreversibly) binds the receptor
-duration of effect is dependent on the turnover rate of receptors

Front 30

Antagonism

Back 30

2 drugs produce opposite effects by interacting with two separate receptor systems

Front 31

What distinguishes an agonist from an antagonist?

Back 31

intrinsic activity = activates a receptor

Front 32

Describe the difference between affinity and intrinsic activity

Back 32

affinity - how well it binds
intrinsic activity - able to produce a measurable effect

~ do not always go hand in hand, ex. antagonist

Front 33

Axises of Michaelis-Menton graph

Back 33

X -> substrate concentration
Y -> reaction velocity

Front 34

Km of Michaelis-Menton kinetics

Back 34

Km = concentration of substrate needed to reach 1/2 Vmax
-measure of the affinity of the substrate for the enzyme

Front 35

What does Potency relate to?

Back 35

drug binding affinity

Front 36

What does efficacy relate to?

Back 36

rate and extent of receptor activation after drug binding

Front 37

What does EC(50) represent?

Back 37

concentration that produces 50% of the maximal effect

Front 38

What does the Law of Mass Action represent?

Back 38

drugs reversible interaction with a receptor

Front 39

Occupational Theory of drug binding

Back 39

magnitude of response is directly proportional to the # of receptors occupied or filled up

-potency is related to affinity for the receptor

Front 40

Kd

Back 40

concentration of drug required to bind 50% of receptor

Front 41

If Kd is low, binding affinity is _____

Back 41

high

Front 42

What is the difference between a full agonist and partial agonist

Back 42

full agonist - drug that produces full effect in a system

partial agonist - drug that interacts with receptor but is unable to produce full effect
*all relative

Front 43

Emax represents?

Back 43

efficacy
-maximum response achieved by an agonist

Front 44

ED50 represents?

Back 44

potency
-drug concentration at which 50% of Emax is achieved

Front 45

What is the graphical representation of potency

Back 45

further to the Left -> more potent

Front 46

Chemical Antagonist

Back 46

-chemical interaction of two substances
-does not require receptor

Front 47

Pharmacological Antagonist

Back 47

-binds to receptors, but does not activate signal transduction

Front 48

What happens to the potency and efficacy when a competitive antagonist is added to an agonist?

Back 48

reduce potency but does not effect efficacy
(need more of drug to produce the same effect)

Front 49

What happens to the efficacy and ED50 when in irreversible antagonist is added to an agonist?

Back 49

decrease Emax => decrease efficacy
- does not affect ED50

Front 50

What happens to the potency and efficacy when a non-competitive antagonist is added to an agonist?

Back 50

still have maximum potency but reduced efficacy

Front 51

Physiological antagonist

Back 51

-opposing effects by 2 agonists that act on different receptors
(both have intrinsic activity)

Front 52

Sensitivity of a cell to an agonist depends on ______ ______ and ______ _______ _______

Back 52

receptor affinity and total receptor concentration

Front 53

What is the role of spare receptors?

Back 53

increase sensitivity of target cells to activation by low levels of ligand

Front 54

What happens in the values of ED50 and Kd with spare receptors?

Back 54

a greater difference between the 2
(normally they are equal)
-due to greater sensitivity created by the spare receptors

Front 55

How do spare receptors affect the curve of a non-competitive antagonist?

Back 55

normally just decrease in the maximal response (decrease in efficacy)
->but see a shift to the Right due to spare receptors

Front 56

ED50

Back 56

=drug dose effective in 50% of population
Effective Dose (ED)

Front 57

LD50

Back 57

=lethal dose for 50% of the population

Front 58

Eq for Therapeutic Index

Back 58

TI = LD50/ED50
-margin of drug's safety
-higher ratio -> more safe/less toxic

Front 59

Eq for Certain Safety Factor

Back 59

CSF = LD1/ED99

Front 60

Concentration of a drug has a _______ effect on the intensity of the effect.

Back 60

direct

Front 61

What is required for passive diffusion

Back 61

concentration gradient

Front 62

First order process

Back 62

proportional to the magnitude of the drug concentration across a membrane
-rate dependent on concentration

Front 63

Eq for partition coefficient

Back 63

PC = ([drug] in lipid phase)/([drug] in aqueous phase)

-larger the # the greater the rate of transfer across a membrane (more lipid soluble)

Front 64

Weak acids become highly ionized as pH ________

Back 64

increases

Front 65

Weak bases become highly ionized as pH _____

Back 65

decreases

Front 66

In general what pH is more conducive to weak acid passage across a membrane?

Back 66

lower pH

Front 67

In general what pH is more conducive to weak base passage across a membrane?

Back 67

higher pH

Front 68

Henderson-Hasselbalch eq. for a weak acid

Back 68

pH = pKa + log (ionized/non-ionized)

Front 69

Henderson-Hasselbalch eq. for a weak base

Back 69

pH = pKa + log (non-ionized/ionized)

Front 70

First Pass Effect

Back 70

metabolism of drug before it reaches systemic circulation
-enzymes of intestinal bacteria
-enzymes of intestinal cells
-liver enzymes on the way to systemic circulation

Front 71

Why aren't absorption and bioavailability always equal?

Back 71

first pass effect

Front 72

Eq for oral absorption extraction ratio

Back 72

ER = (Ci - Co)/Ci

Ci = conc. in
Co = conc. out

Front 73

Do transport proteins require ATP?

Back 73

Yes

Front 74

P-glycoprotein

Back 74

aka. MDR1
-best known ATP binding cassette (ABC) protein

Front 75

Locations of P-glycoprotein

Back 75

-luminal surface of intestinal cells
-hepatocyte biliary canalicular membrane
-luminal surface of the renal proximal tubular cells
-luminal surface of brain endothelial cells

Front 76

2 transporters for uptake into hepatocytes (first pass metabolism)

Back 76

organic anion transporting polypeptide (OATP)
organic cation transporter (OCT)

Front 77

family of transporters responsible fro renal secretion

Back 77

organic anion transporter (OAT)

Front 78

Eq for Bioavailability

Back 78

Foral = AUC(PO)/AUC(IV)

Front 79

Issue with chemically equivalent preparations

Back 79

contain same amount of active ingredient but may not be therapeutically equivalent
-differ in bioavailability -> can not be used as generic substitute

Front 80

4 areas a generic drug is identical, or bioequivalent to a band name drug

Back 80

-dosage form
-safety, strength
-route of administration
-quality, performance characteristics and intended use

Front 81

2 transporters for uptake into hepatocytes (first pass metabolism)

Back 81

organic anion transporting polypeptide (OATP)
organic cation transporter (OCT)

Front 82

family of transporters responsible fro renal secretion

Back 82

organic anion transporter (OAT)

Front 83

Eq for Bioavailability

Back 83

Foral = AUC(PO)/AUC(IV)

Front 84

Issue with chemically equivalent preparations

Back 84

contain same amount of active ingredient but may not be therapeutically equivalent
-differ in bioavailability -> can not be used as generic substitute

Front 85

4 areas a generic drug is identical, or bioequivalent to a band name drug

Back 85

-dosage form
-safety, strength
-route of administration
-quality, performance characteristics and intended use

Front 86

Volume of Distribution (Vd)

Back 86

conceptual description of drug distribution
-volume into which the total amount of drug would be uniformly distributed to give the observed plasma concentration

Front 87

Eq for Volume of Distribution

Back 87

Vd = dose (D)/ measured plasma conc. (Cp)

-does not represent a real volume

Front 88

volume of drug limited to plasma water

Back 88

3L

Front 89

volume of drug limited to plasma water and interstitial water (extracellular water)

Back 89

12L

Front 90

volume of drug limited to intracellular water

Back 90

28L

Front 91

volume of drug found in total body water

Back 91

40L

Front 92

What does a very large Vd indicate?

Back 92

that the drug is not in the plasma

Front 93

What does Vd indicate?

Back 93

if the drug resided mainly in the plasma or tissue

Front 94

Does albumin prefer acidic or basic drugs?

Back 94

acidic
-plasma binding protein

Front 95

Does Alpha-1-acid glycoprotein (AAG) prefer acidic or basic drugs?

Back 95

basic

Front 96

Thiopental

Back 96

drug that redistributes
-transition of a drug from a rapidly perfused tissue to a slowly perfused tissue

Front 97

What is the limiting factor in duration and intensity of a LS drug?

Back 97

rate of metabolism

Front 98

bioactivation

Back 98

activate a drug via metabolism
-prodrug

Front 99

Describe what happens in an acetaminophen overdose

Back 99

-pathway to non-toxic metabolites via glucuronidation and sulfation become saturated
-excess drug metabolized by CYP450 -> produce toxic metabolites -> glutathione becomes depleted -> hepatotoxicity and cellular necrosis

Front 100

Phase I metabolism

Back 100

changes drug to a more polar metabolite
-many phase I metabolites not excreted
-metabolites often inactive

Front 101

Phase II metabolism

Back 101

-conjugation
-endogenous substrate added to drug by acetylation, glucuronidation or sulfation
-form highly polar, inactive metabolite that is renally excreted

Front 102

Phase II metabolism reactions

Back 102

-glucuronidation
-acetylation
-glutathione conjugation
-glycine conjugation
-methylation

Front 103

2 types of phase I metabolism

Back 103

-microsomal 'mixed function oxidases'
-microsomal P450 catalyzed oxidations

Front 104

_______ is involved in the metabolism of ~50% of clinically used drugs

Back 104

CYP3A4

Front 105

Where is CYP3A4 and what is it susceptible to?

Back 105

-found in the liver and intestine
-susceptible to induction and inhibition
(inducer: St. John's Wort)

Front 106

What does grapefruit juice inhibit?

Back 106

intestinal CYP3A4

Front 107

How do polymorphisms of CPY2D6 affect metabolism?

Back 107

creates is significant difference in effective dose due to the variation in individual metabolization
(poor to ultra-rapid metabolizers)

Front 108

What class of medications is CPY2D6 greatly involved in?

Back 108

antipsychotic medications

Front 109

What is the most frequent phase II reaction

Back 109

glucuronidation
(addition of a glucuronic acid)

Front 110

glucuronides

Back 110

drug that is excreted that has under-gone glucuronidation

Front 111

What is major function of glutathione conjugation

Back 111

protection of cells against toxic injury
-protects against free radicals, electrophils, reactive metabolites

Front 112

Phenobarbital

Back 112

classic inducer
-increase enzyme level to increase rate of metabolism

Front 113

autoinduction

Back 113

an inducer increase the rate of its own metabolism
-tolerance

Front 114

cimetidine

Back 114

significant inhibitor of P450 enzymes

Front 115

Which is more affected by age and disease Phase I or Phase II

Back 115

Phase I

Front 116

Clearance

Back 116

quantitative measure of elimination
-typically a measure of renal excretion

Front 117

Capacity-limited elimination

Back 117

clearance varies with concentration
-saturable
-blood concentrations continue to rise with continued doesing

Front 118

3 drugs that have capacity-limited elimination

Back 118

ethanol, phenytoin, aspirin

Front 119

Flow-dependent elimination

Back 119

drug easily cleared by elimination organ (high extraction)
-primarily dependent on rate of drug delivery to the organ

Front 120

Elimination

Back 120

general term for removal of drug from body
-refers to all processes involved

Front 121

Is a drug with a very large Vd readily removed by Dialysis?

Back 121

No, because a drug with a large Vd is tightly protein bound or extensively stored or distributed into a tissue

Front 122

Capacity-limited elimination

Back 122

clearance varies with concentration
-saturable
-blood concentrations continue to rise with continued dosing

Front 123

3 drugs that have capacity-limited elimination

Back 123

ethanol, phenytoin, aspirin

Front 124

Flow-dependent elimination

Back 124

drug easily cleared by elimination organ (high extraction)
-primarily dependent on rate of drug delivery to the organ

Front 125

Elimination

Back 125

general term for removal of drug from body
-refers to all processes involved

Front 126

Is a drug with a very large Vd readily removed by Dialysis?

Back 126

No, because a drug with a large Vd is tightly protein bound or extensively stored or distributed into a tissue

Front 127

Enterohepatic Recirculation

Back 127

phase II glucuronide conjugate is excreted via bile into the intestine -> glucuronidase regenerates the drug -> reabsorption of the drug

Front 128

Glomerular filtration rate

Back 128

100-120 ml/min

Front 129

Factors involved with Glomerular filtration

Back 129

-molecular size is the limiting factor
-protein bound drug is NOT filtered
-non-selective, non-saturable
-dependent on hydrostatic pressure

Front 130

Back diffusion

Back 130

drug move from nephron to circulation
-ionization traps drug

Front 131

In acidic urine what form is the weak acid drug in and what does that mean for reabsorption?

Back 131

greater [H+] causes a shift to HA -> increase reabsorption

Front 132

What is the active transporter for organic anions and conjugated metabolites

Back 132

P-glycoprotein

Front 133

Active transporter for organic cations

Back 133

ABC transporters

Front 134

drug clearance >120 mL/min

Back 134

must involve tubular secretion

Front 135

drug clearance < 120mL/min

Back 135

must involve tubular reabsorption

Front 136

max CL

Back 136

~1500 mL/min
-equal to the liver blood flow

Front 137

Eq. for Clearance

Back 137

Cl (L/hr) = Rate of elimination (mg/hr) / C (mg/L)

Front 138

Total systemic clearance

Back 138

-clearance is additive
CLsystem = CL renal + CL liver + CL other

Front 139

Eq for the rate of elimination

Back 139

rate of elimination = CL x C
-First order elimination

Front 140

Zero order elimination

Back 140

elimination of constant amount of drug per unit time, independent of concentration

Front 141

Eq. of Renal Clearance

Back 141

CLr = (UxV)/(CpxT)
U = urine concentration, V = urine volume
-hypothetical
-amount of plasma that would have to be 100% cleared of drug to obtain that amount in urine

Front 142

Clearance helps determine what PK parameter

Back 142

maintenance dose rate

Front 143

Volume of distribution (Vd) helps determine which PK parameter

Back 143

loading dose (LD)

Front 144

Half-life (t1/2) helps determine which PK parameter?

Back 144

time to steady-state and dosing interval

Front 145

First Order Kinetics

Back 145

-elimination rate dependent on drug concentration
-rate of elim. = CL x Cp
-clearance is fixed but rate is variable

Front 146

Zero Order Kinetics

Back 146

-elimination rate is independent of drug concentration and constant over time
-as conc. goes up the clearance decreases
-dose change will be reflected in proportional change in plasma concentration

Front 147

In 1st order kinetics is the half-life dependent on concentration?

Back 147

No

Front 148

What occurs with the half-life in zero order kinetics?

Back 148

half-life becomes longer as the concentration increases

-hang over!

Front 149

Which drugs display dose dependent kinetics

Back 149

ethanol, aspirin, phenytoin

Front 150

3 Eq. for clearance

Back 150

CL = Does/AUC
CL = (F x Dose)/AUC
CL = (0.693 x Vd)/t1/2

Front 151

Eq. for half-life

Back 151

t1/2 = (0.693*Vd)/CL

Front 152

Significance of 5 t1/2

Back 152

amount of time to reach steady state and amount of time to eliminate drug

Front 153

3.3 t1/2 =

Back 153

90%

Front 154

What are 2 methods to achieve a Plateau of steady state concentrations

Back 154

-give drug at constant intervals of less than 5 t1/2
-continuous infusion

Front 155

Eq for steady state drug concentration

Back 155

Css = infusion rate (R)/ clearance (CL)

Front 156

What does a faster rate of infusion change and not change

Back 156

change: steady-state concentration
does not change: time to steady state

Front 157

Expanded Eq for steady state concentration

Back 157

Css = (1.44 x F x D x t1/2)/(Vd x T)

Front 158

Purpose of a loading dose

Back 158

achieves therapeutic levels with a single dose

Front 159

Eq for loading dose

Back 159

Dose(loading) = Css x Vd

For oral: Dose(loading) = (Css x Vd)/Foral

Front 160

Eq for maintenance dose

Back 160

Dose(maintenance) = Css x CL

For oral: Dose(maintenance) = (Css x CL)/ Foral

Front 161

Eq for intermittent dose for the maintenance dose

Back 161

Dose(maintenance) = Css x CL x Dose interval

Front 162

2 Eq for dose adjustments

Back 162

New Dose = t1/2(normal)/t1/2(disease) x maintenance dose

new dose = CL(diseased)/CL(normal) x maintenance dose

Front 163

2Eq for dose interval adjustment

Back 163

New interval = t1/2(diseased)/t1/2(normal) x old interval

New interval = CL(normal)/CL(disease) x old interval

Front 164

Synergistic drug-drug interactions

Back 164

observed effect of 2 drugs > than additive effect

2+3 = 20

Front 165

Potentiation of drug-drug interactions

Back 165

one drug does not cause a effect but combined with another produces a greater effect

0+2 = 10

Front 166

Idiosyncratic response

Back 166

genetically determined variable response to a drug

Front 167

Type II hypersensitivity

Back 167

immune mediated destruction of RBC
-drug modified RBC induce production of antibodies -> RBC with antibodies are more susceptible to lysis or phagocytosis

Front 168

Pharmacokinetic Tolerance

Back 168

-metabolic in nature
(drug does not work as well as it used to -> increase dose to get the same response)
-lower drug conc. at the receptor site

Front 169

Pharmacodynamic Tolerance

Back 169

-cellular-adaptive in nature
(receptors adapt sensitivity or increase or decrease number of receptors)

Front 170

What are the axises of a Quantal Dose Response Curve

Back 170

x - minimal effective dose
y - frequency of population responding (did they respond, yes/no)

Front 171

What does a Graded Dose Response Curve represent

Back 171

difference in intensity of response in an individual
-info on potency, selectivity, maximal efficacy

Front 172

What does a quantal dose response curve show

Back 172

distribution of effective doses in a GROUP or Population
-info: potency, selectivity, variability (pharmacodynamic variability in pt pop.)

Front 173

Graded Dose effect endpoint relates dose to _______ of effect

Back 173

intensity

Front 174

Quantal dose effect endpoint relates dose to ________ of effect

Back 174

frequency

Front 175

In a quantal dose curve what does a larger standard deviation represent?

Back 175

greater variability