Cmbmp Test 1

Front 1

Henderson-Hasslebach (for both acids and bases)

Back 1

pH = log([A-]/[HA]) + pKa
pH = log([B]/[HB+]) + pKa

Front 2

T/F: Acids are preferentially absorbed under basic conditions (pH>pKa).

Back 2

False.

Acids absorbed under acidic conditions.
Bases absorbed under basic conditions.

Front 3

Intensity and duration of drug action depends on _______ at ________.

Back 3

Intensity and duration of drug action depends on concentration at receptor site.

Front 4

3 Controls of Drug Concentration

Back 4

1. Dose
2. Dosing interval
3. Route of administration

Front 5

Pharmaceutical principles

Back 5

Disintegration and dissolution of drug

Front 6

Pharmacokinetic principles (4)

Back 6

"How the drug gets to the target"

1. Absorption
2. Distribution
3. Biotransformation
4. Excretion

Front 7

Pharmacodynamic principles

Back 7

"How the drug affects the body"

Drug/receptor interactions

Front 8

Biotransformation

Back 8

Conversion of drug molecule to more water-soluble form

Front 9

T/F: The first-pass effect occurs in the liver and explains why administered and received doses are not equal.

Back 9

True

Front 10

________, _______ and _______ are three routes of administration that avoid the first-pass effect.

Back 10

IV, sublingual/buccal cavity and rectal are three routes of administration that avoid the first-pass effect.

Front 11

4 reasons to avoid oral administration

Back 11

1. Nausea or vomiting
2. Unwilling or unable to swallow
3. Drug destroyed by digestive enzymes
4. Drug is not absorbed through gastric mucosa

Front 12

T/F: Insulin can be taken orally.

Back 12

False. Insulin is destroyed by gastric enzymes.

Front 13

T/F: Nitroglycerin is slow-acting and should be swallowed.

Back 13

False. Nitroglycerin is a fast-acting angina medication that should be taken sublingually.

Front 14

3 advantages of controlled-release dosage forms

Back 14

1. Reduce dosing frequency
2. Reduce fluctuations in drug levels
3. More uniform pharmacological response

Front 15

T/F: Drugs administered subcutaneously and intramuscularly are often watery and hydrophilic.

Back 15

False. Drugs administered subcutaneously and intramuscularly are often oily and hydrophobic.

Front 16

T/F: Uncharged molecules often diffuse relatively easy across cell membranes while charged molecules require more active binding and transport.

Back 16

True

Front 17

Fick's Law of Diffusion

(Define the variables)

Back 17

J = -DA(∆C/∆X)

J is rate of diffusion or net flux
D is diffusion coefficient
A is area available for diffusion
∆C/∆X is concentration gradient

Front 18

5 characteristic that impact diffusion

Back 18

1. Size
2. Hydrophobicity
3. Charge
4. Shape
5. Attachments

Front 19

Definition of pKa

Back 19

Ionization constant.

Equal to the pH of a solution when the molar concentrations of the protonated and unprotonated forms are equal ([A-]=[HA] or [B]=[HB+]).

Front 20

Patients suffering from Maple Syrup Urine Disease cannot catabolize which 3 amino acids?

How is it diagnosed?

Back 20

1. Leucine
2. Isoleucine
3. Valine

Diagnosis: ketosis and excess acid in blood

Front 21

T/F: L enantiomers do not exist in proteins, but can be free amino acids.

Back 21

False. D enantiomers do not exist in proteins, but can be free amino acids.

Front 22

The CORN-clock law helps to identify ______ when _____ is read _________ from the ______, ______, and ________ groups of an amino acid.

Back 22

The CORN-clock law helps to identify L enantiomers when "CORN" is read clockwise from the carboxylic acid, functional, and amino groups of amino acid.

Front 23

At physiological pH, the amino group is ______ and the carboxylic acid group is ______, making the amino acid in this form a _______.

Back 23

At physiological pH, the amino group is positive and the carboxylic acid group is negative, making the amino acid in this form a zwitterion.

Front 24

Moving from pH=1 to pH=14, the ______ group is deprotonated first, followed by the _______ group.

Back 24

Moving from pH=1 to pH=14, the carboxylic acid group is deprotonated first, followed by the amino group.

Front 25

Aliphatic Side Chain Amino Acids

Back 25

1. Glycine
2. Alanine
3. Valine
4. Leucine
5. Isoleucine

Front 26

Glycine

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 26

1. Gly
2. G
3. -H

*Flexible and allows for tight folding

Front 27

Alanine

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 27

1. Ala
2. A
3. -CH3

Front 28

Valine

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 28

1. Val
2. V
3. -CH-CH3
-CH3

Front 29

Leucine

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 29

1. Leu
2. L
3. -CH2-CH-CH3
-CH3

Front 30

Isoleucine

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 30

1. Ile
2. I
3. -CH-CH2-CH3
-CH3

Front 31

Aromatic Side Chain Amino Acids

Back 31

1. Phenylalanine
2. Tyrosine
3. Tryptophan

*Bulky, greasy and often buried in soluble proteins

Front 32

Phenylalanine

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 32

1. Phe
2. F
3. -CH2-C6H5

Front 33

Tyrosine

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 33

1. Tyr
2. Y
3. -CH2-C6H5-OH

*Can be phosphorylated

Front 34

Tryptophan

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 34

1. Try
2. W
3. -CH2-C8H6N

Front 35

Sulfur-Containing Chain Amino Acids

Back 35

1. Cysteine
2. Methionine

*Form covalent disulfide bonds in proteins.
*Hydrophobic (like aliphatic chains), so they are located on interior of proteins.

Front 36

Cysteine

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 36

1. Cys
2. C
3. -CH2-SH

Front 37

Methionine

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 37

1. Met
2. M
3. -CH2-CH2-S-CH3

Front 38

Aliphatic Hydroxyl Chain Amino Acids

Back 38

1. Serine
2. Threonine

*Can be phosphorylated
*High potential for H-bonding

Front 39

Serine

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 39

1. Ser
2. S
3. -CH2-OH

Front 40

Threonine

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 40

1. Thr
2. T
3. -CH-OH
-CH3

Front 41

Basic Chain Amino Acids

Back 41

1. Lysine
2. Arginine
3. Histidine

Front 42

Lysine

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 42

1. Lys
2. K
3. -CH2-CH2-CH2-CH2-NH3+

*Long, greasy chain
*Extends interior to exterior of protein
*Can be acetylated

Front 43

Arginine

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 43

1. Arg
2. R
3. -CH2-CH2-CH2-NH-C=NH2+
-NH2

*Long, greasy branched chain

Front 44

Histidine

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 44

1. His
2. H
3. -CH2-C3H4N2+

*Often present at active sites

Front 45

Acidic Chain Amino Acids and Amide Derivatives

Back 45

1. Aspartic Acid
2. Asparagine
3. Glutamic Acid
4. Glutamine

Front 46

Aspartic Acid

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 46

1. Asp
2. D
3. -CH2-CO2H

*Asx and B if indistinguishable from asparagine.

Front 47

Asparagine

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 47

1. Asn
2. N
3. -CH2-CO-NH2

*Asx and B if indistinguishable from aspartic acid.

Front 48

Glutamic acid

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 48

1. Glu
2. E
3. -CH2-CH2-CO2H

*Glx and Z if indistinguishable from glutamine.

Front 49

Glutamine

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 49

1. Gln
2. Q
3. -CH2-CH2-CO-NH2

*Glx and Z if indistinguishable from glutamic acid.

Front 50

Proline

1. Three-letter abbreviation
2. Single-letter abbreviation
3. Structure

Back 50

1. Pro
2. P
3. -CH2-CH2-
-NH2+-CH2-

*"Helix breaker"

Front 51

Non-human Chain Amino Acids

Back 51

1. Selenocysteine (Sec, U)
2. Pyrrolysine (Pyl, O)

*Appear in bacterial enzymes

Front 52

Essential Amino Acids

Back 52

These cannot be synthesized and must be ingested.

Aliphatic: Met, Ile, Leu, Val
Aromatic: Phe, Try, Tyr (if unable to convert Phe)
Basic: Lys, His, Arg (infants/children)
Hydroxyl: Thr

Front 53

Phenylketonuria (PKU) is an inability to break down ________ and convert it into ________.

Back 53

Phenylketonuria (PKU) is an inability to break down phenylalanine and convert it into tyrosine.

Front 54

Peptide bonds exhibit ________ bond character, making them slightly _______ in length than regular single bonds.

Back 54

Peptide bonds exhibit partial double bond character, making them slightly shorter in length than regular single bonds.

Front 55

T/F: For peptide bond isomers, cis dominates.

Back 55

False. For peptide bond isomers, trans dominates. Cis occurs for proline and at active sites.

Front 56

T/F: Oligo-/Polypeptides begin at the amino terminus and end at the carboxyl terminus.

Back 56

True

Front 57

Examples of Covalent Post-Translational Modifications

Back 57

1. Methylation
2. Hydroxylation
3. Acetylation
4. Phosphorylation
5. Glycosylation
6. Myristylation
7. Palmitoylation

Front 58

Techniques for Protein/Peptide Isolation (5)

Back 58

1. Chromatography (size, hydrophobicity, charge)
2. Reverse Phase High Pressure Chromatography (peptides)
3. SDS-PAGE (purity and size)
4. Isoelectric Focusing (charge and size)
5. Mass Spectrometry (protein mixtures)

Front 59

Levels of Protein Structure

Back 59

1. Primary: AA sequence
2. Secondary: helices and sheets
3. Tertiary: 3-D structure of polypeptide
4. Quaternary: multi-polypeptide proteins

Front 60

T/F: Covalent bonding is primarily involved in the secondary, tertiary and quaternary levels of protein structure.

Back 60

False. Non-covalent bonding is primarily involved in the secondary, tertiary and quaternary levels of protein structure. Covalent bonding is responsible for primary structure.

Front 61

Definition of Circular Dichroism

Back 61

Differential absorption of left and right circularly polarized light.

Used to identify secondary protein structures.

Front 62

Characteristics of Alpha Helix (5)

Back 62

1. 3.6 residues per turn
2. 5Å diameter
3. Linked by H-bonding between i and i+4
4. No proline or poly-glycine
5. Net charge dipole (N-positive, C-negative)

Front 63

3 Types of Helices

Back 63

1. 3-10: tight, 3 residues/turn, i to i+3
2. Alpha: medium, 3.6 residues/turn, i to i+4
3. π: loose, ≥4 residues/turn, i to i+5

Front 64

2 Types of ß-Sheets

Back 64

1. Antiparallel: direct H-bonding, flat, contiguous amino acids

2. Parallel: indirect H-bonding, kinked, non-contiguous amino acids

Front 65

A common combination for ß-Turns are the amino acids ______ and ______, but it can be any amino acids.

Back 65

A common combination for ß-Turns are the amino acids proline and glycine, but it can be any amino acids.

Front 66

6 Techniques for Determining Tertiary and Quaternary Structure

Back 66

1. NMR
2. X-ray Crystallography
3. Electron Microscopy
4. Electron Diffraction
5. Single Particle Analysis
6. Modeling

Front 67

T/F: Large proteins fold spontaneously and independently.

Back 67

False. Large proteins may fold spontaneously, but it may incorrect if chaperones are not present to shield small hydrophobic regions of polypeptides.

Front 68

Definition of Prosthetic Groups

Back 68

Parts of proteins required for function consisting of tightly-bound cofactors.

Example: heme group

Front 69

Antacids are a good example of potential drug-drug interactions because...

Back 69

Antacids are a good example of potential drug-drug interactions because they modify the pH of the stomach and GI tract and this can impact absorption of enteral medications.

Front 70

Recent consumption of food often _______ and ______ medication effects and absorption.

Back 70

Recent consumption of food often delays and reduces medication effects and absorption.

*Note: Weak-acid drugs may be better absorbed due to increased acidity of stomach after eating.

Front 71

Enhanced gastric motility often _______ absorption of drugs, though lesioning may _______ absorption of drugs that must be actively transported.

Back 71

Enhanced gastric motility often decreases absorption of drugs, though lesioning may increase absorption of drugs that must be actively transported.

Front 72

Definition of Bioavailability

Back 72

The amount of drug reaching systemic circulation per dose.

Front 73

Drug Effects in High-Perfusion vs. Low-Perfusion Tissues

Back 73

High-perfusion tissues receive rapid dose, while low-perfused tissues receive slow dose and accumulate drug reservoir over time due to relative amount of low-perfusion tissue.

Front 74

Important Characteristics for Drugs Designed to Penetrate the CNS (4)

Back 74

1. Low ionization at plasma pH
2. Low binding to plasma proteins
3. High lipophilicity
4. Small size

Front 75

Volume of Distribution (Vd)

Back 75

Vd = (total amount of drug in the body)/(concentration of drug in the plasma)

*Apparent space in body available to the drug
*Fluid volume required to contain all of the drug at the same concentration as observed in the plasma

Front 76

Vd is _______ related to _______ excretion due to the tendency of _____ Vd drugs to accumulate in fat and muscular tissue.

Back 76

Vd is inversely related to renal excretion due to the tendency of high Vd drugs to accumulate in fat and muscular tissue.

Front 77

T/F: Drug metabolites are generally more polar than their parent drugs.

Back 77

True

This is achieved by oxidation and demethylation.

Front 78

Relative Half-Life of Zero-Order and First-Order Kinetics

Back 78

Zero-Order: enzymes are saturable, so elimination is linear.

First-Order: constant half-life independent of drug concentration

Front 79

Phase 1 Reactions

Back 79

Oxidation, reduction, hydrolysis or cyclization by cP450 mono-oxygenase.

Primarily within endoplasmic reticulum (ER).

Front 80

Rifampin (an antibiotic) acts as a cytochrome P450 ______, causing ______ metabolism of drugs metabolized by the same c-P450.

Back 80

Rifampin (an antibiotic) acts as a cytochrome P450 inducer, causing increased metabolism of drugs metabolized by the same c-P450.

Front 81

Phase 2 Reactions

Back 81

Conjugation and synthesis reactions that increase the polarity of drug metabolites through addition of polar moieties.

Front 82

3 Steps of Renal Excretion

Back 82

1. Glomerular filtration
2. Passive reabsorption of non-polar compounds
3. Active transport and secretion for unfiltered (large) compounds

Front 83

_______ polarity leads to _______ reabsorption into peritubular capillaries of renal system.

Back 83

Increased polarity leads to decreased reabsorption into peritubular capillaries of renal system.

Front 84

T/F: Weak acids are easily excreted in urine.

Back 84

False. Weak acids are difficult to excrete in urine due to acidic environment and tendency of acids to remain protonated (HA) and nonpolar.

Front 85

Definition of Systemic Clearance

Back 85

Volume of plasma from which a substance is completely removed by excretion or metabolism per unit time.

Front 86

Equation for Renal Clearance

Back 86

CL(x) = (([x] in urine)(output of urine))/([x] in plasma)

Front 87

_________ is used as a measure of glomerular filtration rate (GFR).

Back 87

Creatinine clearance is used as a measure of glomerular filtration rate (GFR).

Front 88

T/F: A lowered GFR suggests that a lower dose should be administered to the patient.

Back 88

True

Front 89

What is the enterohepatic cycle and what effect does it have on half-life of a drug?

Back 89

Drugs can be reabsorbed into the liver via the portal vein, pass through the common bile duct, and reenter the duodenum.

It increases the half-life of a drug.

Front 90

For drugs with a narrow therapeutic window, it is necessary to ________.

Back 90

For drugs with a narrow therapeutic window, it is necessary to monitor plasma concentration.

Front 91

Definition of Pharmacogenetics

Back 91

The study of genetic variations that cause differential responses to drugs.

Important for drugs with narrow therapeutic windows and potential applications to personalized medicine.

Front 92

3 Sources of Variable Drug Response

Back 92

1. Differences in organ function (liver, kidneys)
2. Mutations in metabolic enzyme genes
3. Differences in number of functional c-P450 enzyme family genes

Front 93

Which type of assay gauges levels of mRNA expression by relative brightness?

Back 93

Microarrays

Front 94

What is the goal of pharmacogenomics?

Back 94

To correlate inheritance of chromosomal regions with inheritance of diseases.

Front 95

T/F: Multiallelic microsatellites are preferable to single nucleotide polymorphisms (SNPs) for linkage studies.

Back 95

False. SNPs are more frequent and less polymorphic.

Front 96

Apo-E4 and Alzheimer's exhibit linkage disequilibrium. What does this mean?

Back 96

Patients with Alzheimer's have a predictable haplotype of identifiable SNPs.

Front 97

4 Types of Non-covalent Interactions

Back 97

1. Dispersion or van der Waals forces
2. Electrostatic forces
3. Hydrogen bonding
4. Hydrophobic effect

Front 98

T/F: At large interatomic distances (r >> 0), the potential energy between two atoms is always positive and forces are always attractive.

Back 98

False. At large interatomic distances (r >> 0), the potential energy between two atoms is always negative and forces are always attractive.

Front 99

Equation for Coulomb's Law

(Define the variables)

Back 99

F= (Q1•Q2)/(4π(Eo)r^2)

Eo is the dielectric constant or susceptibility of a medium to polarization.
r is the interatomic distance.
Q1,Q2 are the charges.

Front 100

T/F: The dielectric constant of water is high and the dielectric constant of oil is low.

Back 100

True.

Water is easy to polarize, leading to a low attractive force between charges. Oil is not easily polarized, leading to a high attractive force between charges.

Front 101

What accounts for the asymptotic behavior of the relationship of interatomic distance (r) and potential energy (U) as r approaches zero?

Back 101

The hard-sphere limit that prevents complete overlap of nuclei and their associated electron clouds.

Front 102

T/F: Hydrogen bonding is weaker and shorter than covalent bonding.

Back 102

False. Hydrogen bonding is weaker and about twice as long as covalent bonding.

Front 103

The electronegative atom that shares a covalent bond with the hydrogen involved in a hydrogen bond is referred to as the _____, while the other electronegative atom is the ________.

Back 103

The electronegative atom that shares a covalent bond with the hydrogen involved in a hydrogen bond is referred to as the donor, while the other electronegative atom is the acceptor.

Front 104

4 Advantages of Water as a Biological Solvent

Back 104

1. High heat capacity
2. High heat of vaporization
3. High melting/boiling point
4. High capacity for dissolution

Front 105

The structure of a water molecule is an ________ with a bond angle of ______.

Back 105

The structure of a water molecule is an irregular tetrahedron with a bond angle of 104.5°.

Front 106

Definition of Hydrophobic Interactions

Back 106

The tendency of non-polar solutes to self-associate in aqueous environments in order to minimize increases in entropy.

Front 107

Definition of Amphipathic

Back 107

Possession of regions that are polar and regions that are nonpolar.

Front 108

Equation for Ion Product of Water

Back 108

Kw = [H+][OH-]

At 25°C, Kw=10^-14 M^2

Front 109

Equation for pH

Back 109

pH = -log([H+])

*Demonstrates that increased [H+] decreases pH

Front 110

Equation for Clearance (generic)

Back 110

CL = rate of elimination/concentration

Front 111

For steady-state, clearance is equal to...

Back 111

CL = dosing rate/Css

*R(in) = R (out)

Front 112

Since rate of elimination is the same for bound, unbound and total plasma concentrations...

Back 112

CL(p) x C(p) = CL(u) x C(u) = CL(b) x C(b)

p stands for plasma
u stands for unbound
b stands for bound

Front 113

Equation for Clearance of a Given Organ

Back 113

CL = ER x Q

ER is "extraction ratio" equal to (C{in}-C{out})/C{in}
Q is blood flow

Front 114

High extraction has ER close to ____, and clearance is _______ by enzymatic inducers. It is dependent on ______.

Back 114

High extraction has ER close to 1, and clearance is unaffected by enzymatic inducers. It is dependent on blood flow (Q).

Front 115

Low extraction has ER close to ____, and clearance is _______ by enzymatic inducers.

Back 115

Low extraction has ER close to 0, and clearance is dependent on enzymatic inducers.

Front 116

For an average 70 kg adult male,

plasma volume = ?
blood volume = ?
extracellular water volume = ?
total body water volume = ?

Back 116

For an average 70 kg adult male,

plasma volume = 2.8 L
blood volume = 5.6 L
extracellular water volume = 14 L
total body water volume = 42 L

Front 117

Plasma protein binding affinity is ______ related to plasma concentration and ______ related to Vd. Therefore, high affinity leads to _____ Cp and _____ Vd.

Back 117

Plasma protein binding affinity is directly related to plasma concentration and inversely related to Vd. Therefore, high affinity leads to high Cp and low Vd.

Front 118

Equation for Half-Life of Elimination

Back 118

t1/2 = (0.7Vd)/CL

Front 119

Doubling the dose of a drug gains ______ half-life(s).

Back 119

Doubling the dose of a drug gains one half-life.

Front 120

For a graph of plasma concentration over time, why is a continuous administration relationship non-linear?

Back 120

R(in) > R(out) because R(out) is proportional to concentration. As concentration increases, R(out) increases until it equals R(in), which is a steady-state relationship.

Front 121

Equation for Michaelis-Menten Kinetics

Back 121

v = (vmax•C)/(C+Km)

Front 122

Zero-Order Michaelis-Menten Relationship

Back 122

C >> Km, so v=vmax

*Enzyme saturation

Front 123

First-Order Michaelis-Menten Relationship

Back 123

C << Km, so v=(vmax•C)/Km

Front 124

Phenytoin exhibits chaotic effects from changes in dose because it follows _____-order kinetics.

Back 124

Phenytoin exhibits chaotic effects from changes in dose because it follows zero-order kinetics.

Front 125

Equation for Maintenance Dose (Any Route)

Back 125

Dosing rate = CL x C

Front 126

Equation for Priming Dose (Continuous Administration)

Back 126

Dose = Vd x C

Front 127

Equation for Accumulation Factor (Intermittent Administration)

What does it mean?

Back 127

Accumulation = 1/(1-fraction of dose remaining)

Determines maximum accumulation from intermittent dosing and helps identify appropriate priming dose.

Front 128

Equation for Intermittent Dose

Back 128

Intermittent dose = (CL x C x dosing interval)/F

F is bioavailability

Front 129

Equation for Bioavailability

Back 129

F = f x (1-ER{liver})

f is the fraction of dose absorbed into portal circulation

Front 130

Equation for Priming Dose (Intermittent Administration)

Back 130

Priming Dose = Intermittent Dose x Accumulation Factor

Front 131

Equation for Adjustment of Steady-State Concentration

Back 131

(Measured Css)/(Desired Css) = (Current Dose)/(New Dose)

Front 132

Uncatalyzed reactions require A and B to collide with _______ and _______.

Back 132

Uncatalyzed reactions require A and B to collide with sufficient energy and correct orientation.

Front 133

T/F: The ratio of reactants and products at equilibrium is independent of activation energy ("Ef-double dagger").

Back 133

True

Front 134

T/F: The reaction rate dP/dt is independent of activation energy ("Ef-double dagger").

Back 134

False. dP/dt is dependent on the height of kinetic barriers and the kinetic energy of reactants and products.

Front 135

Equation for Free Energy of a Reaction

Back 135

∆G{reaction} = Ef - Eb

*Should be negative for spontaneous reaction

Front 136

Arrhenius Equation

Back 136

dP/dt = Ae^(-Ef/RT)

A is the total number of collisions per unit time
e^(-Ef/RT) is a measure of the probability of a successful collision

Front 137

T/F: Increasing the temperature of a reaction environment increases the probability of both the forward and reverse reactions.

Back 137

True

*May also accelerate unwanted competing reactions

Front 138

T/F: Catalysts speed up reactions for which ∆G>0.

Back 138

False. Catalysts cannot speed up non-spontaneous reactions. ∆G must be negative and is not changed by catalysts.

Front 139

What are the advantages of biological enzymes vs. inorganic catalysts?

Back 139

They are more specific and more efficient.

Front 140

Six Classes of Enzymes and Their Reactions

Back 140

1. Oxidoreductases: oxidation and reduction
2. Transferases: transfer of glycosyl, methyl or phosphoryl groups
3. Hydrolases: hydrolysis of C-C, C-O, C-N, etc. covalent bonds
4. Lyases: cleavage of C-C, C-O, C-N, etc. covalent bonds by atom elimination (formation of double bonds)
5. Isomerases: structural changes
6. Ligases: joining of 2 molecules, often coupled to ATP hydrolysis

Front 141

Equation for Gibbs Free Energy

Back 141

∆G = ∆H - T∆S

Front 142

In enzyme thermodynamics, ∆H accounts for favorable ________ and unfavorable ________.

Back 142

In enzyme thermodynamics, ∆H accounts for favorable enzyme-substrate interactions and unfavorable bond-distortion.

Front 143

In enzyme thermodynamics, ∆S accounts for favorable ________ and unfavorable ________.

Back 143

In enzyme thermodynamics, ∆S accounts for favorable product release and unfavorable loss of substrate freedom and juxtaposition of reactive groups.

Front 144

2 Types of Enzyme-Substrate Binding

Back 144

1. Lock and Key
2. Induced Fit

Front 145

T/F: Lock and key binding ES complex is less stable than induced fit ES complex and has a smaller associated activation energy.

Back 145

False. Lock and key ES complex is very stable because it's an exact fit, but it has a higher activation energy than induced fit.

Front 146

Coenzymes vs. Cosubstrates vs. Cofactors

Back 146

Coenzymes are small organic molecules that associate with catalysts.

Cosubstrates are coenzymes that are altered during the reaction.

Cofactors are inorganic.

Front 147

First Law of Thermodynamics

Back 147

There is a finite amount of energy in the universe and E = Q+W

Front 148

Second Law of Thermodynamics

Back 148

The entropy of the universe is constant or increases (∆S ≥ ∆Q/T)

Front 149

Third Law of Thermodynamics

Back 149

∆G = ∆H - T∆S defines the maximum amount of work that can be obtained from a system.

∆G = 0 is equilibrium.
∆G < 0 is a spontaneous reaction.
∆G > 0 is a non-spontaneous reaction.

Front 150

Equation for Equilibrium Constant

Back 150

Keq = ([C][D])/([A][B])

Front 151

Equation for Gibbs Free Energy During a Reaction

Back 151

∆G = ∆G° + RTln(Keq)

∆G° is defined at standard conditions
R is the gas constant equal to 1.987 cal/mol•deg
T is temperature in Kelvin

Front 152

Spontaneous biological reactions are ________ stable and ________ unstable.

Back 152

Spontaneous biological reactions are kinetically stable and thermodynamically unstable.

Front 153

∆G{AC} = ∆G{AB} + ∆G{BC} indicates a model for _______________ reactions and all will proceed if ∆G{AC} is ________.

Back 153

∆G{AC} = ∆G{AB} + ∆G{BC} indicates a model for energetically coupled reactions and all will proceed if ∆G{AC} is negative.

Front 154

Equation for Dissociation Constant

Back 154

Kd = ([A][B])/[AB] = 1/Ka

Front 155

Equation for Fractional Saturation

Back 155

Y = [AB]/([AB]+[A]) = [B]/([B]+Kd)

Front 156

Equation for Concentration of Drug-Receptor Complex

Back 156

[DR] = R-total ([D]/([D]+Kd))

Front 157

Equation for Effect of Drug

Back 157

E = (Emax•C)/(C + EC50)

EC50 is the 50% effective concentration

Front 158

A competitive antagonist produces what type of change?

Back 158

Given antagonist concentration [i], EC50' = EC50(1+([i]/Ki))

Front 159

An irreversible antagonist is ________ bound and produces what type of change?

Back 159

An irreversible antagonist is covalently bound.

Emax decreases without changing EC50.

Front 160

The concept of spare receptors or receptor reserve explains why __________ is constant but _________ increases even for irreversible antagonists. This holds until EC50 is about equal to Kd, at which point the _________ takes over and EC50 is ________ while Emax _______.

Back 160

The concept of spare receptors or receptor reserve explains why Emax is constant but EC50 increases even for irreversible antagonists. This holds until EC50 is about equal to Kd, at which point the occupancy assumption takes over and EC50 is constant while Emax decreases.

Front 161

T/F: If a receptor reserve exists, only a small percentage of receptors are active all of the time.

Back 161

False. If a receptor reserve exists, all of the receptors are active, but only for a small percentage of time. Receptor reserve implies that full activation of all receptors isn't necessary to achieve a full response.

Front 162

T/F: Antagonists are not subject to the receptor reserve effect.

Back 162

True. This explains why they are used instead of agonists to identify receptors and receptor subtypes.

Front 163

Definition of Efficacy

Back 163

The degree of maximal effect an agonist can produce.

Front 164

Definition of Potency

Back 164

The concentration of agonist needed to reach 50% of the maximal effect (relative EC50).

Front 165

T/F: In a system with a full agonist A and partial agonist D, as [D] increases the total response decreases.

Back 165

True. This is due to the relative efficacy of full and partial agonists.

Front 166

Opiate toxicity produces what symptoms? Name 5.

Back 166

1. Bradypnea
2. CNS depression
3. Miosis
4. Hypotension
5. Hypothermia

Front 167

Anticholinergic and sympathomimetic toxicity can produce what two symptoms?

Back 167

1. Tachycardia
2. Hypertension

Front 168

Why do acetylsalicylic acid (ASA) and dinitrophenol toxicity produce fever?

Back 168

Uncoupled oxidative phosphorylation produces heat instead of ATP.

Front 169

What does SLUDGE stand for and what does it mean?

Back 169

SLUDGE represents the symptoms of cholinergic toxicity.

Salivation
Lacrimation
Urination
Defecation
GI cramping
Emesis

Front 170

Results of Arterial Blood Gas toxicity screening:

Respiratory acidosis implies _______.
Respiratory alkalosis implies _______.

Back 170

Respiratory acidosis implies opiate or sedative hypnotic toxicity (high CO2 leads to shift towards H+)

Respiratory alkalosis implies salicylate or nitrophenol toxicity.

Front 171

Definition and Equation for Anion Gap

Back 171

Difference in amounts of unmeasured cations and unmeasured anions.

Na + K + UC = Cl + HCO3 + UA

Front 172

Unmeasured cations usually include...(2)

Back 172

Magnesium and Calcium

Front 173

Unmeasured anions usually include (4)

Back 173

Phosphate, Sulfate, Proteins, and Organic Acids

Front 174

What does MUDPILES stand for and what is it related to?

Back 174

MUDPILES lists causes of a high anion gap

Methanol
Uremia
Diabetes, alcohol and starvation
Phenformin
Isoniazid and iron
Lactate
Ethylene glucol
Salicylate

Front 175

T/F: High anion gap indicates metabolic alkalosis.

Back 175

False. A high anion gap indicates metabolic acidosis because HCO3- has dropped without an increase in Cl-, so other acids must be fluctuating.

Front 176

Urinalysis with the following results may indicate what conditions?

Crystaluria: ?
Hemoglobinuria: ?
Ketonuria: ?

Back 176

Crystalluria: high levels of oxalates
Hemoglobinuria: hemolysis or rhabdomyolysis
Ketonuria: isopropanol poisoning or ketoacidosis

Front 177

Name 3 Problems with Tox Screens

Back 177

1. Not actually comprehensive
2. Many false positives and false negatives
3. Rapid-acting toxins may not appear in urine before causing damage to other tissues

Front 178

What is meant by extracorporeal removal and when is it used?

Back 178

Extracorporeal removal includes hemodialysis and exchange transfusion for children.

It is used for methanol, ethylene glycol, lithium, theophylline, and salicylates (MELTS)

Front 179

T/F: Gastric decontamination by pumping, charcoal, emetics, etc. is growing in popularity among physicians.

Back 179

False. Gastric decontamination through these methods has severely declined in popularity, though some techniques are still in use in special cases.

Front 180

The initial rate for an uncatalyzed reaction is ________ dependent on ________.

Back 180

The initial rate for an uncatalyzed reaction is linearly dependent on [S].

Front 181

Enzyme-catalyzed reactions encounter _______ conditions, which result in limited increases in the initial rate of the reaction as [S] is increased.

Back 181

Enzyme-catalyzed reactions encounter saturation conditions, which result in limited increases in the initial rate of the reaction as [S] is increased.

Front 182

If vmax is dependent on the total amount of enzyme available, then the relationship is:

Back 182

vmax = k3[E-total]

k3 = kcat = turnover number

Front 183

T/F: v is equal to vmax when [ES] is equal to [E-total].

Back 183

True

Front 184

Equation for ES Formation

Back 184

Rate = k1[E][S]

Front 185

Equation for ES Breakdown

Back 185

Rate = (k2 + k3)[ES]

Front 186

Equation for Steady-State Kinetic Constant for Enzyme-Substrate Complex

Back 186

Km = (k2+k3)/K1 = ([E][S])/[ES]

Front 187

Km of an enzyme-substrate complex reflects its _________. When k2 >> k3, it can also reflect the ES _________.

Large Km implies ________ substrate binding and _________ ES complex.

Small Km implies ________ substrate binding and _________ ES complex.

Back 187

Km of an enzyme-substrate complex reflects its stability. When k2 >> k3, it can also reflect the ES affinity.

Large Km implies weak substrate binding and unstable ES complex.

Small Km implies strong substrate binding and stable ES complex.

Front 188

Equation for Lineweaver-Burk Plot

Back 188

1/v = (Km/Vmax)(1/[S]) + 1/Vmax

Front 189

Competitive inhibitors change ______.

Uncompetitive inhibitors change ______.

Noncompetitive inhibitors change ______.

Back 189

Competitive inhibitors change Km but not Vmax.

Uncompetitive inhibitors change both Km and Vmax.

Noncompetitive inhibitors change Vmax but not Km.

Front 190

T/F: Competitive inhibitors only bind the free enzyme and not the enzyme-substrate complex, but uncompetitive inhibitors bind both.

Back 190

False. Competitive inhibitors only bind the free enzyme and not the enzyme-substrate complex, but noncompetitive inhibitors bind both. Uncompetitive inhibitors only bind the enzyme-substrate complex.