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190 Cards in this Set
- Front
- Back
Henderson-Hasslebach (for both acids and bases)
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pH = log([A-]/[HA]) + pKa
pH = log([B]/[HB+]) + pKa |
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T/F: Acids are preferentially absorbed under basic conditions (pH>pKa).
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False.
Acids absorbed under acidic conditions. Bases absorbed under basic conditions. |
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Intensity and duration of drug action depends on _______ at ________.
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Intensity and duration of drug action depends on concentration at receptor site.
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3 Controls of Drug Concentration
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1. Dose
2. Dosing interval 3. Route of administration |
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Pharmaceutical principles
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Disintegration and dissolution of drug
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Pharmacokinetic principles (4)
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"How the drug gets to the target"
1. Absorption 2. Distribution 3. Biotransformation 4. Excretion |
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Pharmacodynamic principles
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"How the drug affects the body"
Drug/receptor interactions |
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Biotransformation
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Conversion of drug molecule to more water-soluble form
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T/F: The first-pass effect occurs in the liver and explains why administered and received doses are not equal.
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True
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________, _______ and _______ are three routes of administration that avoid the first-pass effect.
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IV, sublingual/buccal cavity and rectal are three routes of administration that avoid the first-pass effect.
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4 reasons to avoid oral administration
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1. Nausea or vomiting
2. Unwilling or unable to swallow 3. Drug destroyed by digestive enzymes 4. Drug is not absorbed through gastric mucosa |
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T/F: Insulin can be taken orally.
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False. Insulin is destroyed by gastric enzymes.
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T/F: Nitroglycerin is slow-acting and should be swallowed.
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False. Nitroglycerin is a fast-acting angina medication that should be taken sublingually.
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3 advantages of controlled-release dosage forms
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1. Reduce dosing frequency
2. Reduce fluctuations in drug levels 3. More uniform pharmacological response |
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T/F: Drugs administered subcutaneously and intramuscularly are often watery and hydrophilic.
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False. Drugs administered subcutaneously and intramuscularly are often oily and hydrophobic.
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T/F: Uncharged molecules often diffuse relatively easy across cell membranes while charged molecules require more active binding and transport.
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True
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Fick's Law of Diffusion
(Define the variables) |
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 |
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5 characteristic that impact diffusion
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1. Size
2. Hydrophobicity 3. Charge 4. Shape 5. Attachments |
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Definition of pKa
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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+]). |
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Patients suffering from Maple Syrup Urine Disease cannot catabolize which 3 amino acids?
How is it diagnosed? |
1. Leucine
2. Isoleucine 3. Valine Diagnosis: ketosis and excess acid in blood |
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T/F: L enantiomers do not exist in proteins, but can be free amino acids.
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False. D enantiomers do not exist in proteins, but can be free amino acids.
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The CORN-clock law helps to identify ______ when _____ is read _________ from the ______, ______, and ________ groups of an amino acid.
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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.
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At physiological pH, the amino group is ______ and the carboxylic acid group is ______, making the amino acid in this form a _______.
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At physiological pH, the amino group is positive and the carboxylic acid group is negative, making the amino acid in this form a zwitterion.
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Moving from pH=1 to pH=14, the ______ group is deprotonated first, followed by the _______ group.
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Moving from pH=1 to pH=14, the carboxylic acid group is deprotonated first, followed by the amino group.
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Aliphatic Side Chain Amino Acids
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1. Glycine
2. Alanine 3. Valine 4. Leucine 5. Isoleucine |
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Glycine
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Gly
2. G 3. -H *Flexible and allows for tight folding |
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Alanine
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Ala
2. A 3. -CH3 |
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Valine
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Val
2. V 3. -CH-CH3 -CH3 |
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Leucine
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Leu
2. L 3. -CH2-CH-CH3 -CH3 |
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Isoleucine
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Ile
2. I 3. -CH-CH2-CH3 -CH3 |
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Aromatic Side Chain Amino Acids
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1. Phenylalanine
2. Tyrosine 3. Tryptophan *Bulky, greasy and often buried in soluble proteins |
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Phenylalanine
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Phe
2. F 3. -CH2-C6H5 |
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Tyrosine
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Tyr
2. Y 3. -CH2-C6H5-OH *Can be phosphorylated |
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Tryptophan
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Try
2. W 3. -CH2-C8H6N |
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Sulfur-Containing Chain Amino Acids
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1. Cysteine
2. Methionine *Form covalent disulfide bonds in proteins. *Hydrophobic (like aliphatic chains), so they are located on interior of proteins. |
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Cysteine
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Cys
2. C 3. -CH2-SH |
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Methionine
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Met
2. M 3. -CH2-CH2-S-CH3 |
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Aliphatic Hydroxyl Chain Amino Acids
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1. Serine
2. Threonine *Can be phosphorylated *High potential for H-bonding |
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Serine
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Ser
2. S 3. -CH2-OH |
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Threonine
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Thr
2. T 3. -CH-OH -CH3 |
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Basic Chain Amino Acids
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1. Lysine
2. Arginine 3. Histidine |
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Lysine
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Lys
2. K 3. -CH2-CH2-CH2-CH2-NH3+ *Long, greasy chain *Extends interior to exterior of protein *Can be acetylated |
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Arginine
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Arg
2. R 3. -CH2-CH2-CH2-NH-C=NH2+ -NH2 *Long, greasy branched chain |
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Histidine
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. His
2. H 3. -CH2-C3H4N2+ *Often present at active sites |
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Acidic Chain Amino Acids and Amide Derivatives
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1. Aspartic Acid
2. Asparagine 3. Glutamic Acid 4. Glutamine |
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Aspartic Acid
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Asp
2. D 3. -CH2-CO2H *Asx and B if indistinguishable from asparagine. |
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Asparagine
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Asn
2. N 3. -CH2-CO-NH2 *Asx and B if indistinguishable from aspartic acid. |
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Glutamic acid
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Glu
2. E 3. -CH2-CH2-CO2H *Glx and Z if indistinguishable from glutamine. |
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Glutamine
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Gln
2. Q 3. -CH2-CH2-CO-NH2 *Glx and Z if indistinguishable from glutamic acid. |
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Proline
1. Three-letter abbreviation 2. Single-letter abbreviation 3. Structure |
1. Pro
2. P 3. -CH2-CH2- -NH2+-CH2- *"Helix breaker" |
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Non-human Chain Amino Acids
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1. Selenocysteine (Sec, U)
2. Pyrrolysine (Pyl, O) *Appear in bacterial enzymes |
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Essential Amino Acids
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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 |
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Phenylketonuria (PKU) is an inability to break down ________ and convert it into ________.
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Phenylketonuria (PKU) is an inability to break down phenylalanine and convert it into tyrosine.
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Peptide bonds exhibit ________ bond character, making them slightly _______ in length than regular single bonds.
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Peptide bonds exhibit partial double bond character, making them slightly shorter in length than regular single bonds.
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T/F: For peptide bond isomers, cis dominates.
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False. For peptide bond isomers, trans dominates. Cis occurs for proline and at active sites.
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T/F: Oligo-/Polypeptides begin at the amino terminus and end at the carboxyl terminus.
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True
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Examples of Covalent Post-Translational Modifications
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1. Methylation
2. Hydroxylation 3. Acetylation 4. Phosphorylation 5. Glycosylation 6. Myristylation 7. Palmitoylation |
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Techniques for Protein/Peptide Isolation (5)
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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) |
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Levels of Protein Structure
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1. Primary: AA sequence
2. Secondary: helices and sheets 3. Tertiary: 3-D structure of polypeptide 4. Quaternary: multi-polypeptide proteins |
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T/F: Covalent bonding is primarily involved in the secondary, tertiary and quaternary levels of protein structure.
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False. Non-covalent bonding is primarily involved in the secondary, tertiary and quaternary levels of protein structure. Covalent bonding is responsible for primary structure.
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Definition of Circular Dichroism
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Differential absorption of left and right circularly polarized light.
Used to identify secondary protein structures. |
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Characteristics of Alpha Helix (5)
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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) |
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3 Types of Helices
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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 |
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2 Types of ß-Sheets
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1. Antiparallel: direct H-bonding, flat, contiguous amino acids
2. Parallel: indirect H-bonding, kinked, non-contiguous amino acids |
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A common combination for ß-Turns are the amino acids ______ and ______, but it can be any amino acids.
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A common combination for ß-Turns are the amino acids proline and glycine, but it can be any amino acids.
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6 Techniques for Determining Tertiary and Quaternary Structure
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1. NMR
2. X-ray Crystallography 3. Electron Microscopy 4. Electron Diffraction 5. Single Particle Analysis 6. Modeling |
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T/F: Large proteins fold spontaneously and independently.
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False. Large proteins may fold spontaneously, but it may incorrect if chaperones are not present to shield small hydrophobic regions of polypeptides.
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Definition of Prosthetic Groups
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Parts of proteins required for function consisting of tightly-bound cofactors.
Example: heme group |
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Antacids are a good example of potential drug-drug interactions because...
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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.
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Recent consumption of food often _______ and ______ medication effects and absorption.
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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. |
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Enhanced gastric motility often _______ absorption of drugs, though lesioning may _______ absorption of drugs that must be actively transported.
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Enhanced gastric motility often decreases absorption of drugs, though lesioning may increase absorption of drugs that must be actively transported.
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Definition of Bioavailability
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The amount of drug reaching systemic circulation per dose.
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Drug Effects in High-Perfusion vs. Low-Perfusion Tissues
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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.
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Important Characteristics for Drugs Designed to Penetrate the CNS (4)
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1. Low ionization at plasma pH
2. Low binding to plasma proteins 3. High lipophilicity 4. Small size |
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Volume of Distribution (Vd)
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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 |
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Vd is _______ related to _______ excretion due to the tendency of _____ Vd drugs to accumulate in fat and muscular tissue.
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Vd is inversely related to renal excretion due to the tendency of high Vd drugs to accumulate in fat and muscular tissue.
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T/F: Drug metabolites are generally more polar than their parent drugs.
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True
This is achieved by oxidation and demethylation. |
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Relative Half-Life of Zero-Order and First-Order Kinetics
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Zero-Order: enzymes are saturable, so elimination is linear.
First-Order: constant half-life independent of drug concentration |
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Phase 1 Reactions
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Oxidation, reduction, hydrolysis or cyclization by cP450 mono-oxygenase.
Primarily within endoplasmic reticulum (ER). |
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Rifampin (an antibiotic) acts as a cytochrome P450 ______, causing ______ metabolism of drugs metabolized by the same c-P450.
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Rifampin (an antibiotic) acts as a cytochrome P450 inducer, causing increased metabolism of drugs metabolized by the same c-P450.
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Phase 2 Reactions
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Conjugation and synthesis reactions that increase the polarity of drug metabolites through addition of polar moieties.
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3 Steps of Renal Excretion
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1. Glomerular filtration
2. Passive reabsorption of non-polar compounds 3. Active transport and secretion for unfiltered (large) compounds |
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_______ polarity leads to _______ reabsorption into peritubular capillaries of renal system.
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Increased polarity leads to decreased reabsorption into peritubular capillaries of renal system.
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T/F: Weak acids are easily excreted in urine.
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False. Weak acids are difficult to excrete in urine due to acidic environment and tendency of acids to remain protonated (HA) and nonpolar.
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Definition of Systemic Clearance
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Volume of plasma from which a substance is completely removed by excretion or metabolism per unit time.
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Equation for Renal Clearance
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CL(x) = (([x] in urine)(output of urine))/([x] in plasma)
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_________ is used as a measure of glomerular filtration rate (GFR).
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Creatinine clearance is used as a measure of glomerular filtration rate (GFR).
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T/F: A lowered GFR suggests that a lower dose should be administered to the patient.
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True
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What is the enterohepatic cycle and what effect does it have on half-life of a drug?
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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. |
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For drugs with a narrow therapeutic window, it is necessary to ________.
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For drugs with a narrow therapeutic window, it is necessary to monitor plasma concentration.
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Definition of Pharmacogenetics
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The study of genetic variations that cause differential responses to drugs.
Important for drugs with narrow therapeutic windows and potential applications to personalized medicine. |
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3 Sources of Variable Drug Response
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1. Differences in organ function (liver, kidneys)
2. Mutations in metabolic enzyme genes 3. Differences in number of functional c-P450 enzyme family genes |
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Which type of assay gauges levels of mRNA expression by relative brightness?
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Microarrays
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What is the goal of pharmacogenomics?
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To correlate inheritance of chromosomal regions with inheritance of diseases.
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T/F: Multiallelic microsatellites are preferable to single nucleotide polymorphisms (SNPs) for linkage studies.
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False. SNPs are more frequent and less polymorphic.
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Apo-E4 and Alzheimer's exhibit linkage disequilibrium. What does this mean?
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Patients with Alzheimer's have a predictable haplotype of identifiable SNPs.
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4 Types of Non-covalent Interactions
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1. Dispersion or van der Waals forces
2. Electrostatic forces 3. Hydrogen bonding 4. Hydrophobic effect |
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T/F: At large interatomic distances (r >> 0), the potential energy between two atoms is always positive and forces are always attractive.
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False. At large interatomic distances (r >> 0), the potential energy between two atoms is always negative and forces are always attractive.
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Equation for Coulomb's Law
(Define the variables) |
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. |
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T/F: The dielectric constant of water is high and the dielectric constant of oil is low.
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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. |
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What accounts for the asymptotic behavior of the relationship of interatomic distance (r) and potential energy (U) as r approaches zero?
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The hard-sphere limit that prevents complete overlap of nuclei and their associated electron clouds.
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T/F: Hydrogen bonding is weaker and shorter than covalent bonding.
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False. Hydrogen bonding is weaker and about twice as long as covalent bonding.
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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 ________.
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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.
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4 Advantages of Water as a Biological Solvent
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1. High heat capacity
2. High heat of vaporization 3. High melting/boiling point 4. High capacity for dissolution |
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The structure of a water molecule is an ________ with a bond angle of ______.
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The structure of a water molecule is an irregular tetrahedron with a bond angle of 104.5°.
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Definition of Hydrophobic Interactions
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The tendency of non-polar solutes to self-associate in aqueous environments in order to minimize increases in entropy.
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Definition of Amphipathic
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Possession of regions that are polar and regions that are nonpolar.
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Equation for Ion Product of Water
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Kw = [H+][OH-]
At 25°C, Kw=10^-14 M^2 |
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Equation for pH
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pH = -log([H+])
*Demonstrates that increased [H+] decreases pH |
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Equation for Clearance (generic)
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CL = rate of elimination/concentration
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For steady-state, clearance is equal to...
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CL = dosing rate/Css
*R(in) = R (out) |
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Since rate of elimination is the same for bound, unbound and total plasma concentrations...
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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 |
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Equation for Clearance of a Given Organ
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CL = ER x Q
ER is "extraction ratio" equal to (C{in}-C{out})/C{in} Q is blood flow |
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High extraction has ER close to ____, and clearance is _______ by enzymatic inducers. It is dependent on ______.
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High extraction has ER close to 1, and clearance is unaffected by enzymatic inducers. It is dependent on blood flow (Q).
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Low extraction has ER close to ____, and clearance is _______ by enzymatic inducers.
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Low extraction has ER close to 0, and clearance is dependent on enzymatic inducers.
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For an average 70 kg adult male,
plasma volume = ? blood volume = ? extracellular water volume = ? total body water volume = ? |
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 |
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Plasma protein binding affinity is ______ related to plasma concentration and ______ related to Vd. Therefore, high affinity leads to _____ Cp and _____ Vd.
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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.
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Equation for Half-Life of Elimination
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t1/2 = (0.7Vd)/CL
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Doubling the dose of a drug gains ______ half-life(s).
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Doubling the dose of a drug gains one half-life.
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For a graph of plasma concentration over time, why is a continuous administration relationship non-linear?
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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.
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Equation for Michaelis-Menten Kinetics
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v = (vmax•C)/(C+Km)
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Zero-Order Michaelis-Menten Relationship
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C >> Km, so v=vmax
*Enzyme saturation |
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First-Order Michaelis-Menten Relationship
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C << Km, so v=(vmax•C)/Km
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Phenytoin exhibits chaotic effects from changes in dose because it follows _____-order kinetics.
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Phenytoin exhibits chaotic effects from changes in dose because it follows zero-order kinetics.
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Equation for Maintenance Dose (Any Route)
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Dosing rate = CL x C
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Equation for Priming Dose (Continuous Administration)
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Dose = Vd x C
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Equation for Accumulation Factor (Intermittent Administration)
What does it mean? |
Accumulation = 1/(1-fraction of dose remaining)
Determines maximum accumulation from intermittent dosing and helps identify appropriate priming dose. |
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Equation for Intermittent Dose
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Intermittent dose = (CL x C x dosing interval)/F
F is bioavailability |
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Equation for Bioavailability
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F = f x (1-ER{liver})
f is the fraction of dose absorbed into portal circulation |
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Equation for Priming Dose (Intermittent Administration)
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Priming Dose = Intermittent Dose x Accumulation Factor
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Equation for Adjustment of Steady-State Concentration
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(Measured Css)/(Desired Css) = (Current Dose)/(New Dose)
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Uncatalyzed reactions require A and B to collide with _______ and _______.
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Uncatalyzed reactions require A and B to collide with sufficient energy and correct orientation.
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T/F: The ratio of reactants and products at equilibrium is independent of activation energy ("Ef-double dagger").
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True
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T/F: The reaction rate dP/dt is independent of activation energy ("Ef-double dagger").
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False. dP/dt is dependent on the height of kinetic barriers and the kinetic energy of reactants and products.
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Equation for Free Energy of a Reaction
|
∆G{reaction} = Ef - Eb
*Should be negative for spontaneous reaction |
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Arrhenius Equation
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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 |
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T/F: Increasing the temperature of a reaction environment increases the probability of both the forward and reverse reactions.
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True
*May also accelerate unwanted competing reactions |
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T/F: Catalysts speed up reactions for which ∆G>0.
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False. Catalysts cannot speed up non-spontaneous reactions. ∆G must be negative and is not changed by catalysts.
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What are the advantages of biological enzymes vs. inorganic catalysts?
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They are more specific and more efficient.
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Six Classes of Enzymes and Their Reactions
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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 |
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Equation for Gibbs Free Energy
|
∆G = ∆H - T∆S
|
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In enzyme thermodynamics, ∆H accounts for favorable ________ and unfavorable ________.
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In enzyme thermodynamics, ∆H accounts for favorable enzyme-substrate interactions and unfavorable bond-distortion.
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In enzyme thermodynamics, ∆S accounts for favorable ________ and unfavorable ________.
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In enzyme thermodynamics, ∆S accounts for favorable product release and unfavorable loss of substrate freedom and juxtaposition of reactive groups.
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2 Types of Enzyme-Substrate Binding
|
1. Lock and Key
2. Induced Fit |
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T/F: Lock and key binding ES complex is less stable than induced fit ES complex and has a smaller associated activation energy.
|
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.
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Coenzymes vs. Cosubstrates vs. Cofactors
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Coenzymes are small organic molecules that associate with catalysts.
Cosubstrates are coenzymes that are altered during the reaction. Cofactors are inorganic. |
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First Law of Thermodynamics
|
There is a finite amount of energy in the universe and E = Q+W
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Second Law of Thermodynamics
|
The entropy of the universe is constant or increases (∆S ≥ ∆Q/T)
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Third Law of Thermodynamics
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∆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. |
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Equation for Equilibrium Constant
|
Keq = ([C][D])/([A][B])
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Equation for Gibbs Free Energy During a Reaction
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∆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 |
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Spontaneous biological reactions are ________ stable and ________ unstable.
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Spontaneous biological reactions are kinetically stable and thermodynamically unstable.
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∆G{AC} = ∆G{AB} + ∆G{BC} indicates a model for _______________ reactions and all will proceed if ∆G{AC} is ________.
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∆G{AC} = ∆G{AB} + ∆G{BC} indicates a model for energetically coupled reactions and all will proceed if ∆G{AC} is negative.
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Equation for Dissociation Constant
|
Kd = ([A][B])/[AB] = 1/Ka
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Equation for Fractional Saturation
|
Y = [AB]/([AB]+[A]) = [B]/([B]+Kd)
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Equation for Concentration of Drug-Receptor Complex
|
[DR] = R-total ([D]/([D]+Kd))
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Equation for Effect of Drug
|
E = (Emax•C)/(C + EC50)
EC50 is the 50% effective concentration |
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A competitive antagonist produces what type of change?
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Given antagonist concentration [i], EC50' = EC50(1+([i]/Ki))
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An irreversible antagonist is ________ bound and produces what type of change?
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An irreversible antagonist is covalently bound.
Emax decreases without changing EC50. |
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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 _______.
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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.
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T/F: If a receptor reserve exists, only a small percentage of receptors are active all of the time.
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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.
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T/F: Antagonists are not subject to the receptor reserve effect.
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True. This explains why they are used instead of agonists to identify receptors and receptor subtypes.
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Definition of Efficacy
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The degree of maximal effect an agonist can produce.
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Definition of Potency
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The concentration of agonist needed to reach 50% of the maximal effect (relative EC50).
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T/F: In a system with a full agonist A and partial agonist D, as [D] increases the total response decreases.
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True. This is due to the relative efficacy of full and partial agonists.
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Opiate toxicity produces what symptoms? Name 5.
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1. Bradypnea
2. CNS depression 3. Miosis 4. Hypotension 5. Hypothermia |
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Anticholinergic and sympathomimetic toxicity can produce what two symptoms?
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1. Tachycardia
2. Hypertension |
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Why do acetylsalicylic acid (ASA) and dinitrophenol toxicity produce fever?
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Uncoupled oxidative phosphorylation produces heat instead of ATP.
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What does SLUDGE stand for and what does it mean?
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SLUDGE represents the symptoms of cholinergic toxicity.
Salivation Lacrimation Urination Defecation GI cramping Emesis |
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Results of Arterial Blood Gas toxicity screening:
Respiratory acidosis implies _______. Respiratory alkalosis implies _______. |
Respiratory acidosis implies opiate or sedative hypnotic toxicity (high CO2 leads to shift towards H+)
Respiratory alkalosis implies salicylate or nitrophenol toxicity. |
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Definition and Equation for Anion Gap
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Difference in amounts of unmeasured cations and unmeasured anions.
Na + K + UC = Cl + HCO3 + UA |
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Unmeasured cations usually include...(2)
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Magnesium and Calcium
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Unmeasured anions usually include (4)
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Phosphate, Sulfate, Proteins, and Organic Acids
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What does MUDPILES stand for and what is it related to?
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MUDPILES lists causes of a high anion gap
Methanol Uremia Diabetes, alcohol and starvation Phenformin Isoniazid and iron Lactate Ethylene glucol Salicylate |
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T/F: High anion gap indicates metabolic alkalosis.
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False. A high anion gap indicates metabolic acidosis because HCO3- has dropped without an increase in Cl-, so other acids must be fluctuating.
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Urinalysis with the following results may indicate what conditions?
Crystaluria: ? Hemoglobinuria: ? Ketonuria: ? |
Crystalluria: high levels of oxalates
Hemoglobinuria: hemolysis or rhabdomyolysis Ketonuria: isopropanol poisoning or ketoacidosis |
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Name 3 Problems with Tox Screens
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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 |
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What is meant by extracorporeal removal and when is it used?
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Extracorporeal removal includes hemodialysis and exchange transfusion for children.
It is used for methanol, ethylene glycol, lithium, theophylline, and salicylates (MELTS) |
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T/F: Gastric decontamination by pumping, charcoal, emetics, etc. is growing in popularity among physicians.
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False. Gastric decontamination through these methods has severely declined in popularity, though some techniques are still in use in special cases.
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The initial rate for an uncatalyzed reaction is ________ dependent on ________.
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The initial rate for an uncatalyzed reaction is linearly dependent on [S].
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Enzyme-catalyzed reactions encounter _______ conditions, which result in limited increases in the initial rate of the reaction as [S] is increased.
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Enzyme-catalyzed reactions encounter saturation conditions, which result in limited increases in the initial rate of the reaction as [S] is increased.
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If vmax is dependent on the total amount of enzyme available, then the relationship is:
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vmax = k3[E-total]
k3 = kcat = turnover number |
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T/F: v is equal to vmax when [ES] is equal to [E-total].
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True
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Equation for ES Formation
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Rate = k1[E][S]
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Equation for ES Breakdown
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Rate = (k2 + k3)[ES]
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Equation for Steady-State Kinetic Constant for Enzyme-Substrate Complex
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Km = (k2+k3)/K1 = ([E][S])/[ES]
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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. |
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. |
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Equation for Lineweaver-Burk Plot
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1/v = (Km/Vmax)(1/[S]) + 1/Vmax
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Competitive inhibitors change ______.
Uncompetitive inhibitors change ______. Noncompetitive inhibitors change ______. |
Competitive inhibitors change Km but not Vmax.
Uncompetitive inhibitors change both Km and Vmax. Noncompetitive inhibitors change Vmax but not Km. |
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T/F: Competitive inhibitors only bind the free enzyme and not the enzyme-substrate complex, but uncompetitive inhibitors bind both.
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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.
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