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87 Cards in this Set
- Front
- Back
What is the graph of most enzymatic reactions following Michaelis-Menten kinetics? What do the axises represent? |
Most follow a hyperbolic curve; however, enzymatic reactions that exhibit a sigmoid curve usually indicate cooperative kinetics (eg, hemoglobin)
Y-axis = Velocity (V) X-axis = [S] |
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According to the Michaelis-Menten equation, what does Km equal?
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Km = [S] at 1/2 Vmax
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What is Km (of the Michaelis-Menten equation) related to?
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Related to the affinity of the enzyme for its substrate
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What is Vmax (of the Michaelis-Menten equation) related to?
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Directly proportional to the enzyme concentration
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What is the slope on a Lineweaver-Burk plot? What do the axises represent?
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Slope = Km / Vmax
Y-axis = 1/V X-axis = 1/[S] |
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What is the X-intercept on a Lineweaver-Burk plot?
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1 / -Km
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What is the Y-intercept on a Lineweaver-Burk plot?
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1 / Vmax
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What value changes as the Y-intercept increases on a Lineweaver-Burk plot?
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As Y-intercept ↑, Vmax ↓
Remember Y-intercept = 1 / Vmax |
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What value changes as the X-intercept increases (gets closer to zero) on a Lineweaver-Burk plot?
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The further to the right the x-intercept, the greater the Km and the lower the affinity
Remember X-intercept = 1 / -Km |
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What happens to the lines of competitive inhibitors on a Lineweaver-Burk plot?
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Competitive inhibitors cross each other competitively
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What happens to the lines of non-competitive inhibitors on a Lineweaver-Burk plot?
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Non-competitive inhibitors do not cross each other
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Which types of inhibitors resemble the substrate? Which do not?
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Resemble substrate:
- Competitive reversible inhibitors - Competitive irreversible inhibitors Do not resemble substrate: - Non-competitive inhibitors |
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Which types of inhibitors can be overcome by ↑ [S]? Which are not?
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Overcome:
- Competitive reversible inhibitors Not overcome: - Competitive irreversible inhibitors - Non-competitive inhibitors |
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Which types of inhibitors canbind the active site? Which do not?
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Bind active site:
- Competitive reversible inhibitors - Competitive irreversible inhibitors Do not bind active site: - Non-competitive inhibitors |
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What is the effect of the different inhibitors on Vmax?
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Unchanged:
- Competitive reversible inhibitors Decreased: - Competitive irreversible inhibitors - Non-competitive inhibitors |
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What is the effect of the different inhibitors on Km?
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Increased:
- Competitive reversible inhibitors Unchanged: - Competitive irreversible inhibitors - Non-competitive inhibitors |
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What is the pharmacodynamic effect of the different inhibitors?
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↓ Potency:
- Competitive reversible inhibitors ↓ Efficacy: - Competitive irreversible inhibitors - Non-competitive inhibitors |
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What is pharmacokinetics?
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The effects of the body on the drug (ADME):
- Absorption - Distribution - Metabolism - Excretion |
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What is pharmacodynamics?
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The effects of the drug on the body
- Includes concepts of receptor binding, drug efficacy, drug potency, and toxicity |
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Which term encompasses the effects of the body on the drug?
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Pharmacokinetics, eg:
- Absorption - Distribution - Metabolism - Excretion |
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Which term encompasses the effects of the drug on the body?
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Pharmacodynamics, eg:
- Concepts of receptor binding, drug efficacy, drug potency, and toxicity |
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What is the term for the fraction of the drug that reaches the systemic circulation unchanged?
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Bioavailability (F)
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What is the bioavailability? What drug/administration has a bioavailability (F) of 100%?
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Fraction of administered drug that reaches the systemic circulation unchanged
For IV dose, F = 100% |
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What causes decreased bioavailability of orally administered drugs?
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F typically <100% because of incomplete absorption and first-pass metabolism in the liver
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What is the volume of distribution (Vd)?
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Theoretical volume occupied by the total absorbed drug amount at the plasma concentration
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What can affect the apparent Volume of Distribution (Vd)?
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Apparent Vd of plasma protein-bound drugs can be altered by LIVER and KIDNEY disease (↓ protein binding, ↑ Vd)
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How do you calculate the volume of distribution?
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Vd = amount of drug in the body / plasma drug concentration
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What are the compartments in which a drug may distribute?
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- Blood
- Extracellular Fluid (ECF) - All tissues including fat |
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What compartment is a drug in that has a low Vd? Drug characteristics?
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Drug is in blood (4-8 L)
- Large / charged molecules - Plasma protein bound drugs |
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What compartment is a drug in that has a medium Vd? Drug characteristics?
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Drug is in ECF
- Small hydrophilic molecules |
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What compartment is a drug in that has a high Vd? Drug characteristics?
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Drug is in all tissues, including fat
- Small lipophilic molecules, especially if bound to tissue protein |
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What is the half-life of a drug?
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The time required to change the amount of drug in the body by 1/2 during elimination (or constant infusion)
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A half-life is a property of what type of elimination?
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First-order elimination
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How long does an infused drug infused at a constant rate take to reach a steady state?
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Takes 4-5 half-lives to reach steady state
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How many half-lives does it take to reach 90% of the steady state level?
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3.3 half-lives
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How do you calculate the half-life of a drug?
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t1/2 = 0.693 * Vd / CL
CL = Clearance Vd = Volume of distribution |
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How much drug is remaining (%) after 1, 2, 3, and 4 half-lives?
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- 1: 50%
- 2: 25% - 3: 12.5% - 4: 6.25% |
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What does the clearance of a drug represent?
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The volume of plasma cleared of drug per unit time
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What can impair clearance of a drug?
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Defects in:
- Cardiac function - Hepatic function - Renal function |
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How do you calculate the clearance of a drug?
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CL = (rate of elimination of drug) / (plasma drug concentration)
CL = Vd * Ke Ke = Elimination Constant |
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How do you calculate what the loading dose should be?
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Loading dose = (Cp * Vd) / F
Cp = target plasma concentration at steady state Vd = volume of distribution F = bioavailability |
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How do you calculate what the maintenance dose should be?
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Maintenance dose = (Cp * CL * π) / F
Cp = target plasma concentration at steady state CL = clearance π = dosage interval (time between doses), if not administered continuously F = bioavailability |
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What is Cp?
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Target plasma concentration at steady state
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What happens to the relative maintenance dose in a patient with renal or liver disease?
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Maintenance dose ↓
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What happens to the relative loading dose in a patient with renal or liver disease?
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Loading dose is unchanged usually
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What determines the time to steady state?
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Depends primarily on t1/2 and is independent of dose and dosing frequency
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What are the types of elimination of drugs?
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- Zero-order elimination
- First-order elimination |
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What type of elimination is characterized by a constant rate of elimination regardless of Cp (constant amount of drug eliminated per unit time)?
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Zero-Order Elimination
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What limits Zero-Order Elimination?
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Capacity-limited elimination
(rate is constant no matter what the concentration is) |
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What happens to the concentration of a drug with time with Zero-Order Elimination?
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Concentration decreases linearly with time
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What drugs have Zero-Order Elimination?
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PEA (a pea is round, shaped like the "0" in "zero-order")
- Phenytoin - Ethanol - Aspirin (at high or toxic concentration) |
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What type of elimination is characterized by a rate of elimination directly proportional to the drug concentration (ie, constant fraction of drug eliminated per time)?
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First-Order Elimination
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What limits First-Order Elimination?
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Flow-Dependent Elimination
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What happens to the concentration of a drug with time with First-Order Elimination?
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Cp decreases exponentially with time
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What gets trapped in urine and is cleared quickly?
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Ionized species
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What drugs are weak acids? How does this affect their elimination?
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- Ex: phenobarbital, methotrexate, aspirin
- Weak acids are trapped in BASIC environments |
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How do you treat an overdose of a weak acid drug (eg, phenobarbital, methotrexate, aspirin)?
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Bicarbonate
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What drugs are weak bases? How does this affect their elimination?
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- Ex: amphetamines
- Trapped in ACIDIC environment |
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How do you treat an overdose of a weak base drug (eg, amphetamines)?
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Treat overdose of weak base with ammonium chloride
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What are the phases of drug metabolism?
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- Phase I
- Phase II |
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What happens in phase I drug metabolism? What does it yield?
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- Reduction
- Oxidation - Hydrolysis with cytochrome P-450 - Usually yields slightly polar, water-soluble metabolites (often still active) |
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What happens in phase II drug metabolism? What does it yield?
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- Conjugation (glucuronidation, acetylation, sulfation)
- Usually yields very polar, inactive metabolites (renally excreted) |
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What phase of drug metabolism do geriatric patients lose first?
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Phase I
- Reduction - Oxidation - Hydrolysis w/ cytochrome P-450 |
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What phase of drug metabolism do geriatric patients usually still have?
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Phase II
- Conjugation (glucuronidation, acetylation, sulfation) Geriatric patients have GAS |
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What type of abnormal drug metabolism in a patient causes greater side effects from certain drugs? Why?
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Slow acetylators - decreased rate of metabolism
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What is meant by drug "efficacy"?
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Maximal effect a drug can produce
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What is meant by drug "potency"?
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Amount of drug needed for a given effect
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What are some examples of high efficacy drug classes?
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- Analgesic (pain) meds
- Antibiotics - Antibiotics - Antihistamines - Decongestants |
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What mediates increased potency of a drug?
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Increased affinity for receptor
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What are some examples of high potency drug classes?
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- Chemotherapeutic (cancer) drugs
- Anti-hypertensive (blood pressure) drugs - Lipid-lowering (cholesterol) drugs |
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What is the effect of a competitive antagonist on potency and efficacy?
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- Shifts curve to right (decreased potency)
- No change in efficacy |
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How can you overcome a competitive antagonist?
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Increase the concentration of agonist substrate
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What is the effect of a non-competitive antagonist on potency and efficacy?
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Shifts curve down (decreased efficacy)
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How can you overcome a non-competitive antagonist?
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Cannot be overcome by increasing agonist substrate concentration
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What is the effect of an irreversible antagonist on potency and efficacy?
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Shifts curve down (decreased efficacy)
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How can you overcome an irreversible antagonist?
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Cannot be overcome by increasing agonist substrate concentration
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What is the effect of a partial agonist on potency and efficacy?
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- Acts at same site as full agonist, but with lower maximal effect (decreased efficacy)
- Potency is an independent variable |
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What is the relationship of flumazenil to diazepam?
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Competitive antagonist at GABA receptor
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What is the relationship of ketamine to glutamate?
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Non-competitive antagonist at NMDA receptor
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What is the relationship of phenoxybenzamine to norepinephrine?
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Irreversible competitive antagonist on α receptors
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What is the relationship of buprenorphine on morphine
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Partial agonist at opioid µ receptors
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What measurement is used to assess drug safety?
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Therapeutic Index
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How do you calculate the therapeutic index (TI)?
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TI = (TD50 / ED50) = (median toxic dose) / (median effective dose)
TITE: Therapeutic Index = TD50 / ED50 |
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What is the therapeutic window?
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Measure of clinical drug effectiveness for a patient
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What relative Therapeutic Index value do safer drugs have?
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Higher Therapeutic Index values
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What are some drugs with low Therapeutic Index values?
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- Digoxin
- Lithium - Theophylline - Warfarin |
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What value often replaces TD50 in animal studies?
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LD50 (lethal median dose)
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