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92 Cards in this Set
- Front
- Back
- 3rd side (hint)
Drug Action
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Molecular action - invisible
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Drug effect
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pharmacologic effect- visible response
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pharmacokinetics
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time course of absorption, action, and elimination
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pharmacodynamics
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physiochemical or receptor interactions
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reversible receptor bonds
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ionic, Van der waals, Hydrogen
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irreversible receptor bonds
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covalent
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EC50 (definition) (tells you what about the agonist?)
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effective concentration for 50% response
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relates to affinity of agonist for receptor
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graded response graph (for drug effects)
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linear format
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dose-response graph (for drug effects)
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logarithmic
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threshold of dose-response graphs (definition) (gives you what info about the agonist?)
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dose of agonist at which response begins
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relates the affinity of agonist for the receptor
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Effect = (of certain dose of drug)
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E(max) [D] ---------------- K(D) + [D]
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K(D) = EC50
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intrinsic activity (definition) (influences?)
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ability to stimulate a receptor once bound
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efficacy and potency
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E(max) (definition) (what % of receptor occupancy needed?)
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maximum response
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not all receptors need to be occupied
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More efficacious agonists need ______ receptors occupied than less efficacious agonist to achieve the same effect.
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less
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Less efficacious agonists need ______ receptors occupied than more efficacious agonist to achieve the same effect.
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more
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secondary receptors
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outside target tissue - mediate side-effects
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strongest agonist has ______ intrinsic activity
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strongest
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These agonists differ by their _____ but not in _____
(how can you tell?) |
binding, activating the receptor
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different EC50's but same E(max)
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three agonists with the same?
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intrinsic activity
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two agonists with different?
(but the same?) |
intrinsic activity
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receptor binding affinity (K(D) is the same)
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Efficacy
(depends on the?) |
the ability of the drug to activate the effector portion of the receptor once bound
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structure of the drug
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Potency
(depends on?) |
relates to the amount of drug that is needed for an effect
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3)Biologic System (receptor density, efficiency of stimulus-response mech)
2)Interaction with the Receptor (affinity, efficacy) |
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double-headed arrows represent differences in?
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A- relative potency (amount of drug needed)
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B- relative efficacy (maximum effect)
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adding of a competative antagonist to a dose of agonist inc/dec the ____ of the Log Dose-response curve of the agonist?
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increases
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K(D) or EC50
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what type of antagonism?
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non-competitive
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(T/F) Non-competitive inhibitors inactivate the effector
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(T)
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(T/F) Noncompetitive antagonists interfere with agonist binding.
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(T)
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(T/F) Competitive antagonists interfere with agonist binding.
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(F)
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(T/F) Competitive inhibitors inactivate the effector.
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(F)
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characteristics of Simple Diffusion
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Lipid Soluble, small, nonionized
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Characteristics of Facilitated Diffusion
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selective, can be saturated
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Characteristics of Filtration
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driven by hydrostatic pressure, transported through pores or channels between cells, size limiting
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Amount of:
Intracellular Fluid Interstitial Fluid Plasma |
28L
9L 3L |
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What characteristics do drug molecules have that can pass through the capillary membrane?
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small molecule, lipid-(in)soluble
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weak acids ____ a proton
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give up
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weak bases ___ a proton
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accept
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Henderson-Hasselbach Equation
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pH= pKa + log A-/HA
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which is greatly absorbed in the stomach, weak acids or weak bases?
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weak acids
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Two fluid compartments, 1: pH=7.4, 2: pH=1.4. Which direction will equilibrium shift for a weak acid?
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Toward compartment 1.
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Two fluid compartments, 1: pH=7.4, 2: pH=1.4. Which direction will equilibrium shift for a weak base?
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Toward compartment 2
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What is trapped in the stomach, weak acids or weak bases?
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weak bases
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Enteral drug administration.
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GI tract
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Parenteral Drug Administration.
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any route of administration not through the GI tract.
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Which is less painful and more rapid in reference to absorption, S.C. or intramuscular injections?
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intramuscular
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label routes of administration. Between which two is inhalation?
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A-IV
B-IM C-SC D-PO and between A and B |
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Bioavailability
(definition) (equation) |
fraction of dose available for biologic action
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AUC (oral)
--------------- X100 AUC (iv) |
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Equation to predict plasma concentration of drug- IV
(pill) |
Cp = Dose/Vd
(Vd = volume of distribution) |
Cp = (F x Dose)/Vd
(F = fraction absorbed) |
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Volume of Distribution
(equation) (values) |
Vd = Dose / Plasma Concentration
(D/Cp) |
40L - sml molec. & lipid-soluble
12L- lipid-soluble 3L- protein bound |
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Why might the Volume of Distribution of a drug appear to be more than 40?
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Tissue Binding or plasma protein binding
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what are the two components of volume distribution of a drug?
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a = drug distribution
b = drug elimination |
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Factors affecting distribution of a drug:
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Blood flow
Ability to enter fluid space (pH, binding, transport, solubility...) Time after administration Redistribution Size of Pt |
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label initial compartments of drug distribution
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Top- Plasma
Dashed- Brain Dotted- Muscle lowest- fat |
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What do you do with an overdose of a weak acid drug for CNS toxicity? (aspirin/barbiturates)
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increase plasma pH (with NaHCO3)
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What do you do with an overdose of a weak base drug for CNS toxicity?
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decrease pH (with HCl)
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What can cause a smaller apparent Vd for a drug?
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reporting of total measured drug in the plasma with drug plasma protein binding
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loading dose
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needing to fill the storage sites of a drug before enough free drug is available to interact with its target tissue... where are these storage sites?
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short term- protein binding
long term- lipid or bone |
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why is it dangerous to give both antibiotics and anticoagulants?
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drug displacement- the antibiotic will displace some of anticoag attached to plasma proteins, releasing more free drug
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Purpose of Biotransformations
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to clear a drug from the plasma
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Basics of preparing a drug for excretion
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make it larger, charged, and more water soluble
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What are the reactions that compose the first two Phases of biotransformation?
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Phase 1: oxidation, reduction, hydrolysis
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Phase 2: conjugation
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term used to describe an increase in metabolism of the primary drug or other drugs in the Liver?
what is the consequence of this? |
induction
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you may need to increase the dose of the drug to achieve the desired effect
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term used to describe when a pt on antibiotics and cardiac drugs experiences an overdose of the cardiac drugs due to the antibiotics blocking the metabolism of the cardiac drugs
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inhibition
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(T/F) The hepatic microsomal drug metabolizing system performs both Phase 1 and Phase II processes
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True
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(T/F) The non-microsomal systems perform both Phase 1 and Phase II processes.
examples of non-microsomal systems? |
False- usually phase I (acetyl cholinesterase, alcohol dehydrogenase)
plasma, red cells |
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What is the most common Phase 1 reaction for the biotransformation of drugs?
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drug oxidation
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What is the most common Phase 1 reaction for the biotransformation of drugs?
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drug oxidation
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Locations (organ and cellular specific) of oxidation of drugs
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plasma, red cells, other tissues
ER, cytoplasm, mitochondria |
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6 components of hepatic mixed function oxidase system
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1) NADPH
2) cytochrome P450 reductase (flavoprotein) 3) cytochrome P450 (hemoproteins) 4) Mg++ 5) phospholipid 6) O2 |
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In the hepatic mixed oxidase system does the drug bind to Ferrous or Ferric iron-P450?
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Ferric +++ iron
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Tylenol Overdoses deplete the body of NADPH. How does this effect the drug metabolism in the liver?
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greatly reduces it. without NADPH cytochrome P-450 reductase oxidized flavoprotein can not be recycled to its reduced state, thus durg-P450-Fe+++ can not be reduced
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(T/F) 1-2% of caucasians but 5-10% of SE asians have poor metabolic activity
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False- %'s are reversed. The 4 types of phenotypes of metabolic activity are: poor, intermediate, extensive, and untrarapid
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cellular areas where drug reductions take place in the liver
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1) microsomes
2) cytoplasm 3) mitochondria |
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(T/F) Phase 1 of drug biotransformation does not inactivate the drug
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False- products of Phase 1 have variable activities, some active, some inactive
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Location of Phase II biosynthetic reactions
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Liver
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The resulting molecule of a Phase II biotransformation reaction is:
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larger, charged, water soluble, and inactive
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What type of energy source is used for the Phase II conjugation reaction of glucaronide to a drug?
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UTP
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Which of the following are components of Phase I and which are Phase II biotransformation reactions?
1) acetyl Co-A 2) H20 3) Fe-+++ 4) S-adenosylmethionine 5) cytochrome P-450 6) UTP 7) Flavoprotein 8) H 9) Glucuronide |
1) acetyl Co-A: Phase II
2) H20: Phase I (hydrolysis) 3) Fe-+++: Phase I (oxidation) 4) S-adenosylmethionine (Phase II) 5) cytochrome P-450: Phase I (oxidation) 6) UTP: Phase II 7) Flavoprotein: Phase I (oxidation) 8) H: Phase I (reduction) 9) Glucuronide: Phase II |
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equation for enzyme reaction with a drug
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Vmax [D]
V=-------------- Km + [D] |
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What order of kinetics occurs at low drug concentrations? (when [D],,Km)
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First Order
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What order of kinetics occurs when there is a large concentration of drug? ([D]>>Km)
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Zero Order
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Explain the enzyme/durg concentration relationship for zero order kinetics.
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the enzyme is at its max efficiency
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Explain the enzyme/durg concentration relationship for First order kinetics.
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enzyme is proportionately responsive to the concentration of drug
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(T/F) The hepatic microsomal drug metabolizing system experiences both induction and inhibition.
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True
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(T/F) The non-microsomal systems experience both induction and inhibition.
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False- they only experience inhibition
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what does saturation of the transport systems in the kidney due to the order of the kinetics of renal clearance?
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changes First order to Zero order (max rate)
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In manipulating the pH of urine (pH partitioning) to enhance the renal excretion of a drug, is the urine made to be more acidic or more alkaline than the plasma?
Is the plasma more acidic or alkaline than the brain? |
urine is more alkaline than the plasma (pH=8)
plasma is more alkaline than the brain (pH=7.5) Brain pH=7.4 |
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What compound is used to alkalinize the urine?
1) Sodium Sulfate 2) Sodium Bicarbonate 3) Phenobarbital |
Sodium Bicarbonate
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What is the role of activated charcoal in overdoses that do not involve the ingestion of the drug?
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To stop the enterohepatic cycling that will keep the drug from being eliminated in bile.
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equation for Clearance
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Clearance Total =
C(metabolic) + C(renal) |
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clearance rate of inulin =
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filtration rate
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clearance rate of glucose =
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zero
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clearance of PAH =
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active transport + filtration (~650ml/min)
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