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77 Cards in this Set
- Front
- Back
The amount of drug excreted by any process per unit time depends on these 2 things
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1. Rate of elimination for that process
2. concentration of drug in plasma |
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A drug with a large Vd (volume of distribution) will be eliminated more slowly or more quickly than a drug with a lower volume of distribution?
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More slowly
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Drugs with a MW < _____ are COMPLETELY filtered when passing through the glomerulus
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5000
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What are the only forms of drugs that are filtered in the Kidney?
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Free, unbound
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Drugs with a MW of ______-_____ are PARTIALLY FILTERED when passing through the glomerulus
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5000-100,000
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Drugs not protein bound or not reabsorbed after being filtered are eliminated at a rate approximately equal to?
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Creatinine clearance = 125 ml/min
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T or F: Both IONIZED and NONIONIZED forms of a drug are filtered in the Kidney
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TRUE
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What are the 3 processes in the kidney in clearance?
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1. Filtration
2. Tubular secretion 3. Reabsorption |
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Creatinine clearance changes depending on what?
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Body mass
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Which form of drugs can undergo ACTIVE SECRETION and ACTIVE or PASSIVE REABSORPTION?
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Non-ionized
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Mechanism by which tubular secretion in the Kidney occurs and where its located
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TRANSPORT mechanism located in the MIDDLE SEGMENT of the PROXIMAL CONVULOTED TUBULE
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What are the two transport systems in Tubular Secretion?
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1. Anionic = weak organic acids
2. Cationic = weak organic bases and quaternary ammoniums |
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Rapid process: drugs eliminated by Tubular Secretion and NOT reabsorbed (penicillin) are cleared at a rate approaching ______ flow = _____ ml/min
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Renal Plasma flow
660 |
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An organic acid that is actively secreted and is used to measure renal plasma flow
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p-aminohippurate (PAH)
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What drug inhibits penicillin secretion in the kidney?
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Probenicid
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T or F: Tubular secretion is not a saturable process
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False -> transporters are the site of interactions
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Molecule used to measure anion secretion
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PAH = p-aminohippurate
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Molecule used to measure cationic secretion rate
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N-methylnicotinamide
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7 Acids (anionic) that are tubular secreted
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1. PAH
2. Penicillins 3. Cephalosporins 4. Salicylates 5. Thiazide diuretics 6. Glucuronide conjugates 7. Uric Acid PPG-CUTS |
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8 bases (cations) that are tubular secreted
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1. N-methylnicotinamide
2. Procaine 3. Quinine 4. TetramethylammonIUM 5. TetraethylammonIUM 6. HexamethonIUM 7. Neostigmine 8. Pyridostigmine QUIN, the NEW SMOKING PRO PYRAMID has 3 AMMONIUMs |
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Compound that is actively secreted and actively reabsorbed
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Uric Acid
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Type of drugs that can be reabsorbed in the Kidney
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Lipid soluble drugs (nonionized) = have relatively longer 1/2 lives
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What could be added to urine to increase the renal excretion of Weak Acids by "ion-trapping"?
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1. Sodium bicarbonate (NaHCO3)= base
2. Acetazolamide |
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3 Weak acidic drugs whose excretion can be increased by "ion-trapping"
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Phenobarbital
Methotrexate Aspirin |
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What could be added to urine to increase the renal excretion of Weak Bases by "ion-trapping"?
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Ammonium Chloride (NH4Cl) = acid
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2 weak basic drugs whose excretion can be increased by "ion-trapping"
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Amphetamine
Phencyclidine |
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Drugs secreted into bile are not always excreted but often go through this cycle
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Enterohepatic
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T or F: Drugs that enter the Enterohepatic cycle often have long half-lives
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True
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T or F: Smaller compounds are secreted into bile
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False -> larger compounds MW > 325 are secreted into bile
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Some glucuronides that are secreted into the bile are cleaved by glucuronidases in the Small Intestine. What does this allow for?
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It releases the parent compound for re-absorption
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What are 2 agents that bind drugs in the intestine that enhance excretion?
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1. Charcoal
2. Cholestyramine *they are Glucuronidase binding agents = inhibits the cleavage of Gluronides from the Parent Compound and enhances excretion |
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Does Enterohepatic Circulation of drugs increase or decrease the Apparent Volume of Distribution?
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Increase
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What do these 5 drugs have in common?
1. bile acids 2. Bilirubin glucuronide 3. Sulphobromphthalein 4. Penicillins 5. Glucuronide conjugates |
ANIONIC drugs that are present in BILIARY secretions
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List 2 Neutral molecules/drugs that are involved in Biliary secretion
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Steroids
Ouabain |
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List 2 Cationic molecules/drugs involved in Biliary Secretion
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N-methynicotinamide
Tubocurarine |
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In general, small glucuronide conjugates = _______ secretion
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urinary
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In general, large glucuronide conjugates = _______ secretion
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Biliary
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The lungs are most important for the excretion of this group of drugs
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Gaseous Anesthetics
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T or F: The walls of the stomach and intestine constitute a large lipid membrane across which lipid drugs can be transferred from blood to lumen
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True
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In zero-order kinetics using the log scale, is the slope straight or curved?
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Curved
*Arithmetic scale = straight |
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In first-order kinetics using the log scale, is the slope straight or curved?
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Straight
Arithmetic = curved |
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What is rate limiting in Zero-order kinetics
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The biological system = enzymes or transporters are saturable
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In Zero-order kinetics, the rate is independent of _________
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drug concentration
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Explain the rate in Zero-order kinetics
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A constant amount of drug is eliminated per unit time
Example: 10 mg eliminated every hour -40->30->20->10->0 -4 hours to be eliminated |
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What drug/chemical always follows Zero-order kinetics?
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Ethanol
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In zero-order kinetics, the pseudo half-life is proportional to what?
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the dose
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Name 2 drugs that, as you increase the dose there is a switch from 1st order to zero-order kinetics = Dose-dependent pharmacokinetics
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Phenytoin
Salicylates *due to saturation of elimination mechanisms |
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First-order kinetics is proportional to what?
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Concentration of the drug
*the higher the amount, the more rapid the elimination |
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What is rate-limiting in First-Order kinetics?
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Drug concentration
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In First-order Kinetics, drug concentration changes by some _______ per unit of time
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constant fraction eliminated (i.e. 0.1/h)
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What is constant in First-order kinetics?
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Half-life
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Is First-order kinetics Dose-dependent or Dose-independent?
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Independent
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Rate constant equation equals = ?
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-
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Half-life equation
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-
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Equation for the Amount of Drug in the body
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-
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Properties of the Log Scale in the One Compartment Kinetic Model (3)
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1. Straight Lines
2. Parallel lines 3. Rapid equilibrium between plasma and tissues |
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Properties of the Log Scale in the Multicompartment Kinetic Model
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1. Multiphasic Curves
2. Un-parallel lines 3. Slow equilibrium between plasma and tissues |
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What is the alpha phase in Multicompartment kinetics
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Distribution
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What is the beta phase in the Multicompartment kinetic model?
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Elimination
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When is the Multicompartment Kinetic model common?
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Drugs with high avidity for tissues
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Definition of Clearance
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Apparent volume from which a drug is COMPLETELY CLEARED per unit time (mL/min)
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Clearance = ?
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Rate of elimination from the body / plasma concentration
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What is Clearance independent of?
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Concentration and Dose
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How is Clearance calculated?
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-
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Clearance approaches _____blood flow for very rapidly metabolized drugs = ____ mL/min
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Liver
1500 |
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Clearance approaches ______ blood flow for drugs SECRETED by the renal tubule = _____ mL/min
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Renal
660 |
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Clearance approaches ________ rate for drugs eliminated by filtration = _____ mL/min
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Glomerular
123-130 |
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The Elimination Rate Constant (K-el) depends on these 2 UNRELATED physiological variables
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1. Plasma clearance (Cl-b)
2. Apparent Volumes of Distribution (Vd) |
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Plasma Clearance equation
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Kel = Elimination Constant
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The extent to which the drug reversibly leaves the circulation and enters the tissues of the body
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Apparent Volumes of Distribution
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The ability of the organs of elimination to extract the drug from the general circulation and remove it from the body
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Plasma Clearance
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Renal Clearance equation for SECRETION
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Clearance = (urine flow) X (Concentration of drug in urine/Concentration of drug in plasma)
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Renal Clearance equation for Glomerular Filtration
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Clearance = Urine flow X (conc. of drug in urine / conc. of free drug in plasma)
***only FREE drug is filtered*** |
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Relative amount of administered drug that reaches the general circulation
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Bioavailability
*IV doses have 100% bioavailability |
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What scale is used for AUC?
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Arithmetic
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What does AUC represent?
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total amount of drug available over time
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Bioavailability equation
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-
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