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147 Cards in this Set
- Front
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allows the clinician to take into account the various pathologic and physiologic features of the patient that make them different from the average individual in responding to a drug
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pharmacokinetics
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clarify dose effect relationships
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pharmacokinetics
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achieve therapeutic goal of having desired beneficial effect with minimal adverse effect
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pharmacodynamics
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What is the significance of pharmacokinetics and pharmacodynamics?
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improvement of therapeutic benefits and reduction of toxicity
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science that deals with the relationship between the dose, drug concentration, and effects on the body
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pharmacokinetics
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What 4 things does pharmacokinetics deal with?
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absorption
distribution metabolism elimination |
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The ____ dose of a drug is based on trials on healthy volunteers and patients with average ability to absorb, distribute, and eliminate a drug.
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standard
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What 2 processes dictate the dose adjustments in individuals?
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physiological processes
pathological processes |
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What is an example of a physiological process that dictates dose adjustments?
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maturation of organ function in infants
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What is an example of a pathological process that dictates dose adjustments?
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renal failure
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deals with ability of body to eliminate the drug
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clearance (Cl)
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deals with the apparent space in the body available to contain the drug
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volume of distribution (Vd)
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What are 2 pharmacokinetics parameters?
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clearance
volume of distribution |
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volume of the compartment into which drug diffuses
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volume of distribution
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____ can affect both the Vd and clearance
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disease states
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relates the amount of drug in the body to the concentration of the drug in the blood or plasma
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Vd= amount of drug/concentration
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rate of elimination of drug in relation to drug concentration
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Cl= rate of elimination/concentration
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Where in the body does the elimination of drug occur?
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kidney
lung liver other organs |
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What are 2 major sites of drug elimination in the body?
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kidney
liver |
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occurs via biotransformation of a parent drug to one or more metabolites
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liver drug elimination
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T/F: clearance is constant for most drugs
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true
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T/F: rate of drug elimination is not directly proportionate to concentration
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false
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Where is unchanged drug excreted into?
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bile
liver both |
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time profile after a dose
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area under the curve (AUC)
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How is clearance calculated?
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clearance= dose/AUC
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also known as saturable dose, concentration dependant nonlinear, and Michaelis Menton elimination?
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capacity limited elimination
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T/F: most drug elimination pathways will become saturated if the dose is high enough
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true
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T/F: if dosing rate is less than elimination rate, steady state (SS) cannot be achieved.
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false (more, not less)
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T/F: concentration will keep rising as long as dosing continues.
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true
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T/F: clearance has no meaning for drugs with capacity limited elimination.
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true
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T/F: concentration can be used to describe elimination of drugs.
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false
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Name a drug with which capacity limited elimination is common.
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Phenytoin
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drug elimination pathways become saturated if dose is high
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capacity limited elimination
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elimination on drug is dependant primarily on rate of drug delivery to the organ of elimination
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flow dependant elimination
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drugs that are cleared very rapidly by organ of elimination
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high extraction drugs
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Name 2 types of elimination.
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capacity limited elimination
flow dependant elimination |
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time required to change the amount of drug in the body by one half during elimination
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half life
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What is the time course of a drug in the body dependant on?
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volume of distribution
clearance |
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indicates the time required to attain 50% steady state (SS) or to decay 50% SS
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half life
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What should you do if a patient ODs on something with a long half life?
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give antedote
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What should you do if a patient ODs on something with a short half life?
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just stop the transfusion
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state of saturation where amount of drug given in each dose is equal to amount eliminated
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steady state (SS)
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When is 50% of steady state concentration reached?
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after 1 half life
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When is 75% SS concentration reached?
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after 2 half lives
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When is >90% SS concentration reached?
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after 4 half lives
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How many half lives must elapse after starting a drug dosing regimen before full effects can be seen?
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4 half lives
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the fraction of unchanged drug reaching the systemic circulation following administration by any route
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bioavailability
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common measure of extent of bioavailability of a drug
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area under the curve (AUC)
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What percent of bioavailability is seen with IV administration?
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100%
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What percent of bioavailability is seen with oral administration?
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<100% because of incomplete absorption and first pass effect
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What is reverse transportation associated with?
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P-glycoprotein
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process that pumps drug out of the gut wall cell back to the lumen
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reverse transportation
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What is an example of how P-glycoprotein may be associated with increased drug absorption?
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grapefruit
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absorption from the gut wall leads to portal blood delivering drug to liver prior to entry into the systemic circulation
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first pass elimination/first pass effect
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Where might a drug be metabolized?
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gut wall
portal system liver |
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What sites contribute to decreased bioavailability?
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gut wall
portal system liver |
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determined by site of administration of drug
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rate of absorption
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What 2 things influence clinical effectiveness of a drug?
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rate of absorption
extent of absorption |
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rate of absorption is independant of concentration or amount of drug remaining in gut
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zero order kinetics
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determined by rate of gestric emptying
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zero order kinetics
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rate of absorption is dependant on concentration
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first order kinetics
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full dose is dissolved in GI fluids and rate of absorption is usually proportional to GI concentration
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first order kinetics
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drug effects directly related to plasma concentration
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immediate effects
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T/F: relationship between drug concentration and effects is not linear.
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true
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What is an example of a drug with immediate effects?
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IV hypertension drug
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may be reflective of time required for drug to distribute from plasma to site of action
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delayed effects
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What might the delay of effects in some drugs account for?
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lag effect
IV injection of CNS active agent |
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What is an example of a drug that experiences lag effect?
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IV injection
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What is an example of a drug that is an IV injection of a CNS active agent?
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thiopental
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related to cummulative action of drugs
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cummulative effects
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What is an example of cummulative effects?
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renal toxicity of amino glycosides
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T/F: cummulative effects are greater when given by constant infustion than by intermittent dosing.
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true
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What is the difference between constant infusion and intermittent dosing?
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intermittent dosing has higher peaks, but less total accumulation
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concentration that will produce desired therapeutic effects, but that may need individualization
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target concentration
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T/F: initial concentration of a drug should be at higher end of range.
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false (lower)
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What is the target concentration for digoxin for atrial fibrillation?
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2 ng/ml
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What is the target concentration for digoxin for CHF?
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1 ng/ml
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dose needed to maintain steady state of the drug in the body
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maintenance dose (MD)
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amount of drug given in each dose to replace drug that is eliminated
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maintenance dose (MD)
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When must the dosing rate "rate in" equal the rate of elimination?
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steady state
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maintenance dose calculation
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dosing rate= Cl x target concentration
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convert MD to oral formulation
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MD= (dosing rate/oral bioavailability) x dosing interval
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What is the steady state concentration achieved by continuous infusion or the average concentration following intermittent dosing dependant on?
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clearance
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What must be known to determin the average plasma concentration expected from a given dose?
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volume of distribution
half life |
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dose that promptly raises the concentration of drug in the plasma to target concentration in order to achieve faster steady state
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loading dose (LD)
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often used for drugs with long half lives
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loading dose
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Give an example of a drug with a long half life.
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Dilantin
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What are 2 drug characteristics?
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hydrophilic
lipophilic |
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cannot cross the lipid cell membrane
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hydrophilic
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What is an example of a hydrophilic drug?
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atenolol
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not soluble enough to cross the water layer adjacent to the cell membrane
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lipophilic
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What is an example of a lipophilic drug?
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acyclovir
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What are the 3 major PK variables?
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absorption
clearance volume of distribution |
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rate and extent of transfer from site of administration to the blood; dependant on compliance
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absorption
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____ can be determined by concentration measurement
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failure of compliance
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If compliance is adequate, what can cause low concentration?
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absorption abnormalities in small bowel
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What may be indicated when major impairment of liver or heart present?
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abnormal clearance
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a useful indicator of renal function
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creatinine clearance (CrCl)
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shown to decrease clearance and prolong half life of many drugs
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hepatic disease
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T/F: no marker exists for hepatic drug metabolism to predict changes in hepatic clearance similar to use of CrCl as a marker for renal drug clearance.
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true
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reflects balance between binding to tissues which increase plasma concentration and makes Vd larger and binding to plasma proteins which increase plasma concentration and makes Vd small
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volume of distribution
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What can cause increased Vd for drugs like gentamicin, which are hydrophilic and have a small Vd?
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abnormal accumulation of fluid
(ie., edema, ascites, pleural effusion) |
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What has a Vd similar to total body weight/body water?
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theophylline
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____ persons have relative smaller Vd.
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older
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Vd may be overestimated in ____ patients based on body weight.
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obese
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clearance and half life important in determining effect of disease state on drug disposition
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half life
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Half life of diazepam ____ with age change in Vd with age.
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increases
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T/F: Clearance of diazepam changes with age.
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false
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What are 2 Pd variables?
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maximum effect attainable in target tissue
sensitivity of the tissue to the drug |
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What can modify Pd parameters?
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disease
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What is important in predicting the dose in cases of disease?
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ability to predict effect of disease state
Pk parameters |
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no matter how high drug concentrations go, a point is often reached beyond which no further increment in response is achieved
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maximum effect
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recognition can help avoid unnecessary increase in dose that can lead to toxicity
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maximum effect
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reflected by the concentration required to produce 50% of maximum effect
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sensitivity of an organ to a drug concentration
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can be reflected by failure to respond to drug (ie., not getting better)
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decreased sensitivity
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signaled by an exaggerated response to a small or moderate dose
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increased sensitivity
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may be confirmed by measuring drug concentrations that are low in response to effect observed
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increased sensitivity
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single most important factor in determining drug clearance
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clearance
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What 3 factors influence clearance?
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dose
organ blood flow intrinsic function of liver or kidney |
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What is the interpretation of measurements of drug clearance dependant on?
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dose
organ blood flow intrinsic function of liver or kidney |
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T/F: changes in plasma protein binding do not affect clearance.
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true
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What are some drugs that are extensively bound to plasma protein?
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phenytoin
salicylates |
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What can affect protein binding?
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albumin concentration
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What limits to the binding of drugs to plasma protein?
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capacity
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What is essential to obtain maximum value from a drug concentration measurement?
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drug history
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What will make drug concentration measurement lose predictive value?
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is dosing history unknown or incomplete
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occurs during first 2 hours of a drug dose; varies according to food intake, posture, and activity
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absorption
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How long should you avoid drawing blood to make sure absorption is complete?
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2 hrs after oral dose
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How long after a last dose should digoxin samples be taken?
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6 hrs
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When should lithium samples be taken?
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just before next dose
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When should aminoglycosides be sampled?
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at lease an hour after dose, even though it distributes very rapidly
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typically calculated using body weight
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volume of distribution
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If a patient is obese and the drugs do not penetrate fat, how should the Vd be calculated?
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using IBW
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JS, a 5ft 20in male obese patient is about to recieve gentamicin. It is important to calculate the patient's Vd. Calculate the patient's IBW:
A. 76kg B. 90kg C. 73kg D. 56kg |
c
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IBW men
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50 + (2.3 x in >5ft)
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IBW women
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45.5 + (2.3 x in >5ft)
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Ms, a 5ft 10in female obese patient, is about to receive gentamicin. It is important to calculate the patient's Vd. Calculate the patient's IBW:
A. 70kg B. 68.5kg C. 76kg D. 78.5kg |
b
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What do drugs that are cleared renally require adjustment in proportion to?
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renal function
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What determines CrCl?
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muscle mass
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Why does age appear in the Cockcroft Gault equation?
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muscle mass decreases with age
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What is decreased renal function with age independant of?
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decrease creatinine production
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What do you use for calculating CrCl obese patients?
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IBW
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What parameters are essential for optimal drug dosing?
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PK
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Why is optimal/individualized drug dosing essential to?
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avoidance of toxicity
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What parameters are essential for therapeutic benefits?
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PD
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CrCl (male)
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[140-age (IBW)]/(Scr x 72)
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CrCl (female)
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{[140-age (IBW)]/(Scr x72)} x 0.85
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