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41 Cards in this Set
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504 PHARM: DRUG DISPOSITION III: PHARMACOKINETICS
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504 PHARM: DRUG DISPOSITION III: PHARMACOKINETICS
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What is the study of pharmacokinetics?
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Study of conc of drug present in blood as a function of time.
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What is the goal of pharmacokinetics?
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1. attaining therapeutically effective plasma conc of drugs.
2. devising dosing regiments to avoid toxicity. |
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Limitations of pharmacokinetics
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1. math analyses are just an oversimplification of physiological processes.
2. varied clinical char of pts |
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First Order Kinetics of Elimination
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1. constant FRACTION of drug eliminated per unit time, NOT a constant amount.
2. plot of plasma conc against time is exponential. Plot of log conc against time is linear. |
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What is the 1st order kinetic rate constant?
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The fractional rate of elimination Ke in units of reciprocal time.
Ex. Ke = .2/hr means 1/5 of drug is eliminated per hour. |
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Biological half life
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Time required to reduce plasma conc by 50%.
Takes about 5 half lives for a dose to be effectively eliminated. |
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Eqtn for Biological Half life?
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T1/2 = 0.693/ Ke
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How can Ke and T1/2 be determined?
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From the slope of the log plasma conc versus time plot.
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What is the slope eqt?
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Slope = -Ke/ 2.3 or
Ke = -slope*2.303 or T1/2 = -0.301/sope |
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What is the importance of half life?
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Determines the duration of action of a single dose.
Determines time to reach a new steady state when rate of adm changes. Detemines choice of dosage interval. |
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Simple two compartment model
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1. small CENTRAL compartment (Vc)
2. large PERIPHERAL compartment. (Vp) Single IV dose where elimination is not complicated by absorption |
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Vol of distribution (Vd)
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Vd = Vc + Vp
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Distribution Phase
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Initial rapid fall in plasma conc after IV dose.
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Extrapolation of distribution phase gives us what fact?
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The vol of central compartment Vc.
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Which phase follows distribution phase?
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Elimination phase
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Extrapolation of the elimination phase gives us?
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Vd
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What is the MEC?
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.
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Absorption of a single dose usually follows which order kinetics?
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First order
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What is zero order kinetics of absorption?
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Constant amount of drug absorbed per unit time, e.g. continuous IV infusion or gaseous anesthetic, or even chronic multiple dosing.
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What is a condition precedent?
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A condition precedent is the most common and it must occur before an absolute duty of immediate performance arises in the other party.
Ex: I’ll buy the house if I can get financing. |
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Fast absorption
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More rapid onset, higher peak levels, but shorter duration of action.
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Slow absorption
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Slower onset, lower peak levels, but usually longer duration of action.
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Onset and duration of action depend on what?
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MEC relative to the plasma levels.
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Plateau Principle
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Explain the time course of drug action.
It applies whenever a drug or nutrient is infused or ingested at a relatively constant rate and when a constant fraction is eliminated during each time interval. Dosage intervals less than 5-6 half lives lead to accumulation in the body. Plasma conc increases until rate of adm and rate of elimination become equal. |
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Plateau principle only applies to which order elimination?
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First order elimination
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Clearance (CL) defined
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Vol of plasma from which drug is eliminated per unit time.
CL = rate of elim / plasma conc |
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Application of CL
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Determines the rate of adm required to reach the desired steady state plasma conc.
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At steady state, how is rate of elimination and adm related?
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They are equal.
They also equal to: = [CL x Css] / F Css: steady state conc. |
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Eqtn relating T1/2 , Vd, and CL
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T1/2 = 0.693 (Vd) / CL
NOTE: Vd and CL are independent of each other. |
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Time reach steady state concentration depends ONLY on what?
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T1/2
5-6 half lives are required to reach plateau conc. |
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Fluctuations in plasma conc at steady state over the time between doses are proportional to what ratio?
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Ratio of the dose interval : T1/2
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Magnitude of fluctuation w.r.t longer dose interval?
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Larger fluctuation for longer dose interval assuming same rate of adm.
NOTE: drugs with longer half lives can be given less frequently. |
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Effect on fluctuation if concentration is slowed?
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Fluctuation becomes blunted.
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Loading dose
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Initial higher dose of a drug that may be given at the beginning of a course of treatment before dropping down to a lower maintenance dose.
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Loading dose is how much greater than maintenance dose when dose interval is equal to T1/2?
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~ 1.5-2X
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What is the total loading dose eqtn?
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Total loading dose = CONCss (Vd) / F
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Char of zero order elimination
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Constant absolute amount of drug eliminated per unit time.
Amount of drug eliminated is INDEPENDENT of conc of drug present. |
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When does zero order elimination occur?
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When metabolism or excretion system is saturated or a required cofactor is limiting.
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Does plateau principle apply?
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NO
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Under zero order kinetics, what would happen if drug is continually administered?
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Toxic plasma concentration will be reached.
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