• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

Card Range To Study

through

image

Play button

image

Play button

image

Progress

1/41

Click to flip

Use LEFT and RIGHT arrow keys to navigate between flashcards;

Use UP and DOWN arrow keys to flip the card;

H to show hint;

A reads text to speech;

41 Cards in this Set

  • Front
  • Back
504 PHARM: DRUG DISPOSITION III: PHARMACOKINETICS
504 PHARM: DRUG DISPOSITION III: PHARMACOKINETICS
What is the study of pharmacokinetics?
Study of conc of drug present in blood as a function of time.
What is the goal of pharmacokinetics?
1. attaining therapeutically effective plasma conc of drugs.
2. devising dosing regiments to avoid toxicity.
Limitations of pharmacokinetics
1. math analyses are just an oversimplification of physiological processes.
2. varied clinical char of pts
First Order Kinetics of Elimination
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.
What is the 1st order kinetic rate constant?
The fractional rate of elimination Ke in units of reciprocal time.

Ex. Ke = .2/hr means 1/5 of drug is eliminated per hour.
Biological half life
Time required to reduce plasma conc by 50%.

Takes about 5 half lives for a dose to be effectively eliminated.
Eqtn for Biological Half life?
T1/2 = 0.693/ Ke
How can Ke and T1/2 be determined?
From the slope of the log plasma conc versus time plot.
What is the slope eqt?
Slope = -Ke/ 2.3 or

Ke = -slope*2.303 or

T1/2 = -0.301/sope
What is the importance of half life?
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.
Simple two compartment model
1. small CENTRAL compartment (Vc)
2. large PERIPHERAL compartment. (Vp)

Single IV dose where elimination is not complicated by absorption
Vol of distribution (Vd)
Vd = Vc + Vp
Distribution Phase
Initial rapid fall in plasma conc after IV dose.
Extrapolation of distribution phase gives us what fact?
The vol of central compartment Vc.
Which phase follows distribution phase?
Elimination phase
Extrapolation of the elimination phase gives us?
Vd
What is the MEC?
.
Absorption of a single dose usually follows which order kinetics?
First order
What is zero order kinetics of absorption?
Constant amount of drug absorbed per unit time, e.g. continuous IV infusion or gaseous anesthetic, or even chronic multiple dosing.
What is a condition precedent?
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.
Fast absorption
More rapid onset, higher peak levels, but shorter duration of action.
Slow absorption
Slower onset, lower peak levels, but usually longer duration of action.
Onset and duration of action depend on what?
MEC relative to the plasma levels.
Plateau Principle
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.
Plateau principle only applies to which order elimination?
First order elimination
Clearance (CL) defined
Vol of plasma from which drug is eliminated per unit time.

CL = rate of elim / plasma conc
Application of CL
Determines the rate of adm required to reach the desired steady state plasma conc.
At steady state, how is rate of elimination and adm related?
They are equal.

They also equal to:

= [CL x Css] / F

Css: steady state conc.
Eqtn relating T1/2 , Vd, and CL
T1/2 = 0.693 (Vd) / CL

NOTE: Vd and CL are independent of each other.
Time reach steady state concentration depends ONLY on what?
T1/2

5-6 half lives are required to reach plateau conc.
Fluctuations in plasma conc at steady state over the time between doses are proportional to what ratio?
Ratio of the dose interval : T1/2
Magnitude of fluctuation w.r.t longer dose interval?
Larger fluctuation for longer dose interval assuming same rate of adm.

NOTE: drugs with longer half lives can be given less frequently.
Effect on fluctuation if concentration is slowed?
Fluctuation becomes blunted.
Loading dose
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.
Loading dose is how much greater than maintenance dose when dose interval is equal to T1/2?
~ 1.5-2X
What is the total loading dose eqtn?
Total loading dose = CONCss (Vd) / F
Char of zero order elimination
Constant absolute amount of drug eliminated per unit time.

Amount of drug eliminated is INDEPENDENT of conc of drug present.
When does zero order elimination occur?
When metabolism or excretion system is saturated or a required cofactor is limiting.
Does plateau principle apply?
NO
Under zero order kinetics, what would happen if drug is continually administered?
Toxic plasma concentration will be reached.