Pharmacokinetics Flashcards
are xenobiotics
Drugs
chemical which is found in an organism but which is not normally produced or expected to be present in it) (Biocompatible)
xenobiotic
Disciplines Involved in Drug Development
Physiology and Pharmacology required to select appropriate drug candidates.
Physics and Physical Chemistry and Mathematics involved in dosage form design.
Kintics, Analytical Chemistry and Therapeutics required to determine appropriate dose.
the study of the kinetics of drug absorption, distribution, metabolism and excretion of drugs (ADME) (body action)
Pharmacokinetics
the study of factors that affect the bioavailability of drugs in animals and man.
Biopharmaceutics
the study of the biochemical and physiological effects of drugs on the body or on microorganisms or parasites within or on the body and the mechanisms of drug action and the relationship between drug concentration and effect.
Pharmacodynamics
ADME
Pharmacokinetics
Transfer of drug from the absorptions site (stomach, intestine) to the blood. Rapid and not reversible.
Absorption
Fate of drug after Absorption (Distribution and Elimination).
Disposition
Transfer of drug from the blood to extravascular fluid, tissue, plasma proteins or other fluids. Rapid and reversible. Usually occurs much more rapidly than elimination.
Distribution
Rate of distribution to tissue/organ is determined by
blood flow
Biotransformation of drug, mainly in liver (Also kidney, skin).
Metabolism
Removal of drug compound and metabolites from the body.
Elimination
Goals of Pharmacokinetics
A. To compare the pharmacology and toxicology of drugs and their relationship to Cp of both the drug and its metabolite/s.
B. To determine the accumulation characteristics of drugs for the evaluation of chronic toxicity.
C. To individualize and optimize the therapeutic management of individual patients (dose, time).
D. To determine patient compliance
E. To evaluate the effect of disease states on drug elimination.
used an alternative to treadmill stress and used for elderly patients.
Dipyridamole (Persantine)
can increase the blood flow up to four to five times than in normal value.
Adenosine (Adenocard)
Used for increase of cerebral blood flow in cerebral perfusion imaging
Acetazolamide (diamox)
quantity that is always unchanged
Constant
mathematical constants
. π and e
physical constants
R, k (Boltzmmann constant) and N (Avagadro’s number)
constant that is not universal but does not vary in a particular instance.
Parameter
Examples of parameters
Rate constants, equilibrium constants, slopes and intercepts of graphs
a quantity that is changing during the course of an experiment
Variable
Examples of variables
axes of a graph - In a rate process time and concentration are variable.
the half-life of a drug is 2 hrs, and the concentration at 30 minutes were found 20 mg/mL - What is the half-life
half-life, t1/2 = 0.693/k
Decay Function
f(t)=e^-kt=exp(-kt)
Growth Function
f(t)=1-e^-kt
Intravascular routes
Intravenous
Intra-arterial
Extravascular routes
Oral Buccal Rectal Pilmonary Intramuscular and subcuteaneous injection Etc.
Intravascular Administration (bolus) characteristics
No absorption phase
Immediate onset of action
Entire dose is available
Route used frequently in life threatening situations
Adverse reactions difficult to reverse. Accurate dosing is thus essential.
Which function would be used for a bolus
Decay Function
An absorption phase is present.
Onset of action determined by a number of factors including formulation, route of administration (Oral, pulmonary, etc.), drug physicochemical properties, and physiological properties.
The entire administered dose may not be available.
Extravascular Administration
Which function would be used for extravascular administration
Combined Decay and Growth Function
Which function would be used for intravascular infusion
Growth Function
represent the area under the curve (AUC)
Definite integrals
In pharmacokinetics the integral is often referred to as
AUC
How to get AUC
Integration or Trapezoid Rule
Trapezoid Rule Equation
(b-a) ( h(a) – h(b))
Area= —————————
2
a technique for approximating the definite integral
Trapezoid Rule
How does the Trapezoid Rule work
The trapezoidal rule works by approximating the region under the graph of the function f(x) as a trapezoid and calculating its area
assumes quadratic dependence in this small interval - more accurate than trapazoid rule.
Simpson’s Rule
assumes function is linear in the small interval h
Trapezoid rule
AUC provides
the pk information such a duration of drug in blood, tmax, cmax, bioavailability etc.
Rate Equation
Rate depends on concentration
Decomposition reactions in the solid phase often show
zero order kinetics - not dependent on concentration
characterized by exponential decay
First order reactions
time required for concentration to become half
Half-Life
half life is 2 hr, how much will be left after 4 hrs?
25%
Is Half-life of first order reactions constant or variable
constant
How do Drug diffuse from compartments
Drug diffuses from compartments with high concentration to those with low concentration.
Pharmacokinetic models recognize that _____is an important mechanism for the absorption, distribution and excretion of drugs and their metabolites.
passive diffusion
What is the central compartment
blood and organs which are perfuse such as heart, kidney have same blood flow as in the blood vessel
considered as peripheral compartment.
Tight tissues such as muscle, bone where blood flow is more slower
