(3) Pharmacokinetics (Wolff) Flashcards
What are the four basic pharmacokinetic processes?
ADME
Absorption, Distribution, Metabolism, Excretion
What factors can affect drug absorption?
Rate of dissolution
Surface area
Blood flow
Lipid solubility
pH partitioning
What is the most common way that drugs travel accross the membrane?
SIMPLE DIFFUSION
What type of drug can readily cross a cell membrane?
Non polar drugs
Could these compounds cross the membrane?
NO!!!
Quaternary ammonium compounds have a fixed charge and CANNOT readily cross cell membranes
When can weak acids and weak bases cross membranes?
ONLY when they are in their unionized form
Aspirin is a weak acid.
Where would it be well absorbed?
Where would it be trapped?
Stomach.
Trapped in basic compartments.
Amphetamine is a weak base.
Where would it be well absorbed?
Where would it be trapped?
NOT the stomach.
Trapped in acidic compartments
Pharmacokinetic Math Terms
Ka =
S =
F =
Amount absorbed =
Ka =rate constant for absorption
S = “salt factor”
F = bioavailability, fraction of drug that reaches the bloodstream
Amount absorbed = S * F * Dose
How do you calculate bioavailability?
What are the factors that affect drug distribution?
Ability of drugs to enter the cells
Blood flow to tissues
Ability of drugs to exit the vascular system
What is the significance of protein binding of drugs?
You can get partial retention of drugs in vasculature
*There are a finite # of protein binding sites in the plasma, due to this, the addition of new drug can displace the bound drug
DRUGS ARE ONLY BIOACTIVE IF FREE (use alpha to denote free)
What are special considerations you must make with drug admin. w/ the blood brain barrier?
In an adult, ionized/polar drugs will not cross the BBB unless there is a specific transporter
This is why LIPID drugs are the typical class of drug to target the brain
How do you calculate the concentration of drug in the plasma?
How do you calculate the volume of distribution (Vd)?
Where is the primary site of biotransformation/metabolism of drugs?
LIVER
What is a PHASE I reaction in regard to biotransformation/drug metabolism?
*What’s the famous system that performs phase I reactions?
Oxidation, reduction, hydrolysis
Goal = Unmask functions
Products are usually more polar
*Cytochrome P-450
What is a PHASE II reaction in regard to biotransformation/drug metabolism?
Conjugation
***Attaching a charge
Glucuronidation, sulfation, acetylation, methylation
These help INACTIVATE drugs
What is the significance of GRAPEFRUIT JUICE in relationship to drug metabolism?
Grapefruit juice is an inhibitor of cytochrome P450 CYP34A enzyme
–> Inhibition of this enzyme in the intestinal epithelial cells increases the bioavailability of OTHER DRUGS metabolized by that enzyme since a dose is not destroyed to the same extent before entering the blood
What is the major way drugs are excreted?
What are the other ways?
RENAL = major route of drug excretion
Others= Bile, sweat, breath, breast milk
Elimination Terminology
Define:
Excretion rate
Clearance
Excretion rate = the mass eliminated per unit time
Clearance = the plasma volume from which all of the solute is removed per unit time (i.e, ml/min = a flow rate)
Describe
Zero order kinetics
Constant amount eliminated per unit
eg. Shoveling snow. No matter how much snow there is, you can only shovel so much you know?!
Describe
First order kinetics
Constant fraction eliminated per unit time
The mass of drug eliminated is directly related to the drug concentration
elimination constant * the half life = ???
k * t1/2 =???
0.693
How do you calculate clearance?
Kel = Cl/ Vd
kel= first order elimination rate constant
Cl=clearance
Vd=apparent volume of distribution
