Unit 4 Pharmacology: Pharmacokinetics Flashcards
What is the volume of distribution?
Describes the relationship between a drug dose and the drug’s plasma concentration, it is a theoretical measure of how a drug distributes throughout the body.
What 2 things does Vd assume?
- The drug distributes instantaneously (full equilibrium at t=0)
- The drug is not subjected to bio transformation or elimination before it fully distributes
What is the formula for Vd?
Vd = amount of drug / desired plasma concentration
What is the body water distribution?
total body water 60% Intracellular volume 40% Extracellular volume 20% -interstitial fluid 16% - plasma fluid 4%
What is the Vd of a lipophilic drug? What does this mean for distribution and dose?
It exceeds total body water, >0.6 L/kg
This means it distributes into the total body water as well as into the fat.
It will require a higher dose to achieve a given plasma concentration
What is the Vd of a hydrophilic drug? What does this mean for distribution and dose?
It is less than total body water <0.6 L/kg
It distributes into some or all of the total body water, but not the fat.
It will require a lower dose to achieve a given plasma concentration
What affects the volume of distribution?
Drug characteristics:
Molecular size
Ionization
Protein binding
Patient characteristics:
Pregnancy
Burns
What is the formula for loading dose?
Loading dose = Vd x (desired plasma concentration / bioavailability)
What is the bioavailability for an IV drug?
1
Because it is injected right into the bloodstream
What is drug clearance?
The volume of plasma that is clear of drug per unit time
Clearance is directly proportional to what 3 things?
- Blood flow to clearing organ
- Extraction ratio
- Drug dose
Clearance is inversely proportional to what 2 things?
- Half-life
2. Drug concentration in the central compartment
What is steady state?
It occurs when the amount of drug entering the body is equivalent to the amount of the drug being eliminated by the body, there is a stable plasma concentration. Each compartment has equilibrated.
After how many half-times is steady state achieved?
After 5 half-times
In a 2 compartment model what part of the curve correlates with drug elimination from the plasma?
The less steep portion (the second part) represent elimination from the plasma, it is called beta phase
In a 2 compartment model what does the steepest part of the slope represent?
Redistribution from the plasma to the tissues, it is alpha phase
The slope of alpha phase in a 2 compartment model is influenced by a drug’s what?
Volume of distribution
As a general rule, the more lipophilic the drug, the larger the Vd, and the _____ the slope
Steeper
What is another name for the alpha portion of a 2 compartment model
t1/2 alpha
What is another name for the beta portion of the 2 compartment model?
t1/2 beta
What is a rate constant?
The speed at which a reason occurs, or how fast a molecule moves between compartments
Define the 3 rate constants:
k12
k21
ke
k12: rate constant for drug transfer from central to peripheral compartment
k21: rate constant for drug transfer from peripheral to central compartment
ke: rate constant for drug elimination from body
What is the difference between elimination half-life and elimination half-time?
Elimination half-life: the time it takes for 50% of the drug to be removed from the body after a rapid IV injection
Elimination half-time: the time it takes for 50% of the drug to be removed from the plasma during the elimination phase
When are elimination half-life and half-time different?
When the rate of drug removal from the plasma is not the same as the rate of drug removal from the body
By convention we say that a drug has been cleared from the body when what percent of the dose has been eliminated from the plasma? This is how many half-times?
96.9%
5 half-times
Half Time : % of drug eliminated : amount of drug remaining 0 1 2 3 4 5
0 : 0% : 100% 1 : 50 : 50 2 : 75 : 25 3 : 87.5 : 12.5 4 : 93.75 : 6.25 5 : 96.875 : 3.125
The half-times measures a constant fraction not constant amount, what does this mean
It takes the same period of time for the plasma concentration to a drug to fall from 200 to 100 as it does for 50 to 25
What is a context sensitive half-time?
The time required for the plasma concentration to decline by 50% after the infusion is stopped.
An acid donates ____
A base donates _____
Acid donates H+
Base donates OH-
If you put a strong acid or strong base in what it will _____ completely.
Ionize
If you put a weak acid or a weak base in water ______
A fraction will ionize and the remaining will be unionized.
What is ionization?
The process where a molecule gains a positive or negative charge, and this molecular charge affect a molecule’s ability to diffuse through lipid membranes.
What 2 things does the amount of ionization depend on?
pH of the solution
pKa of the drug
What is another name for pKa?
Dissociation constant
When is 50% of a drug ionized and 50% unionized?
When pKa and pH are the same
What is the solubility of ionized and unionized molecules?
Ionized: hydrophilic, lipophobic
Unionized: hydrophobic, lipophilic
Which form of a molecule is the active form, ionized or unionized?
Unionized
When is a drug more likely to undergo hepatic elimination, ionized or unionized?
Unionized
When is a drug more likely to undergo renal elimination, ionized or unionized?
Ionized
What form of the drug crosses lipid bilayers?
Unionized
What happens when you put an acid in a basic solution?
Acidic drug becomes highly ionized in basic pH.
The acidic drug donates its proton to the base and the acid becomes ionized.
What happens when you put an acidic drug into an acidic solution?
Like dissolves like.
The acidic drug will be highly unionized in an acidic pH.
Both want to donate a proton, so neither do and the drug remains unionized.
What happens when you put a base in an acidic solution?
A basic drug will be highly ionized in an acidic pH.
The basic drug wants to accept a proton and the acidic solution wants to donate one.
What happens when you put a base in a basic solution?
Like dissolves like.
A basic drug will be highly unionized in a basic pH.
Both want to accept a proton, but there are no donators so the basic drug remains unionized.
Drugs are usually prepared as a salt that dissociates in solution, a weak acid is paired with:
A positive ion: sodium, calcium, magnesium
Drugs are usually prepared as a salt that dissociates in solution, a weak base is paired with:
A negative ion: chloride, sulfate
The unionized fraction predominates if:
A molecule is a weak base and pH of the solution is _____
A molecules is a weak acid and pH of the solution is _____
> pKa of the drug (a base in a base)
< pKa of the drug (an acid in an acid)
The ionized fraction predominates if:
The molecule is a weak base and the pH is ____
The molecule is a weak acid and the pH is ____
< pKa of the drug (base in an acid)
> pKa of the drug (acid in a base)
