Chapter 3 - Pharmacokinetics Flashcards
Test 1
List the pharmacokinetic variables (ADME).
Absorption
Distribution
Metabolism
Excretion
What are the four ways a drug gets across barriers
Aqueous diffusion
Lipid diffusion
Special carriers
Endocytosis and exocytosis
Permeation refers to…
The ways to get drugs from outside of the body to where it’s going to work
Describe Aqueous diffusion
Water soluble drugs crossing membranes into large aqueous compartments (ECF, blood, cytosol)
Cells may have water channels called aquaporins; Diffusion by concentration gradient
Highly charged molecules and molecules bound to large proteins carriers cannot cross via aqueous diffusion
Describe Lipid diffusion
Lipid soluble drugs
diffusion by concentration gradient
Describe Special carriers
Molecule binds to drug and moves across barrier
Active transport and facilitated transport
Describe Endocytosis and Exocytosis
Give an example
Endocytosis: membrane engulfment- then membrane swallows the drug and spits it out on the other side
Exocytosis: merging of vesicle with membrane
Ex) Cathrin coated pit
What does rational dosing refer to?
desired effects with minimal adverse effects
Once we give a certin dose, where will the drug be distributed to? How much will be eliminated? How much will actually make it to the site that is needed?
What is Volume of distribution?
V(d)
The space available in the body to contain a drug.
It tells us how much of the drug stayed in the blood vs how much went to other areas
What happens when V(d) is increased? Decreased?
When V(d) is high a lot leaves the blood
When V(d) is low alot stays in the blood
What is the V(d) formula?
V(d) = (X(0) - Dose given) / (C(0) - drug concentration in the blood)
What are the units for V(d)?
Liters
When should you draw blood for drug concentration?
PO- after 30 mins
IV - 1-2 mins or immediately
Standard drug dosing starts with ______ volunteers
Healthy
What is Clearance?
The ability of the body to eliminate the drug
Refers to multiple body organs not just the kidneys
** Elimination changes based on clearance and they are NOT the same thing**
What are the Whole blood values?
0.08L/Kg
5.6L in 70kg
What are plasma values?
0.04L/kg
2.8L in 70kg
What is concentration?
The amount of a drug in the blood
What is the formula for dose?
V(d) x Target concentration
He will give us V(d)
What are the units for dose?
mg or mcg / kg
What is Target concentration?
The desired concentration of the drug in the body to achieve the desired effect
Pharmacokinetics play a role in this so different per person.
What is Rate of Elimination?
How fast youre getting rid of the drug
What is the Rate of elimination formula?
Rate of elimination = Concentraton x Clearance
What is First-Order Elimination?
ROE = CL x C
ROE is dependent on concentration
Clearance is constant
Where Clearance will stay the same but the rate of elimination will vary because after time the amount of concentration decreases.
What is Zero Order Elimination?
ROE = CL x C
ROE is constant
CL varies
Elimination mechanisms are saturated and cant get rid of faster. The body’s ability to eliminate a drug has reaches its maximum capacity.
Dose/drug concentration increases = the amount of drug eliminated does NOT increase = fraction of drug removed declines.
What are the 3 main drugs Zero order elimination applies to?
Phenytoin, Ethanol, and Aspirin
Any drug can reach Zero order elimination if given in a high enough dose/concentration (Michaelis-Menten therory)
What is a high extration drug?
A drug that is eliminated via an organ with unrestricted blood flow and highly sensitive to first pass metabolism
What are the extration ratios?
> 0.7 - high
0.3 - 0.7 - intermediate
<0.3 - low
How does the extration ratio (E) and blood flow (Q) effect Clearance?
High E ; High Q = High CL
All other combos are lowwww
What is Half-life (T1/2)?
Example?
Time required to change drug in body to 1/2 of concentration
Drug concentration is 10. Half life is 4.
-After 4 hours the concetration is 5
-after 8 hours the concentration is 2.5
-after 12 hours the concentration is 1.25
What is the Half-life formula?
T(1/2) = (0.7 x V(d)) / CL
Why is half life important?
Tells us how often and when we should dose the patient
Tells us how soon theyll reach target concentration or how soon they’ll get to 0 concentration
What does a high Clearance indicate?
The drug will be eliminated at a higher rate
How long does it take to reach target concentration without a bolus?
4 half lifes
Ex) half life 4 hours
16 hours to reach target concentration
How long does it take for a drug concentration to effectively reach 0?
4 half lifes
What is the purpose of steady state dosing?
to keep the patient at the desired effect; to replace what we’re getting rid of.
What effects half life?
Disease states.
THINK what affects clearance? Kidney failure… liver failure… etc depends on what is metabolizing/eliminating the drug
What does accumulation mean?
Drug accumulates until dosing stops
Needs to wait 4 half lifes before taking next dose!!!!!!
Can reach toxic levels
What is bioavailability?
How much of the drug reaches systemic circulation (CVS).
What is the bioavailability of IV?
100%
What is the bioavailability of PO?
5 - 100%
What is 1st-Pass Elimination
In PO meds…
Portal circulation: Biotransformaton may occur prior to reaching circulation
PO drugs absorbed in the small intestines via tiny blood vessles and taken to the liver 1st where the bioavilability changes (Drug could be eliminated/metabolized, could be stronger, could become weaker)
Therefore high gut absorption does not equate to high bioavailability
How do you bypass the 1st-Pass elimination?
Non-PO route.
Inhalation has some 1st pass effects
Describe rectal suppositories and the 1st pass elimination
The rectum vessels bypass portal circulation. Suppositories usually migrate upward therefore about 50% bypass portal circulation
List the 7 routes of drug administration
- PO
- Parenteral (IV,IM,SQ)
- Topical
- Transdermal
- Inhalation
- Sublingual
- Rectal
Dose ________ equal concentration
Does not
Target concentration is _____________
Therapeutically determined
What is the formula for dosing rate for steady state at 100% bioavailability?
Dosing rate (ss) = (CL x TC) x (Pt WT)
What is the formula for dosing rate for bioavailability less than 100%?
Dosing rate (oral) = Dosing rate (calc) / F(oral)
F = bioavailbility
What is the formula for intermittent doses?
Called maintenance dose
Maintenance dose = dosing rate x dosing interval
Describe Therapeutic Drug Monitoring (Peak and trough).
Therapeutic drug monitoring involves measuring peak and trough drug concentrations to ensure the drug is within the therapeutic range.
The peak is measured 5-10 mins after iv administration
Trough is measured 30 mins prior to next dose
List the test used to determine kidney function.
Glomerular Filtratration Rate (GFR)
Can be estimated using the creatinine clearane
What is a Loading Dose?
A bolus when we need to reach steady state quickly
What must we consider when giving a loading dose?
The Volume of distribution
THINK; whats going to happen if we give this drug in 1 push? Loading dose doesnt mean push… Normally over a faster period of time like 5 minutes
What is the loading dose formula?
LD = V(d) x TC
When do we use the Ideal body weight formula instead of the actual body weight?
When the drug does not penetrate fat
professor will tell us if the drug does*
What is the formula for Ideal body weight?
IBW(men) = 52 + (1.9kg x (# of inches over 5 ft))
IBW(women) = 49 + (1.7kg x (# of inches over 5 ft))
