Pharmacokinetics - steady state Flashcards
What is the drug half-life?
The time required for the drug concentration to change by 50%.
What are the two half-lives for a drug?
Distribution half-life
Elimination half-life
Half-life follows what order kinetics?
First order
What is the equation for Ct?
Ct = C0e^-kt
Ct - concentration of drug at various times
C0 - initial concentration of drug at time zero
k - elimination rate constant
What is the equation for half-life, first order elimination?
t1/2 = 0.693/k
i.e.
t1/2 = 0.693Vd/CL
How is k determined?
k = CL/Vd
The rate constant in the half-life equation is dependent on what two parameters?
Clearance and Vd.
A drug that is cleared quickly will have a _____ half-life.
A drug with a ____ Vd value has a ____ half-life value.
low
low
low
Drug half-life is used in the determination on what?
1 - The duration of action after a single dose
2 - Time required to reach steady state
3 - The frequency of drug administration
4 - Time required to clear and free of drug
One drug (A) reaches the therapeutic range quickly but the Cp drops quickly after that.
Another drug (B) takes longer to reach the therapeutic range but stays there for longer.
Both are taken orally.
There are two patients, one has difficulty falling asleep but, once asleep stays asleep.
The other, can fall asleep easily, but wakes up many times during the night.
Which drug is better for which patient?
Drug A is better for patient 1 since he just needs to reach the therapeutic range to fall asleep.
Drug B is better for patient 2 since he can easily fall asleep but needs a longer therapeutic range to stay asleep.
A higher Cl value means what?
It takes longer to clear out the drug (think backwards).
Oftentimes, when a drug is given to a patient, it is not given in a single dose to maintain the therapeutic concentration.
For an orally administered drug, for each half-life there is an increase, then a decrease. What do each correspond to?
increase - absorption/distribution
decrease - elimination (/metabolism)
Steady state is attained after how many half-lives?
5-6
The time to reach the steady state is independent of _______.
dosage
Fluctuations (on the Cp/half-life graph) are proportional to what?
dosage interval/half-life
The steady state concentration is proportional to what?
dose/dosage interval
Determination of the time needed to reach steady state is determined when?
Phase 1 - clinical trial
When a drug has a short half-life, what is done to compensate?
Increase dosage.
Steady state is achieved when _____ _______ is equal to ____ _________.
drug elimination = drug administration
Ideally, we want the drug plasma concentration (CP) to be (________) within the ________ range.
fluctuated
therapeutic
What is the equation to determine the maintenance dose rate?
DR = CL * Css
DR - maintenance dose rate - mg/hr
CL - clearance (L/hr)
Css - plasma drug concentration at the steady state condition - mg/L
For a drug that is rapidly eliminated, will give a _____ dose to maintain it longer.
larger
The frequency of drug administration is ultimately completed to what?
Keep the drug within the therapeutic range
To keep a drug within the therapeutic range, what does this depend on?
- The property of the drug (i.e. physico-chemical properties, interaction with other macromolecules in body comparments)
(i. e. bioavailability) - elimination
The frequency of drug administration is also referred to as what?
interval
How is the interval of administration determined?
What are the units?
Interval (h) = (Bioavailability * Dose(mg))/Css (mg/L) * Clearance (L/hr)
What do these commonly used terms mean? stat B.i.d. t.i.d. q.i.d. q.h. Q4H
stat - immediately B.i.d - twice a day t.i.d. - three times a day q.i.d. - four times a day q.h. - hourly Q4H - every 4 hours
Both clearance and bioavailability are _____ properties.
drug
How many half-lives does it take for the body to be clear of a drug?
5-6 half lives after administration has been stopped
Which organ is most responsible for drug metabolism?
the liver
Where are blood clot factors made?
liver
What are some functions of the liver?
Glycogen storage
Plasma protein synthesis
Drug detoxification
What capillary type does the liver have?
Sinusoidal
What is the portal triad of the liver?
Vein, artery, bile duct
What does the gallbladder store? What is it used for?
Stores bile, important for fat digestion
What does the portal triad do related to drugs?
Blood flow can go from one part of the triad to another.
Due to this intermingling, some drugs absorbed by the portal vein can go to the gallbaldder and get secreted back to the Gi and absorbed back again.
What is the hepatic portal system’s function?
Gather/monitor nutrients (Drugs) from the GI tract.
What is the entero-hepatic circulation?
Secretion of bile
Absorption and reabsorption of nutrients (Drugs) and drugs from the GI tract
Where are drugs metabolized?
Mostly in the liver, but also in the GI tract, kidney and lungs
Describe how a drug goes through the liver.
Drug taken orally, asborbed passively from the GI and directed to the liver.
First pass metabolism occurs.
The drug either goes to the blood or is actively secreted by the gallbladder back into the GI, where the drug undergoes a later pass metabolism.
