Pharmacokinetics Flashcards
What is the diffference between clearance and elimination half-life?
Clearance - Body’s Efficiency of drug removal
Elimination Half-life - Rate of Drug Removal
What is the difference between Bioavailability and Volume of Distribution?
Bioavailability - Fraction of Drug Absorbed
Volume of Distribution - Apparent Space the Drug Resides in
- **What is the most important concept to be considered when designing a regimen for long-term drug administration?
- Define this term.
- **How can this be calculated?
- Define the variables
Clearance
Clearance - theoretical Volume of Fluid from which the drug is removed per unit of time
CL = Rate of Elimination/Concentration CL = Q [(Ca-Cv)/Ca] = QE
Q = Blood Flow to the organ Ca = Arterial Concentration of Drug Cv = Venous Concentration of Drug E = [(Ca-Cv)/Ca] - Extraction ratio
How do you ensure that you maintain steady-state concentrations of a drug within the therapeutic window?
- Administer the Drug at the same rate that it is eliminated
What is the Rate Limiting Variable in Clearance of a drug?
Blood Flow to the Organ
What are the two methods by which all drugs are eliminated?
- which is most common?
0 order and 1st order kinetics
- 1st order is by far the most common
Between 0 order and 1st order kinetics, which eliminates a constant fraction of the remaining concentration per unit of time?
1st order - specific fraction of the drug is elminated from the remaining concentration per unit time
What is Ke?
- how is it obtained
Elimination Rate constant obtained by taking the log of [Drug] and graphing it against time
What is the volume of distribution?
- What is the formula?
The fluid volume that would be required to contain all of the dose at the same concentration as exists in the blood plasma
Vd = Dose / Cb
Cb = Blood concentration
How do you find the elimination constant for a drug eliminated by 1st order kinetics?
Ke= Q [(Ca-Cv)/Ca] / Vd
also,
Ke = CL/Vd
What is the relationship of half life to dosing interval?
A drug is often given at half-life intervals
What are the 4 main factors that make 1/2 life a clinically important thing?
- Determination of Dosing Interval
- A factor in Determining Dose
- May Determine Route
- Good indicator of the time required to reach steady-state after a dosage regimen is initiated
What is the one compartment pharmacokinetic Model?
- how accurate is it?
- Kinetics?
*Assumes the Body is One Compartment
***ONLY WORKS FOR DRUGS THAT ARE DISTRIBUTED UNIFORMLY THROUGHOUT THE BODY
- Not a very adequate model
- 1st order Elimination
What is the two compartment model?
- how does the graph of the two compartment model differ from that of the one compartment model?
Two Compartment Model - assumes drug is injected into the blood then must equilibrate between two compartments
- Graphically you’ll see in initial large drop in concentration that corresponds to equilibration between the two compartments
How do you find clearance rate for a multicompartment model?
Clearance Rate = Dose / AUC
AUC = area under the curve
How do you determine dosing while taking into account bioavailability?
F(Dosing Rate) = CL/Css
F Dose/T = CL/Css
Dose = (CssCLT) / F
Where:
- T = Dosing Interval
- CL = clearance
- Css = Steady State Concentration (in plasma)
How many half-lives does it typically take to reach steady state?
- what is the time to steady state strictly dependent on?
FIVE
***SINCE it takes 5 half lives then time to steady state is DEPENDENT ONLY ON T(1/2)
When determining what drug to give a patient, what are the only two factors that the physician can control?
- Dose and Dosing Interval
PHYSICIANS CAN ONLY CONTROL STEADY STATE MAX AND MIN*
T or F: for IV administration the time to steady state is still 5 half lives
True
How do you determine how fast to administer a drug intravenously to get to a given concentration?
Css = Infusion Rate / Total Body Clearance
When would you administer a loading dose?
- Heart Attacks
- Serious Heart Failure
- Overwhelming Bacterial Infections
What is the formula for Loading dose?
LD = (Css * Vd) / F
where: LD - Loading Dose Css - Steady State Concentration (DESIRED) Vd - volume of distribution F - Bioavailability
What are patients given following a loading dose?
- what is the formula for calculating this?
Dosing Rate
Dosing Rate = (Target Css * CL) / F
What are some drugs that exibit zero order kinetics?
Ethanol
Heparin
Aspirin
Tetracycline
(Phenytoin, Amobarbital)
When do drugs display zero order kinetics?
When the enzyme is overloaded with drug
What is the formula for loading dose in zero order kinetics?
LD = (Vd x Css)/F
What is the formula for steady state concentration for zero order kinetics?
Css = (Km*DR)/(Vm-DR)
Km = CONCENTRATION/dose for 50% max Rate
What is the formula for Dosing rate for zero order kinetics?
DR = (Css*(Vm-DR))/Km
Km = CONCENTRATION/dose for 50% max rate Vm = Max Rate
