Drug Dosing Flashcards
When you adminster a drug and graph its concentration plasma, the resulting graph looks like an upside down half moon. What does the left side (ascending) represent? What about the right (descending)?
Ascending - Absorption
Descending - Metabolism and excretion
What is the threshold that has to be reached before you start seeing effects? What 2 “ranges” is it between on a drug dosage chart?
Minimum effective concentration
Between the therapeutic and ineffective ranges
Regarding how a drug will work, what is more important; the plasma concentration or the administered dose.?
Plasma conc. Tells you what will get to receptors
The fraction of Administered Drug Reaching the Systemic Circulation in its Active Form is _. The symbol for this is _. What route of admin has the highest? What route of admin has the lowest?
Bioavailability
F
IV
Oral
What are the 3 major factors that affect oral bioavailabilty that were mentioned in the notes?
Gastric emptying time (oral)
Intestinal transit time (oral)
First pass effect (oral)
How is bioavailability measured graphically? In a situation where bioavailability is low, how do you rectify that?
Measure bioavailability by measuring AUC
Increase the administered dose
Increasing the administered dose of a drug will change what 3 specific parameters?
Onset of action
Duration of action
Apparent efficacy
What are 2 factors that will affect the rate of availability?
Dissolution of drug into absorbable form
Blood flow
What is the definition of volume of distribution? What is its symbol? What is the formula?
The apparent volume in which a drug dissolves
Vd
Vd = Amount (of drug in body) / C-plasma (or Cp)
To calculate the Vd, how do you determine the plasma concentration?
Plot all the descending plasma concentrations, change Y axis to log scale and then extrapolate to time zero (Cp0)
What is the biggest volume in the body? What type of drugs will have the largest volume of distribution? Why?
Total body water
Lipophillic drugs
Lipophillic drugs generally excluded from plasma, low concentrations in formula -> high Vd
What are the 4 factors mentioned that affect Vd?
Body weight
Body composition
Age
Disease
The elimination of Active Drug after its Distribution is called _. What is the symbol? What is the formula?
Clearance
CL
CL = Rate of elimination / Cp
What are the 2 components of clearance?
Excretion
Metabolism
What are the 2 factors that determine rate of elimination?
Amount of drug delivered to elimination mechanism
Capacity of elimination mechanism
A capacity limited elimination system is termed _. This mean that there is more _ than _ [capacity / drug].
Zero order
Drug than capacity
For a zero order system, capacity is _ [limited / not limited]. Rate of elimination is _ [dependent / independent] of plasma concentration. Clearance is [constant / variable]
Limited
Independent
Variable
What happens if you increase the plasma concentration of the drug in a zero order elimination system?
Nothing, The capacity is already maxed out
A delivery limited elimination system is termed _. This mean that there is more _ than _ [capacity / drug].
First order
capacity than drug
For a first order system, capacity is _ [limited / not limited]. Rate of elimination is _ [dependent / independent] of plasma concentration. Clearance is [constant / variable]
Not limited
Dependent
Constant
First order, vs zero order. Which is going to give you a fixed amount of removed drug per unit time? Which will give you a fixed percent of removed drug per unit time?
Fixed amount - Zero order
Fixed percent - First order
The first order plasma concentration vs time graph is curved. How can you linearize it?
Change the Y axis to a log scale
What is the example of a drug that follows a zero order mechanism? Under what conditions does a zero order elimination become a first order elimination?
Ethanol follows zero order
At levels below saturation, zero order becomes first order
What are the 4 factors affecting clearance?
Body weight
Blood flow to organs
Age
Disease
What is the difference between a maintenance and a loading dose?
Loading - one time bolus
Maintenance - subsequent doses to maintain Cpss
What is the objective if the loading dose? What is the main factor affecting loading dose i.e. what might cause the loading dose to change?
To fill the volume of distribution (areas where drug can “hide”) to quickly reach therapeutic ranges in plasma
Volume of distribution
What is the objective of the maintenance dose? What is the main factor affecting maintenance dose?
Replace drug lost to elimination
Dependent on elimination
Simply put, the loading dose is dependent of _ while the maintenance dose is dependent on _
Volume of distribution
Elimination
What is the major factor affecting dosing frequency? How is it calculated i.e. what is the formula?
Plasma half life
t1/2 = 0.693 x Vd/CL
Approxinmately how many half lifes does it take to reach steady state levels?
4-5 half lifes
Both renal and hepatic disease will affect what 2 pharmacokinetic variables?
Decreases clearance
Prolongs half life
What pharmacokinetic variable will hepatic disease affect that renal disease won’t? Why (2)?
Increases oral bioavailability
- Decreased first pass
- Decreased plasma protein (made in liver)
Under what 2 conditions would a target concentration strategy for drug dosing be used?
an effect cannot be readily determined
drug has a low T.I.
Under what condition would a maximal dose strategy be used?
A drug that has a high therapeutic index
