Lecture 2 Flashcards
Which of the following patient scenarios is associated with a smaller Vd
A. Dose= 500 mg and initial serum conc. is 40 mg/L
B. Dose= 20 mg and initial serum conc. is 1.5 mg/L
__________: fluid portion + elements ( white cells, red cells, and platelets)
Blood
_________: only fluid portion of the blood (including soluble proteins but not elements)
Plasma
_________: when the soluble protein of fibrinogen is removed from plasma
Serum
Serum refers only to the fluid portion of blood , including soluble proteins but not cellular elements
False!
If Cfinal is greater than Cinitial then it is _________an organ
clearing
_____________ is a measure of the removal of the drug from body
CL(Clearance)
Describes the removal of drug from a volume of plasma in a given unit of time
Clearance
Clearance (Cl) = Volume of __________cleared (“cleansed”) of drug, per unit of time (conceptual definition); always in units of volume/time (e.g., L/hr, ml/min)
plasma
Clearance Does NOT indicate the amount of drug being removed, but, the VOLUME of plasma from which the drug is completely removed
Cl and Vd determine the _______________
half-life
Clearance (Cl)
Cl(total body) = Cl(metabolic) + Cl(renal) + Cl( bile) + Cl(other)
Drugs removed primarily by kidneys: Clr makes up most of the total body Cl
Clearance is independent of the ________
dose
EXAMPLE:For drug X, individual organ clearances have been determined as follows:
Renal Cl
180 mL/min
Hepatic CL
22 mL/min
Pulmonary Cl
5.2 mL/min
How would you describe the clearance of drug X?
How much is total body Cl of drug X?
Vd and Cl
Plasma drug concentrations are affected by: _______ at which drug is administered, the ___________ in which it distributes, and its CL
rate, volume
Clearance is not the ______________
elimination rate
Large clearance will result in low ______________
AUC
The drug CL of any organ is determined by _______________and the extraction ratio:
blood flow
Understanding the Importance of Clearance in Clinical Scenarios
Dosage Recommendations: Clearance is invaluable for formulating ______________ in clinical settings.
Drug Disposition Parameter: It’s the primary metric detailing the ____________ at which drugs are eliminated from the body.
Index of Removal Capacity: Clearance serves as an indicator of the capacity of body organs to remove a drug.
Example: Propranolol: This drug is primarily eliminated by the liver with an efficiency (E) of 0.9. This indicates that a significant portion of the drug presented to the liver is cleared in one pass. Hence, its clearance (Cl) is approximately equal to the liver’s blood flow rate (Q).
dosage suggestions
speed
_________________: The quantity (expressed in terms of mass, NOT volume) of the drug removed from the body over a specific time duration.
Measurement: Always in units of mass/time (e.g., mg/min)
Dynamics: As the drug concentration decreases, the elimination rate also drops over time.
elimination rate
Clearance:
Relationship with Elimination Rate: Clearance remains constant and is calculated as the ratio between ____________ and _____________.
Independence: Clearance operates independently of the drug quantity present. Consequently, introducing more of the drug will not alter the clearance rate
elimination rate
drug concentration
k is the proportionality constant relating the rate of change of drug concentration and the concentration (1st order elimination)
k is the first order rate constant describing _________________
drug elimination
REMEMBER : elimination rate constant represents the fraction of drug removed over a unit of time. e.g., if k = 0.25 hr-1 then 25% of the drug remaining in the body is removed each hour
REMEMBER : In a 1storder elimination process, although the amount of drug eliminated may change with the amount of drug in the body, the fraction of a drug eliminated over a given time remains constant
The meaning of 1st order elimination k
The actual amount of drug eliminated is different for each fixed time period depending on the initial amount in the body but, the ____________ removed is the same
fraction
Practical term: fraction or percentage of drug being removed is the same either with high or low concentration
Question: With a drug that follows 1st order elimination, the amount of drug eliminated per unit time: decreases while the fraction of the drug eliminated remains constant
Because the extraction ratio can maximally be 1, the maximum value that hepatic clearance can approach is that of :
Hepatic blood flow
