Lecture 2 Flashcards
Drugs are extracted by liver to different degrees
Hepatic ER : The fraction of drug removed during one pass through the liver ; the efficiency of the liver in removing drug from the bloodstream
Drugs with a low HER ( ≤ 0.3) tend to be more bioavailable (____________)
low clearance
Drugs with a high HER ( ≥ 0.7) tend to be less bioavailable (___________)
high clearance
Drugs with 0.3 ≤ HER ≤ 0.7 termed intermediate extraction
Hepatic clearance
Mathematical model: To relate hepatic Cl to hepatic physiology
_____________:
The liver’s innate ability to clear unbound drug from via metabolism or biliary excretion
Instrinsic clearance
Intrinsic Clearance
The total ability of the liver to metabolize a drug in the _____________
Reflects the “ intrinsic” efficiency of the hepatic elimination
Can take any value, i.e., not limited to the blood flow
absence of flow limitation
ClT can be used as a monitoring parameter for the function of the ___________
eliminating organ
Patients with different degree of eliminating organ dysfunction who are taking the same drug, eliminate
the drug at different rates, and may require different dosage adjustment
𝐓𝐨𝐭𝐚𝐥 𝐛𝐨𝐝𝐲 𝐞𝐥𝐢𝐦𝐢𝐧𝐚𝐭𝐢𝐨𝐧=𝐝𝐫𝐮𝐠 𝐞𝐱𝐜𝐫𝐞𝐭𝐞𝐝 ___________ +𝐝𝐫𝐮𝐠 ________________
unchanged+metabolized
Cl of some specific markers can be used to determine the function of the eliminating organ e.g.,creatinine is an endogenous byproduct of muscle metabolism that is excreted only by kidney
Drugs can be excreted through urine, bile, sweat, expired air, breast milk
Renal excretion: drug elimination in the unchanged form (as administered)
For drugs primarily excreted in the urine, elimination is dependent on ________________
renal function
Renal excretion is the net effect of 3 distinct mechanism within
the kidneys
Renal excretion is the sum of:
________________ (GFR)
Tubular secretion
Tubular reabsorption
Drug excretion may involve one or more of these mechanism
glomerular filtration
Factors influencing glomerular filtration:
Molecular size
______________
_______________
Protein binding
Glomerular integrity
Renal function: decreased with __________, _____________, shock
age, heart failure
____________
Definition: A measure of the flow rate of filtered fluid through the kidneys.
Normal Range: Typically, between 90-125 mL/min, serving as an indicator of renal function
Glomerular Filtration Rate (GFR)
___________and __________ in Renal Filtration
Special Property: Both substances are solely filtered in the nephron without being secreted or reabsorbed
Significance: This unique characteristic makes them reliable markers for assessing the filtration rate of the kidneys.
creatinine and inulin
Creatinine Clearance (CrCl) = GFR
Determination: CrCl is equivalent to GFR and can be calculated: Directly from the amount of creatinine excreted in __________ over a 24-hour period.
Indirectly from serum creatinine levels using specific formulas.
urine
Renal clearance and glomerular filtration rate
For drugs exclusively eliminated renally, where the only renal process is glomerular filtration, GFR is linearly related to drug ______
drug clearance
Drugs cleared solely by renal mechanisms will have a y-intercept of _________
zero
Drugs with extra-renal routes will have ___________ y-intercepts
larger
Drug Distribution and Protein Binding
Factors affecting drug distribution
Characteristics of _______________
Disease states that alter physiology
______________of the drug
Regional differences in physiologic pH
Extent of ____________ of the drug
body tissues
lipid solubility
protein binding
Drug Distribution and Protein Binding
Body Tissue Characteristics
Rate of drug delivery from blood to a tissue is highly dependent on _______________
Drugs distribute more rapidly to the areas with higher blood flow ___________, lungs, and kidneys : highly perfused with blood
________,__________ and bone: much Less perfused
Skeletal Muscle :Intermediate perfusion
blood flow
heart
fat, tissue
Differences in pH lead to localization of drug in tissues
Excretion of drugs in breast milk: Alkaline drugs , unionized at physiological pH, pass through
lipid membranes into breast tissue
Breast tissue has acidic pH, the alkaline drug becomes_____________-, and trapped in the tissue
ionized
