Module 5 Flashcards
What are six sites of drug excretion?
- Kidney
- Bile
- Lung
- Breast milk
- Hair
- Saliva
- Sweat (bonus)
Define drug excretion
Is the removal of parent drug and drug metabolites from the body
What is the most important site of drug excretion in the body?
Kidney
What organ accounts for the majority of drug excretion?
Kidney
True or False: healthy kidneys serve to limit the duration and intensity of drug effects?
True
What condition prolongs the duration of action and intensity of drug effects?
Kidney disease/decreased kidney function
This is especially important for patients with end stage kidney disease.
What is the basic structural and functional unit of the kidney?
The nephron
What are the functions of the nephron?
- Regulates water, electrolyte, and drug excretion
- Controls blood volume, blood pressure, pH and solute (including drug) excretion
List the factors affecting renal drug excretion
1) Glomerular Filtration
2) Tubular Secretion
3) Tubular Reabsorption
Drugs enter the kidney from where?
The renal artery
Which drugs are filtered at the glomerulus?
Only non-protein bound (free) drugs
Which type of Starling’s forces force low molecular weight drugs into the renal tubules?
Hydrostatic pressure within glomerular capillaries
What does not affect glomerular filtration?
lipid solubility and pH
In order for drugs to be filtered by means of glomerular filtration, they must be what?
small and unbound
The major determinant of what fits through at the glomerulus is what?
size
Describe tubular secretion
- Drugs not filtered by the glomerulus leave the glomerulus by the efferent arteriole.
- The efferent arterioles divide to form capillaries that surround the proximal tubule.
- Drugs can be secreted from the blood surrounding the tubules into the lumen of the proximal tubule.
- Drug secretion in the kidney primarily occurs by two transport systems, one for weak acids and one for weak bases.
Describe tubular reabsorption
- As drugs move toward the distal tubule, their concentration increases.
- This is primarily due to the actions of the loop of Henle which functions to concentrate tubular solutes (by absorbing water).
- Once in the distal tubule the drug concentration often exceeds the concentration in the blood that immediately surrounds the distal tubule.
- If the drug is uncharged or lipid soluble, it’s able to leave the tubule and be reabsorbed back into the blood.
Kidney function is low in which age group?
Newborn infant
By two years old the GFR reaches that of a healthy adult (120 mL/min/1.73m2).
As a person ages what happens to renal function?
It decreases
If renal function is decreased, renal excretion is what?
Decreased
Some drugs are eliminated into the bile and ultimately excreted where?
In the feces
List the characteristics of drugs eliminated in the bile
- molecular weight > 300 Da
- have both polar and lipophilic groups (amphipathic molecules)
- are glucuronidated
Where is the primary site for drug reabsorption in the kidney?
Distal Tubule
As drugs move through the nephron their concentration increases mostly due to reabsorption of water. Once in the distal tubule the concentration of drug in the tubule often exceeds that of the surrounding plasma. If sufficiently lipid soluble drugs will move from an area of high concentration (i.e. in the distal tubule) to an area of low concentration (i.e. in the blood).
What does BCRP stand for?
Breast Cancer Resistance Protein
What transports a variety of amphipathic molecules into bile?
P-GP
What transports glucuronidated metabolites into bile?
MRP2
Transporters on the canalicular membrane of hepatocytes transport drugs and metabolites from the liver into where?
Bile
True or False: Drugs released into the bile are ultimately released into the intestine during digestive processes.
True
True or False: Drugs released into the intestine may be excreted into the feces or undergo enterohepatic recycling.
True
What are amphipathic molecules?
they have both polar and lipophilic functional groups
Describe enterohepatic recycling
- Drugs and drug conjugates excreted in the bile enter the intestinal lumen.
- Intestinal bacteria can cleave conjugate metabolites leaving the original drug.
- The original drug may be reabsorbed in the intestine to re-enter the body.
- This process is known as enterohepatic recycling.
- Drugs that undergo enterohepatic recycling persist in the body for substantially longer periods.
5.4 pulonmary left off
