Module 5 Flashcards
The removal of parent drug and drug metabolites from the body
Drug excretion
What are the different sites of drug excretion?
Kidney, bile, lung, breast milk
Account for the majority of drug excretion.
Kidneys
Healthy kidneys serve to limit the _______ and ______ of drug effects.
duration
intensity
Basic structural and functional unit of the kidney.
Nephron
Carries blood into the glomerulus for filtration.
afferent arteriole
Bed of capillaries that make up the first stage of filtering blood to form urine; surrounded by Bowman’s capsule
glomerulus
Carries blood away from the glomerulus
efferent arteriole
Essential for regulating the pH of the filtrate and is very important for the reabsorption of essential molecules such as glucose and sodium and is also an important site for drug excretion
PCT
creates a concentration gradient in the medulla of the kidney; results in reasborption of water, creating a concentrated filtrate
loop of henle
if water is reabsorbed in the LoH, and drugs are not, what does that mean?
Drugs become more concentrated in the filtrate
Regulates electrolyte levels and filtrate pH; site of action for drugs that control BP; concentrations of drugs in the filtrate is often higher than that of blood
DCT
Important site for drug reabsorption in the kidney
DCT - since the filtrate concentration is higher than that of the blood
Series of tubules that connect various nephrons to the ureter; final step in the production of urine
Collecting duct(s)
What are the factors affecting renal drug excretion?
Glomerular filtration
Tubular secretion
Tubular reasborption
What is the major determinant of whether a drug is filtered or not?
Size - lipid solubility and pH do not affect glomerular filtration of drugs
What is the force that filters drugs into the renal tubules?
Hydrostatic pressure within the glomerular capillaries force low MW drugs into the renal tubules
Drug secretion primarily occurs by two transport systems. These are?
One for weak acids; one for weak bases
Where are secretory transporters located in the kidney?
Basolateral surface (facing the blood)
Secretion is a ______, _____ capacity process.
rapid, high
After the action of the LoH, drug concentration in the filtrate is often higher than that of the surrounding blood. What type of drugs are reabsorbed?
Uncharged or lipid soluble drugs are able to leave the tubule and be reabsorbed back into the blood
What is the typical GFR?
~120mL/min/1.73m2
Describe the effect of age on renal function.
Kidney function is low in newborns (40mL/min/1.73m2)
Renal function peaks in early adulthood, and decreases with age
If renal function is decreased, renal drug excretion is ________.
decreased
Some drugs are eliminated in the bile, and ultimately excreted in the _____.
feces
What are the characteristics of drugs that are excreted in the bile?
MW > 300Da
Amphipathic
Glucuronidated
Transporters on the ________ membrane of hepatocytes transport drugs and metabolites from the liver into the bile.
canalicular
___________ transports a variety of amphipathic drugs into the bile; and __________ transports glucuronidated metabolites into the bile.
P-glycoprotein - amphipathic
MRP2 - glucuronidated
What are the two fates of drugs released back into the intestine from the bile?
Excreted in the feces
Enterohepatic recycling
Carries blood (and drugs) from the intestine to the liver
portal vein
Major cells in the liver; contain drug metabolizing enzymes
hepatocytes
A thin tube that collects bile and drugs excreted by the liver
bile canaliculus
Carries bile and drugs from the liver to the gallbladder, where they can then be secreted back into the intestine
hepatic duct
Describe enterohepatic recycling
Drugs and drug conjugates get excreted in the bile, into the intestinal lumen.
Intestinal bacteria cleave conjugates off the metabolites, leaving the original drug
The original drug gets reabsorbed into the portal vein
Drugs excreted by pulmonary excretion are usually ________ and/or highly ________.
gaseous, volatile
What is the best example of a drug excreted by the pulmonary route?
general anesthetics
Pulmonary drug excretion in different from most other excretion, how?
Not heavily reliant on drug metabolism
What are factors affecting pulmonary drug excretion?
Rate of respiration
Cardiac output
Solubility of drug in blood
Describe how drug solubility affects pulmonary excretion?
Low solubility in blood - high pulmonary secretion
High solubility in blood - low pulmonary excretion
____ of women take at least one drug in the first week post-partum
> 90%
Drugs excreted in breast milk have what characteristics?
Low protein binding
low MW
high lipophilicity
What transports drugs into breast milk?
the drug transproter BCRP - breast cancer resistance protein (active pump)
Describe how ion trapping works in breast milk.
The pH of breast milk is lower than that of blood, weakly basic drugs are thus trapped there
What are other routes of drug excretion (minor ones)?
Hair, saliva, sweat
Describe the importance of drug excretion in hair.
Can be used to determine how long a person has been exposed
At what rate does hair grow?
1cm/month
Describe saliva drug excretion.
Drug excreted in saliva is usually swallowed and then subject to either intestinal absorption or fecal excretion
Describe drug excretion through sweat.
drugs excreted in sweat are mostly washed away although a minor amount of dermal reabsorption may occur
