Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
33 Cards in this Set
- Front
- Back
|
What are the 2 major methods of drug excretion?
|
1. Renal
2. Biliary/fecal |
|
|
What determines the amount of drug that enters the renal tubule lumen?
|
The GFR - glomerular filtration
|
|
|
What is the only form of drug that can be filtered by the glomerulus?
|
Unbound to protein
|
|
|
What 2 other processes add to renal excretion of drugs?
|
1. Active tubular secretion
2. Passive tubular reabsorption |
|
|
What will the renal excretion of a drug be if only glomerular filtration occurs, and no secretion or reabsorption?
|
The same as the GFR
|
|
|
What allows for active tubular secretion of a drug?
|
-Carriers
-ATP |
|
|
What are 2 specific transporters involved in active secretion of drugs at the renal tubules?
|
-P glycoprotein
-MRP2 |
|
|
Does active REABsorption of drugs occur? Where?
|
A little - at the distal renal tubule
|
|
|
How does active secretion of a drug change its overall excretion rate?
|
It increases it so that it is greater than the GFR
|
|
|
How does passive tubular reabsorption of a drug change its overall excretion rate?
|
It decreases it
|
|
|
Where does each process occur?
-Active secretion -Passive reabsorption |
Active secretion = proximal tubule
Passive reabsorption = proximal and distal tubules |
|
|
What is required for passive reabsorption of drugs?
|
-Concentration gradient must favor passive diffusion
-The drug must not be ionized |
|
|
How does the concentration gradient favoring passive reabsorption get established?
|
Water is reabsorbed as urine flows through the tubules; this increases the drug conc in the filtrate relative to its conc in the blood.
|
|
|
What determines the reabsorption of weak acids and base drugs from glomerular filtrate?
|
The pH of the urine, which alters the ionization state of the drugs.
|
|
|
What type of drugs will be nonionized if the urine is more alkaline?
|
-Acids will be ionized (A-)
-Bases will be not (B) |
|
|
What drugs will not be passively reabsorbed from urine then, and hence get excreted when urine is more alkaline?
|
Acids - they are trapped in the urine
|
|
|
What drugs get excreted if the urine is more acidic?
|
Bases
|
|
|
What is a scenario in which making the urine more alkaline or more basic is useful?
|
To hasten drug excretion in poisoning or drug overdoses
|
|
|
What 2 factors determine the degree of effectiveness altering urine pH will have?
|
1. The extent and persistence of the pH change
2. The contribution that passive reabsorption of the drug makes to its elimination |
|
|
When does altering urine pH have the greatest effect on excretion of a drug?
|
When the drug's pKa is in the range of urinary pH
|
|
|
What is the range of urinary pH?
|
5-8
|
|
|
How can drugs be excreted with bile?
|
By protein carriers present in the canalicular membrane of the hepatocyte
|
|
|
By what process do the protein carriers for drugs in the bile canalicular membranes operate?
|
Active transport
|
|
|
What are 2 such protein carriers in bile canalicular membranes? What type of molecule does each transport?
|
-P-glycoprotein - transports amphipathic liposoluble drugs
-MRP2 - transports conjugated drug metabolites |
|
|
Where do drugs and metabolites that are excreted by the biliary transporters go?
|
Into the GI tract during digestion (ampulla of vater)
|
|
|
What is a nonbiliary mechanism of fecal drug excretion?
|
Excretion of drugs by carriers present on the apical membranes of enterocytes
|
|
|
What does enterohepatic recycling refer to?
|
The ability of enterocytes to both excrete and reabsorb drugs and metabolites from the GI tract
|
|
|
What is the general result of enterohepatic recycling?
|
Prolonged presence of the drug in the body.
|
|
|
How can we counteract enterohepatic cycling?
|
By giving a resin or substane to soak up the drug in the intestine and prevent reabsorption.
|
|
|
What is a possible method of drug excretion in women of childbearing age?
|
Breastmilk
|
|
|
What form of drugs are readily excreted in breastmilk?
|
Lipophilic drugs ie ethanol
|
|
|
How does the pH of breastmilk compare to plasma?
|
It is more acidic
|
|
|
So what drugs may be found in higher concentration in breastmilk than in the plasma?
|
Weak bases
|
