Lecture 10 Flashcards
Drug Excretion/Elimination
1
Q
Excretion
A
- Removes a chemical from the body and prevents drug accumulation
- Liver and kidneys are the primary sites of excretion
- Metabolism, aka biotransformation, is important component of excretion since metabolites are usually charged, hydrophilic, and conjugated (larger)
- Metabolic changes alter the physicochemical properties of the drug and can make it more or less likely to be excreted
2
Q
Renal v.s. Biliary Secretion
A
- The one that occurs is a consequence of drug properties (ionization, adducts, etc.)
- Renal - excretion into urine, polar, glomerular filtration, active secretion, passive reabsorption/excretion
- Hepato/Biliary - excretion into bile (stable adducts), diffusion AND active transport
3
Q
Renal Drug Clearence
A
- Many can be excreted unchanged
- Clearance is proportional to renal function
- Metabolites MAY be excreted into urine
4
Q
Key Renal Excretion Mechanisms (3)
A
- Glomerular Filtration - Bulk flow (remove)
- Tubular Secretion - active transport (remove)
- Tubular Reabsoprtion - passive reabsorption and active reabsoprtion
5
Q
Glomerular Filtration
A
- Non-selective, size limited
- Most “free” drugs are small enough to be filtered, MW cut off ~1000-2000
- Specialized pores/fenestrations and the size, shape, and charge affect the filtration
- Pressure gradient regulates filtration, very sensitive to blood pressure
6
Q
Tubule Secretion
A
- Diffusion AND active transport
- Passive diffusion utilized for small, uncharged molecules
- Active transport for large, ionized molecules allow for greater urine concentrations
- Depends on specific transport systems for acids or bases: transporters can be saturated, inhibited, require energy, or a specific carrier for a certain drug
7
Q
Tubule Reabsorption
A
- Mediated by passive diffusion
- The concentration gradient usually favor reabsorption
- Ionization of solutes, solute size, and solute liquid solubility may modulate passive reabsorption
- Passive reabsorption favors small, neutral, lipophilic molecules
8
Q
Renal Summary
A
- Renal elimination is a balance of transport between kidney tubules and plasma
- Multiple transport mechanisms (active and passive)
- Drug characteristics are important for renal elimination
- Slow decline in renal function (~1% per year) throughout adulthood occurs
9
Q
Hepato-Biliary Excretion
A
- Many drugs eliminated after hepatic metabolism
- Excretion is into bile which enters the feces
- Liver is optimized for drug metabolism and excretion
- About 5% of administered drug dose will enter bile passively and active secretion can increase this up to 95%
10
Q
General Pathway of Drug to Plasma to Bile
A
- Enters hepatocytes by passive diffusion or active transport from the plasma
- Drugs then transported to biliary epithelium by active secretory process
- Enterohepatic cycling then occurs where a drug is secreted into the bile and is reabsorbed from the intestine into the blood.
11
Q
Biliary Excretion
A
- Drugs enter hepatocytes actively or passively
- Hepatocytes secrete bile which flow to duaodenum for eleimination
- Conjugation from Phase II aids biliary excretion by increases the molecule’s polarity and molecular size
- Biliary excretion favors drugs with MW > 300
- Drug conjugates are not usually reabsorbed from the bile since they are poorly recognized by reuptake systems, too ionized, and too large
- Most drugs are excreted via the feces
- If reabsobed, enterohepatic cycles occur
12
Q
Other Routes of Secretion
A
- Milk - concerning for babies whose Phase I and II activity may not be fully developed until at least 6 years of age, sometimes later
- Lungs
- Intestines
- Sweat
- Saliva
- Other bodily fluids
13
Q
Drug Clearance
A
- Clearance is the decrease of drug in the bloodstream
- For most drugs, clearance is constant over the concentration range encountered in the clinical settings (1st order elimination)
- Total Clearance is an additive of the eliminations from all tissues
14
Q
Excretion Definition
A
Removal of drugs from the body
15
Q
Clearance Definition
A
The volume of plasma cleared of the drug per unit time.
16
Q
Glomerular Filtration Definition
A
Removal of drugs by bulk flow
17
Q
Tubular Secretion Definition
A
Active transport of drug from the blood into the urine
18
Q
Tubular Reabsorption Definition
A
Passive and active reabsorption of drug from tubules back into blood
19
Q
Enterohepatic Cycling Definition
A
Biliary excretion and intestinal reabsorption of a solute, sometimes with hepatic conjugation and intestinal deconjugation
