T2 - Drug Elimination E2 Flashcards
What is drug excretion?
The process by which intact drugs and its metabolites are irreversibly removed from the body
What is the principle organ for excretion?
Kidneys
What are other organs used for excretion besides the kidneys?
- Lungs
- Biliary system
- Salivary
- Sweat glands
What is a nephron?
The functional unit of the kidney involved in excretion
What are the components of the nephron?
Vascular and tubular
What are glomerulus?
A network of glomerular capillaries
What is the filter of the glomerulus?
Bowman’s capsule
What happens when blood enters the glomerulus?
Blood is filtered so that free filtrate can pass through the tubule
What are the mechanisms of renal excretion?
- Glomerular filtration
- Tubular secretion
- Tubular reabsorption
What mechanisms remove drugs from circulation?
- Glomerular filtration
- Tubular secretion
What mechanisms moves drug from inner tube back into circulation?
Tubular reabsorption
What drives glomerular filtration?
Passive diffusion
What is the size of molecules that undergo glomerular filtration?
MW < 6kDa
What is type of drugs undergo glomerular filtration?
Molecules that are unbound to plasma proteins
How is glomerular filtration rate determined?
Insulin and creatinine
Why is insulin and creatine used to determine GFR?
They undergo filtration without tubular secretion and reabsorption and are not bound to plasma proteins
What is the GFR of a healthy individual?
110 - 130 mL/min (180 L/day)
What kind of process is tubular secretion?
Active
What are secretion transporters of the PCT and what are do they secrete?
- OATP secrete organic anions (acids)
- OCT secrete organic cations (bases)
What happens is probenecid is taken with penicillin?
Causes a drug-drug interaction where competitive inhibition that inhibits the secretion of penicillin because both drug are secreted from the same transporter
What drives tubular reabsorption?
A large concentration gradient across the tubule and plasma is a driving force for passive reabsorption of solutes back into circulation
How are small MW drugs reabsorbed?
Reabsorption can take place if drug is sufficiently lipophilic and remains un-ionized
How are weak acidic and basic drugs effected by tubular reabsorption?
The pH of the glomerular fitrate influences their ionization
How are large MW, polarized, or ionized molecules reabsorbed?
There are not reabsorbed
Where do drug molecules go when they escape reabsorption?
They will exit the body through urine
What are the factors that influence drug excretion?
- Phyico-chemical properties
- Plasma drug concentration
- Plasma protein binding of the drug
- Miscellaneous factors such as age, disease, and DDI
What are the ways drug elimination can be quantified?
- Half-life
- Clearance
What is half-life?
The time required for 50% of the drug to be eliminated from the body
How is the t1/2 of drugs affected by elimination in the first-order?
T1/2 is independent of dose and concentration
What is the most useful parameter to quantify drug elimination?
Clearance
Why is clearance referred over t1/2 of quantifying drug elimination?
- t1/2 is a function of clearance and volume of distribution
- Half-life fails to provide insight to drug elimination and can’t predict the impact of disease or drug interactions on drug elimination
What does ClH quantify?
Drug elimination by hepatic metabolism
What does ClR quantify?
Unchanged (not-metabolized) drug elimination by renal excretion
What are the components of total clearance in the body?
ClH + ClR
