kinetics exam 2 - renal elimination Flashcards
Drug Elimination: Introduction
what does drug excretion have to do with
what does drug biotransformation have to do with
what does drug elimination =
how is clearance different from elimination rate
Drug excretion has to do with removal of unchanged drug (typically via the kidney but also sometimes via the lungs, breast milk, sweat, etc….)
- Drug biotransformation has to do with the enzymatic modification of the drug (facilitating its excretion and/ or altering its pharmacodynamic potential). Enzymes are usually hepatic but may be found in other tissues.
- Drug Elimination = Drug excretion + biotransformation
, Unlike clearance, the elimination rate is not invariant for first-order processes ***** What do you mean by this?
SCHEMATIC OF NEPHRON UNIT
renal artery going across then down to the renal vein
drug excretion mechanisms:
- glomerular filtration
- active secretion
- tubular resorption
“to ureter” is down at the bottom
**Glomerular capillary network and Bowman’s capsule
*Loop of Henle and Proximal Tubule
&Distal Tubule
Drug Elimination: The Kidney and
Blood Supply
what % of the cardiac input does it receive
what is RBF
what is RPF
what does RPF equal
how much Hct does an average adult have
how much GFR does an average adult have
what is the filtration fraction
Receives 20 – 25% of cardiac output
- Renal Blood Flow (RBF) = volume of blood flowing through kidney blood vessels per unit time
- Renal plasma flow (RPF) = RBF – the volume of red blood cells present
- i.e. RPF = RBF (1 – Hematocrit)
- For the average adult, Hematocrit (Hct) = 45%;
Glomerular filtration rate (GFR) = 125 mL/min - Filtration Fraction = GFR/RPF
Drug Elimination: The Kidney and Urine Formation
what does the kidney regulate
what is GFR controlled by
The kidney regulates fluid volume as well as
the levels of various solutes and
electrolytes
- *Recall which
- GFR is controlled by hydrostatic pressure differences in the glomerulus. Kidney arterial pressure ~ 100 mmHg; drops to 1⁄2 its value in the glomerulus.
Drug Elimination: The Kidney and Drug Excretion
what are the 3 factors that renal drug excretion is comprised of
what sized molecules undergo glomerular filtration
do proteins and protein-bound drugs undergo glomerular filtration
what does the GFR of a drug correlate to
what two molecules are used to determine GFR and why
Renal drug excretion is a composite of glomerular filtration, active tubular secretion, and tubular reabsorption
- Most small molecules (MW < 500 daltons) undergo glomerular filtration
- Proteins and protein-bound drugs do not undergo glomerular filtration
- The GFR of a drug correlates well with the free levels of the drug in the blood
- Inulin and creatinine, are neither actively secreted nor reabsorbed; consequently, their clearances are ~ the GFR (125 – 130 mL/min). They used in the determination of the GFR.
Active tubular secretion
is it passive or active and what does that mean for its energy
does it have a carrier
is it against or towards the [ ] gradient
what is it dependent on
what two molecules are used to measure active tubular secretion
their clearances are a measure of what
an active transport process (requires energy input, is carrier-mediated, the transported item is transported against its concentration gradient)
- Is dependent on renal blood flow
Iodopyracet and p-amino-hippuric acid are both glomerulus-filtered and secreted by tubule cells; they are used to measure active tubular secretion; their clearances are a measure of the effective renal plasma flow (ERPF)
Drug Elimination: The Kidney and Drug Excretion III
can the the carrier system be saturated and what does that mean for drugs of like structure
is there a carrier system for weak acids and weak bases
what kind of drugs dissociate rapidly as they are secreted from the kidneys
how does that affect the half life of a drug excreted largely by secretion
The carrier system is saturable and can be the subject of competition by drugs of like structure
- There is a carrier system for weak acids and one for weak bases
- Drugs bound to plasma proteins dissociate rapidly as they are secreted by the kidneys; consequently, the elimination half-life of a drug excreted largely by secretion is unaffected by protein binding
Tubular reabsorption
is it active or passive
what kind of drugs are more lipid soluble and thus are more capable of penetrating the cell membrane – how easy is it to reabsorb these kind of drugs
what eqn governs the extent of dissociation and what does it depend on
can either be active or passive
- Undissociated (unionized) drugs are more lipid soluble and more capable of penetrating cell membranes; they are thus more easily reabsorbed
- The extent of dissociation is governed by the Henderson-Hasselbalch equation i.e. it depends on the urine pH and the pKa of the drug
Example - can you do this :)
Phenobarbital is a weak acid with a pKa of 7.2.
(i) Calculate the percent ionized in blood (pH 7.4).
(ii) Calculate the percent ionized in urine (pH 6.4).
Example - can you do this!
Itraconazole is a weak base with a pKa of 3.8.
(i) Calculate the percent ionized in blood (pH 7.4).
(ii) Calculate the percent ionized in stomach (pH 1.8).
Example - can you do this :)
A 39-year-old woman is admitted to an emergency room following a phenobarbital overdose. Her urine pH is 5.8 at the time of admission. She is given 9g of sodium bicarbonate IV over 24 hours to alkalinize the urine. If her urine pH afterward is 8, by how much is the resorption of the phenobarbital reduced? (about 30% of phenobarbital is eliminated by kidneys and phenobarbital pKa = 7.24; assume blood pH is 7.4)
is this by infusion or bolus?
PAWAPILL has renal clearance greater than the renal clearance of inulin. Which of the following statements is true?
A
PAWAPILL is actively secreted
B
PAWAPILL is exclusively filtered at the glomerulus
C
PAWAPILL is partly reabsorbed
D
None of the above
E
All of the above
A
PAWAPILL is actively secreted
