Elimination Flashcards
Drug elimination if divided into what major components?
excretion
biotransformation
____ is the removal of the intact drug
excretion
nonvolatile drugs are excreted by what?
renal excretion or other pathways
volatile drugs are excreted by what?
lungs
Clearance definition
process of drug elimination from body or single organ
- volume of fluid cleared of drug from body
T/F clearance applies to all elimination processes
True
The kidney is the main excretory organ for removing ____
metabolic waste
Metabolism of a drug occurs via
a. enzymatic
b. nonenzymatic
c. bacterial
d. all of the above
all of the above
How can you quantify elimination?
clearance rate
GFR
120 ml/min
What is GFR controlled by?
changes in glomerular capillary hydrostatic pressure
_____ maintains a constant blood flow in the presence of large fluctuations in arterial blood pressure
autoregulation
How much fluid is filtered through kidneys a day?
180L
_% of fluid volume filtered at the glomerulus is reabsorbed
99%
3 major processes of renal drug excretion
- glomerular filtration
- active tubular secretion
- tubular reabsorption
Drugs that are nonvolatile, water soluble, low MW or slowly biotransformed by liver are eliminated by what?
renal excretion
T/F protein bound drugs get filtered at the glomerulus
false!
What is the major driving force in the glomerular capillaries?
hydrostatic pressure
How is GFR measured?
using a drug that is eliminated primarily by filtration with no reabsorption
clearance is equal to GFR
What is a biomarker of renal function?
creatinine
blood levels rise when kidney is deficient
Glomerular filtration of drugs is directly related to what?
free drug concentration in plasma
Active tubular secretion
- active transport
- carrier mediated
- against concentration gradient
- capacity limited, may be saturated
What is active tubular secretion dependent on?
renal plasma flow
Two carrier systems for active tubular secretion
- organic anion transporter (OAT) for WA
- organic cation transporter (OCT) for WB
What drugs are used to measure active tubular secretion?
PAH
iodopyracet
How is PAH secreted?
glomerular filtration
active filtration
T/F PAH active secretion is very slow
False!
very fast, almost all eliminated in a single pass
T/F active tubular secretion is not affected by protein binding
true
When dose tubular reabsorption occur?
after the drug is filtered through glomerulus
Tubular reabsorption
- active or passive
- transport back to plasma
If a drug is completely reabsorbed the clearance of the drug is what?
0
For drugs that are partially reabsorbed, clearance is what?
less than 120 ml/min
The reabsorption of drugs that are acids or weak bases is influenced by what?
pH of fluid in renal tubule
pKa of drug
_____ affects transit time within renal tubules, where drug reabsorption takes place
urine flow
HH for WA tubular reabsorption
pH = pka + log (I/U)
10^pH-pka/ 1+ 10^pH-pka
HH for WB tubular reabsorption
pH = pka + log (U/I)
10^pka-pH/1 + 10^pka-pH)
Where does the greatest effect of urinary pH on reabsorption occur?
WB with aka 7.5 - 10.5
T/F for a weak acid drug, the extent of dissociation is more affected by changes in urinary pH if pKa = 3 than if pka = 5
False
pKa = 5 than if pKa = 3
What is more easily reabsorbed by tubular reabsorption?
nonionized acids and bases
Urine pH range
4.5 -8
What can acidify urine?
protein rich diet
ascorbic acid
What can alkalinize urine?
carbohydrates fruit veggies HCO3- antacids
HH U/P ratio tubular reabsorption for WA
U/P
1 + 10^pHurine - pka/ 1 + 10^pHplasma -pka)
HH U/P ratio tubular reabsorption for WB
P/U
1 + 10^pka - pHurine/ 1 + 10^pka - pHplasma
Glomerular filtration transport
passive
location of active tubular secretion
proximal tubule
location of tubular reabsorption
distal tubule
Drug ionization in glomerular filtration
either
Drug ionization of active tubular secretion
mostly WA and WB
Drug ionization of tubular reabsorption
non-ionized
Drug protein binding glomerular filtration
only free drug
drug protein binding active tubular secretion
no effect
Glomerular filtration is influenced by…
protein binding
Active tubular secretion is influenced by…
Competitive inhibitors
Tubular reabsorption is influenced by…
urinary pH and flow
drug pKa
Drug clearance definition
describe drug elimination from body w/o identifying mechanism of processmL/min
T/F drug clearance considers the entire body as a single drug eliminating system
True!
Clearance equation
Clt = elimination rate/CP
What rate order is clearance?
1st order
Physiologic organ clearance model
- based on drug clearance through individual organs
- clearance depends on blood flow and ability of organ to eliminate drug
Non-Compartment clearance model
- clearance determined directly from plasma time concentration curve
Renal clearance (Clr)
volume of plasma cleared through kidney
- for any drug cleared through kidney, the rate of the drug passing through the kidney must equal the rate of drug excreted in the urine
Clr equation
filtration rate + secretion rate - reabsorption rate /Cp
Clearance <1
drug partially reabsorbed
Clearance >1
drug actively secreted
Clearance = 1
drug filtered only
If glomerular filtration is the sole process for drug excretion and no drug is reabsorbed, then the amount of drug filtered at any time will always be _____
Cp x GFR
For drugs that are primarily filtered and secreted, with negligible reabsorption, thee overall excretion rate will _____ GFR
exceed
At low concentrations, active secretion is not saturated and the drug is excreted by _______
filtration and active secretion
At high concentrations, the % of drug excreted by active secretion ______ due to saturation
decreases
Explain the extraction ratio
fraction of a substance removed from blood flow through organ
E = Cl/blood flow
Clearance is limited by what factor?
Q (blood flow to organ eliminating drug)
What is the max Q value in body?
1.5 L/min
As Cl increases, what happens to drug’s half life?
t1/2 decreases
