Lecture 7.5 Flashcards
What drug, bound or free, enters glomerular filtrate and filtered at the glomerulus?
free drug
bound drugs do not enter the glomerular filtrate
Which part of the kidney does active secretion enters the kidney?
proximal tubule
Which part of the kidney does passive reabsorption of lipid-soluble unionized drug into the body take place in?
distal tubule
What happens to ionized, lipid-insoluble drug after it enters kidney?
excreted through urine
Water soluble drugs and metabolites of lipid soluble drugs are largely eliminated by ___________ and _________________.
renal glomerular
tubular mechanisms
Can the efficiency of transport system for individual drugs vary widely?
Yes
Can competition occur between drugs using the same transport system?
Yes
Besides renal elimination, how else could drugs and their metabolites be eliminated?
in bile, breast milk, and sweat, and by the lungs.
What does the excretion of drugs from the kidneys depend on?
- absorption of drugs from the GI tract
- lipid solubility of drug
- the degree of ionization of drugs
- pH of the urine
What drugs are reabsorbed and not eliminated by kidneys?
Nonionized lipid-soluble drugs
Generally drugs that are bases are excreted when the urine is _________ .
acidic
Acidic compounds are excreted in greater quantities if the urine is _________.
alkaline
State the influcne of renal tubular fluid pH on the excretion of salicylic acid (a metabolite of aspirin).
if fluid alkanine: acid ionized into salicylate ion and excreted thru urine
If fluid acidic: salicylic acid exist in acid form and pass into blood thru renal tubular cells
State the influcne of renal tubular fluid pH on the excretion of amphetamine (a weak base).
if fluid alkanine: exist as lipid soluble free base, passed into blood
if fluid acidic: exist as salt –> excreted thru urine
What is an approach to eliminate amphetamine from the body during amphetamine toxicity?
acidification of the urine with ammonium chloride
*if fluid acidic: exists as salt –> excreted thru urine
What is an approach to eliminate phenobarbital (a weak acid) from the body during phenobarbital poisoning?
alkalinization of the urine with sodium bicarbonate
if fluid alkanine: the weak acid is ionized into salicylate ion and excreted thru urine
What are the 2 parameters to measure drug clearance?
- rate of extraction of drug from blood
- rate of clearance by the kidney
both depend on blood flow and the ability of the kidney to extract the drug (the extraction ratio)
What is the extraction ratio if all the drug is removed from the blood as it passes through the kidneys?
1
how to calculate renal extraction rate?
ER= (A−V)/A
where,
A = Arterial concentration of the substance
V = Renal venous concentration of the substance
What is the range of extraction ratio?
0<ER<1
ER=1 when all of the drug is removed from the blood as it passes through the kidneys
What is the outcome if the renal extraction ratio of a substance is low?
toxicity is likely to occur in renal failure.
e.g. digoxin
What is the outcome if the hepatic extraction ratio of a substance is low?
toxicity is likely to occur in hepatic failure
e.g. digitoxin
Name drugs that should be avoided in patients suffering from liver and renal failure
digitoxin and digoxin
because of low hepatic extraction and low renal extraction respectively
What is Vd?
pharmacokinetic parameter that describes the theoretical volume in which a drug would need to be uniformly distributed to account for its observed concentration in the blood or plasma. It provides insight into how a drug is distributed in the body relative to the blood plasma.
What are the possible values of Vd and what does it indicate?
Low Vd (<10 L)
–> Drug is largely restricted to the plasma.
Intermediate Vd (10–30 L):
–> drug is distributed in extracellular fluid (plasma + interstitial fluid).
High Vd (>40 L)
–> Drug is distributed extensively into tissues (beyond total body water)
How to calculate Vd?
Amount of drug in the body/ Plasma drug conc (per L)
For drugs that are eliminated by first-order kinetics, the drug half-life is calculated by:
0.693 × Vd / Clearance
clearance is the volume of the drug cleared of the drug per unit time
What is meant by half-life?
the time required for its concentration in the blood to be reduced by one-half
Do both the intravenously and orally administered identical drugs have the same half-lives once they reach the general circulation?
Yes
Drugs that undergo both glomerular filtration and active tubular secretion have a very short half-life.
True or false
State how the half-life of penicillin is porlonged.
coadministered with probenecid (a uricosuric drug) that inhibits the tubular secretion of penicillin
Explain why penicillin has a very short half-life
it undergoes both glomerular filtration and active tubular secretion
Why do most drugs have relatively longer half-lives than that of penicillin?
they undergo glomerular filtration, partial tubular resorption, and no active tubular secretion
