Lesson 8

Question 1

Describe the structure of a nephron

Answer 1

• The glomerulus: where happens the filtration
• Different tubules and collecting ducts: where urine is secreted
  o Proximal tubule
  o Loop of Henle
  o Distal tubule
  o Collecting ducts

Question 2

Which characteristics are important to undergo renal excretion?

Answer 2

• ionized forma at physiological pH
• Low lipid solubility

Question 3

Which compounds are eliminated through glomerular filtration and why?

Answer 3

Water, electrolytes and other endogenous compound are excreted in this way. The limit in term of molecular weight is 66000 in order to avoid the elimination of proteins

Question 4

Which transporters are necessary for the tubula excretion?

Answer 4

ABC drug transporters (P-gp and MRP).
SLC drug transporters (OAT, OCT, MATE) -> minor role

Question 5

What is a victim drug?

Answer 5

A drug administered at the same time of another one with a higher affinity to the transporters. It’s no longer able to be excreted so it remain in the blood and may create toxicity

Question 6

Give some examples of drugs that undergo tubular excretion

Answer 6

• Antidiabetic drug metformin
• Antineoplastic drug methotrexate
• Weak acid (penicillin, salicylates, phenobarbital, glucoronoconjugates and sulphoconjugates
• Weak basis (morphine)

Question 7

Despite glomerular filtration and tubular secretion, the renal clearance of a xenobiotic may be relatively low, why?

Answer 7

due to the occurrence of important reabsorption mechanisms:
- Active or facilitated reabsorption, occurs in proximal tubules and involves in almost all cases electrolytes (Na+/K+), sugars, aminoacids, lactate, vitamins…
- Passive reabsorption: mainly occurs in both distal tubules and collecting ducts, according to chemical lipophilicity, pKa and urinary pH, etc.

Question 8

Which factors affect renal clearance?

Answer 8

• Higher plasma concentration, higher renal clearance
• The more a given compound is lipophilic, the more it is excreted
• The extent of plasma protein binding: if they’re bound, they’re excreted in a longer time.
  This is less important for drug excreted through tubular excretion
• The extent of drug ionization, Pka and pH.
  The pH of urine depends on the diet, omnivorous and carnivorous have urine with pH around 5.5-6.5, herbivores (and probably vegans) have a pH around 7-8. Weak acids are best reabsorbed in animals with acid urine, and weak bases are normally absorbed better in a basic environment.
• Renal diseases: the associated reduction in the rate of glomerular filtration and tubular secretion will prolong the body persistence of drugs. Adjustments in drug dosages is necessary.

Question 9

Definition of renal clearance

Answer 9

Renal clearance is the volume of plasma completely cleared by the kidneys via the urine per unit of time.