Pharmacology 2060A/B Lecture Notes - Lecture 5: Renal Blood Flow, Efferent Arteriole, Distal Convoluted Tubule
15 May 2018
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Module 5 – Pharmacokinetics – Excretion
5.1 - Routes of drug excretion
Drug excretion
- Is the removal of parent drug and drug metabolites from the body
- Most common sites of drug excretions are the kidney and bile
Renal drug excretion
- The kidneys account for the majority of drug excretion
- Healthy kidneys serve to limit the duration and intensity of drug effects
- Decreased kidney function prolongs the duration of action and intensity of drug effects
- This is important in patients with end stage kidney disease
o Kidney disease at the final stage requires dialysis
o At this stage, drug excretion in the urine is almost negligible
o Doses of many drugs must be reduced in these patients
The nephron
- Kidney has an outer cortex and inner medulla
- The basic structural and functional unit of the kidney is the nephron
o Spans from the renal cortex to the renal medulla
- Regulates water, electrolyte levels and drug excretion
- Controls blood volume, blood pressure, blood pH and solute (including drug) excretion
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- Afferent arteriole: carries blood to the glomerulus for filtration
- Efferent arteriole: carries blood away from the glomerulus
- Glomerulus: bed of capillaries that make up the first stage of filtering blood to form urine
o Surrouded Boa’s apsule: space for fluids + solutes to flow into after they
have been filtered but before they enter into the kidney tubules
o Fluids ad solutes filtered the gloerulus eter the spae i Boa’s apsule
before entering the tubules
- Proximal tubule: from Bowman’s apsule, the filtrate eters the proial tuule
o Essential for regulating pH of the filtrate and is an important site for the reabsorption of
essential molecules such as glucose and sodium
o Important site for drug secretion
- Loop of Henle: creates a concentration gradient in the medulla of the kidney
o Results in the reabsorption of water creating a concentrated filtrate
o If water is reabsorbed and the drugs are not, the drugs become more concentrated in
this stage of the kidney as well
- Distal tubule: regulates electrolyte levels and filtrate pH
o Site of action for drugs that control blood pressure
o Concentration of drugs in the filtrate at this distal tubule is often higher than that of
blood, therefore this is an important site for drug reabsorption from the filtrate back
into the blood
- Collecting duct: series of tubule connecting the nephron to the ureter
o Final step in the production of urine
5.2 - Factors affecting renal drug excretion
Factors that determine how much of a drug gets into the nephron, moves through the nephron and
leaves the body through the urine:
1. Glomerular filtration
2. Tubular secretion
3. Tubular reabsorption
1) Glomerular filtration
- Drugs leave blood and enter kidney tubules through glomerular filtration at the glomerulus
- Drugs enter the kidney from the renal artery and afferent arteriole
- Water and drugs/salt in the blood are filtered at the glomerulus but the proteins are too large to
fit through the slits
o Proteins in the blood are not filtered at the glomerulus
o Small molecules such as drugs and ions are filtered
- Hydrostatic pressure within glomerular capillaries forces low molecular weight drugs into the
renal tubules from the blood
- Major determinant of what fits in through the glomerulus is the size of the molecule
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- Glomerular filtration rate is ~ 120 ml/min/1.73 m2 or about 20% of total renal plasma flow
- Lipid solubility and pH do not affect glomerular filtration of drugs
- Only non-protein bound (i.e. free) drugs are filtered at the glomerulus
2) Tubular secretion
- Not all drugs are filtered at the glomerulus
- Drugs not filtered by the glomerulus leave the glomerulus by the efferent arteriole
- Tubular secretion occurs in the proximal tubule
- The efferent arterioles divide to form capillaries that surround the proximal tubule
- This provides a site where drugs can be secreted from the blood surrounding the tubules into
the lumen of the proximal tubule
- Drug secretion in the kidney primarily occurs by two transport systems (transport mediated
processes)
o Drugs that are weak acids are transported by one transport system
o Drugs that are weak bases will be transported by another transport system
- Secretion is a rapid high capacity process
o Occurs fast and has the ability to transport a lot of drugs from the blood into the lumen
of he tubules
- Blood supply surrounds the proximal tubule
o There are transport proteins located on the basolateral surface of tubule cells
o Basolateral membrane faces the blood
o When drugs come into the efferent arteriole and surround the tubules, the transporter
moves them into the lumen to be eliminated in the urine
3) Tubular reabsorption
- Tubular reabsorption occurs along the distal tubule
- As drugs can be secreted from the blood into the tubule lumen, they can move from the tubular
lumen back into the blood
- As drugs move toward the distal tubule, the concentration of the drug in the tubule increases
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Document Summary
Is the removal of parent drug and drug metabolites from the body. Most common sites of drug excretions are the kidney and bile. The kidneys account for the majority of drug excretion. Healthy kidneys serve to limit the duration and intensity of drug effects. Decreased kidney function prolongs the duration of action and intensity of drug effects. Kidney has an outer cortex and inner medulla. The basic structural and functional unit of the kidney is the nephron: spans from the renal cortex to the renal medulla. Regulates water, electrolyte levels and drug excretion. Controls blood volume, blood pressure, blood ph and solute (including drug) excretion. Afferent arteriole: carries blood to the glomerulus for filtration. Efferent arteriole: carries blood away from the glomerulus. Proximal tubule: from bowman"s (cid:272)apsule, the filtrate e(cid:374)ters the pro(cid:454)i(cid:373)al tu(cid:271)ule: essential for regulating ph of the filtrate and is an important site for the reabsorption of essential molecules such as glucose and sodium.
