Drugs and the Kidney Flashcards
Give 4 reasons why the kidneys are susceptible to damage from drugs.
High vascularity
Large surface area for binding & transport of molecules, including drugs
Reabsorption of water concentrates some drugs in the nephron
Main route of excretion for most of the common and important drugs
What is a diuretic?
A substance that promotes the production of urine
In which part of the nephron do loop diuretics work?
Thick ascending limb of the loop of Henle
In which part of the nephron do thiazides work?
Early part of the DCT
In which part of the nephron do potassium-sparing diuretics work?
Late part of the DCT + cortical collecting tubule
Name a loop diuretic drug.
Furosemide
What is the MOA of loop diuretics?
Inhibit the Na+K+2Cl- co-transporter (NKCC)
What is a key side effect of loop diuretics?
Hypokalaemia
How do loop diuretics cause hypokalaemia?
There is increased delivery of NaCl to the distal tubule, which causes increased Na+ uptake there by the principal cells via a sodium-potassium pump, which actively transports sodium out of the cells in exchange for potassium, leading to potassium secretion into the urine
Loop diuretics can cause reduced reabsorption of which 2 ions?
Calcium and magnesium
Give the 3 conditions for which loop diuretics are often used for.
Peripheral oedema in chronic heart failure
Acute pulmonary oedema
Resistant hypertension
Give 2 symptoms of hypokalaemia.
Muscle paralysis + abnormal heart rhythm
Name 3 thiazide drugs.
Bendroflumethiazide, hydrochlorothiazide, indapamide
What is the MOA of thiazides?
Inhibit the Na+Cl- co-transporter
Give the 2 conditions for which thiazides are often used for?
Peripheral oedema in chronic heart failure
Control of hypertension
What is a key side effect of thiazides?
Hypokalaemia
Thiazides can increase plasma levels of what and therefore increase the risk of which condition?
Uric acid, increasing the risk of gout
Which cells do potassium-spring diuretics act on?
Principal cells
What is the MOA of potassium-spring diuretics?
Either inhibit the mineralocorticoid receptor / aldosterone antagonist (spironolactone) or inhibit epithelial sodium channels (ENaC)(amiloride)
What is a key side effect of potassium-spring diuretics?
Hyperkalaemia
How does spironolactone (aldosterone antagonist) increase luminal concentration of sodium and retain potassium in the blood?
Prevents the synthesis of ENaC and Na+K+ATPase activation, and therefore reduced potassium secretion into the tubular lumen.
What is the most common combinations of diuretics drug classes?
Either loop or thiazide with potassium-sparing diuretic
Briefly describe the RAAS.
A drop in blood pressure / low sodium levels causes juxtaglomerular cells in the kidneys to release an enzyme called renin into the bloodstream. Renin acts on a protein produced by the liver called angiotensinogen. Renin converts angiotensinogen into angiotensin I. Angiotensin I is converted into angiotensin II by angiotensin-converting enzyme (ACE) which is produced by the lungs
What are the 3 key effects of angiotensin II which allow it to increase blood pressure?
Vasoconstriction
Increased sodium and water reabsorption in the kidneys
Stimulation of aldosterone release
