M3 L1: Diuretics Flashcards
functional anatomy of kidney
- nephron: renal corpuscle - glomerulus, bowman’s capsule - renal tubule: PCT, Loop of Henle, DCT
- collecting ducts
Nephron is the factory, makes urine, surrounded by bowman’s capsule, all these elements stay in the blood, everything can be filtered except plasma
renal excretion
Glomerular Function:
- Filtration: filtrate = plasma - plasma proteins
Tubular Function:
- Reabsorption: water & useful materials -> back to blood
- Secretion: waste products -> urine
Excretion = filtration - reabsorption + secretion
Filtration: takes away plasma
Reabsorption: of most of water, and substances that we need like potassium, calcium, and bring back to blood
Secretion: things we want to get rid of that wasn’t filtered already
Diuretics
Nephron has lots of stations
Best diuretic: water if you want to lose water drink water!
Substances that increase urine output
Act on the kidney:
- Directly or indirectly
- Different locations
Different mechanisms
major classes of diuretics
- Thiazide diuretics
- Loop diuretics
- Potassium sparing diuretics
- Carbonic anhydrase (CA) inhibitors
- Osmotic diuretics
Thiazide diuretics
Site of action: DCT
Mechanism: Decreased Na+ - Cl- cotransporter -> decreased NaCl reabsorption -> water stays in urine
Advantage: gentle diuresis -> safe in the elderly
Gentle
Have adverse effects: hypokalemia (decreased potassium level in the blood) is most common, hypomagnesemia (decreased magnesium level), hyperglycemia (glucose level high), hypercalcemia, hypercholesterolemia, hyperuricemia (high ureic acid)
We don’t have to memorize all this (just the important ones, for example this one: hydrochlorothiazide or HCT)
Not very aggressive which can make them ideal
Work on the early part of the DCT
Prevents the reabsorption of sodium chloride
Works on the protein transporter (the cotransporter)
NaCl brings water back
Loop Diuretics
Site of action: thick segment of the ascending limb of loop of Henle
Mechanism: decreased Na+ - K+ - 2Cl- - cotransporter -> decreased NaCl reabsorption -> water stays in urine. Increased Ca+ and Mg2+ excretion
Characteristics: strong (high ceiling diuretic)
Adverse effects: similar to thiazides - EXCEPT: hypocalcemia -> osteoporosis
Same as thiazides, but hypocalcemia instead of hyper
Remember furosemide over the others (others: bumetanide, ethacrynic acid)
More aggressive
They work on another transporter
Cotransporter brings it back to blood, blue in diagram
Prone to hypocalcium and hypomagnesium
Potassium Sparing Diuretics: Aldosterone antagonists
Competitive inhibition of aldosterone at the receptor site
Ex: spironolactone
Retaining potassium here (getting rid of everything but potassium here)
Reabsorbs sodium
Both compete, inhibit receptors
what is aldosterone
- hormone produced by the adrenal gland
- regulates the balance of salt and water, particularly in the kidneys
- increases reabsorption of salt and excretion of potassium
- helps control bp and electrolytes within a narrow range
- Hormone
- Produced by adrenal cortex
- Acts on DCT and collecting ducts
- Activated via RAAS
- Effect
○ Na+ and water reabsorption
○ K+ excretion
Potassium Sparing Diuretics: Renin -Angiotensin-Aldosterone System
Aldosterone:
- Hormone
- Produced by adrenal cortex
- Acts on DCT and collecting ducts
- Activated via RAAS
- Effect
○ Na+ and water reabsorption
○ K+ excretion
This is the RAAS system
These are a few cells in kidney, they make renal enzyme this enzyme converts angiotensinogen to angiotensin then into angiotensin 2 (come from angiotensin 1 from an angiotensin converting enzyme)
Angiotensin 2: cause vasoconstriction of blood vessels and trigger release of antidiuretic hormone stim release of aldosterone
Ace inhibitor: angiotensin enzyme in them
Used for patients with hypertension
Hyper anemic if you retain potassium
Potassium Sparing Diuretics: sodium channel blockers
- Decreased Na+ reabsorption -> water stays in urine
- Weak diuretics
- Ex: amiloride - triamterine
Nothing to do with aldosterone
Block the sodium channels to prevent Na from going back into the body
Inhibit sodium reabsorption by blockage of the channels
Weak diuretics
Potassium Sparing Diuretics
1. site of action
2. main effect
3. adverse effects
- DCT (late segment) and collecting ducts
- NaCl and water loss in urine. K+ sparing.
- Hyperkalemia. Spironolactone: androgen or estrogen-like effects
Retain potassium - could cause hyperkalemia
Aldosterone antagonist have an extra adverse effect which is spironolactone, in structure has a steroid ring so sometimes it can affect sex hormones: for example can make women grow facial hair, or give men boobs
Carbonic Anhydrase Inhibitors
1. mechanism
2. site of action
3. other actions
4. adverse effects
5. examples
- decreased enzyme -> decreased H+ excretion -> increased Na+ and K+ excretion
- PCT
- decreased intraocular pressure
- metabolic acidosis, hypokalemia
- acetazolamide
This enzyme can be found in kidney, lungs, heart, etc. its in many places
Makes hydrogen and bicarb, then excreted in urine
Sodium would be excreted
Osmotic Diuretics
1. site of action
2. mechanism
3. other actions
4. adverse effects
5. example
- quite aggressive, if you want to drain your patient*
1. throughout the nephron specially PCT
2. - filtered in glomeruli and cannot be reabsorbed from renal tubules -> remain in tubular lumen ->
- increase osmolarity of tubular fluid -> retains water in urine
- Moves hypo to hyper, more water will come therefore it’ll increase
3. decreased intracranial pressure, decreased intraocular pressure
4. increase ECF volume, may aggravate HF and pulmonary edema
5. ex: mannitol
therapeutic uses of diuretics
Treat edema, gets rid of extra water
Treatment of heart failure, and hypertension
Treatment of glaucoma and intracranial pressure
CA inhibitors and osmotic diuretics
diuretics and potassium
K+ losing diuretics
(thiazides and loop diuretics)
- cause hypokalemia
- require K+ supplements
K+ sparing diuretics
- cause hyperkalemia
- a combo is helpful:
ex: amiloride + hydrochlorothiazide
