P17: Dierutic Drugs Flashcards
What is the primary purpose of diuretic drugs?
Increase excretion of Na+ and Cl-
Increase water loss
What are the two major mechanisms by which diuretics work?
- Direct action on epithelial cells of the nephron
- Indirectly modifying the filtrate content
Give 1 example of a loop diuretics
- Furosemide
bumetanide
torasemide
What is a negative action of a loop diuretic?
Leads to an accumulation of intracellular K+ in the cell as not enough Cl- in cell to make K+/Na+ pump work and move K+ out.
This results in back diffusion of K+ into tubular lumen which increases membrane potential and causing magnesium and calcium excretion
What are the uses of loop diuretics? (5)
- Pulmonary oedema*** due to left ventricular failure
- Congestive heart failure***
- Diuretic-resistant oedema***
- Control of resistant hypertension
- Hypercalcaemia
How and why does a loop diuretic enter the body?
Enter tubular lumen via proximal tubular secretion, this is due to the fact that the body treats the drug as a poison so it tries to excrete it via the proximal tubule.
How does a loop diuretic work?
- Causes excretion of 15-20% of filtered Na+
- It inhibits {Na+/K+/2Cl-} transporters, reducing NaCl reabsorption in the ascending limb of the loop of henle so more water and sodium lost.
What are some of the side effects of loop diuretics?
- Hypokalaemia
- Hyperuricaemia
- Metabolic alkalosis
- Hyponatremia
- Ototoxicity (ear damage)
- Mg2+ depletion
Give 2 examples of Thiazide diuretics
Thiaz(i)”de”
- Chlortalidone
- Indapamide
- Xipamide
- Hydrochlorothiazide
How does a Thiazide diuretic work?
Inhibits Na+ reabsorption at the beginning of the distal convoluted tubule.
Reduction of intraepithelial Na+ activates the Na+/Ca2+ antiporter, indirectly increasing Ca2+ reabsorption
What is a negative action of a Thiazide diuretic?
Leads to an accumulation of intracellular K+ in the cell as not enough Cl- in cell to make K+/Na+ pump work and move K+ out.
This results in back diffusion of K+ into tubular lumen which increases membrane potential and causing magnesium and calcium excretion
BUT TO LESSER EXTENT TO LOOP DIURETIC
What are the uses of Thiazide diuretics?
- Hypertension (effective at low doses)
- Kidney stones - increased DCT Ca2+ reabsorption, slows stone growth
- Heart failure
What are some of the side effects of Thiazide diuretics? (4)
*the hypers
- Hypokalaemia, aggravates cardiac arrhythmias
- Metabolic alkalosis
- Hyperuricaemia, aggravating gout
- Hyperglycaemia – impaired pancreatic insulin release (K+ dependent)
Give 2 examples of osmotic diuretics
Os(m)ot(i)c
- Mannitol***
- Isosorbide(inert)***
How do osmotic diuretics work?
They are pharmacologically inert molecules that simply pass through the glomerulus and increase filtrate osmotic pressure. Therefore drawing water into the filtrate so more can be urinated out.
Reduces tubular and LOH water reabsorption
What are the uses of osmotic diuretics? (3)
- Acute renal failure
- Cerebral oedema
- Glaucoma
What are some of the side effects of osmotic diuretics?
- Headache
- Nausea
- Vomiting
Give 3 examples of potassium sparing diuretics
“hard as doing my SATs”
- Spironolactone (MR antagonist)
- Amiloride (ENaC blocker)
- Triamterene (ENaC blocker)
MR and ENaC = main types
How do potassium sparing diuretics work? (2)
Either
- Mineralocorticoid receptor antagonists.. inhibits aldosterone action which stops Na+ movement so no concentration gradient is formed.
- Epithelial Na+ channel blockers… Na+ cannot enter cell so no concentration gradient so water cannot be reabsorbed.
What are the uses of potassium sparing diuretics? (2)
- Prevent hypokalaemia more effectively than K+ supplements
- Given with loop or thiazide diuretics as these are weak
What are some of the side effects of potassium sparing diuretics?
- Hypokalaemia
- GI tract disturbance
- Nausea
- Vomiting
- Sexual disfunction
Give examples of Carbonic Anhydrase Inhibitors (CAIs)
Acetazolamide
Dorzolamide
Brinzolamide
How do Carbonic Anhydrase Inhibitors work?
Carbonic anhydrase catalyses the conversion of water and CO2 into bicarbonate and H+
Therefore block of HCO3- production leads to less bicarbonate reabsorption and consequently less Na+ reabsorption. Therefore no concentration gradient can form.
What are the uses of Carbonic Anhydrase Inhibitors?
- Treatment of glaucoma
- Acute mountain sickness
- Treatment of metabolic alkalosis - as great bicarbonate loss leads to metabolic acidosis
What are the 5 classes of diuretic
- Osmotic diuretics
- Carbonic anhydrase inhibitors (CAIs)
- Loop diuretics
- Thiazide diuretics
- K+-sparing diuretics -Na+-channel blockers, Mineralocorticoid receptor (MR) antagonists
What classes of diuretic have high, mid and low effectiveness
High-effective: Loop diuretics
Mid-effective: Thiazide diuretics, osmotic diuretics
Low-effective: K+-sparing diuretics and CAIs
What are the secondary effects of osmotic diuretics on Na+
The volume of the filtrate increases
So the Na+ gradient increases and the Na+ excretion increases
What must K+ sparing diuretics not be used alongside and why
K+ supplements, ACE inhibitors, or ATII antagonists
will cause severe hyperkalaemia and cardio toxicity
How is acetazolamide administrated and are its side effects
Orally
weak diuresis and metabolic acidosis
How are dorzolamide and brinzolamide administrated and what are its side effects
Topical
No diuretic effect, and no systemic metabolic effect
What does NaHCO3 treatment do to the urine
Raises urinary pH, which aids the excretion of some drugs with a lower pKa as charged molecules will not be excreted as well
Name 2 drugs that treat gout
Allopurinol
Probencid
