Pharmacology of diuretics Flashcards
What do volume sensors regulate and what are they used to control?
- Vascular tone (to control organ perfusion)
- Renal Na excretion (to control total fluid volume)
Where are the low and high pressure sensors located?
- Low pressure sensors located in the pulmonary vasculature
- High pressure sensor located in the atria
How does the body monitor pressure changes?
- By using pressure sensors
In the kidneys the water follows the Na. TRUE OR FALSE?
TRUE
What happens when the pulmonary vasculature is activated?
It actiaves the PNS, CNS which actiavtes
- Renal sympathetic nerves
- Renin-angiotensin aldosterone axis
- Pituitary release vasopressin
- Causes constriction and cardiac output
What do sensors that dectect high pressure changes excrete in response to this high pressure?
- Natriuteric peptides
What does Natriuteric peptides cause?
- Vasodilation and causes Na to be excreted from the kidney
How much urine does an adult excrete per day?
- 180ml
Urine output is 1-2 L for an adult. TRUE OR FALSE?
TRUE
ACE inhibitors (RAAS), AT receptors antagonists can be used as a therapeutic strategy for volume regulation. TRUE OR FALSE?
TRUE
What is vasopressin and where is it secreted from and in response to what?
An anti-diuretic hormone ADH
Secreted by the pituitary in response to low blood volume
What are the receptors are used by vasopressin?
-GPCR (V1 (smooth muscle) and V2 (collecting duct)
V1 (smooth smuscle) in vasopressin causes an increase in calcium levels which leads to vasoconstriction. TRUE OR FALSE?
TRUE
V2 (Collecting duct) in vasopressin increases aquaporin 2 which leads to an increase in water reabsorption. TRUE OR FALSE?
TRUE
What is desmopressin and what is it indicated for?
- A synthetic agonist with low affitnity for V1 (no vasoconstriction)
- Indicated for diabetes insipidus
What is diabetes insipidus and how can it be treated?
- It is excess dilute urine due to the lack of vasopressin secretion from pituitary
- treatment - nasal spray which lasts 4-6 hours
What occurs in the renal sympathetic nervous system?
- Induces B1 receptors which leads to an increase in renin production juxtaglomerular cells, this stimulates the afferent arteriole to constrict whuch decreases glomerular pressure and therefore decreasing GFR
What are some of the clinical uses of diuretics?
- Oedema
- Hypertension
- Hypercalcemia
- Renal failure
- Diabetes insipidus
What is oedema?
- Increase in interstitial fluid in any organ e.g pulmonary oedema, causes severe breathlessness
What occurs in nephrotic syndrome (oedema)?
- Renal damage causes an increase in permeability of glomerular basement membrane which leads to proteinuria and a decrease in protein in plasma leading to an increased fluid, this leads to ankle and legs swelling
What occurs in heart failure (oedema)?
- decreased cardiac output triggers kidney to respond as if hypovolemia, causing increased salt and fluid retention
what occurs in hepatic cirrhosis (oedema)?
Portal vein flow obstructed which leads to fluid escape into the peritoneal cavity
Carbonic anhydrase inhibitors are rarely used as diuretics. TRUE OR FALSE?
TRUE
With Carbonic anhydrase inhibitors, there is a potential for rapid development of tolerance. TRUE OR FALSE?
TRUE
What are carbonic anhydrase inhbitors used to treat?
Glaucoma
Loop diuretics are the most efficacious diuretics. TRUE OR FALSE?
TRUE
What are the indications for loop diuretics?
- For the treatment of oedema commonly after heart failure/acute p.o (i.v admin)
- Hypertension (used as last resort)
- hypercalceamia (hyperparathyroidism)
- hyperkaleamia (resulting from renal insufficiency/drugs causing K retention)
- Hyponatraemia
What are the names of loop diuretic drugs?
- Furosimide
- Bumetanide
- Torasemide
What is the half life of furosimide and how is it cleared?
- 1hr (variable absorption i.v or i.m)
- clearedd by the kidneys
What is the half life of bumetanide and Torasemide and how are they cleared?
- bumetanide - 1.5hr (well absorbed p.o)/cleared hepatic metabolism
- Torasemide - 3hr (well absorbed p.o)/cleared by hepatic metabolism
Bumetadine is a not potential advanatge if patient’s renal function is impaired. TRUE OR FALSE?
FALSE
What are some of the ADR’s of Loop diuretics?
- Greater risk of ADR with furosemide in renal disease
- Hypokalaemia (arrythmia, muscle weakness,metabolic alkilosis)
- Hypotension
- Hypocalcaemia and hypomagnesaemia
- Hyperuricaemia and gout
- Ototoxicity
Names thiazide and thiazide like diuretic drugs and their half life?
- Bendroflumethiazide - 6hr
- Indapamide (lowers bp at dose where no eefct on diuresis) - 16hr
- Metolazone - 4hr (preferred in advanced renal failure)
- Chlortalidone
What are some of the indications for thiazide and thiazide like diuretics?
- Mild oedema
- Hypertension
- Diabetes insipidus
What are some of the ADR’s for Thiazide and thiazide like diuretics?
- Hypokalaemia
- Nocturia
- Hypotension
- Hyponatremia
- Hypomagnesaemia
- Decreased ca excretion
How is hypokalaemia classified and with which type of diuretics is it most common with and why?
<3.5 mM serum K+
- thiazide diuretics because of longer half life
What are some treatments for hypokalaemia?
- K+ sparing diuretics
- K+ supplement
- Diet - bananas
What can hypokalaemia cause?
- Arrhythmia
- Encephalopathy
- Diabetes mellitus because reduced insulin secretion
- Fatigue and lethargy
Potassium sparing diurtics are often used in combination with loop diuretics or with thiazides to counteract K+ loss. TRUE OR FALSE?
TRUE
What are potassium sparing diuretics particularly used for?
- Conserving potassium if loop diuretic or thiazide are used
- Concomitant digoxin therapy
- Secondary hyperaldosteronism
- Elderly
potassium sparing diuretics are not used on their own to treat oedema. TRUE OR FALSE?
TRUE
Spirinolactone has a slow onset of effect because of mechanism of action. TRUE OR FALSE?
TRUE
What are the ADR’s for potassium sparing diuretics?
- Hyperkalemia
- Metabolic acidosis
- Spirinolactone also inhibits androgen receptor (a related steroid receptor)
What is metabolic alkalosis and what arethe symptoms?
- Increased alkalinity (loop and thiazide diuretics cause H+ loss)
- Tremor, muscle twitching, numbness, possible coma
What is metabolic acidosis and what are its symptoms?
- Increased blood acidity (K+ sparing diuretics inhibit H+ loss)
- Rapid breathing, confusion, may lead to shock or death
loop and thiazide diuretics cause H+ loss
K+ sparing diuretics inhibit H+ loss
Are these statements TRUE OR FALSE?
TRUE
How does Mannitol (osmotic diuretic) work?
- It undergoes glomerular filtration, it is not reabsorbed in renal tubule, this leads to a decrease in osmotic gradient in descending limb of loop of henle, less water is reabsorbed which leads to more diuresis
What are the indications for osmotic diuretics (mannitol) and ADR’s?
- emergency use - cerebral oedema
- ADR - heart failure/ hypokalaemia
