Diuretics Flashcards
how much urine does an adult filter per day and what is the urine output?
- Adult filters 180L per day
- Urine output 1-2L
what do volume sensors regulate? and describe what each type does?
- Vascular tone –to control organ perfusion
- Renal Na+ excretion -to control total fluid volume
what are the low pressure sensors in the pulmonary vasculature?
- renal sympathetic nerves
- renin-angiotensin aldosterone axis
- pituitary release vasopressin
What is the main purpose of diuretics?
- To decrease BP by incresaing the excretion of water and Na+ (less burden on cardiovascular disease)
Where is the main site for Na+ reabsorption? How much Na+ is absorbed?
Proximal convulated tubules
- Absorbs about 60-70%
Where can NAHCO3 also be absorbed?
proximal convulated tubules
Where is water reabsorbed in the nephron?
In the descending limb
What is the golden rule of the kidney?
- Water tends to follow Na+
Name the different types of duiretics?
- Thiazides
- Osmotic
- Loop
- K+ sparing
- Carbonic anhydrase inhibitors
Where does each type of diuretics work in the nephron?
- Thiazides: Distal convulated tubule
- Loop: Thick ascending limb of the loop of Henle
- K+ sparing: Cortical collecting duct
- Carbonic anhydrase inhibitors: Proximal convulated tubule
What does Angiotensin 2 control?
- Aldosterone secretion
- Na+ Re-absorption (renal proximal tubule)
- Constriction of the renal afferent arterioles
- Thirst (Hypothalamus vasopressin secretion)
When and where is vasopressin or Anti-diuertic hormone ADH secreted?
- secreted from the pituitary in response to low blood volume
What is an oedema and provide an example?
- An increase in interstitial fluid in any organ e.g pulmonary oedema causes severe breathlessness
Describe nephrotic syndrome?
- Renal damage
- Leads to increase in permeability of glomerular basement membrane
- Leads to proteinura and a decrease in plasma
- Which leads to an increase in interstitial fluid
What are the symptoms of nephrotic syndrome?
- Swelling of ankles and legs
describe oedema in heart failure?
- Decreased cardiac output triggers kidney to respond as if hypovolemia causing increased salt and fluid retention
What occurs in hepatic cirrhosis?
- Portal vein flow obstructed
- Leads to fluid escape into the peritoneal cavity
When are carbonic anhydrase inhibitors used to treat?
- Used for treatment in glaucoma
But rapid development of toletance
What are loop diuretics indicated for?
- Most efficacious diuretics
- Used to treat marked oedema commonly after heart failure, acute pulmonary oedema (i.v admin) and other oedema (P.O)
Loop diuretics are less useful in hypertension. TRUE OR FALSE?
TRUE
What are the side effects of loop duiretics?
- Hyperkalaemia
- Hypercalcaemia
- Hyponatraemia
Name some loop diuretic drugs and describe how each drug is cleared?
- Furosemide (P.O) - cleared by the kidney
- Bumetanide (P.O) - cleared by hepatic metabolism
- Torasemide (P.O) - Cleared by hepatic metabolism
Name some Thiazide and thiazide-like diuretics and the half lifes?
- Metolazone (t1/2 4hr)
- Indapamide (t1/2 16hr) - lowers bp at dose where no effect on diuretics (for hypertension)
- Chlortalidone
- Bendroflumethiazide (t1/2 6hr)
What are Thiazide and thiazide-like diuretics indicated for?
- mild oedema e.g Heart failure, hepatic cirrhosis, nephrotic syndrome
- Hypertension
- Diabetes insipidus
Thiazide and thiazide-like diuretics are less efficacious compared to loop diuretics? TRUE OR FALSE?
TRUE
Define hypokalaemia?
- < 3.5 mM serum K+
In which two types of diuretics drugs is hypokalaemia common?
- Loop
- Thiazide
Why is hypokalaemia more severe in thiazide?
- Because they have longer t1/2
Patients are at increased risk of hypokalaemia if aldosterone levels are high. TRUE OR FALSE?
TRUE
What can hypokalaemia cause?
- Arrythmia (in case of myocardial ischemia)
- Encephalopathy
- Diabetes mellitus because of reduced insulin secretion
- Fatigue and lethargy
What are the treatments of hypokalaemia?
- K+ sparing diuretics
- K+ supplement
- Diet - bananas
What are the indications for potassium sparing diuretics?
-Mild diuretics on own - often used in combination with loop diuretics or with thiazides to counteract K+ loss
What are potassium sparing diuretics particularly useful for?
- Conserving potassium if loop diuretic or thiazide used
- Concomitant digoxin therapy (because of interaction of digoxin and loop/thiazides)
- Secondary hyperaldosteronism
- Elderly
potassium sparing diuretics are generally used on own to treat oedema? TRUE OR FALSE?
- FALSE
what is an advantage of using potassium sparing diuretics?
- Avoids extensive diuresis
Name a potassium sparing diuretics and what is the half life of the drug?
- Spirinolactone - variable absorption but improved if taken with food
- Short t1/2 1hr - but rapidly metablosied to more stable metabolite canrenone with a t1/2 20hr
Why does Spirinolactone have a slow onset of action?
- Because it has to be metabolised into the more stable form canrenone which has a half life of 20hr
What are some ADRs of potassium sparing diuretics?
- Hyperkalemia - due to reduced K+ loss at CCD
- Metabolic acidosis - H+ secretion at CCD is also inhibited
- Spirinolactone also inhibits androgen receptor
What are some drug interactions with potassium sparing diuretics?
- NSAIDS can impair renal function and cause hyperkalemia with spirinolactone
- Amiloride - direct inhibition of ENaC
What is metabolic alkalosis and name some symptoms?
- Increased alkalinity (Loop and thiazide diuretics cause H+ loss at CCD)
- Tremor, muscle twitching
- Numbness
- lightheaded, confusion, possible coma
What is metabolic acidosis and name some symptoms?
- Increased blood acidity
- K+ sparing diuretics inhibit H+ loss at CCD
- Rapid breathing, confusion, lethargy
- May lead to shock or death
Name an osmotic diuretic drug?
- Mannitol
Describe how mannitol works?
- Undergoes glomerular filtration
- Not reabsorbed in renal tubule
- Decreases osmotic gradient in descending limb of loop of henle
- less water reabsorbed
- More diuresis
What are indication for osmotoc diuetics?
- Emergency use - cerebral oedema
- Excreted unchanged in urine
What are some ADR of osmotoc diuetics?
- Heart failure
- Hypokalaemia
