Loop diuretics, thiazide and K+ sparing diuretics Flashcards
loop of Henle - very permeable to
water, interstitium hyperosmotic – water is reabsorbed
TAL – impermeable to
water
TAL - reabsorbed
of sodium, potasium and chloride (co-transport)
how much sodium from the original filtrate is reabsorbed in the TAL
25%
what does TAL stand for
thick ascending limb
where are positive ions reabsorbed into
the blood
which pump is present in the ascending limb
Na+, K+, 2Cl-
how do loop diuretics work
Sodium is not reabsorbed into blood – don’t build up gradient – all the ions stay in the urine
Delivers hyperosmotic urine – ions stay inside the tubule
what drags the gradient
the sodium potassium ATPase - moves 3Na into the blood 2 K into epithelial cell -
what kind of diuretic is furosemide?
loop diuretic
what is the main action of the loop diuretic Furosemide?
inhibit Na+/K+/2Cl-
what does furosemide cause?
Cause 15-25% of filtered Na+ to be excreted – “Torrential urine production”
Result in increased osmotic pressure in filtrate delivered to distal tubule (decreases water reabsorption)
when is furosemide used/
Heart failure – chronic/or acute pulmonary oedema
Hypertension
Hepatic cirrhosis complicated by ascites
Nephrotic syndrome
Renal failure
Hypercalcaemia
what is hepatic cirrhosis?
high pressure in portal vein – get oedema in abdomen
nephrotic syndrome
filtration doesn’t work – get protein in the urine
what are the unwanted effects of furosemide? - directly related to the drugs renal action
Hypovolaemia/Hypotension – Excessive Na+ loss and diuresis
Hypokalaemia – K+ loss
Metabolic or “contraction” alkalosis – Increase plasma [HCO3-]
what are the unwanted effects of furosemide? - unrelated to the drugs renal action (rare)
dose-related hearing loss
allergic reactions: rashes, bone marrow depression
A 64-year old man with known congestive heart failure is admitted to the A&E with signs of acute pulmonary edema. He is immediately treated with oxygen by face-mask, morphine for respiratory distress, nitrates as vasodilators to reduce the pre-load as well as a bolus of diuretics intravenously to stimulate diuresis.
Which is the diuretic of choice to be used in this clinical condition?
furosemide
Pulmonary edema – water in the lungs
Furosemide – acts fast – gets liquid out lungs
Wouldn’t use mannitol – drags water from tissue – don’t want to keep water in alveroli – mannitol could stay in the alveoli too – keep water ther
where do thiazides act
on the sodium chloride cotransporter in the distal convoluted tubule (DCT)
what is absorbed in the DCT?
5% of sodium is reabsorbed
the DCT is impermeable to
water
what kind of pump is the sodium chloride pump that thiazides work on
atp ase
Na gets into the cell then into the blood, if the pump is blocked
can’t be reabsorbed into the cell
what kind of diuretic is hydrochlorothiazide
thiazide
how do thiazides work?
Block Na+/Cl- co-transporter
results in higher osmolarity of urine and decreased water reabsorption
why is the effect of thiazides self limiting?
lower blood volume - refine secretin - angiotensin and aldosterone - limitation of the effect of thiazides (pleatueu)
what are thiazides used for
Long term of diuretics
adjunct in congestive heart failure / hypertension
nephrogenic diabetes insipidus (“thiazide paradox”)
Variable oral absorption
10-20% for hydrochlorothiazide
what are the unwanted effects of thiazides related to renal action
Hypokalaemia, metabolic alkalosis (as in Loop diuretics)
Hypocalciuria
Hypomagnesaemia
Hyponatraemia
what are the rare unwanted effects of thiazides unrelated to renal action
Hyperuricaemia precipitating gout (thiazide competes with uric acid for tubular secretion)
Hyperglycaemia – impaired pancreatic release of insulin and diminished tissue utilization of glucose
Higher plasma cholesterol level
what are the rare unwanted effects of thiazides unrelated to renal action
Hyperuricaemia precipitating gout (thiazide competes with uric acid for tubular secretion)
Hyperglycaemia – impaired pancreatic release of insulin and diminished tissue utilization of glucose
Higher plasma cholesterol level
how much sodium is reabsorbed in the collecting duct
1-2%
what is potassium exchanged with in the collecting duct
hydrogen
what is the collecting duct activity dependent on?
tubular conc of sodium
what is activity in the collecting duct regulated by?
aldosterone
where is aldosterone secreted frm
the adrenal cortex
what are aquaporins and where would you find them?
water channels that are in the wall of collecting duct
how does vasopressin affect the number of aquaporins
decreases the number of aquaporins
ADH
how does aldosterone affect the number of aquaporins
increases the number of aquaporins - helps the reabsorption of water and electrolytes
what are the 2 classes od K+ sparing diuretics?
ENaC blocker and aldosterone antagonist
examples of ENac blockers
triamterene and amiloride
what is the action of ENas blockers
Directly block epithelial Na+ channel (ENaC) in distal tubule, collecting tubules and collecting ducts (limited diuretic efficacy)
Used in conjunction with loop and thiazide diuretics to maintain K+ balance
what are the unwanted effects of ENaC blockers
Hyperkalaemia
Gastrointestinal disturbance (rare)
Idiosycratic reactions: rashes (rare)
example of an aldosterone antagonist
spironolactone
Actions of Aldosterone on Na+ reabsorption
Early phase: increasing opening of ENaC
Late phase: promotes DNA transcription
Increase synthesis of ENaC
Increase synthesis of Na+, K+- ATPase
aldosterone antagonist uses
in conjunction with loop and thiazide diuretics to maintain K+ balance adjunct therapy in heart failure hyperaldosteronism primary (Conn’s syndrome)-rare secondary (due to hepatic chirrhosis)
aldosterone antagonist unwanted effects
Hyperkalaemia (can be fatal if ACE inhibitor, angiotensin receptor antagonist or b-blocker are co-prescribed)
Gastrointestinal disturbance (common)
Menstrual disorders or testicular atrophy (acting on progesterone or androgen receptors
what is hyperkalemia and what can it cause
high potassium – arthimia in the heart
A 55-year old woman with known hypertension has been treated with furosemide and hydrochlorothiazide for peripheral edema. At a regular check-up the GP finds she still has ankle edema. Blood work shows K+ 2.8mEq/L.
What is the best recommendation:
add spironolactone
Potassium is a bit low
Want to decrease dieuretic effect – spironolcatone – gives potassium
Low potassium is dangerous
A patient with congestive heart failure becomes refractory to a loop diuretic even if the normal doses where progressively increased 5-fold. Blood work shows K+ 4.0mEq/L.
What do you do next?
add spinonolactone
angiotensin II
INCRESES:
- sympathetic activity
- tubular Na Cl reab, K excretion, and H2O retention
- aldosterone secretion
- arterial vasoconstriction - inc.BP
- ADH secretion - collecting duct H2O absorption
what does ACE do
converts angiotensin I to angiotensin II
what do ACE inhibitors end in
-pril
what does enalapril do/
inhibits the production of angiotensin II - used reduce oedema resulting in heartfaliure
what can other kidney drugs do
alter pH of urine, alter excretion of organic molecules, used in renal faliure
what would you use to treat cardiac decompression
Loop diuretics
Thiazides
K-sparing diuretics
Maintain [K+]o balance is particularly crucial as Low [K+]o is likely to increase toxicity of digitalis, thus is hazardous
Hypertension
treat with
Thiazides
Loop diuretics
Maintain [K+]o balance is particularly crucial as
High [K+]o can be fatal if ACE inhibitor, angiotensin receptor antagonist or b-blocker are coprescribed
Ascites treat with
Periodic administration of diuretics either eliminates the necessity for or reduces the interval between paracentesis
Contributes to the comfort of the patient
Conserves proteins, which otherwise will be lost when ascitic fluid is mechanically withdraw
Loop diuretics
Thiazides
Chronic renal failure
Patient is more frequent subject to electrolyte imbalance
Diuretics are less effective in patients with primary renal disease
Higher doses of the thiazides may decrease the glomerular filtration rate
acute renal failure
Diuretics are not recommended in incipient acute renal failure
Nephrotic syndrome
Response to diuretics is often disappointing
