Flashcards in L45 – Diuretics and ACE Inhibitors Deck (79):
3 types of diuretics?
Name three common loop diuretics? FEB
Name 2 common thiazide diuretics? HI
Name 3 common potassium sparing diuretics? SEA
Major effect of diuretics ?
Increase fluid excretion, lower blood volume, decrease BP
Difference in effect of diuretic agents in oedematous and non-oedematous states?
Oedematous: decrease peripheral or pulmonary oedema WITHOUT significant decrease in blood volume
Non-oedematous: decrease hypertension
Result of excessive diuresis?
Further compromise the effective arterial blood volume > decrease perfusion to vital organs
Where do loop diuretics act on the kidney tubule?
Thick ascending limb of loop of Henle
@ Na/K/2Cl co-transporter at apical membrane
Effect on electrolyte and water balance after loop diuretic action on Loop of henle?
Inhibit Na+/K+/2Cl transporter > decrease reabsorbing Na+, K+, Cl- from filtrate > less medullary hypertonicity + decrease reabsorption of Ca, Mg > increase renal excretion of water, Na+, K+ Ca2+, Mg2+, Cl-, H+
How does Loop diuretic help treat oedema during heart failure?
Increase Na+ secretion = less retention of salt = less oedema
How does Loop diuretic help treat congestive heart failure and pulmonary oedema?
Increase venous capacitance and lower blood volume = less Left Ventricular filling pressure due to less venous return = relieve congestion
Is loop diuretics used in treatment of hypertension?
Limited use due to short half-life > causes post-diuretic Na+ reabsorption > kidney try to maximally absorb Na to compensate for natriuria > cause undesired fluctuations in BP
What are the adverse effects of loop diuretics on electrolytes and what complications entail?
Loop diuretics > depletion of H+, K+, Na+, Mg
Cause Metabolic alkalosis, hypokalemia, Hyponatremia, Hypomagnesemia
Complication of hypokalemia caused by loop diuretics? How to reverse effect?
Exacerbate cardiac arrhythmia
Reverse by decrease Na intake or K+ supplement
Complication of hyponatremia caused by loop diuretics? How to reverse effect?
Cause ECF depletion, hypotension, reduced GFR, hepatic encephalopathy, thromboembolism
Complication of Metabolic alkalosis caused by loop diuretics? How to reverse effect?
Further compromise cardiac function
Reverse by K+ supplement
Apart from electrolyte imbalance cause by loop diuretics, How does loop diuretic cause gout?
Increase diuresis > hypovolemia > increase re-absorption of uric acid and water > gout
Complication of hypomagnesemia caused by loop diuretics on heart?
Exacerbate cardiac arrhythmia
Complication of lipid levels caused by loop diuretics?
Adverse effect of loop diuretics on ear? which loop diuretic most likely to cause adverse effect? How to alleviate?
Ototoxicity due to inhibition of electrolyte transport in the ear > hearing problem
Most likely with ethacrynic acid
Least likely with oral loop diuretics
What type of allergic reaction can loop diuretics cause?
Sulfonamide- related allergic reactions
some loop diuretics and thiazides cause this
3 causes of resistance to loop diuretics?
Reduction in renal blood flow
Increased proximal tubular Na+ reabsorption
Which 2 drugs can counteract loop diuretics?
1) Nonsteroidal anti-inflammatory drugs (NSAIDs)
Increases expression of NAK2Cl co-transporter which is blocked by loop diuretics
Compete for organic acid transport system in PCT
How does reduction in renal blood flow cause resistance to loop diuretics?
low renal blood flow (e.g. renal failure or drug-induced)
Decrease delivery of diuretics to kidneys + accumulation of endogenous organic acids at PCT = decrease active transport of loop diuretics at PCT
How can heart failure, nephrotic syndrome or hepatic cirrhosis cause loop diuretics resistance?
Increased proximal tubular Na+ reabsorption (e.g. heart failure > hypotension > increase RAAS activation > increase salt retention)
Lower delivery of Na+ to loop of Henle, site of action for loop diuretics
Which part of kidney tubule does Thiazide target?
Explain the action of Thiazides on distal tubule and the electrolyte changes (in Ca2+) it causes?
Inhibit the Na+/Cl- co-transporter in DCT
inhibit Na+ & Cl- re-absorption > decrease intracellular Na+ increases Na+ conc. gradient > drive Na+/Ca2+ exchanger > depletion of Ca2+ in cell causes increase reabsorption of Ca2+
Compare action of drug on filtrate Ca2+ between loop diuretics and thiazides?
Loop = excrete more Ca2+
Thiazide = reabsorb more Ca2+
Loop D. or Thiazide more potent? Why is one chosen over the other to treat oedema?
Loop D. is more potent
Loop D. to treat oedema
Thiazide acts on DCT where most Na+ is already reabsorbed, less control of Na+ levels
Compare the net results in excretion between Loop D and thiazide?
Loop D: increase excretion of Mg, Ca, Na, K, Cl, H+, water
Thiazide: increase excretion of water, Na+, Cl-
Which diuretic is used most clinically for mild hypertension and list 3 reasons why?
As efficacious as other drugs for mild hypertension but few contraindications
Longer acting (once daily dose), safe profile, well-tolerated
Name one drug that is synergistic with Thiazide?
Calcium channel blockers
Explain the effect of thiazide under chronic administration?
Acute = affect renal only
Long-term administration = decrease TPR > direct vasodilation
How does thiazide cause hypokalemia?
Inhibit Na+/Cl- co-transporter in DCT > less intracellular Na > causes increase Na+ reabsorption via Na/K exchanger > more K+ exchanged into filtrate > hypokalemia
How does thiazide cause gout?
Hypovolemia > increase uric acid and water reabsorption > uric acid accumulate in joints > gout
Compare the side effects of thiazide with loop diuretics?
Same but milder, add on Hypercalcemia
Hypokalemia, Hyponatremia, Hypomagnesemia, Hyperuricemia, hyperlipidemia, hyperglycemia, sulfonamid-related allergic reactions
Under what circumstances does thiazide cause hypercalcemia?
Rare, doesnt occur if the Ca2+ regulation is fine
occur if patient has other cause e.g. hyperparathyroidism
How could thiazide exacerbate diabetes? (think pancreas)
Thiazide > activate ATP-sensitive K+ channels > hyperpolarize pancreatic b-cells > reduce insulin secretion and tissue use of glucose > hyperglycemia
How can hyperglycemia caused by diuretics be reversed?
by correcting hypokalemia by K+ supplement
Because thiazide affect K+ channels in b-cells in pancreas to cause reduced insulin secretion
Site of action of potassium sparing diuretics?
Inhibit epithelial Na+ influx and K+ efflux
inhibit reabsorption of Na+ and decrease secretion of K+ (& H+) > decrease water reabsorption (water follows Na)
Explain difference in action between Amiloride vs Spironolactone and eplerenone?
Amiloride = inhibit Na+ channel activity in collecting tubule
Spironolactone, Eplerenone = antagonize aldosterone receptor
How does aldosterone lead to change in NaCl reabsorption in collecting tubule?
Aldoesterone > activate epithelial Na+ channels > increase Na+ conductance in luminal membrane > increase activity of Na+?K+ ATPase in basolateral membrane (by increasing synthesis and distribution of channels)
INCREASE reabsorption of NaCl in collecting tubule
How do Aldoesterone antagonists inhibit increase in reabsorption in NaCl in collecting tubule?
block collecting tubule epithelial Na+ membrane> cannot be activated by aldosterone > inhibit Na+ reabsorption and K+ excretion
Compare diuretic effect of potassium sparing diuretics with the other 2 types?
Most diuretic: Loop D. > Thiazide > Potassium- sparing diuretic
Why is potassium- sparing diuretics least diuretic of all diuretics?
Acting on site where most Na+ is already absorbed
Is potassium-sparing diuretics used in the treatment of oedema or hypertension?
Not on its own
Used in combo with other diuretics to increase response and decrease K+ secretion
Name and explain 2 electrolyte adverse effects of potassium sparing diuretics?
Hyperkalemia > inhibited secretion of K+ into filtrate
Metabolic acidosis > inhibited secretion of H+
Which 2 drugs cant be used with potassium-sparing diuretics and why?
intake of ACE inhibitors, angiotensin receptor blockers > decrease renal excretion of K+ > further exacerbate hyperkalemia > exacerbate cardiac arrhythmia
Under what condition is K+ sparing diuretics not used?
Renal disease patients
Adverse effect of hyperkalemia caused by K+ sparing diuretic is reversed by what?
What sexual changes can K+ sparing diuretics cause?
Gynecomastia (breast enlarge)
Spironolactone is antagonist for androgen and progesterone receptors
Which 2 combo diuretics therapies are given ?
Loop + thiazide
K+ sparing + Loop or thiazide
What precautions is taken with Loop + thiazide combo therapy?
Resultant hemodynamic changes and hypokalemia
When is K+sparing + loop/thiazide combo given?
To manage hypokalemia
What are the 2 effects of angiotensin II on angiotensin receptors?
1) vasoconstriction on SM (increase sympathetic function)
2) Fluid retention (increase Na+ reabsorption in PCT, increase release of Vp and aldosterone)
When are aldosterone antagonists used?
high aldosterone level (e.g.
heart failure, liver cirrhosis, kidney disease)
reduce cardiac remodeling (e.g. fibrosis in heart failure)
Compare the diuretics in electrolyte changes (Na, Ca, K, H)
Na+ : all diuretics excrete
K+: Loop and Thiazide excrete, K+ sparing retention
Ca2+ : Loop excrete, Thiazide retention, K+ sparing no effect
H+ : Loop and thiazide excrete, K+ sparing retention
What two molecules is converted by angiotensin converting enzyme?
Angiotensin I > II
Bradykinin > inactive metabolite
What is the role of Bradykinin?
Which 2 components of RAAS can be blocked?
Name of 2 drugs to inhibit RAAS?
Angiotensin converting enzyme inhibitor (ACEi)
Angiotensin receptor blocker (ARB)
Name 4 common ACEi?
Name 2 common ARB?
Difference of action between ARB and ACEi?
ACEi inhibits formation of angiotensin II
ARB inhibits actions of angiotensin II (selective of AT1 receptor)
Explain the effects of ACEi and ARB?
both: decrease fluid retention and OEDEMA
decrease vasoconstriction and lower TPR = treat HYPERTENSION
lower ventricular remodeling = less fibrosis = improve survival (HEART FAILURE)
Is ACEi and ARB better than Loop D to treat oedema?
Loop D is better for oedema
What are very common adverse effects of ACEi / ARB? Why?
More selective to ACE inhibitor due to increased level of BRADYKININ, can switch to ARB
What are rarer and more severe adverse effects of ACEi and ARB?
Severe hypotention (in patients with fluid loss)
Acute renal failure
Hyperkalemia (dont use with K+ sparing diuretic, exacerbate retention of K+)
Why are ARB and ACEi not used in pregnant patients?
Risk of fetal hypotension, renal failure, malformation
List advantages of ARB over ACEi?
More complete blockage of RAAS
Do not affect AT2 receptors which causes vasodilation and bradykinin release
How is ARB and ACEi naturally counteracted in body?
Natural angiotensin II feedback mechanism interrupted by ACEi/ARB
Body compensate by increase release of renin from JG cells
Limit effectiveness of ACEi and ARB
What drug is used to conteract body's compensation towards ARB and ACEi?
since body naturally boost renin secretion to compensate for the interrupted angiotensin II feedback mechanism
Name one renin inhibitor?
compare the action and side effects of renin inhibitors with ARB/ACEi?
pretty much the same action
without dry cough, angioedema, severe hypotension
Same adverse effects on fetus, hyperkalemia and acute renal failure
What is aldosterone escape?
inability of ACE inhibitor or ARB to reliably suppress aldosterone release
Alternative mechanisms e.g. ACTH hormone and high K+ can make aldosterone
What drug is used for controlling aldosterone escape?
K+ sparing diuretics (spironolactone, eplerenone)
How do aldosterone antogonists improve oedema?
Decrease sodium reabsorption from collecting tubule > less oedema
What effects do aldosterone antagonist have on baroreceptors and ventricular remodeling?
Lower sympathetic activation and lower parasym. inhibition > decrease baroreceptor dysfunction
Decrease ventricular remodeling