Diuretics Flashcards
What are the indications of thiazides? (2)
- To relieve edema in CHF
2. To reduce BP (in lower doses)
When are loop diuretics indicated?
For the treatment of pulmonary edema due to ventricular failure and in patients with CHF
When is treatment with combination diuretic therapy indicated?
In patients with edema resistant to treatment with one diuretic
Rapid reduction of plasma volume should be avoided however; vigorous diuresis, particularly with loop diuretics, may induce acute hypotension
Name the thiazide and thiazide-like diuretics referred to in the BNF (9)
- Chlorthalidone
- Indapamide
- Bendroflumethiazide
- Xipamide
- Metolazone
- Benzathiazide
- Clopamide
- Hydrochlorothiazide
- Hydroflumethiazide
What class of drug is chlorthalidone?
Thiazide-like diuretic
Which drugs are considered thiazide-like diuretics? (3)
- Chlorthalidone
- Indapamide
- Metolazone
Which drugs are considered thiazide-type diuretics? (3)
- Chlorothiazide
- Hydrochlorothiazide
- Bendroflumethiazide
(And others)
What dosage of thiazides is preferred in the treatment of HTN?
Low dose; in the management of hypertension a low dose of a thiazide produces a maximal or near-maximal blood pressure lowering effect, with very little biochemical disturbance. Higher doses cause more marked changes in plasma potassium, sodium, uric acid, glucose, and lipids, with little advantage in blood pressure control
Which thiazide diuretics are preferred in the management of HTN? (2)
- Chlorthalidone
2. Indapamide
Which thiazide diuretic is preferred for the treatment of mild-moderate HF?
Bendroflumethiazide
Which thiazide diuretic is preferred for the treatment of HTN in patients with metabolic disorders like diabetes?
Indapamide; claimed to lower blood pressure with less metabolic disturbance, particularly less aggravation of diabetes mellitus.
Which diuretic is most effective when combined with a loop diuretic?
Metolazone; profound diuresis can occur and the patient should therefore be monitored carefully
Which thiazide diuretic can also be used in the managnement of ascites due to cirrhosis in stable patients (under close supervision)?
Chlorthalidone, up to 50 mg daily PO
What is the mechanism of action of thiazides?
Inhibition of the Na/Cl co-transporter a the distal convoluted tubule of the nephron; this prevents reabsorption of sodium and its osmotically-associated water
What are the side effects of thiazide diuretics? (9)
- Hypochloremic alkalosis (loss of Cl > loss of bicarb AND contraction alkalosis)
- Hyponatremia
- Hypokalemia (vs “K-sparing diuretics”)
- Hypotension
- Hyperglycemia
- Hyperlipidemia
- Hyperuricemia (may precipitate gout)
- Hypercalcemia
- also may induce impotence
(4 hypo and 4 hyper; Hypers can be remembered with the acronym, “HyperGLUC”)
What are the contraindications to thiazide use? (5)
- Addison’s disease (increased risk of electrolyte imbalance)
- Hypercalcemia
- Hyponatremia
- Refractory hypokalemia
- Symptomatic hyperuricemia
For which patients should particular caution be used when prescribing thiazides? (5)
Patients with:
- Diabetes
- Gout
- Risk of hypokalemia
- SLE
**all may be exacerbated by thiazides
(AND in the elderly)
Are thiazides safe to use in pregnancy and lactation?
No, they may cause neonatal thrombocytopenia, bone marrow suppression, jaundice, electrolyte disturbances, and hypoglycemia; placental perfusion may also be reduced
May be used during breastfeeding BUT large doses may suppress lactation
Are thiazides safe to use in renal impairment?
Caution in mild to moderate impairment due to risk of electrolyte imbalance and reduced renal function
Avoid in severe impairment (creatinine clearance less than 30 mL/min)
Are thiazides safe to use in hepatic impairment?
Caution in mild to moderate impairment; avoid in severe impairment
Is monitoring required for patients using thiazides?
Electrolytes should be monitored, particularly with high doses and long-term use
The list of drug interactions for thiazides is LONG. However, which particular types of interactions should you be on the look-out for? (5)
Other drugs that increase the risk of
- Hypokalemia (this is the main one)
- Acute renal failure
- Hypercalcemia
- Hypotension
- Hyponatremia
What is the mechanism of action of loop diuretics?
Inhibition of the Na/K/2Cl cotransporter at the ascending limb of the LoH to cause loss of all three electrolytes along with water, thereby inducing diuresis. This also destroys the osmotic gradient of the salty medulla (ultimately decreasing the concentrating ability of the LoH)
*loop diuretics also have a direct effect on the vasculature, dilating capacitance veins to decrease cardiac preload and improve contractile function in acute HF
What are the main indications of loop diuretics? (4)
(Edema and HTN)
- Pulmonary edema due to LV failure
- CHF
- Diuretic-resistant edema when combined with thiazides (except lymphedema and edema due to peripheral venous stasis or CCBs)
- Treatment of HTN in those with resistant HTN or impaired renal function or HF
What are the three loop diuretics listed in the BNF?
- Furosemide
- Bumetanide
- Torasemide
Loop diuretics can exacerbate which conditions? (3)
- Diabetes (but hyperglycemia is less than with thiazides)
- Gout
- Urinary retention in patients with prostatic enlargement
What are the main side effects of loop diuretics?
- Dehydration
- Hypotension
- Low electrolyte state (hyponatremia, hypokalemia, hypochloremia, hypocalcemia, hypomagnesemia)
- Hearing loss, tinnitus (at high doses; due to presence of Na/K/2Cl co-transporter in the inner ear)
- Metabolic alkalosis (loss of Cl AND contraction alkalosis)
Thiazides cause a(n) _____ in serum Ca, while Loop diuretics cause a(n) ____.
Increase; decrease
Therefore, thiazides are preferred in patients with nephrolithiasis and osteoporosis
*notably, BOTH drug classes can exacerbate gout
What are the contraindications to loop diuretic use? (7)
- Hypovolemia
- Dehydration
- Anuria
- Comatose and precomatose states associated with liver cirrhosis
- Renal failure due to nephrotixic or hepatotoxic drugs
- Severe hypokalemia
- Severe hyponatremia
How should loop diuretics be prescribed in patients with prostatic enlargement?
Use small doses and less potent diuretics initially to avoid urinary retention
Can loop diuretics be used in hepatic impairment?
Hypokalemia induced by loop diuretics may precipitate hepatic encephalopathy and coma, therefore, K-sparing diuretics are preferred
Diuretics can increase the risk of hypomagnesemia in alcoholic cirrhosis, leading to arrhythmias
Can loop diuretics be used in patients with renal impairment?
High doses may occasionally be needed in renal impairment; however high doses or rapid IV administration can cause tinnitus and deafness
What, if any, monitoring requirements are there for loop diuretics?
Monitor electrolytes during treatment
Which electrolyte imbalances can occur with loop diuretic administration? (5)
- Hyponatremia
- Hypokalemia
- Hypochloremia
- Hypocalcemia
- Hypomagnesemia
And metabolic alkalosis
What are potassium-sparing diuretics?
Weak diuretics that can be used in combination with another diuretic to counteract the potassium loss and enhance diuresis; treat hypokalemia arising from loop- or thiazide-diuretic therapy as an alternative to potassium supplements
This includes amiloride and related drugs co-amilofruse (with a loop diuretic), and co-amilozide (with a thiazide diuretic), as well as triamterene
Aldosterone antagonists (eg spironolactone) also have potassium-sparing effects and may be used as an alternative
What are the drug interactions of loop diuretics?
Loop diuretics have the potential to affect drugs that are excreted by the kidneys eg
- lithium
Risk of digoxin toxicity is increased due to hypokalemia
They should also be prescribed with caution alongside other drugs that can cause
- hypokalemia
- hypotension
- hyponatremia
- ototoxicity (eg aminoglycosides)
Can potassium supplements be given alongside potassium-sparing diuretics?
NOPE, can cause severe hyperkalemia
Administration of a potassium-sparing diuretic to a patient receiving an ACE inhibitor or an angiotensin-II receptor antagonist can also cause severe hyperkalaemia.
Can potassium-sparing diuretics be co-prescribed with ACE inhibitors/ARBs?
No, may cause severe hyperkalemia
What are the main 2 aldosterone antagonists?
- Spironolactone
- Eplerenone
Both also potassium-sparing diuretics
Can potassium supplements be given with aldosterone antagonists?
NOPE, risk of hyperkalemia
What are the indications of spironolactone? (5)
- Edema and ascites caused by cirrhosis (furosemide can be used as an adjunct)
- Moderate to severe HF (adjunct)
- Resistant HTN (unlicensed; adjunct)
- Nephrotic syndrome
- Primary hyperaldosteronism (Conn’s syndrome) in patients awaiting surgery
What are the indications of eplerenone?
- LV dysfunction with evidence of HF after MI (adjunct)
- Chronic mild HF with LV systolic dysfunction (adjunct)
**unlike spironolactone, which has androgen antagonistic effects, eplerenone is NOT known to cause gynecomastia
What is the mechanism of action of potassium-sparing diuretics, amiloride and triamterene?
Acts on distal convoluted tubules in the kidney to inhibit reabsorption of sodium by ENaC channels, leading to sodium and water excretion and retention of potassium
What is the mechanism of action of aldosterone antagonists?
Inhibition of aldosterone at the mineralocorticoid receptors of the collecting duct (principal cells), thereby causing modest diuresis and natriuresis and inhibition of potassium and hydrogen ion secretion
What is the primary function of aldosterone in the body?
Increase Na and water retention in exchange for K excretion
What are the main side effects of potassium-sparing diuretics?
- Hypotension
- Urinary and GI symptoms
- Electrolyte disturbances (risk is low but should still be monitored, especially K)
What are the main contraindications to potassium-sparing diuretic use (including aldosterone antagonists)? (5)
- Addison’s disease (hyperkalemia)
- Anuria
- Severe renal impairment
- Hyperkalemia
- Co-prescription with aldosterone antagonists or potassium supplements
What are the long-term side effects associated with spironolactone use? (8)
- Gynecomastia (but NOT eplerenone)
- Hyperkalemia
- Decreased libido
- Erectile dysfunction
- Breast pain
- Menstrual irregularities
- Dehydration
- Cramping and muscle pain
**due to anti-androgen and anti-mineralocorticoid effects
Is spironolactone safe to use in pregnancy?
ONLY if benefits outweigh risks; risk of feminization of male fetus
Safe to use while breastfeeding
What (if any) monitoring should be used when patients are taking spironolactone?
Monitor plasma-potassium concentration (especially in patients with renal impairment due to risk of hyperkalemia)
Is spironolactone safe to use in renal impairment?
Avoid in acute renal insufficiency or severe impairment; may use in mild-moderate impairment but monitor plasma K closely for hyperkalemia
How often should plasma potassium levels be measured in patients with severe HF taking spironolactone?
in severe heart failure monitor potassium and creatinine:
- 1 week after initiation and after any dose increase,
- monthly for first 3 months,
- then every 3 months for 1 year,
- then every 6 months
Are potassium-sparing diuretics necessary in the routine treatment of HTN?
Not unless hypoalemia develops
What are the indications of mannitol?
- Cerebral edema
- Raised ICP
- Cystic fibrosis (adjunct)
What is the mechanism of action of mannitol?
Osmotic diuretic, promotes diuresis in the kidneys by increasing the concentration of filtrâtes in the kidney and blocking reabsorption of water by the tubules
What is the mechanism of action of acetazolamide?
A carbonic anhydrase inhibitor and weak diuretic (not often used for its diuretic effect; more commonly used for prophylaxis against mountain sickness)
By blocking renal carbonic anhydrase, it causes a build up of carbonic acid, leading to greater production of bicarbonate and loss of bicarb, Na, K, and water in the urine
(Also used in the treatment of glaucoma)
