3.2.1 Diuretics Flashcards
What medical conditions are diuretics useful for?
Chronic Heart Disease
Primary hypertension
Nephrotic syndrome- loop diuretic
CKD
Decompensated liver disease, ascites causes RAAS activation
What are some common adverse drug effects of diuretics?
Hypovolaemia and hypotension, lead to activation of RAAS, can lead to AKI
Electrolyte disturbance (Na+, K+, Mg2+, Ca2+)
Metabolic abnormalities
Anaphylaxis/ photo-sensitivty rash
What is the mechanism of action of thiazides? Give 2 examples of thiazides
Inhibit NaCl transporter
Reduced Na+Cl- into epithelium, water follows and is excreted
Bendroflumethiazide
Indapamide
What are the adverse effects of thiazides?
Hyperuricaemia- thiazides use same OAT transporter as uric acid, preventing excretion
Hyperglycaemia- decreases insulin sensitivity of cells
Erectile dysfunction- affects vasoconstriction
Increased LDL+TG
Hypercalcaemia- NaCa exchanger on basolateral membrane increases in activity due to lower concentration of Na+
Hyperkalaemia- Less Na+ arrives in the collecting duct, therefore less sodium enters through ENaC thus there is less K+ driven out of cells by RomK
When can you not give thiazides?
Addisons disease
Hypercalcaemia
Hyponatraemia
Refractory hypokalaemia
Hyperuricaemia/ gout
Important drug interactions for thiazides
Alcohol
Amlodipine
What is the mechanism of action of loop diuretics? Give 2 examples of loop diuretics
Inhibit NK2Cl transporter
Reduced Na+, K+ and Cl- into epithelium
Direct dilation of capacitance veins, reduces preload
Furosemide
Bumetanide
What do we use loop diuretics for?
Acute pulmonary oedema
Fluid overload in HF
Adjunct in nephrotic syndrome
What are some adverse effects of loop diuretics?
Dehydration
Hypotension
Hypokalaemia
Hyponatraemia
Hyperuricaemia- loops diuretics compete for same OAT transpoter as uric acid does (with chronic treatment)
Arrhythmias
Tinnitus- ototoxicity
Increased cholesterol and TG
Why can you get tinnitus with loop diuretics?
Loop diuretics are given intravenously, so the diuretic spreads to entire body
Inner ear has NaK2Cl channel, this channel is also targeted causing tinnitus
When can you not give loop diuretics?
Hypokalaemia
Hyponatraemia
Gout
Hepatic encephalopathy
Important drug interactions of loop diuretics
Aminoglycosides
Digoxin
Lithium
What is the mechanism of action of potassium-sparing drugs? Give an example
Block ENaC channels
Reduces Na+ reabsorption in DCT, reducing K+ excretion
Amiloride
When are potassium-sparing diuretics used?
Adjunct to loop diuretics in HF to limit loss of K+
What are some adverse effects of potassium sparing diuretics?
Hyperkalaemia
Potential arrhythmia
When can you not give potassium sparing diuretics?
Addison’s disease
Anuria
Hyperkalaemia
Important drug interactions of potassium sparing diuretics
Other K+ sparing drugs
ACEi
ARBs
How can potassium sparing drugs also act?
Mineralocorticoid receptor antagonists
Spironolactone
Eplerenone (Works in the same way as spironolactone and does not cause gynaecomastia, not used due to price)
What are the adverse effects of aldosterone receptor antagonists?
Gynaecomastia
Hyperkalaemia
Severe cutaneous adverse reactions
Why can aldosterone antagonists cause gynaecomastia?
Acts on androgen receptors
Androgens can be aromatised to oestrogen causing breast tissue to develop
Oestradiol is also displaced from sex hormone binding globulin
When can you not give aldosterone receptor antagonists?
Addison’s disease
Anuria
Hyperkalaemia
Important drug reactions of mineralocorticoid receptor antagonists
Alcohol
Amiloride
ACEi
ARBs
Amiloride vs spironolactone/eplerenone?
Amiloride blocks ENaC in colelcting ducts/ distal DCT on the apical side
Spironolactone/eplerenone block mineralocorticoid receptors where aldosterone binds preventing insertion of ENaC channels and NaKATPase, basolateral side
What is the mechanism of action of carbonic anhydrase inhibitors?
Inhibits carbnoic anhydrase
Carbonic acid not converted to H2O and CO2
H2O cannot be reabsorbed and less HCO3- reabsorbed
What can carbonic anhydrase inhibitors cause?
Loss of NaHCO3 leading to
Hypokalaemic metabolic acidosis
What is the mechanism of action of osmotic agents, mannitol?
Exert osmotic pressure in the lumen of the tubule
Water pulled down osmotic gradient into the tubule lumen and excreted in urine
Mannitol-manitee in the sea
What can mannitol cause?
Hypernatraemia, increased water loss, Na+ concentration increases
Reduced intracellular volume- hypotension
What is the mechanism of action of SGLT2 inhibitors?
Less Na+ and glucose absorbed together in PCT
Increased osmotic pressure in tubule, water follows
Increased NaCl delivery to macula densa, RAAS not activated, vasoconstriction of AA
What clinical findings may be present after using SGLT2 inhibitors?
What are ADH antagonists also known as?
Aquaretics
e.g. Tolvaptan and Lithium
What does tolvaptan do?
ADH antagonist
Diuretic but not natriuretic
Used to treat hyponatraemia and prevent cyst enlargement in APCKD
What does lithium do?
Mainly used to prevent episodes of mania but,
Inhibits ADH (unwated side effect)
Diuretic not natriuretic
What drinks cause diuresis?
Alcohol - inhibits ADH release
Caffeine- Increases GFR and decreases tubular Na+ reabsorption
Challenges for patients when delivering diuretics to the renal tubule
Gut oedema can prevent absorption of diuretic
Low albumin levels (due to liver issue potentially), less albumin available for binding
Reduced blood flow to kidney- heart issue
PCT cells must be able to transport diuretics across, in kidney disease may not be able to due to damage
How do we change dosing of diuretics for patients with heart failure and other diseases affecting diuretic delivery?
Increase the dose
What advice should we give to patients with hypertension?
Lifestyle-
Salt from diet has large effect
Other general lifestyle factors, e.g. smoking, alcohol etc…
How do we balance patients with hyperkalaemia and hypertension?
- Optimise intravascular volume status
- Hourly urine output measuring
- Check K+ on VBG 45-60 minutes after treatment
If hypovalaemic give 500ml bolus of 0.9% saline, if overloaded consider furosemide
