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Clinical Pharmacology > 3.2.1 Diuretics > Flashcards

3.2.1 Diuretics Flashcards

1
Q

What medical conditions are diuretics useful for?

A

Chronic Heart Disease
Primary hypertension
Nephrotic syndrome- loop diuretic
CKD
Decompensated liver disease, ascites causes RAAS activation

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2
Q

What are some common adverse drug effects of diuretics?

A

Hypovolaemia and hypotension, lead to activation of RAAS, can lead to AKI

Electrolyte disturbance (Na+, K+, Mg2+, Ca2+)

Metabolic abnormalities

Anaphylaxis/ photo-sensitivty rash

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3
Q

What is the mechanism of action of thiazides? Give 2 examples of thiazides

A

Inhibit NaCl transporter

Reduced Na+Cl- into epithelium, water follows and is excreted

Bendroflumethiazide
Indapamide

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4
Q

What are the adverse effects of thiazides?

A

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

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5
Q

When can you not give thiazides?

A

Addisons disease
Hypercalcaemia
Hyponatraemia
Refractory hypokalaemia
Hyperuricaemia/ gout

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6
Q

Important drug interactions for thiazides

A

Alcohol
Amlodipine

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7
Q

What is the mechanism of action of loop diuretics? Give 2 examples of loop diuretics

A

Inhibit NK2Cl transporter

Reduced Na+, K+ and Cl- into epithelium

Direct dilation of capacitance veins, reduces preload

Furosemide
Bumetanide

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8
Q

What do we use loop diuretics for?

A

Acute pulmonary oedema
Fluid overload in HF
Adjunct in nephrotic syndrome

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9
Q

What are some adverse effects of loop diuretics?

A

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

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10
Q

Why can you get tinnitus with loop diuretics?

A

Loop diuretics are given intravenously, so the diuretic spreads to entire body

Inner ear has NaK2Cl channel, this channel is also targeted causing tinnitus

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11
Q

When can you not give loop diuretics?

A

Hypokalaemia
Hyponatraemia
Gout
Hepatic encephalopathy

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12
Q

Important drug interactions of loop diuretics

A

Aminoglycosides
Digoxin
Lithium

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13
Q

What is the mechanism of action of potassium-sparing drugs? Give an example

A

Block ENaC channels

Reduces Na+ reabsorption in DCT, reducing K+ excretion

Amiloride

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14
Q

When are potassium-sparing diuretics used?

A

Adjunct to loop diuretics in HF to limit loss of K+

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15
Q

What are some adverse effects of potassium sparing diuretics?

A

Hyperkalaemia
Potential arrhythmia

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16
Q

When can you not give potassium sparing diuretics?

A

Addison’s disease
Anuria
Hyperkalaemia

17
Q

Important drug interactions of potassium sparing diuretics

A

Other K+ sparing drugs
ACEi
ARBs

18
Q

How can potassium sparing drugs also act?

A

Mineralocorticoid receptor antagonists

Spironolactone
Eplerenone (Works in the same way as spironolactone and does not cause gynaecomastia, not used due to price)

19
Q

What are the adverse effects of aldosterone receptor antagonists?

A

Gynaecomastia
Hyperkalaemia
Severe cutaneous adverse reactions

20
Q

Why can aldosterone antagonists cause gynaecomastia?

A

Acts on androgen receptors

Androgens can be aromatised to oestrogen causing breast tissue to develop

Oestradiol is also displaced from sex hormone binding globulin

21
Q

When can you not give aldosterone receptor antagonists?

A

Addison’s disease
Anuria
Hyperkalaemia

22
Q

Important drug reactions of mineralocorticoid receptor antagonists

A

Alcohol
Amiloride
ACEi
ARBs

23
Q

Amiloride vs spironolactone/eplerenone?

A

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

24
Q

What is the mechanism of action of carbonic anhydrase inhibitors?

A

Inhibits carbnoic anhydrase

Carbonic acid not converted to H2O and CO2

H2O cannot be reabsorbed and less HCO3- reabsorbed

25
Q

What can carbonic anhydrase inhibitors cause?

A

Loss of NaHCO3 leading to
Hypokalaemic metabolic acidosis

26
Q

What is the mechanism of action of osmotic agents, mannitol?

A

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

27
Q

What can mannitol cause?

A

Hypernatraemia, increased water loss, Na+ concentration increases

Reduced intracellular volume- hypotension

28
Q

What is the mechanism of action of SGLT2 inhibitors?

A

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

29
Q

What clinical findings may be present after using SGLT2 inhibitors?

A
30
Q

What are ADH antagonists also known as?

A

Aquaretics

e.g. Tolvaptan and Lithium

31
Q

What does tolvaptan do?

A

ADH antagonist

Diuretic but not natriuretic

Used to treat hyponatraemia and prevent cyst enlargement in APCKD

32
Q

What does lithium do?

A

Mainly used to prevent episodes of mania but,

Inhibits ADH (unwated side effect)

Diuretic not natriuretic

33
Q

What drinks cause diuresis?

A

Alcohol - inhibits ADH release

Caffeine- Increases GFR and decreases tubular Na+ reabsorption

34
Q

Challenges for patients when delivering diuretics to the renal tubule

A

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

35
Q

How do we change dosing of diuretics for patients with heart failure and other diseases affecting diuretic delivery?

A

Increase the dose

36
Q

What advice should we give to patients with hypertension?

A

Lifestyle-

Salt from diet has large effect

Other general lifestyle factors, e.g. smoking, alcohol etc…

37
Q

How do we balance patients with hyperkalaemia and hypertension?

A
  • 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

Clinical Pharmacology (45 decks)

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