6.4.2 - Aldosterone Antagonists & Potassium Sparing Diuretics

Front 1

K-sparing diuretics
- Drugs in class

Back 1

1. Spirinolactone
2. Eplerenone
3. Amiloride
4. Triameterence (only available with HCTZ in hydrene)

Front 2

MOA

Back 2

Spirinolactone and eplerenone are aldosterone antagonists. They reduce Na and water retention, and increase potassium retention, in the distal tubule
Triamterene and amiloride block the sodium channels themselves, in the distal convuluted tubule

Front 3

Difference between amiloride and triamterene (MOA)

Back 3

Amiloride causes mg retention
Triamterene inhibits dihydrofolate reductase and may cause megaloblastic anemia

Front 4

Difference between spirinolactone and eplerenone
(a) MOA
(b) Clinical usefulness

Back 4

Spirinolactone has more ANTI-ANDROGENIC effects than eplerenone. Spirinolactone is more likely to cause SE such as gynaecomastia, menstrual abnormalities and sexual dysfunction. Spirinolactone can be used for hirsutism in postmenopausal females

Spirinolactone has more evidence; shown to reduce mortality and morbidity in HF patients on a loop and an ACEI
Eplerenone shown to reduce morbidity and mortality when used for HF secondary to MI when initiated 3-14 days after MI

Front 5

Indications

Back 5

Triamterene with HCTZ: HTN
Amiloride
- hypertension (with HCTZ)
- prevention of diuretic induced hypokalaemia
- oedema due to secondary hyperaldosteronism (HF, hepatic cirrhosis, nephrotic syndrome)
- primary hyperaldosteronism (not preferred)
Spirinolactone
- heart failure (without oedema)
- primary hyperaldosteronism
- hirsutism (spirinolactone)
- secondary hyperaldosteronism (e.g. cirrhosis, HF)
Eplerenone - just HF with MI

Front 6

K-sparring diuretics
- CI/Cautions
- RF/LF

Back 6

1. CI in hyperkalaemia (>5.5mmol/L or >5 with spirinolactone); Caution with drugs increasing K, elderly, and debilitated patients.
2. CI in RF/I
3. Avoid in LF (triamterene CI) - may precipitate RF and encephalopathy

Front 7

K-sparring diuretics
- pregnancy
- breast feeding

Back 7

Eplereonone - B3
Spirinolactone - B3 (avoid; may cause feminisation of male fetus); appears safe for breast feeding
Amiloride - C (electrolyte disturbance in fetus; avoid); appears safe for breast feeding

Front 8

K-sparring diuretics
- Adverse effects

Back 8

Common
- hyperkalaemia, hyponatremia,
- dizziness, muscle cramps

Infrequent
- orthostatic hypotension
- gynaecomastia, impotence (common with amiloride), menstrual irregularities, renal impairment

Front 9

Spirinolactone
- dose forms, brands
- doses for
(a) hirsutism
(b) HF
(c) oedema
(d) primary hyperaldosteronism

Back 9

25mg.100, 100mg.100 tab Aldactone, Spiractin

1. Hirsutism in females: 50-100mg d
2. Severe HF: 25mg d, increase to 50mg d if progression of HF occurs, decrease to 25mg every second day if hyperkalaemia
3. Oedema: start on 100mg d, maintain on 25-200mg d
4. Primary hyperaldosteronism: 50-200mg d

Front 10

Spirinolactone
- monitoring required

Back 10

- RF and K
In HF with interacting drugs: weekly for 1 month, monthly for 2 months, every 3 months

Front 11

Eplerenone
- dose forms, brands
- doses

Back 11

25mg.30, 50mg.30 tabs (Inspra)

Start on 25mg d, and increase within 4 weeks to 50mg d

Front 12

Inspra
- Monitoring required

Back 12

K, CrCl similar to spirinolactone

Front 13

Amiloride
- dose forms, brands, inc combos
- doses for
(a) Hypokalaemia prevention
(b) odemea
(c) primary hyperaldosteronism
(d) use of the combo in both HTN and oedema

Back 13

5mg.100 tab (Kaluril)
5mg/50mg tab with HCTZ (Amizide, Moduretic)

Prevention of hypokalaemia: 2.5-5mg d
Oedema: 5mg initally, then reduce
Primary hyperaldosteronism: 5-20mg d
In combo: 0.5 tab d for HTN, 1-2 d for oedema

Front 14

Kaluril
- should it be used with diuretics?

Back 14

Not routinely required; use only if K <3.5mmol/L

Front 15

Triameterene
- dose form, brand
- dose in both HTN abd oedema

Back 15

25mg/50mg.100 HCTZ/triamterene tabs (Hydrene)

HTN: 0.5-1 tab d
Oedema: start on 1 bd, max 2 bd

Front 16

K sparing diuretics
- DIs

Back 16

1. Potassium retention (cyclosporine, trimethoprim, NSAIDs)
2. NSAIDs - increase K and cause reduced RF; monitor K and SeCr; low dose aspirin is probably ok
3. Digoxin conc increased by spirinolactone
4. Eplerenone is a CYP3A4 substrate; Manufacturer CI use with potent inhibitors ketoconazole and itraconazole. Concentration also increased by amiodarone, diltiazem, verapamil, erythromycin, and fluconazole