Diuretics, Heart Failure and Hypertension

Question 1

Thiazides diuretics- mechanism?

Answer 1

Block NCC in DCT

Question 2

Amiloride- mechanism?

Answer 2

Block ENaC in late DCT/collecting duct

Question 3

Spironolactone- mechanism?

Answer 3

Inhibit aldosterone -> reduce expression of Na/K ATPase, ENaC, ROMK, -> reduce Na reabsorption/K secretion

Question 4

Diuretics- general ADRs?

Answer 4

Electrolyte disturbances, metabolic disturbances, rash/anaphylaxis, hypotension/hypovolaemia (-> AKI)

Question 5

Spironolactone- ADRs?

Answer 5

Hyperkalaemia, painful gynaecomastia

Question 6

Thiazide diuretics- ADRs?

Answer 6

Gout, erectile dysfunction

Question 7

Loop diuretics- mechanism?

Answer 7

Block NKCC2 in thick ascending limb

Question 8

Furosemide- ADRs?

Answer 8

Ototoxicity, hypokalaemia

Question 9

DDIs- aminoglycoside and loop diuretic?

Answer 9

Ototoxicity and nephrotoxicity

Question 10

DDI- ACE I and K+ sparing diuretic?

Answer 10

Hyperkalaemia!!

Question 11

DDI- beta blocker and thiazide diuretic?

Answer 11

Metabolic disturbance- increased urea, lipids, glucose

Question 12

ACE inhibitors- mechanism?

Answer 12

Inhibit ACE -> stop conversion of Ang I -> Ang II -> reduce SNS vasoconstriction, reduce bradykinin breakdown (increase vasodilation), reduce aldosterone (reduced salt and water uptake -> reduce blood volume) = decrease preload and afterload!

Question 13

ACE inhibitors- ADRs?

Answer 13

Dry cough, angio-oedema, hyperkalaemia, renal failure

Question 14

ARBs- mechanism?

Answer 14

Block Ang II receptors (AT1 receptors) -> reduced vasoconstriction and reduced aldosterone

Question 15

ARBs- ADRs?

Answer 15

Less than ACE I, renal failure, hyperkalaemia

Question 16

Calcium channel blockers e.g. amlodipine (dihydropyridine), mechanism?

Answer 16

Bind to L-type calcium channel and block calcium entry into cell -> vasodilation!

Question 17

Calcium blockers- (Dihydropyridine) ADRs

Answer 17

SNS activation-> flushing, hypertension, palpitations, headache, oedema

Question 18

Beta blockers- mechanism?

Answer 18

Block beta adrenoceptors -> slow heart rate, reduce cardiac output, inhibit renin release = lower blood pressure and cardiac workload

Question 19

Beta blockers- ADRs?

Answer 19

Reduced exercise capacity, bronchospasm (wary in asthmatics!), bradycardia, can cause heart failure,

Question 20

Alpha blockers (doxazosin) mechanism?

Answer 20

Block alpha 1 receptors -> vasodilation of vascular smooth muscle

Question 21

Alpha blockers- ADRs

Answer 21

Postural hypotension, dizziness, headache, oedema

Question 22

Hypertension- treatment steps?

Answer 22

1. ACE inhibitors (under 55) or calcium channel blocker (over 55 or black)
2. ACE inhibitor AND calcium channel blocker
3. Add thiazide diuretic
4. Add a beta blocker

Question 23

Heart failure- treatment steps?

Answer 23

1. ACE inhibitor AND beta blocker
2. ADD spironolactone OR ARB OR hydralazine and nitrate (if black)
3. Digoxin if severe and worsening
4. Implantable pacemaker/ defibrillator
5. Transplant!

Question 24

Heart failure- monitoring?

Answer 24

Functional capacity, cognitive function, fluid status, electrolytes, urea, creatinine, eGFR, heart rate and rhythm, blood pressure

Question 25

Nitrates mechanism?

Answer 25

NO activates guanylate cyclase -> increases cGMP -> vascular smooth muscle relaxation (VENOdilation) -> decrease preload