PHARM: Diuretics, HTN, CHF

Question 1

loop diuretics
- MOA
- indications
- A/Es
- e.g.

Answer 1

• block Na/K/Cl pump to inhibit Na+/H2O reabsorption in thick ascending loop of Henle
• indications: HTN, HFrEF, oedema
• A/Es: hypotension, hypokalaemia (non-K+ sparing = increased digoxin toxicity + arrhythmia), hypovolaemia, hearing loss, hypocalcaemia, hypomagnesaemia, hyperuricaemia
• e.g. furosemide (end in -ide)

Question 2

thiazide diuretics
- MOA
- indications
- A/Es
- C/I

Answer 2

• inhibits NaCl pump = decreased Na+/H2O reabsorption @ DCT (less potent than loop)
• indications: milder HTN (1st line), HFrEF, oedema
• A/Es: hypotension (decreased CO), hypokalaemia (non-K+ sparing = increased digoxin toxicity + arrhythmia), hypercalcaemia, hyperuricaemia, hypomagnesaemia, hyperglycaemia, hypercholesterolaemia
• C/I: pregnancy

Question 3

aldosterone antagonists
- MOA
- indications
- A/Es
- e.g.

Answer 3

• inhibits action of aldosterone on mineralocorticoid receptor = decreased expression of Na+/K+ ATPase pump in basolateral membrane @ DCT/CD = increased Na+/H2O excretion (weak diuretic)
• also blocks the ECM deposition function of aldosterone which can prevent cardiac fibrosis
• indications: HTN, HFrEF, used with loop/thiazide diuretics to prevent hypokalaemia, hyperaldosteronism
• A/Es: hyperkalaemia (K+ sparing - arrhythmia), gynaecomastia (androgen inhibitor)
• e.g. spironolactone (end in -one)

Question 4

Na+ channel blockers (renal)
- MOA
- indications
- A/Es
- e.g.

Answer 4

• MOA: inhibits Na+ channels in DCT = K+ sparing diuretic
• indications: HTN, aldosteronism, commonly used w/ thiazides/loops to prevent hypokalaemia
• A/Es: hyperkalaemia (K+ sparing - arrhythmia)
• e.g. amiloride

Question 5

osmotic diuretics
- MOA
- indication
- e.g.

Answer 5

• decreases Na+/H2O reabsorption in whole nephron
• LOCALISED oedema (e.g. glaucoma, increased intracranial pressure), NOT for generalised oedema b/c not enough Na+ excreted
• e.g. mannitol

Question 6

triple whammy medication

Answer 6

• RAAS inhibitor (ACE inhibitor/ARB): cause dilation of efferent arteriole
• NSAID: cause constriction of afferent arteriole
• diuretic: causes volume depletion = decreased renal perfusion
• this combo causes decreased hence GFR = potential for renal failure in elderly/high risk Pts

Question 7

4 main drug classes for hypertension

Answer 7

• A = ACE inhibitors + ARBs
• B = beta blockers
• C = DHP Ca2+ channel blockers
• D = diuretics (thiazides, loop, K+ sparing)

Question 8

4 main drug classes for heart failure

Answer 8

• A = ACE inhibitors + ARBs
• B = beta blockers
• C = contractility increasers (digoxin, dobutamine - B1 agonist)
• D = diuretics

Question 9

ACE inhibitors
- MOA
- indications

Answer 9

• end in -pril
• prevents conversion of angiotensin I to II = vasodilation and decreased aldosterone = increased Na+/H2O excretion
• indications: HTN (esp. w/ diabetes, CKD), heart failure

Question 10

MOA and indications of angiotensin receptor blockers (ARBs)
- what suffix do they end in?

Answer 10

• end in -sartan
• antagonists @ AT1 receptors = inhibit USE of angiotensin II = vasodilation and decreased aldosterone = increased salt/water excretion
• indications: HTN, heart failure with renal issues (used when Pt is intolerant to ACE inhibitors)

Question 11

adverse effects and contraindication of ACE inhibitors and ARBs

Answer 11

• A/Es: dry cough (ACE inhibitor only - due to increased bradykinin), hypotension, hyperkalaemia, rash, itch, angioedema
• C/I: pregnancy

Question 12

vasopeptidase inhibitors MOA and indications

Answer 12

• inhibits AT1 receptor and NEP (enzyme which breaks down natriuretic peptides) = vasodilation and increased Na+/H2O excretion = decreased BP
• indications: HTN, FHrEF

Question 13

MOA and indications of B blockers

Answer 13

• blocks B1 receptors = decreased rate (-ve chronotrope) and force of contraction (-ve inotrope)
• indications: HTN (decreases BP), HFrEF, angina (decreases O2 consumption), tachyarrhythmias (decreased force of contraction)

Question 14

adverse effects and contraindication of B blockers

Answer 14

• A/Es: cold extremities, bradycardia, bronchoconstriction, fatigue
• contraindicated in asthma, UNSTABLE heart failure and with class IV anti-arrhythmics (non-DHP Ca2+ channel blockers)

Question 15

digoxin MOA and indications

Answer 15

• binds to K to inhibit Na/K pump = indirectly increases intracellular calcium = increased contractility of heart (+ve inotrope) but decreased rate (-ve chronotrope)
• indications: HFrEF + arrythmias (last resort)

Question 16

adverse effects and contraindications of digoxin

Answer 16

• A/Es: arrhythmia, GIT, visual disturbances, hallucinations
• contraindications: hypokalaemia (e.g. thiazides + loop diuretics) > causes less Na/K pump competition = increased toxicity. also C/I in hypercalcaemia > arrhythmias

Question 17

A/Es and C/Is of dobutamine

Answer 17

• A/Es: hypotension, tachyarrhythmias, nausea
• C/I: VF, tachyarrhythmia

Question 18

DHP Ca2+ channel blockers MOA + indications

Answer 18

• MOA: inhibit L-type Ca2+ channels in blood vessels = vasodilation = decreased afterload = decreased BP (for HTN) and decreased O2 consumption (for angina)
• indications: HTN, angina (stable + vasospastic)

Question 19

adverse effects + contraindications of DHP Ca2+ channel blockers

Answer 19

• A/Es: oedema, headache, flushing, dizziness, nausea, hypotension, tachycardia, pedal oedema
• C/Is: HFrEF, B blockers

Question 20

endothelin

Answer 20

• both a vasoconstrictor (ETA receptor) and vasodilator (ETB receptor - releases NO and PGI2)
• vasoconstriction is dominant

Question 21

endothelin receptor antagonists
- indication
- interactions
- 2 e.g.s

Answer 21

• vasodilator: used in pulmonary HTN
• interacts with nitrovasodilators
• bosentan (non-selective = ETA and ETB antagonist)
• ambrisentan (selective = ETA antagonist)

Question 22

2 drug classes for pulmonary HTN

Answer 22

• endothelin blockers
• inhaled or continuous IV prostacyclins e.g. epoprostenol
• PDE5 inhibitors

Question 23

PDE5 inhibitors

Answer 23

• MOA: prevents breakdown of cGMP = smooth muscle relaxation = pulmonary vasodilation
• indications: pulmonary HTN
• C/I: with nitrovasodilators
• e.g. sildenafil

Question 24

non-DHP Ca2+ channel blockers
- MOA
- indications
- C/Is
- A/Es

Answer 24

• MOA: blocks L-type Ca2+ channels in nodal tissue = decreased conduction and contractility of heart
• indications: HTN, tachyarrhythmias, IHD
• C/Is: B blockers, HFrEF, bradyarrhythmias
• A/Es: hypotension, constipation, bradycardia

Question 25

which anti-hypertensive agents are preferred in diabetes?

Answer 25

- ACE inhibitors or ARBs (renal protection) - thiazide diuretics or B-blockers can worsen glucose control

Question 26

methyldopa - MOA - indication - A/Es

Answer 26

- a2 agonist = decreased sympathetic activity - indication: HTN during pregnancy - A/Es: dry mouth etc