heart failure

• how is heart failure diagnosed?

  here

  
• what is heart failure?

  • Reduced cardiac output – everything is relative
  • use the NYHA functional classification
  • AKA chronic or congestive heart failure (CHF)
• what signs/ symptoms can be seen in left sided heart failure?

  •Dyspnoea•Orthopnoea: dyspnoea  on lying down

  •Paroxysmal nocturnal  dyspnoea

  •Pulmonary congestion  and oedema (crackles)

  •Exercise intolerance
• what signs/ symptoms can be seen in right sided heart failure?

  •Oedematous swelling of feet,  ankles, legs

  •Hepatomegaly: enlarged,  palpable, tender liver (cf nutmegs*)

  •Ascites: ↑↑ abdominal fluid

  •Excessive nocturnal urination

  •↑ jugular venous pressure

  •Exercise intolerance
• can right and left sided heart failure happen together?

  • common for left and right to co-exist = BIVENTRICULAR FAILURE
• what is the vicious cycle in heart failure? which drugs can be used for a patient with heart failure?

  here

  
• when treating patients with heart failure the concept that the heart is failing already is key in pharmaceutical treatment which drug is prescribed that actually lowers the CO of the heart?

  beta blockers -> review this once done flash card
• which drugs are prescribed in the treatment of heart failure? which one on the list is more prescribed in hypertension?

  •ACEI (-pril): see hypertension lectures

  •ARB (-sartan): see hypertension lectures

  •β blockers (BB) (-lol): see hypertension lectures

  •Diuretics: this lecture

  •SGLT2 inhibitors (-gliflozin): this lecture

  •Neprilysin inhibitors (-tril): this lecture

  •Cardiac glycosides: this lecture (ANTI-DYSRHYTHMIC)

  •Ivabradine: see angina lecture

  •Vasodilators: see angina lecture

  •Calcium-channel blockers: see hypertension lectures –

  mostly NOT for CHF
• how is CHF managed according to NICE guidelines?

  here

  
• which type of diuretics is not used anymore?

  mercurials and carbonic anhydrase inhibitors
• which diuretic drugs are currently used in CHF

  • thiazides
  • potassium-sparing diuretics (rarely used alone)
  • loop diuretics
• which diuretic in heart failure is normally not used alone in CHF treatment?

  Potassium-sparing diuretics
• Mannitol is not used in chronic hypertension and CHF, what is it used for in an acute setting?

  when there is a rapid loss of fluid needed like cerebral oedema

  
• why types of drug is dapagliflozin and what is it's mechanism of action?

  here

  decreased workload due to decreased fluid in the CVS system -> heart has to work less, improve symptoms of heart failure

  
• outline the MOA of dapagliflozin

  here

  
• which diuretic affects the thick ascending loop of henle?

  Loop diuretics

  
• which diuretic affects the which diuretics affect the beginning of the nephron?

  • osmotic diuretics
  • CA inhibitors
  • SGLT2 inhibitors

  
• which diuretics affect the end of the nephron?

  • thiazides
  • K+-sparing

  
• what type of drug is sacubitril and what is its mechanism of action in heart failure?

  sacubitril -> prodrug, active metabolite -> sacubatrilat

  cleaves/degrades ANP, BNP and AT-II

  use -> CHF, always use with ARB to counter increased AT-II, NEVER use with ACEi to avoid increased bradykinin (angioedema risk)

  
• Sacubatril is often prescribed with valsartan explain why?

  here

  
• Sacubatril is often prescribed with valsartan (an Ang II receptor bolcker), explain the MOA of valsartan

  here

  
• sacubitril works by enhancing the effects of ANP and BNP, explain how this helps with heart failure


  here

  
• what is the mechanism of action for digoxin?


  here

  
• what is happening with the ions in the cardiac myocytes in digoxin?

  here

  
• what is happening with the ions in the cardiac myocytes in digoxin?

  here

  
• how would you manage heart failure?

  here

  
• Acetazolamide is a CAI, outline the mechanism of action for Aceetazolamide

  Acetazolamide blocks CA -> affects the H2CO3 levels inside the cell -> decreased H+ from the H2CO3 to dissociate into H+ -> decreased Na/H antiporter activity -> less sodium reabsorption -> see picture

  
• Hydrochlorothiazide is a thiazide diuretic, explain its mechanism of action


  inhibit symporter

  •↓Na⁺ reabsorption in DCT → ↑urine flow (~3 ml.min⁻¹)

  •Mild diuretic action

  •Some loss of HCO₃⁻ → alkaline urine/metabolic acidosis, BUT…

  •↑K⁺ loss → hypokalaemia & ↑H⁺ loss → mild metabolic alkalosis

  •Secreted by OATs* into PCT → ↑concentration in tubule lumen

  •↓uric acid secretion (competes for OATs) → uricaemia → ↑risk of gout

  
• outline the mechanism of action of furosemide (loop diuretic)

  NKCC2 inhibitor

  •↓Na⁺ reabsorption in thick ascending Loop of Henle → ↑urine flow (~8 ml.min⁻¹)

  •Potent diuretic action (up to 15-25% of filtered load)

  •↑↑K⁺ loss → hypokalaemia (↑H⁺ loss → metabolic alkalosis)

  •Secreted by OATs in PCT → ↑↑ concentration in tubules

  •↓uric acid secretion (competes for OATs) → uricaemia → ↑risk of gout

  
• outline the mechanism of action for spironolactone


  here

  
• outline the MOA of amiloride

  here

  
• which diuretics cause hypokalemia and which cause hyperkalemia?

  hypo -> loop, thiazide, CAI

  hyper -> MRA like spironolactone and non-MRA like amiloride
• where are the channels that K+ sparing diuretics act on in the DCT epithelial cells?


  here

  
• which two K+ sparing drugs in the lecture

  MRA -> spironolactone

  non-MRA -> amiloride
• 2 non potassium sparing diuretics have a weak effect and one has a potent effect, which is which?

  weak diuretic action -> acetazolamide (CAI), hydrochlorothiazide (thiazide)

  potent diuretic action -> furosemide (loop)
• which three diuretics can be used to treat HT, oedema and heart failure?

  furosemide

  spironolactone

  amiloride
• why do all diuretics except K+-sparing diuretics cause hypokalemia?

  •In the late DCT, most Na⁺ has already been reabsorbed

  •Hence, K⁺-sparing diuretics are weak

  •Reabsorption of remaining tubular  Na⁺ used to regulate ECF

  •As Na⁺ is reabsorbed through ENaC, K⁺ is lost through ROMK

  •ALL diuretics (except K⁺-sparing)  increase delivery of Na⁺ to DCT

  •This is why they ALL increase K⁺ loss