Heart failure

Question 1

Loop Diuretics

Common indications

Answer 1

• For relief of breathlessness in acute pulmonary oedema in conjunction with oxygen and nitrates
• For symptomatic treatment of fluid overload in HF
• Symptomatic treatment of fluid overload in other oedematous states- H+R failure, where they may be given in combination with other diuretics

Question 2

Loop diuretics

MOA

Answer 2

• As their name suggests, loop diuretics act principally on the ascending limb of the loop of Henle, where inhibit Na+/K+/2Cl- Co-transporter
• This protein is responsible for transporting sodium and potassium and chloride ions from the tubular lumen into the epithelial cell
• Water then follows by osmosis. Inhibiting this process has a potent diuretic effect
• Also, loop diuretics have a direct effect on blood vessels, causing dilation of capacitance veins
• In acute HF, this reduces preload and improves contractile function of the overstretched heart muscles
• Indeed, this is probably the main benefit of loop diuretics in acute HF, as illustrated by the fact that the clinical response is usually evident before a diuresis is established

Question 3

Loop diuretics

Adverse effects

Answer 3

• Water losses due to diuresis can lead to dehydration and hypotension
• Inhibiting the Na/K/2Cl co-transporter increases urinary sodium, chloride and pottasium loss
• Indirectly also causes increased excretion Mg, Ca and H ions
• You can therefore associate loop diuretics with almost any low electrolyte state
• A similar Na/K/2Cl co-transporter is responsible for regulating endolymph composition in the inner ear
• At high doses, loop diuretics can affect this too, leading to hearing loss and tinnitus

Question 4

Loop diuretics

Warnings

Answer 4

• Loop diuretics are contraindicated in patients with hypovolaemia or dehydration
• They should be used with caution in patients at risk of hepatic encephalopathy
• Severe hypokalaemia and hyponatraemia
• Taken chronically, loop diuretics inhibit uric acid excretion and this can worsen gout

Question 5

Loop diuretics

Interactions

Answer 5

• Loop diuretics have the potential to affect drugs that are excreted by the kidneys
• For example, Lithium levels are increased due to reduced excretion
• Digoxin toxicity may also increase
• Increase ototoxicity and nephrotoxicity of aminoglycosides

Question 6

Loop diuretics

Monitoring

Answer 6

• For safety, periodic monitoring of serum sodium, pottasium and renal function is also advisable, particularly in the first few weeks of therapy

Question 7

ACE inhibitors

Common indications

Answer 7

• Hypertension- for the first or second-line treatment of hypertension
• Chronic HF
• Ischaemic heart disease
• Diabetic nephopathy and CKD with proteinuria

Question 8

ACE inhibitors

MOA

Answer 8

• ACE inhibitors block the action of the ACE to prevent conversion of angiotensin I => II
• Angiotensin II is a vasoconstrictor and stimulates aldosterone secretion
• Blocking its action reduces peripheral vascular resistance (afterload), which lowers BP
• It particularly dilates the efferent glomerular arteriole, which reduces intraglomerular pressure and slows the progression of CKD
• Reducing the aldosterone level promotes sodium and water excretion
• This can help to reduce venous return (pre-load), which has a beneficial effect in HF

Question 9

ACE inhibitors

Adverse effects

Answer 9

• Common side effects include hypotension (particular after the first dose), persistent dry cough (due to increased levels of bradykinin, which usually inactivated by ACE) and hyperkalaemia (because a lower aldosterone level promotes potassium retention)
• They can cause or worsen renal failure
• This is particularly relevant in patients with renal artery stenosis, who rely on the constriction of the efferent glomerular arteriole to maintain glomerular filtration
• If detected early, these adverse effects are usually reversible on stopping the drug
• Rare but important side effects of ACEI include angioedema and anaphylactoid reactions

Question 10

ACE inhibitors

Warnings

Answer 10

• ACEI should be avoided in patients with renal artery stenosis or acute kidney injury
• Pregnant and breastfeeding
• CKD, lower doses should be used and the effect on renal function monitored closely

Question 11

ACE inhibitors

Interactions

Answer 11

• Due to the risk of hyperkalaemia, avoid prescribing ACEI with other potassium-elevating drugs, including supplements and K-sparring diuretics
• Incombination with other diuretics (profound first dose hypotension)
• NSAID and ACEI increases the risk of renal failure

Question 12

ACE inhibitors

Communication

Answer 12

• Take the first dose before bed to reduce symptomatic hypotension
• Common side effects: Dry cough, dizzieness, allergic reactions
• Need blood test monitoring, explaining that ACEI can interfere with renal function and upset K balance
• Advise to avoid taking OTC NSAID

Question 13

ACE inhibitors

Monitoring

Answer 13

• Monitor efficacy for reduced symptoms of breathlessness in HF
• Check electrolyte and renal function before starting treatment
• Repeat 1-2 weeks into treatment and increasing dose
• Creatinine concentration should not rise by more than 30%
• eGFR should not fall by more than 25%
• K levels should not be above 6mmol/L

Question 14

Beta-Blockers

Common indications

Answer 14

1. Ischaemic heart disease- first line option to improve symptoms and prognosis associated with angina and acute coronary syndrome
2. Chronic HF- as a first line option to improve prognosis
3. Atrial fibrillation- As a first-line option to reduce the ventricular rate and in paroxysamal AF, to maintain sinus rhythm
4. Supraventricular tachycardia (SVT)- first-line option in patients without circulatory compromise
5. Hypertension

Question 15

Beta-Blockers

MOA

Answer 15

• Beta₁-adrenoreceptors are located mainly in the heart, whereas B2-adrenoreceptors are found mostly in the smooth muscle of blood vessels and the airways
• Beta-Blockers reduce the force of contraction and speed of conduction in the heart
• This relieves myocardial ischaemia by reducing cardiac work and oxygen demand, and increasing myocardial perfusion
• They improve prognosis in heart failure by protecting the heart from the effect of chronic sympathetic stimulation
• They slow the ventricular rate in AF mainly by prolonging the refractory period of the atrioventricular node
• In HTN, BB lower BP through a variety of means, one of which is by reducing renin secretion from the kidney, since this is mediated by B1-receptors

Question 16

Beta-Blockers

Adverse effects

Answer 16

• Beta-Blockers commonly cause fatigue, cold extremities, headache and GI disturbances
• They can cause sleep disturbances and nightmares as well as impotence in men

Question 17

Beta-Blockers

Warnings

Answer 17

• Asthma- BB can cause life-threatening bronchospasm and should be avoided
• The effect is mediated by blockade of B2-adrenoreceptors in the airways
• BB is usually safe in COPD, although it is prudent to choose a B1 selective receptor
• In HF, BB should be started at a low dose and slowly increased, as they initially impair cardiac function
• They should be avoided in patients with haemodynamic instability and are contraindicated in heart block
• BB generally require dosage reduction in significant hepatic failure

Question 18

Beta-Blockers

Interactions + monitoring

Answer 18

• BB must not be used with non-dihydropyridine calcium channel blockers
  
  • This combination can cause HF, bradycardia and asystole
• The best guide to dosage adjustment is the patient’s symptoms and HR should be around 60BPM

Question 19

Statins

Common indications

Answer 19

• Primary prevention of cardiovascular disease: to prevent cardiovascular events in people over 40 years of age with a 10-year cardiovascular risk >20%.
• Secondary prevention of cardiovascular disease: the first-line alongside lifestyle changes, to prevent further cardiovascular events in those who already have evidence of cardiovascular disease.
• Primary hyperlipidaemia: first-line, in conditions such as primary hypercholesterolaemia, mixed dyslipidaemia and familial hypercholesterolaemia.

Question 20

Statins

MOA

Answer 20

• Statins reduce serum cholesterol levels. They inhibit 3-hydroxy-3- methyl-glutaryl coenzyme A (HMG CoA) reductase, an enzyme involved in making cholesterol
• They decrease cholesterol production by the liver and increase the clearance of LDL-cholesterol from the blood, reducing LDL-cholesterol levels
• They also indirectly reduce triglycerides and slightly increase HDL-cholesterol levels. Through these effects, they slow the atherosclerotic process and may even reverse it

Question 21

Statins

Adverse effects

Answer 21

• Statins generally safe
• headache and GIT disturbances
• Myopathy and rhabdomyolysis
• Raise in liver enzymes

Question 22

Statins

Warnings

Answer 22

• Hepatic impairment- use with cautions
• Renal impairment- use with caution- renal excretion
• Pregnant/Breastfeeding- ChE essential for normal fetal development

Question 23

Statins

Interactions

Answer 23

• CYP P450 inhibitors (Amiodarone, diltiazem, macrolides) leads to accumulation of statin in body increasing risk of adverse effects
• Amlodipine- has a similar interaction though the mechanism is less clear. If taking the 2 together stop statin during acute antibiotic course (clarithromycin)

Question 24

Statins

Communication

Answer 24

• Should be taken in the evening, as there is some evidence that they have a greater effect when food intake is at its lowest
• Must seek medical attention if they experience muscle symptoms (pain or weakness)
• Ask for blood tests in 3 and 12 months
• Avoid grapefruit juice

Question 25

Statins

Monitoring

Answer 25

• Primary prevention of CVD- Blood test before treatment but does not need regular check-ups
• Secondary prevention-
• For safety check Lover enzymes at 3 and 12 months
• A rise in ALT up to three times the upper limit of normal may be acceptable, but above this should lead to discontinuation. The statin can be restarted at a lower dose when liver enzymes have returned to normal. You do not need to check creatine kinase routinely, but you should ask patients to report muscle symptoms

Question 26

Sacubitril

Indications + MOA

Answer 26

• Symptomatic chronic HF with reduced ejection fraction (in combo with Valsartan)
• Inhibiting neprilysin- increase cGMP, which results in vasodilation, natriuresis and diuresis, increased GFR and renal blood flow, inhibit renin and aldosterone release, Reduce sympathetic activity and antihypertrophic effect