BNF Chapter 2: The Cardiovascular System Flashcards
Which thiazide diurectic is first-line for hypertension?
Bendroflumethiazide 2.5mg
Why are thiazide-like diuretics second-line when compared to thiazide diurectics?
More expensive
What loop diuretic is first-line for hypertension?
Furosemide
What is the ONLY indication for spironolactone?
Heart failure (it is first-line for heart failure with reduced ejection fraction)
What type of diuretic is spironolactone?
Potassium-sparing
Which diuretics can cause a fall in potassium during the first few weeks of treatment?
Thiazide
Loop
What three types of drugs should not be combined when treating heart failure due to potentially fatal hyperkalaemia?
ACE inhibitor
ARB
Mineralocorticoid receptor antagonist (spironolactone)
What three drugs are anti-arrythmics, and when would they be used?
Amiodarone- initiated with a loading dose, require monitoring up to 12-months after discontinuing
Dronedarone- maintaining sinus rhythm after successful cardioversion
Mexiletine for life-threatening ventricular arrhythmias
What are some examples of beta blockers?
Atenolol
Bisoprolol
Carvedilol
Labetalol
Target doses of beta-blockers in heart failure (if tolerated):
- Bisoprolol- 10mg OD
-Carvedilol- 25-50mg BD
What type of drug is doxazosin, and when would it be used for hypertension and heart failure?
Alpha-adrenoceptor blocking drug, as a fourth line add on therapy
ACEi (Ramipril, Lisinopril)
- Not for use in pregnancy
-Black/african american patients should use an ARB over an ACEi as first-line for hypertension
-Perindopril can only be used on advice from a stroke physician for secondary stroke or cardiovascular incident prevention
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ARBs (Losartan, Candesartan)
-Losartan is the first-choice ARB for all indications except heart failure
- Candesartan is the first-choice ARB for heart failure.
-Not recommended in pregnancy
-Should be reserved for patients that are completely intolerant to ACEis.
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When would losartan be a first-choice ARB as a medication?
For all cardiovascular indications except HF
When would candesartan be a first choice ARB?
HF
When would sacubitril/valsartan be used?
For treating symptomatic chronic heart failure with reduced ejection fraction
REMEMBER: The use of ACEis and ARBs in combination is NOT recommended- they are both renin-angiotensin hormone system blocking agents.
In HF, a few patients may medically require both an ACEi and ARB; candesartan and valsartan are licensed as add on therapy to ACEi for symptomatic heart failure if needed.
When would the use of an ACEi and an ARB in combination be licensed?
Symptomatic heart failure (only if necessary)
Target Doses of ACEis and ARBs in HEART FAILURE (if tolerated)
Lisinopril: 20-35mg OD
Ramipril: 10mg OD or 5mg BD
Enalapril: 10-20mg BD
Losartan: 150mg OD
Candesartan: 32mg OD
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SGLT2i in HF
- Includes dapagliflozin and empagliflozin
- Add on treatment option for HF- not to be used for T1 diabetic patients
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NITRATES FOR ANGINA
- GTN spray/tabs
-Isosorbide mononitrate
-Initiated at a low dose, gradually increase
-Isosorbide mononitrate- BD regimen (OD preparations not cost-effective), second dose after 8hr rather than 12hr to allow a nitrate-free period (avoids tolerance developing)
Why should the second daily dose of isosorbide mononitrate be taken 8hr after the first?
Allows for a nitrate-free period to prevent tolerance from developing
What are some examples of CCBs?
Amlodipine
Diltiazam
Nifedipine
Verapamil
Why should verapamil not be prescribed to patients taking beta-blockers?
Together they may precipitate profound bradycardia or hypotension
What are the two types of oral anti-coagulants?
Non-vitamin K antagonist oral anti-coagulant (NOAC)
Vitamin K antagonist (warfarin)
What are some examples of NOACs?
Edoxaban
Rivaroxaban
Apixaban
Dabigatran
What is the first-line NOAC for AF patients when anticoagulation is necessary?
Edoxaban
NOACs
-Not recommended for patients who have antiphospholipid syndrome
-Interacts with erythromycin and clarithromycin potentially
Warfarin- initiated with a loading dose
Which oral
anticoagulant is first choice in breastfeeding women?
Warfarin
What are some examples of antiplatelet agents?
Aspirin 75mg disp
Clopidogrel 75mg
Prasugrel
Ticagrelor
What is the recommended first-choice antiplatelet therapy for the secondary prevention of CVD?
Aspirin (aspirin and clopidogrel are NOT recommended for primary prevention of CV events)
Why should enteric coated aspirin not be routinely used?
No evidence to suggest that EC aspirin has a lower DI bleed risk than dispersible, also is more expensive
What three things can you do if a patient experiences dyspepsia whilst on low dose aspirin?
- Take aspirin with food
-Reduce dose to the minimum effective dose
-Conisder co-prescribing antacid or low dose PPI
When would clopidogrel be recommended as the first choice antiplatelet therapy?
In patients who have had an ischaemic stroke, TIA or have peripheral arterial disease.
Which PPIs are preferred if given alongisde clopidogrel?
Lanzoprazole or pantoprazole
What can tranexamic acid 500mg tablets be used to treat?
Menorrhagia
What statin can be used in patients with swallowing difficulties?
Atorvastatin chewable tablets
When may rosuvastatin be used as a second-line to atorvastatin?
If a patient has a complete intolerance to atorvastatin or a partial tolerance to other statins but is not achieving target lipid reduction
When would ezetimibe be a treatment option for cholesterol reduction?
When a patient is truly intolerant to statins
Pharmacological treatment of angina
- Short-acting nitrate (e.g. GTN) to prevent and treat episodes
1st line: either a beta-blocker (e.g. atenolol 100mg OD) or CCB (diltiazam or verapamil 80-120mg TDS)
2nd line: combination of the previous two
3rd line: Isosorbide mononitrate with asymmetrical dosing.
Pharmacological treatment of angina
- Short-acting nitrate (e.g. GTN) to prevent and treat episodes
1st line: either a beta-blocker (e.g. atenolol) or CCB (diltiazam or verapamil)- decide which based on pt preference, comorbidities and contraindications.
2nd line: combination of the previous two
3rd line: Isosorbide mononitrate with asymmetrical dosing.
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Why are rate-limiting CCBs such as diltiazam and verapamil preferred to a dihydropyridine CCB (e.g. amlodipine) when treating angina using monotherapy?
RL CCBs have the additional act of decreasing myocardial contractility and HR
Dihydropyridine CCBs can sometimes cause reflex tachycardia, which can worsen angina symptoms
COMBINATION THERAPY:
-Pt on a beta-blocker: prescribe dihydropyridine CCB such as amlodipine
-Pt not taking a beta-blocker: prescribe a rate-limiting CCB such as verapamil or diltiazam.
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Blood Pressure Targets:
Under 80= below 140/90
Over 80= below 150/90
Type 1 diabetics with hypertension with CKD and ACR (albumin:creatinine ratio) below 70mg/mmol: below 140/90
^^^ but with ACR above 70: below 130/80
T1 diabetic aged 80 or over: below 150/90
xx
What is the first-choice medication type to treat a diabetic patient that has just been diagnosed with hypertension?
An ACEi or ARB
What would be added after an ACEi/ARB if BP was still unsatisfactory (T2 diabetic patient)?
Thiazide-like diuretic (would add a CCB if this was still ineffective)
What would be the first-line antihypertensive treatment for someone under 55 that was not black african?
ACEi or ARB (would then progress the same as if the pt was type 2 diabetic)
What would be the first line antihypertensive for a patient over 55 or a black african patient?
CCB
For a patient over 55 or black african, what would be the next step if a CCB did not work?
Add in an ACEi or ARB or Thiazide-like diuretic
Hypertension treatment in patients with CKD
Diabetes:
-ACR >3mg/mmol with or without hypertension or
CKD stage1 = Offer ACEi or ARB
-Type 2 diabetes and ACR >30 mg/mmol = offer an SGLT2 inhibitor, in addition to the ACEi or ARB
-Type 2 diabetes and ACR >3 mg/mmol
(NICE NG28)= same as above
Non-diabetic:
-Hypertension and ACR <30mg/mmol = offer choice of antihypertensive treatment according to NICE
Hypertension and ACR ≥30mg/mmol1= offer ACEi or ARB
Summary- treat with ACEi first and move to ARB if the ACEi is not tolerated. Must titrate the drug to the maximum tolerated therapeutic dose before adding a second-line agent.
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Which CCBs can potentially cause ankle swelling (oedema)?
Dihydropyridine CCBs, such as amlodipine and felodipine
Antiplatelet therapy for the prevention of occlusive vascular events
Had an ischaemic stroke/TIA: Clopidogrel —> Aspirin + Dipyridamole MR (if one of these two is CI or not tolerated then just use the other one by itself)
Had an MI: Aspirin —> Clopidogrel
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Which antiplatelet agent should be used first-line following a stroke or TIA?
Clopidogrel
Which antiplatelet agent should be used first-line following a heart attack?
Aspirin
When is the long-term use of low-dose aspirin recommended?
In patients with established CVD (secondary prevention)
When is the long-term use of low-dose aspirin recommended?
In patients with established CVD (secondary prevention)
What is clopidogrel used for?
Prevention of atherothrombotic events in patients with a history of symptomatic ischaemic disease, e.g. ischaemic stroke
Can also be used in combination with low-dose aspirin for the prevention of atherothombotic and thromboembolic events in patients with AF, and for whom warfarin is unsuitable
Antiplatelets for Secondary CVD Prevention
-Antiplatelet treatment for secondary CVD prevention should be offered to people with ACS, angina, AF, peripheral arterial disease. Also to people following a stroke or TIA, MI or stent implantation.
-Angina- Aspirin 75mg, clopidogrel 75mg is aspirin unsuitable
-AF- Aspirin 75mg daily plus clopidogrel 75mg daily (dual antiplatelet therapy)- usually anticoagulants are used (apixaban, edoxaban, etc) BUT ANTIPLATELETS CAN BE USED IN PATIENTS WHO DO NOT WANT TO TAKE ANTICOAGULANTS.
PCI in patients with stable coronary artery disease- DAPT of aspirin+clopidgrel
-ACS which is medically managed OR PCI for people with ACS OR ACS patients undergoing coronary artery bypass grafting- aspirin 75mg daily plus ticagrelor 90mg BD for 12 months
-Stroke or TIA- clopidogrel 75mg daily, or MR dipyridamole 200mg BD with aspirin 75mg if clopidogrel is unsuitable.
What is acute coronary syndrome (ACS)?
Encompasses a spectrum of conditions such as MI with or without ST-segment elevation (STEMI or NSTEMI), and unstable angina. Results from the formation of a thrombus on an atheromatous plaque in a coronary artery. Definitive diagnosis is based on clinical presentation, ECG changes and measurement of biochemical caridac markers.
What usually causes a STEMI?
A complete and persistent blockage of an artery resulting in myocardial necrosis with ST-segment elevation seen on the ECG.
What usually causes an NSTEMI and unstable agina?
A partial or intermittent blockage of the artery, usually resulting in myocardial necrosis in NSTEMI but not in unstable angina.
Non-Drug Treatment of ACS
-Revascularisation procedures such as percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) are often appropriate, alongside drug treatment, for patients with an ACS. The decision regarding choice of these management options depends on multiple factors such as the type of ACS, time since symptom onset, the patient’s clinical condition, comorbidities, and their formally-assessed risk of future cardiovascular events
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Initial ACS Management
-Support and pain relief (GTN, morphine), and prevention of progression of the cardiac injury.
-Aspirin loading dose ASAP
-Closely monitor for _, and insulin administered if BG is above 11mmol.litre.
Hyperglycaemia
STEMI Management
-Aim is to restore cornonary blood flow asap
-Coronary reperfusion therapy (primary PCI or fibrinolysis) should be deliverd asap. Primary PCI is preferred for most patients.
-In addition to aspirin, most patients should be offered a second antiplatelet (prasugrel, ticagrelor, clopidogrel)- depends on planned intervention and bleed risk. Prasugrel preferred for most patients undergoing a primary PCI.
-Fibrinolysis will require patients to receive an antithrombin agent at the same time.
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What are the two coronary reperfusion therapy options for a STEMI?
Primary PCI
Fibrinolysis
NSTEMI and Unstable Angina Management
-May be managed with reperfusion therapy, similar to STEMI management
-Should be offered a second antiplatelet agent in addition to aspirin, choice is dependent on planned intervention.
-Antithrombin therapy with fondaparinux should also be offered, heparin used in patients with significant _ impairment.
Renal
Secondary Prevention of Cardiovascular Events
-Offer all patients that have had an ACS a cardiac rehabilitation programme- lifestyle advice, stress management ect.
-Secondary prevention should involve an ACE inhibitor, a beta-blocker, dual antiplatelet therapy and a statin.
-ACE inhibitor should be started asap and continued indefinitely, an ARB can be used if they are intolerance to the ACEi.
-Beta-blocker started asap and continued indefinitely for patients with a reduced left ventricular ejection fraction (LVEF). Without LVEF, may be appropirate to discontinue after 12 months.
-Aspirin should be continued indefinitely. Dual antiplatelet therapy (aspirin + second antiplatelet) should be continued for up to 12 months unless CI. Clopidogrel monotherapy is an alternative in patients where aspirin is unsuitable.
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What medication should a patient be started on following an ACS?
ACEi (or ARB is not tolerated)- continued indefinitely
Beta-blocker- stopped after 12 months if no LVEF
Dual antiplatelet therapy (aspirin continued indefinitely, DAT stopped by 12 months)
Statin
What are the two ways that atrial fibrillation can be managed?
Controlling the ventricular rate (‘rate control’)
OR
Attempting to restore and maintain sinus rhythm (‘rhythm control’)
If a patient presents with arrhythmias, rate OR rhythm control can be offered if the onset was less than 48 hours. Rate control is preferred if the arrhythmia onset is over 48 hours or uncertain.
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Cardioversion
-Sinus rhythm can be restored by electrical cardioversion or by pharmacological cardioversion with an anti-arrhythmic drug (flecainide acetate or amiodarone hydrochloride)
-If AF has been present for over 48 hours, cardioversion is preferred over drugs, but delay until pt has been fully anticoagulated for at least 3 weeks.
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What are some examples of anti-arrhythmic drugs?
Flecainide acetate
Amiodarone hydrochloride
Is ‘rate control’ or ‘rhythm control’ the preferred first-line treatment strategy for AF?
Rate control (except in patients with new onset AF, AF with a reversible cause or heart failure primarily caused by AF)
What drugs can be used for ‘rate control’ associated with arrhythmias?
Ventricular rate can be controlled with a standard beta-blocker (not sotalol)
OR
a rate-limiting CCB such as diltiazem or verapamil as monotherapy
Choice of drug should depend on individual symptoms, HR, comorbidities and patient preference
Drug Treatment for ‘Rate Control’ of Arrhythmias
-Standard beta-blocker or rate-limiting CCB such as diltiazem or verapamil. Atenolol may be preferred as it is taken OD.
-Digoxin monotherapy can be considered for initial rate control in patients with non-paroxysmal AF who are predominantly sedentary
-If monotherapy fails to accurately control ventricular rate, consider combination therapy with any of the two: beta-blocker, digoxin or diltiazem.
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If monotherapy fails to control ventricular rate in arrhythmia, what drugs can be used in combination?
Any two from:
-A beta-blocker
-Diltiazem
-Digoxin
A beta-blocker and digoxin combination tends to be preferred.
Drug Treatment for ‘Rhythm Control’ in Arrhythmia
-Drug treatment first-line is a standard beta-blocker (NOT sotalol)
-If a beta-blocker is not appropriate/ineffective the consider an anti-arrhythmic drug: amiodarone, flecainide, propafenone or sotalol.
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What drugs can be used for rhythm control in arrhythmia if standard beta-blockers are appropriate?
Amiodarone
Flecainide
Propafenone
Sotalol
Anticoagulation and Stroke Prevention
-Patients with AF should be assessed individually for their risk of stroke vs risk of bleeding.
-Offer anticoagulation to all patients with a CHA2DS2-VASc of 2 or above.
-Heparin should be offered to patients with new-onset AF who are receiving subtherapeutic or no anticoagulation therapy, untill assessment is made and appropriate anticoagulation is started.
Oral anticoagulation should be offered to patients with a confirmed AF diagnosis where stable sinus rhythm has not be successfully restored within 48h of onset.
-DOACs such as apixaban, dabigatran, edoxaban or rivaroxaban for non-valuvular AF.
-Offer warfarin if DOAC unsuitable
-Aspirin as monotherapy not recommended for stroke prevention in AF patients
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What is the first-line anticoagulation option for patients with AF if anticoagulation is supported?
DOACs such as apixaban, dabigatran, edoxaban or rivaroxaban.
Atrial Flutter
-Same as atrial fibrillation for treatment options, but generally responds less well to drug treatment
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How should paroxysmal supraventricular tachycardia be treated if the arrhythmia is causing severe symptoms?
IV adenosin
IV verapamil is adenosine is ineffective or CI
Anti-Arrhythmic Drugs
Can be classified according to their effects on the elictral behaviour of myocardial cells during activity:
-Class I: Membrane stabilising drugs, e.g. lidocaine, flecainide
-Class II: Beta-blockers
-Class III: Amiodarone, sotalol (also Class II)
-Class IV: CCB (including verapamil but not dihydropyridines)
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What is usually the drug of choice for treating supraventricular arrhythmias?
Adenosine
What are some examples of water-soluble beta-blockers?
Atenolol
Celiprolol
Nadolol
Sotalol
Why are water-soluble beta-blockers less likely to cause sleep disturbances and nightmares?
They are less likely to enter the brain
What are some examples of beta-blockers that have arteriolar vasodilating action?
Labetalol
Celiprolol
Carvedilol
Nebivolol
Why should beta-blockers usually be avoided in patients with a history of asthma?
They can precipitate bronchospasm
What are some examples of cardioselective beta-blockers?
Atenolol
Bisoprolol
Metoprolol
Nebivolol
Why should CCBs, besides amlodipine, be avoided in heart failure?
They can further depress cardiac function and exacerbate symptoms
What are some examples of dihydropyridine CCBs?
Amlodipine
Felodipine
Lacidipine
Lercanidipine
Nicardipine
Nifedipine
Nimodipine
What is verapamil used for?
The treatment of angina, hypertension and arrhythmias- reduces cardiac output, slows heart rate.
What is IV nicardipine licensed for the treatment of?
Acute life-threatening hypertension
What is digoxin used for?
Controlling ventricular response in persistent and permanent AF and atrial flutter. Also has a role in heart failure.
What is cardiovascular disease?
A group of disorders of the heart and blood vessels caused by atherosclerosis and thrombosis, which includes coronary heart disease, stroke, peripheral arterial disease and aortic disease
Primary Prevention of Cardiovascular Disease in Patients of High Risk
-Antiplatelet therapy should not routinely be prescribed.
-Antihypertensive therapy if they have consistent high BP.
-Lipid-lowering therapy for high cholesterol (low dose atorvastatin is recommended for patients who have a 10% or greater 10-year risk of developing CVD from the QRISK2 calculator).
Low-dose atorvastatin should also be considered in all patients with type 1 diabetes mellitus, and be offered to patients with type 1 diabetes who are either aged over 40 years, have had diabetes for more than 10 years, have established nephropathy, or have other CVD risk factors.
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Secondary Prevention
-Antiplatelet therapy- low-dose aspirin, or clopidogrel if the patient is intolerant to aspirin (follow the guidance according to different co-morbidities, e.g. AF)
Clopidogrel or a combination of dipyridamole with aspirin should be considered to prevent recurrence of stroke and other vascular events in all patients with a history of stroke or TIA.
-Antihypertensive therapy
-Lipid-lowering therapy (atorvastatin)
What is heart failure?
A progressive clinical syndrome caused by structural or functional abnormalities of the heart, reducing cardiac output.
What are some symptoms of heart failure?
SOB
Persistent coughing or wheezing
Ankle swelling
Reduce exercise tolerance
Fatigue
What is the most common cause of heart failure?
Coronary heart disease
Heart failure can either have a reduced ejection fraction, or a preserved ejection fraction.
True or false?
True
What is heart failure with reduced ejection fraction?
The left ventricle loses its ability to contract normally and therefore presents with an ejection fraction of less than 40%.
Chronic Heart Failure with Reduced Ejection Fraction
-Rate-limiting CCBs (verapamil and diltiazem) and short-acting dihydropyridines (nifedipine or nicardipine) should be AVOIDED.
-Amlodipine is safe.
-Loop diuretics (furosemide,etc) first-line for relief of breathlessness and oedema
-ACEi (ramipril, lisinopril etc) or beta-blocker (bisoprolol) first-line to reduce morbidity and mortality- use clinical judgement to determine whether to start an ACEi or beta-blocker first.
-If symptoms persist or worsen after first-line treatments, aldosterone antagonists such as spironolactone should be offered.
-Digoxin can be added on for patients in sinus rhythm- reduces symptoms.
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What are the first-line treatments for chronic heart failure with reduced ejection fraction?
Loop diuretics, e.g. amlodipine to reduce oedema and breathlessness
ACEi or beta-blockers to reduce morbidity and mortality (make sure they are licensed for HF, some aren’t)
Monitoring Drug Treatment in Heart Failure
-When initiating ACE inhibitors, ARBs and aldosterone antagonists: serum _ and sodium, _ function, and blood pressure should be checked prior to starting treatment, 1-2 weeks after starting treatment, and at each dose increment. Once the target, or maximum tolerated dose is achieved, treatment should be monitored monthly for 3 months and then at least every 6 months, and if the patient becomes acutely unwell.
When initiating beta blockers, heart rate, blood pressure and symptom control should be assessed at the start of treatment and after each dose change.
In patients with chronic kidney disease, lower doses and slower dose titrations of ACE inhibitors, ARBs, aldosterone antagonists and digoxin should be considered. Advice from a renal specialist should be considered where appropriate.
Potassium
Renal
Diuretics
-Thiazides are used to relieve oedema due to chronic heart failure and, in lower doses, to reduce blood pressure.
-Loop diuretics are used in pulmonary oedema due to left ventricular failure and in patients with chronic heart failure.
-Combination diuretic therapy may be effective in patients with oedema resistant to treatment with one diuretic. Vigorous diuresis, particularly with loop diuretics, may induce acute hypotension; rapid reduction of plasma volume should be avoided.
Thiazides and Related Diuretics
-Indapamide and Chlortalidone are the preferred diuretics for hypertension management
-Bendroflumethiazide can be used for mild-moderate heart failure.
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Loop Diuretics
-Used in pulmonary oedema due to left ventricular failure and also chronic heart failure.
-Diuretic-resistant oedema- treat with loop diuretic+thiazide.
-Can exacerbate diabetes
-Can add loop diuretics to antihypertensive treatment to achieve better control.
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Which diuretics are first-line for treatment of hypertension?
Indapamide
Chlortalidone
BOTH ARE THIAZIDE OR RELATED
Which diuretic is first-line for mild-moderate heart failure?
Bendroflumethiazide
Potassium-Sparing Diuretics
-Given alongside thiazide or loop diuretics as they are weak when used alone.
-Do NOT give potassium supplements alongside potassium-sparing diuretics.
-Potassium-sparing diuretics should not be given to patients receiving an ACEi or ARB- can cause severe hyperkalaemia.
Aldosterone Antagonists
-Spironolactone- can treat oedema and ascites caused by liver cirrhosis.
-Low doses beneficial in moderate to severe heart failure
-Can be used in primary hyperaldosteronism
How do ACE inhibitors work?
They inhibit the conversation of angiontensin I to angiontensin II.
What are the main indications for ACE inhibitors?
Heart Failure
Hypertension
Diabetic nephropathy
Prophylaxis of cardiovascular events
ACE Inhibitors in Heart Failure
-Usually used in combination with beta-blockers
-K+ supplements and potassium sparing diuretics should be discontinued due to risk of _.
-Can be used in combination with spironolactone as long as potassium levels are monitored closely.
Hyperkalaemia
ACE Inhibitors and Hypertension
-Most appropriate initial drug treatment for hypertension in:
-Younger caucasian patients (under 55)
-Hypertensive patients with type 2 diabetes
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Effects of ACE Inhibitors on the Renal System
-Check renal function and electrolytes before starting ACE inhibitors.
-Use alongside NSAIDs increase renal damage risk
-Avoid in patients with renovascular disease
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What is a potentially fatal effect from taking nitrates with sildenafil?
Hypotension
What CCB should never be prescribed with a beta-blocker?
Verapamil
Following a STEMI, all patients should be given what unless CI?
Aspirin
Which class of antihypertensives should generally be avoided in diabetic patients?
Beta blockers- can mask hypoglycaemic symptoms
Mrs HA has heart failure and is taking bisoprolol 10mg and perindopril 5mgdaily but remains symptomatic. What drug should be added to her regimen?
Spironolactone
Which beta-blocker is least suitable for an asthmatic patient?
Propranolol
Which drug would be most suitable to add to an African-carribean man who still has hypertension despite being on amlodipine and ramipril?
Bendroflumethiazide
Anithypertensive Prescribing
-Patients with hypertension with type 2 diabetes/ no diabetes but under 55 and not black:
ACEi or ARB—> + CCB OR Thiazide —> Final of ACEi OR ARB + CCB + Thiazide
-Patients over 55 or black:
CCB —> + ACEi OR ARB OR Thiazide—> Final of ACEi or ARB + CCB + Thiazide
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What drug can be given to reverse the effects of warfarin?
Phytomenadione
Remember, with INR:
- 1.1 or less= normal in healthy people
-2.0-3.0= effective therapeutic range for people taking warfarin.
The higher the INR, the higher the bleeding risk.
Lower INR is a greater clot risk.
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Peri-Operative Anticoagulation
-Stop warfarin 5 days before elective surgery; give phytomenadione the day before surgery if INR is 1.5 or higher.
-Patients stopping warfarin for surgery but are a high risk of blood clotmay require ‘bridging’ with a LMWH- stop the LMWH 24 hours before surgery.
How long before surgery should warfarin be stopped?
5 days
Direct-acting Oral Anticoagulants (DOACs)
-Apixaban, Edoxaban, Rivaroxaban and Dabigatran.
-Used for the prevention of stroke and systemic embolism in patients with non-valvular AF, and for the treatment and secondary prevention of DVT and/or PE.
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What are DOACs indicated for?
-Stroke prevention
-Systemic embolism prevention in patients with non-valvular AF
-Treatment and secondary prevention of DVT and PE.
What is stable angina?
Characterised by predictable chest pain or pressure, often precipitated by physical exertion or emotional stress causing an increase in myocardial oxygen demand.
What usually causes stable angina?
Atherosclerotic plaques in the coronary arteries that restrict blood fow and oxygen supply to the heart; can lead to stroke, unstable angina, myocardial infarction and sudden cardiac death.
Antianginal Drug Treatment
-Manage acute attacks with sublingual GTN.
-Long-term prevention of chest-pain: a beta-blocker (atenolol, bisoprolol, metoprolol or propranolol= first-line
-Rate-limiting CCB (verapamil or diltiazem) is an alternative if a beta-blocker is CI, e.g. decompensated HF.
-Combination of beta-blocker + CCB if symptoms not controlled adequately by monotherapy.
-Long-acting nitrate (ivabradine, nicorandil or ranolazine) if beta-blocker and CCB are not tolerated.
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What is first-line for long-term chest-pain prevention in patient’s with stable angina?
Beta-blocker
(RL CCB if beta-blocker CI)
Secondary Prevention of Cardiovascular Events in Stable Angina
-All patients with angina are at high-risk for cardiovascular events
-Smoking cessation, weight management, exercise, drug treatment and psychological support etc.
-Low-dose aspirin and a statin (Atorvastatin 80mg) should be given as lon-term prevention treatment.
-Also consider an ACE inhibitor, especially if pt has diabetes.
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What should all patients with stable angina be given for secondary prevention of CV events?
Low-dose aspirin and a statin (Atorvastatin 80mg)
Consider ACEi, especially if pt diabetic
What is the difference between stable and unstable angina?
Stable angina (most common)- attacks have triggers, such as stress or exercise and stop within a few minutes of resting.
Unstable (more serious)- attacks are more unpredictable, may not have a trigger and continue despite resting.
Transient Ischaemic Attack
-Immediately give the patient aspirin
-Give suitable alternative if aspirin CI.
Following diagnosis, give patients suitable secondary prevention of CV event treatment.
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Ischaemic Stroke- Initial Management
-Alteplase should be given if it can be administered within 4.5 hours of symptom onset.
-If intracranial haemorrhage is excluded, give _ ASAP witin 24 hours of symptom onset.
-Anticoagulants NOT recommended as alternative to antiplatelet in acute ischaemic stroke.
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Ischaemic Stroke or TIA- Long-Term Management
Not associated with AF:
-Clopidogrel 75mg OD is recommended, MR dipyridamole 200mg BD with aspirin 75mg OD if clopidogrel CI.
-Initiate high-intensity statin 48h after stroke symptom onset.
-Do not use beta-blockers for hypertension management following a stroke, unless indicated for a co-existing condition.
-Anticoagulants not recommended in long-term prevention except with AF is present.
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What medications should be given for secondary prevention of CV events following a TIA or ischaemic stroke in patients without AF?
Clopidogrel 75mg OD (MR dipyridamole 200mg BD + aspirin 75mg OD if not tolerated)
High-intensity statin (20-80mg atorvastatin)
Remember: VTE includes both DVT and PE.
A blood clot forms in a vein and partially or completely obstructs blood flow.
What are some risk factors for VTE?
Surgery
Trauma
Significant immobility
Malignancy
Obesity
Pregnancy
Hormone therapy
VTE Pharmacological Prophylaxis
-Start ASAP or within 14 hours of hospital admission: if patient has risk factors for bleeding, they should only receive prophylaxis when their risk of VTE outweighs their bleed risk.
-LMWH is suitable for most surgical patients an anticoagulation, followed by fondaparinux or unfractionated heparin.
VTE Treatment
-Apixaban or rivaroxaban for patients with confirmed DVT or PE
-If unsuitable, offer LMWH for 5 days followed by dabigatran, etexilate or edoxaban.
How do ACEi work?
Inhibits the formation of angiotensin II, which causes vasodilation
How dfo ARBs work?
Blocks the binding of angiotensin II to the AT1 receptor
How do dihydropyridine CCBs work?
Causes relaxtion of arterial smooth muscle, which reduces arterial pressure by decreasing calcium entry into cells.
How do thiazide-like diuretics work?
Blocks the binding of angiotensin II to the AT1 receptor
DOAC Doses in Atrial Fibrillation
Apixaban- 5mg BD
-2.5mg BD if 2/3 from: 80<, <60kg, creatinine >133/CrCl 15-29mL
Dabigatran- 150mg BD
-110mg BD if >80 or pt also takes verapamil.
Edoxaban- 60mg OD
-30mg OD if weight <60kg or CrCl is 15-50mL
Rivaroxaban- 20mg OD
-15mg OD if CrCl 15-49 mL.
Warfarin target INR will be 2.5
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What is the target INR in patients on warfarin that have AF?
2.5
What is the standard dose of apixaban for patients with AF?
5mg BD
Statins for the Primary Prevention of CVD
-Patients with QRISK >10% and T1 diabetics over 40 years old with established nephropathy etc.
-Atorvastatin 20mg OD is the standard medication
Secondary Prevention of CVD
-Follows a TIA, angina, MI, stroke etc
-High intensity statin, Atorvastatin 80mg.
-Aspirin IS NOT indicated for primary prevention.
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Hypertension in Pregnancy
-ACEi and ARBs can increase the risk of congenital malformations- offer alternatives
-Thiazide-like/thiazide diuretics can also increase the risk
-Other antihypertensives are considered safer
-TargetBP is 135/85mmHg in pregnant patients with chronic hypertension (where they had high BP before getting pregnant)
-Labetalol is first-line, nifedipine if lebetalol unsuitable. Methyldopa if both unsuitable.
-Pregnant women with chronic hypertension should be offered aspirin 75mg-150mg OD from 12 weeks.
What are the preferred options of antihypertensives in pregnancy?
Labetolol (first line)
Nifedipine
Methyldopa
Heart Failure Management
Requires an ACEi/ARB, beta blocker, an aldosterone receptor antagonist (spironolactone or eplerenone) and a SGILT2 inhibitor. Add each drug in one at a time.
-Initiate an ACEi or beta-blocker first, start one at a time. Then would add spironolactone or eplerenone (aldosterone antagonist + ACEi can cause hyperkalaemia- monitor potassium).
-Then would add SGLT2 inhibitor
-Digoxin can be added if there is coexistent AF.
-Sacubitril-valsartan if left ventricular fraction is less than 35% and patient is symptomatic despite ACEi.
-Hydrazlazine + nitrate may be indicated in afro-caribbean patients.
-Also requires a loop diuretic if symptoms of fluid overload are present, which is usually _ , at a dose of 40mg taken in the morning. Bumetanide is an alternative.
-Need to determine if other drugs may be required, such as a statin or antiplatelet agent.
-Primary aim is symptom control and reducing disease progression.
Furosemide
What drugs are always required for the management of heart failure?
-Requires an ACEi/ARB, beta blocker, an aldosterone receptor antagonist (spironolactone or eplerenone) and a SGILT2 inhibitor.
-Also requires a diuretic, which is usually furosemide, at a dose of 40mg taken in the morning. Bumetanide is an alternative.
Why should furosemide be taken in the morning?
It is a diuretic, so can result in needing the toilet during the night.
Which risk assessment tools can be used to calculate CVD risk?
QRISK®2 and JBS3.
Both tools assess cardiovascular risk of coronary heart disease (angina and myocardial infarction), stroke, and transient ischaemic attack. This is based on lipid profile, systolic blood pressure, sex, age, ethnicity, smoking status, BMI, chronic kidney disease (stage 4 or above), diabetes mellitus, atrial fibrillation, treated hypertension, rheumatoid arthritis, social deprivation, or a family history of premature CVD.
REMEMBER: ACEi and ARBs can cause HYPERkalaemia and HYPOnatraemia
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Which beta blocker is most likely to increase QT interval prolongation?
Sotalol
How long after starting a statin should someone book in for blood tests?
3 months
What is the usual INR target for someone on warfarin?
2.5
ACE Inhibitiors can cause hyperkalaemia
Beta Blocker Contraindications
ABCDE:
Asthma
Block (Heart block)
Cardiac failure
Diabetes mellitus (hypoglycaemic shock)
Extremities (occlusivearterial disease)
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Warfarin is safe in pregnancy.
True or False?
False
It should not be given in pregnancy
Warfarin
-Mainly prescribed for people at risk of thrombosis- Pulmonary embolism, DVT, AF etc
INR can be affected by many things, including:
-Alcohol, should be avoided but sporadic alcohol intake is worse than consistent drinking.
-Dark green vegetables- cabbage, kale, broccoli
-OTC Drugs
-Herbal medicines- ginger, St John’s Wort (reduce anticoagulation effect)
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What are some things that can affect INR for patients on warfarin?
-Alcohol, should be avoided but sporadic alcohol intake is worse than consistent drinking.
-Dark green vegetables- cabbage, kale, broccoli
-OTC Drugs
-Herbal medicines- ginger, St John’s Wort (reduce anticoagulation effect)
Warfarin Interactions
-Alcohol- INR fluctuations
-Azole antifungals- enhance anticoagulant effect
-Allopurinol- may enhance anticoagulation effect
-Clarithromycin- use azithromycin as alternative
-Erythromycin- elderly at most risk, closely monitor
-Metronidazole- avoid where possible, may need to reduce warfarin dose by up to half
-Carbamazepine- increases warfarin metabolism
-Cimetidine- inhibits warfarin metabolism
-Cranberry- increased anticoagulation effect
-Miconazole- AVOID, use nystatin when possible
-NSAIDS- increased bleeding risk
-Rifampicin- reduced anticoagulant effect
-SSRIs-Reduced anticoagulation effect
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What are some drugs that warfarin interacts with, and how?
-Alcohol- INR fluctuations
-Azole antifungals- enhance anticoagulant effect
-Allopurinol- may enhance anticoagulation effect
-Clarithromycin- use azithromycin as alternative
-Erythromycin- elderly at most risk, closely monitor
-Metronidazole- avoid where possible, may need to reduce warfarin dose by up to half
-Carbamazepine- increases warfarin metabolism
-Cimetidine- inhibits warfarin metabolism
-Cranberry- increased anticoagulation effect
-Miconazole- AVOID, use nystatin when possible
-NSAIDS- increased bleeding risk
-Rifampicin- reduced anticoagulant effect
-SSRIs-Reduced anticoagulation effect
What is a potential side-effect of using a diuretic alongside digoxin?
Hypokalaemia
What are the main side-effects of ACEi?
First dose hypotension
Renal impairment
Dry cough
Angioedema
Sinusitis
Rash
ACEi and ARBs are not suitable in patients with idiopathic angiodema.
True or false?
True
When is moxonidine licensed as treatment?
As a last resort for hypertension
Eplerenone is NOT licensed to treat hypertension. What is it licensed to treat?
Heart failure. It can also be used to treat hyperaldosteronism
Hypertension Medication Summary: ACE Inhibitors
Side-Effects:
-Angioedema
-Dry _
-Dry mouth
-Myalgia
-Tinnitus
-Hepatitis
Interactions:
-Allopurinol (dangerous skin reaction, Steven’s-Johnson syndrome)
-Azathioprine (decreased ability to form blood cells)
-Lithium (lithium toxicity)
-Antihypertensives
-Spironolactone (hyperkalaemia)
-Potassium (hyperkalaemia)
Cough
Hypertension Medication Summary- CCBs
Side-Effects:
-Flushing
-Headache
-Peripheral oedema
-Vomiting
-_ hyperplasia
Interactions:
-Mefloquine (bradycardia)
-Antihypertensives
-Magnesium (increased side-effect risk0
-CTN
-Grapefruit (increased CCB concentration)
Gingival
Hypertension Medication Summary: Diuretics
Side-Effects:
-_ disturbances
-Hyperglycaemia
-Hyperuricaemia
-_ dysfunction
-Constipation
Interactions:
-Allopurinol (increased clearance of allopurinol)
-Amiodarone (increased arrhythmia risk)
-Aspirin and NSAIDs (reduced diuretic effect)
-Clarithromycin (hypokalaemia)
-Digoxin (potassium loss, and therefore increased digoxin toxicity risk)
Electrolyte
Erectile
What anticoagulant/antiplatelet is the only licensed option for a patient with a mechanical heart valve?
Warfarin
Remember: DOACs are contraindicated in patients with prosthetic heart valves, with a BMI over 40, weight over 120kg- underdosing risk. Warfarin would be more suitable.
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What would be the dosing instructions for treating a DVT with rivaroxaban?
15mg BD for 21 days, then 20mg daily thereafter
Patients once stabilised on amiodarone require which tests every 6 months?
Liver, thyroid and renal functions
Which drug class is CI in renal artery stenosis?
ACE inhibitors
NSAIDs are CI in patients with heart failure.
True or False?
True
Diuretics Overview
-Thiazides: relieve _ due to chronic heart failure and, in lower doses, to reduce blood pressure.
-Loop diuretics: used in pulmonary oedema due to left ventricular failure and in patients with heart failure.
-Combination may be effective if patients have oedema resistant to monotherapy. Can induce acute hypotension.
Oedema
Which diuretics are the preferred option for managing hypertension?
Chlortalidone or indapamide (Thiazides/thiazide-like are first-line diuretics, namely these two). Chlortalidone has a longer duration of action than thiazides. Indapamide is believed to lower BP with less metabolic disturbances, especially in the aggrevation of diabetes.
Bendroflumethiazide can be used for mild-moderate HF, it is licensed for hypertension treatment, but is no longer first-line.
Loop Diuretics
Furosemide and bumetanide both act within one hour when given orally and diuresis is complete within 6 hours- can be given BD and not interfere with sleep.
-Used in pulmonary oedema due to left ventricular failure, and in chronic HF.
-Diuretic-resistant oedema can be treated with a loop diuretic combined with a thiazide or related diuretic, e.g. bendroflumethiazide or metolazone.
-Can be added to antihypertensive treatment in those with resistant hypertension or in patients with impaired renal function or heart failure.
-Can exacerbate _ (but hyperglycaemia is less likely than with thiazides) and also can exacerbate gout.
-High doses can cause _ and deafness
-Hypokalaemia induced by loop diuretics can precipitate hepatic _; potassium-sparing diuretics can be used to prevent this.
Diabetes
Tinnitus
Encephalopathy
Mineralocorticoid Receptor Antagonists: Spironolactone
-Treatment of oedema and ascites caused by cirrhosis of the liver. Low doses also beneficial in moderate to severe heart failure.
-Also used in primary hyperaldosteronism (Conn’s syndrome)
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REMEMBER: Diuretics can exacerbate diabetes. Indapamide tends to be the best option to not exacerbate diabetes.
Thiazide/Thiazide like Diuretics
-Chlortalidone or indapamide (Thiazides/thiazide-like are first-line diuretics, namely these two). Chlortalidone has a longer duration of action than thiazides. Indapamide is believed to lower BP with less metabolic disturbances, especially in the aggrevation of diabetes.
-Bendroflumethiazide can be used for mild-moderate HF, it is licensed for hypertension treatment, but is no longer first-line.
-Cautioned in both mild-moderate hepatic and renal impairment; avoid in severe.
REMEMBER: Digoxin and loop diuretics can improve symptoms of heart failure, but do not reduce mortality. ACEi, beta-blockers and CCBs reduce mortality.
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What is a potential adverse effect from combining ACEi with spironolactone?
Hyperkalaemia- monitor potassium
-Pregnant Women with Chronic Hypertension: Aim for BP below 135/85
-Elderly (over 80): Aim for below 150/90
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After opening, how long are GTN tablets stable for before they would need to be discarded?
8 weeks
What is the target BP for hypertensive patients with renal disease?
<140/90
What is the target BP for hypertensive patients with type 1 diabetes and an ACR <70mg/mmol?
<140/90
What is the target BP for hypertensive patients that are diabetic and have eye problems or kidney problems?
<130/80
What is the target BP in a hypertensive patient with CVD and CKD?
<135/85
Remember: Rivaroxiban should be taken with food.
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Which two antihypertensives should be taken 30-60 minutes before food?
Lercanidipine
Peridopril
Which anticoagulants/antiplatelet is safe for use in antiphosphotlipid syndrome?
Warfarin
What is the onset of action for indapamide? How long do the effects last?
Onset: 1-2 hours
Duration: 12-24 hours
What is the target BP for a patient with renal disease?
<140/90
Furosemide Summary
Key interactions include aminoglycosides (ototoxicity risk) and lithium (increased toxicity risk)
-Diuresis effect lasts _ hours
-U&E’s should be checked within a week of commencing
6
Anticoagulation Length in DVT
-Consider stopping anticoagulation therapy after 3 months (3-6 in active cancer) after a PROVOKED DVT or PE, if the provoking factor is no longer present and the clinical course has been uncomplicated.
-Unprovoked VTE/PE: 3-6 months
-Proximal DVT/PE: 3 months (3-6 months in active cancer)
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