CV Drugs Flashcards
Name some ACE inhibitors
Ramipril, Enalipril, Lisinopril, Perindopril
ACE Inhibitor side effects and contra indications
SIDE EFFECTS OF ACE INHIBITORS
• Dizziness
• Orthostatic hypotension
• GI distress
• Cough
• Acute kidney injury
Contra-indicated
• Bilateral or renal artery stenosis
• Hyperkalaemia
• Hypotension
Rarely
• Angioedema
• Swelling of mouth , lips and throat
• Black people and smokers most at
risk
• May be severe and life-threatening
Action of an ACE inhibitor:
Inhibits angiotensin l being converted to angiotensin ll
No angiotensin ll means:
No aldosterone release ~ reduces Na~ reduces fluid
Limited vasoconstriction so blood vessels dilate
No release of ADH (less fluid and less vasoconstriction)
What should be used if ACE inhibitor can’t be tolerated eg if causes persistent dry cough
ARB
Angiotensin receptor blocker
Do not inhibit the breakdown of bradykinin so no persistent dry cough
Drugs: candesartan, irbesartan, losartan
Name some ARB’s
Candesartan, Irbesartan, Losartan
Name some calcium channel blockers
Two types
Dihydropyridines (nifedipine, amlodipine, felodipine) - predominantly
affecting vascular smooth muscle causing vasodilation
Non- dihydropyridines (verapamil & diltiazem) – SLOW THE HEART RATE affecting myocardial tissue
Calcium channel side effects
Flushing
Headache
Ankle swelling
Dizziness
• Tend to disappear within a few days
Constipation
Bradycardia
Action of calcium channel blockers
Inhibit calcium channels on smooth muscle cells of arteries
Reduced Ca influx, reduced contraction strength,
Reduced rate and force of contraction
Peripheral vasodilation
Coronary vasodilation
Name some thiazide type diuretics
Bendroflumethiazide, indapamide
Action of diuretics
Cause urine loss from the kidneys, by inhibiting sodium and water re absorption
Decrease blood volume, cardiac output, total peripheral resistance
Not first line treatment
Side effects of thiazide type diuretics
Common
Dizziness
Electrolyte imbalance
Gastrointestinal disturbances
Rare
Blood disorders
Bone marrow suppression
Impotence
Name some beta blockers
Atenolol, carvedilol, metoprolol
Action of beta blockers
• Blocks to B1 adrenergic receptors of the heart and the kidneys therefore causing reduction in calcium uptake, reducing force and velocity of contractions
• Vasodilating affects
Reduction in sympathetic drive, therefore heart rate decreases overall reducing cardiac output and BP
Side effects of beta blockers
Side Effects: Bronchospasms in susceptible individuals (due to having beta || receptors on the lungs) so avoid in asthma patients, fatigue, cold extremities, Nightmares, affect carbohydrate metabolism and increase risk of T2 diabetes
Case Study:
49 year old cashier
Caucasian
Type 2 diabetes for last 12 years
BP 150/95 at routine diabetic check
Similar readings in notes going back over four months
BMI 35
Smoked since teenage years
What should you do?
ACE inhibitor or ARB (check renal function first)
Then add CCB or thiazide type diuretics
Then all 3
Step 4- consider seeking expert advice or low dose spironolactone if blood potassium is < or equal to 4.5 mmol/l, alpha blocker or beta blocker if blood potassium is > 4.5 mmol/l
Name some nitrates
GTN spray- under tongue
GTN IV nitrates- severe
Action and when to use of nitrates:
Vasodilators increasing coronary blood flow
Decrease after and pre load
Decrease myocardial workload, decreased oxygen demand
Use: prophylaxis of angina/ acute heart failure
Side effects and contraindications of nitrates:
Headache- make sure to warn people and that’s when you know its working (treat with paracetamol)
Hypotension - dizzy so take sat down
Syncope
Facial flushing
Contraindications:
Acute circulatory failure, shock, head trauma, severe hypotension, aortic stenosis
Describe the use for beta blockers:
Hypertension, angina, myocardial infarction, arrhythmias, heart failure
Describe the use for calcium channel blockers:
Prophylaxis of angina, hypertension, arrhythmias, use when beta blockers aren’t appropriate
Name some antiplatelets
Aspirin, Ticagrelor, Clopidogrel, Plasugrel
Can use them together as they block different pathways
Describe the action of antiplatelets
Disrupt platelet activation via a number of mechanisms including inhibition of platelet agonists, adhesion or aggregation
What is the use of antiplatelets?
Revascularisation to restore sufficient blood flow to affected vessel (repercussion).
Inhibit clot formation and support plaque stabilisation
Secondary prevention of CV disease, TIA, stroke
Side Effects and contraindications of anti platelets:
Bronchospasms, GI bleeds, GI irritation, tinnitus
Contraindications:
Bleeding risk, low platelet count, allery
What dose should aspirin, ticagrelor and prasugrel be given?
Aspirin:
Loading at 300mg, then carry on at 75mg
Ticagrelor:
Loading at 180mg, 90mg BD
Prasugrel:
60mg stat then 10 or 5 mg daily (PCI)
Name some glycoprotein ||b / |||a antagonists.
ABICIXIMAB,EPTIFIBRATIDE, TIOFIBRAN
Describe the action and use of glyco proteins:
Action:
Inhibit the final common pathway involved in platelet aggregation
Use:
prevention of ischaemic cardiac complications in patients undergoing PCI
Short term prevention of MI in patients with unstable angina not responding to conventional treatment & who are scheduled for a PCI
Side effects and contra indications of glycoproteins:
Bleeding, back pain, fever, headaches, hypotension, nausea
Active internal bleeding, hypertensive retinopathy, majorly surgery within last 2 months.
Name some anticoagulants and what is it used for?
Heparin- Enoxaparin, deltaoarin, tinzaparin
Fondaparinux- subcutaneous injection
Uses: thromboprophylaxis, unstable angina, STEMI, NSTEMI, DVT, PE
Describe the action of anticoagulants.
Prevents blood from clotting by suppressing the synthesis or function of various clotting factors
Anti- thrombotic
Doesn’t thin the blood, it just makes it less likely to clot
Side effects and contra indication of anticoagulants:
Side effects- bleeding, hyperkalaemia, HIT
Contra indication- after major trauma, peptic ulcer, severe hypertension
Use of ACE Inhibitors/ ARB’s
Heart failure, hypertension, prophylaxis post MI
Describe the use and action of nicorandil
Prevention and long term management of angina
Potassium channel activator with nitrate component too
Arterial and venous vasodilating
Side effects and contraindications of nicrorandil (angina)
Headaches, Ulceration, Dizziness, Flushing
Severe hypotension, LV Failure, hypovolaemia, acute pulmonary oedema
Use and Action of ranolazine
Use s an adjunct in stable angina
Facilitates myocardial relaxation (decreases calcium)- does not affect heart rate or BP
Side effects and contra indications of ranolazine (angina)
Dizziness, headache, constipation, nausea, vomiting
CI - Severe renal impairment, Caution long QT syndrome
Use and action of ivabradine
Use- treatment of angina in patients with normal sinus rhythm
Action- lowers heart rate by acting on sinus node
- decreases myocardial oxygen demands
- no effect on BP or contraction
Side effects and contra indications of ivabradine (angina)
GI, nausea, constipation, diarrhoea
CI heat rate <75
Acute MI, unstable angina, unstable heart failure
(MANY DRUG INTERACTIONS)
Describe the use and action of statins:
Primary or secondary prevention of CV events, hyperlipidaemia
Action- HMG - CoA reductive inhibitors
Block the enzyme involved in cholesterol synthesis
Common side effects and contra indications of statins:
Muscle aches and pains
Myopathy - Rhabdomyolysis
Nausea, insomnia
CI - liver disease
Name some thrombolytics and describe when they should be used.
Streptokinase, Tenectoplase, Alteplase
Use between 6-12 hours of symptoms, ideally within 90mins in primary PCI unavailable
Use for: acute myocardial infarction, PE, ischaemic stroke
How do thrombolytics work and what are some side effects?
Fibrinolytic drug activate plasminogen which turns to plasmin which then degrades the fibrin in th clot, breaking up the thrombus
Side effects: risk of cerebral bleed
(MANY ABSOLUTE/RELATIVE CONTRAINDICATIONS) - must decide what is more beneficial towards the patient
Describe the secondary prevention management treatment following an MI
Aspirin - 75 mg once daily
Another antiplatelets eg clopidogrel or ticagrelor (low risk of bleeding) for up to 12 months
Atorvastatin - 80mg once daily
ACE Inhibitors (eg ramipril titrated as tolerated to 10mg once daily)
Atenolol or other beta blocker (bisnoprolol) titrated as high as tolerated
Aldosterone antagonist for those with clinical heart failure (ie eplerenone titrated to 50mg once daily)
NICE guidelines for stable angina.
Either a beta blocker or a calcium channel blocker first line
If the symptoms are not adequately controlled (or cannot tolerate) consider switching to an alternative or use a combination of the first two
If the patients symptoms are not adequately controlled by one or a combination then consider a third line – long acting nitrate, ivabradine or ranolazine
If in combination with a beta blocker – not verapamil or diltiazem
Only if patient cannot tolerate calcium channel blockers or beta blockers should monotherapy with nitrate, ivabradine or ranolazine be offered.
Triple therapy should be considered whilst awaiting revascularisation
Management of NSTEMI/ Unstable angina
Sub lingual GTN or IV nitrates § Morphine
Oral Beta Blockers
Aspirin
Ticagrelor / Clopidogrel § ACE inhibitor
Statin
Fondaparinux
Acute NSTEMI treatment (BATMANO):
B- Beta blockers unless contraindicated
A – Aspirin 300mg stat dose
T – Ticagrelor 180mg stat dose (clopidogrel 300mg is an alternative)
M – Morphine titrated to control pain
A – Anticoagulant: Low Molecular Weight Heparin (LMWH) at treatment dose (e.g. enoxaparin 1mg/kg twice daily for 2-8 days)
N – Nitrates (e.g. GTN) to relieve coronary artery spasm
O - oxygen only if their oxygen saturations are dropping (i.e. <95%).
Initial treatment for an MI:
§ Pain relief & antiplatelets
§ Diamorphine / Morphine
§ Oxygen
§ Sublingual GTNitrate or IV
§ Aspirin
§ Cyclizine or metoclopramide
§ Thrombolysis with or without heparin
§ IV beta blockers, IV nitrates (if suitable)
§ Aspirin , ACE inhibitors , oral beta blockers . Lipid lowering agents, dual antiplatelets
§ Angiography as needed , revascularisation as needed
Which of the following drugs must not be given with verapamil:
Bisoprolol,
Telimisartan,
Ticagrelor,
Aspirin
Bisoprolol
Nam the three types of diuretics for HF symptom relief:
Loop (target the loop of Henley)
Thiazide (target the distal convoluted tube)
Aldosterone antagonist
Nam some loop diuretics to treat HF symptoms:
Furosemide , Bumetanide , Torasemide
How do loop diuretics work in the symptom relief of HF?
Inhibit reabsorption from the ascending limb of the loop of Henlé in the renal tubule
• Inhibit the sodium-potassium-chloride cotransporter in the thick ascending limb
• This transporter normally reabsorbs about 25% of the sodium load
• leads to both diuresis (increased water loss) and natriuresis (increased sodium loss).
• They
– Reduce preload, thus reducing ventricular filling
– Improve pulmonary vascular congestion by decreasing filling pressures.
What tests Ned to be performed before starting HF patient on loop diuretics?
Measure of:
Renal Function
Serum Electrolytes
Blood pressure
Make sure to start on a low dose
Recheck measurements 1-2 weeks after starting treatment and each time dose increases.
• Earlier monitoring (after 5-7 days) may be required for people:
• With existing chronic kidney disease stage 3 or higher.
• Aged 60 years or over.
• With relevant comorbidities such as diabetes mellitus or peripheral arterial disease.
• Taking a combination of a diuretic plus an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin-II receptor antagonist (AIIRA), or an aldosterone antagonist.
Time of the day and dose of loop diuretics for HF
Titrate the dose of loop diuretic up or down according to symptoms and signs of fluid overload; use the lowest possible dose to control symptoms.
● once a day, in the morning, but it can be given twice a day (morning and lunchtime) for additional diuresis.
● Adjust the timing of doses to suit their social needs.
● With heart failure and preserved ejection fraction the maximum initial dose is up to 80 mg
furosemide.
● SICK DAY RULES :
If they develop diarrhoea and vomiting while taking, a diuretic, they should
● maintain their fluid intake and stop the diuretic for 1-2 days until they recover.
● If symptoms persist beyond 2 days they should see a GP and have their bloods checked..
Who should you not prescribe loop diuretics to?
Do not prescribe loop diuretics to people with:
– Hypovolaemia and dehydration (with or without accompanying hypotension).
– Severe hypokalaemia or severe hyponatraemia.
– Anuria, acute kidney injury or chronic kidney disease due to nephrotoxic or hepatotoxic drugs, or associated with hepatic coma.
– Chronic kidney disease (CKD) with a creatinine clearance below 30 mL/min/1.73m2. – Addison’s disease.
– Liver cirrhosis associated with comatose and pre-comatose state.
– Porphyria.
– Cardiac arrhythmias (contraindication for torasemide).
Adverse effects of loop diuretics:
Adverse effects of loop diuretics include:
– Water and electrolyte imbalance : Na , Chloride, K , Mg, Ca
•Hyponatraemia e.g. confusion, muscle cramps, muscle weakness, dizziness, drowsiness, and vomiting
•Hypochloraemia,
•Hypokalaemia, - neuromuscular symptoms (muscular weakness and paralysis), intestinal symptoms (including vomiting and constipation), renal symptoms (polyuria), and cardiac symptoms (including palpitations).
•Hypomagnesaemia
•Hypocalcaemia
Hypotension
Name some thiazide diuretics:
Bendroflumethiazide, indapamide, metolazone, chlorthalidone
Thiazide diuretic in HF symptom relief:
Bendroflumethiazide, indapamide, metolazone, chlorthalidone
• Inhibit the sodium-chloride transporter in the distal tubule.
• Less efficacious than loop diuretics in producing diuresis and natriuresis.
• Can be added in addition to Loop diuretic to potentiate their action
• Maximum diuresis at low doses
• Act within 1-2 hours and last 6-24 hours
• Oral only
Name some aldosterone antagonists:
spironolactone, eplerenone
How does aldosterone antagonist work?
Block the activity of aldosterone, an adrenal cortex hormone that causes sodium retention.
• Useful in heart failure following an MI
• Recommended in moderate-to-severe heart failure
• Aldosterone antagonists (spironolactone and eplerenone) are recommended in patients with – NYHA class II to IV heart failure
– LVEF of 35% or less, unless contraindicated
• Decrease the morbidity and mortality associated with symptomatic chronic heart failure
• Spironolactone and eplerenone can both cause hyperkalaemia
If experiencing gynacasmastia swap to eplerenone
ACEInhibitors for AF
• Reduce the load on the heart pre & post load
• Decrease symptoms, slow disease progression & prolong life in heart failure
• Most appropriate vasodilators as they lower both the arterial & venous resistance by preventing the increase in angiotensin 2 often present in heart failure.
• Cardiac output increase because the renovascular resistance falls there in an increase in renal blood flow.
• Can use ARB ( ACE II) if ACE not tolerated • E.g. ramipril, lisinopril, candesartan, losartan
How do you monitor ACE Inhibitors / ARB in a HF patient?
• Measure renal function, serum electrolytes, and blood pressure before prescribing – Recheck 1-2 weeks after starting treatment & dose titration.
• Maintain at the target dose (or highest tolerated dose) indefinitely unless adverse effects occur.
• Once treatment is stable, measure renal function and serum electrolytes at least every 6
months.
• Sick day rules :
– Advise the person that if they develop diarrhoea and vomiting while taking they should maintain their fluid intake and stop for 1-2 days until they recover.
– If symptoms persist beyond 2 days they should see a GP and have their renal function checked.
Beta Blockers for HF patients:
• Acutely can decrease myocardial contractility & worsen heart failure.
• Long term improve survival of stable patients with heart failure by blocking the damaging effects of
overactive sympathetic activity
• Avoid adverse effects by starting low dose
• Carvedilol, bisoprolol & metoprolol given with an ACE inhibitor & diuretic for about 1 year have been
found in trials to decrease mortality from 11-17% to 7-12%
• Most patients with heart failure with reduced ejection fraction should be offered treatment with a beta
blocker
• the beta-blockers licensed in the UK for the treatment of heart failure are bisoprolol, carvedilol, and nebivolol.
Isosorbide Dinitrate & Hydralazine
• In some situations HF patients are unable to tolerate either or both ACEI or ACEII
• Can be used as alternative vasodilator in these patients.
• This combination improves exercise tolerance in heart failure patients but produces only modest reduction in mortality.
• Evidence available suggests this combination is of particular benefit to Afrocarribean patients although its benefit to Caucasians is yet to be fully established.
Ivabradine:
• In the UK, ivabradine is now recommended for patients with symptomatic heart failure with reduced ejection fraction (class II to IV) who :
– Are in sinus rhythm with a resting heart rate of 75 beats per minute or more, and
– Are symptomatic in spite of standard treatment including a beta blocker, an ACE inhibitor and an
aldosterone antagonist OR who are genuinely intolerant of beta blockers, and – Have a left ventricular ejection fraction of 35% or less
• Carefully monitor patients taking ivabradine for bradycardia or its symptoms (for example dizziness, fatigue and hypotension)
Digoxin (HF)
• Beneficial in patients with current or prior symptoms of heart failure or reduced LVEF, especially those with atrial fibrillation.
• When added to ACE inhibitors, beta-blockers, and diuretics, digoxin can reduce symptoms, prevent hospitalisation, control rhythm, and enhance exercise
• Digoxin should be used cautiously with plasma level monitoring. • Digoxin toxicity ( digifab anti toxin)
Check bloods 6 hour post dose
ENTRESTO – Sacubitril / valsartan (HF)
Stops breakdown of BNP
• Sacubitril valsartan is recommended as an option for treating symptomatic chronic heart failure with reduced ejection fraction, only in people:
– with New York Heart Association (NYHA) class II to IV symptoms and
– with a left ventricular ejection fraction of 35% or less and
– who are already taking a stable dose of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor-blockers (ARBs).
• Concomitant administration of an angiotensin-II receptor antagonist plus neprilysin with an ACE inhibitor, or within 36 hours of the last dose of an ACE inhibitor, is not recommended.
• Treatment with sacubitril/valsartan reduces cardiovascular death by reducing both worsening heart failure and sudden cardiac death
• The most commonly reported adverse reactions during treatment with sacubitril valsartan were hypotension, hyperkalaemia and renal impairment
Dapagliflozin & Empagliflozin (HF)
• Dapagliflozin & Empagliflozin are recommended as an option for treating symptomatic chronic heart failure with reduced ejection fraction in adults, only if it is used as an add-on to optimised standard care with:
• ACE inhibitors or ARBs, with beta blockers, and, if tolerated, MRAs, or • sacubitril valsartan, with beta blockers, and, if tolerated, MRAs.
• Start treatment of symptomatic heart failure with reduced ejection fraction with on the advice of a heart failure specialist.
• Monitor for adverse events
NICE treatment for chronic heart failure:
• To relieve symptoms of fluid overload:
o Prescribe a diuretic (e.g. furosemide).
o Titrate the dose up or down according to symptoms.
o Review the dose and adjust as necessary after introducing other drug treatments for heart failure.
• To reduce morbidity and mortality prescribe:
o An angiotensin-converting enzyme (ACE) inhibitor and a beta-blocker.
o An angiotensin-II receptor antagonist (AIIRA) may be considered if the person develops intolerable side effects to the ACE inhibitor.
• Introduce one drug at a time.
• Add the second drug once the person is stable on the first drug.
What patient advice should you give to someone with heart failure?
Reduce salt consumption
Fluid restriction 1.5 - 2litres
Stop smoking/ alcohol
Increase PA
Improve nutritional status
Recommend immunisations
Complications of heart failure:
Complications of heart failure
• Cardiac arrhythmias
• Depression
– Major depressive disorder is present in up to 20% of people with heart failure
• Cachexia (wasting)
– This is defined as the loss of 6% or more of total body weight within the previous 6-12 months. Wasting occurs in lean tissue (muscle mass), and fat
• Chronic kidney disease (CKD)
– CKD is common in people with heart failure and is strongly associated with increased morbidity and
mortality
• Sexual dysfunction
– Sexual dysfunction is common in people with heart failure. This may be related to cardiovascular
disease, fatigue, weakness, the use of drugs (such as beta-blockers), or depression and anxiety
• Sudden cardiac death
– About half of the deaths in people with heart failure are related to sudden cardiac death
Acute Heart Failure:
• Develops rapidly and can be immediately life-threatening due to a lack of time to undergo any compensatory changes.
• Due to acute infection (sepsis), acute myocardial infarction, heart valve dysfunction, severe arrhythmias or operations (cardiopulmonary bypass).
• managed by pharmacological, mechanical and surgical interventions despite its aetiology
Symptoms:
Coughing up pink foamy mucus
Lack of appetite/ nausea
Sudden swelling of the abdomen, legs, ankles and feet
Severe shortness of breath
Rapid, irregular heart beat
Fatigue and weakness
Sudden weight gain from fluid retention
Symptoms of atrial fibrillation
Breathlessness
Palpitations
Syncope or dizziness
Chest discomfort
Stroke or transient ischaemic attack
Detection and diagnosis of AF:
Perform a manual pulse palpate on to assess for presence of an regular pulse
Perform 12 lead ECG to diagnose AF
If suspected paroxysmal AF do ambulatory ECG
CHADSVAS vs HASBLED
To assess the risk of using an anti coagulation against the risk of bleeding out
What is the treatment pathway for a patient with AF?
Haemodynamically unstable - direct current cardioversion
HD Stable
1) Rate control
2) Anti-coagulate (check CHADSVAS)
3) consider cardioversion:
If AF <48 hours + low risk of stroke = cardiovert + anticoagulants for 4 weeks
If AF >48 hours + risk of stroke either TEE echocardiogram to check for a current clot in atrium if not present cardiovert + oral AC for 4 weeks
or if thrombus present oral AC for 3 weeks, re check then potentially cardiovert
Rate Control Drugs for AF:
Block the AV node to decrease HR
Beta Blockers
- Bisoprolol, Atenolol
Contra Indication - COPD as block B2 receptors
Calcium Channel Blockers
- Veraprimil, diltiazem
Contra Indication- Heart Failure
Digoxin - take a while to kick in
Good for hypertension / HF
Amioderone (Rhythm + Rate)
Rhythm control drugs for AF:
Drug = pharmacological cardioversion
Type 1a
Type 1c
Type 3
CI- Increase risk of tossades de point
Flecanide, BB- sotalol, Amiodarone
○ Long term rhythm control drugs: ▪ Beta blockers – 1st line ▪ Dronedarone – 2nd line, maintain normal rhythm when they’ve had successful cardioversion ▪ Amiodarone – in patients with heart failure or left ventricular dysfunction
what does CHA2DS2VAS stand for?
CHF +1
HTN +1
Age >75 +2
Diabetes +1
Stroke/ TIA +2
Vascular Disease +1
Age 65-74 +1
Sex- Female +1
2 or more = AC NEEDED
Types of anticoagulants for AFib:
Warfarin
DOACs
Heparin
Treatment for narrow regular and irregular tachyarrhythmias:
AVRT/AVNRT
AFlutter
Fat
Vagal Monouver - Increases vagal tone, Decrease AV node
Adenosine (6mg) - Blocks AV Node
AFlut or FAT BB/CCB
Cardiovert - priority if haemodynamically unstable
Long Term:
Catheter Ablation
Treatment for wide regular tachyarrhythmia:
VTach vs SVT BBB
TREAT FOR VTACH
Put pads on first
Amiodarone or Procainimide
Cardioversion
Treatment for SVT BBB- only if you are 100% it is this and not V Tach
Adenosine
Cardioversion
Look for underlying cause
If MI- PCI? Auto implantable cardiac debrillators?
Treatment for tossades de point (polymorphic VTach)
Amiodarone
Cardiovert
D Fib on stand by
Once stable give Mg Sulphate, K+, discontinue offending meds, isoprotenolol to increase HR
DONT GIVE ABCD (adenosine, beta blocker, CCB, Digoxen)
Treatment of heart block (bradyarrhythmias):
Discontinuation of AV nodal blocking drugs
Atropine to decrease PNS and increase HR
Epi
PACE
Once patient is stable treat underlying cause:
Inferior wall MI
Hypercalaemia
Overdose on CCB/BB/Digoxen
Limes disease
Advantages and disadvantages of anticoagulation:
Benefits
Can save life & limb from thrombo-embolism
For people with AF – overall 60% reduction of stroke
-about 80-90 strokes will be prevented each year for every 1000
-about 25 strokes will be prevented each year for every 1000
Problems
Anticoagulants are one of the classes of medicines most frequently identified as causing preventable harm & admissions to hospital (NPSA 2007)
Major cause of bleeding which can be fatal (NPSA 2007)
Major cause of litigation (use or non-use) stroke vs bleeding risk
Dose adjustments frequently required to avoid over or under anticoagulation
What are some things we use anticoagulants for?
AF
Deep Vein Thrombosis
Pulmonary Embolism
Mode of Action of Warfarin
Inhibits vitamin K clotting factors.
Use with heparin as doesn’t work instantly
Prevents the vitamin K promoted carboxylation of glutamic acid residues of factors II, VII, IX and X.
50% drop in factor VII levels in 24 hours
50% drop in factor II levels in 4 days
Full anticoagulation in 48-72 hours
Rapid fall in protein C and S levels-in first 2-3days can increase risk of thrombosis.
What is INR?
International normalised range
As 1 size doesn’t fit all
To see the dose of warfarin which should be used in AC medication
Contra Indication to warfarin
Bleeding risk
Haemorrhagic stroke
Pregnancy
Re occurrent falls
Uncontrolled hypertension
Medication - eg ibroprofen, aspirin as increase risk of GI bleed
What tests should be performed prior to commencing with warfarin?
Prothrombin time (PT)
Activated partial thromboplastin time (APTT) u Platelet count
Full Blood Count
Liver Function Test
Baseline INR
(if INR >1.4 review management plan) check why its higher than 0
What strengths of warfarin are availed and what colours are they?
1mg brown
3mg blue
5mg pink
0.5mg white
If a patient is allergic or resistant to warfarin, what alternatives are there?
Acenocoumarol
Phenindione
DOACs - rivaroxaban
Heparins
Unfractioned heparin:
AnticoagulantHigh molecular weight molecule- highly ionised
Therefore – not absorbed via the GI tract
So – it must be given by IV infusion or by subcutaneous injection.
When do you use? : High risk patients / renal impairment
Monitoring & dose adjustment needed – check your trust protocol!
Protamine used to reverse action
What should you monitor if a patient is on unfractionated heparin?
Prothrombin time (PT) - heparin
Activated partial thromboplastin time (APTT) - heparin
Platelet count - HIT (heparin infused thrombolysis <100 don’t use AC)
Full blood count
Liver function test
Potassium
What are ad name some low molecular weight heparins?
Enoxaparin, dalteparin, tinzaparin sodium, bemiparin
Longer half life - once or twice a day dosing
Dosage based on body weight
Advantages: fixed dose , no lab, highly predictable plasma levels
Disadvantages: more expensive
What can you use a LMWH for? Give some examples
PE
DVT
Thromboprophylaxis
Acute coronary syndrome
Examples
Fondaparinux
Enoxaparin
Daltaparin
Tinzaparin
DOSE ADJUSTMENTS – Renal , Body weight, Increased risk
Contrainications of Enoxaparin.
Risk of bleeding, Low platelet
BNF:
Acute bacterial endocarditis; after major trauma; avoid injections containing benzyl alcohol in neonates; epidural anaesthesia with treatment doses; haemophilia or other haemorrhagic disorders; peptic ulcer; recent cerebral haemorrhage; recent surgery to eye; recent surgery to nervous system; spinal anaesthesia with treatment doses; thrombocytopenia (including history of heparin-induced thrombocytopenia)
Name some direct oral anticoagulants (DOACS)
Dabigatran Rivaroxaban Apixaban Edoxaban
DOAC Indications:
Licensed for:
Non-valvular AF (NB differences in criteria)
DVT / PE Treatment & prophylaxis of recurrent VTE
Thromboprophylaxis of DVT or PE after an acute DVT/PE
Thromboprophylaxis after hip or knee replacement (except edoxaban)
Rivaroxaban : Prophylaxis of atherothrombotic events following an acute coronary syndrome with elevated cardiac biomarkers (in combination with aspirin alone or aspirin and clopidogrel)
Check NICE guidance as indications can change regularly.
Benefits of DOACS?
Small half life - good if they need taking off them
No need for INR monitoring
Predictable Anticoagulant response
Rapid onset (1-4 hours)
Lower risk of bleed overall with much reduced intracranial bleed (0.3% vs. 0.76%)
Give stroke protection equivalent to Warfarin (only Dabigatran 150mg gives added benefit)
Rivaroxaban , Apixaban & Edoxaban : can go in compliance aids / can be crushed
Who would use DOAC’S?
Patients who cannot tolerate Warfarin due to:
Significant side effects e.g. Alopecia
Poor INR control despite being compliant (Time in therapeutic range should be less than 65%- Rosendaal score- Cardiac Network )
INR> 5 while compliant with no known cause more than twice in a year
Now first line treatment in majority of patients with PE / DVT/ non valvular AF
Contraindications of DOAC’S
• a lesion or condition, if considered a significant risk factor for major bleeding.
This may include:
• current or recent gastrointestinal ulceration
• presence of malignant neoplasm at high risk of bleeding
• recent brain or spinal injury
• recent brain, spinal, or ophthalmic surgery
• recent intracranial haemorrhage
• known or suspected oesophageal varices
• arteriovenous malformation
• vascular aneurysms, or major intraspinal or intracerebral vascular abnormalities
• concomitant treatment with any other anticoagulant agent—eg:
• unfractionated heparin
• low molecular weight heparin (such as enoxaparin or dalteparin)
• heparin derivatives (such as fondaparinux)
• oral anticoagulants (such as warfarin).
DOAC specific cautions / dosage
Check;
Interactions
Indications ( may differ )
Age (Apixaban & Dabigatran dosage advice)
Weight (Apixaban & Edoxaban )
Renal function - - impaired renal function may constitute a contraindication or recommendation not to use the anticoagulant medicine, or may require a dose reduction
- -other conditions, procedures, and concomitant treatments (eg, non-steroidal anti- inflammatory drugs, antiplatelets), which may increase the risk of major bleeding
Rivaroxaban : WITH FOOD
80% biovailability with food u 66% without food
How do you reverse DOAC’S?
Specific reversal agents are available for dabigatran (Praxbind▼, idarucizumab)
Apixaban and Rivaroxaban (Ondexxya▼, andexanet alfa)
Currently no specific authorised reversal agent available for Edoxaban.
