2 CARDIOVASCULAR SYSTEM PLEASE SELECT A TOPIC 21

2 CARDIOVASCULAR SYSTEM PLEASE SELECT A TOPIC 21
30 CARDIOVASCULAR DRUGS AND THERAPY SPECIAL ISSUE UPDATE ON
410416 §4104—SCHEDULE OF RATINGS–CARDIOVASCULAR SYSTEM 410416 §4104 SCHEDULE OF

AD HOC CARDIOVASCULAR DEVELOPMENT AND REPAIR DEPARTMENT SEMINAR PERE
ADAPTIVE ROLES OF ADIPONECTIN AND RESISTIN IN CARDIOVASCULAR DISEASE
ARTYKUŁ DEVELOPMENT OF THE EUROPEAN NETWORK IN ORPHAN CARDIOVASCULAR

2: Cardiovascular system

Please select a topic:

2.1 Positive inotropic drugs	2.2 Diuretics
2.3 Anti-arrhythmic drugs	2.4 Beta-adrenoceptor blocking drugs
2.5 Drugs affecting the renin-angiotensin system and some other antihypertensive drugs	2.6 Nitrates, calcium-channel blockers, and other anti-antianginal drugs
2.7 Sympathomimetics	2.8 Anticoagulants and protamine
2.9 Antiplatelet drugs	2.10 Myocardial infarction and fibrinolysis
2.11 Antifibrinolytic drugs and haemostatics	2.12 Lipid-regulating drugs
2.13 Local sclerosants

2.1 Positive inotropic drugs

Digoxin 62.5, 125, 250 microgram tablets
Digoxin 250 micrograms/5ml elixir
Digoxin 250 micrograms/ml injection
Enoxamine 100mg/20ml injection (Emergency Drug Cupboard only)
Digibind 38mg injection (restricted)

Dose

- Digoxin tablets 62.5micrograms, 125micrograms, 250micrograms; elixir 50micrograms/mL: rapid digitalisation, 1-1.5mg in divided doses over 24 hours; less urgent digitalisation, 250-500micrograms daily (higher dose may be divided). Maintenance, 62.5-500micrograms daily.
- Digoxin injection 250micrograms/mL: according to local guidance.

- Enoxamine injection 100mg/20ml: see BNF

- Digibind injection 38mg: see BNF

Prescribing notes

Digoxin is indicated for rate control in atrial fibrillation and symptomatic heart failure; it has no role in the prophylaxis of atrial fibrillation.

For rapid rate control in atrial fibrillation, a loading dose of digoxin may be given intravenously or orally.

Regular measurements of plasma digoxin concentrations are not usually required except to confirm toxic or sub-therapeutic levels, or to check compliance.

Digoxin should be used with particular caution in the elderly and patients with renal impairment.

Hypokalaemia predisposes to digoxin toxicity.
Digoxin levels may be increased by drugs such as amiodarone, calcium channel blockers, quinine, hydroxychloroquine.

Older Patients - Digoxin

Loading and maintenance doses of digoxin should be adjusted according to renal function: age, sex and weight need to be considered. A lower maintenance dose (i.e. 62.5-125 micrograms daily) is usually adequate in older patients.

2.2 Diuretics

Thiazides and related diuretics

Bendroflumethazide/Bendrofluazide 2.5mg, 5mg tablet
Metolozone 5mg tablet
Chlorothiazide 250mg/5ml and 100mg/5ml suspension

Dose

- Bendroflumethiazide tablets 2.5mg, 5mg: hypertension, 2.5mg daily.

- Metolozone tablets 5mg: see BNF

- Chlorothiazide suspension 250mg/5ml, 100mg/5ml: see BNF for Children

Prescribing notes

Allow 4 weeks for maximal antihypertensive effect of bendroflumethiazide.
Bendroflumethiazide may be prescribed with furosemide (frusemide) for severe heart failure under hospital supervision; this must be carefully monitored.

Loop diuretics

Furosemide 20mg, 40mg, 500mg tablet
Furosemide 20mg/5ml, 40mg/5ml liquid
Furosemide 50mg/5ml injection
Bumetanide 1mg, 5mg tablet
Bumetanide 1mg/5ml liquid
Bumetanide 1mg/2ml injection

Dose

- Furosemide tablets 20mg, 40mg, 500mg; liquid 20mg/5ml, 20mg/5ml: oedema, initially 40mg daily then adjusted according to response.
- Furosemide injection 10mg/mL: slow intravenous injection, initially 20-50mg. Furosemide may be given by intravenous infusion at a rate not exceeding 4mg/minute.

- Bumetanide tablets 1mg, 5mg; liquid 1mg/5ml: initially 1mg in the morning the adjusted according to response

Prescribing notes

Furosemide produces a dose-dependent diuresis within 1 hour if given orally or 30 minutes if given intravenously; duration of action, 6 hours.
Furosemide 500mg tablets are scored and can be halved.
Bumetanide may be an option in those patients that are not responding to furosemide (1mg bumetanide is equivalent to furosemide).

Potassium-sparing diuretics

Amiloride 5mg tablet
Amiloride 5mg/5ml solution

Dose

- Amiloride tablets 5mg; oral solution 5mg/5ml: 5-20mg daily.

Prescribing notes

Amiloride is a weak diuretic with potassium-sparing properties, given with other diuretics if hypokalaemia is a problem; may take 2-3 days for full effect.

Use with caution in renal impairment.
Potassium-sparing diuretics such as amiloride are usually only necessary if hypokalaemia develops

Aldosterone antagonists

Eplerenone 25mg, 50mg tablet
Spironolactone 25mg, 100mg tablet
Spironolactone 50mg/5ml suspension

Dose

- Eplerenone tablets 25mg, 50mg: initially 25mg once daily, increased within 4 weeks to 50mg once daily.

- Spironolactone tablets 25mg, 50mg, 100mg: heart failure in conjunction with ACE inhibitor, 25mg daily; higher doses may be needed in liver failure.

Prescribing notes

Spironolactone is an aldosterone antagonist used for oedema in hepatic cirrhosis or heart failure, and primary hyperaldosteronism.

Spironolactone 25mg daily has been shown to reduce mortality in patients with severe heart failure receiving standard therapy including ACE inhibitors; renal function and electrolytes should be monitored.
Use with caution in renal impairment.
Eplerenone is to be used as an adjunct in stable patients with left ventricular dysfunction with evidence of heart failure following myocardial infarction (start therapy within 3-14 days of event).
Eplerenone is an alternative aldosterone antagonist which may be prescribed for patients who develop gynaecomastia with spironolactone.

Osmotic diuretics

Mannitol 10%, 20% infusion polyfusor

Older Patients - Diuretics

All diuretics have the propensity to cause postural hypotension and thus collapse and falls in older patients.

2.3 Anti-arrhythmic drugs

Supraventricular arrhythmias

Adenosine 3mg/ml injection
Adenosine 30mg/10ml (Restricted/unlicensed)
Dronedarone 400mg tablet

Supraventricular and ventricular arrhythmias

Amiodarone 100mg, 200mg tablet
Amiodarone 150mg/3ml injection
Amiodarone 300mg in 10ml prefilled syringe

Atenolol 25mg, 50mg, 100mg tablets
Atenolol 25mg/5ml syrup

Atenolol 5mg/10ml injection
Disopyramide 100mg capsule
Disopyramide 50mg/5ml injection
Flecainide 100mg tablet
Flecainide 150mg/15ml injection
Propafenone 150mg tablet

Sotalol 40mg, 80mg, 160mg tablet

Ventricular arrhythmias

Lidocaine/Lignocaine 0.2% in 500ml infusion
Lidocaine/Lignocaine 1% 10ml minijet
Mexiletine 50mg capsules

Dose

Anti-arrhythmics are complex agents; intravenous injections or infusions should be given according to specialist advice.

- Disopyramide capsules 100mg: orally 300-800mg daily in divided doses

- Lidocaine injection 10mg/mL (1%), 20mg/mL (2%); infusion 1mg/mL (0.1%) and 2mg/mL (0.2%) in glucose 5%, 500mL.
- Flecainide tablets 50mg, 100mg; injection 10mg/mL: orally, ventricular arrhythmias, 100mg twice daily; max 400mg daily, reduced after 3-5 days if possible; supraventricular arrhythmias, 50mg twice daily; max 300mg daily.
- Atenolol tablets 25mg, 50mg, 100mg; syrup 25mg/5mL; injection 500micrograms/mL: orally, 50-100mg daily.
- Amiodarone tablets 100mg, 200mg; injection 50mg/mL: orally, 200mg 3 times daily for 1 week, then 200mg twice daily for 1 week, then usually 100-200mg daily thereafter.

- Dronedarone tablets 400mg: orally, 400mg twice daily
- Sotalol (with ECG monitoring and measurement of corrected QT interval) tablets 40mg, 80mg, 160mg: orally, initially 80mg daily in 1-2 divided doses increased every 2-3 days to 160-320mg daily in 2 divided doses; 480-640mg daily for life-threatening ventricular arrhythmias.
- Verapamil tablets 40mg, 80mg, 120mg; m/r tablets 120mg, 240mg; m/r capsules 120mg, 180mg, 240mg; injection 2.5mg/mL: orally, supraventricular arrhythmias, 40-120mg 3 times daily for standard preparation; m/r verapamil, dose according to brand. See BNF.
- Adenosine injection 3mg/mL.
- Atropine injection 100micrograms/mL, 200micrograms/mL, 300micrograms/mL, 600micrograms/mL.
- Digoxin tablets 62.5micrograms, 125micrograms and 250micrograms; elixir 50micrograms/mL; injection 250micrograms/mL.

- Mexiletene capsules 50mg: see BNF

Prescribing notes

Amiodarone may cause corneal microdeposits, thyroid dysfunction, pneumonitis, peripheral neuropathy and hepatotoxicity. Liver-function and thyroid-function tests should be performed before treatment, and 6 monthly thereafter; chest X-ray should be done before treatment.

Patients receiving amiodarone should avoid exposure of the skin to direct sunlight or sun lamps; a sunscreening product providing SPF 25 should be applied if amiodarone is prescribed.

Amiodarone interacts with many drugs. There is a potential for drug interactions to occur for several weeks (or even months) after treatment with it has been stopped.
Sotalol may cause atypical VT (torsades de pointes); it should be given with extreme caution with drugs known to prolong the QT interval e.g. erythromycin, chloroquine, haloperidol, lithium, tricyclic antidepressants, chlorpromazine. It should not be used for angina, hypertension, thyrotoxicosis or secondary prevention after myocardial infarction. Sotalol should be avoided in patients on diuretics or with hypokalaemia.
For patients prescribed dronedarone, liver function tests should be performed:
- Prior to treatment
- On a monthly basis for six months
- At months 9 and 12, and periodically thereafter

With dronedarone if alanine transaminase (ALT) levels are elevated to ≥3 x upper limited of normal (ULN), levels should be re-measured within 48 to 72 hours. If ALT levels are confirmed to be ≥3 x ULN after re-measurement, dronedarone treatment should be withdrawn.

Patients on dronedarone should be advised to contact healthcare professionals immediately in case of signs or symptoms of liver injury.

2.4 Beta-adrenoceptor blocking drugs

Atenolol 25mg, 50mg, 100mg tablets
Atenolol 25mg/5ml syrup
Atenolol 5mg/10ml injection
Bisoprolol 1.25mg, 2.5mg, 3.75mg, 5mg, 10mg tablet (For use in the treatment of heart failure only)
Esmolol 100mg/10ml
Esmolol 2.5g/250ml (ITU only)
Labetolol 50mg, 100mg tablet
Labetolol 5mg/ml injection
Metoprolol 5mg/5ml injection
Metoprolol 25mg/5ml suspension
Metoprolol 50mg, 100mg tablet
Nebivolol 5mg tablet
Propranolol 10mg, 40mg tablet
Propranolol 10mg/5ml and 80mg/5ml SF solution
Propranolol 1mg/ml injection
Propranolol M/R 80mg, 160mg capsule
Sotalol 40mg, 80mg, 160mg tablet

Dose

- Atenolol tablets 25mg, 50mg, 100mg; syrup 25mg/5mL: 25-100mg daily according to response.
- Bisoprolol tablets 1.25mg, 2.5mg, 3.75mg, 5mg, 7.5mg, 10mg: stable, chronic heart failure, 1.25mg daily for 1 week, increased, if well tolerated, to 2.5mg daily for 1 week, then 3.75mg daily for 1 week, then 5mg daily for 4 weeks, then 7.5mg daily for 4 weeks, then 10mg daily maintenance.

- Labetolol tablets 50mg, 100mg: see BNF

- Metoprolol tablets 50mg, 100mg, suspension 25mg/5ml: see BNF
- Propranolol tablets 10mg, 40mg, 80mg, 160mg: thyrotoxicosis (adjunct), anxiety tachycardia, 10-40mg 3-4 times daily. Anxiety with symptoms such as palpitations, sweating, tremor, 40mg once daily increased to 40mg 3 times daily if necessary. Migraine prophylaxis, essential tremor: initially 40mg 2-3 times daily, maintenance 80-160mg daily.

Prescribing notes

Bisoprolol is second-line for patients intolerant of atenolol in hypertension.

Bisoprolol is first choice beta-blocker for stable, chronic heart failure initiated under specialist supervision.

Beta-blockers may cause bronchospasm; avoid in patients suffering asthma. If a beta-blocker is required, a cardioselective beta-blocker should be selected, initiated at a low dose and the patient closely monitored.

Sotalol is only used as an anti-arrhythmic.
Propranolol is indicated for treatment of migraine, anxiety, thyrotoxicosis and essential tremor.

2.5 Drugs affecting the renin-angiotensin system and other antihypertensive drugs

Vasodilator antihypertensive drugs

Hydralazine 25mg tablet
Hydralazine 20mg injection
Minoxidil 5mg tablet
Sodium nitroprusside 50mg/5ml injection

Centrally acting antihypertensive drugs

Methyldopa 125mg, 250mg, 500mg tablet
Moxonidine 200 microgram, 300 microgram, 400 microgram tablet
Clonidine 25 microgram and 100 microgram tablet
Clonidine 150 microgram/ml injection

Alpha-adrenoceptor blocking drugs

1^st Choice

Doxazosin 1mg, 2mg, 4mg tablet
Doxazosin 4mg XL, 8mg XL tablet

Alternatives

Prazosin 1mg tablet
Terazosin 2mg, 5mg tablet

Dose

- see BNF

Prescribing notes

Doxazosin is a third-line agent in the treatment of hypertension. It should be used with caution in patients with heart failure or impaired left ventricular function.

Doxazosin may cause postural hypotension and first dose hypotension. Treatment should be initiated at the lowest dose possible.

Angiotensin-converting enzyme inhibitors

Captopril 12.5mg, 25mg tablet
Enalapril 2.5mg, 5mg, 10mg tablet
Lisinopril 2.5mg, 5mg, 10mg, 20mg tablet
Perindopril 2mg, 4mg tablet
Ramipril 1.25mg, 2.5mg, 5mg, 10mg capsule

Dose

- see BNF

Prescribing notes

ACE inhibitors are useful alternatives for hypertension when thiazides and beta-blockers are contra-indicated, not tolerated or fail to control blood pressure.

For heart failure the dose of the ACE inhibitor should be titrated to a 'target' dose (or to the maximum tolerated dose if lower). See BNF.

Urea and electrolytes should be checked within 1 week of commencing therapy.
Enalapril should be prescribed once daily for hypertension.
Ramipril should be prescribed as a once daily dose. Patients who have been initiated on twice daily dosing should be switched to an equivalent once daily dose/

Angiotensin-II receptor antagonists

Candesartan 2mg, 4mg, 8mg, 16mg and 32mg tablets
Irbesartan 75mg, 150mg tablet
Valsartan 40mg, 80mg and 160mg capsules

Dose

- Candesartan tablets 2mg, 4mg, 8mg, 16mg, 32mg: recommended dose is 4-32 daily. See BNF.
- Irbesartan tablets 75mg, 150mg, 300mg: recommended dose is 150-300mg once daily (in haemodialysis or in elderly over 75 years, initial dose of 75mg once daily may be used). See BNF.

- Valsartan capsules 80mg, 160mg: 40mg-160mg daily. See BNF

Prescribing notes

Angiotensin-II receptor antagonists should be reserved for patients who develop a persistent cough with ACE inhibitors.
Urea and electrolytes should be checked within 2 weeks of commencing therapy and after any change in dose.
Losartan is available as a generic product and is less expensive currently than the other angiotensin-II receptor antagonists.

Miscellaneous

Phenoxybenzamine 10mg capsules
Phentolamine 10mg/ml injection
Guanethidine 10mg/ml injection (Theatres only)
Iloprost nebules 10microgram/ml (Critical Care Only)

2.6 Nitrates, calcium-channel blockers, and other anti-anginal drugs

Nitrates

Glyceryl trinitrate 400 microgram/dose spray
Glyceryl trinitrate 2mg, 3mg, 5mg buccal m/r tablet
Glyceryl trinitrate 5mg, 10mg skin patch
Glyceryl trinitrate 5mg/5ml injection
Isosorbide mononitrate 10mg, 20mg tablet
Isosorbide dinitrate 10mg, 20mg tablet
Isosorbide dinitrate 25mg/50ml injection

Dose

- Glyceryl trinitrate spray 400micrograms per puff; sublingual tablets 300micrograms, 500micrograms: sublingually, 300microgram-1mg repeated as required.
- Glyceryl trinitrate buccal tablets m/r 2mg, 3mg, 5mg: treatment of angina, 2mg as required (1mg in sensitive patients), increased to 3mg if necessary; prophylaxis 1-3mg 3 times daily; 5mg in severe angina. Unstable angina (adjunct), up to 5mg with ECG monitoring. Congestive heart failure, 5mg 3 times daily, increased to 10mg 3 times daily in severe cases. Acute heart failure, 5mg repeated until symptoms abate.
- Isosorbide mononitrate tablets 10mg, 20mg:: 20 - 40mg twice daily (10mg twice daily in those who have not previously received nitrates); up to 120mg daily in divided doses if required.

- Isosorbide dinitrate tablets 10mg, 20mg: see BNF

Prescribing notes

To reduce the risk of nitrate tolerance, isosorbide mononitrate should be given twice daily 6-8 hours apart.

Long-acting and transdermal nitrate preparations are significantly more expensive than standard formulations. A cost-effective branded long-acting preparation should be prescribed only for patients who have a problem with compliance.
Glyceryl trinitrate (GTN) intravenous injection may be given when sublingual or buccal GTN is ineffective in patients with chest pain due to myocardial infarction or severe ischaemia, and in treatment of acute left ventricular failure.

Calcium-channel blockers

Amlodipine 5mg, 10mg tablet
Diltiazem 60mg M/R tablets (Tildiem®
Diltiazem 120mg, 240mg, 180mg, 300mg and 360mg s/r capsule (Viazem XL®)
Diltiazem 200mg M/R capsules (Tildiem LA®)
Lercanidipine 10mg tablets
Nifedipine 5mg, 10mg capsule - Instant release formulation
Nifedipine 10mg, 20mg s/r tablet (Adalat retard®) - 12 hourly formulation
Nifedipine 10mg, 20mg m/r capsules (Coracten SR®) - 12 hourly formulation
Nifedipine 30mg and 60mg XL capsules (Coracten XL®) - 24 hourly formulation
Nimodipine 30mg tablet, 10mg/50ml injection
Verapamil 40mg, 80mg,120mg tablet
Verapamil 120mg s/r capsule
Verapamil 40mg/5ml SF solution
Verapamil 2.5mg/ml injection

Dose

- Amlodipine tablets 5mg, 10mg: hypertension or angina, initially 5mg once daily; max. 10mg once daily.
- Diltiazem m/r tablets 60mg, 90mg, 120mg; m/r capsules 60mg, 90mg, 120mg, 180mg, 200mg, 240mg, 300mg, 360mg: dose according to brand. See BNF.
- Verapamil tablets 40mg, 80mg, 120mg; m/r capsules 120mg: dose according to brand. See BNF.

Prescribing notes

Nifedipine m/r is first choice calcium-channel blocker for hypertension. The brand of different calcium-channel blockers should be specified since different formulations may have different clinical effects. The most cost-effective brand should be prescribed.

Sudden withdrawal of calcium-channel blockers may exacerbate angina; withdraw if ischaemic pain occurs or worsens after starting treatment.

Nifedipine should not be given without a beta-blocker for angina.

Short-acting formulations of nifedipine capsules have been associated with large variations in blood pressure and reflex tachycardia; they are no longer recommended for angina or hypertension.

Diltiazem is first choice calcium-channel blocker for angina if a beta-blocker cannot be used; it is also given for hypertension. It has less negative inotropic effects than verapamil and significant myocardial depression is rare. Use caution if given with beta-blockers due to risk of bradycardia. The most cost-effective brand should be prescribed.
Verapamil is used for angina, hypertension and arrhythmia; it reduces cardiac output, slows the heart rate and may affect atrioventricular conduction. It may produce heart failure, exacerbate conduction disorders, and high doses may cause hypotension. It should not be used with beta-blockers.

Other Anti-anginal drugs

Nicorandil 10mg, 20mg tablet
Ivabradine 5mg, 7.5mg tablets

Dose

- see BNF

Prescribing notes

Nicorandil is used when other anti-anginal drugs are insufficient; they have similar efficacy to other anti-anginal drugs in controlling symptoms but there is little evidence regarding their efficacy in combination with other anti-anginal drugs.
Ivabradine is approved for use, on the initiation of a cardiologist, chronic stable angina in patients for whom heart rate control is desirable and also have a contra-indication or intolerance of beta-blockers and rate limiting calcium channel blockers.

Peripheral vasodilators and related drugs

Cinnarizine 75mg capsules
Pentoxyfilline 400mg tablets
Naftidrofuryl 100mg capsules

Prescribing notes

Patients suffering intermittent claudication should be advised to exercise and stop smoking. First-line management of Raynaud's phenomenon includes avoiding exposure to cold and stopping smoking.
Peripheral vasodilators are of limited value.
Cilostazol, pentoxifylline and inositol are not recommended for the treatment of intermittent claudication.

2.7 Sympathomimetics

Inotropic sympathomimetics

Dobutamine 250mg/20ml injection
Dopamine 200mg/5ml injection
Dopexamine 50mg/5ml injection
Isoprenaline 2.25mg/2ml injection (unlicensed)

Vasoconstrictor sympathomimetics

Ephedrine 30mg/ml injection
Metaraminol 10mg/ml injection
Noradrenaline/Norepinephrine 2mg/ml injection
Phenylephrine 10mg/ml injection (ITU only)

Cardiopulmonary resuscitation

Adrenaline/Epinephrine 100 micrograms/ml(1:10,000) minijet
Adrenaline/Epinephrine 100 micrograms/ml(1:10,000) injection

Dose

- See BNF for dosing recommendations.
- Adrenaline injection 100micrograms/mL: during cardiopulmonary resuscitation (CPR), 1mg (10mL) intravenously flushed with saline, and repeated every 3 minutes.
- Dobutamine strong sterile solution,12.5mg/mL and 50mg/mL.
- Dopamine sterile concentrate, 40mg/mL and 160mg/mL; intravenous infusion, 400mg or 800mg in 250mL glucose 5%.
- Noradrenaline acid tartrate injection 2mg/mL (equivalent to noradrenaline base 1mg/mL).

Prescribing notes

Low dose dopamine induces vasodilatation and increases renal perfusion; higher doses (more than 5micrograms/kg/min) produce vasoconstriction and may exacerbate heart failure.
Inotropic and vasoconstrictor sympathomimetics should preferably be used only in the intensive care setting with invasive haemodynamic monitoring.

2.8 Anticoagulants and protamine

Parenteral anticoagulants

Fondaparinux 2.5mg syringe (Haematology advice only)

Standard heparins

Heparin 20000units/20ml, 5000units/5ml injection
Heparin 5000 units/0.2ml (Calciparine®)
Heparin 50 units/5ml (Hepsal®)

Low molecular weight heparins

Enoxaparin 20mg, 40mg, 60mg, 80mg, 100mg and 150 mg pre-filled syringe
Tinzaparin 20000 units/ml (2ml) vial
Tinzaparin 20000 unit/ml pre-filled syringes (10000, 14000, 18000, 40000 units)
Tinzaparin 10000/ml pre-filled syringes (3500, 4500 units)

Dose

- See BNF for dosing recommendations.
- Standard heparin 1000units/mL, 20 000units/20mL.
- Enoxaparin 100mg/mL (0.2mL, 0.4mL, 0.6mL, 0.8mL and 1mL syringes); 150mg/mL (0.8mL, 1mL syringes).
- Tinzaparin 10,000 units/mL (0.25mL, 0.35mL, 0.45mL syringes or 2mL vial) or 20,000 units/mL (0.5mL, 0.7mL, 0.9mL syringes or 2mL vial).

Prescribing notes

See Trust “Unfractionated Heparin Dosing Guidelines”.
See Trust Thrombophylaxis guidelines on use of LMWHs.
Treatment with standard heparin is continued until no longer required, or until warfarin takes effect (at least 3 days).

Heparin is monitored using activated partial thromboplastin time (APTT) to give a patient/control ratio of 1.5-2.5.

Low molecular weight heparin does not require APTT monitoring; if necessary, anti-factor Xa can be monitored.

Heparins may induce two types of thrombocytopenia: the first, usually develops within 1-4 days of initiation, is acute, usually mild, and may resolve spontaneously. The second type has an immunological basis and is more serious: it usually occurs after 7-11 days, or more quickly in previously exposed patients, and is often associated with serious thromboembolic complications or bleeding. Serial platelet counts should be measured if heparin is given for longer than 5 days (or sooner if previously exposed), and heparin stopped if thrombocytopenia develops.
Lepirudin injection will be discontinued in the UK from 1^st April 2012.

Epoprostenol

Epoprostenol 500 microgram vial

Oral anticoagulants

Warfarin 1mg, 3mg and 5mg tablets
Phenindione 10mg, 25mg and 50mg tablets
Dabigatran 75mg capsules
Dabigatran 110mg and 150mg capsules

Dose

- Warfarin tablets 500micrograms (white), 1mg (brown), 3mg (blue), 5mg (pink): induction dose 10mg daily for 2 days, then adjusted according to INR. A lower induction dose may be required by some patients; see BNF for details.

Prescribing notes

See Trust “GUIDELINES FOR WARFARIN- INDUCTION and MAINTENANCE DOSES”
The warfarin dose is adjusted according to the international normalised ratio (INR). The target INR should be clearly identified at initiation of therapy, and measured daily or on alternate days initially, then at longer intervals (depending on response) then up to every 12 weeks.

Indication and duration of treatment should be clearly recorded at initiation of treatment; the patient-held anticoagulant treatment booklet should be used. See BNF for details.

The plasma half-life of warfarin is 35 hours; a steady anticoagulant effect is achieved after about one week. If immediate anticoagulation is required, heparin must be given concomitantly.

There are many clinically important interactions with warfarin; clinicians are strongly advised to consult BNF before prescribing.
Vitamin K (phytomenadione) can be given to reverse the effects of warfarin but takes 6-12 hours to become effective. Immediate reversal of the anticoagulant effect of warfarin may be achieved with fresh frozen plasma or prothrombin complex concentrate; see BNF for details. Specialist haematological advice should be sought.
Dabigatran is approved for use in hip and knee replacement surgery for prophylaxis of venous thromboembolism.
Warfarin will continue to be the first line drug of choice for prevention of stroke in patients with non-valvular AF but Dabigitran be considered for patients with a warfarin allergy or an absolute contra-indication to warfarin (Dabigatran may also be contra-indicated in some of these indications). Please note that a bleeding risk that would lead to a contra-indication to warfarin would also contra-indicate to Dabigatran.

Older Patients - Warfarin

Warfarin should be used with caution in patients with confusion or a tendency to fall.

Protamine

Protamine 50mg/5ml injection

Prescribing notes

Protamine sulphate reverses the effects of standard heparin, but only partially reverses the effects of low molecular weight heparins.

2.9 Antiplatelet drugs

Aspirin 75mg and 300mg dispersible tablets
Aspirin 75mg and 300mg e/c tablets
Aspirin 150mg suppositories
Clopidogrel 75mg tablets
Dipyridamole 50mg/5ml suspension
Dipyridamole 200mg s/r capsules
Prasuguel 5mg and 10mg tablets
Tirofiban 12.5mg/50ml injection

Dose

- Aspirin dispersible tablets 75mg, 300mg: prophylaxis of cerebrovascular disease or myocardial infarction, initial loading dose of 150-300mg, then 75mg daily.

- Clopidogrel tablets 75mg: for acute coronary syndrome, 75mg once daily for up to 12 months in combination with aspirin. An initial loading dose of clopidogrel 300mg is recommended.

- Dipyridamole SR capsules 200mg: for secondary prevention of ischaemic stroke and transient ischaemic attacks (used alone or combination with aspirin) 200mg capsule twice daily.

- Prasugrel tablets 5mg, 10mg: (with aspirin) initially 60mg as a single dose then body-weight over 60kg, 10mg once daily or body-weight under 60kg or over 75 years, 5mg once daily.

- Tirofiban injection 12.5mg/50ml: see BNF

Prescribing notes

The e/c formulations of aspirin are not recommended.

Dipyridamole m/r or low dose aspirin may be used with warfarin for prophylaxis of thromboembolism due to prosthetic heart valves.

Patients with proven intolerance to aspirin may be prescribed clopidogrel to prevent further events in stroke, myocardial infarction or peripheral vascular disease.

Aspirin and clopidogrel may be prescribed concomitantly for acute coronary syndrome for up to 12 months, after which clopidogrel is discontinued.
Hospital specialists may prescribe clopidogrel for up to 3 months to prevent coronary artery stent occlusion.
The combination of dipyridamole and clopidogrel has not been adequately evaluated and is therefore not recommended.
There is a clinically significant interaction between clopidogrel and omeprazole making clopidogrel less effective. If concomitant use of clopidogrel and a proton pump is necessary, then lansoprazole would be an appropriate choice.
Prasugel in combination with aspirin 75mg is an option for treatment acute coronary syndrome undergoing PCI.

2.10 Myocardial infarction and fibrinolysis

Alteplase 20mg and 50mg injection
Streptokinase 1.5million and 250000 unit injection
Tenecteplase and 50mg injection

(a) acute myocardial infarction

First choice: tenecteplase

Prescribing notes

Thrombolysis is effective if given as soon as possible after acute myocardial infarction; urgent transfer to hospital is essential.

Tenecteplase has the advantage of availability as a single, weight adjusted, intravenous bolus injection. It can also be used in patients who have ever received streptokinase, suffered a recent streptococcal infection or developed a hypersensitivity reaction to streptokinase.
If severe bleeding occurs, the fibrinolytic should be discontinued; coagulation factors and/or tranexamic acid may be required.

(b) acute ischaemic stroke

First choice: alteplase

Prescribing notes

Alteplase must be used in strict accordance with detailed protocols in a specialist acute stroke unit.
Treatment must be started within 3 hours of onset of symptoms and after exclusion of intracranial haemorrhage by means of appropriate imaging techniques.

2.11 Antifibrinolytic drugs and haemostatics

Etamsylate 500mg tablets
Tranexamic acid 100mg/ml injection
Tranexamic acid 500mg tablets
Factor VIIa 1mg and 5mg injection (Novoseven®)
Prothrombin complex 250unit and 500unit injection (Beriplex®)

Dose

- Tranexamic acid tablets 500mg; injection 100mg/mL: orally, menorrhagia (initiated when heavy bleeding has started), 1-1.5g 3-4 times daily for 3-4 days. Slow intravenous injection: local fibrinolysis 0.5-1g 3 times daily.

- Other products: see BNF or product literature

Prescribing notes

The manufacturer recommends regular eye examinations and liver function tests when tranexamic acid is used long-term for hereditary angioneurotic oedema; however, the BNF states that the need for regular eye examinations during long-term treatment is based on unsatisfactory evidence.

2.12 Lipid-regulating drugs

Anion-exchange resins

Colestyramine 4g sachets

Fibrates

Bezafibrate 200mg tablets
Bezafibrate 400mg m/r tablets
Ciprofibrate 100mg tablets
Fenofibrate MR 160mg tablets

Prescribing notes

Fibrates have been less well tested in clinical trials. They are mainly of benefit in those with mixed hyperlipidaemia and low HDL cholesterol.

Statins

Atorvastatin 10mg, 20mg, 40mg and 80mg tablets
Pravastatin 10mg, 20mg and 40mg tablets
Simvastatin 10mg, 20mg and 40mg tablets
Rosuvastatin 5mg, 10mg and 20mg tablets

Dose

- Atorvastatin tablets 10mg, 20mg, 40mg, 80mg: hyperlipidaemia, 10-80mg at night
- Simvastatin tablets 10mg, 20mg, 40mg, 80mg: hyperlipidaemia, 10-80mg at night; coronary heart disease, initially 20mg at night, max 80mg at night.

- Pravastatin tablets 10m, 20mg, 40mg: see BNF

- Rosuvastatin tablets 5mg, 10mg, 20mg: see BNF

Prescribing notes

Lowering cholesterol is associated with reduced mortality and morbidity in patients at high and moderate risk of, or with established, cardiovascular and cerebrovascular disease.

Pravastatin is less likely to interact with other drugs than atorvastatin or simvastatin and may be preferred in certain situations, such as in patients receiving warfarin, digoxin or ciclosporin.
Generic simvastatin is substantially lower cost than other lipid lowering agents.
Caution should be exercised when prescribing other drugs with statins. Simvastatin and atorvastatin interact with many drugs including azole antifungals, macrolide antibiotics, amiodarone, verapamil, grapefruit juice and warfarin. See BNF for full list of interactions.
Caution should be exercised when prescribing simvastatin 80mg daily due to the increased risk of adverse effects.

Other

Ezetimibe 10mg tablets
Omacor capsules

Dose

- Ezetimibe tablets 10mg: 10mg once daily.

- Omacor capsules: see BNF

2.13 Local sclerosants

Ethanolamine oleate 5% injection
Sodium tetradecyl sulphate 0.5%, 1% and 3% injection

Red = Hospital use only

Green = GP & Hospital use. Drugs not classified as Red, Amber or Amber 2 are classified as Green by default

Amber 1 = Drugs with shared care agreement

Amber 2 = Initiated by Hospital specialist only

Gateshead Health NHS Foundation Trust Page 24 of 24 Date: 1.2.2012

Drug Formulary

Drug & Therapeutics Committee

B CRF CARDIOVASCULAR COMPLICATIONS E 01 PRIMITIVE HYPERTENSION EFFECTS
CALCIUM SUPPLEMENTS AND CARDIOVASCULAR DISEASE IN OLDER WOMEN BACKGROUND
CARDIOVASCULAR & THORACIC SURGERY IMS BHU SPECIFICATION FOR 2D

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