Cardiology

Guidelines for under 55s with hypertension

1) ACE inhibitor or ARB

2) Add CCB

3) ACEi/ ARB + CCB + Thiazide like diuretic (TLD)

4) Low dose spironolactone or high dose TLD. If contraindicated consider alpha or beta blocker

Hypertension in over 55s or afro-Caribbean

1) Strat with CCB, if contraindicated TLD

2) Add and ACE/ARB

3) Add a TLD if not already on

4) Add low dose spironolactone or high dose alpha/ beta blocker

Hypertension in pregnant women

• Labetalol → 100mg BD - 200mg BD - max 2.4g per day

• Methyldopa → 250mg TDS max 3g daily

• Nifedipine

Inalapril is suitable for patients who are breast feeding

Side effects of ACE inhibitors

• Dry cough

• Hyperkalaemia - high risk to patients with renal disease or diabetes

• Anaphylactoid reactions - angioedema

Renal effects of ACE inhibitors

• Renal protective in CKD

• Nephrotoxic in AKI

Side effects of ARBs

Aside from the dry cough they generally cause similar side effects as ACE inhibitors

• Hyperkalaemia- increased risk in T2DM

• Anaphylactoid reactions eg angioedema

• Reno protective in CKD, nephrotoxic in AKI

• Stop is LFTs x3

Intrinsic sympathomimetic activity beta blockers

P- Pinolol

A- Acebutolol

C- Cellprolol

O- Oxprenolol

Less bradycardia activities and less coldness of of extremities

Contraindications with intrinsic sympathomimetic activity beta blockers

• Asthma

• Worsening AF

• Second/third degree heart block

• Severe hypotension or bradycardia

Water soluble b-blockers

Less likely to cause nightmares and sleep disturbances

C- Celiprolol

A- Atenolol

N- Nadolol

S- Sotalol

Cardioselective b-blokers

Lees likely to cause brochospasms

B- Bisoprolol

A- Atenolol

M- Metoprolol

A- Acebutolol

N - Nebivolol

Interactions of b-blockers

• With verapamil can cause asystole and hypotension

• Be careful in diabetics

Rate limiting CCBs

• Verapamil → only CCB licensed for arrhymias but can cause constipation.

• Diltiazem → Maintain on same brand with doses >60mg

Dihydropyradines CCB

• Amlodipine

• Felodipine

• Lacidipine

• Lercanidipine

• Nefidipine

ALL should be avoid in AF apart from amlodipine

Side effects of CCBs

• ankle swelling

• headaches

Loop diuretics

Work by increasing urine output by inhibiting sodium reabsorption

• Bumetanide - increase risk of muscle aches

• Furosemide - gout, otoxicity if infused too fast

• Torsemide - muscle skeletal pain

Max infusion dose for furosemide

anything over 4mg/min can cause issues

Side effects of loop diuretics

• hyperglycaemia

• hyperuricaemia

• hypocalcaemia

• hyponatremia

• hypomagnesia

Thiazide and thiazide- like diuretics

• Bendroflumethiazide

• Cyclopenthiazide

• Chlorothiazide

• Indapamide

• Xipamide

• Metolazone

• Chlorothalidone

Side effects of thiazide like diuretics

• GI disturbances

• Lack of effect

• High LDLs and triglycerides

• Hypercalcaemia

Potassium sparing diuretics

• Thianthrene- may turn urine blue

• Amiloride

Side effects of potassium sparing diuretics

• Hyperkalaemia

• Aldosterone antagonist

Aldosterone antagonists (type of potassium sparing diuretic)

Inhibit aldosterone which causes Na+ reabsorption, as a result there is less K+/H+ exchange/ excretion which results in H+ retention - so when you inhibit it you dont retain water so you reduce blood pressure

• Spironolactone

• Epleperone

Sodium channel blockers (potassium sparing diuretic)

• Thianthrene

• Amiloride

Indication and common doses of eplerone

Used in HF where you have reduced ejection fraction </= 40% following MI (start therapy in 3-14 days)

• initially 25mg daily

• 50mg daily then, increase within 4 weeks of treatment

Cautions with potassium sparing diuretics

• Elderly more susceptible to side effects - you wouldnt give pottassium sparing diuretics if on ace inhibitor

• Diabetics

Contraindications with potassium sparing diuretics

• Anuria - when someone isn’t passing any urine

• Addisons disease - aldosterone is critical for Na+/K+ balance

• Severe hyperkalaemia

MHRA warnings of potassium sparing diuretics

Risk of ototoxicity at high doses

Mannitol

Osmotic diuretic

• Can be used to treat cerebral oedema and raised ocular pressure

• Inhibits na+/h2o reabsorption

Acetazolamide

Weak diuretic

Dorzolamide/ brinzolamide

Generally used in glaucoma

Management of ACS

Initial management - Short acting nitrate - GTN spray

Isosorbide mononitrate (sublingual) - 8 week expiry

Both of theses work in 20-30 mins

How do you prevent tolerance of nitrates

Modified relief preparations have a duration of up to 12 hours, to prevent tolerance in nitrates, leave patches off overnight and take tablets after 8 hours not 12

Angina prophylaxis and prevention of angina attacks

• Beta blocker or rate limiting CCB

• Combination of beta blocker or CCB (not rate limiting). You could also consider adding a long acting nitrate, ivabradine (only in normal sinus rhythm), ranolazine or nicorandil (second line due to ulcer complications, only use if others aren’t tolerated).

Side effects of nitrates

• Vasodilation

• Headaches

• Flushing

• Throbbing

• Hypotension

• Dizziness

• Tachycardia

• Dyspepsia

• Heart burn

Management of unstable angina

• O2 in patients with hypoxia

• Nitrates (GTN spray or isosorbide dinitrate) for ischaemic pain, or you can use IV diamorphine/ morphine + metoclopramide

• You can load patient with 300mg aspirin and 300mg clopidegrol. Prasugrel is an alternative for patients undergoing a PCI

• Heparin, LMWH or fondaparinux is used to prevent reclusion in PCI

Long term management of ACS

• Statin → Atorvastatin 80mg or simvastatin 40mg

• ACE Inhibitor → 2.5mg up to 10mg

• Aspirin → Dual antiplatelet therapy with clopidegral, prasugrel or ticagrelor

• Beta blockers 2.5mg-10mg

• Prevention also includes lifestyle changes or even rivaroxaban and aspirin at low doses

What’s commonly given in community with unstable angina

NSTEMI

• Aspirin 300mg

• GTN spray or 0.3mg tablets

STEMI

• Add morphine or metoclopramide

Occlusive vascular disease

This is where there is a blockage of the artery due to a plaque - painful ache when walking

• Aspirin 75mg OD and a statin for secondary prevention

Vasospastic vascular disease

This is when your blood vessel goes into a temporary spasm, can be triggered by anxiety or stress

• Stop smoking and avoid cold conditions

• Nifedipine 5mg TDS up to 20mg TDS - opens blood vessels

MOA of aspirin

Acts by inhibiting the COX-1 enzyme which is important in the formation of thromboxane A2 which is the enzyme which causes platelets to get sticky

MOA of clopidegrol

Binds to the P2Y12 receptor on the surface of platelets preventing platelet aggregation

Dipyramidole MOA

Targets the cAMP → AMP receptor which prevents platelet aggregation

Main side effects of antiplatelets

• GI irritation

• Bleeding

• Bronchospasms (aspirin in asthmatics)

Antiplatelets and surgery

Discontinue 7 days prior to elective surgery

Contraindications of antiplatelets

• Active bleeding

• Aspirin - analgesic dose in HF will cause more fluid retention

Timolol

Used in glaucoma as helps to prevent intraocular pressure

Interactions of beta blockers

• When given with IV verapamil, beta blockers can cause asystole and hypotension

• Hyperglycaemia when given with thiazide like diuretics

MOA of beta blockers

They reduce secretion of renin from the kidneys which help reduce blood pressure and decrease HR and consequently work on the heart

Beta blocker dosing

Doses should be increased in 2 week intervals to highest possible tolerated dose

Osophageal varacities

Carvedilol is used in particularly in the management of oesophageal veracities - these generally come about due to the increase in the portal pressure in the liver

6.25mg OD increased if necessary up to 12.5mg

Side effects of Beta blockers

• Bradycardia

• Hypotension

• Bronchospasms

• Cold extremities

Cautions with beta blcokers

• Diabetes → Beta blockers mask tachycardia

• First degree AV block - beta blockers worsen this

• Asthma

• Worsening symtoms of myasthenia gravis

• Thyrotoxicosis

MHRA warnings with beta blockers

Avoid abrupt withdrawal - can worsen angina or precipitate MI

NA+ channel blockers (class 1)

• Flecainide

• Propafenone

• Disopyramide

• Quinidine

All block sodium channels which cause the heart to pump

Class 3 K+ channel blockers

• Amiodarone

• Dronidarone

• Sotalol

Prevents potassium leaving the cell so prolongs the hyperpolarisation period making it longer for another action potential to be initiated

Management of AF

• Pharmacological cardioversion

• Electrical cardioversion - opted for if life threatening - Direct current is recommended for symptoms which persist > 48 hours, after this period there is a requirement for anticoagulation

• With direct current correction if it has been more than 48hours, consider amiodarone for 4 weeks before cardioversion and up to 12 months after

Treatment of non life threatening AF where the patient is haemodynamically unstable

• <48hours rate or rhythm control can be opted for

• >48hours rate control

If rhythm control has been opted for when AF >48hours or unknown, electrical cardioversion is preferred. But delay cardioversion until anticoagulated for at least 3 weeks pre procedure and 4 weeks post procedure - this is done because of the risk of a thrombus. If this isnt possible a left arterial thrombus should be ruled out and parenteral heparin commenced immediately

Maintenance therapy for AF

Maintenance therapy can involve either rate control or rhythm control

• Rate control - beta blocker (NOT sotalol) or rate limiting CCB like diltiazem or verapamil

• Rhythm control - beta blockers (such as sotalol) or another anti arrhythmic such as amiodarone, flecainide, propafenone or dronedarone

Paroxysmal AF

AF which resolves in 48 hours

• Given pill in the pocket eg a beta blocker or anti- arrhythmic

NICE guidance on anti-coagulants in AF

• <65s with no other risk factors of stroke except gender do NOT require anti-coagulation - but have annual reviews

• CHADVAS score >2 offer an anti-coaggulant, if CHAD

Treatment of unstable ventricular tachycardia

• Cardioversion immediately

• If that doesn’t work intravenous amiodarone and then repeat direct current for cardioversion

Treatment of proximal super ventricular tachycardia

Adenosine - treatment of choice with a very short duration of action with t1/2 around 10 seconds

• Adenosine works by increasing potassium conduction which causes hyperpolarisation reducing the action potential from restarting

In asthmatics adenosine causes bronchoconstriction - in this case give IV verapamil

Sotolol

Prior to using sotolol it is recommended to correct hypokalaemia and hypomagnesia

• Dose should be reduced in renal impairment

Emergency treatment of a serious arrhythmia

IV magnesium sulphate 2g over 10-15 mins - dose should be repeated once if necessary

Loading period of ORAL amiodarone for arrhythmias

• 200mg TDS one week

• 200mg BD for further week

• Followed by a maintenance dose of 200mg or minimum dose required to control an arrhythmia

Role of amioderone

It is a class 3 anti-arrhythmic which means it prolongs the refractory period of cardiac myocytes making it harder for depolarisation to happen prematurely

It is used in the treatment of severe cardiac rhythm disorders where other treatments cannot be used or have failed

Loading dose of IV amiodarone for arrhythmias

Initially 5mg/kg over 20-120mins with ECG monitoring, subsequent infusion if necessary. Max 1.2g per day for arrhythmias

Amiodarone dose for ventricular fibrillations

Initially 300mg from a pre-filled syringe or diluted in 20ml glucose 5% the 150mg if required

Monitoring of amiodarone

• Thyroid function before treatment as amiodarone contains iodine - this is done every 6months if hyperthyroidism occurs consider swapping to carbimazole, or levothyroxine in hypothyroidism

• Liver function

• Lung function - X-ray should be taken before treatment as amiodarone can cause pneumonitis pulmonary fibrosis - report SOB or dry cough

• Nerve function

• Eye function - amiodarone can cause microdeposits

• Skin- Phototoxicity - grey skin

Interactions of amioderone

It is an enzyme inhibitor so will interact with warfarin, phenytoin, digoxin - increased conc of all

Risk of myopathy with statins

Increased risk of AV node block, bradycardia, myocardia and depression when used with beta blockers and rate limiting CCBs

MOA of digoxin

Inhibits the sodium-potassium pump, leading to increased calcium levels making the heart pump more efficiently. It also slows the heart rate down through the AV node which helps in AF - so lowers HR without effect BP

Dose of digoxin for AF or flutter

• 0.75- 1.5mg in divided doses to be given over 24 hours - reduced dose in elderly

• Maintenance 125-250mcg dose in accordance to renal function

• Emergency loading dose - IV infusion 0.75-1mg over at least 2 hours then maintenance by mouth

Digoxin dose in HF

No requirements for loading digoxin

62.5-125mcg OD in HF, reduce in elderly

Therapeutic range of digoxin

1-2mcg/l - loading is NOT required in HF

Risk factors for digoxin toxicity

• Drug interaction with digoxin

• Electrolyte imbalance - hypokalaemia - less K+ means more digoxin is binding to sodium/potassium ATPase pump - results of digoxin will be much greater

• Hypokalaemia can be caused by - diuretics, insulin, b2 agonists, insulin, corticosteroids, theophylline

• Decreased plasma concentration- amioderone is a potent enzyme inhibitor so can increase exposure of digoxin

Acronym for interactions with digoxin

C - CCBs

R - Rifampacin

A - amioderone

S - St johns wart

E - Erythromycin

D - Diuretics

MHRA warnings for amioderone

• Regular monitoring required

• Anti-virals increase the exposure of amioderone which can cause severe bradycardia and heart block

Interactions of amioderone

Amioderone is a very potent enzyme inhibitor of cytochrome P450 so will interact with warfarin and digoxin - so the dose of digoxin should be halved when on amioderone

Prophylaxis of VTE

• Mechanical - patients undergo surgery when pharmacological therapy is contraindicated

• Pharmacological - when VTE risk > bleeding risk - should be started asap or within 14 hours of admission

  • Parenteral LMWH/ UFH/ fondaparinux

  • Oral non vitamin k anticoaggulants - dabigatran, rivaroxaban, apixaban, endoxaban

  • Warfarin

Duration of VTE prophylaxis

• General surgery - 5-7 days or until sufficiently mobile

• Major cancer surgery in abdomen or pelvis - 28 days after surgery

• Spinal surgery - 30 days after surgery

• Hip replacements - LMWH heparin for 10 days (Eg daltaparin or endoxaban), followed by low dose aspirin for 28 days, or LMWH with stockings or rivaroxaban

• Elective knee surgery - low dose asprin for 14 days or LMWH 14 days with stockings or rivaroxaban

Medical patients first line for thrombosis

LMWH heparins are first line LMWH are PREFFERED over UFH as lower risk of osteoporosis and heparin induced thrombocytopenia

Fondaparinux is an alternative

If renally impaired an unfractionated heparin

UFH vs LMWH

UFH:

• Shorter duration of action with great with increased bleed risk and reduced renal function

• Requires measurements of APTT

• Not usually recommended unless patients have renal impairment

LMWH

• Longer duration of action

• Prefered in pregnancy as there is a low risk of osteoporosis and HIT

Pharmacological approaches to prevent the reoccurrence of VTE

• Rivaroxaban - 50mg BD for 21 days then down to 20mg OD or 15mg OD if low CrCl (15-49) for 7 days

• Apixaban

• If not an option consider LMWH for 5 days followed by dabigatran or endoxaban

• If all above arent an option consider LMWH with a vitamin K antagonist (warfarin) for 5 days or until INR is at least <2 for 5 days, followed by warfacrin alone

Warfarin counselling acronym

C- Cranberry juice and grapefruit juice can assist the bleeding effects and so should be avoided

A- antivirals - enzyme inhibitors

M- Miconazole (daktarin - enzyme inhibitor)

P- Pomegranate juice should be avoided

S- Statins lead to elevation of INR and bled risk

Leafy greens and Warfarin

Leafy greens are a source of vitamin K so you want to make sure that patients don’t have sudden changes in their diet as warfarin is a vitamin k antagonist

What do you do if there is bleeding with warfarin

STOP warfarin and start IV phytomenadione or additionally dried prothrombin complex or fresh frozen plasma (if major bleed)

• If INR is 5-8 - withhold 1-2 doses and reduce maintenance dose

• INR 5-8 and bleeding - stop warfarin and give IV phytomenadione. Restart warfarin again when INR <5

• INR >8 stop warfarin and give ORAL phytomenadione but with bleeding give IV

BNF doses of IV phytomenadione

In major bleeding in patients on warfarin (in combination with dried prothrombin complex or fresh frozen plasma) → Slow IV injection 5mg, stop warfarin

INR>8 with MINOR bleed → slow IV injection 1-3mg, may need to repeat again if INR is still too high after 24hours. Restart warfarin when INR <5

INR >8 NO BLEED → 1-5mg ORALLY

INR 5-8 with MINOR BLEED → 1-3mg IV

Warfarin and surgery

Elective surgery → stop 5 days prior, if INR is greater than 1.5 day before surgery give oral phytomenadione one day prior to surgery. RESTART warfarin evening of or following day of surgery

Emergency surgery delay 6-12 hours if possible and give IV phytomenadione, if not possible to dlay give dried thrombin complex and IV phytomenadione

Following surgery youll have to bridge with LMWH- start 48 hours post surgery

Factor Xa inhibitors

• Apixaban

• Rivaroxaban

• Edoxaban

Direct thrombin inhibitor

Dabigatran

Antidote for dabigatran is idoracizumab

Initiating treatment of DOACs following a PE and DVT

• Apixaban and rivaroxaban you can go straight into treatment

• Dabigatran and edoxaban you need 5 days of parenteral anticoaggulation eg enoxaparin then you can move over to a DOAC

What are you giving for portal vein thrombosis

Warfarin

• DOACs are STRICTLY NOT LISCENSED

MOA of warfarin

Inhibits vitamin k reductase for all the clotting factors in the clotting cascade - so levels of active vitamin k are reduced which results in a reduction in other clotting factors

MHRA warnings for warfarin

• Changes in liver function may effect efficacy of vitamin k

• Acute illness may cause the effect of warfarin to be exaggerated

• Warfarin has also been reported to cause calelphylaxis so if patients report a painful skin rash then that would be a referral

• Interaction with tramadol - increases INR

MHRA warnings for DOACs

• Any lesions which could pose risk to extreme bleed

• Contaminant with any other anti-coagulant

• Rivaroxaban is contraindicated in transcatheter aortic valve replacement

• DOACs are reversible → Andexanet alfa is the reversible agent for rivaroxaban

Cholesterol targets (5,4,3,2,1…)

• <5mmol/l → Total cholesterol in adults

• <4 → Total cholesterol in those at risk

• <3 → LDL in heathy adults

• <2 → LDL in high risk adults

• >1 → HDL levels

• <1.7 → triglycerides

Pharmacological causes of hyperlipidaemia

• Anti-psychotics

• Immunosuppressants

• Corticosteroids

• Antiretroviral

Statins and pregnancy

When initiating a statin in a women at child bearing age you want to consider contraception during statin treatment due to the risk of adverse effects

• Statins should be stopped 3 months prior to trying to conceive

• Statins shouldnt be restarted until breast feeding has ended

Aim of statins

High intensity statins are those that achieve a reduction in LDL levels greater than 50%, doses of statins should be titrated to achieve that reduction

MOA of statins

Work by inhibiting HMG CoA reductase

• Reduces cholesterol and increased clearance of LDL cholesterol