Download Pharmacological management of Ischaemic heart disease stroke

Pharmacological
management of Ischaemic
heart disease and acute
myocardial infarction
October 2006
Atherosclerosis
The complications of atherosclerosis
constitute the greatest cause of
morbidity and mortality in the Western
World accounting for 40% of all
deaths
Atherosclerosis
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Progressive luminal narrowing
- angina pectoris
- intermittent claudication
Plaque rupture and thrombosis
- acute coronary syndromes
- transient ischaemic attack
Aneurysm formation
Aims of treatment
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Relieve symptoms
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Slow disease progression
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Reduce risk of acute event
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Improve survival
Management overview
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Pharmacological treatment
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Managing risk factors
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Interventional procedures
Angina pectoris
Myocardial oxygen demand
exceeds supply  chest pain
 Stable angina
- transient myocardial ischaemia
- predictable, reproducible
- relieved by rest or GTN
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Principles of treatment
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Increase oxygen supply or reduce
oxygen demands of myocardium
Reduce heart rate
Reduce preload
Reduce afterload
Improve coronary blood flow
Symptomatic treatment
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Nitrates
Beta blockers
Calcium channel blockers
Potassium channel activators
Selective pacemaker If current
inhibitorIvabradine (Procolalan)
Describing any drug
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MOA and pharmacological properties
Indications
Cautions/Contraindications
Side effects
Important interactions
Dose/overdose
Nitrates - Mode of action
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Metabolised to release Nitric oxide (NO)
 cGMP
Dephosphorylation of myosin light
chains
Increased intracellular calcium
Muscle relaxation
Nitrates - Mode of action
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Venodilation -  preload
Coronary artery vasodilation -  supply
Moderate arteriolar dilation -  afterload
Pharmacological properties
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Glyceryl trinitrate (GTN)
short acting, first pass metabolism
sublingual/intravenous/patch administration
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Isosorbide dinitrate
intermediate acting
sublingual/intravenous/oral administration
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Isosorbide mononitrate
long acting
oral administration
Alfred Nobel
Pharmacological properties
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Tolerance (tachyphylaxis)
- reduced therapeutic effects
“Monday morning sickness”
? due to depletion of free tissue –SH
Long-acting preparations
/infusions/transdermal patches
“Nitrate free period”
Indications
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Relief of acute angina attack
Prophylaxis of stable angina
(prior to exercise GTN or long-acting)
Left ventricular failure
Cautions/Contraindications
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Hypotension
Aortic stenosis
HOCM
Constrictive pericarditis
Side effects
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Headache
Flushing
Dizziness
Postural hypotension
Tachycardia
Overdose rarely precipitates
methaemoglobinaemia
Important interaction
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Phosphodiesterase inhibitors eg sildenafil
Inhibits cGMP breakdown
severe hypotension –
nitrates contraindicated if taken within
the previous 24 hours
Infusion reduces anticoagulant effect of
heparin
Beta blockers
Mode of action
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Competitive inhibitors of catecholamine at
beta-adrenoceptor sites
Inhibit sympathetic stimulation of heart
and smooth muscle
 HR  contractility β1
Vasoconstriction & bronchoconstriction β2
Pharmacological properties
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Cardioselective – eg atenolol metoprolol
Non selective – eg propranolol
Intrinsic sympathomimetic (partial agonist)
activity – eg celiprolol pindolol
Alpha-blocking activity eg carvedilol
Lipid soluble (eg propranolol) versus water
soluble (eg atenolol)
Up-regulation of receptors – withdrawal
syndrome
Indications
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Symptomatic angina
Hypertension
Acute coronary syndromes
Post myocardial infarction
Stable heart failure
Arrhythmias
Thyrotoxicosis/Benign essential tremor
Cautions/Contraindications
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C/I in asthma
Uncontrolled heart failure
Bradycardia
Heart block
Phaeochromocytoma without prior alpha
blockade
Caution coronary spasm/COPD/PVD
Avoid abrupt withdrawal
Important Interaction
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Verapamil and beta blockers 
precipitate heart block +- asystole
Must NOT give IV verapamil to beta
blocked patients
Extreme caution combined orally
Side effects
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Beta-1 effects – Bradycardia, heart block,
heart failure
Beta-2 effects – bronchospasm, worsening
PVD, Raynaud’s phenomenon
Fatigue, depression, nightmares, impotence
May mask hypoglycaemia and worsen
glycaemic control in IDDM
Dose
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Rational choice - long-acting
cardioselective beta blocker od or bd
Anti-anginal effects are dose related
Titrate to resting heart rate 50-60 bpm
Calcium antagonists
Mode of action
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Prevent opening of voltage-gated calcium
channels
Bind to -1 subunit of cardiac and smooth
muscle L-type calcium channels
Vasodilator effect on resistance vessels 
afterload
Coronary artery dilation
Negative chronotropic
Negative inotropic effects
Pharmacological properties
3 classes
 Phenylalkylamines eg verapamil
- relatively cardioselective
- -ve chronotropic and inotropic
 Dihydropyridines eg nifedipine amlodipine
- relatively smooth muscle selective
- potent vasodilator
 Benzothiazepines eg diltiazem
- intermediate
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Indications
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Symptomatic control of angina
Coronary spasm
Hypertension
Arrhythmias
Subarachnoid haemorrhage
(nimodipine)
Side effects
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Peripheral vasodilation
- flushing, headache, ankle oedema
Cardiac effects
- AV block, heart failure
Constipation
Short-acting dihydropyridines a/w 
mortality and MI
Potassium channel
activators
Potassium channel
activators - nicorandil
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Activates K ATP channel
NO donor effects
Arterial and venodilator
S/E Flushing, dizziness, headache
Usually 3rd or 4th line agent
Selective pacemaker If
current inhibitor
 Ivabradine (Procolalan)
 reduces spontaneous beating rate of the
sinus node by slowing the diastolic
depolarization slope of the action potential
 selective and prolonged reduction in heart
rate, both at rest and during exercise
 Indicated for angina where cannot give a
beta blocker
 Ongoing trials (Beautiful trial)
Additional therapy in
stable angina
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Low-dose aspirin
Lipid lowering therapy
ACE inhibitors
Treat BP and diabetes
Smoking cessation
Weight reduction
Intervention
Antiplatelet agents
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Aspirin – inhibits cyclo-oxygenase and
thromboxane A2 synthesis
Theinopyridines – clopidogrel – block
binding of ADP to platelet receptor
Glycoprotein IIb/IIIa inhibitors
(abciximab) – inhibit cross-bridging of
platelets by fibrinogen
Acute coronary syndrome
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Angina at rest >20mins
New onset angina severely affecting
exercise tolerance
Increasing frequency or duration or
occurring with lesser exertion
Acute coronary
syndromes
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Plaque rupture and coronary thrombosis
Unstable angina
Non-ST elevation MI (subendocardial
infarction)
Acute transmural myocardial infarction
Goals of treatment
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Relief of ischaemic pain
Assess haemodynamic state
Anti-platelet therapy to prevent further
thrombosis
Initiate reperfusion therapy with
percutaneous angioplasty or
thrombolysis if appropriate
Secondary prevention
Initial Management
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Oxygen
Aspirin 150-300mg chewed/dispersible
Nitrates GTN 0.4mg sublingual +- IV
Intravenous morphine 2.5-10mg+ antiemetic cyclizine 50mg
Decide on definitive treatment
Beta-blocker atenolol 5mg over 5 mins repeated after 10-15
mins
Clopidogrel 300mg if undergoing PCI
Glycoprotein IIb/IIIa inhibitors (abciximab) if undergoing PCI
ACE inhibitor within 24 hours
Tight glycaemic control
Optimise potassium and magnesium
Definitive treatmentST elevation Myocardial
infarction
Primary coronary angioplasty
90% recanalisation
Door to balloon time <90mins ? up to 3hrs
Ideal where cardiogenic shock and when
thrombolytics contraindicated
clopidogrel 300mg loading dose then 75mg od
Glycoprotein IIb/IIIa inhibitors (abciximab)
Definitive treatmentST elevation Myocardial
infarction
Primary PCI not available
Thrombolysis
50-60% recanalisation
Door to needle time <30mins
Effective up to 12 hours
Fibrinolytic agents
Mode of action
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Activate plasminogen to form plasmin
which degrades fibrin breaking up thrombi
Streptokinase, alteplase, reteplase,
tenecteplase
Streptokinase – antibodies within 4 days
Alteplase, reteplase followed by heparin for
48 hours
Indications
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Acute ST elevation myocardial
infarction
Acute pulmonary embolism
Acute ischaemic stroke within 3 hours
Contraindications
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Recent haemorrhage trauma or surgery
Recent dental extraction
Coagulation defects;bleeding disorders
Aortic dissection
History of cerebrovascular disease
Active peptic ulceration
Severe menorrhagia
Severe hypertension
Active cavitating lung disease
Acute pancreatitis
Severe liver disease
Oesophageal varices
Previous reaction to streptokinase (Streptokinase)
Relative contraindications
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Venepuncture (non-compressible site)
Recent invasive procedure
External chest compressions
Pregnancy
Abdominal aortic aneurysm
Diabetic retinopathy
Anticoagulant therapy
Side effects
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Nausea and vomiting
Bleeding
Reperfusion arrhythmias
Hypotension
Back pain
Allergic reactions (esp streptokinase)
Unstable angina/NSTEMI
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“MONA” – morphine; O2; nitrate; aspirin
Heparin eg enoxaparin 1mg/kg 12 hourly
Beta-blocker atenolol 5mg over 5 mins repeated
after 10-15 mins
Clopidogrel
Glycoprotein IIb/IIIa inhibitors (abciximab) if
undergoing PCI
ACE inhibitor if indicated
Tight glycaemic control
Optimise potassium and magnesium
Reading/Website list
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British national formulary BNF
www.uptodate.com
American heart association guidelines