Title: Pharmacological management of Ischaemic heart disease and acute myocardial infarction
1Pharmacological management of Ischaemic heart
disease and acute myocardial infarction
- Hamid Shamsolkottabi MD
- Cardiologist
- Sina Heart Center, Esfahan, IRAN
2Atherosclerosis
- The complications of atherosclerosis constitute
the greatest cause of morbidity and mortality in
the Western World accounting for 40 of all deaths
3Atherosclerosis
- Progressive luminal narrowing
- - angina pectoris
- - intermittent claudication
- Plaque rupture and thrombosis
- - acute coronary syndromes
- - transient ischaemic attack
- Aneurysm formation
4Aims of treatment
- Relieve symptoms
- Slow disease progression
- Reduce risk of acute event
- Improve survival
5Management overview
- Pharmacological treatment
- Managing risk factors
- Interventional procedures
-
6Angina pectoris
- Myocardial oxygen demand
- exceeds supply ? chest pain
- Stable angina
- - transient myocardial ischaemia
- - predictable, reproducible
- - relieved by rest or GTN
7Principles of treatment
- Increase oxygen supply or reduce oxygen demands
of myocardium - Reduce heart rate
- Reduce preload
- Reduce afterload
- Improve coronary blood flow
8Symptomatic treatment
- Nitrates
- Beta blockers
- Calcium channel blockers
- Potassium channel activators
- Selective pacemaker If current inhibitorIvabradine
(Procolalan)
9Describing any drug
- MOA and pharmacological properties
- Indications
- Cautions/Contraindications
- Side effects
- Important interactions
- Dose/overdose
10Nitrates - Mode of action
- Metabolised to release Nitric oxide (NO)
- ? cGMP
- Dephosphorylation of myosin light chains
- Increased intracellular calcium
- Muscle relaxation
11Nitrates - Mode of action
- Venodilation - ? preload
- Coronary artery vasodilation - ? supply
- Moderate arteriolar dilation - ? afterload
12Pharmacological properties
- Glyceryl trinitrate (GTN)
- short acting, first pass metabolism
- sublingual/intravenous/patch administration
- Isosorbide dinitrate
- intermediate acting
- sublingual/intravenous/oral administration
- Isosorbide mononitrate
- long acting
- oral administration
-
13Alfred Nobel
14Pharmacological properties
- Tolerance (tachyphylaxis)
- - reduced therapeutic effects
- Monday morning sickness
- ? due to depletion of free tissue SH
- Long-acting preparations /infusions/transdermal
patches - Nitrate free period
15Indications
- Relief of acute angina attack
- Prophylaxis of stable angina
- (prior to exercise GTN or long-acting)
- Left ventricular failure
16Cautions/Contraindications
- Hypotension
- Aortic stenosis
- HOCM
- Constrictive pericarditis
17Side effects
- Headache
- Flushing
- Dizziness
- Postural hypotension
- Tachycardia
- Overdose rarely precipitates methaemoglobinaemia
18Important interaction
- Phosphodiesterase inhibitors eg sildenafil
- Inhibits cGMP breakdown
- severe hypotension
- nitrates contraindicated if taken within the
previous 24 hours - Infusion reduces anticoagulant effect of heparin
19Beta blockers
20Mode of action
- Competitive inhibitors of catecholamine at
beta-adrenoceptor sites - Inhibit sympathetic stimulation of heart and
smooth muscle - ? HR ? contractility ß1
- Vasoconstriction bronchoconstriction ß2
21Pharmacological properties
- 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
22Indications
- Symptomatic angina
- Hypertension
- Acute coronary syndromes
- Post myocardial infarction
- Stable heart failure
- Arrhythmias
- Thyrotoxicosis/Benign essential tremor
23Cautions/Contraindications
- C/I in asthma
- Uncontrolled heart failure
- Bradycardia
- Heart block
- Phaeochromocytoma without prior alpha blockade
- Caution coronary spasm/COPD/PVD
- Avoid abrupt withdrawal
24Important Interaction
- Verapamil and beta blockers ? precipitate heart
block - asystole - Must NOT give IV verapamil to beta blocked
patients - Extreme caution combined orally
25Side effects
- Beta-1 effects Bradycardia, heart block, heart
failure - Beta-2 effects bronchospasm, worsening PVD,
Raynauds phenomenon - Fatigue, depression, nightmares, impotence
- May mask hypoglycaemia and worsen glycaemic
control in IDDM
26Dose
- Rational choice - long-acting cardioselective
beta blocker od or bd - Anti-anginal effects are dose related
- Titrate to resting heart rate 50-60 bpm
27Calcium antagonists
28Mode of action
- 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
29Pharmacological 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
30Indications
- Symptomatic control of angina
- Coronary spasm
- Hypertension
- Arrhythmias
- Subarachnoid haemorrhage (nimodipine)
31Side effects
- Peripheral vasodilation
- - flushing, headache, ankle oedema
- Cardiac effects
- - AV block, heart failure
- Constipation
- Short-acting dihydropyridines a/w ? mortality and
MI
32Potassium channel activators
33Potassium channel activators - nicorandil
- Activates K ATP channel
- NO donor effects
- Arterial and venodilator
- S/E Flushing, dizziness, headache
- Usually 3rd or 4th line agent
34Selective 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)
35Additional therapy in stable angina
- Low-dose aspirin
- Lipid lowering therapy
- ACE inhibitors
- Treat ?BP and diabetes
- Smoking cessation
- Weight reduction
- Intervention
36Antiplatelet agents
- 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
37Acute coronary syndrome
- Angina at rest gt20mins
- New onset angina severely affecting exercise
tolerance - Increasing frequency or duration or occurring
with lesser exertion
38Acute coronary syndromes
- Plaque rupture and coronary thrombosis
- Unstable angina
- Non-ST elevation MI (subendocardial infarction)
- Acute transmural myocardial infarction
39Goals of treatment
- 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
40Initial Management
- 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
41Definitive treatment-ST elevation Myocardial
infarction
- Primary coronary angioplasty
- 90 recanalisation
- Door to balloon time lt90mins ? up to 3hrs
- Ideal where cardiogenic shock and when
thrombolytics contraindicated - clopidogrel 300mg loading dose then 75mg
od - Glycoprotein IIb/IIIa inhibitors
(abciximab)
42Definitive treatment-ST elevation Myocardial
infarction
- Primary PCI not available
- Thrombolysis
- 50-60 recanalisation
- Door to needle time lt30mins
- Effective up to 12 hours
43Fibrinolytic agents
44Mode of action
- 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
45Indications
- Acute ST elevation myocardial infarction
- Acute pulmonary embolism
- Acute ischaemic stroke within 3 hours
46Contraindications
- Recent haemorrhage trauma or surgery
- Recent dental extraction
- Coagulation defectsbleeding 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)
47Relative contraindications
- Venepuncture (non-compressible site)
- Recent invasive procedure
- External chest compressions
- Pregnancy
- Abdominal aortic aneurysm
- Diabetic retinopathy
- Anticoagulant therapy
48Side effects
- Nausea and vomiting
- Bleeding
- Reperfusion arrhythmias
- Hypotension
- Back pain
- Allergic reactions (esp streptokinase)
49Unstable angina/NSTEMI
- 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
50Reading/Website list
- British national formulary BNF
- www.uptodate.com
- American heart association guidelines