ROLE OF Β BLOCKERS AND ANTI PLATELETS IN MI

WHAT IS MYOCARDIAL INFARCTION??

MYOCARDIAL INFARCTION commonly referred to as HEART ATTACK ,is death of cardiac muscle due to prolonged ischaemia

TYPES NSTEMI STEMI

β-BLOCKERS IN MI

CARDIOSELECTIVE β1 BLOCKERS Metoprolol Atenolol Acebutolol Esmolol Bisoprolol

NON SELECTIVE β1&β2 BLOCKERS Without intrinsic sympathomimetic

activity Propranolol Sotalol

MECHANISM OF ACTION OF β-BLOCKERS

β-Blockers Block cardiac β1 receptors

Decreases FOC ,HR ,BP

decrease myocardial oxygen demand

NEGATIVE CHRONOTROPIC EFFECT

NEGATIVE INOTROPIC EFFECT

METOPROLOL It is a cardioselective β1 blocker.(prototype) PK - it is well absorbed orally low bioavailabilty due to significant first pass metabolism.It is hydroxylated by CYP2D6 before excretion.Plasma t1/2 3-6 hrsDOSAGE-IV dose of 5mg over 2 min repeated every

5 min(total 3 doses) followed by 50 -100mg orally every 12 hrs.

PROPRANOLOL It is a non selective β blocker Well absorbed orally but low oral

bioavailability due to high first pass metabolism.

Lipid soluble Bioavailability is increased with food Its metabolites are excreted in urine mostly

as glucuronides.

contd. Plasma t½ is 3-5hrs More than 90% of propranolol is

protein bound DOSAGE- IV dose of 0.1mg per kg

divided into 3 doses at 5-10 min followed by 20-40mg orally every 6-8hrs

ATENOLOL Selective β1 blocker PK-incompletely absorbed orally but first

pass metabolism is not significant. Low lipid solubility Because of longer duration of action once

daily dose is sufficient. DOSAGE-IV dose of 5-10mg followed by

100mg orally once daily

BENEFITS OF β BLOCKERS High risk pts those who had large

infarcts should be put on β blockers for at least 2 yrs.

1 .SECONDARY PROPHYLAXIS OF MI prevents re-infarction prevents sudden ventricular

fibrillation at subsequent attack of MI

2.MYOCARDIAL SALVAGE DURING EVALUATION OF MI

Limit infarct size by reducing O2 consumption.

Prevent arrhythmias including ventricular fibrillation.

ADVERSE EFFECTS OF β BLOCKERS PROPRANOLOL Worsens peripheral vascular

diseases. GI upset Lack of drive Sleep disturbances Impotence in male pts Dry eyes and hair loss Sudden stoppage of propranolol

worsens the condition.

METOPROLOL Side effects are milder compared to

propranolol so it is most commonly used.

CONTRAINDICATIONS of non selective β blockers

Bronchial asthma DM Heart rate less than 60 /min systolic blood pressure less than 100 mmHg

β-blockers preferred in bronchial asthma and DM

Metoprolol Atenolol

ROLE OF ANTI PLATELETS IN MI• Drugs - Aspirin Dipyridamole P2Y 12 Receptors blockers Ticlopidine Clopidogrel

Prasugrel GP ןןb/ןןןa Antagonists Abciximab Eptifibatide Tirofiban

Mechanism of Antiplatelets

ASPIRIN It inhibits COX 1 and TX synthase

irreversibly. so thromboxane A2 formation is inhibited at low doses.

Inhibition of COX1 by aspirin in vessel wall decreases PGI2 formation at high doses

DOSAGE - Low dose 75 -150 mg per day or 300mg twice weekly

High dose greater than 900mg /day

CLOPIDOGREL Newer and more potent irreversible inhibitor

of platelets(P2Y12 receptor blocker) It is a slow acting drug activated in liver by

CYP2C19 . Omeprazole,an inhibitor of CYP2C19

reduces metabolic activation of clopidogrel Action lasts for 5 -7 days and t1/2 is 8hrs. Adverse effects are

bleeding,neutropenia,thrombocytopenia,epigastric pain

DOSAGE- 75mg OD

PRASUGREL Latest most potent and fast acting

P2Y12 receptor blocker. It is rapidly absorbed, completely

activated resulting in faster and more consistent platelet inhibition.

Activated by CYP2C19 but omeprazole interference is not prominent.

S/E –bleeding

CONTRAINDICATIONS- pts of ischaemic stroke and transient ischaemic attacks due to risk of intracranial hemorrhage.

DOSAGE-10mg OD For elderly and for

those less than 60 kg bodyweight 5mg OD is given.

loading dose of 60 mg is given for immediate action.

ABCIXIMAB(Gpııb/ıııa Antagonist)

It is Fab fragment of a chimeric monoclonal antibody against GPןןb/ןןןa protein.

Platelet inhibition occurs for 12 -24 hrs. It is non antigenic. T1/2 is 10 -30 min. It is expensive

S/Es – Haemorrhage Thrombocytopenia constipation

arrhythmias DOSAGE-0.25 mg per kg IV 10 -60

min before PCI followed by 10µg/min for 12 hrs.

COMBINATION THERAPY NSTEMI- aspirin + clopidogrel for 1 yr. STEMI –prasugrel+aspirin for pts

undergoing PCI Prasugrel is preferred over clopidogrel

in diabetes Aspirin + GPןןb/ןןןa antagonists for high risk pts

undergoing PCI Abciximab /eptifibatide/tirofiban infused

IV along with oral aspirin and s.c heparin reduce incidence of restenosis and subsequent MI after

coronary angioplasty

contd. GPןןb/ןןןa antagonists are infused for a maximum

of 72 hrs .• Aspirin and/or clopidogrel given to ACS pts treated

with thrombolysis.• Aspirin +GPןןb/ןןןa antagonists /prasugrel for

coronary Artery bypass surgery• Patency of recanalised coronary artery or

implanted vessel is improved and incidence of re occlusion is reduced by continuing aspirin+clopidogrel/prasugrel

THANKYOU