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Management of ischaemic

heart disease (stable angina)

Dr R Gounden

Division of Clinical Pharmacology

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Stable angina

Angina pectoris which is precipitated by

physical activity, is relieved by rest and is

usually of short duration (under 2 minutes)

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The drugs used in stable angina

Aspirin

Beta-blockers (verapamil if asthmatic)

HMG Co-A reductase inhibitors (statins)

Nitrates

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Aspirin

Is an irreversible inhibitor of plateletcyclooxygenase

Cyclooxygenase leads to platelet aggregation

The antiplatelet effect of aspirin lasts for theentire lifespan of the platelet (8 to 10 days)

Reduces cardiovascular events when used instable angina

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Mechanism of action and toxicity

Cyclooxygenase (COX)

COX-1 is foundthroughout the

body: gastricmucosa andplatelets

COX 2 isproduced at sites

of inflammation

Protects gastricmucosa

Pain and inflammation

aspirin

Leads to plateletaggregation

Regulates renal blood flow

Produces prostacyclin(vasodilator and inhibitor ofplatelets)

aspirin

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Adverse effects of aspirin

Gastric and duodenal ulcers (by inhibiting theproduction of protective prostaglandins)

Bronchoconstriction in asthmatics (by drivingleukotriene production)

Nephrotoxicity (by impairing renal blood flow)

Hepatotoxicity (rare)

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Atheromatous plaque

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HMG Co-A Reductase Inhibitors (Statins)

These are used in IHD even when thefasting lipogram is normal

In this setting it is used as secondaryprevention to prevent progression ofatherosclerosis

It may also stabilize plaques and preventplaque rupture

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The Statins

HMG- Co A is converted to mevalonate by reductase

Rate limiting step in cholesterol synthesis

Statins are competitive inhibitors of HMG Co-A

Decreased hepatic cholesterol synthesis- up regulates LDLreceptors

LDL is therefore scavenged from the peripheral circulation

Decreases mortality

The major adverse effects are myopathy and increases in serumtransaminases

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Beta blockers

Beta blockade reduces the oxygen demand on the heart

Beta-blockers are negatively inotropic and chronotropic

They restrict the increase in heart rate during exercise

However beta blockers are contraindicated in asthma,

uncontrolled heart failure and heart block

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Calcium channel blockers

Verapamil is an alternative to the beta-

blockers in patients with asthma

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The nitrates

Used for symptomatic relief of angina or prevention of angina

Nitrates are an exogenous source of vasodilatory nitric oxide-produce coronary vasodilation

It is a venodilator and therefore decreases the preload and leftventricular end- diastolic pressure- less wall stress

As the dose increases, afterload is also reduced by arteriolardilation

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Problems associated with nitrate

use

Headaches are common

Hypotension and syncope

Tolerance is a problem when used prophylactically- nitrate free interval is important or eccentricdosing

Discard 60 days after opening- keep in original container

(they are volatile and adsorb to plastic containers)

Tachycardia or bradycardia

Nitrates should be used with caution in patients who have used Sildenafil in the last 24- 48hours

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How to use nitrates

To relieve chest pain

Patient should be sitting

Take one every five minutes till pain stops or 4 to 5 tablets have been taken-(gyceryl trinitrate, isosorbide dinitrate)

Can be given as a sublingual spray

To prevent angina (prophylactic use)

Isosorbide dinitrate or mononitrate for prophylaxis (long acting oral tablets

The patch can also be used but this can promote tolerance