BY: DR. MARWA SHAALAN

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Definition

Types of Angina

Management of Angina

Antianginal drugs BY: DR. MARWA SHAALAN

Transient Myocardial Transient Myocardial ischemiaischemia

Severe Chest painSevere Chest pain

Myocardial Blood Flow

Myocardial O2 Demands

Angina Pectoris

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Chest pain caused by transient

myocardial ischemia due to an

imbalance between myocardial

oxygen supply and demand.

Chest pain caused by transient

myocardial ischemia due to an

imbalance between myocardial

oxygen supply and demand.

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Types of AnginaTypes of Angina1. Stable Angina.

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2. Unstable Angina.

3. Variant Angina.

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1.1. Stable Angina .

Retrosternal painRetrosternal pain

Radiating to left arm & Radiating to left arm & shouldershoulder

The commonest cause isThe commonest cause is ADVANCED ADVANCED ATHEROSCELEROSISATHEROSCELEROSIS

Lasting less than 15 min.Lasting less than 15 min.

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ExertionExertionEmotionEmotion

Heavy mealsHeavy mealsExposure to cold Exposure to cold

weatherweather

Predisposing factors Relieving factors

RestRest

sublingual nitroglycerin

Stable Angina

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Exercise ECG showing typical severe down sloping Exercise ECG showing typical severe down sloping ST ST segmentsegment : :

Anginal pain is often associated with Depression Anginal pain is often associated with Depression of of STST segment segment

Standing 1 min. 3 min. 7 min. 9 min.

Stable Angina

In between attacks In between attacks :: ECG is entirelyECG is entirely NORMALNORMAL

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2.2. Unstable Angina .Increased frequencyIncreased frequency, , severity or duration severity or duration of pain in a patient of Stable Anginaof pain in a patient of Stable Angina

Myocardial infarction may occur in 10-20% of patients.Myocardial infarction may occur in 10-20% of patients.

N.B.N.B.

Pain occurs with less exertion Pain occurs with less exertion or at restor at rest

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The underlying cause isThe underlying cause is

•Atheroscelerotic changesAtheroscelerotic changes

Fissuring of atheroscelerotic plaques Fissuring of atheroscelerotic plaques

Platelet aggregation Platelet aggregation

ThrombosisThrombosis

Coronary artery spasmCoronary artery spasm

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3.3. Variant Angina .(Prinzmetal)

Chest pain at rest due to Chest pain at rest due to coronary artery spasmcoronary artery spasm

ECG ECG changeschanges::

Acute elevation of Acute elevation of STST segmentsegment

The baseline ECGWith chest pain ,

marked ST segment elevation

Return of the ST segment to the baseline after

nitroglycerin administration

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Management of Angina

Management of Stable Angina

Management of Unstable Management of Unstable AnginaAngina

Management of Variant Angina

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A-Management of Stable Angina

1- 1- General measures.General measures.

2- 2- Drug Treatment.Drug Treatment.

3- 3- Coronary artery Coronary artery revascularization.revascularization.

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Stop smokingStop smoking Reduce weightReduce weight

Treat Hypertension , Treat Hypertension , Hypercholestrolimia Hypercholestrolimia

and Diabetes and Diabetes

AVOID AVOID Severe Severe exertionexertion

Heavy mealHeavy meal EmotionsEmotions Cold WeatherCold Weather

General measures

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•Graduated exercise may open new collaterals

a.a. For an acute attackFor an acute attack

b.b. For immediate pre-exertional For immediate pre-exertional

prophylaxisprophylaxis

c.c. For long-term prophylaxisFor long-term prophylaxis

d.d. Antiplatelet therapy.Antiplatelet therapy.

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Treatment of an acute attack of angina1-Sublingual1-Sublingual nitroglycerin nitroglycerin (0.5 mg ) or (0.5 mg ) or

isosorbide dinitrate (5 mg ) isosorbide dinitrate (5 mg ) or Oral sprayOral spray nitroglycerinnitroglycerin (0.4 mg/metered (0.4 mg/metered

dose), dose), isosorbide dinitrateisosorbide dinitrate(1.25 mg/metered (1.25 mg/metered dose) dose)

Relief within 1-3 min. Persistence of pain

Repeat nitroglycerin at 5 min. Repeat nitroglycerin at 5 min. interval (3 tab. max.)interval (3 tab. max.)

Relief not relieved

InfarctionHOSPITALIZATION15


2-Immediate pre-exertional prophylaxis of 2-Immediate pre-exertional prophylaxis of AnginaAngina

Sublingual nitroglycerin (0.5 mg) or isorbide dinitrate (5 mg) should be taken 5 min. before effort.

3-For Long term prophylaxis:3-For Long term prophylaxis:Long acting nitrates, Ca++ channel blockers,

-blockers or combinations of these drugs.

4-Antiplatelet therapy:4-Antiplatelet therapy:

Aspirin in small dose (75-150 mg daily orally)Aspirin in small dose (75-150 mg daily orally)

or Dipyridamole (75 mg t.d.s orally)or Dipyridamole (75 mg t.d.s orally)16


Coronary artery bypass grafting Coronary artery bypass grafting (CABG)(CABG)

Percutaneous Transluminal Percutaneous Transluminal coronary Angioplasty (PTCA)coronary Angioplasty (PTCA)

For patients not responding to For patients not responding to adequate medical therapyadequate medical therapy

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B-Management of Unstable AnginaNitrateNitrate

++-blocker-blocker

++Aspirin (low dose) and/orAspirin (low dose) and/or

Heparin orHeparin orThrombolytic (stryptokinase)Thrombolytic (stryptokinase)to minimize risk of infarctionto minimize risk of infarction

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C-Management of Variant Angina

Nitrates andNitrates and/or /or Ca++Ca++ Channel blockersChannel blockers

For the acute attack & For the acute attack & prophylaxisprophylaxis

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What are the antianginal drugs?

1-Organic nitrates.

3-Calcium channel blockers.

2-- adrenoceptor blockers.

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NITRATESNITRATES

VeinsVeins

ArteriesArteries

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Relaxation of smooth Relaxation of smooth muscles Dilatationmuscles Dilatation

Cellular Mechanism of Vasodilatation

NitratesNitrates Formation of Formation of Nitric oxide (NO)Nitric oxide (NO)

Activation of Activation of Guanylate cyclaseGuanylate cyclase

Synthesis of Synthesis of cyclic GMPcyclic GMP

Relaxation of Vascular Relaxation of Vascular smooth musclessmooth muscles

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N.B. (-SH) groups are required for formation of NO.

Effect of Nitrates :Effect of Nitrates :

On Stable Angina :On Stable Angina :

Venodilatation Arteriolar dilatation

PreloadPreload AfterloadAfterload

Myocardial Myocardial Oxygen demandOxygen demand

2- Redistribution of coronary flow towards subendocardium

3- Dilatation of coronary collateral vessels.

1-1-

On Variant Angina :On Variant Angina :

Relax smooth muscles of the epicardial coronaries relieve coronary artery spasm

On Unstable Angina :On Unstable Angina :

Dilatation of epicardial coronary arteries + reducing O2 demands

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Preparations :

Short actingShort actingFor acute attacksFor acute attacks

Long actingLong acting For antianginal prophylaxisFor antianginal prophylaxis

Nitroglycerin Nitroglycerin (sublingual, buccal (sublingual, buccal spray)spray)

Isosorbide Isosorbide dinitrate(sublingual, dinitrate(sublingual, buccal spray)buccal spray)

NitroglycerinNitroglycerin

oral SR (6.25-12mg) 2-4 oral SR (6.25-12mg) 2-4 times/daytimes/day

- 2% ointment (1-1.5 - 2% ointment (1-1.5 inch/4hrs)inch/4hrs)

- patches (1 patch=25mg)/day- patches (1 patch=25mg)/day

Isosorbide dinitrate (oral) 10-Isosorbide dinitrate (oral) 10-40mg t.d.s.40mg t.d.s.

Isosorbide mononitrate (oral) Isosorbide mononitrate (oral) 20mg/12 hrs.20mg/12 hrs.

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Duration of Action of Various Preparations of

Organic Nitrates

Preparation Duration of

action

" Short-acting"1-Nitroglycerin

2- Isosorbide dinitrate

a) Sublingual b) Spray

a) Sublingual b) Spray

10-30 min 10-30 min

Up to 60 min. 1.5 hours

" Long-acting" 1-Nitroglycerin

2- Isosorbide dinitrate 3-Isosorbide mononitrate

a) Oral; sustained releaseb) Ointmentc) Transdermal patches Oral Oral

4-8 hours3-6 hours 8-12 hours

4-6 hours 6-10 hours

Adverse Reactions :Adverse Reactions :1- Postural Hypotension & 1- Postural Hypotension &

SyncopeSyncope2- Tachycardia2- Tachycardia

5- Throbbing Headache5- Throbbing Headache

4- Facial Flushing4- Facial Flushing

3- Drug Rash3- Drug Rash

6- Prolonged high dose 6- Prolonged high dose MethaemoglobinaemiaMethaemoglobinaemia

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How does it occur?

The main limitation of chronic nitrate therapy is

TOLERANCE

It develops as SH groups in vessel wall become oxidized by constant exposure to nitrates, this prevents the production of NO & hence stimulation of Guanylate cyclase which is believed to be fundamental to smooth muscle relaxation produced by the drugs.

Tolerance to the antianginal effect occurs as a result of chronic administration

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“NITRATE FREE INTERVAL” of 8-10 hrs reduces or prevents development of nitrate tolerance.e.g. isosorbide dinitrate is given at 7am, noon and 5pm; trnsdermal patches should be used for about 12 hrs daily

What are nitrosamines & what is their medical importance ?

What is the effect of nitroglycerin on platelet aggregation ?

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These are small molecules formed from the combination of nitrates and nitrites with amines.

They are also found in tobacco and cigarette smoke. Some of them may cause cancer in humans, but there is no evidence that the small doses of nitrates used in treatment of angina result in significant body levels of nitrosamines.

It decreases platelet aggregation.

-blockers are effective in STABLE & UNSTABLE angina

In contrast they are not useful for

vasospastic angina (Variant) {Prinzmetal}&

may worsen the condition. This deleterious effect is likely due to an increase in coronary resistance caused by the unopposed effects of catecholamines acting at -adrenoceptors.

The effectiveness of The effectiveness of -adrenoceptor blockers in the -adrenoceptor blockers in the treatment of exertional angina is attributable to a fall treatment of exertional angina is attributable to a fall in myocardial Oin myocardial O22 requirement at rest & during requirement at rest & during

exertion due to :exertion due to :

1- A -ve chronotropic effect (particularly during 1- A -ve chronotropic effect (particularly during

exercise).exercise).

2- A -ve inotropic effect. 2- A -ve inotropic effect.

3- A reduction in arterial blood pressure (particularly 3- A reduction in arterial blood pressure (particularly

systolic pressure) during exercise.systolic pressure) during exercise.

Mechanism of antianginal action:Mechanism of antianginal action:

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However the net effect of -blockers is to myocardial O2 requirement particularly during exercise; their potentially deleterious effects can be balanced by concomitant use of nitrates

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Rate & contractility

Undesirable effects of -blockers in treatment of angina:

Systolic ejection period & left ventricular end diastolic vol. Myocardial O2 requirements

Dosage and Route of Administration

Drug Route Dosage

Propranolol Oral 30-360 mg/day in 2-4 divided doses

Nadolol Oral 40-80 mg ONCE daily

Atenolol Oral 50-100 mg ONCE daily

Metoprolol Oral 50-100 mg TWICE daily

Adverse ReactionsAdverse Reactions : :

CHFCHF A-V blockA-V block BronchospasmBronchospasm

Cold Cold extremitiesextremities Worsening Worsening

symptoms of PVDsymptoms of PVDHypotensionHypotension

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Fatigue & Fatigue & weaknessweakness

Mask signs of Mask signs of HypoglycemiaHypoglycemia

Nightmares , Hallucinations , Nightmares , Hallucinations , Depression.Depression.

Plasma Triglycerides & HDL Plasma Triglycerides & HDL CholesterolCholesterol Discontinuation after Discontinuation after

long ttt exacerbates long ttt exacerbates AnginaAngina

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Adverse ReactionsAdverse Reactions : :

CHFCHF A-V blockA-V block

Peripheral Peripheral Vascular Vascular diseasedisease

HypotensionHypotension

Contraindications :Contraindications :

Bronchial Bronchial asthmaasthma

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Verapamil (80-160 mg) /8 hr(80-160 mg) /8 hr

Diltiazem (60-120 mg) /8 hr(60-120 mg) /8 hr

Dihydropyridine group

Nifedipine (10-40mg) /8 hr

Amlodipine 5mg/day

Used in treatment of all types of angina.

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BlockBlock

Voltage -dependent calcium Voltage -dependent calcium

channels (L-type) in cardiac and channels (L-type) in cardiac and

smooth muscles.smooth muscles.

CCAALLCCIIUUMM

Mechanism of anti-anginal action :Mechanism of anti-anginal action :

1 - Coronary artery dilatation and relief of coronary spasm (variant angina)

•(Verapamil & Diltiazem)

•Decrease HR.

•Decrease contractility

•Decrease AV conductivity

•Arteriolar dilatation

Vascular resistance Afterload

2 -Decrease myocardial O2 demand due to:

Dosage and Route of Administration

Drug Route Dosage

Verapamil Oral 80-160 mg every 8 hours

Nifedipine Oral 10-40 mg every 8 hours

Diltiazem Oral 60-120 mg every 8 hours

Adverse reactions :Adverse reactions :

DizzinessDizzinessAnkle Ankle edemaedema

HypotensionHypotensionHeadacheHeadache

FlushingFlushingConstipationConstipation

A-V block & HF A-V block & HF onlyonly with Verapamil & with Verapamil &

DiltiazemDiltiazem

Reflex Reflex Tachycardia Tachycardia

with Nifedipinewith Nifedipine

3 - Bradycardia.

Contraindications of Contraindications of Verapamil & Diltiazem:Verapamil & Diltiazem:

1 - HF

2 - Sinus or A-V node

disease.

-blocker + Long

acting Nitrate

-blocker +

Nifedipine

Verapamil or

Diltiazem +

Nitrate

-blocker +

Nitrate +

Nifedipine

????

??

??

-blockers block reflex tachycardia produced by nitrates

•Nitrates attenuate the increased left ventricular end-diastolic volume associated with -blockers

-blockers decrease reflex tachycardia produced by nifedepine.

•Verapamil or Diltiazem decrease tachycardia produced by nitrates.

•In patients with stable angina not controlled by two types of antianginal drugs the use of three agents may provide improvement.

THANK YOU

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BEST WISHES & GOOD LUCK

BY: DR. MARWA SHAALAN

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