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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.
HOME
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
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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
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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
•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.