Angina Pectoris

ARUN DUBEY M.D.

2019
 Learning Objectives

At the end of this session you will be able to:

 Explain the factors that determine myocardial oxygen
demand and supply.
 List the group of drugs used in treatment of angina.
 Mention the effects of each antianginal drug or drug
class on the determinants of myocardial oxygen
consumption (heart rate, myocardial wall tension,
etc.) and/or oxygen supply (coronary blood flow).
Learning Objectives

 Enumerate the molecular mechanisms and hemodynamic

effects of nitrates.
 Mention
the basis for using nitrates in angina, their
common side effects and different preparations available.
 Discuss the adverse effects, drug interactions and
contraindications of nitrates
 Highlight
the problem of dose intervals and tolerance
development with nitrates.
 Highlight the basis for combining nitrates with beta
blockers/ CCBs in angina pectoris.
Myocardial Oxygen demand

Three Factors determining myocardial

oxygen demand:
1. Heart Rate

2. Force of Contraction

3. Lt Ventricular wall
tension( Preload and
afterload)

***Important:
all the Drugs used in angina pectoris
decrease myocardial oxygen demand/requirement
 Types of angina
1. Stable/ Exertional angina: 75% narrowing of coronary artery lumen,
attack of angina only on exertion (lasting up to 5 mins) and
relieved on rest or by sublingual nitroglycerine. ECG during
attack shows ST depression. Treated by Nitrates, beta-
blockers/CCBs and if required PCIs and CABG.
2. No chest pain at rest !! Also , called classical Angina.

3. Unstable angina: complete block of a coronary artery due to

ruptured atheromatous plaque & thrombosis. Pain at rest,
continuous (more than 20 mins), not relieved by rest or sublingual
nitroglycerine. ECG shows ST segment depression (cardiac
enzymes are normal, elevation=infarction), treated by
anticoagulants, anti-platelets. No thromobolytics * only for infarction.
(but in the case of Myocardial Infarction, thrombobolytics are the
drug of choice)
 Types of angina

3.Prinzmetal / Vasospastic angina : attack

precipitated by spasm (unlike the other types of
angina which involves atherosclerosis) of
coronary arteries. Intracoronary ergonovine**
injected* test is confirmatory/ use acetelycholine
– you see sudden spasm to confirm . ECG might
show ST elevation. Treated by nitrates, CCBs but
beta blockers contraindicated-
 **DON’Tuse B-BLOCKERS (risk of
unopposed alpha1 -action).
 Noepi work on alpha- 1 – vasoconstriction
Drugs used in angina pectoris

1. Organic nitrates :
Acute attack: glyceryl trinitrate (GTN) or nitroglycerine, given
sublingually every 5 mins maximum of 3 tabs –
Nitroglycerine also cause vasodilation – droping of bp
Prophylaxis* to prevent further attacks : Isosorbide dinitrate, isosorbide
mononitrate * product of dinitrate(Longest acting), Nitroglycerine
ointment* used in nocturnal attacks , Transdermal preparation.
Amyl nitrates -
2. Calcium channel blockers
3. Beta-adrenergic receptor antagonists

Beta blockers and CCBs are usually combined with Nitrates

for long term treatment??
Organic nitrates
Mechanism of action

 **Undergo denitration to release nitric oxide (

NO), activates cGMP which leads to
dephosphorylation of Myosin Light Chain
and relaxation of smooth muscles
Hemodynamic effects
 Nitrates : Mechanism in Angina--

 Low dose results in venodilation increased peripheral pooling of

blood decreased return of blood to heart & decreased preload *dec wall
tension decreased myocardial oxygen demand.
 Higher dose also causes arterial dilation & decreased after load.
 Together they decrease myocardial oxygen demand- most important
mechanism of relief in angina by nitrates.

 Nitrates are venodilatators !!

Redistribution of blood flow from
epicardium to endocardium

 Nitrates dilate large epicardial vessels.

 Auto-regulatory mechanism at obstruction
site dilates blood vessel around
obstruction
 Decreased preload decreases ventricular
wall tension & increases blood flow
across the myocardium
 Nitrates helping blood to go ischemic
area – by the help of dilating big
vessels and local factors
 Reducing the wall tension – more blood
Adverse effects of nitrates

 flushing of face, nausea, hypotension & reflex

tachycardia (combine with cardio-selective Beta
blockers). Except prinzmental angina – only give
nitrates
 Most common S/E: headache -- **
 Tolerance: overcome by “Eccentric dosing schedule”.

 Drug Interaction : Combination of sildenafil (Viagra)

and other PDE5 inhibitors with nitrates can cause
severe hypotension.
Sildenafil, Vardenafil, Tadalafil- Inhibits
PDE 5 & increase cGMP levels
 Nitrates & beta-blockers - true
friends
Nitrates Beta-blockers
Can cause sudden fall in BP Will prevent reflex
& reflex tachycardia tachycardia caused by
Nitrates

Nitrates cause venodilation Beta-blockers might increase

and decrease pre-load pre-load

Nitrates cause dilation of Beta-blockers might constrict

coronary vessels coronary vessels because of
unopposed alpha adrenergic
stimulation.
Newer drugs for angina
A. Ranolazine: reduces calcium overload in the ischemic heart
muscle cell through inhibition of the late sodium current (INa).
Myocardial ischemia produces a cascade of complex ionic
exchanges that can result in intracellular acidosis, excess
cytosolic Ca2+, myocardial cellular dysfunction, and, if sustained,
cell injury and death. By inhibiting the excess calcium in the cells,
cellular function would be maintained.

B. Ivabradine : Reduction of pacemaker activity in

sinus node( blocks If Na+ channels)
Reduction of funny channels
C. Nicorandil: opening the mitochondrial adenosine triphosphate-
sensitive potassium channels( ATP K+ channels) 
 How different groups of drugs help in angina?

Nitrates results in venodilation increased peripheral pooling of blood decreased

return of blood to heart & decreased preload decreased myocardial oxygen
demand.

Beta blockers decrease HR & FOC and thereby decrease Myocardial O2

demand. Also prevent reflex tachycardia.

Cardioselective CCBs( Verapamil & Diltiazem)decrease HR &

FOC and thereby decrease Myocardial O2 demand.
SAME MEHANISM AS B-BLOCKERS
Vasoselective CCBs( Nifedipine..) cause arteriolar dilation, decrease
PVR, decrease after load & decrease Myocardial O2 demand.
Arteriolar dilatator
Cyanide poisoning and nitrates

1st step: Immediate exposure to amyl nitrite and intravenous Na Nitrite: Forms
methemoglobin. Methemoglobin has higher affinity for cyanide and forms
cyanomethemoglobin.
Block all the cyanide
x
2nd step: Intravenous Na Thiosulfate: converts cyanomethemoglobin to thiocyanate-
less toxic and excreted in urine b/c it is water soluble .
 Hydroxycobalamine ( Vitamin B12) is also preferred in treatment of cyanide
poisoning.
Let’s recall

Nitrates
 How cause venodilation,
nitrates help in anginadecrease
pectoris? Preload ( EDV) ,
decrease LV wall tension & thereby decrease Myocardial O2
demand. .
 Why Cardioselective CCBs ( Verapamil, Diltiazem) and
Beta blockers should not be combined together?
Both group of drugs decrease HR & FOC and thereby can
cause severe bradycardia, cardiac arrest and HF.

 Why beta-blockers and nitrates are often combined

together?
Nitrates can cause sudden drop in BP and reflex tachycardia,
beta blockers prevent reflex tachycardia
Must Know
 Acute attack of angina is treated by SL nitroglycerine: Fast action,
avoids first pass effect. Long acting preparation like Isosorbide
mono-nitrate is mainly used for prophylaxis along with Beta blockers
or CCBs (if beta-blockers are contraindicated).

 Nitratesmainly act by causing venodilation decreasing preload and

thus reducing myocardial oxygen demand. Other mechanisms??

 Most common side effects include headache, flushing and tolerance.

 Short acting nitrates like Isosorbide dinitrate can cause reflex

tachycardia. Beta blockers are combined to prevent this side effect.
 Prinzmetal's or vasospastic angina requires nitrates or CCBs but beta
blockers are contraindicated.
 Unstable angina requires IV nitrates, anti-platelets and anti-
coagulants.