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Drugs used in angina pectoris
Antianginal drugs
Learning Objectives
By the end of this class, you can…
 Describe the antianginal mechanism of
Nitrites, β-blockers and CCBs
 Clarify the vasodilatory mechanism of NO
 Select antianginal agents for the treatment
of different types of angina pectoris
Methods for treatment
■
To improve perfusion:
■
To reduce metabolic demand
Factors affecting myocardial oxygen
demand and oxygen supply
Regional
myocardial
distribution
Contractile
state
Ventricular
volume
Heart
rate
Wall
tension
LV
pressure
Oxygen
Oxygen
= supply
demand
Coronary
vascular
resistance
>
Coronary
blood flow
Aortic
pressure
Drugs classifications
▲
▲
▲
Organic nitrates: Nitroglycerin
Calcium antagonists
β-Receptor blockers
Chemical structures of two nitrates
Nitroglycerin
Isosorbide dinitrate (IDSN)
Longer lasting effect
Rapid onset effect
-O-NO2
Mechanism of action in VSM
NO(EDRF)
activate GC
increase c-GMP
activate cGMPdependent kinase
decrease Ca
induce de-phosphorylation of the
myosin light chain
relaxation
Nitroglycerin
↓ SH
NO/SNO
↓+
guanylate cyclase
↓+
PDE
cGMP ↑
Inhibition
platelet
Ca2+ influx↓
Ca2+ efflux↑
5’GMP
Activation of
protein kinase
Concentration of Ca2+ in VSMC↓
VASODILATION
Organic nitrates
Pharmacological effects and mechanism:
■ dilate peripheral vein
preload
Oxygen
■ dilate peripheral artery
afterload
consumption
■
Dilate coronary artery
perfusion of
ischemic myocardium
Pharmacokinetics:
■
■
■
■
very low bioavailability per os
Sublingual Rapid onset(2~5min)
Acute adverse effects: postural
hypotension, throbbing headache
Tolerance : depletion of free –SH
(hydrosulfuryl ) groups
NITRATES
TOLERANCE
" Decrease in the effect of a drug
when administered in a long-acting form"
Develops with all nitrates
Is dose-dependent
Disappears in 24 h. after stopping the drug
Tolerance can be avoided
- Using the least effective dose
- Creating discontinuous plasma levels
NITRATES
CONTRAINDICATIONS
Previous hypersensitivity
Hypotension ( < 80 mmHg)
1st trimester of pregnancy
β-Receptor blockers

Pharmacological effects:
Oxygen
consumption

Myocardial contractility
Heart rate

Clinic use : stable and unstable angina

Propranolol

not for variant angina because of coronary
artery contraction due to its β-receptor blocked and α receptor relatively activated.
ß-ADRENERGIC BLOCKERS
CONTRAINDICATIONS
Hypotension: BP < 100 mmHg
Bradycardia: HR < 50 bpm
Chronic bronchitis, ASTHMA
Severe chronic renal insufficiency
Effects of nitrates alone and with β-blockers
in angina pectoris
Nitrates
alone
βblockers
Heart rate
Reflex
increase
Decrease
Combined
nitrates with
β-blockers
Decrease
Arterial
pressure
Decrease
Decrease
Decrease*
End-diastolic
volume
Decrease
Increase
None
decrease
Contractility
Reflex
increase
Decrease
None
Coronary
vasospasm
Decrease
Increase
None
or
Pharmacological effects of CCB
■
■
■
■
■
Myocardial
oxygen
consumption
Cardiac contractility,
heart rate
Peripheral vessels dilation , afterload
dilate coronary artery, release its spasm
Ca2+ overload
apoptosis,necrosis
Calcium channel blockers
▲ Clinic
use : variant angina
▲ Nifedipine
not for unstable angina?
▲ Reflex increase in heart rate and
cardiac contractility
▲ How to control ?
▲ β-Receptor blockers
Other drugs for angina
■
■
Anti-platelet drugs:
aspirin, persantin
Chinese medicine:
salvia miltiorrhiza, panax notoginseng
-promoting blood circulation to remove blood stasis
Non-Pharmacologic Management








Limit alcohol
No high saturated fat/high cholesterol foods
Maintain normal blood lipid levels
Maintain blood pressure within normal range
Regular exercise
Optimal weight
Maintain blood glucose within normal range
No tobacco
The Original Question from Step1-USMLE
A 60 y-o woman with a history of smoking presents
with the chief complaint of chest pain that occurs at
night while at rest. A treadmill test is negative. A 24
hr holter recording reveals transient ST elevation and
AV block (suggestive of occlusion of her right
coronary artery) that are temporally associated with
anginal attacks. A coronary angiography with
provocative testing with acetylcholine injection
reproduces her chest pain & ECG changes. Which
drug will be contraindicated in her treatment?
A.
B.
C.
D.
E.
diltiazem
isosorbide dinitrate
metoprolol
nitroglycerin sublingually
verapamil
Features & diagnosis of Variant angina
Symptoms typically occur at rest, rather than on
exertion (thus attacks usually occur at night).
▲ The treadmill stress test is always negative.
▲ It is associated with specific ECG changes
(elevation rather than depression of the ST
segment).
▲ The gold standard is coronary angiography with
injection of provocative agents into the coronary
artery. Depending on the local protocol,
provocation testing may involve substances such
as ergonovine, methylergonovine or acetylcholine.
▲
Beta blockers (both beta-1 selective and
nonselective types) are contraindicated
in vasospastic angina because of the
concern about blocking beta-2
receptors in coronary arteries, and
leaving "alpha receptors
unopposed"...resulting in enhanced
likelihood of vasospasm.