ANTI ANGINA

PRAJOGOWIBOWO
 OVERVIEW

Coronary vessels: blood supply for the heart

Coronary atherosclerosis:
cause of cardiac ischemia
Distribution of coronary arteries in the heart
Ischemia (angina pectoris ):
imbalance between oxygen demand and supply
 OVERVIEW
Classification of angina pectoris:
Exertional angina
 Stable angina
 Initial onset angina
 Accelerated angina

Spontaneous angina
 Angina decubitus
 Variant or vasospastic
angina
 Acute coronary
insufficiency
 Postinfarction angina

Mixed angina
 Unstable angina
 OVERVIEW
Myocardial oxygen demand is chiefly determined by:

 Contractility
 Heart rate
 Wall tension
 Preload (venous return )

 Afterload (arteriolar resistance)

afterload preload
 OVERVIEW

Myocardial oxygen demand is

diminished by:

 Reducing contractility
 Reducing heart rate
 Reducing the preload
Wall tension 
 Reducing the afterload
OVERVIEW
Myocardial oxygen supply is
chiefly determined by:

 AV oxygen difference
 Regional myocardial
distribution
 coronary blood flow:

 vascular resistance, artery pressure

 1. OVERVIEW
Effects of antianginal drugs:

Reducing oxygen demands

Reducing heart rate and contractility
Dilating systemic arteries and veins (  wall tension by
lowering heart loads)
Increasing oxygen supply
Dilating conduct coronary arteries (  coronary blood flow)
Promoting regional distribution (  in ischemic regions)
Others:
Anti- platelet coagulation and thrombus formation
 Antianginal drugs
Nitrates
Nitroglycerin

A. Pharmacological actions
Dilating vessels and reducing heart loads
wall tension  ; reflex tachycardia
Redistribution of coronary circulation
dilating conduct artery:
collateral circulation 
reducing wall tension:
blood flow in ischemic subendocardial area 
 2. Antianginal drugs

Mechanism of the effect of nitroglycerin and other nitrates

Mechanism of the effect of nitroglycerin and other nitrates
 Antianginal drugs
B. Clinical uses
 Angina pectoris: all kinds, especially stable type
 Heart failure ： reducing heart loads due to vasodilation

C. Adverse reactions
 Increase in heart rate and contractility
 Symptoms due to vasodilation: headache, flash, postural
hypotension, collapse, ect.
 Others: methaemoglobinaemia
 Tolerance : avoiding steady-state plasma concentration;
 supplement of agents containing –SH (captopril)
 Antianginal drugs

Other nitrates

Isosorbide dinitrate
Isosorbide-5-mononitrate
Compared with nitroglycerin:
 Similar but weaker effect
 Acting slowly but lasting longer
 Larger individual variation and more adverse effects
 Antianginal drugs
 blockers

A. Pharmacological action
 Reducing oxygen demand:
heart rate and contractility 
 Increasing oxygen supply:
 diastolic period  : perfusion time 
 vascular tone in normal regions  :
 blood flow in ischemic regions 
 Others:
 Improving myocardial metabolism
 Inhibiting coagulation of platelets
 Antianginal drugs
Clinical uses
stable and unstable angina pectoris, especially associated
with hypertension or arrhythmias, even with myocardial
infarction; but not used for variant angina pectoris

Notes
 Dose individualization: starting from small dose
 Withdraw gradually and slowly: symptom rebound
 Combination with nitroglycerin
 Antianginal drugs

Calcium channel blockers

 Antianginal drugs
Calcium channel blockers

A. Pharmacological actions
 Reducing myocardial oxygen remand:
 heart loads  : nifedipine
 heart rate and contractility  : verapamil and
diltiazem
 Increasing myocardial blood supply
 Protecting ischemic myocardial cells
 Inhibiting coagulation of platelets
Actions of calcium channel blockers
 Antianginal drugs
Clinical uses

stable and variant type:

nifedipine, verapamil, diltiazem

unstable type:

verapamil, diltiazem

Actions of DHP (like nifedipine) are similar to those of nitroglycerin

Actions of verapamil and diltiazem are similar to those of  blockers
 2. Antianginal drugs
Other drugs

ACEIs
Treating HT and preventing ischemic heart disease
Reducing heart loads
Inhibiting cardial remodeling

Nicorandil
 Opening ATP-sensitive K+ channel (KATP)
 Lowering intracellular Ca2+
 Providing NO (like nitroglycerin)
Inducing ischemic preconditioning
 Antianginal drugs
Molsidomine
Inhibiting adenosine uptake and cAMP degradation
Inhibiting pletelet aggregation
Promoting collateral circulation after long-term use

Dipyridamole
 Inhibiting adenosine uptake and cAMP
degradation
Inhibiting pletelet aggregation
Promoting collateral circulation after long-term use
 Summary of antianginal drugs
nitroglycerin  blockers Ca2+ antagonists combination*

Heart rate    

Contractility     /

Wall tension    /  /

Oxygen demand    

Blood pressure    

 : increase,   : markedly increase;  : decrease,   : markedly decrease;  : variable

according to the dose and effect of each drug ; *  blockers combined with nitroglycerin
or Ca antagonists (nifedipine; combination with verapamil/diltiazem not be
2+
recommendated)

Caution: Combination may potentiate the antianginal effects, but may induce
severe hypotension
VASODILATOR
Calcium Channel Blockers
 Calcium channel blockers reduce heart rate
 Dilate the blood vessels of the heart
 Decrease oxygen demand
 Increase oxygen supply

 Net drop in BP
 Alpha-Blockers
 Alpha-adrenergic blocking
agents

 In both arteries and smooth

muscles

 The blocked adrenergic

receptors are G protein-
coupled receptors
 Catecholamines –
adrenaline/noradrenaline[
epi/norepi]
 If catecholamines bind,
increased HR,
vasoconstriction

 However, if B-adrenergic
receptors are bound by epi or
norepi, vasodilation occurs
More on Alpha Adrenergic
Receptors
 Nitric Oxide [NO] Inducers

 Glyceryl trinitrate (Nitroglycerin)

 Prodrug, must be denitrated to produce active NO
 Once active, these nitrates are called
“nitrovasodilators”
 Mechanisms for
Denitration
Nitroglycerin can be denitrated in many ways
There are many hypotheses as to the
mechanism of bioactivation
Nitrates react with sulfhydryl groups
Enzymatic breakdown
Glutathione S-transferase, Cytochrome P450, Xanthine
oxidoreductase
 Catalyzed denitration by mitochondrial aldehyde
dehydrogenase
Ultimately, GTN is broken down into 1,2-
glyceryl dinitrate + Free NO
 Other Nitric Oxide [NO]
Inducers
 Isosorbide mononitrate & Isosorbide dinitrate
 Preventatives of angina, reduced heart workload
 Pentaerythritol Tetranitrate (PETN)
 Lentonitrat – drug commonly used, pure PETN
 So reactive…one of the strongest high explosives known
 Sodium nitroprusside
 Salt that is a source of NO, often administered via IV
 For patients with extreme hypertension
 PDE5 inhibitors: these agents indirectly increase the
effects of nitric oxide
 Sildenafil (Viagra)
 Tadalafil
 Vardenafil
 Now what? Free NO
 NO is a potent activator of guanylyl cyclase (GC)
by heme-dependent mechanisms
 Activation results in cGMP formation from
guanosine triphosphate (GTP)
 Thus, NO increases the level of cGMP within the
cell.
 Nitroglycerin
 GENERIC NAME: nitroglycerin
 USES: frequently used to lower blood pressure when treating
angina pectoris, and also used during anginal attacks [both
as a prevention method, and as an acute treatment]
 Extended release tablets, translingual spray, and
transdermal patches
 Literature recommends not to stack with other high blood
pressure medications, because of additive effects
 ACE inhibitors
 Class of Drugs: ACE
(angiotensin converting
enzyme) inhibitors

 Generic (Brand Name)

 captopril
 benazepril
 enalapril
 lisinopril
 fosinopril
 ramipril
 perindopril
 quinapril
 moexipril
 trandolapril

 USES:
 Hypertension treatment
 Heart failure
 sildenafil citrate
 More than 65% of men with high blood pressure
also have ED.
 PDE5 Inhibitor
 Side Effects
 Priaprism
 Sudden blindness
Cardiovascular
pharmacology

Summary
 Overview of Cardiovascular
Diseases
 Common Cardiac Diseases

 Abnormal contractility ： Heart failures

 Abnormal rhythms ： Arrhythmias

 Abnormal blood supply ： Ischemic heart diseases

 Myocardial disorders

 Common vascular diseases

 Abnormal systematic resistance ： Hypertension

 Dysfunction of coronary vessels ： Coronary vascular diseases

 Dysfunction of cerebral vessels ： Cerebral ischemia, hemorrhage

 Dysfunction of pulmonary vessels ： Pulmonary hypertension

 Dysfunction of peripheral vessels: Peripheral vascular disorder

 Arteriosclerosis: basis of most CVS diseases

 Overview of Cardiovascular
Drugs
Classification based on target organs/tissues
 Heart ： Heart failures, arrhythmias, cardiac ischemia
 Vessels ： Vasodilatation, vasoconstriction,
arteriosclerosis

Classification based on the mechanisms

 Ion channels ： Ca2+, Na+, K+ channels
 Receptors ： Adrenoceptors, AT1 receptors, etc.
 Enzymes ： ACEI, Na+-K+-ATPase, HMG-CoA reductase
 Others ： Diuretics
 Cardiovascular Drugs
 Antiarrhthemic drugs
 Classification; Typical drugs and their properties

 Antihypertensive drugs
 Classification; Properties of 6 main drug classes

 Drugs for treating heart failure

 Classification; ACEIs,  blockers, cardiac glycoide

 Antiatheroscleotic drugs
 HMG CoA reductase inhibitors (statins)

 Antianginal drugs
 Nitroglycerin;  blockers; Ca2+ antagonists