ISCHEMIC HEART DISEASE

Antianginal Drugs

There are 35 risk factors for development

of IHD
3 the most important ones are
big triple
hypercholesterolemia
arterial hypertension
smoking

95 % of patients with IHD are observed

to have atherosclerotic changes in
coronary arteries

Angina Pectoris
Angina pectoris is the principle symptom
of ischemic heart disease
The condition is characterized by
sudden, severe substernal pain or
pressure
The primary cause of angina is an
imbalance between myocardial oxygen
demand and oxygen supplied by coronary
vessels
This imbalance may be due to:
a decrease in myocardial oxygen delivery
an increase in myocardial oxygen demand
or both

Symptoms of Angina
Angina pectoris is a characteristic sudden, severe,
pressing (or strangling) chest pain radiating to the
neck, jaw, back, and arms, or epigastrium.
Severe chest discomfort (heaviness,
pressure, tightness, choking, squeezing)
Sweating
Dizziness
Dyspnea
Chest pain due to imbalance of oxygen
supply and demand
Oxygen demand is related to heart rate,
strength of contraction, and resistance to
blood flow

Factors Affecting
Myocardial Oxygen Delivery
Coronary artery blood flow is the primary
determinant of oxygen delivery to the
myocardium
Myocardial oxygen extraction from the blood is nearly
complete, even at rest

Coronary blood flow is essentially negligible

during systole and is therefore determined by:
Perfusion pressure during diastole (aortic diastolic
pressure)
Duration of diastole
Coronary vascular resistance
Coronary vascular resistance is determined by
numerous factors including:
Atherscelorosis
Intracoronary thrombi
Metabolic products that vasodilate coronary
arterioles
Autonomic activity
Extravascular compression

Factors Affecting
Myocardial Oxygen Demand
The major determinants of myocardial
oxygen consumption include:

Ventricular wall stress

Both preload (end-diastolic pressure) and
afterload (end-systolic pressure) affect
ventricular wall stress
Heart rate
Inotropic state (contractility)
Myocardial metabolism (glucose vs fatty acids)

A commonly used non-invasive index of

myocardial oxygen demand is the double
product:
[Heart rate] X [Systolic blood pressure]
Also known as the rate-pressure product

3 Types of Angina
Stable
Effort-induced pain from physical activity or
emotional stress
Relieved by rest
Predictable and reproducible
Unstable
Pain occurs with increasing frequency
Diminishes patients ability to work
Has decreasing response to therapy
May signal an oncoming MI
Variant
Pain due to coronary artery spasm
Pain may occur at certain times of the day, but
is not stress induced

Risk Factors for Angina

Advanced age
Coronary artery disease
Hypertension
Increased serum glucose levels
(diabetes)
Increased serum lipoprotein levels
Obesity
Smoking
Type A personality

Initiating Factors of an Attack

Cold weather
Emotions
Heavy meals
Hypoglycemia
Pain
Smoking

Stable Angina
Stable angina is also known as:

Exertional angina
Typical or classic angina
Angina of effort
Atherosclerotic angina

The underlying pathology is usually

atherosclerosis (reduced oxygen delivery)
giving rise to ischemia under conditions
where the work load on the heart increases
(increased oxygen demand)
Anginal episodes can be precipitated by
exercise, cold, stress, emotion, or eating
Therapeutic goals: Increase myocardial blood
flow by dilating coronary arteries and
arterioles (increase oxygen delivery),
decrease cardiac load (preload and afterload;
decrease oxygen demand), decrease heart rate
(decrease oxygen demand), [alter myocardial
metabolism?]

Unstable Angina
Unstable angina is also known as:
Preinfarction angina
Crescendo angina
Angina at rest

Associated with a change in the character,

frequency, and duration of angina in patients
with stable angina, and episodes of angina at
rest
Caused by recurrent episodes of small platelet
clots at the site of a ruptured atherosclerotic
plaque which can also precipitate local vasospasm
May be associated with myocardial infarction
Therapeutic rationale: Inhibit platelet
aggregation and thrombus formation (increase
oxygen delivery), decrease cardiac load (decrease
oxygen demand), and vasodilate coronary arteries
(increase oxygen delivery)

Vasospastic Angina
Vasospastic angina is also referred to
as:
Variant angina
Prinzmetal's angina

Caused by transient vasospasm of the

coronary vessels
Usually associated with underlying
atheromas
Chest pain may develop at rest
Therapeutic rationale: Decrease
vasospasm of coronary vessels (calcium
channel blockers are efficacious in >70%
of patients; increase oxygen delivery)

History of Antianginal Drugs

Amyl nitrate and nitroglycerin were found
to provide transient relief of angina in
the mid-to late 1800s
Subsequently many other vasodilators were
introduced for the treatment of angina,
but double-blinded clinical trials showed
many were no better than placebo
Some of the classic studies of the
placebo effect were carried out in
patients with angina
Beta-adrenergic blockers and calcium
channel blockers were developed during
the early 1960s and are now also widely
used in the prophylactic therapy of
angina
pFox inhibitors, the first new drugs for
angina in more than 20 years, are likely
to be approved by the FDA in the near
future

Antianginal (coronary active)

drugs
a group of drugs which by different
mechanisms abolish irregularities (imbalance)
between myocardium oxygen demand and
insufficient coronary blood flow
clinically it is manifested by removal or
prevention of stenocardia attacks (improvement
of disease currency) and increasing of patients
tolerance to physical load

ANTIANGINAL (CORONARY
ACTIVE) DRUGS
. Nitrates and sidnonimins

. Beta-adrenoblockers
. Antagonists of calcium ions
. Activators of potassium channels
Inhibitors of ACE
Platelet
inhibitors
and
anticoagulants
Drugs with metabolic influence on
myocardium

Pharmacology of Antianginal
Agents

Three major classes of agents are used individually or in

combination to treat angina:
Organic nitrates
Vasodilate coronary arteries
Reduce preload and aferload
Calcium channel blockers
Vasodilate coronary arteries
Reduce afterload
The non-dihydropyridines (verapamil and diltiazem)
also decrease heart rate and contractility
Beta-adrenergic blockers
Decrease heart rate and contractility
Decrease afterload 2 to a decrease in cardiac
output
Improve myocardial perfusion 2 to a decrease in
heart rate
*All of these may also reduce platelet aggregation
A new class of drugs, pFox inhibitors, are in the final
stages of approval for chronic angina
Reduce myocardial oxygen consumption by shifting
metabolism from fatty acid to glucose metabolism
No hemodynamic effects

NITRATES
nitroglycerin
isosorbid dinitrate
isosorbid-5mononitrate

MECHANISM OF ACTION OF
NITRATES
Interaction with sulfhydryl (SH-)
groups
(nitrate receptors) inside
cells of vascular smooth muscles
Stimulation
of
formation
of
endothelial factor of relaxation of
vessels (RF) nitric oxide (NO)
Decreasing of ionized 2+ content
Relaxation
of
smooth
muscles,
dilation
of
vessels,
including
coronary vessels

Organic Nitrates /
Nitrovasodilators

All of these agents are enzymatically converted

to nitric oxide (NO) in the target tissues
NO is a very short-lived endogenous mediator
of smooth muscle contraction and
neurotransmission
Veins and larger arteries appear to have
greater enzymatic capacity than resistance
vessels, resulting in greater effects in these
vessels
NO activates a cytosolic form of guanylate
cyclase in smooth muscle
Activated guanylate cyclase catalyzes the
formation of cGMP which activates cGMPdependent protein kinase
Activation of this kinase results in
phosphorylation of several proteins that
reduce intracellular calcium and
hyperpolarize the plasma membrane causing
relaxation

Mechanism of Action of Nitrovasodilators

Nitrates become denitrated by glutathione S-transferase
to release
Nitric Oxide
activates
Guanylate Cyclase*
converts
GTP

cGMP
activates
cGMP-dependent protein kinase

Activation of PKG results in phosphorylation

of several proteins that reduce intracellular calcium
causing smooth muscle relaxation

MECHANISM OF ACTION OF NITRATES

a decrease in tone of veins a decrease of preload (venous return
to the heart during diastole) a decrease of work of left ventricle
and heart output
a decrease in tone of arterioles a decrease of afterload (a
decrease of arterial pressure, end diastolic pressure in left
ventricle and its volume, decreasing of tension of myocardium
wall)
a decrease in oxygen demands of heart because of decreased
heart work
improvement of blood flow in ischemic zone of myocardium
redistribution of coronary blood flow with increasing of perfusion
of subendocardial areas
dilation of large coronary vessels if they are in spasm or
narrowed with atherosclerotic mass
development of anastomoses between arteries in myocardium (in
case of prolonged administration)

Effects of Nitrovasodilators
Peripheral vasodilation:

Dilation of veins predominates over that of

arterioles

Increased coronary blood flow:

Large epicardial coronary arteries are dilated

without impairing autoregulation in small
coronary vessels
Collateral flow may be increased
Decreased preload improves subendocardial
perfusion
Although organic nitrates can relax vasospastic
coronary arteries, they have little or no
effect on total coronary blood flow in patients
with typical angina due to atherosclerosis
Dilation of coronary arteries can paradoxically
result in aggravation of angina - a phenomenon
known as coronary steal

Inhibition of platelet function:

May contribute to their effectiveness in the

treatment of unstable angina

Nitrates
Most commonly used drugs for angina
Relax vascular smooth muscle and cause
vasodilation
Helps with pulmonary edema in CHF

Agents for Angina

Nitrates
isosorbide dinitrate (Dilatrate-SR,
Isordil)
isosorbide mononitrate (Imdur, Ismo)
nitroglycerin (Minitran, Nitrolingual,
Nitrostat)

nitroglycerin (Minitran,
Nitrolingual, Nitrostat)
Drug of choice for acute attacks
Spray and tablets taken sublingually
May also be used as a prophylaxis
If using a patch, it should not remain
on the skin for a full 24 hours, there
needs to be free time

NITROGLYCERINE
Tablets (under the tongue)
1 % alcohol or oil solution (under the
tongue)
aerosol
Onset - 2-3 min
Duration of action - 20-30 min
ampoules 1 % solution intravenously
dropply 0,01% solution
prolonged forms of nitroglycerine:
trinitrolong, sustak, nitrong, ointment,
plaster

Pharmacokinetic Properties of
Organic Nitrates
Hepatic first-pass metabolism is high and
oral bioavailability is low for nitroglycerin
(GTN) and isosorbide dinitrate (ISDN)
Sublingual or transdermal administration of
these agents avoids the first-pass effect
Isosorbide mononitrate (5-ISMN) is not
subject to first-pass metabolism and is 100%
available after oral administration
Hepatic blood flow and disease can affect the
pharmacokinetics of GTN and ISDN
Property
Half-life (min)
Plasma clearance (L/min)
Apparent volume of distribution (L/kg)
Oral bioavailability (%)

GTN

ISDN

5-ISMN

3
50
3
<1

10
4
4
20

280
0.1
0.6
100

Routes of Administration
Amyl nitrate is a gas at room temperatures
and can be administered by inhalation
Rapid onset, short duration (3-5 min)
GTN and ISDN have a rapid onset of action
(1-3 min) when administered sublingually,
but the short duration of action (20-30 min)
is not suitable for maintenance therapy
IV nitrogylcerin can be used to treat severe
recurrent unstable angina
Slowly absorbed preparations of
nitrovasodilators (oral, buccal,
transdermal) can be used to provide
prolonged prophylaxis against angina (3-10
hrs), but can lead to tolerance
(tachyphylaxis)

PROLONGED FORMS OF
NITROGLYCERINE
Trinitrolong polymer films (0,001 g or
0,002 g of nitroglycerine) action develops
immediately, lasts for
3-5 hours
Sustac - Susta-mite (contains 0,0026 g
of
nitroglycerine)
and
Sustac-forte
(0,0064 g of nitroglycerine)
onset after 10 min,
maximal action after 1 hour,
duration of action 4-5 hours
Nitrong

microcapsule
form
of
nitroglycerine of prolonged action
onset 30-60 min,
maximal effect - after 3-4 hours,
Duration of action - 6-8 hours

Contraindications for
nitroglycerine administration
Closed-angle glaucoma
increasing of intracranial pressure,
insult
acute myocardium infarction (in case of
presence of hypotonia and collapse)

Tolerance and Dependence with

Nitrovasodilators
Continuous or frequent exposure to
nitrovasodilators can lead to the development of
complete tolerance
Transdermal GTN may provide therapeutic levels of drug for
24 hours or more, but efficacy only lasts 8-10 hrs
Nitrate-free periods of at least 8 hrs (e.g.- overnight)
are recommended to avoid or reduce tachyphylaxis

The mechanism of tolerance is not completely

understood but appears to relate to the enzymes
involved in converting the nitrates to NO, or to
the enzyme that produces cGMP
Industrial (occupational) exposure to organic
nitrates has been associated with Monday disease
and physical dependence manifest by variant angina
occurring 1-2 days after withdrawal
Has resulted in myocardial infarction in some patients
No evidence that dependence occurs in normal therapy, even
with high doses

MONDAY DISEASEIndustrial

disease

caused

by

chronic

exposure to vasodilating concentrations of

organic

nitrates

in

the

workplace;

characterized by headache, dizziness, and

tachycardia on return to work after 2 days
absence (every Monday). Development of
tolerance occurs during the work week, and
loss of tolerance over the weekend.

Other nitrates
Nitrosorbid isosorbid dinitrate
onset - 30-50 min,
duration of action 4-6 hours and more
With sublingual administration of the drug onset
decreases
to 3-5 min

buccal form (Dinitrolslrbilong)

tablets of prolonged action (Isoket-retard)

ointment

aerosol
drugs for intravenous introduction
Isosorbid-5-mononitrate
- pharmacologically active metabolite of
isosorbid dinitrate
duration of action - from 6 till 24 hours

Adverse Effects of
Nitrovasodilators

The major acute adverse effects of

nitrovasodilators are due to excessive
vasodilation
Orthostatic hypotension
Tachycardia
Severe throbbing headache
Dizziness
Flushing
Syncope
Organic nitrates are contraindicated in
patients with elevated intracranial pressure
Sildenafil (Viagra) and other PDE-5
inhibitors used for erectile dysfunction can
potentiate the actions of nitrovasodilators
because they inhibit the breakdown of cGMP
(they should not be taken within 6 hours of
taking a nitrovasodilator)
See the movie Somethings Gotta Give
(Jack Nicholson & Diane Keaton)!!!

Calcium Channel Blockers

Relaxes vascular smooth muscle
Some of these drugs should be taken with
food and caffeine should be limited
Constipation is most common side effect

Chemistry of Ca++ Channel

Blockers
Five major classes of Ca++ channel
blockers are known with diverse chemical
structures:
Benzothiazepines: Diltiazem
Dihydropyridines: Nicardipine,
nifedipine, nimodipine, amlodipine,
and many others
There are also dihydropyridine Ca ++-channel
activators (Bay K 8644, S 202 791)

Phenylalkylamines: Verapamil
Diarylaminopropylamine ethers:
Bepridil
Benzimidazole-substituted tetralines:
Mibefradil

Agents for Angina

Calcium Channel
Blockers

amlodipine (Norvasc)
bepridil (Vascor)
diltiazem (Cardizem, Dilacor XR)
felodipine (Plendil)
isradipine (DynaCirc)

Agents for Angina

Calcium Channel
Blockers

nicardipine (Cardene)
nifedipine (Procardia)
nisoldipine (Sular)
verapamil (Calan, Covera HS, Isoptin,
Verelan)

Effects on Vascular Smooth

Muscle

Ca++ channel blockers inhibit L-type and/or

T-type voltage-dependent Ca++ channels
Little or no effect on receptor-operated
channels or on release of Ca++ from SR
Vascular selectivity is seen with the Ca+
+ channel blockers
Decreased intracellular Ca ++ in arterial smooth
muscle results in relaxation (vasodilatation) ->
decreased cardiac afterload (aortic pressure)
Little or no effect of Ca ++-channel blockers on
venous beds -> no effect on cardiac preload
(ventricular filling pressure)
Specific dihydropyridines may exhibit greater
potencies in some vascular beds (e.g.nimodipine more selective for cerebral blood
vessels, nicardipine for coronary vessels)
Little or no effect on nonvascular smooth muscle

Effects on Cardiac Cells

Magnitude and pattern of cardiac effects
depends on the class of Ca++channel blocker
Negative inotropic effect (myocardial L-type
channels)
Reduced inward movement of Ca++ during action
potential plateau phase
Dihydropyridines have very modest negative
inotropic effect
Mibefradil (T-type) has no negative inotropic
effect

Negative chronotropic/dromotropic effects

(L- and T-type channels)
Verapamil, diltiazem, and mibefradil depress SA
node and AV conduction
Dihydropyridines have minimal direct effects on
SA node and AV conduction (but they can cause
reflex tachycardia)

Relative Cardiovascular Effects

of Calcium Channel Blockers
(adapted from Goodman & Gilman, 9th ed.)

Compound

Coronary
vasodilation

Suppression
of cardiac
contractility

Suppression
of
SA node

Suppression
of
AV node

Verapamil

++++

++++

+++++

+++++

Diltiazem

+++

++

+++++

++++

Nifedipine

+++++

Nicardipine

+++++

Usage of calcium ions antagon

Drugs

Illness
Hypertension

Verapamil

Dylthiazem

Nifedipin

Stenocardia

Verapamil

Dylthiazem

Nifedipin

Supraventric
ular tachyarrhythmia

Verapamil

Dylthiazem

Possible
combination with
-blockers
-rec-recommended drug
ommended drug

Dylthiazem

Nifedipin

Felodipin

Amlodipin

Amlodipin

Felodipin

--sho--should be used carefully

uld be used carefully

Amlodipin

Desired Therapeutic Effects of

Calcium Channel Blockers for
Angina

Improve oxygen delivery to ischemic

myocardium
Vasodilate coronary arteries
May inhibit platelet aggregation
Particularly useful in treating
vasospastic angina
Reduce myocardial oxygen consumption
Decrease afterload (no effect on
preload)
Non-dihydropyridines also lower heart
rate and decrease contractility
(* Dihydropyridines may aggravate
angina in some patients due to reflex
increases in heart rate and
contractility)

Ca++ Channel Blockers:

Toxicities

Adverse effects are typically direct extensions of

their therapeutic effects and are relatively rare
Major adverse effects:
Depression of contractility and exacerbation of heart
failure
AV block, bradycardia, and cardiac arrest

Minor adverse effects

Hypotension, dizziness, edema, flushing

Patients with ventricular dysfunction, SA node or

AV conduction disturbances, WPW syndrome, and
systolic blood pressures below 90 mm Hg should
not be treated with verapamil or diltiazem
Immediate-release forms of dihydropyridines may
increase mortality in patients with myocardial
ischemia
Bepridil is associated with several serious
toxicities including DILQT syndrome (which can
lead to the ventricular proarrhythmia, torsades de
pointes)

Ca++ Channel Blockers: Drug

Interactions
-blockers in combination with verapamil,
diltiazem, or bepridil
Bradycardia, AV block, depression of inotropic
state
Some channel blockers (verapamil, diltiazem) can
cause an increase in plasma digoxin levels
AV block can also occur with concurrent
treatment with channel blockers and digitalis
Quinidine in combination with some calcium channel
blockers
Results in decreased clearance of both and an
increased risk of bradycardia and AV nodal block
Bepridil in combination with other drugs that are
known to cause DILQT syndrome (e.g. quinidine,
sotalol)

BETA-ADRENOBLOCKERS
Mechanism of action during stenocardia
blockade of 1-adrenoreceptors of heart: decrease
of cardiac output and frequency of heart
contractions and as follows cardiac need in oxygen
decreasing of platelets aggregation and prevention
of plug formation
increasing duration of diastole improvement of
coronary vessels saturation with blood
improvement of perfusion of ischemic areas of
myocardium
Decreasing of calcium ions accumulation
releasing of cardiac muscle tension, improvement
of metabolic processes, increasing of ATP
synthesis
in case of acute myocardium infarction
increasing of blood supply of ischemic areas of
heart, decreasing of size of infarction area,
prevention of development of cardiac arrhythmias

-Adrenergic Blockers in the

Treatment of Angina
Though most beta-blockers do not cause
coronary vasodilation like the
nitrovasodilators or calcium channel
blockers, beta-blockers are important in the
treatment of angina because of their effects
on the heart
Desired effects of beta-blockers
Reduce myocardial oxygen consumption by
reducing contractility and heart rate
Reducing cardiac output also reduces
afterload
Some -blockers can cause vasodilation
directly or by acting as -blockers
Improve myocardial perfusion by slowing
heart rate (more time spent in diastole)

Adverse Effects and

Contraindications for Blockers

May exacerbate heart failure

Contraindicated in patients with asthma
Should be used with caution in patients
with diabetes since hypoglycemia-induced
tachycardia can be blunted or blocked
May depress contractility and heart rate
and produce AV block in patients
receiving non-dihydropyridine calcium
channel blockers (i.e. verapamil and
diltiazem)

Partial Fatty Acid Oxidation (pFox)

Inhibitors

Ranolazine (Ranexa, piperazine acetamide) is under

review by the FDA for the treatment of chronic
angina, acute coronary syndromes (ACS) , and longterm prevention of ACS
First new antianginal drug in more than 25 years
Acts by partially inhibiting fatty acid oxidation
in the myocardium, thus shifting metabolism to
glucose which requires less oxygen to metabolize
No hemodynamic effects
MARISA and CARISA clinical trials have studied more
than 3300 angina patients and healthy volunteers;
ERICA and MERLIN trials are ongoing for safety
FDA advisory committee (12/9/2003) recommended use
only in refractory cases of angina until safety
concerns have been addressed
QT prolongation and testicular toxicity are the
among the possible toxicities so far

ACTIVATORS OF POTASSIUM CANALS

NICORANDIL

activates 2+-depending potassium

canals
causes relaxation of smooth muscles
of vessels
coronary, arteriolar and venous
vasodilatation
improves
of
blood
supply
of
myocardium, decreasing of pre- and
afterloads of heart, decreasing of
myocardial
need
in
oxygen,
of
ischemic damage zone

Acetylsalicylic acid

80-100 mg per day against platelets

aggregation, decreases risk of development of
acute myocardium infarction and decreases
mortality of patients with IHD
Throughout the world it is also used as a drug
for basic treatment of IHD (can be used for
years)

Combination Therapy of Angina

Use of more than one class of antianginal agent can
reduce specific undesirable effects of single agent
therapy
Beta-Blockers or
Nitrates Plus
Channel Blockers
Beta-Blockers or
Alone
Channel Blockers

Effect

Nitrates Alone

Heart Rate

Reflex Increase

Decrease*

Decrease

Afterload

Decrease

Decrease

Decrease

Preload

Decrease

Increase

Contractility

Reflex increase

Decrease*

None

Ejection time

Decrease

Increase

None

None or decrease

Undesireable effects are shown in italics

* Dihydropyridines may cause the opposite effect due to a reflex increase
in sympathetic tone

Antianginal Combination
Therapies

Good Ones:
A dihydropyridine calcium channel blocker and a
beta-blocker (coronary vasodilation, decreased
afterload, lower heart rate, suppression of reflex
tachycardia)
A nitrovasodilator and a beta-blocker (coronary
vasodilation, decreased preload, lower heart rate,
suppression of reflex tachycardia)
A nitrovasodilator and a non-dihydropyridine calcium
channel blocker (coronary vasodilation, decreased
preload and afterload, lower heart rate, suppression
of reflex tachycardia)
A nitrovasodilator, a dihydropyridine calcium
channel blocker, and a beta-blocker (coronary
vasodilation, decreased preload and afterload, lower
heart rate, suppression of reflex tachycardia)
Bad Ones:
A beta-blocker and non-dihydropyridine calcium
channel blocker (bradycardia, AV block, depressed LV
function)

Additional Considerations in Treating

Angina
Modify risk factors associated with atherosclerosis
(smoking, hypertension, hyperlidemia)
Statins can reduce coronary artery disease in some
patients
Patients with stable angina who are refractory to drug
therapy may require surgical revascularization
(bypass) or angioplasty
Patients with vasospastic angina are not good
candidates for these surgical procedures
Unstable angina is an acute coronary syndrome that may
require maximally tolerated doses of conventional
antianginal drugs, and additional drugs including:
Antiplatelet drugs (aspirin, platelet glycoprotein
IIB/IIIA inhibitors, and/or platelet ADP
antagonists)
Thrombolytic drugs (tissue plasminogen activator,
streptokinase, or similar fibrinolytic agent)
Heparinoid anticoagulants including heparin or low
molecular weight heparins
Surgical revascularization or angioplasty is often
required in these patients

Myocardial Infarction
AKA heart attack
Leading cause of death in industrialized
nations
Heart muscle is deprived of oxygen and
muscle cells die
If healing occurs, scars form, and there
is less contractility of the heart
muscle

ACUTE MYOCARDIUM
INFARCTION
one of the main reasons of disablement and
mortality of people of employed age in many world
countries, including Ukraine
men suffer from MI almost 5 times more often than
women
Mortality of patients with MI during first two hours
after beginning of the process makes around 50
% of all mortal cases connected with MI
the most often death causes acute cardiacvascular insufficiency (angina pectoris, lung
edema, cardiogenic shock), heart rupture, severe
cardiac arrhythmias
other complications of MI thrombosis and
emboli, acute and chronic heart aneurisms,
Dresslers syndrome, chronic cardiac insufficiency

Causes of MIs
Prolonged decrease in oxygen supply
Occurs if one or more of the 3 major
arteries is narrowed by 70% or more
Risk factors:
History of angina, alcohol
consumption, reduced pulmonary vital
capacity, cigarette smoking,
atherosclerosis

Lifestyle Changes
To reduce the risk of an MI:
Eliminate smoking
Control diabetes
Reduce hypertension
Exercise moderately
Achieve and maintain ideal body weight
Decrease alcohol consumption
Use aspirin therapy
Reduce dietary
cholesterol/triglycerides

Symptoms of a Heart Attack

Oppressive or burning tightness or
squeezing in the chest
Feeling of choking
Sense of impending doom
Substernal pain with radiations to the
neck, throat, jaw, shoulders, and one or
both arms
Pain can last 30 mins to several hours

TREATMENT OF MYOCARDIUM
INFARCTION
three stages

Immediate treatment decreasing

pain and treatment of cardiac
arrest
Early treatment separation of
zone
of
infarction
seat
and
prevention
of
early
life
threatening complications (cardiac
arrhythmias,
acute
cardiac
insufficiency)
Further treatment prevention and
therapy of late complications of
MI, prophylaxis of recurrent MI
and death of the patients

TREATMENT OF ACUTE MYOCARDIUM INFARCTION

Releasing of pain and

prophylaxis of cardiogenic shock
nitroglycerin (1 tablet under the tongue every
7-10 min.)
Neuroleptanalgesia (fentanil with droperidol),
morphine, omnopon, promedol (in combination
with atropine, dimedrol, aminasine)
Nitrous Oxide in combination with neuroleptics
in case of remaining pain non narcotic
analgesics in combination with antihistamine
and neuroleptic drugs
to
increase
arterial
pressure
during
cardiogenic
shock

intravenously
dropply
dopamine
(drugs
of
choice),
noradrenalin,
mesaton
sometimes glucocorticosteroids are used

TREATMENT OF ACUTE MYOCARDIUM

INFARCTION

Size limitation
of infarction zone

Intravenous dropply introduction

of
0,01 % nitroglycerin solution
Administration of adrenoblockers

TREATMENT OF ACUTE
MYOCARDIUM INFARCTION
Treatment and prophylaxis of cardiac arrhythmias
Treatment of ventricular arrhythmias
i.v. slowly 0,2 % solution of xycain,
novocainamid intramuscularly
Prophylaxis of ventricular extrasystolia
and tachycardia magnesium sulfate
(intravenous dropping introduction of 45 % solution), -adrenoblockers
Arrhythmias of atrial origin cardiac
glycosides, antagonists of calcium ions
Bradycardia - isadrin, atropine sulfate,
alupent (i.v.)

TREATMENT OF ACUTE
MYOCARDIUM INFARCTION
CORRECTION OF BLOOD CLOTTING

thrombolytic drugs

streptokinase (1,5 mln OD), urokinase (2

mln OD), aktilise recombinant tissue
activator of plasminogen (100 mg)
intravenously
after performing of thrombolytic therapy
intravenous introduction of heparin, at
first 10 000 OD, after 1000 OD per hour
during 24-48 hours
anticoagulants of indirect action

acetylsalicylic acid
(80-100-300 mg per day)

TREATMENT OF ACUTE
MYOCARDIUM INFARCTION
Treatment of cardiac insufficiency
i.v. furosemid (40-120 mg); i.v. dropply
nitroglycerine (12-20 hours), morphine
i.v. dropply dopamin and dobutamin
heart glycosides in tachysystolic form
of
scintillating
arrhythmia
or
fluttering of atria with moderate leftventricular insufficiency

General measures
oxygen inhalation
correction of acid-base balance

Myocardial Drug Therapy

Aimed at allowing the heart to rest and
undergo normal healing
Slow the heart (Beta Blockers)
Reduce blood clot formation (Aspirin
Therapy)

Beta Blockers Used

after an MI

acebutolol (Sectral)
atenolol (Tenormin)
betaxolol (Kerlone)
bisoprolol (Zebeta)
carvedilol (Coreg)

Beta Blockers Used

after an MI

esmolol (Brevibloc)
labetalol (Normodyne, Trandate)
metoprolol (Lopressor, Toprol XL)
nadolol (Corgard)
pindolol (Visken)
propranolol (Inderal)
sotalol (Betapace)
timolol (Blocadren)