pharmacotherapeutics of myocardial-infarction

pharmacotherapeutics of myocardial-infarction

1. INTRODUCTION

® Myocardial infarction (MI)
refers to the process by which Myocardial Infarction
as a result of a blocked

heart are permanently destroyed. nn

areas of myocardial cells in the

© It occurs when myocardial
tissues are abruptly and
severely deprived of oxygen.

2. DEFINITION

® Myocardial infarction is a
diseased condition which is
caused by reduced blood flow
in a coronary artery due to
atherosclerosis and occlusion

of an artery by an embolus or
thrombus.

Insufficient blood flow to the heart
muscle from narrowing of coronary
artery may cause chest pain

FADAM.

3. Right
Coronary
Artery

4. LOCATION / TYPES OF MYPCARDIAL INFARCTION

» Obstruction of the left anterior descending artery (LAD)
results in anterior or septal wall MI.

Blocked
of Left Coronary Artery

Anterior Infarct

5. + Obstruction of the circumflex artery results in posterior
wall MI or lateral wall MI.

+ Obstruction of the right coronary artery results in inferior

wall MI. Coronary Arteries

Diagonal Branch of

\ Left Anterior Descending
D

lor Descending

6. Alassification

The two main types of acute myocardial infarction, based

on pathology, are:

» Transmural infarction- Transmural infarcts extend through
the whole thickness of the heart muscle and are usually
a result of complete occlusion of the area's blood
supply.

Subendocardial (nontransmural) infarction - involves a
small area in the subendocardial wall of the left
ventricle, ventricular septum, or papillary muscles.

A transmural infarct is sometimes referred to as an “ST
elevation myocardial infarct” (STEMI) and a subendocardial
infarct as a “non-ST elevation infarct” (NSTEMI).

9. NON-MODIFIABLE RISK
FACTORS ,

10. e More than 40 years.

@FAMILY HISTORY:
Myocardial infarction can
be inherited from parents
to children.

OGENDER: Myocardial
infarction is 3 times more in
men than women.

11. MODIFIABLE RISK FA

12. Cu u

PATHOPHYSIOLOGY

13. Atherosclerosis of coronary artery

Narrowing of lumen

led heart +— insufficient blood flow to myocardium
Contractility fed O,demand of myocardial cells

Inadequate creates an O, deficit
one

myocardial cell death inflammation
Oliguria | l

CK-MB & Troponine released Fever

14. Anaerobic glycolysis
Accumulation of lactic acid
Irritation of myocardial nerve fibers
Transmission of pain to myocardium

Chest pain & radiation towards shoulder & arm

|

15. ————— ]———Z

center
| increased
Nausea & Vomiting catecholamine
Diaphoresis Increased
(perfuse i Heart Rate
Cold & Clammy skin
“Cold Sweat”

16. ®Characteristics: Severe, immobilizing sauna
chest pain.

® Usually described as heaviness, pressure,
tightness, burning.

® Location: Substernal, Retrosternal or
Epigestric.

® Radiation: It may radiate to neck, jaw,
arm or back.

® Duration: Lasts for 20 minutes or more.

17. Pain interpreted as
originating im Gistrebuticn
of somatic sensory nerves

Patent perceives

2 3. 109 diffuse pain in

T1—4 dermatome

18. , ~ NAUSEA & VOMITING

% Stimulation of vomiting center by severe pain causes
nausea & vomiting.

FEVER

© 100.4 to 102.2°F

© It is due to inflammatory process caused by
Myocardial cell death.

19. SYMPATHE

STIMULATION

* Increased catecholamine releases.
% Diaphoresis (perfuse sweating).

* Cold & clammy skin (“cold sweat”).

20. ARDIOVASCULAR MANIFESTATIONS

C
€ Hypotension

Decrease cardiac output
Shock

Urine output (Oliguria): <30ml/day.
$ Dyspnoea

21. DIAGNOSTIC TESTS

22. » Electrocardiogram-
ECG provides information that
assists in diagnosing acute MI.
+ The classic ECG changes are-
* T wave inversion
* ST segment elevation
= Abnormal Q wave

23. MYOCARDIAL INFARCTION...

Area OF
Infarction
O, Deprived

Damage
Irreversible

Causes “Q" Wave
on EKG.

rct. Tissue
long as

Next to inf.

Area OF
Ischemia

Viability may not be
damaged as long as
MI doesn't extend and
collateral circulation
able to compensate

Causes depressed

eg

24. RETURNS TO
NORMAL WITHIN
24 HOURS.

TROPONIN

MOST SENSITIVE
AND SPECIFIC

RISES IN
44-12 HOURS

MAY REMAIN
ELEVATED FOR UP
TO TWO WEEKS

25. ANGIOGRAPHY

To detect percentage of blockage & type of MI.

CHEST X-RAY
To detect cardiomegaly.

26. A
Isotope scanning

= Technetium-99m pyrophosphate
accumulates in damaged myocardium
whereas thallium-201 produces a deficient
uptake in territories supplied by occluded
or narrowed arteries. Thallium is most
commonly used as a screening technique
in patients with suspected coronary artery
disease.

27. DRUG THERAPY IN MYOCARDIAL INFRACTION

® Pharmacological therapy in MI has following
objectives.

1.To reduce pain, anxiety and apprehension .
2.Oxygenation .

3.Maintenance of blood volume, tissue perfusion, and
microcirculation .

4.correction of acidosis.
5.Prevention and treatment of arrhythmias.
6.To manage cardiac output .

28. 08. Threrikilye and reperfusion.
© 9.Prevention of remodeling and subsequent CHF
2 10.Prevention of future attacks

a. platelet inhibitors.
b. beta blockers
c. control of hyperlipidemia .

29. A. Drugs for the treatment of acute myocardial infarction

30. 1.To reduce pain anxiety and apprehension

© 1. After pain is not relieved by 3 doses of GTN given 5
min. apart , an opioid analgesic [morphine
/pethidine] or diazepam is administered parentally.

31. 2.Prevention and treatment of arrhythmias.

® Prophylactic i.v. infusion of beta blockers as soon as the
MI patient is seen ,reduces the incidence of arrhythmia
and mortality .

® Beta blockers used early in evolving MI can reduce the
infract size and complications.

® Tachyarrhythmias may be treated with i.v lidocaine,
procainamide, or amiodarone.

32. PROTECTIVE EFFECTS OF BETA BLOCKERS IN
ISCHEMIA

o Reduce the myocardial oxygen demand via
» negative inotropic action
- reduction of heart rate
» blood pressure decrease
o Increase coronary blood flow via
+ increase in diastolic perfusion time by reducing heart
rate
» augmentation of collateral blood flow and
» redistribution of blood flow to ischemic areas
o Alter the myocardial substrate utilization
o Decrease the microvascular damage

© Stabilize the cell and lysosomal membranes

33. _—— AS

3. To manage cardiac output-

© The objective is to increase c.o. and to decrease filling
pressure without increasing cardiac work or lowering
BP-

A. Furosemide- indicated if pulmonary wedge pressure
is > 20 mm Hg. It decreases cardiac preload.

B. Vasodilators - GTN or nitoprusside have been manily
used,

C. Inotropic agents- dopamin or dobutamine to
augment pumping action of heart.

34. Heart Failure

Inotropic drugs, Digoxin

Reduced CO

Digoxin

Sympathetic
NS activation

Vasoconstriction

Beta blockers Cardiac filling pressure

inhibitors

Angiotensin |

Na & water retention

inhibitors

Angiotensin II

AT, receptor
antagonists

Aldosterone

Spironolactone

Beta blockers

Cardiac
Remodeling

Adapted from: Maron & Rocco, 2011

35. ps revention of thrombus extension, embolism,

venous thrombosis-

® 1. Aspirin [162- 325 mg] as soon as MI is suspected. This is
continued at 80-160 mg / day.

® 2. Anticoagulants [heparin followed by oral
anticoagulants Jare used to prevent deep vein thrombosis
and pulmonary or arterial embolism.

36. Step!
binds with

Step ll
inactivates
Antithrombin i

Step I

Inhibits conversion of

Clot prevented

37. 5.Thrombolysis and reperfusion

® 1. Fbrinolytic agents i.e. streptokinase /urokinase/
alteplase are used to achieve reperfusion of infracted
area

® 2.Thrombolysis should be started within 1- 2 hours of
MI symtom onset.

© 3. Primary percutaneous coronary intervention with
stenting is preferred revascularization procedure.

38. Plasminogen

'Urokinase +
Alteplas >
Tenecteplase A
Plasmin
Thrombin
+ | + E
Fibrinogen ——> Fibrin
Degradation Degradation

products products

39. _ ——

6.Prevention of remodeling and subsequent
CHF

© 1.ACE inhibitors/ARBs are of proven efficacy and
afford long- term survival benefit.

ACE inhibitors
block the action
= [Renin ) of this enzyme

Nw ewe ee ee ee

40. Change in

Peripheral Resistance

Mechanisms
Direct Vasoconstriction

‘Sympathetic Discharge

4 Adre

Catech

Noradrenergie Enhancement
(1) decreased reuptake

ne Release

(2) increased release

(3) increased vascular
responsiveness

Rapid Pressor Response

Y

Change in
Renal Function
Mechanisms

Sodium Reabsorption
(direct and aldosterone mediated)

Direct renal vasoconstriction

Noradrenergic transmission

tone

4 Renal sympathe

Slow Pressor Response

Y

Structural Changes
Remodeling

echanisms

1 Proto-one ogene
expression

4 Growth Factors

4 Afterload

4 Wall T

Vascular and Cardiac
Hypertrophy & Remodeling

41. 7.Prevention of future attacks-
© Platelet inhibitors- asprine or clopidogrel.

® Beta blockers- reduce risk of re infaraction, CHF, and
mortality.

® Control of hyperlipidemia.

42. y ~~ SURGICAL MANAGEMENT

®PTCA (Percutaneous Ay ua
Transluminal Coronary ==
Angioplasty) Er LS

Expanded Stent Inflated Balloon

Stenting

43. STENT PLACEMENT

44. eel

ATHERECTOMY

+ With Atherectomy the plaque is shaved off using a
type of rotational blade.
ne

45. Before

CORONARY
ARTERY
BYPASS GRAFT

(CABG)

+ A portion of saphenous
vein from leg is
removed & is
anastmosed proximally
to the ascending aorta
& distally to coronary
artery.

Decreased blood flow Normalized blood flow

46. ocardial Infarction
1. Optimsing the Outcomes Of PPCI

Thrombus aspiration during PPCI

Rheolytic thrombectomy (RT) before direct infarct artery stenting as compared
to direct stenting (DS) alone to improve the results of myocardial reperfusion
and clinical outcome in patients with acute myocardial infarction.

Intracoronary Gp llb/llla inhibitors

Intracoronary administration of drugs increases local drug concentration
several fold. The increased concentration of Gp IIb/Illa inhibitors like
Abciximab, Eptifibatide, Tirofiban are shown to improve the outcomes of
PCI safely and efficaciously in terms of reduction in infarct size,
peri-procedural MI .

Adenosine

Intracoronary administration of vasodilators such as adenosine during

and after PPCI has been shown to improve flow in the infarct-related

coronary artery and myocardial perfusion and reduces infarct size.

47. lew oral anti-platelet drugs for AMI

Ticagrelor, unlike the thienopyridines Clopidogrel and Prasugrel, is not a pro-
drug and therefore has a faster onset of action with less variability than the
thienopyridines. It causes stronger platelet inhibition, particularly in the early
phase, and it is reversible, which maybe an advantage in reducing bleeding.
The ticagrelor group suffered fewer cardiovascular events, with the primary
end point of MI, stroke, or vascular death being significantly reduced without
any increase in major bleeding complications.

Antiplatelet Therapy:
Targets

Clopidogrel! bisulfate
Ticlopidine hydrochloride
Prasugrel hydrochloride
Ticagrolor

Dipyridamolo

Phosphodiostoraso

Gp 2b/3a Inhibitors
Collagen
Thrombin

od ss

Aspirin + J

Altmann cxpnowpnate, COC yen, FA = Thromboxane A,

Bosco: Sotater Ai Antptataiet Trerapy, Min did 1906:101:100-200

48. oprotection Agai
Reperfusion Injury

The restoration of blood flow to ischemic myocardium sometimes leads
to myocardial injury termed as reperfusion injury which can be more
detrimental than ischemia itself and paradoxically reduce the advantage
of early restoration of blood flow. This type of injury is called as
Ischemic -Reperfusion injury.

49. A

a. The drugs which target these pathways are

cyclosporine, erythropoietin, glucagon-like peptide 1
and atrial nitriuretic peptides. The new strategies for protection
against reperfusion injury are Ischemic conditioning, targeting
the RISK [reperfusion injury salvage kinase]pathway, targeting
mitochondrial[phosphotyrosyl phosphatase activator] PTPa

b. The ischemic conditioning can be defined as preconditioning

when performed before reperfusion and post-conditioning . In clinical
practice the remote ischemic preconditioning is carried out with brief
occlusion of blood flow to either upper or lower limb by periodically inflating
and releasing the blood pressure cuff. The remote ischemic
preconditioning is believed to activate changes in intracellular
kinase and mitochondria that are cardio-protective..

C. The ischemic post-conditioning is carried out by transient

balloon occlusion of the infarct related artery. The remote
ischemic post-conditioning is carried out by transient occlusion
of other than the infarct related coronary artery.

50. proinflammatory genas

% a”

+ Antinflammatory elect
on circulating leukocytes

51. air and Regenerat

F_—-

The Transplantation of Progenitor Cells And Regeneration Enhancement
in Acute Myocardial Infarction investigated both safety, feasibility, and
potential effects on parameters of myocardial function of intracoronary
infusion of either circulating progenitor cells (CPC) or bone
marrow-derived progenitor cells (BMC) in patients with acute myocardial
infarction (AMI).

Sono - thrombolysis

The use of Ultrasonic waves along with the fibrinolytic agent is
described as Sono-thrombolysis.

ST-segment resolution was better in patients who received
tenecteplase and sono-thrombolysis compared with those
who received tenecteplase alone. The exact mechanism of
benefit of sono-thrombolysis is not known, however the nitric
oxide release by vibrating endothelial cells and opening of
collateral channels have been contemplated

52. Isolation of
Patient’s Stem Cells
# from Blood, Bone

A E É = bi: e dd
A %
Y

Cell Amplification

Therapy of Cells

Cell
Grafting

2 © Stem cells, ESC, iPS, ..
Y

a A A = Cardiac myocytes
vessels

Pro-survival Cocktails,
Hydrogels, Patches

53. DU

Complications of myocardial infarction Dominique Yeie

Myocardial infarction

Impaired Electrical Pericardial
contractility = instability inflammation

Pagillary muscle an
Es wall rupture ES
Y
un
=
= fee]

Ventricular Hypotension -+
thrombus L coronary perfusion —+