Acute Myocardial Infarction and Related Drugs

Jianing Zhong

School of Chemistry, The University of Nottingham, Nottingham, NG7 2RD, U.K.

Keywords:

Acute Myocardial Infarction, Aspirin, Clopidogrel.

Abstract:

As the medical name for a heart attack, acute myocardial infarction (AMI) is a common disease with serious

symptoms and no relevant targeted drugs. Extremely critical consequences of AMI in mortality, morbidity,

and cost to the society have been the great challenge in the long-term development of human society. In

addition, the advent of AMI and results of clinical trials on therapy have major implications from the

epidemiological, societal, and patient points of view. Hence, it is of great significance to develop drugs related

to acute myocardial infarction with excellent pharmacokinetics. This paper discusses the pathophysiology,

evolving drugs on therapy of acute myocardial infarction and incorporates the chemical structure,

pharmacology, underlying economics of pertinent drugs and further discussion of the drugs related to the

AMI.

1 INTRODUCTION

1.1 Definition and Categories

Acute myocardial infarction, commonly defined as

myocardial necrosis due to acute, persistent ischemia

and hypoxia of the coronary arteries; Also known as

a sudden heart attack, it is a life-threatening condition

that occurs when blood flow to the heart muscle is

suddenly interrupted, leading to tissue damage

(White, Chew, 2008). Furthermore, a new definition

of myocardial infarction has been consensus group

put forward in 2000 from the European Society of

Cardiology and the American College of Cardiology,

with the definition being based on myocyte necrosis

as determined by troponins in the clinical setting of

ischemia (White, Chew, 2008).

Acute myocardial infarction is a major cause of

morbidity and mortality worldwide, with two

entities. According to the difference between ST

segment elevation and non-elevation on

electrocardiogram, acute myocardial infarction can

be classified as ST segment elevation myocardial

infarction (STEMI) and non-ST segment elevation

myocardial infarction (NSTEMI) (Boersma, 2003).

In addition to distinguishing from by ST segment, the

two types of acute myocardial infarction can also be

clinically distinguished by coronary angiographic

findings (Most of the coronary arteries in NSTEMI

are not completely occluded).

1.2 Factors and Symptoms

Acute myocardial infarction can be caused by several

factors, such as age, genetics. However, extreme

lifestyles may be the biggest culprit. Epidemiological

studies have highlighted the role of lifestyle factors

in acute myocardial infarction. Poor lifestyle habits,

such as obesity and alcohol abuse, can potentially put

people at risk for acute myocardial infarction. While

chest pain and shortness of breath are typical

symptoms of an acute myocardial infarction, there

are several different symptoms, including nausea,

anxiety, or dizziness (Boersma, 2003).

1.3 The Number of Cases in China and

Other Countries

According to incomplete statistics, there are 3

million people suffer from STEMI each year, and

there are also more than 4 million cases of NTSEMI

(White, Chew, 2008). Acute myocardial infarction, a

common disease in developed countries, affects

more than 1 million people in the United States each

year. However, acute myocardial infarction is also on

the rise trend in developing countries at present. For

example, acute myocardial infarction has become a

major cause of hospitalization and mortality in

China. According to incomplete statistics, there are

approximately 4 million cases of acute myocardial

infarction in China (White, Chew, 2008).

574

Zhong, J.

Acute Myocardial Infarction and Related Drugs.

DOI: 10.5220/0011238600003443

In Proceedings of the 4th International Conference on Biomedical Engineering and Bioinformatics (ICBEB 2022), pages 574-578

ISBN: 978-989-758-595-1

1.4 Drugs Used to Treat the Disease

As the main potential incentive of acute myocardial

infarction, platelet hypperaggregation is constantly

devouring human life. Based on extensive

pharmacological evidence, antithrombotic

medications such as Aspirin and Clopidogrel are the

most potentially effective antiplatelet agents

contribute to treat platelet hypperaggregation. In

addition, Nitrates and Stains as other first-lines

medicine are adopted in improving the long-term

outlook in survivors of the acute phase. Although, the

majority of pharmacological evidence are based on

the clinal trials from patients with STEMI, the first-

lines medicine also available optional for the

NSTEMI patients (Boersma, 2003). In this paper,

Aspirin and Clopidogrel are discussed in the next

stages as the main treatment agents for acute

myocardial infarction in the article.

2 DESCRIPTION OF CHEMICAL

STRUCTURE OF DRUGS

In the description, the structures for aspirin and

clopidogrel are shown by two figures. In addition,

there are two more figures of the chemistry

properties for aspirin and clopidogrel.

2.1 Aspirin

Figure 1: the structure of aspirin

As known as acetylsalicylic acid, with the IUPAC

name 2-Acetoxybenzoic acid, is a salicylic acid class

of drugs. As a white crystalline or crystalline powder,

odorless or with a slight odor of acetic acid, slightly

soluble in water, soluble in ethanol, soluble in ether

and chloroform, and acidic in aqueous solutions. The

structure of aspirin and the properties of Aspirin can

be demonstrated as Figure 1 and Table 1:

Table 1: the properties of Aspirin

Formula

𝐶



𝐻



𝑂



Boiling point

321.4°C at 760 mmHg

Molar mass

180.16

Solubility in wate

3.3𝑔/𝐿

Density

1.35𝑔 𝑐𝑚



Vapor pressure

0.000124𝑚𝑚𝐻𝑔 𝑎𝑡 25°𝐶

Boiling Point

136  140℃

2.2 Clopidogrel

Figure 2: The structure of 𝑐𝑙𝑜𝑝𝑖𝑑𝑜𝑔𝑟𝑒𝑙.

As known as a drug that inhibits platelet

aggregation， with the IUPAC name (+) − (𝑆) −

𝑚𝑒𝑡h𝑦𝑙 2 − (2 − 𝑐h𝑙𝑜𝑟𝑜𝑝h𝑒𝑛𝑦𝑙) − 2 − (6,7 −

𝑑𝑖h𝑦𝑑𝑟𝑜𝑡h𝑖𝑒𝑛𝑜[3,2 −𝑐]𝑝𝑦𝑟𝑖𝑑𝑖𝑛 − 5(4𝐻) −

𝑦𝑙)𝑎𝑐𝑒𝑡𝑎𝑡𝑒 (J.-M. Pereillo, 2002). The structure of

clopidogrel and the properties of Aspirin can be

demonstrated as Figure 2 and Table 2:

Table 2: The properties of Clopidogrel

Formula

𝐶



𝐻



𝐶𝑙𝑁𝑂



𝑆

Boiling point

423.7°C at 760 mmHg

Molar mass

321.86

Density

1.32𝑔 𝑐𝑚



Acute Myocardial Infarction and Related Drugs

575

3 DISCUSSION OF DRUG

PHARMACOLOGY

In the discussion of pharmaceutical pharmacology,

aspirin and clopidogrel would be discussed in three

separate parts, which are pharmacodynamics,

Pharmacokinetics, and the Mode of Delivery.

3.1 Aspirin

3.1.1

Pharmacodynamics

As one of the earliest antiplatelet drugs, aspirin was

synthesized in the late 19th century, and its

antiplatelet action was discovered British

pharmacologist John Robert Vane in 1970s.

As an antithrombotic drug, aspirin is an inhibitor

of cyclooxygenase (COX) (Warner, 2002). The

irreversible acetylation of aspirin with

cyclooxygenase leads to the inactivation of COX,

which in turn disables the pathway of thromboxane

formation and ultimately prevents high platelet

aggregation. (The main involved in antithrombotic is

COX-1 (Warner, 2002). Studies have shown that

COX-2 plays a significant role in prostaglandin

production.)

3.1.2

Pharmacokinetics

As a weak acid, aspirin dissociates very slight in the

stomach. As a result, aspirin is quickly absorbed by

cell membranes in the stomach. Nevertheless, in the

small intestine, as the PH value gradually increases,

the amount absorbed gradually decreases.

According to long-term clinical trials, only 20 to

50 percent of aspirin is ionized; the rest is absorbed

into the bloodstream. Aspirin has a half-life of two to

three hours (Bond, 2007). For example, the half-life

of a single dose of 0.65g aspirin in breast milk is about

3.8 to 12.5 hours. (Because aspirin is excreted in

breast milk, large doses can have an adverse effect on

infants.)

3.1.3

Mode of Delivery

Aspirin is mainly taken orally. The daily dose needs

to be determined according to the stage of the disease

and the patient's constitution. Generally, small doses

are given priority to, usually 50 to 150mg per day

(Bond, 2007). However, during an acute myocardial

infarction, 325 mg of aspirin can be taken orally for

the first time, and then 100 mg a day (Ferguson,

1970).

3.2 Clopidogrel

3.2.1

Pharmacodynamics

As one kind of antithrombotic agent, clopidogrel is a

P2Y12 purine receptor antagonist (Mega, 2009).

P2Y12 receptor plays an important role in mediating

the sustained activation of stimulated by ADP, and is

a major receptor that mediates platelet adhesion.

P2Y12 receptor antagonist can inhibit the activation

and amplification of platelet induced by ADP and

produce effective antithrombotic effect.

3.2.2

Pharmacokinetics

As a prodrug, clopidogrel in activated in two steps by

two enzymes. The enzyme in first step mainly is

CYP2C19 (Mega, 2009). There are many different

enzymes involved in the second step (Hydrolysis

reaction), such as CYP2C19, CYP2C9. The figure 3

briefly describe the progress of pharmacokinetics for

clopidogrel.

Figure 3: the progress of pharmacokinetics for clopidogrel. The primarily step is oxidation with CYP2C19 enzyme as catalyst.

The two structures at bottom are tautomer. Moreover, the second step is reaction of hydrolysis.

ICBEB 2022 - The International Conference on Biomedical Engineering and Bioinformatics

576

Specifically, clopidogrel was not effective in

treating acute myocardial infarction for about 2 hours

after oral administration, since clopidogrel itself is

not effective in inhibiting platelets. However, after

being activated by cytochrome P450 enzyme

(CYP2C19) in liver, clopidogrel structure is

destroyed (thiophene ring is opened), resulting in the

formation of new substances that can fight

thrombosis (Simon, 2009). The entire clopidogrel is

digested in the human body, and it takes about 3.5 to

4.5 hours for the drug to take effect and wear off.

3.2.3 Mode of Delivery

Clopidogrel was mainly taken orally once a day and

can be taken for a long time. Dosages vary from

50mg to 150mg, depending on age (best taken after

meals). For rapid action, clopidogrel can also be

taken orally in 300 to 600mg doses at a time (Collet,

2009).

4 DISCUSSION OF DRUG

ECONOMICS

In order to discuss the drug Economics, the cost and

the number of prescription and sales of aspirin and

clopidogrel are briefly shown.

4.1 Aspirin

According to Clinical (2018), aspirin prescription

costed around $4.48 in the United States and as little

as £1.28 in the UK. It proves that aspirin is within the

reach of almost everyone. Meanwhile, In the United

States, there are more than five million patients who

need aspirin and a staggering 19 million aspirin

prescriptions (Boersma, 2003).

4.2 Clopidogrel

Clinical (2017) stated that nearly all clopidogrel is

covered by most Medicare and insurance plans and

each patient effectively treats acute myocardial

infarction for about $10 per month (Boersma, 2003).

In 2018, this is projected to be more than 4 million

AMI patients in America and number of

prescriptions in the United States is exceeding 20

million.

In a word, the low cost of aspirin and Clopidogrel

is an appropriate guarantee for acute myocardial

infarction. At the same time, the large number of

patients and prescriptions suggests that there still be

a large market and a sound momentum of growth for

them.

5 FURTHER DISCUSSION

As same as the other drugs, clopidogrel and aspirin

own side effects as well. In the further discussion,

both adverse effects are discussed and other types of

antithrombotic drugs for acute myocardial infarction

is briefly covered as well.

5.1 Aspirin

Serious side effect associated with aspirin treatment

include:

Gastrointestinal reaction. Oral aspirin can

directly affect the stimulation of gastric mucosa and

cause nausea and vomiting, and long-term use will

lead to gastritis membrane damage and gastric ulcer

and gastric bleeding and other symptoms

(Vishweshwar, 2005).

Allergic reaction to aspirin. Aspirin can cause

rashes, angioedema, asthma, and other allergic

reactions in allergic people.

Aspirin may also influence the central nervous

system. Generally, when taking a large dose, there

will be headaches, vertigo, tinnitus and other

symptoms, and there will be coma and other

symptoms when taking too much.

Liver and kidney damage. Side effects of aspirin

include toxicity to the liver and kidneys. Aspirin is

broken down in the liver and then excreted through

the kidneys, resulting in decreased liver and kidney

function.

5.2 Clopidogrel

As an inhibitor of platelets, clopidogrel affects the

lifespan of platelets by irreversibly changing the

ADP receptor of platelets, leading to

thrombocytopenia, and the lack of platelets is the

culprit of the bleeding. Therefore, the main side

effect is bleeding, such as subcutaneous bleeding,

gingival bleeding. Side effects includes

gastrointestinal reactions, allergies, liver and kidney

dysfunction, and leukopenia are usual in clinical

treatment as well (Diener, 2004).

Platelet membrane glycoprotein IIb/IIIa

(GPIIb/IIIa) receptor antagonists are also

antithrombotic agents (GPIIb/IIIa antagonists are

ligand mimics that prevent fibrinogen from binding

to activated platelets, thereby directly inhibiting

platelet aggregation) (Kaufman, 1972). Three drugs

Acute Myocardial Infarction and Related Drugs

577

are currently on the market: tirofiban, a small non-

peptide molecule that mimics fibrinogen binding

sites; Etibateptide, a cyclic heptapeptide with a

lysine-glycine-aspartic acid (KGD) sequence, also

mimics the fibrinogen binding sequence in

GPIIb/IIIa; And accimab, a humanized antigen-

binding fragment of a murine monoclonal antibody

(Simon, 2009).

6 CONCLUSION

This article provides a brief overview to acute

myocardial infarction from the perspective of its

definition and introduces two drugs for the

prevention and treatment of AMI from an

antithrombotic perspective——aspirin and 1.

chemical structure, and corresponding chemical

properties of these two drugs are described in detail

in the follow section. Furthermore, through the parts

of pharmacodynamics and pharmacokinetics, the

pharmacology of these two drugs is referred at

length.

However, these two drugs also own assignable

underlying adverse effects. Unfortunately, there is

still no specific drug to treat or prevent acute

myocardial infarction. These two points are cursorily

discussed likewise in further discussion.

Overall, as a common cardiovascular disease,

acute myocardial infarction owns a higher mortality

rate than the parallel diseases. Nevertheless, due to

the understanding of its pathogenesis and the timely

investment of related drugs, it has declined

significantly in the past decades. On the contrary,

both number and the age range of the acute

myocardial infarction are increasing year by year.

Therefore, as a kind of cardiovascular disease, acute

myocardial infarction is still a kind of disease should

not be ignored and worthy of study.

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