The document discusses cardiovascular diseases and provides information on the heart, its structure and function. It defines different types of heart diseases such as myocardial infarction, arrhythmias, congestive heart failure, atherosclerosis, congenital heart disease, and ischemic heart disease. Risk factors for heart diseases are described. Antihypertensive drugs and their mechanisms of action are explained. Specifically, the document discusses the cardiotonic agent methyldopa, providing its synthesis, mechanism of action, and uses for treating hypertension.

1. Cardiovascular
Diseases
Pharm.D III Year

2. The Heart

3. Heart
• The heart, is a hollow muscular organ, is located in the
center of the chest.
• The right and left sides of the heart each have an upper
chamber (atrium), which collects blood and pumps it into
a lower chamber (ventricle), which pumps blood out.
• To ensure that blood flows in only one direction, each
ventricle has an “in” (inlet) valve and an “out” (outlet)
valve.

4. Function of heart
The heartbeats are evidence that the heart is
Pumping.
The heart’s only function is to Pump blood.
The contraction of the Muscle Fibers in the
heart is very organized and highly controlled.

5. Heart diseases
• Heart disease is any disorder that affects the
heart's ability to function normally.
• Heart disease is a general term that refers to
a variety of acute and chronic medical
conditions that affect one or more of the
components of the heart.

6. Myocardial infarction
• Myocardial infarction (MI or AMI for acute
myocardial infarction), commonly known as a
heart attack, occurs when the blood supply to
part of the heart is interrupted.

7. Myocardial Necrosis
• Myocardial necrosis refers to the death of
certain segment of the heart muscle
(myocardium), usually the result of complete
blockage in one of the main coronary arteries
or a branch thereof.

8. Different types of heart diseases
• Alcoholic Cardiomyopathy, Aortic Regurgitation, Aortic
Stenosis, Arrhythmias, Cardiogenic Shock.
• Congenital Heart Disease, Coronary Artery Disease (CAD),
Dilated Cardiomyopathy.
• Endocarditis, Heart Attack (Myocardial Infarction), Heart
Failure, Heart Tumor, Hypertrophic Cardiomyopathy.

9. Contn..
• Idiopathic Cardiomyopathy, Ischemic
Cardiomyopathy, Acute Mitral Regurgitation,
Chronic Mitral Regurgitation, Mitral Stenosis,
Mitral Valve Prolapse, Peripartum
Cardiomyopathy, Pulmonary Stenosis, Stable
Angina, Unstable Angina, Tricuspid
Regurgitation.

10. Arrhythmias
• Arrhythmias is a disorder of the heart rate
(pulse) or heart rhythm, such as beating too
fast (tachycardia), too slow (bradycardia), or
irregularly.

11. Congestive Heart Failure
Congestive heart failure (CHF), or heart failure, is
a condition in which the heart can't pump
enough blood to the body's other organs.
Common causes of heart failure include
myocardial infarction and other forms of ischemic
heart disease, hypertension, valvular heart
disease and cardiomyopathy.

12. Atherosclerosis
Atherosclerosis is a condition in which fatty
material collects along the walls of arteries.
This fatty material thickens, hardens and may
eventually block the arteries.
It is a syndrome affecting arterial blood vessels, a
chronic inflammatory response in the walls of
arteries.

13. Congenital Heart Disease
o Congenital heart disease (CHD) is a heart-
related problem that is present at birth.
o There are many different types of congenital
heart defects that vary in severity.

14. Congenital Heart Disease
• The defects may affect various structures in
the heart, including the valves, the veins
leading to the heart, the arteries leaving the
heart, the connections and interrelationships
among these various parts, and even the
location of the heart within the chest.

15. Ischemic Heart Disease
• Ischemia or ischemic heart disease (IHD), or
myocardial ischemia, is a disease characterized by
reduced blood supply to the heart muscle,
usually due to coronary artery disease
(atherosclerosis of the coronary arteries).
• Its risk increases with age, smoking,
hypercholesterolaemia (high cholesterol levels),
diabetes, hypertension (high blood pressure).

16. Hypertension
• Blood pressure is defined as the pressure
which pushes or forces the blood across the
blood vessels when the heart is pumping.
• Blood pressure is said to be normal if the
systolic blood pressure is 120mm Hg and
diastolic blood pressure is 80mm Hg, i.e
120/80mm Hg.

17. Hypertension, also referred to as high blood
pressure, HTN or HPN, is a medical condition
in which the blood pressure is chronically
elevated.
In current usage, the word "hypertension"
without a qualifier normally refers to systemic,
arterial hypertension.

18. • Hypertension can be classified as either essential
(primary) or secondary.
• Essential hypertension indicates that no specific
medical cause can be found to explain a patient's
condition.

19. • About 95% of hypertension is essential
hypertension.
• Secondary hypertension indicates that the
high blood pressure is a result of (i.e.,
secondary to) another condition, such as
kidney disease or tumors (adrenal adenoma or
pheochromocytoma).

20. Introduction
Hypertension
Systolic Blood
Pressure (SBP)
Diastolic Blood
Pressure (DBP)
> 120 mmHg > 80 mmHg
****************************************************

21. Types of
Hypertension
Essential
A disorder of unknown
origin affecting the
Blood Pressure
regulating mechanisms
Secondary
Secondary to other
disease processes
****************************************************

22. Environmental
Factors
Stress Na+ Intake Obesity Smoking

23. Risk factors for heart diseases:
Diabetes
High blood pressure
High cholesterol
High-fat diet
Obesity
Personal or family history of heart disease
Smoking

24. Antihypertensive
Drugs

25. Antihypertensive Drugs
Drugs that are used for treating hypertonic
diseases as well as symptomatic hypertensions
are called Antihypertensive drugs.
Hypertension is a syndrome characterized by
elevated arterial blood pressure that depends
on a number of factors.

26. Cardiotonic Agents.
Drugs that increase the contractile power of the
myocardium and thus enhance its capability and
efficacy are called Cardiotonic Agents.
This definition has traditionally referred to a group of
drugs called Cardiac Glycosides (Strophanthin,
Digitoxin, Digoxin).
However, new cardiotonic drugs that exhibit similar
properties have recently been introduced into medical
practice.

27. Cardiac glycosides
• Cardiac glycosides are drugs used in the
treatment of congestive heart failure or cardiac
arrhythmia, by inhibiting the Na+/K+ pump.
• This inhibition increases the amount of Ca2+ ions
available for contraction and improves cardiac
output and reduces distention of the heart.
• Cardiac glycosides are extracted from plant
material.

28. Cardiotonic agents
• Cardiotonic agents are sometimes called positive
inotropic drugs, i.e. substances that enhance the
strength of muscle contractions, and in this case
those that enhance the strength of myocardium
contraction.

29. • Cardiotonic drugs are intended for treating
cardiac insufficiency.
• Cardiac insufficiency is a very common
disease.
• It can be defined as an inability of the heart
to pump a sufficient amount of blood to
supply oxygen and nutrients to organs and
tissue, which leads to fatigue, shortness of
breath, and edema

30. Methyldopa
• Methyldopa,(-)-3-(3,4-dihydroxyphenyl)-2-methylalanine
(22.2.5), is synthesized by a few methods that are only
slightly different.
• Synonyms of this drug are Aldomet, Dopegit, Mopatil, and
Others.
• It is structurally similar to levodopa
and chemically it is a derivative of
phenylethyl amine.

31. Synthesis of Methyldopa
• Dimethoxyphenylacetone, which undergoes a
Strecker–Zelinski reaction using potassium
cyanide and ammonium carbonate, to give 4-
methyl-4-(3,4-dimethoxybenzylhydantoin)
(22.3.3), which is further hydrolyzed in the
presence of barium hydroxide to give (-)-3-(3,4-
dimethoxyphenyl)-2-methylalanine (22.3.4).

32. Synthesis of Methyldopa
• This undergoes acetylation at the amino group, and
the racemic mixture is then separated using (-)-1-
phenylethylamine.
• The isolated isomer is hydrolyzed using hydrobromic
acid, which simultaneously removes the methoxy-
and acetyl groups to give the desired product (-)-3-
(3,4-dihydroxyphenyl)-2-methylalanine (22.3.5)

33. Synthesis of Methyldopa

34. Mechanism of action
 Methyldopa is a prodrug which is converted to
an active metabolite, α-methyl noradrenaline
in the adrenergic neurons.
 This active metabolite of the drug acts centrally
by stimulating α2-adrenergic receptors in the
vasomotor Centre of the medulla there by
reducing noradrenaline release, the net result
being the decrease in blood pressure.

35. Moa
• The drug acts by lowering the total peripheral
resistance and has very little effect on cardiac
output and heart rate.
• A decrease in sympathetic activity may lead to
decrease in renin secretion which in turn may
contribute to its hypotensive effect.

36. Uses
• It is prescribed for arterial hypertension and
hypertensive crises.
• Methyldopa is used in the treatment of
moderate hypertension in combination with
diuretics.