Chapter 4

Drugs acting on cardiovascular system

By KedirD

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 Outline
At the completion of this chapter, you will be able to:
• Describe cardiovascular system and its function
• Identify common cardiovascular diseases and drugs used to treat the
diseases
• Discuss the common side effects and contraindications of drugs used treat

various cardiovascular diseases

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 Cardiovascular System and Its
Functions
• The cardiovascular system, also known as the circulatory system, consists of
the heart, blood vessels (arteries, veins, and capillaries), and blood. Its
primary functions include:
1.Transportation: The system transports oxygen, nutrients, hormones, and waste
products throughout the body.

2.Regulation: It helps regulate body temperature, pH levels, and fluid balance.

3.Protection: The cardiovascular system plays a role in immune responses and clotting
mechanisms to prevent blood loss.
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 Common Cardiovascular
Diseases
1.Coronary Artery Disease (CAD): Narrowing or blockage of coronary arteries, often due
to atherosclerosis.

2.Heart Failure: The heart's inability to pump blood effectively, leading to fluid buildup and
other complications.

3.Hypertension: Chronic high blood pressure that can lead to heart disease and stroke.

4.Arrhythmias: Irregular heartbeats that can affect blood flow.

5.Myocardial Infarction (Heart Attack): Occurs when blood flow to the heart is blocked,
causing damage to heart muscle.
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 Drugs Used to Treat
Cardiovascular Diseases
1.Antihypertensives: Used to lower blood pressure (e.g., ACE inhibitors, beta-blockers,
calcium channel blockers).

2.Antiplatelet Agents: Reduce blood clotting (e.g., aspirin, clopidogrel).

3.Statins: Lower cholesterol levels (e.g., atorvastatin, simvastatin).

4.Diuretics: Help reduce fluid buildup in heart failure (e.g., furosemide,

hydrochlorothiazide).

5.Beta-Blockers: Decrease heart rate and workload (e.g., metoprolol, carvedilol).

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 Common Side Effects and Contraindications
• Side Effects

1.Antihypertensives: Dizziness, fatigue, and hypotension.

2.Antiplatelet Agents: Increased risk of bleeding and gastrointestinal upset.

3.Statins: Muscle pain, liver enzyme abnormalities, and digestive issues.

4.Diuretics: Dehydration, electrolyte imbalances, and increased urination.

5.Beta-Blockers: Fatigue, depression, and bradycardia (slow heart rate).

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 Contraindications
1.Antihypertensives: Caution in patients with renal
impairment or hypotension.
2.Antiplatelet Agents: Contraindicated in individuals with
active bleeding disorders.
3.Statins: Not recommended for patients with active liver
disease or pregnancy.
4.Diuretics: Caution in patients with renal failure or
electrolyte imbalances.
5.Beta-Blockers: Contraindicated in patients with severe
asthma or certain heart block types.

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 3.3. Anti-Hypertensive drugs

What is Hypertension?
• Hypertension is defined as systolic BP above 140 mm Hg or diastolic BP above 90 mm Hg.

• Classification of hypertension

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3.3. Anti-Hypertensive drugs……
There are 2 general types of Hypertension:
Essential Hypertension
There is an absence of identifiable secondary cause.
This accounts for ~95% of all cases of hypertension.
Also referred to as primary or idiopathic hypertension.
 It is a heterogeneous disorder with numerous risk factors including sedentary lifestyle,
obesity, insulin resistance (metabolic syndrome), salt/sodium sensitivity, alcohol intake,

age, family history.

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 3.3. Anti-Hypertensive drugs……

Secondary Hypertension

Where hypertension can be attributed to an identifiable cause (e.g. aldosteronism,

hyperthyroidism, glucocorticoid excess, renovascular disease, renal failure,
pheochromocytoma)

Treatment is targeted to the underlying cause

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Why should we treat hypertension?

Sustained arterial hypertension damages blood vessels in kidney, heart and brain and leads to

an increased incidence of renal failure, cardiac failure, and stroke.

Effective pharmacologic lowering of blood pressure prevents the damage to blood vessels and

reduces the morbidity and mortality rate.

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Treatment of hypertension

Two therapeutic Interventions

Non-pharmacologic
Pharmacologic
a. Non- pharmacological therapy of hypertension
  Low sodium chloride diet
 Weight reduction
 Exercise
 Cessation of smoking
 Decrease in excessive consumption of alcohol
 Avoid stress

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 Treatment of hypertension ….
b. Pharmacological therapy of hypertension
 Currently available drugs lower blood pressure by decreasing either cardiac output (CO) or total peripheral
vascular resistance (PVR) or both
 Anti-hypertensive drugs are classified according to the principal regulatory site or mechanism on which
they act into:
Beta adrenergic blockers: eg. Atenolol, propranolol, metoprolol, labetalol
Alpha blockers: eg. prazosin
Centrally acting anti-hypertensive eg. Methyldopa
Diuretics
Direct vasodilators
Angiotensin converting enzyme inhibitors
Angiotensin II receptor blockers
Calcium channel blockers

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 1.Diuretics

Diuretics are medications that promote the excretion of urine and increase the

elimination of sodium (salt) and other electrolytes from the body.

 They play a critical role in managing conditions like hypertension (high blood

pressure), heart failure, and edema (fluid retention).

 By acting primarily on the kidneys, diuretics help regulate blood pressure and

fluid balance.
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 Mechanism of Action

1. Location of Action: Diuretics exert their effects at specific sites within the nephron, the
functional unit of the kidney.

The main types include:

1. Loop Diuretics: Act on the loop of Henle (e.g., furosemide).

2. Thiazide Diuretics: Act on the distal convoluted tubule (e.g., hydrochlorothiazide).

3. Potassium-Sparing Diuretics: Act on the collecting ducts (e.g., spironolactone).

2. Increase in Urinary Excretion:

1. Water and Electrolytes: Diuretics increase the elimination of water, sodium (Na+), potassium (K+), chloride
(Cl-), and bicarbonate (HCO3−).

2. Blood Volume Reduction: By promoting the excretion of these substances, diuretics reduce blood volume,
leading to a decrease in cardiac output and ultimately lowering blood pressure.
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 Types of Diuretics
1.Loop Diuretics:
1. Examples: Furosemide, bumetanide.

2. Use: Effective for rapid diuresis and often used in heart failure and acute edema.

2.Thiazide Diuretics:
1. Examples: Hydrochlorothiazide, chlorthalidone.

2. Use: Commonly prescribed for hypertension and mild heart failure.

3.Potassium-Sparing Diuretics:
1. Examples: Spironolactone, eplerenone.

2. Use: Help prevent potassium loss, often used in combination with other diuretics.
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Diuretics …..
Effects on Blood Pressure

• Diuretics help lower blood pressure by:

• Decreasing blood volume through increased urine output.

• Reducing the workload on the heart.

• Promoting vasodilation (widening of blood vessels) in some cases.

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 2.Direct Vasodilators

1.Hydralazine
Mechanism of Action: Dilates arterioles but not veins, leading to reduced
peripheral vascular resistance.
Indications: Used primarily for severe hypertension.
Common Adverse Effects:
Headache
Nausea
Anorexia
Palpitations
Sweating
Flushing

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 2.Direct Vasodilators…..

2.Sodium Nitroprusside
Mechanism of Action: A potent vasodilator that dilates both arterial and venous
vessels, reducing peripheral vascular resistance and venous return.
Indications: Used in hypertensive emergencies; administered via intravenous infusion.

Serious Toxicities:
• Metabolic acidosis

• Arrhythmias

• Excessive hypotension

• Risk of death
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 2.Direct Vasodilators…..

3.Angiotensin-Converting Enzyme (ACE) Inhibitors

Examples: Captopril, Enalapril

Mechanism of Action: Lower blood pressure primarily by decreasing peripheral vascular

resistance.

Common Adverse Effects:

• Chronic cough

• Angioedema

• First-dose hypotension

• Hyperkalemia

Contraindications:
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 2.Direct Vasodilators…..

4.Angiotensin II Receptor Blockers (ARBs)

Examples: Losartan, Candesartan, Irbesartan

Mechanism of Action: Block the binding of angiotensin II, inhibiting its

effects on blood vessels and reducing ventricular and arterial hypertrophy.
Benefits: Produce less dry cough compared to ACE inhibitors since they do
not increase bradykinin levels.
Indications: First-line therapy for hypertension, especially effective for
patients with diabetes and coronary artery disease who cannot tolerate ACE
inhibitors.
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 2.Direct Vasodilators…..

5.Calcium Channel Blockers

Examples: Nifedipine, Amlodipine, Verapamil

Mechanism of Action: Relax blood vessels, leading to lower blood pressure.

Common Adverse Effects: Ankle swelling

Serious Toxic Effects:

Cardiac arrest

Bradycardia

Atrioventricular block

Congestive heart failure

Contraindications: Should not be used in patients with heart failure or significant heart block.
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 2.Direct Vasodilators…..
6.Beta-Blockers(“A-MEN BP”)
Mechanism of Action: Reduce heart rate and myocardial workload, thereby lowering

blood pressure.
Indications: Reduce the risk of vascular events.

Contraindications: Not suitable for patients with obstructive pulmonary disease.

Adverse Effects:

Fatigue

Cold extremities

May exacerbate heart failure, heart block, or claudication in predisposed individuals.

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 3.4. Drugs for Heart Failure (HF)

Heart failure (HF) is a syndrome characterized by the heart's inability to

pump adequate blood to meet the metabolic demands of tissues.
 It is a serious condition with a high mortality rate, conventionally estimated
at about 50% over five years.
Common presenting symptoms include:
Weakness

Dyspnea (shortness of breath)

Orthopnea (difficulty breathing while lying down)

Body swelling (edema)

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 3.4 Drug Classes Used for Heart
Failure
1.Diuretics (: Furosemide, Hydrochlorothiazide, Spironolactone)
 Furosemide is the drug of choice for patients with severe heart failure.

 Help reduce fluid overload and alleviate symptoms of edema and dyspnea.

2.Cardiac Glycosides: Digoxin

Mechanism: Increases myocardial contractility, thereby improving cardiac output.

3.Beta-Adrenergic Stimulants: Dopamine, Dobutamine

Used for acute heart failure management to enhance cardiac output.

4.Angiotensin-Converting Enzyme (ACE) Inhibitors: Captopril, Enalapril

Mechanism: Decrease peripheral vascular resistance, reducing the workload on the heart.
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 Drug Classes Used for Heart
Failure…..
6.Digoxin
Mechanism of Action
• Increases myocardial contractile force, enhancing cardiac output.
• Risks and Considerations
• Dangerous Drug: Digoxin can cause severe dysrhythmias, especially
at doses close to the therapeutic range.
• Common Adverse Effects
• Gastrointestinal: Anorexia, nausea, vomiting
• Neurological: Confusion
• Cardiac: Dysrhythmia

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3.5. Anti-anginal drugs
Definition: Angina pectoris is characterized by sudden, severe, pressing chest
pain that may radiate to the neck, jaw, back, and arms.
Cause: It occurs when the oxygen supply to the heart is insufficient to meet its
oxygen demand.
Factors that Affect Oxygen Supply and Demand:
Reduced Oxygen Supply:
• Thrombus (blood clot)
• Vasospasm (sudden constriction of a blood vessel)
Increased Oxygen Demand:
• Elevated heart rate: The heart pumps more frequently, consuming more oxygen.
• Increased contractility of the heart muscle: Stronger heart contractions require more
oxygen.

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 3.5. Anti-anginal drugs…
Treatment:

Angina can be managed with medications that either:

Increase oxygen supply to the heart

Decrease oxygen demand of the heart

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 3.5. Anti-anginal drugs…..

There are three primary families of antianginal agents:

1. Organic Nitrates: Nitroglycerin, Isosorbide dinitrate

• Usage: Most frequently used antianginal drugs.

• Mechanism: Cause vasodilation, thereby increasing oxygen supply to the heart.

Adverse Effects:
Headache

Postural hypotension

Facial flushing

Reflex tachycardia
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 3.5. Anti-anginal drugs…..

2. Beta Blockers: Propranolol, Atenolol

Mechanism: Decrease the oxygen demands of the myocardium by:
Lowering heart rate
Reducing the force of contraction

3. Calcium Channel Blockers: Verapamil, Nifedipine

Mechanism:

• Cause relaxation of the coronary arteries, increasing oxygen supply.

• Verapamil: Also produces modest reductions in oxygen demand by
suppressing heart rate and contractility.
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3.6 Drugs for cardiac arrhythmia

The heart's electrical system normally maintains a regular and organized rhythm,
represented on an electrocardiogram (EKG).
An arrhythmia is an abnormal heart rhythm that can disrupt the heart's ability to
pump effectively.
Common types of arrhythmias include:
Tachycardia (rapid heartbeat)

Bradycardia (slow heartbeat)

Flutter (rapid, organized contractions)

Fibrillation (rapid, chaotic contractions)

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 3.6 Drugs for cardiac arrhythmia ….

(
Antiarrhythmic Drugs "No Bad Knowledge, Please!“)

Antiarrhythmic drugs are used to prevent or correct cardiac arrhythmias and are
traditionally classified into the following categories:
Class I: Sodium Channel Blockers: Quinidine, Lidocaine, Phenytoin

Class II: Beta Adrenergic Blockers: Propranolol, Atenolol

Class III: Potassium Channel Blockers: Amiodarone, Bretylium

Class IV: Calcium Channel Blockers: Verapamil

Others:

Digitalis: e.g., Digoxin

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Atropine
 3.7. Anti-hyperlipidemia

Anti-hyperlipidemic are used to lower high cholesterol levels, which can lead to blood vessel
blockage and increase the risk of coronary heart disease (CHD).
 Cholesterol is an essential lipid present in the body, and it is measured as:
Total Cholesterol: The sum of all cholesterol types in the blood, including LDL, HDL, and other lipids.
High levels can indicate an increased risk of heart disease.
LDL (Low-Density Lipoprotein): Known as "bad" cholesterol, high LDL levels can lead to plaque
buildup in arteries, increasing the risk of atherosclerosis, heart attacks, and strokes.
HDL (High-Density Lipoprotein): Referred to as "good" cholesterol, HDL transports cholesterol back
to the liver for removal. Higher HDL levels are associated with a lower risk of heart disease.
Triglycerides: Another type of fat in the blood, elevated triglyceride levels can also raise cardiovascular
disease risk.
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 3.7. Anti-hyperlipidemia…
Statins("Loving Some Awesome People Really“)
Statins are a class of drugs primarily used to lower LDL cholesterol levels.
Mechanism:
• Potent competitive inhibitors of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A
reductase (HMG CoA reductase), which is the rate-limiting enzyme in cholesterol
biosynthesis.
• Effectiveness:
• Statins are the most effective drugs for lowering LDL cholesterol.
• They also cause small increases in HDL cholesterol.
• Examples:
• Lovastatin
• Simvastatin
• Atorvastatin
• Pravastatin
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Rosuvastatin 35
Adverse Effects:
• Muscle pain
• Rash
• Headache
• Hepatotoxicity

Contraindications:
• Statins are contraindicated in pregnant and lactating women.
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 Thank you

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