Cardiovascular System - Drugs for Angina, MI, and CVA

What is atherosclerosis?

Presence of plaque within arterial walls, leading to narrowing of arteries (causing increased peripheral resistance) and reducing vascular elasticity (ability to vasoconstrict + vasodilate).

Can lead to deprivation of oxygen and nutrients to vital organs -> angina, MI, cerebrovascular accident

What causes atherosclerosis?

Endothelial injury and inflammation of blood vessel wall (from hypertension) leads to accumulation of immune cells, leading to increased vascular permeability.

This leads to LDL leaking into the bv intima, resulting in oxidization of LDL by macrophages, resulting in formation of foam cells.

The body attempts to wall off the oxidized LDL + foam cells, resulting in stiff vessels + unstable plaque -> angina

Rupturing of plaque results in formation of clots -> leading to MI, cerebrovascular accident

What is angina?

Characterized by steady, intense chest pains arising from inadequate oxygen supply compared to oxygen demand of the myocardium (due to atherosclerosis)

Results in symptoms of panic, pallor, dyspnea, diaphoresis, tachycardia, and elevated BP due to the stress response

Onset typically from increased physical exertion or emotional excitement

What is stable angina?

Angina with predictable frequency, duration and intensity, and improves with rest + administration of nitroglycerin

Usually does not constitute a medical emergency

What is the immediate treatment strategy for stable angina?

1. Encourage patient to rest to reduce stress response

2. Administration of nitroglycerin (nitrates), terminates angina attack via dilation of veins, resulting in decreased cardiac workload

What is unstable angina?

Angina with variable intensity, increased frequency, and occurs during periods of rest. Associated with increased risk of MI due to atherosclerotic plaque causing fissures, creating clots that narrows bvs

Constitutes a medical emergency

What are overall pharmacological management strategies for treatment of angina?

Termination of angina attack

Reduce intensity and frequency of attacks

Mainly through decreasing oxygen demand of the myocardium (also via increasing oxygen supply to the myocardium - less impact on damaged bvs)

Mechanism of actions include

Slow HR and reduce contractility -> decrease demand

Venous vasodilation, decrease preload -> decrease demand

Arteriolar vasodilation, decrease afterload -> decrease demand, increase supply

What are non-pharmacological preventative measures for angina?

-Abstain from alcohol, limit to 2 drinks per day

-Eliminate foods high in cholesterol, saturated fats, and sodium

-Control hyperlipidemia

-Control hypertension

-Regular exercise and maintain optimal weight

-Control blood glucose levels

-Abstain from tobacco products

Can prevent CAD and slow progression of atherosclerosis

What three drug classes are prescribed for treatment of angina?

1. Nitrates

Terminate attack

Venous and arterial vasodilation

2. B adrenergic antagonists

Prevent attack

Reduce HR and contractility

3. Calcium channel blockers

Prevent attack

Arteriolar vasodilation and reduce HR

What are nitrates? (Use, Mechanism of Action, Route of Administration, Adverse Effects, Cautions, Drug-Drug Interactions)

Use

Used to terminate an angina attack

Mechanism of Action

Primary Action - Venous vasodilation, decreases amount of blood returning to heart and cardiac workload (decreased demand)

Secondary Action - Arterial vasodilation, increases blood flow back to myocardium, improving oxygen supply of myocardium, limited effect on non healthy coronary arteries

Route of Administration

Fast-acting -> terminate attack, sublingual route

Rest - take drug - wait 5 min - repeat X3

Long-acting -> prevention of attack, oral + transdermal route, no longer used due to lots of adverse effects from drug tolerance

Adverse Effects

Related to hypotension

-Reflex Tachycardia (can make angina worse)

-Dizziness

-Throbbing headache

Caution

Primarily for hypotension

-Hx of hypotension

-Hypovolemia

-Pre-existing conditions that limit cardiac output

Drug Interactions

-Synergistic with alcohol, increases vasodilation

-Synergistic with phosphodiesterase-5 inhibitors for erectile dysfunction, increases vasodilation

Can result in life-threatening hypotension

What is the use of nitrates?

Used to terminate an angina attack by decreasing cardiac workload through venous vasodilation, lowering preload

What is the mechanism of action of nitrates?

Primary Action - Venous vasodilation, decreases amount of blood returning to heart and cardiac workload (decreased demand)

Secondary Action - Arterial vasodilation, increases blood flow back to myocardium, improving oxygen supply of myocardium, limited effect on non healthy coronary arteries

What is the route of administration of nitrates?

Route of Administration

Fast-acting -> terminate attack, sublingual route

Rest - take drug - wait 5 min - repeat X3

Long-acting -> prevention of attack, oral + transdermal route, no longer used due to lots of adverse effects from drug tolerance

What are adverse effects of nitrates?

Related to hypotension

-Reflex Tachycardia (can make angina worse)

-Dizziness

-Throbbing headache

What are cautions of the use of nitrates?

Primarily for patients predisposed to hypotension

-Hx of hypotension

-Hypovolemia

-Pre-existing conditions that limit cardiac output

What are drug interactions of nitrates?

Primarily with other substances/drugs that increase vasodilation -> greater risk of life-threatening hypotension

-Synergistic with alcohol, increases vasodilation

-Synergistic with phosphodiesterase-5 inhibitors for erectile dysfunction, increases vasodilation

What are B-adrenergic antagonists for angina? (Use, Mechanism of Action, Caution, Adverse Effects)

Use

Used as primary prevention for stable angina - reducing frequency and intensity

Ideally used in pts with hypertension and CAD as it reduces risk of MI

Mechanism of Action

Slows HR and reduces contractility of the heart, resulting in reduced cardiac workload and decreased oxygen demand

Caution

Asthma (effect on B2 receptors)

COPD (effect on B2 receptors)

^Use B1 selective antagonists^

Depression

Diabetes (inhibition of SNS makes it harder to detect symptoms of hypoglycemia)

Adverse Effects

Associated with inhibition of SNS

Fatigue

Weakness

Bradycardia

Hypotension

Sleep disturbances

Rapid withdrawal with quick termination (reduce dose over 1-2 weeks)

What is the use of B-adrenergic antagonists for angina?

Used as primary prevention for stable angina - reducing frequency and intensity

Ideally used in pts with hypertension and CAD as it reduces risk of MI

What is the mechanism of action of B-adrenergic antagonists for angina?

Slows HR and reduces contractility of the heart, resulting in reduced cardiac workload and decreased oxygen demand

What are cautions for the use of B-adrenergic antagonists for angina?

Asthma (effect on B2 receptors)

COPD (effect on B2 receptors)

^Use B1 selective antagonists^

Depression

Diabetes (inhibition of SNS makes it harder to detect symptoms of hypoglycemia)

What are adverse effects of B-adrenergic antagonists for angina?

Associated with inhibition of SNS

Fatigue

Weakness

Bradycardia

Hypotension

Sleep disturbances

Rapid withdrawal with quick termination (reduce dose over 1-2 weeks)

What are calcium channel blockers for angina? (Use, Mechanism of Action, Adverse Effects, Drug Interactions)

Use

Used for primary prevention of stable angina for patients who can not tolerate beta-blockers

Mechanism of action

Causes vasodilation of arterioles, resulting in lower afterload and decreased cardiac workload as well as increased myocardial oxygen supply

Causes decreased heart rate (px of non-selective CCBs)

Adverse Effects

Associated with hypotension

-Dizziness

-Lightheadedness

-Fatigue

-Bradycardia

-Flushing

-Nausea

-Reflex Tachycardia

Drug Interactions

Metabolized by CYP3A4 enzymes, impacted by grapefruit juice

What is the use of calcium channel blockers for angina?

Used for primary prevention of stable angina for patients who can not tolerate beta-blockers

What is the mechanism of action of calcium channel blockers for angina?

Causes vasodilation of arterioles, resulting in lower afterload and decreased cardiac workload as well as increased myocardial oxygen supply

Causes decreased heart rate (px of non-selective CCBs)

What are adverse effects of calcium channel blockers for angina?

Associated with hypotension

-Dizziness

-Lightheadedness

-Fatigue

-Bradycardia

-Flushing

-Nausea

-Reflex Tachycardia

What is a myocardial infarction?

Caused by complete occlusion of coronary artery from atherosclerosis rupture, leading to death of myocytes - which release enzyme markers (can confirm MI vs unstable angina)

What are overall pharmacological management strategies for treatment of MI?

1. Restore blood supply

2. Reduce oxygen demand

3. Prevent MI-associated dysrhythmias

4. Reduce post-MI mortality

5. Manage severe pain associated with MI

What drug classes are prescribed to restore blood supply for MI?

Thrombolytics - administer within 12 hours of onset, ideally within 30 minutes (to destroy clots causing MI)

What drug classes are prescribed to reduce myocardial oxygen demand for MI?

Nitrates -> Venous + Arterial vasodilation - Decreased preload + afterload

Beta-blockers -> Slowed HR and contractility - Decreased workload

ACE inhibitors -> Lower bp

What drug classes are prescribed to prevent MI-associated dysrhythmias for MI?

Beta-blockers -> slow impulse conduction

What drug classes are prescribed to reduce post-MI mortality?

Aspirin -> COX 1 + COX 2 enzyme inhibition

Beta-Blockers -> Reduce HR and contractility - Decreased workload

ACE inhibitors -> Lower bp

Statins -> Lower cholesterol

What drug classes are prescribed to manage severe pain for MI?

Opioids -> moderate-severe pain management

What is a stroke?

Two types

Thrombotic stroke -> associated with atherosclerotic plaque and clot formation

Hemorrhagic stroke -> associated with hypertension

Signs and symptoms dependent on brain area affected - common signs include facial drooping, paralysis+numbness, slurred speech, vision changes, andsevere headache

What drugs + treatment are prescribed for prevention of strokes?

1. Lifestyle management

2. Antihypertensive drugs (thrombotic + hemorrhagic stroke)

3. Anticoagulant therapy (thrombotic stroke)

4. Antiplatelet therapy (thrombotic stroke)

What drugs + treatment are prescribed for treatment of strokes?

Thrombolytics -> thrombotic stroke, administration within 3 hours can completely restore brain function