ANTIARRHYTHMIC AGENTS

Drug classifications:
• Class I
• Class II
• Class III
• Class IV

Arrhythmias
⁃ involves changes to the automaticity (breathing) or conductivity
(impulse generation)

Hemodynamics
⁃ study of the forces that move blood throughout the CV system

ANTIARRHYTHMIC AGENTS
⁃ affect the action potential of the cardiac cells by altering their
automaticity, conductivity or both
⁃ Used in emergency cases

Cardiac Action Potential

⁃ brief change in voltage across the cell membrane of heart cells

CLASS I ARRHYTHMICS
⁃ Drugs that block the sodium channels in the cell membrane during an
action potential
⁃ Subclasses
⁃ Class I A antiarrhythmiccs
⁃ Class I B antiarrhyhthmics
⁃ Class I C antiarrhythmics

Therapeutic effects
⁃ stabilize the cell membrane by binding to sodium channels; affects
phase 0

Contraindications
⁃ presence of allergy
⁃ Bradycardia/heart block
⁃ Heart failure
⁃ Hypotension
⁃ Electrolyte imbalances
⁃ Renal & hepatic function
⁃ Pregnancy
⁃ Lactation

Adverse effects
⁃ dizziness
⁃ Light headedness
⁃ Fatigue
⁃ Arrhythmias
⁃ Cardiac arrest
⁃ Nausea
⁃ Vomiting
⁃ Anaphylaxis

CLASS II ANTIARRHYTHMICS
⁃ beta-adrenergic blockers that block beta receptors, causing a
depression on phase 4 of the action potential (acebutolol, esmolol, propanolol)

Therapeutic effects
 ⁃ competitively block beta receptors sites in the heart and kidney
⁃ Relax heart

Contraindications
⁃ Sinus Bradycardia
⁃ AV block
⁃ Cardiogenic shock
⁃ Heart failure
⁃ Asthma
⁃ Respiratory depression
⁃ Pregnancy
⁃ Lactation
⁃ Diabetes

Adverse Effects
⁃ Associated with blocking the Sympathetic Response
⁃ Bradycardia
⁃ Heart failure
⁃ CArdiac Arrhythmia
⁃ Heart blocks
⁃ CVA
⁃ Pulmonary edema
⁃ Gastric Pain
⁃ Flatulence
⁃ Nausea
⁃ Vomiting
⁃ Diarrhea
⁃ Impotence
⁃ Decreased exercise intolerance

CLASS III ARRHYTHMICS

⁃ Blocks potassium channels & slow the outward movement of potassion
during phase 3 of action potential and prolonging it

Contraindications
⁃ Presence of AC block
⁃ shock
⁃ Hypotension
⁃ R. Depression
⁃ Prolonged QT
⁃ Renal & Hepatic disease

Adverse effects
⁃ Malaise
⁃ Fatigue
⁃ Dizziness
⁃ Heart Failure
⁃ Cardiac Arrhythmia
⁃ Cardiac arrest
⁃ Constipation
⁃ Nausea & vomiting
⁃ Hepatoxicity
⁃ Pulmonary toxicity
⁃ Corneal microdeposits
⁃ Vision change

CLASS IV ARRHYTHMICS
⁃ block the movement of calcium ions across cell membrane, depressing the
generation of action potential and delaying phase 1 & 2 phases
Contraindications
⁃ Known allergy
⁃ Heart block
⁃ Pregnancy & lactation
⁃ Heart failure
⁃ Hypotension
⁃ Impaired renal & hepatic function

Adverse effects
⁃ Dizziness
⁃ Light headedness
⁃ Headache
⁃ Asthenia (severe weakness)
⁃ Peripheral edema
⁃ Bradycardia
⁃ AV block
⁃ Flushing
⁃ Nausea
⁃ Hepatic injury

Other antiarryhthmics:
⁃ Adenosine: used to convert supraventricular tachycardia to sinus rhythm
if vagal movements (valsalva maneuver) have been ineffective.
⁃ Digoxin: slows calcium leaving the cell, prolonging the action
potential slowing conduction and HR
⁃ Dronedarone: has properties of all 4 classes of antiarrhythmics

ANTIANGINAL AGENTS
• Nitrates
• Beta-blockers
• Calcium Channel Blockers
• Piperazine Acetamide Agents

Coronary Artery Disease

⁃ involves changes in the coronary vessels that promote atheromas
(tumors; fat deposits), which narrow the coronary arteries and decrease their
elasticity and responsiveness to normal stimuli

Angina Pectoris
⁃ occurs when the narrowed vessels cannot accommodate the myocardial
demand for oxygen
⁃ Anaerobic metabolism — lactic acid — causes chest pain
Types:
• Stable Angina - occurs when heart muscle is perfused adequately except
during exertion or increased demand
• Unstable / Preinfarction Angina - occurs when blood vessels are so
narrow that the myocardial cells are deprived of sufficient Oxygen even at rest
• Prinzmetal Angina - spasm of a coronary vessel that decreases the flow
of blood through the narrowed lumen

Myocardial Infarction
⁃ when a coronary vessel is completely occluded the cells that depend on
that vessel for oxygen to become ischemic, then necrotic, and die

ANTIANGINAL AGENTS
⁃ used to help restore the appropriate supply-and-demand ration in oxygen
delivery to the myocardium when rest is not enough.
 ⁃ works in 2 ways:
⁃ by dilating blood vessels
⁃ Decreasing the work of the heart

Nitrates
⁃ Drugs that act directly on smooth muscle to cause relaxation and to
depress muscle tone.

Therapeutic effects
⁃ Relax & dilate veins, arteries, and capillaries, allowing increased
blood flow through the vessel and lowering systemic BP because of drop in
resistance.
⁃ Increase blood flow to healthy coronary arteries; helping heart
compensate

Contraindications
⁃ Presence of allergy
⁃ Severe anemia
⁃ Head trauma/cerebral hemorrhage
⁃ Pregnancy
⁃ Lactation
⁃ Hepatic & renal disease
⁃ Hypotension
⁃ Hypovolemia
⁃ Limited cardiac output

Adverse effects
⁃ hypotension
⁃ Headache
⁃ Dizziness
⁃ Tachycardia
⁃ Rash
⁃ Flushing nausea
⁃ Vomiting
⁃ Sweating
⁃ Chest pain

Beta-Adrenergic Blockers
⁃ used to block stimulatory effects of the SNS

Therapeutic actions
⁃ competitively block beta-adrenergic receptors & juxtaglomerular
apparatus, decreasing the influence of the SNS on these tissues
⁃ Decrease in the excitability of the heart, a decrease in cardiac
output, decrease in cardiac oxygen consumption, and lowering of blood pressure
⁃ Indicated for long-term management of angina pectoris caused by
atherosclerosis.
⁃ Not indicated for the treatment of Prinzmetal angina because they could
cause vasospasm

Contraindications
⁃ bradycardia
⁃ Heart block
⁃ Cardiogenic shock
⁃ Pregnancy
⁃ Lactation
⁃ Diabetes
 ⁃ PVD (Peripheral Vascular disease)
⁃ Asthma
⁃ COPD
⁃ thyrotoxicosis

Adverse Effects
⁃ Dizziness
⁃ Vertigo
⁃ Heart failure
⁃ Arrhythmias
⁃ Gastric pain
⁃ Flatulence
⁃ Diarrhea
⁃ Vomiting
⁃ Impotence
⁃ Decreases exercise tolerance

Calcium-Channel Blockers
⁃ Inhibit the movement of calcium ions across the membranes of myocardial
and arterial muscle cells

Therapeutic Actions
⁃ Indicated for the treatment of Prinzmetal angina, chronic angina,
effort associated angina and hypertension

Contraindications
⁃ presence of allergy
⁃ Pregnancy
⁃ Lactation
⁃ Heart block
⁃ Renal/hepatic dysfunction
⁃ Heart failure

Adverse Effects
⁃ dizziness
⁃ Light-headedness
⁃ Headache
⁃ Fatigue
⁃ Nausea
⁃ Hepatic injury
⁃ Hypotension
⁃ Bradycardia
⁃ Peripheral edema
⁃ Heart block
⁃ Flushing & rash

Piperazine Acetamide Agent

⁃ Ranolazine
• Newest drug approved for treatment of angina
• Prolongs QT intervals, does not slow heart rate or decrease BP
• Decreases myocardial oxygen demand

LIPID-LOWERING AGENTS
• Bile Acid Sequestrants
• HMG-CoA reductase inhibitors
• Cholesterol Absorption Inhibitor
• Fibrates
• Vitamin B
 • Omega 3 Fatty Acids

Hyperlipidemia
⁃ refers to an increase level of lipids in the blood

Fats
⁃ taken into the body as dietary fats, then broke down in the stomach to
fatty acids, lipids & cholesterol

Bile Acids
⁃ Act like detergents to breakdown or metabolize fats into smaller
molecules

Cholesterol
⁃ A fat that is used to make bile acids
⁃ Serve as base for steroid hormones and cell membrane structure

HMG-CoA Reductase
⁃ An enzyme that controls the early rate-limiting step in the production
of cellular cholesterol

Lipid Lowering Agents

⁃ lower the serum levels of cholesterol and various lipids

Bile Acid Sequestrants

⁃ Used to decrease plasma cholesterol levels

Therapeutic Actions
⁃ bind with bile acids in the intestine to form a insoluble complex that
is then excreted in the feces

Contraindications
⁃ Presence of allergy
⁃ Complete biliary obstruction
⁃ Abnormal intestinal funtion
⁃ Pregnancy
⁃ Lactation

Adverse Effects
⁃ Rash
⁃ Headache
⁃ Anxiety
⁃ Vertigo
⁃ Dizziness
⁃ Constipation
⁃ Exacerbation of hemorrhoids
⁃ Flatulence
⁃ Nausea
⁃ Increased bleeding tendencies
⁃ Vit. A, D and K deficiencies (fat soluble)
⁃ Muscle and joint pains

HMG-CoA Reductase Inhibitors

Therapeutic Actions
⁃ block HMG-CoA reductase from completing the synthesis of cholesterol.
⁃ Inhibits early rate-limiting step in the synthesis of cellular
cholesterol involves the enzyme HMG-CoA
⁃ Serum cholesterol and LDL levels decrease
Contraindications:
⁃ Presence of allergy
⁃ Active liver disease
⁃ Pregnancy
⁃ Lactation
⁃ Impaired endocrine functions

Adverse effects
⁃ Headaches
⁃ Flatulence
⁃ Abdominal pain
⁃ Cramps
⁃ Constipation
⁃ Rhabdomyolysis with acute renal failure

Cholesterol Absorption Inhibitors

⁃ Ezetimibe (Zetia)
• First new class of drugs to lower cholesterol levels
• Works in brush border of the small intestine to decrease the absorption
of dietary cholesterol from the small intestine

Contraindications
⁃ presence of allergy
⁃ Pregnancy
⁃ Lactation
⁃ Severe liver disease

Adverse effects
⁃ headache
⁃ Dizziness
⁃ Abdominal pain
⁃ Diarrhea
⁃ URI
⁃ Back pain
⁃ Myalgia
⁃ Arthralgia

Fibrates
⁃ stimulates the breakdown of lipoproteins from the tissues and their
removal from the plasma
⁃ Lead to decrease in lipoprotein and triglyceride synthesis and
secretion.

Vitamin B
⁃ known as Niacin or Nicotinic acid
⁃ Inhibits the release of free fatty acids from adipose tissue

Omega-3 Fatty Acids

⁃ inhibits the liver enzyme systems to decrease the synthesis of
triglycerides, lowering triglyceride levels