Drugs for Ischemic Heart Disease class notes

Drugs for Ischemic Heart Disease

Ischemic Heart Disease

• Group of disease processes characterized by insufficient perfusion/ oxygenation to myocardium.

• Includes:

  • Angina Pectoris

  • Myocardial Infarction

  • Heart Failure with Preserved EF

Pharmacological Agents

• Beta Blockers

• Nitrates

• Calcium Channel Blockers

Beta Blockers

• Designed by Nobel Prize winner Sir James Black.

• Counteract adverse effects of adrenergic stimulation.

• Decrease myocardial oxygen demand and reduce angina symptoms.

Beta Adrenergic Receptors

• Beta 1:

  • Located on cardiac sarcolemma

  • Adenylyl Cyclase System (AC) activated

  • AC produces cyclic adenosine monophosphate cAMP

  • Opens calcium channels

  • Promotes calcium uptake

  • Positive Inotropic, Chronotropic, and Dromotropic effects

• Beta 2:

  • Located in bronchial and vascular smooth muscle

• Beta 3:

  • Located in endothelial tissue

Action of Beta Blockers

• Blocks beta adrenergic receptors

• Negative Inotropic (lowers contractility)

• Negative Chronotropic (lowers rate)

• Lowers myocardial oxygen consumption

Mechanism of Action

• Prevents epinephrine and norepinephrine from binding to receptors.

• Inhibition of SA node/ AV node

• Shortens myosin and actin interaction

• Switches myocardial metabolism from fatty acids to glucose.

Pharmokinetic Properties

• Plasma half life: Amount of time for 50% of drug concentration to disappear from plasma

• Protein Binding: Extent at which drug binds to plasma proteins, especially albumin and alpha-1-acid glycoprotein (only unbound medication is active).

• First pass hepatic metabolism: Substance enters portal vein from GI system, liver removes substance effectively stopping distribution.

Selectivity

• Cardio Non-Cardio-Selective: Affects the heart and respiratory system

• Cardio-Selective: Targets cardiac beta 1 receptors

Vasodilatory Selectivity

• Vasodilatory-Non-Selective: Works on heart and dilates blood vessels

• Vasodilatory Selective: Selective for Beta 1 receptors and vasodilates through different pathway

Metabolism and Interactions

• Hydrophilic:

  • Excreted by kidneys

  • Carteolol

  • Nadolol

  • Atenolol

• Lipophilic:

  • Metabolized by liver

  • More prone to interactions

  • Metoprolol (Lopressor)

  • Carvedilol (Coreg)

  • Labetolol

  • Propranolol

Clinical Indications

• Angina Pectoris

• Acute Coronary Syndromes

• Early STEMI

• CVA

• Vascular Surgery

Angina Pectoris

• Classic effort angina tends to be reversable

• Inadequate coronary vasodilation

• Increased myocardial oxygen demand

• Any beta blocker will work in the absence of other diseases

Acute Coronary Syndromes

• Management based on risk stratification

• Anti-thrombolytic therapy

• In hospital quadruple therapy includes beta blockers, statins, ACE inhibitors and antiplatelet therapies

Acute ST Elevation MI

• Useful for ongoing chest pain, tachycardia, hypertension, ventricular arrhythmias

• In USA only Metoprolol and Atenolol are available as IV therapies for acute MI

CVA

• B_1 selective agents shown to reduce stroke

• Non-selective Propranolol modestly useful

Vascular Surgery

• Protective effect

• Death from cardiac causes and MI reduced

• Not helpful for low cardiac risk patients

Cardiac Contraindications

• Severe Bradycardia

• High Degree Heart Block

• Cardiogenic Shock

• Untreated LV Failure

Pulmonary Contraindications

• Severe Asthma or Bronchospasm

• Mild Asthma or Bronchospasm

Organic Nitrates

• 1st line agents for angina

• Reduce myocardial oxygen demand

• Vasodilator

• Increases cyclic guanosine monophosphate

Examples

• Glyceryl Trinitrate

• Isosorbide Dinitrate

Clinical Actions

• Reduces preload due to vasodilation and decreased venous return

• Reduces afterload due to vasodilation

• Improves coronary perfusion (more direct effect)

• Reduced renal and visceral perfusion

Absorption

• Administered sublingually due to high first pass metabolism.

• Short half life

• Too much use can create tolerance

Indications

• Angina

• MI and Acute Coronary Syndromes

• Esophageal Spasm

Contraindications

• Viagra

• Cialis

• Hypotension

• Hypovolemia

• Constrictive Pericarditis

Side Effects

• Headache

• Hypotension

• Tachycardia

• Facial Flushing

Calcium Channel Blockers

• Calcium sustains contraction

• Increases interaction of myosin and actin

• Calcium channel blockers inhibit movement of calcium ions into cells

Mechanism

• Bind to L-type calcium channels

• L-type calcium channels are found on cardiomyocyte surfaces and blood vessels

Types

• Dihydropyridines:

  • Affect blood vessels

  • Used to control blood pressure

  • Relaxes smooth muscle

  • Widends vessel

• Non-Dihydropyridines:

  • Affect the heart

  • Reduce contractility

  • Slow heart rate

  • Reduce conduction rate

Indications/ Contraindications

• Indications:

  • Angina

  • High Blood Pressure

• Contraindications:

  • Heart Failure

  • Hypotension

  • Heart Block

  • Sick Sinus Syndrome

  • Drug Interactions

Adverse Reactions

• Fatigue/ Dizziness

• Heart Failure

• Edema