Pharmacology of Ischemic Heart Disease

Part 2: Drugs for Angina

Heart, Lung, and Kidney
Uzoma Ikonne PhD
IkonneUS@evms.edu
757-446-7448
Learning Points
1.Discuss Angina Pectoris: Stable angina (exertional angina), unstable angina, variant angina
2.Describe the therapeutic use, mechanism of action, adverse effects and contraindications of :
Nitrates: Nitroglycerin, Isosorbide mononitrate/ dinitrate
Voltage-gated Ca2+ channel blockers: Verapamil, Diltiazem, Nifedipine, Amlodipine
β-Blockers : Propranolol, Metoprolol, Atenolol
Ranolazine
3. Discuss treatment of Angina
Ischemic Heart Disease and Angina Pectoris
 Pathophysiology of Angina syndromes

Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy, 3e

David E. Golan, Armen H. Tashjian, Jr.;Ehrin J. Armstrong, April W. Armstrong
Angina Pectoris : Pharmacologic Therapies
Organic Nitrates
Organic Nitrates

Nitrates MOA:
Activates soluble guanylyl
cyclase (sGC)

Agents:
Nitroglycerin
Isosorbide mononitrate/
dinitrate

Note: soluble guanylate

cyclase alternate name for
soluble guanylyl cyclase
Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy, 3e
David E. Golan, Armen H. Tashjian, Jr.;Ehrin J. Armstrong, April W. Armstrong
Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy, 3e
David E. Golan, Armen H. Tashjian, Jr.;Ehrin J. Armstrong, April W. Armstrong
Organic Nitrates
• Therapeutic Uses
• Stable Angina
• Exertional Angina (treat/prevent)
• Variant Angina
• Unstable Angina

• Pharmacokinetics
• Route of Administration: sublingual (preferred), oral (low bioavailability), transdermal
• Rapid onset and offset
• Isosorbide mononitrate is an active metabolite of isosorbide dinitrate (long-acting)
Organic Nitrates
• Adverse Effects
• Orthostatic hypotension
• Tachycardia
• Throbbing headache

• Tolerance
• Tolerance
• Nitrate-free intervals to attenuate tolerance

• Contraindications
• Intracranial pressure is elevated
• PDE-5 inhibitors
Ca2+ Channel Blockers
Calcium Channel Blockers MOA:
decrease influx of Ca2+ from
L-type calcium channels that :

• leads to a reduction in
contractility

• dilation vascular smooth muscle

Agents:
Verapamil
Diltiazem
Nifedipine
Amlodipine

Dihydropyridines Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy, 3e

David E. Golan, Armen H. Tashjian, Jr.;Ehrin J. Armstrong, April W. Armstrong
Pharmacodynamics
 Dihydropyridines
more effects at
vascular smooth
muscle

Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy, 3e

David E. Golan, Armen H. Tashjian, Jr.;Ehrin J. Armstrong, April W. Armstrong
 Drug stem alert:
“-dipine”
identifies a vasodilating
calcium channel blocker
14
Ca2+ Channel Blockers (CCBs)
Therapeutic Uses
• Stable Angina
• Variant Angina (prophylactic)
• Unstable Angina

Pharmacokinetics
• Route of administration: oral
verapamil & diltiazem (IV)
• Extensive metabolism

Adverse Effects
• Headache, dizziness, flushing, light-headedness
• Constipation (common w/ verapamil)
• Peripheral Edema
• Cardiac Depression (CD)
• Cardiac arrest, bradycardia, atrioventricular (AV) block, heart failure

Contraindications
• Heart Failure
β-Blockers
Agents
• Propranolol
• Metoprolol
• Atenolol

Mechanism of Action:
Block sympathetic activation

*cornerstone of medical treatment

regimens for Stable Angina
β-Blockers in Angina

*Beta receptor activation leads to

increased current through L-type Ca2+
channels

*van der Heyden, Marcel AG, Tessa JM Wijnhoven, and Tobias Opthof. "Molecular aspects of
Pathophysiology of Heart Disease, 5e adrenergic modulation of cardiac L-type Ca2+ channels."Cardiovascular research 65.1 (2005): 28-
Leonard S. Lilly 39.
FYI
Receptor Location Result from Stimulation Result from Blockade
Increased HR Decreased HR
Increased Contractility Decreased Contractility
β1 Heart Increased Nerve Conduction Slow conduction

Lung Bronchodilation Bronchoconstriction

Uterus Relaxation ----
β2
Arterial Smooth Muscle Vasodilation Vasoconstriction

β3 Bladder Relaxation ---

 
Therapeutic Uses of Beta-Blockers: Migraine, Hypertension, Angina, Heart Failure,
Hyperthyroidism, Arrhythmias, Glaucoma (topical use)
 
β-Blockers in Angina
• Therapeutic Uses
• Stable Angina (cornerstone)
• Frequently co-administered with Nitrates or CCB
• Unstable Angina

• Pharmacokinetic
• Route of administration: Low bioavailability

• Adverse Effects
• Fatigue
• Impotence
• Lethargy
• Insomnia

• Contraindications
• Asthma and other vasospastic conditions
• Severe Bradycardia
 Ranolazine

Mechanism of Action:

Antianginal action unknown

Therapeutic level inhibitor slow

inward Na+ channel

diastolic tension
contractility

Vadnais, D. S., & Wenger, N. K. (2009). Management options in chronic stable angina pectoris: focus on ranolazine. Clinical
Medicine. Therapeutics, 1, CMT-S2214.
Ranolazine
• Therapeutic Use
• Chronic angina
• Alternative or combined with β-blocker
• Antiarrhythmic

• Pharmacokinetics
• Oral

• Adverse Effects
• dizziness
• Nausea

• Precautions
• CAD patients prolong QT interval
 Treatment of Angina

Vasospastic Angina:
Ca+ Channel Blockers
Nitrates

Braun, M. M., Stevens, W. A., & Barstow, C. H. (2018). Stable Coronary Artery Disease: Treatment. American family
physician, 97(6).
 Treatment of Angina

Braun, M. M., Stevens, W. A., & Barstow, C. H. (2018). Stable Coronary Artery Disease: Treatment. American family
physician, 97(6).
References