Cardiovascular Pharmacology: Calcium Channel Blockers, Antianginals, and Management of Myocardial Infarction

Comprehensive practice flashcards defining key vocabulary, drug classes, specific agents, and pathophysiological concepts from lectures on calcium channel blockers, organic nitrates, newer antianginals, and myocardial infarction management.

Sarcolemma

The plasma membrane of a muscle cell that undergoes depolarization during an action potential, opening voltage-gated ion channels to facilitate ion entry and exit.

Sarcoplasmic Reticulum

The intracellular storage organelle that releases large amounts of stored $\text{Ca}^{2+}$ into the cytoplasm during excitation, enabling actin and myosin filaments to slide and produce muscle contraction.

L-type Calcium Channel

The most important, voltage-regulated calcium channel found on the sarcolemma of cardiac and smooth muscle; it is relatively slow and facilitates sustained inward flow of $\text{Ca}^{2+}$.

L-Type Calcium Channel Blockade

The process by which an antagonist binds to the channel receptor, altering its conformation, closing the channel pore, preventing calcium influx, and triggering muscle relaxation.

T-type Calcium Channel

A calcium channel type localized in vascular smooth muscle, the SA node, and other tissues; selectively blocked by the anticonvulsant medication ethosuximide (Zarontin).

N-type Calcium Channel

A calcium channel distributed throughout the nervous system that regulates neurotransmitter release at synapses and transmits pain signals in the spinal cord; selectively blocked by ziconotide.

Negative Inotropic Effect

A reduction in the force of myocardial contraction, causing the heart to beat with less mechanical force.

Positive Inotropic Effect

An enhancement of myocardial contractility, resulting in the heart beating with increased force.

Negative Chronotropic Effect

A reduction in heart rate resulting from decreased automaticity and fewer action potentials fired by the sinoatrial (SA) node.

Positive Chronotropic Effect

An elevation in heart rate mediated by autonomic or pharmacologic stimulation.

Dihydropyridines

A chemical subclass of calcium channel blockers that bind reversibly to closed-type calcium channels, acting selectively on arterial vascular smooth muscle to reduce systemic vascular resistance (SVR) without affecting inotropy, chronotropy, or dromotropy.

Non-Dihydropyridines

A subclass of calcium channel blockers that bind to open-type L-type channels on distinct subunits, acting on both vascular smooth muscle and the myocardium to decrease systemic vascular resistance, contractility, sinus node rate, and AV node conduction velocity.

Calcium Channel Blocker Classification Comparison

Dihydropyridines decrease systemic vascular resistance (SVR) with no effect on contractility, sinus rate, or AV node velocity; non-dihydropyridines decrease SVR, contractility (inotropy), sinus rate (chronotropy), and AV nodal conduction velocity (dromotropy).

Amlodipine (Norvasc)

A dihydropyridine calcium channel blocker featuring the longest elimination half-life and once-daily dosing; indicated for hypertension, chronic stable angina, and Prinzmetal's variant angina.

Clevidipine (Cleviprex)

An injectable emulsion dihydropyridine calcium channel blocker that produces rapid blood pressure reduction within minutes.

Felodipine (Plendil)

A dihydropyridine calcium channel blocker utilized for hypertension that demonstrates greater vascular smooth muscle selectivity.

Isradipine

The most potent dihydropyridine calcium channel blocker, indicated for hypertension either alone or in combination with a thiazide diuretic.

Verapamil (Calan, Isoptin, Verelan)

A phenylalkylamine non-dihydropyridine calcium channel blocker and Class IV antidysrhythmic that inhibits calcium influx into cardiac and vascular smooth muscle; contraindicated in AV heart block and sick sinus syndrome.

Diltiazem (Cardizem, Dilacor, Taztia XT, Tiazac)

A non-dihydropyridine calcium channel blocker indicated for atrial dysrhythmias, hypertension, chronic stable angina, vasospastic angina, and off-label migraine prophylaxis.

Sick Sinus Syndrome

A cardiac condition where the sinoatrial (SA) node is damaged and fails to discharge normal electrical impulses, representing a strict contraindication for non-dihydropyridine CCBs.

Myocardial Ischemia

A state in which the myocardium receives an insufficient supply of oxygen to meet its metabolic demands, resulting from an imbalance between coronary oxygen supply and myocardial oxygen demand.

Myocardial Oxygen Supply

The volume of oxygen delivered to cardiac myocytes via coronary arterial blood flow, primarily determined by hemodynamic factors (most critically blood pressure), blood volume, and oxygen-carrying capacity.

Myocardial Oxygen Demand

The amount of oxygen consumed by the heart, which increases proportionally with cardiac workload factors including heart rate, inotropic contractility, and ventricular wall tension.

Atherosclerosis

A progressive disease of the arteries characterized by the subendothelial accumulation of lipid-rich atheromas and fibrous plaques, impairing arterial elasticity and narrowing vessel lumens.

Arteriosclerosis

A pathological vascular condition defined by structural thickening and hardening of the inner and central tunica walls of an artery.

Atherosclerosis vs. Arteriosclerosis

Atherosclerosis involves the formation of focal lipid plaques (atheromas) that occlude luminal flow, whereas arteriosclerosis denotes diffuse wall thickening of the inner and central arterial layers.

Angina Pectoris

Acute chest pain caused by transient myocardial ischemia, classically characterized by a crushing anterior substernal sensation radiating down the left arm and left scapula (or predominantly to the jaw in females).

Stable Angina

Predictable anginal discomfort of consistent frequency, intensity, and duration, characteristically provoked by physical exertion or emotional stress and relieved promptly by rest.

Vasospastic (Prinzmetal's) Angina

A form of chest pain caused by dynamic spasms of coronary arterial smooth muscle, which may occur either with or without underlying atherosclerotic lesions.

Silent Angina

Asymptomatic myocardial ischemia occurring in the complete absence of chest pain, associated with a elevated risk of acute myocardial infarction and sudden death.

Unstable Angina

A cardiovascular emergency characterized by sudden-onset, unexpected myocardial ischemic pain that occurs unpredictably or at rest.

Mechanisms of Antianginal Drugs

Beta-adrenergic antagonists lower heart rate and contractility to reduce cardiac output and workload; CCBs dilate arterial smooth muscle and reduce afterload; organic nitrates dilate veins to reduce preload and dilate coronary arteries.

Organic Nitrates

Antianginal agents (e.g., nitroglycerin, isosorbide dinitrate, isosorbide mononitrate) that generate nitric oxide in vascular smooth muscle, dilating systemic veins (reducing preload), dilating arterioles, and widening coronary arteries.

Nitric Oxide

An endogenous gaseous cell-signaling molecule and potent vasodilator formed in vascular smooth muscle that triggers an intracellular cascade releasing calcium ions to relax arterial and venous muscle.

Beta-Adrenergic Blockers

First-line prophylactic drugs for chronic stable angina (e.g., atenolol, metoprolol, propranolol, timolol) that selectively block cardiac $\beta_1$-receptors to reduce heart rate, contractility, blood pressure, and myocardial oxygen demand.

Partial Fatty-Acid Oxidation Inhibitors

Metabolic antianginal drugs that reduce the intracellular influx of sodium and calcium ions into ischemic myocardium, thereby lowering cellular metabolic rate and myocardial oxygen demand.

Myocardial Infarction (MI)

Complete cessation of blood flow to a portion of the myocardium following rupture of an atherosclerotic plaque and occlusive coronary thrombus formation, resulting in ischemic myocardial cell necrosis.

Thrombolytics

Clot-dissolving medications (such as alteplase) indicated for early acute MI; effective if given within $20\text{ minutes}$ to $12\text{ hours}$ (optimally within $30\text{ minutes}$), but offering zero clinical benefit after $24\text{ hours}$.

Cardiac Remodeling

A pathological progression of molecular, cellular, and structural alterations that alter the size, mass, geometry, and mechanical performance of the injured ventricles, contributing to heart failure and fatal arrhythmias.

Cardiopulmonary Arrest

The complete cessation of cardiac pumping and respiratory ventilation, most frequently precipitated by a lethal dysrhythmia or pulseless ventricular tachycardia.

Epinephrine

The primary sympathomimetic vasopressor administered during cardiopulmonary resuscitation to elevate systemic blood pressure and restore coronary and cerebral perfusion.

Sarcolemma

The muscle plasma membrane containing voltage-gated channels that open in response to action potential depolarization, allowing ions to enter and leave the muscle cell.

L-type Calcium Channel

The most important, voltage-regulated calcium channel found on the sarcolemma of cardiac and smooth muscle; it is relatively slow and facilitates a sustained flow of calcium into the cell.

T-type Calcium Channel

A type of calcium channel present in vascular smooth muscle, the SA node, and other tissues; ethosuximide (Zarontin) is the only medication that acts by blocking these channels.

N-type Calcium Channel

A calcium channel found throughout the nervous system that regulates neurotransmitter release at synapses and is involved in spinal cord pain transmission; selectively blocked by ziconotide.

Negative Inotropic Effect

A drug effect or physiological action that reduces the force of myocardial contraction.

Positive Inotropic Effect

A physiological or pharmacological action that causes the heart to beat with greater muscular force.

Negative Chronotropic Effect

An effect that decreases heart rate, resulting from the SA node generating fewer action potentials and slowing automaticity.

Positive Chronotropic Effect

An autonomic or drug-induced effect that increases heart rate.

Dihydropyridines

A class of calcium channel blockers (including amlodipine, felodipine, nifedipine, and nicardipine) that reversibly bind to closed-type calcium channels, primarily inducing arterial smooth muscle vasodilation to reduce systemic vascular resistance without directly altering contractility or SA/AV node rate.

Non-dihydropyridines

A class of calcium channel blockers (diltiazem and verapamil) that bind to open-type L-type calcium channels on both vascular smooth muscle and the myocardium, decreasing contractility, slowing sinus node firing, and slowing AV node conduction velocity.

Clevidipine (Cleviprex)

A dihydropyridine calcium channel blocker administered as an injectable emulsion to lower blood pressure within minutes.

Isradipine

The most potent dihydropyridine calcium channel blocker, indicated for hypertension either as monotherapy or in combination with a thiazide diuretic.

Amlodipine (Norvasc)

A dihydropyridine calcium channel blocker indicated for hypertension, chronic stable angina, and Prinzmetal's variant angina, distinguished by having the longest half-life and once-daily dosing.

Myocardial Ischemia

A condition in which the heart receives an insufficient supply of oxygen to meet its cellular metabolic demands, caused by an imbalance between myocardial oxygen supply and demand.

Atherosclerosis

A disease of the arteries characterized by progressive deposition of plaques composed of fatty, fibrous material (atheromas) along inner vessel walls, impairing elasticity and reducing blood supply.

Arteriosclerosis

A vascular condition defined specifically by the thickening of the inner and central walls of an artery.

Angina Pectoris

Acute chest pain resulting from myocardial ischemia, classically characterized by a steady increase in pain, a crushing sensation in the anterior chest, emotional distress, and radiation to the left arm and scapula (or predominantly to the jaw in females).

Stable Angina

A form of angina pectoris that is predictable in frequency, intensity, and duration, and is consistently relieved by rest.

Vasospastic (Prinzmetal's) Angina

Angina caused by spasms of coronary artery smooth muscle, which may occur with or without the presence of atherosclerotic plaque.

Silent Angina

Myocardial ischemia that occurs without chest pain or symptoms, placing the patient at high risk for acute myocardial infarction and sudden death.

Unstable Angina

A sudden medical emergency where anginal chest pain occurs at rest.

Organic Nitrates

Antianginal agents that form nitric oxide in vascular smooth muscle, causing relaxation of arterial and venous vessels (reducing preload and afterload) to alleviate or prevent anginal attacks.

Partial Fatty-Acid Oxidation Inhibitors

Antianginal drugs that reduce the flow of sodium and calcium ions into the myocardium, decreasing the metabolic rate and oxygen demands of myocardial cells.

Alteplase (Activase)

A thrombolytic agent used in early acute myocardial infarction to dissolve active blood clots and restore perfusion; most effective within $30\,\text{minutes}$ of presentation and carries no benefit after $24\,\text{hours}$.

Cardiac Remodeling

A group of molecular, cellular, and interstitial changes that alter the size, mass, geometry, and function of the heart after injury, leading to poor prognosis due to ventricular dysfunction and malignant arrhythmias.

Cardiopulmonary Arrest

The complete cessation of cardiac and respiratory activity, typically caused by a dysrhythmia or pulseless ventricular tachycardia.