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Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers)

Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blockers (CCBs) are a class of medications that inhibit voltage-dependent L-type calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channels Channels The Cell: Cell Membrane of cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) and vascular smooth muscle cells. The inhibition of these channels Channels The Cell: Cell Membrane produces vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs and myocardial depression. There are 2 major classes of CCBs: dihydropyridines Dihydropyridines Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. Pulmonary Hypertension Drugs and non- dihydropyridines Dihydropyridines Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. Pulmonary Hypertension Drugs, which differ in their selectivity for cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) or vascular smooth muscle cells. Broadly, these agents are used to treat hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, angina, and tachyarrhythmias. Side effects are from vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs ( headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, peripheral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema, reflex tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children) or a consequence of reduced myocardial contractility and nodal conduction velocity ( bradycardia Bradycardia Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias).

Last updated: 18 May, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blockers (CCBs)

  • Medications that block the L-type calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channels Channels The Cell: Cell Membrane (mostly found in the myocardium Myocardium The muscle tissue of the heart. It is composed of striated, involuntary muscle cells connected to form the contractile pump to generate blood flow. Heart: Anatomy, vascular smooth muscles Smooth muscles Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. Muscle Tissue: Histology, and pancreatic β islet cells)
  • Common uses: hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, angina, and supraventricular dysrhythmias

Pharmacologic classes

  • Dihydropyridine: 
    • Binds more selectively to vascular smooth muscle calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channels Channels The Cell: Cell Membrane (vasodilator)
    • Can lead to reflex tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
    • Example: amlodipine Amlodipine A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. Hypertension Drugs
  • Non-dihydropyridine Non-Dihydropyridine Pulmonary Hypertension Drugs:
    • Affects the heart contractility and conduction and with less effect on vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs
    • Does not lead to reflex tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
    • Benzothiazepine Benzothiazepine Pulmonary Hypertension Drugs:
      • Mainly acts on the myocardium Myocardium The muscle tissue of the heart. It is composed of striated, involuntary muscle cells connected to form the contractile pump to generate blood flow. Heart: Anatomy (myocardial depressant), with some effect on vascular smooth muscles Smooth muscles Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. Muscle Tissue: Histology 
      • Acts as a cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) depressant and a vasodilator
      • Example: diltiazem 
    • Phenylalkylamine Phenylalkylamine Pulmonary Hypertension Drugs:
      • Acts on cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) myocytes Myocytes Mature contractile cells, commonly known as myocytes, that form one of three kinds of muscle. The three types of muscle cells are skeletal, cardiac, and smooth. They are derived from embryonic (precursor) muscle cells called myoblasts. Muscle Tissue: Histology (strong myocardial depressant), with minimal effect on the vascular smooth muscles Smooth muscles Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. Muscle Tissue: Histology
      • Example: verapamil Verapamil A calcium channel blocker that is a class IV anti-arrhythmia agent. Pulmonary Hypertension Drugs

Physiology

  • Cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) muscle contraction involves:
    • Action potential Action Potential Abrupt changes in the membrane potential that sweep along the cell membrane of excitable cells in response to excitation stimuli. Membrane Potential generation produced by the sinoatrial (SA) node 
    • Impulse conduction to the atrial cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) myocytes Myocytes Mature contractile cells, commonly known as myocytes, that form one of three kinds of muscle. The three types of muscle cells are skeletal, cardiac, and smooth. They are derived from embryonic (precursor) muscle cells called myoblasts. Muscle Tissue: Histology → the atrioventricular node Atrioventricular node A small nodular mass of specialized muscle fibers located in the interatrial septum near the opening of the coronary sinus. It gives rise to the atrioventricular bundle of the conduction system of the heart. Heart: Anatomy → ventricular myocytes Myocytes Mature contractile cells, commonly known as myocytes, that form one of three kinds of muscle. The three types of muscle cells are skeletal, cardiac, and smooth. They are derived from embryonic (precursor) muscle cells called myoblasts. Muscle Tissue: Histology
  • Contractile cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) myocyte action potential Action Potential Abrupt changes in the membrane potential that sweep along the cell membrane of excitable cells in response to excitation stimuli. Membrane Potential:
    • Depolarization Depolarization Membrane Potential: Fast-voltage gated sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia channels Channels The Cell: Cell Membrane open, and sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia enters the cell. 
    • Plateau Plateau Cardiac Physiology
      • Sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia channels Channels The Cell: Cell Membrane close; some potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia moves outward.
      • Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes ions enter via the L-type calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channels Channels The Cell: Cell Membrane
      • Release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes from the sarcoplasmic reticulum Sarcoplasmic Reticulum A network of tubules and sacs in the cytoplasm of skeletal muscle fibers that assist with muscle contraction and relaxation by releasing and storing calcium ions. Muscle Tissue: Histology is triggered, facilitating myocyte contraction.
    • Repolarization Repolarization Membrane Potential
      • Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channels Channels The Cell: Cell Membrane close and with increased potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia efflux. 
      • Intracellular calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes decreases and myocytes Myocytes Mature contractile cells, commonly known as myocytes, that form one of three kinds of muscle. The three types of muscle cells are skeletal, cardiac, and smooth. They are derived from embryonic (precursor) muscle cells called myoblasts. Muscle Tissue: Histology relax.
  • Cardiovascular effects of calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes entry to the cells:
    • Myocardial contraction
    • Smooth muscle contraction Smooth muscle contraction Smooth muscle is primarily found in the walls of hollow structures and some visceral organs, including the walls of the vasculature, GI, respiratory, and genitourinary tracts. Smooth muscle contracts more slowly and is regulated differently than skeletal muscle. Smooth muscle can be stimulated by nerve impulses, hormones, metabolic factors (like pH, CO2 or O2 levels), its own intrinsic pacemaker ability, or even mechanical stretch. Smooth Muscle Contraction (vascular smooth muscles Smooth muscles Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. Muscle Tissue: Histology are the most sensitive)
    • SA node impulse generation 
    • Atrioventricular (AV) node conduction
Cardiac myocyte action potential

Cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) myocyte action potential Action Potential Abrupt changes in the membrane potential that sweep along the cell membrane of excitable cells in response to excitation stimuli. Membrane Potential:
1. Sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia channels Channels The Cell: Cell Membrane open, and sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia enters the cell.
2. Sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia channels Channels The Cell: Cell Membrane close; some potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia moves outward. Intracellular calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes increases from entry through L-type calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channels Channels The Cell: Cell Membrane and release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes from the sarcoplasmic reticulum Sarcoplasmic Reticulum A network of tubules and sacs in the cytoplasm of skeletal muscle fibers that assist with muscle contraction and relaxation by releasing and storing calcium ions. Muscle Tissue: Histology.
3. Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channels Channels The Cell: Cell Membrane close and with increased potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia efflux. Cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) myocytes Myocytes Mature contractile cells, commonly known as myocytes, that form one of three kinds of muscle. The three types of muscle cells are skeletal, cardiac, and smooth. They are derived from embryonic (precursor) muscle cells called myoblasts. Muscle Tissue: Histology relax.

Image: “ Action Potential Action Potential Abrupt changes in the membrane potential that sweep along the cell membrane of excitable cells in response to excitation stimuli. Membrane Potential in Cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) Contractile Cells” by Philschatz. License: CC BY 4.0, edited by Lecturio

Pharmacology of CCB

Mechanism of action

  • CCBs bind BIND Hyperbilirubinemia of the Newborn the L-type calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channels Channels The Cell: Cell Membrane in cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) myocytes Myocytes Mature contractile cells, commonly known as myocytes, that form one of three kinds of muscle. The three types of muscle cells are skeletal, cardiac, and smooth. They are derived from embryonic (precursor) muscle cells called myoblasts. Muscle Tissue: Histology, cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) nodal tissues, and vascular smooth muscle cells leading to:
    • Closed L- type channels Channels The Cell: Cell Membrane
    • Decreased calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes entry
Antiarrhythmics mechanism of action

Diagram demonstrating a cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) action potential Action Potential Abrupt changes in the membrane potential that sweep along the cell membrane of excitable cells in response to excitation stimuli. Membrane Potential and the phases of action for different antiarrhythmic drug classes:
The cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation begins with phase 4, the resting potential. Phase 0 is when rapid depolarization Depolarization Membrane Potential happens due to an influx of sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia ions into the cell. Repolarization Repolarization Membrane Potential follows, with an efflux of potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia through fast potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia channels Channels The Cell: Cell Membrane in phase 1 Phase 1 Skin: Structure and Functions, calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes influx in phase 2 Phase 2 Skin: Structure and Functions causing a plateau Plateau Cardiac Physiology (site of action for calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blockers), and an efflux of potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia through delayed potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia channels Channels The Cell: Cell Membrane in phase 3 Phase 3 Skin: Structure and Functions.

Image by Lecturio.

Effects

  • Smooth muscle relaxation (especially vascular muscles) → systemic vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs:
    • Reduction of cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) afterload Afterload Afterload is the resistance in the aorta that prevents blood from leaving the heart. Afterload represents the pressure the LV needs to overcome to eject blood into the aorta. Cardiac Mechanics: ↓ blood pressure (effective in hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
    • Dihydropyridines Dihydropyridines Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. Pulmonary Hypertension Drugs > diltiazem > verapamil Verapamil A calcium channel blocker that is a class IV anti-arrhythmia agent. Pulmonary Hypertension Drugs
  • Reduced myocardial contractility:
  • Decreased atrioventricular node Atrioventricular node A small nodular mass of specialized muscle fibers located in the interatrial septum near the opening of the coronary sinus. It gives rise to the atrioventricular bundle of the conduction system of the heart. Heart: Anatomy conduction velocity:
    • Negative dromotropic effect
    • Slows conduction through AV node (used in supraventricular arrhythmia)
    • Verapamil Verapamil A calcium channel blocker that is a class IV anti-arrhythmia agent. Pulmonary Hypertension Drugs, diltiazem
  • Decreased automaticity (SA node effect):
Cardiovascular effects of calcium channel blockers (ccbs)

Cardiovascular effects of calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blockers
1. Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blockers slow down the sinoatrial node Sinoatrial node The small mass of modified cardiac muscle fibers located at the junction of the superior vena cava and right atrium. Contraction impulses probably start in this node, spread over the atrium (heart atrium) and are then transmitted by the atrioventricular bundle (bundle of His) to the ventricle (heart ventricle). Heart: Anatomy, causing lowered heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology.
2. Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blockers intake leads to vascular smooth muscle relaxation, causing vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs.

Image by Lecturio.

Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption and excretion

Indications

Drug class Examples Indications Key points
Dihydropyridines Dihydropyridines Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. Pulmonary Hypertension Drugs Nifedipine, nicardipine, amlodipine Amlodipine A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. Hypertension Drugs, felodipine, nimodipine Nimodipine Subarachnoid Hemorrhage
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Stable angina Stable angina Persistent and reproducible chest discomfort usually precipitated by a physical exertion that dissipates upon cessation of such an activity. The symptoms are manifestations of myocardial ischemia. Stable and Unstable Angina
  • Vasospastic angina Vasospastic Angina Vasospastic angina, also known as Prinzmetal or variant angina, is an uncommon cause of chest pain due to transient coronary artery spasms. The pathophysiology is distinguished from stable or unstable angina secondary to atherosclerotic coronary artery disease (CAD). Vasospastic Angina/ coronary vasospasm Coronary vasospasm Spasm of the large- or medium-sized coronary arteries. Vasospastic Angina
  • Cerebral vasospasm (especially nimodipine Nimodipine Subarachnoid Hemorrhage prophylaxis Prophylaxis Cephalosporins after subarachnoid hemorrhage Subarachnoid Hemorrhage Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most SAHs originate from a saccular aneurysm in the circle of Willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage)
  • Raynaud’s phenomenon (especially amlodipine Amlodipine A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. Hypertension Drugs)
  • Vasodilators Vasodilators Drugs used to cause dilation of the blood vessels. Thromboangiitis Obliterans (Buerger’s Disease); + risk of reflex tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
  • Amlodipine Amlodipine A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. Hypertension Drugs: long half-life Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Pharmacokinetics and Pharmacodynamics (up to 50 hours); safer and preferred
  • Nifedipine: short half-life Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Pharmacokinetics and Pharmacodynamics (2–5 hours); can be infused
Benzothiazepines Diltiazem
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Stable angina Stable angina Persistent and reproducible chest discomfort usually precipitated by a physical exertion that dissipates upon cessation of such an activity. The symptoms are manifestations of myocardial ischemia. Stable and Unstable Angina
  • Vasospastic angina Vasospastic Angina Vasospastic angina, also known as Prinzmetal or variant angina, is an uncommon cause of chest pain due to transient coronary artery spasms. The pathophysiology is distinguished from stable or unstable angina secondary to atherosclerotic coronary artery disease (CAD). Vasospastic Angina/ coronary vasospasm Coronary vasospasm Spasm of the large- or medium-sized coronary arteries. Vasospastic Angina
  • Supraventricular tachyarrhythmias without accessory pathways ( atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation)
  • Esophageal hyperperistalsis
  • Myocardial depression; blunts the reflex tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children caused by vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs
Phenylalkylamines Verapamil Verapamil A calcium channel blocker that is a class IV anti-arrhythmia agent. Pulmonary Hypertension Drugs
  • Stable angina Stable angina Persistent and reproducible chest discomfort usually precipitated by a physical exertion that dissipates upon cessation of such an activity. The symptoms are manifestations of myocardial ischemia. Stable and Unstable Angina
  • Coronary vasospasm Coronary vasospasm Spasm of the large- or medium-sized coronary arteries. Vasospastic Angina
  • Supraventricular tachyarrhythmias without accessory pathways ( atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation)
  • Cluster headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess prophylaxis Prophylaxis Cephalosporins
  • Migraine Migraine Migraine headache is a primary headache disorder and is among the most prevalent disorders in the world. Migraine is characterized by episodic, moderate to severe headaches that may be associated with increased sensitivity to light and sound, as well as nausea and/or vomiting. Migraine Headache prophylaxis Prophylaxis Cephalosporins

Adverse Effects

  • Dihydropyridines Dihydropyridines Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. Pulmonary Hypertension Drugs:
    • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess (cerebral vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs)
    • Reflex tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children (especially with short-acting nifedipine)
    • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
    • Flushing
    • Peripheral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema (dose-dependent; usually with amlodipine Amlodipine A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. Hypertension Drugs)
    • Gingival hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation
  • Non- dihydropyridines Dihydropyridines Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. Pulmonary Hypertension Drugs:
    • Constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation (dose-dependent)
    • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
    • Bradycardia Bradycardia Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias
    • AV nodal block
    • Worsening of cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) output
    • Gingival hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation

Contraindications

  • Common contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation:
    • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
    • Hypersensitivity to CCBs
    • Acute coronary syndrome:
      • Avoid nifedipine or short-acting dihydropyridines Dihydropyridines Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. Pulmonary Hypertension Drugs.
      • Short-acting dihydropyridines Dihydropyridines Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. Pulmonary Hypertension Drugs cause reflex tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children and worsen myocardial ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage.
  • Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation to non- dihydropyridines Dihydropyridines Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. Pulmonary Hypertension Drugs:
    • Heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) with a reduced ejection fraction Ejection fraction Cardiac Cycle 
    • Sick sinus syndrome Sick Sinus Syndrome Sick sinus syndrome (SSS), also known as sinus node dysfunction, is characterized by degeneration of the sinoatrial (SA) node, the heart’s primary pacemaker. Patients with SSS may be asymptomatic or may present with tachycardia or bradycardia. Sick Sinus Syndrome
    • 2nd and 3rd AV block AV block Atrioventricular (AV) block is a bradyarrhythmia caused by delay, or interruption, in the electrical conduction between the atria and the ventricles. Atrioventricular block occurs due to either anatomic or functional impairment, and is classified into 3 types. Atrioventricular block (AV block)
    • Supraventricular tachyarrhythmias caused by an accessory pathway (i.e., Wolff-Parkinson-White syndrome Wolff-Parkinson-White Syndrome A form of ventricular pre-excitation characterized by a short PR interval and a long QRS interval with a delta wave. In this syndrome, atrial impulses are abnormally conducted to the heart ventricles via an accessory conducting pathway that is located between the wall of the right or left atria and the ventricles, also known as a bundle of kent. The inherited form can be caused by mutation of prkag2 gene encoding a gamma-2 regulatory subunit of amp-activated protein kinase. Supraventricular Tachycardias)
    • Avoid using with β-blockers.
  • Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation to dihydropyridines Dihydropyridines Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. Pulmonary Hypertension Drugs:
    • Moderate to severe aortic stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS)
    • Hypertrophic obstructive cardiomyopathy Cardiomyopathy Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). Cardiomyopathy: Overview and Types

References

  1. Bloch M, Basile J, Bakris G, Elliott W, Forman J. (2020). Major side effects and safety of calcium channel blockers. UpToDate. Retrieved Nov 6, 2020, from https://www.uptodate.com/contents/major-side-effects-and-safety-of-calcium-channel-blockers
  2. Eschenhagen, T. (2017). Treatment of ischemic heart disease. Brunton, L.L., Hilal-Dandan, R., Knollmann, B.C. (Eds.), Goodman & Gilman’s: The Pharmacological Basis of Therapeutics, 13th ed. McGraw-Hill.
  3. Katzung B.G. (2017). Vasodilators & the treatment of angina pectoris. Katzung B.G.(Ed.), Basic & Clinical Pharmacology, 14th ed. McGraw-Hill.
  4. Masom C.P., Tomaszewski C (2020). Calcium channel blockers. Tintinalli J.E., Ma O, Yealy D.M., Meckler G.D., Stapczynski J, Cline D.M., Thomas S.H. (Eds.), Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th ed. McGraw-Hill.
  5. McKeever R, Hamilton R. (2020). Calcium channel blockers. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK482473/
  6. Mohrman D.E., Heller L (Eds.) (2018). Characteristics of cardiac muscle cells in Cardiovascular Physiology, 9th ed. McGraw-Hill.

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