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Calcium channel blockers (CCBs), also known as calcium channel antagonists, have been approved by the US Food and Drug Administration (FDA) and are widely used to treat various conditions such as hypertension, coronary heart disease, and chronic stable angina. However, despite their widespread use, this class of cardiovascular drugs is one of the primary contributors to drug-related fatalities. CCBs are often classified into 2 major categories—non-dihydropyridines or dihydropyridines. The non-dihydropyridines include verapamil, classified as a phenylalkylamine, and diltiazem, categorized as a benzothiazepine. Cardiovascular indications include hypertension, coronary spasm, angina pectoris, supraventricular dysrhythmias, hypertrophic cardiomyopathy, and pulmonary hypertension. In addition, CCBs can also be used to treat certain off-label indications, such as Raynaud phenomenon, subarachnoid hemorrhage, and migraine headaches. This activity reviews the indications, mechanism of action, adverse event profile, toxicity, dosing, pharmacokinetics, and monitoring of therapy using CCBs essential for the interprofessional healthcare team to recognize and utilize these agents effectively for their intended therapeutic purposes. This activity also helps clinicians distinguish CCBs from other classes of cardiovascular drugs, thereby enhancing their practice within a spectrum of medical settings and patient outcomes. Objectives: Identify appropriate indications for calcium channel blockers in cardiovascular and non-cardiovascular conditions. Implement evidence-based dosing strategies and monitoring protocols for patients prescribed calcium channel blockers. Select appropriate calcium channel blocker formulations and dosages tailored to the patient's clinical condition and comorbidities. Collaborate with the interprofessional healthcare team to optimize the use of calcium channel blockers, coordinate patient care, and ensure their safe and effective use in clinical practice. Access free multiple choice questions on this topic.

Managing CCB Overdose Hypotension and bradycardia are the primary features of CCB poisoning, particularly with diltiazem and verapamil. These findings are due to peripheral vasodilatation and reduced cardiac contractility.[14] Hypotension may be profound and life-threatening and results from peripheral vasodilation, bradycardia, and decreased ionotropy. Cardiac conduction may also cause impairment with AV conduction abnormalities, complete heart block, and idioventricular rhythms. Patients may present asymptomatic initially and progress rapidly to severe hypoperfusion and cardiovascular collapse. Symptoms may include lightheadedness, fatigue, change in mentation, syncope, coma, and sudden death. Non-cardiac symptoms may include nausea and vomiting, metabolic acidosis secondary to hypoperfusion, and hyperglycemia from the blockade of insulin release in the pancreas. The insulin blockade also impairs glucose uptake by myocardial cells, which further contributes to the reduction of cardiac contractility and worsens hypotension. Severe poisoning can lead to pulmonary edema, presumably due to precapillary vasodilation and increased transcapillary pressure. Dihydropyridines in mild-to-moderate overdose may cause reflex tachycardia; however, receptor selectivity may be lost in severe overdose, leading to bradycardia. Many factors may affect the severity of overdose, including the CCB dose, the formulation, ingestion with other cardioactive medications such as β-blockers, the patient's age, and comorbidities. These medications may also be life-threatening, with only 1 tablet in small pediatric patients. Hyperglycemia has been considered a prognostic indicator of the severity of CCB toxicity. Beta-islet cells in the pancreas depend on calcium influx through the L-type calcium channels to release insulin. In the case of CCB overdose, a reduction in the release of insulin and subsequent hyperglycemia ensues.

Many factors may affect the severity of overdose, including the CCB dose, the formulation, ingestion with other cardioactive medications such as β-blockers, the patient's age, and comorbidities. These medications may also be life-threatening, with only 1 tablet in small pediatric patients. Hyperglycemia has been considered a prognostic indicator of the severity of CCB toxicity. Beta-islet cells in the pancreas depend on calcium influx through the L-type calcium channels to release insulin. In the case of CCB overdose, a reduction in the release of insulin and subsequent hyperglycemia ensues. As in any other overdose, it is crucial to maintain a patent airway. Healthcare providers should obtain an ECG and place the patient on continuous monitoring, including pulse oximetry. Healthcare providers should obtain a chest x-ray and conduct basic labs, including acetaminophen and salicylate levels, if necessary. Early initiation of gastrointestinal decontamination is recommended, particularly in cases involving large ingestions or sustained-release formulations, within appropriate settings, such as normal mental status and recent ingestion. Activated charcoal should be administered if the patient presents early and is awake, alert, oriented, and able to protect their airway. Whole bowel irrigation is an important option for patients with massive overdoses or overdoses of sustained or extended-release formulations that do not already cause an ileus. Managing CCB-Induced Hypotension In cases of hypotension, initial treatment with intravenous (IV) fluids requires caution in those with congestive heart failure, pulmonary edema, or kidney disease. IV calcium administration may reverse the decreased cardiac contractility. Calcium chloride 10% (10 mL for 0.1 to 0.2 mL/kg) or calcium gluconate 10% (20 to 30 mL for 0.3 to 0.4 mL/kg) may be administered IV and repeated every 5 to 10 minutes. Caution is necessary with calcium chloride as it may cause dermal necrosis when given through a peripheral line.[2]

In cases of hypotension, initial treatment with intravenous (IV) fluids requires caution in those with congestive heart failure, pulmonary edema, or kidney disease. IV calcium administration may reverse the decreased cardiac contractility. Calcium chloride 10% (10 mL for 0.1 to 0.2 mL/kg) or calcium gluconate 10% (20 to 30 mL for 0.3 to 0.4 mL/kg) may be administered IV and repeated every 5 to 10 minutes. Caution is necessary with calcium chloride as it may cause dermal necrosis when given through a peripheral line.[2] Atropine is a reasonable initial treatment option, but it typically does not reverse the effects of CCB poisoning. Glucagon may be administered as a bolus of 5 to 10 mg IV, with close monitoring for nausea and vomiting; patients may receive antiemetics as a pre-medication to mitigate these adverse effects. In cases where patients are refractory to these interventions, healthcare providers should consider initiating vasopressor therapy using IV norepinephrine or push-dose phenylephrine while simultaneously preparing hyperinsulinemia/euglycemia (HIE) therapy. HIE increases cardiac contractility through enhanced glucose transport into myocardial cells, thereby correcting hypo-insulinemia. A bolus of insulin of 1 unit/kg should be administered, followed by an infusion of 1 to 10 units/kg/h.[19][20] The patient's glucose levels should be monitored for hypoglycemia initially every 10 minutes and then every 30 to 60 minutes to maintain glucose levels between 100 and 200 mg/dL. To sustain these levels, healthcare providers should utilize a concurrent dextrose infusion as needed.

Atropine is a reasonable initial treatment option, but it typically does not reverse the effects of CCB poisoning. Glucagon may be administered as a bolus of 5 to 10 mg IV, with close monitoring for nausea and vomiting; patients may receive antiemetics as a pre-medication to mitigate these adverse effects. In cases where patients are refractory to these interventions, healthcare providers should consider initiating vasopressor therapy using IV norepinephrine or push-dose phenylephrine while simultaneously preparing hyperinsulinemia/euglycemia (HIE) therapy. HIE increases cardiac contractility through enhanced glucose transport into myocardial cells, thereby correcting hypo-insulinemia. A bolus of insulin of 1 unit/kg should be administered, followed by an infusion of 1 to 10 units/kg/h.[19][20] The patient's glucose levels should be monitored for hypoglycemia initially every 10 minutes and then every 30 to 60 minutes to maintain glucose levels between 100 and 200 mg/dL. To sustain these levels, healthcare providers should utilize a concurrent dextrose infusion as needed. If the initial glucose is less than 200 mg/dL, a bolus dose of glucose should be administered to patients, and their glucose and potassium levels should be closely monitored. IV lipid emulsion therapy lacks clear evidence for efficacy but may be considered if all other interventions fail. A bolus of IV lipid emulsion 20% at a dose of 1.5 mL/kg should be administered, repeated if necessary, followed by an infusion of 0.25 to 0.5 mL/kg/min for 1 hour. Reports suggest that methylene blue, particularly in amlodipine overdose patients, may be effective in managing vasodilatory shock.[21] Phosphodiesterase inhibitors represent another option in CCB therapy; they increase cardiac output by inhibiting the breakdown of cAMP. In cases refractory to the aforementioned interventions, extracorporeal membrane oxygenation has succeeded as it sustains perfusion to vital organs and continues hepatic metabolism.

Healthcare providers responsible for prescribing, administering, or dispensing CCBs should thoroughly understand their indications, interactions, and potential adverse effects. Patients receiving CCBs are at risk of experiencing hypotension and bradycardia, which could pose life-threatening risks and necessitate immediate attention. Close monitoring of patients throughout their treatment course is imperative. Any symptomatic patients manifesting hypotension or bradycardia should be promptly transported to the emergency department. Medication administration should be suspended for asymptomatic patients, and consideration should be given to dosage adjustments or alternative medications. Nurses in intensive care settings should be proficient in managing hypotension and bradycardia. Due to the adverse event profile and the numerous interactions associated with CCBs, optimal therapeutic outcomes and prevention of adverse events necessitate the involvement of an interprofessional healthcare team. This team comprises physicians, advanced practice practitioners, nursing staff, and pharmacists collaborating to coordinate actions, maintain open communication, and uphold meticulous record-keeping. They strive to achieve the best patient outcomes with CCB therapy by working together.