What is the mechanism of action of Clevidipine (Clevidipine is a brand name, its generic name is not specified in the context but it is a dihydropyridine calcium channel blocker)?

Mechanism of Action of Clevidipine

Clevidipine is a dihydropyridine L-type calcium channel blocker that reduces blood pressure by selectively blocking calcium influx into arterial smooth muscle cells, causing arterial vasodilation and decreasing systemic vascular resistance. 1

Pharmacological Properties

• Clevidipine specifically targets L-type calcium channels in vascular smooth muscle, inhibiting the transmembrane influx of calcium ions, which reduces intracellular calcium availability for muscle contraction 1, 2
• As a dihydropyridine calcium channel blocker, clevidipine has high selectivity for vascular L-type calcium channels, producing pronounced vasodilation with minimal effects on cardiac conduction and contractility 3, 2
• Unlike non-dihydropyridine calcium channel blockers (such as verapamil and diltiazem), clevidipine does not significantly affect myocardial contractility, AV conduction, or sinus node function 3, 4
• Clevidipine does not reduce cardiac filling pressure (preload), confirming its lack of effects on venous capacitance vessels 1

Pharmacokinetics and Metabolism

• Clevidipine has an ultra-short onset of action (2-4 minutes) and short duration of effect (5-15 minutes after infusion is stopped) 1, 5
• The drug is rapidly metabolized via hydrolysis by esterases in the blood and extravascular tissues, making its elimination unlikely to be affected by hepatic or renal dysfunction 1
• Clevidipine has an initial phase half-life of approximately 1 minute (accounting for 85-90% of elimination) and a terminal half-life of approximately 15 minutes 1, 5
• It is highly protein-bound (>99.5%) in plasma and has a low volume of distribution 1

Clinical Applications

• Clevidipine is FDA-approved for the reduction of blood pressure when oral therapy is not feasible or desirable 1, 5
• It is particularly useful in the management of acute hypertension in perioperative settings, especially during cardiac surgery 4, 5
• The 2017 ACC/AHA hypertension guideline mentions clevidipine as a safe and effective treatment for acute hypertension in patients undergoing cardiac surgery 4
• Clevidipine is also used in the management of acute severe hypertension and hypertensive emergencies 5, 6

Advantages Over Other Antihypertensive Agents

• Clevidipine's rapid onset and offset of action allow for precise blood pressure control with easy titration 5, 7
• Unlike sodium nitroprusside, clevidipine does not produce toxic metabolites and doesn't require special monitoring 5
• Clevidipine has been shown to be more effective than sodium nitroprusside or nitroglycerin in controlling perioperative blood pressure during cardiac surgery 5, 6
• Its metabolism by blood and tissue esterases rather than hepatic or renal pathways makes it suitable for patients with organ dysfunction 7, 8

Side Effects and Precautions

• The most common side effects include atrial fibrillation, sinus tachycardia, headache, nausea, and vomiting 5, 9
• An increase in heart rate is a normal response to vasodilation and decrease in blood pressure; in some patients, these increases may be pronounced 1
• There is potential for rebound hypertension following discontinuation, particularly in patients not transitioned to other antihypertensive therapies 1, 8
• Clevidipine is formulated in a lipid emulsion, which should be considered in patients with disorders of lipid metabolism 5

Differences from Other Calcium Channel Blockers

• Unlike non-dihydropyridine calcium channel blockers (verapamil, diltiazem), clevidipine does not significantly affect cardiac conduction or contractility 3, 4
• Compared to other dihydropyridines, clevidipine's ultra-short half-life allows for more precise titration and control of blood pressure 5, 7
• While oral dihydropyridines like nifedipine and amlodipine have similar mechanisms of action, clevidipine's intravenous formulation and pharmacokinetic profile make it uniquely suited for acute hypertension management 4