Vascalpha
Vascalpha Uses, Dosage, Side Effects, Food Interaction and all others data.
Vascalpha is a long-acting 1,4-dihydropyridine calcium channel blocker (CCB)b. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, felodipine prevents calcium-dependent myocyte contraction and vasoconstriction. Vascalpha is the most potent CCB in use and is unique in that it exhibits fluorescent activity. In addition to binding to L-type calcium channels, felodipine binds to a number of calcium-binding proteins, exhibits competitive antagonism of the mineralcorticoid receptor, inhibits the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase, and blocks calcium influx through voltage-gated T-type calcium channels. Vascalpha is used to treat mild to moderate essential hypertension.
Vascalpha belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. It was widely accepted that CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction; however, some studies have shown that felodipine also binds to and inhibits T-type calcium channels. T-type calcium channels are most commonly found on neurons, cells with pacemaker activity and on osteocytes. The pharmacologic significance of T-type calcium channel blockade is unknown. Vascalpha also binds to calmodulin and inhibits calmodulin-dependent calcium release from the sarcoplasmic reticulum. The effect of this interaction appears to be minor. Another study demonstrated that felodipine attenuates the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) by binding to the PDE-1B1 and PDE-1A2 enzyme subunits. CaMPDE is one of the key enzymes involved in cyclic nucleotides and calcium second messenger systems. Vascalpha also acts as an antagonist to the mineralcorticoid receptor by competing with aldosterone for binding and blocking aldosterone-induced coactivator recruitment of the mineralcorticoid receptor. Vascalpha is able to bind to skeletal and cardiac muscle isoforms of troponin C, one of the key regulatory proteins in muscle contraction. Though felodipine exhibits binding to many endogenous molecules, its vasodilatory effects are still thought to be brought about primarily through inhibition of voltage-gated L-type calcium channels. Similar to other DHP CCBs, felodipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives felodipine additional arterial selectivity. At therapeutic sub-toxic concentrations, felodipine has little effect on cardiac myocytes and conduction cells.
| Trade Name | Vascalpha |
| Availability | Prescription only |
| Generic | Felodipine |
| Felodipine Other Names | Felodipina, Felodipine, Felodipino, Felodipinum |
| Related Drugs | amlodipine, aspirin, lisinopril, metoprolol, losartan, furosemide, hydrochlorothiazide, atenolol, diltiazem, nitroglycerin |
| Type | Tablet |
| Formula | C18H19Cl2NO4 |
| Weight | Average: 384.254 Monoisotopic: 383.069113515 |
| Protein binding | 99%, primarily to the albumin fraction. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | Accord-UK Ltd |
| Available Country | United Kingdom |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Vascalpha is a calcium channel blocker used to treat hypertension.
For the treatment of mild to moderate essential hypertension.
Vascalpha is also used to associated treatment for these conditions: High Blood Pressure (Hypertension)
How Vascalpha works
Vascalpha decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through voltage-gated L-type calcium channels. It reversibly competes against nitrendipine and other DHP CCBs for DHP binding sites in vascular smooth muscle and cultured rabbit atrial cells. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of felodipine result in an overall decrease in blood pressure. Vascalpha may be used to treat mild to moderate essential hypertension.
Toxicity
Symptoms of overdose include excessive peripheral vasodilation with marked hypotension and possibly bradycardia. Oral rat LD50 is 1050 mg/kg.
Food Interaction
- Avoid grapefruit products.
- Take with or without food. The absorption is unaffected by food.
[Moderate] GENERALLY AVOID: The consumption of grapefruit juice may be associated with significantly increased plasma concentrations of some calcium channel blockers (CCBs) when they are administered orally.
The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.
The interaction has been reported with the dihydropyridine CCBs (in roughly decreasing order of magnitude) felodipine, nisoldipine, nifedipine, and nimodipine, often with a high degree of interindividual variability.
Grapefruit juice caused more than twofold increases in felodipine, nifedipine, and nisoldipine AUCs.
MANAGEMENT: The manufacturers of nifedipine and nisoldipine recommend avoiding grapefruit juice.
Patients treated orally with other calcium channel blockers should be advised to avoid consumption of large amounts of grapefruits and grapefruit juice to prevent any undue fluctuations in serum drug levels.
Increased effects on blood pressure may persist for up to 4 days after the consumption of grapefruit juice.
Monitoring for calcium channel blocker adverse effects (e.g., headache, hypotension, syncope, tachycardia, edema) is recommended.
Vascalpha multivitamins interaction
[Moderate] Calcium-containing products may decrease the effectiveness of calcium channel blockers by saturating calcium channels with calcium.
Calcium chloride has been used to manage acute severe verapamil toxicity.
Management consists of monitoring the effectiveness of calcium channel blocker therapy during coadministration with calcium products.
Vascalpha Drug Interaction
Moderate: aspirin, aspirin, metoprolol, metoprololUnknown: rosuvastatin, rosuvastatin, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, atorvastatin, atorvastatin, acetaminophen, acetaminophen, clopidogrel, clopidogrel, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol
Vascalpha Disease Interaction
Major: cardiogenic shock/hypotension, coronary artery disease, liver diseaseModerate: CHF/AMI
Volume of Distribution
- 10 L/kg
Elimination Route
Is completely absorbed from the gastrointestinal tract; however, extensive first-pass metabolism through the portal circulation results in a low systemic availability of 15%. Bioavailability is unaffected by food.
Half Life
17.5-31.5 hours in hypertensive patients; 19.1-35.9 hours in elderly hypertensive patients; 8.5-19.7 in healthy volunteers.
Clearance
- 0.8 L/min [Young healthy subjects]
Elimination Route
Although higher concentrations of the metabolites are present in the plasma due to decreased urinary excretion, these are inactive. Animal studies have demonstrated that felodipine crosses the blood-brain barrier and the placenta.
Innovators Monograph
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