Pathways

Verapamil is a cardioselective non-dihydropyridine calcium channel blocker that is typically administered orally or intravenously in a clinical setting to reduce angina (chest pain), lower hypertension (high blood pressure), and treat certain types of arrhythmias (also known as dysrhythmias: abnormal heartbeats). As a Class IV antiarrhythmic agent, it elongates the phase 3 (plateau) period of a cardiac action potential. Humans have at least five different types of calcium channels: L-, N-, P/Q-, R-, and T-type; verapamil targets the Cav1.2 portion of the alpha-1 subunit of L-type voltage-dependent calcium channels. As a phenylalkylamine, verapamil is thought to enter the pore subunit of the channel from the cytoplasmic side to block the channel intracellularly. Verapamil binds to these channels in a voltage- and frequency-dependent manner. These channels are highly expressed in vascular smooth muscle and myocardial tissue. Blocking L-type calcium channels decreases conduction and increases the refractory period, slowing conduction through the AV node to alter electrical activity mediating the heart rate such that there is an increase in the PR interval duration. Verapamil’s effects on pacemaker cells enable its use as a rate-controlling agent in atrial fibrillation. Verapamil decreases cardiac myocyte contractility by inhibiting the influx of calcium ions. Calcium ions entering the cell through L-type calcium 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 cardiac myocytes and results in an overall decreased force of contraction by the heart. Thus, there is a reduction in inotropy, chronotropy, and heart rate, making verapamil effective for supraventricular dysrhythmia (e.g. atrial fibrillation). Verapamil affects smooth muscle contraction and subsequent vasoconstriction in peripheral arterioles and coronary arteries by the same mechanism. Decreased cardiac contractility and vasodilation lower blood pressure as inhibition of calcium influx prevents the contraction of vascular smooth muscle, causing relaxation/dilation of blood vessels throughout the peripheral circulation, which lowers systemic vascular resistance (i.e. afterload) and thus blood pressure. This reduction in vascular resistance also reduces the force against which the heart must push, decreasing myocardial energy consumption and oxygen requirements and thus alleviating angina. The pain of angina is caused by a deficit in oxygen supply to the heart. Calcium channel blockers like verapamil dilate blood vessels, which increases the supply of blood and oxygen to the heart, reducing angina. Due to potential interactions of verapamil with other calcium channels, potassium channels, and adrenergic receptors, it is used off-label for cluster headaches.

Verteporfin is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Verteporfin passes through the liver and is then excreted from the body mainly through the kidney.

Very long-chain acyl-CoA dehydrogenase deficiency (VLCAD), also called ACADL and VLCAD, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder, which is caused by a defective very long-chain specific acyl-CoA dehydrogenase. Very long-chain specific acyl-CoA dehydrogenase breakdown certain fats to energy. This disorder is characterized by a large accumulation of fatty acids such as L-Palmitoylcarnitine in the mitochondria. Symptoms of the disorder include muscle weakness, lethargy (lack of energy) and hypoglycemia (low blood sugar). Treatment with diet modifications such as consuming supplemental calories is suggested. It is estimated that very long-chain acyl-CoA dehydrogenase deficiency affects 1 in 40,000 to 120,000 individuals.

Very long-chain acyl-CoA dehydrogenase deficiency (VLCAD), also called ACADL and VLCAD, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder, which is caused by a defective very long-chain specific acyl-CoA dehydrogenase. Very long-chain specific acyl-CoA dehydrogenase breakdown certain fats to energy. This disorder is characterized by a large accumulation of fatty acids such as L-Palmitoylcarnitine in the mitochondria. Symptoms of the disorder include muscle weakness, lethargy (lack of energy) and hypoglycemia (low blood sugar). Treatment with diet modifications such as consuming supplemental calories is suggested. It is estimated that very long-chain acyl-CoA dehydrogenase deficiency affects 1 in 40,000 to 120,000 individuals.

Very long-chain acyl-CoA dehydrogenase deficiency (VLCAD), also called ACADL and VLCAD, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder, which is caused by a defective very long-chain specific acyl-CoA dehydrogenase. Very long-chain specific acyl-CoA dehydrogenase breakdown certain fats to energy. This disorder is characterized by a large accumulation of fatty acids such as L-Palmitoylcarnitine in the mitochondria. Symptoms of the disorder include muscle weakness, lethargy (lack of energy) and hypoglycemia (low blood sugar). Treatment with diet modifications such as consuming supplemental calories is suggested. It is estimated that very long-chain acyl-CoA dehydrogenase deficiency affects 1 in 40,000 to 120,000 individuals.

Very long-chain acyl-CoA dehydrogenase deficiency (VLCAD), also called ACADL and VLCAD, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder, which is caused by a defective very long-chain specific acyl-CoA dehydrogenase. Very long-chain specific acyl-CoA dehydrogenase breakdown certain fats to energy. This disorder is characterized by a large accumulation of fatty acids such as L-Palmitoylcarnitine in the mitochondria. Symptoms of the disorder include muscle weakness, lethargy (lack of energy) and hypoglycemia (low blood sugar). Treatment with diet modifications such as consuming supplemental calories is suggested. It is estimated that very long-chain acyl-CoA dehydrogenase deficiency affects 1 in 40,000 to 120,000 individuals.