by egpat 28 May 2024
The suffix -lol indicates that carvedilol is a non-selective beta blocker, but this drug also has additional activity. This drug has non-selective beta-blocker activity along with alpha-blocker activity. So carvedilol is both an alpha and beta blocker. Normally, beta blockers have the suffix -olol, but within the name of this drug, we cannot identify the suffix -olol. The letter "-o" is not present; instead, we can see the suffix -dilol. As usual, the suffix -lol indicates this drug is a beta blocker, and the term -di can be remembered as this drug can act on both of the adrenergic receptors. Similarly, within the name, we can identify the prefix car. This car indicates this drug has a carbazole ring system. Therefore, carvedilol is a carbazole ring containing alpha and beta blockers.
Carvedilol can be used in the management of chronic heart failure because it blocks beta-adrenergic receptors, thereby reducing cardiac work and improving symptoms in patients. Similarly, this drug can also be used in patients with left ventricular dysfunction, particularly after acute myocardial infarction. In the post-myocardial infarction, the patients may have left ventricular dysfunction with an ejection fraction less than or equal to 40 percent. In such patients, carvedilol can be given again to reduce the cardiac work as well as to increase the systemic circulation by vasodilation. Finally, this drug can also be used in the management of hypertension because it acts as a vasodilator by blocking alpha receptors.
Carvedilol acts as an antagonist on beta-1 receptors, which are expressed in the cardiac system. Therefore, it can reduce the rate of contraction as well as the force of contraction. This results in a reduction in cardiac work. That's why this drug can be used in the treatment of heart failure as well as left ventricular dysfunction. Similarly, this drug can also act on the alpha-1 receptors, which are expressed in the vascular smooth muscle. By blocking these alpha-1 receptors, it can produce vasodilation; that's why this drug acts as an anti-hypertensive.
Being a non-selective beta blocker, this drug can also act on beta-2 receptors so that it can produce mixed types of sympathetic actions and affect glucose as well as thyroid hormone levels.
On the heart, beta 1 receptors are present, which are G-protein-coupled receptors. When norepinephrine binds to these beta-1 receptors, they are activated, leading to stimulation of the adenylyl cyclase (AC) system. This adenylyl cyclase can convert the ATP into one of the important secondary messengers, cyclic AMP.
Cyclic AMP plays an important role within the cardiac system in producing a contraction. It can activate a group of phosphorylating enzymes called protein kinase A, which are responsible for the release of calcium from the sarcoplasmic reticulum as well as increased calcium permeability. By all of these means, the calcium levels within the heart are going to be increased. Calcium binds to the troponin, and it removes it from the actin and myosin filaments so that these filaments can slide on each other to produce contraction of the cardiac muscle. In this way, norepinephrine can produce the cardiac contraction, resulting in an increased rate as well as the force of contraction of the heart.
Carvedilol is a non-selective beta-blocker with alpha-blocker activity. Because of beta-blocking activity, this drug can now bind to these beta-1 receptors expressed in the heart. By inhibiting these beta-1 receptors, it can inhibit the contraction of the cardiac system so that the rate and force of contraction can be reduced. In this way, carvedilol can reduce cardiac work, thereby reducing angina or any myocardial infarction, and it also improves cardiac efficiency by reducing cardiac oxygen consumption.
Vascular smooth muscle is expressed by alpha-1 adrenergic receptors. These alpha-1 adrenergic receptors are again G-protein-coupled receptors, and norepinephrine can again bind to these alpha-1 receptors. Upon activation, they can stimulate the phospholipase C system (PLC). This phospholipase C is a cleavage enzyme that can convert the phosphatidyl inositol biphosphate into IP3 inositol triphosphate plus DAG diacyl glycerol. Now this diacyl glycerol can activate a few of the phosphorylating enzymes, such as protein kinase C, which are going to increase the permeability of inward-going calcium channels.
Calcium can more easily enter the vascular smooth muscle, and IP 3 can also release the intracellular calcium so that intracellular calcium levels are increased, which produces contraction of the vascular smooth muscle. In this way, norepinephrine can produce vasoconstriction, thereby increasing the blood pressure. Carvedilol can block the alpha 1 receptors so that it can inhibit contraction, resulting in vasodilation. In this way, carvedilol can reduce blood pressure; that's why it is used as an antihypertensive agent.
Carvedilol can act through beta-1 receptors, so it can inhibit sympathetic activity in the heart. As sympathetic activity is reduced, it can reduce the rate of contraction as well as the force of contraction. At a high dose, it can produce a more pronounced effect where the force of contraction is significantly reduced. It results in the worsening of heart failure and reduced capillary permeability, leading to fluid retention.
In such conditions, diuretics such as furosemide can be given in order to reduce the body volume and improve the symptoms. That's why this drug should be carefully used in high doses and should be started at low doses. The dose should be gradually increased.
Similarly, this drug should not be stopped suddenly because it can worsen heart failure as well as precipitate angina because of increased sympathetic activity. Carvedilol can also block beta-2 receptors in the respiratory system. This can reduce the bronchodilation mediated through the beta-2 receptors, leading to bronchospasm.
Carvedilol can induce bradycardia. Therefore, when the pulse rate is reduced by 55, the dose of the drug should be reduced. Carvedilol can block the alpha-1 receptors, resulting in vasodilatation and hypotension. Sometimes, it can produce postural hypotension.
Catecholamines like epinephrine and norepinephrine can control the glucose levels; they can act on the liver such that they can produce hepatic glucose production, so the sympathetic system can increase the glucose levels; similarly, they can also block the insulin release, and when insulin is not released, it can further increase the glucose levels. In this way, catecholamines can increase glucose levels.
Carvedilol can block the actions of catecholamines, thereby producing sudden hypoglycemia in patients. So care should be taken in diabetic patients, where the action of oral hypoglycemic agents is more pronounced with the co-administration of carvedilol. However, it can also produce fluctuations in glucose levels that may result in hyperglycemia.
Carvedilol can increase thyroid hormone levels, resulting in thyrotoxicosis, and it can also increase the risk of pheochromocytoma. This is a condition of adrenal tumor that can produce severe hypertension due to the release of catecholamines. Carvedilol can block alpha-1 receptors, but it can still increase the risk of pheochromocytoma.
This drug mainly produces a few of the side effects such as bradycardia, hypotension, fatigue, syncope, and hyperglycemia, and sometimes it can also produce hypoglycemia, diarrhea, dizziness, headache, asthenia, lack of energy and weight gain.
Carvedilol is available as a tablet as well as a capsule. It is available in different strengths, starting at 3.125 mg, then doubling to 6.25 mg, 12.5 mg, and 25 mg. Doubling of the strengths can be observed in the different types of tablets, and the dose of the drug depends on the type of clinical indication. In cases of heart failure, this drug is started at a low dose of 3.125 mg given twice daily, but in cases of hypertension or left ventricular dysfunction, this drug can be used at an initial dose of 6.25 mg again, given twice daily. In both cases, the dose can be slowly increased such that the maximum dose of 25 mg can be achieved, and the dose adjustment should be done after one to two weeks of the treatment.
Carvedilol, which is a non-selective beta blocker with alpha blocker activity. This drug blocks the beta receptors so that it can reduce the cardiac work, resulting in a decreased rate and force of contraction. That's why bradycardia is one of the important precautions that should be considered with this carvedilol, and it can also block alpha-1 receptors, resulting in vasodilation and hypotension in patients. That's why this drug can be used as an antihypertensive agent along with other drugs such as diuretics.