From the Guidelines
The mechanism of propranolol in treating infantile hemangioma is not fully understood, but proposed mechanisms include vasoconstriction, inhibition of angiogenesis, downregulation of matrix metalloproteinases and interleukin-6, regulation of the renin–angiotensin system, and inhibition of nitric oxide production. When considering the treatment of infantile hemangioma, it is crucial to understand the mechanism of action of propranolol, a nonselective blocker of β-adrenergic receptors. According to a study published in Pediatrics in 2015 1, the exact mechanism of propranolol is still not fully understood. However, several proposed mechanisms have been identified, including:
- Vasoconstriction
- Inhibition of angiogenesis
- Downregulation of matrix metalloproteinases and interleukin-6
- Regulation of the renin–angiotensin system
- Inhibition of nitric oxide production These mechanisms contribute to the effectiveness of propranolol in treating infantile hemangioma, as demonstrated in a large 2015 randomized controlled trial of Hemangeol, an oral formulation of propranolol, which showed effectiveness when dosed at 3.4 mg/kg per day for 6 months 1.
From the FDA Drug Label
Mechanism of Action: Nitroglycerin forms free radical nitric oxide (NO) which activates guanylate cyclase, resulting in an increase of guanosine 3'5' monophosphate (cyclic GMP) in smooth muscle and other tissues. These events lead to dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle, and result in vasodilatation The mechanism of action of nitroglycerin is through the formation of free radical nitric oxide (NO), which activates guanylate cyclase, leading to an increase in cyclic GMP and resulting in vasodilatation 2.
- The key steps in this mechanism are:
- Formation of nitric oxide (NO)
- Activation of guanylate cyclase
- Increase in cyclic GMP
- Dephosphorylation of myosin light chains
- Resulting vasodilatation
From the Research
Mechanism of Nitroglycerin
- Nitroglycerin is converted to nitric oxide, a potent vasodilator, in the body, leading to venodilation at lower dosages and arteriodilation at higher dosages, resulting in both preload and afterload reduction, respectively 3
- The potential mechanisms for relief of myocardial ischemia with nitrates are multiple, including the formation of nitric oxide (NO) within vascular smooth muscle cells, which stimulates the enzyme guanylate cyclase, resulting in increases in cyclic guanosine monophosphate and vasodilation 4
- Nitroglycerin also has antiplatelet effects, and recent evidence confirms that these drugs decrease platelet aggregation and thrombosis formation, which may play an important role in the therapy of acute unstable myocardial ischemia, including unstable angina and myocardial infarction 4
Effects on Myocardial Oxygen Consumption
- Nitroglycerin reduces pacing-induced increases in myocardial oxygen consumption and enhances metabolic coronary vasodilation in patients with coronary artery disease, in whom endogenous nitric oxide activity may be reduced 5
- The pacing-induced increase in myocardial oxygen consumption is blunted by nitroglycerin dose-dependently, with higher doses resulting in greater reductions in myocardial oxygen consumption 5
Hemodynamic Effects
- Nitroglycerin induces vasodilation, which can lead to a significant increase in stroke volume and urinary output while lowering cardiac filling pressures in patients with acute heart failure 6
- The exact hemodynamic effects of nitroglycerin remain uncertain in the clinical setting of acute decompensated heart failure, but it is hypothesized that intravenous nitroglycerin can promote diuresis and natriuresis 6
Clinical Applications
- Nitroglycerin is commonly used as a first-line agent for angina in the emergency department and to manage chest pain due to acute coronary syndromes, as well as for other disease states such as acute heart failure, pulmonary edema, and aortic dissection 3
- Nitroglycerin is often given intravenously in the emergency department, enabling titration to effect with predictable pharmacokinetics 3