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Recent Advances: New Drugs for Angina

  1. Ranolazine  
    1. Ranolazine has its effects via altering the trans-cellular late sodium current. It is by altering the intracellular sodium level that ranolazine affects the sodium-dependent calcium channels during myocardial ischemia. 
    2. Thus, ranolazine indirectly prevents the calcium overload that causes cardiac ischemia.
    3. Ranolazine also a partial fatty acid oxidation inhibitor, shifts ATP production from fatty acid to more oxygen efficient carbohydrate oxidation. It was also discovered that inhibition of fatty acid oxidation sensitizes human leukemia cells to apoptosis induction. 
    4. Ranolazine is indicated for the treatment of chronic anginait has been shown to both decrease angina episodes and increase exercise tolerance Ranolazine is known to increase the QT interval on the electrocardiogram.
    5. Ranolazine is metabolized in the liver, particularly by one of the cytochrome CYP3A enzymes, it has been approved a new, first line indication for the treatment of chronic angina.
  2. Trimetazidine:
    1. Trimetazidine is an anti-ischemic (anti-anginal) metabolic agent, which improves myocardial glucose utilization through inhibition of fatty acid metabolism, also known as fatty acid oxidation inhibitor (PFOX inhibitor)                                                                                                                                                        
    2. Trimetazidine is described as the first cytoprotective anti-ischemic agent. Trimetazidine is usually prescribed as a long-term treatment of angina pectoris.
  3. Ivabradine:  
    1. It is indicated for the symptomatic treatment of chronic stable angina pectoris in patients with normal sinus rhythm, who have a contraindication to or intolerance to beta-blockers.
    2. Ivabradine acts on the If (f is for "funny", so called because it had unusual properties compared with other current systems known at the time of its discovery) ion current, which is highly expressed in the sinoatrial node.
    3. If is a mixed Na+–K+ inward current activated by hyperpolarization and modulated by the autonomic nervous system.
    4. It is one of the most important ionic currents for regulating pacemaker activity in the sinoatrial (SA) node.
    5. Ivabradine selectively inhibits the pacemaker If  current in a dose-dependent manner.
    6. Blocking this channel reduces cardiac pacemaker activity, slowing the heart rate and allowing more time for blood to flow to the myocardium  patients taking ivabradine experience luminous phenomena (by patients described as sensations of enhanced brightness in a fully maintained visual field).
    7. This is probably due to blockage of Ih ion channels in the retina which are very similar to cardiac.
  4. Fasudil:
    1. It is a potent Rho-kinase inhibitor and vasodilator. 
    2. It is used for the treatment of cerebral vasospasm, which is often due to subarachnoid hemorrhage, as well as to improve the cognitive decline seen in stroke victims.
    3. It is effective for the treatment of pulmonary hypertension. 
    4. It is used to enhance memory and improve the prognosis of Alzheimer’s patients. Effective in angina too.

Molecular Mechanism

  1. Fasudil is a selective RhoA/Rho kinase (ROCK) inhibitor
  2. ROCK is an enzyme that plays an important role in mediating vasoconstriction and vascular remodeling in the pathogenesis of PH.
  3. ROCK induces vasoconstriction by phosphorylating the myosin-binding subunit of myosin light chain (MLC) phosphatase, thus decreasing MLC phosphatase activity and enhancing vascular smooth muscle contraction. 
  1. Detanonoate:
    Donate two molecules of NO, & hence vasodilator.

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