Angina Pectoris
 Myocardial ischaemia-coronary blood flow inadequate
to meet myocardial oxygen demand.
 Angina-most comm...
Goals of management of Angina
 Decrease severity and frequency of angina
 Improve prognosis
 Improve patients’ life qua...
Modalities of
management
Pharmacological treatment Myocardial revascularization
1.Nitrates
(a)Short acting –
GTN,nitroglyc...
Unmet needs of current therapy
 Agents like beta blockers , CCBs and nitrates have
their limitations.
 Beta blockers-abs...
Nicorandil-An overview
 Class- K+channel activators
(Other drugs – Minoxidil, Diazoxide
,Pinacidil)
• Novel drug used in ...
Pharmacology
 Hybrid compound- comprises of nicotinamide vitamin
group and an organic nitrate
 Mechanism of action-(a)ni...
 (b) K+ channel activation-
preferential activity on K+ ATP channels reducing sensitivity to
its inhibitor(ATP)
Increased...
Nicorandil Dual Action
Nitrate like action K+ ATP channel opener
Dilates epicardial Venodilatation Dilates peripheral Dila...
Pharmacodynamics
 Hemodynamic effects-
Decreases ventricular volume, coronary vascular
resistance and MAP ; HR and corona...
Clinical Efficacy & Indications
 In Stable Angina-significant improvement in exercise
tolerance tests compared to baselin...
 Acute MI-
-Nicorandil infusion before reperfusion and
intracoronary injection is more effective than ISDN
-Perserves myo...
Ischaemic Heart Disease
 Intravenous Nicorandil before reperfusion on AMI
patients with stress hyperglycaemia improved
epicardial flow and preven...
Dosage and administration
 Recommended adult dosage- 10 mg BD ;reduced to 5
mg BD in patients prone to headache
 Can be ...
Adverse Reactions
 Headache-mild to moderate
 Gastrointestinal events(nausea and vomiting)
 Dizziness ,malaise and fati...
Contraindications
 Known or idiosyncratic hypersensitivity to the drug
 Cardiogenic shock
 Hypotension
 Left ventricul...
Nicorandil-Place in therapy
 Angina does significantly impair the qualily of life of
the patient
 Life style modificatio...
Bibliography
 Harrison’s textbook of Medicine,18th Ed
 Katsung Lange Pharmacology
 Nikoran product monograph,Torrent ph...
New pharmocological agents in the management of angina nicorandil
New pharmocological agents in the management of angina nicorandil
New pharmocological agents in the management of angina nicorandil
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New pharmocological agents in the management of angina nicorandil

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Nicorandil-K+channel opener

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New pharmocological agents in the management of angina nicorandil

  1. 1. Angina Pectoris  Myocardial ischaemia-coronary blood flow inadequate to meet myocardial oxygen demand.  Angina-most common clinical presentation d/t chemical and mechanical stimulation of sensory nerve endings.
  2. 2. Goals of management of Angina  Decrease severity and frequency of angina  Improve prognosis  Improve patients’ life quality
  3. 3. Modalities of management Pharmacological treatment Myocardial revascularization 1.Nitrates (a)Short acting – GTN,nitroglycerine (b)Long acting-Isosorbide dinitrate/mononitrate 2.Beta blockers- Propanolol,Metaprolol,Atenolol 3,Calcium channel blockers- Verapamil,Diltiazem,Nifedipine 4.K+ channel opener- Nicorandil 5.Others- Dipyramidole,Trimetazidine 1.Surgical revascularisation(CABG) 2.Percutaneous coronary intervention(PCI)
  4. 4. Unmet needs of current therapy  Agents like beta blockers , CCBs and nitrates have their limitations.  Beta blockers-absolute or relative contraindication in asthma ,COPD and peripheral vascular disease.  CCBs- heart failure in patients with poor LVEF, ineffective in preventing no reflow phenomenon,ADRs(flushing & peripheral oedema)  Nitrates- long term use associated with tolerance
  5. 5. Nicorandil-An overview  Class- K+channel activators (Other drugs – Minoxidil, Diazoxide ,Pinacidil) • Novel drug used in treatment of angina –having arterio and venodilating properties • Only drug in the class approved for use in angina • Key advantages- no tolerance, comparable efficiency and tolerability to existing agents ,potent cardioprotective action
  6. 6. Pharmacology  Hybrid compound- comprises of nicotinamide vitamin group and an organic nitrate  Mechanism of action-(a)nitrate like action increased level of cyclic guanosine monophosphate decrease in cytosolic calcium vascular smooth muscle relaxation dilatation of coronary epicardial arteries
  7. 7.  (b) K+ channel activation- preferential activity on K+ ATP channels reducing sensitivity to its inhibitor(ATP) Increased K+efflux leading to more negative RMP Shortens action potential and inhibits Ca influx Decreased intracellular Calcium resulting in vasodilatation Ischaemic preconditioning Dilatation of coronary resistance arterioles
  8. 8. Nicorandil Dual Action Nitrate like action K+ ATP channel opener Dilates epicardial Venodilatation Dilates peripheral Dilates coronary Coronary arteries arterioles microvessels decreased preload decreased after load Inceased coronary decreased decreased increased flow myocardial myocardial coronary O2 requirement O2 requirement bloodflow
  9. 9. Pharmacodynamics  Hemodynamic effects- Decreases ventricular volume, coronary vascular resistance and MAP ; HR and coronary blood flow increased or remain unchanged  Cardioprotective effects- Ischaemic preconditioning-single or multiple brief periods of ischaemia and reperfusion preceding a prolonged ischaemia- cardioprotective in nature
  10. 10. Clinical Efficacy & Indications  In Stable Angina-significant improvement in exercise tolerance tests compared to baseline -effects comparable to nitrates ,CCBs and beta blockers  Unstable Angina-randomised trials revealed decreased episodes of silent and painful transient myocardial ischemia -another study revealed efficacy better than nitrates
  11. 11.  Acute MI- -Nicorandil infusion before reperfusion and intracoronary injection is more effective than ISDN -Perserves myocardial microcirculation in reperfused AMI area -Results in better left ventricular wall motion -Recovery of ST segment elevation was 55% with nicorandil compared to 19.2% with ISDN after reperfusion  In PCI- I/v administation prevents slow coronary flow phenomenon and results in better preservation of myocardial viability
  12. 12. Ischaemic Heart Disease
  13. 13.  Intravenous Nicorandil before reperfusion on AMI patients with stress hyperglycaemia improved epicardial flow and prevents occurrence of severe microvascular reperfusion injury and resulted in better outcomes  Single intravenous administration in STEMI resulted in accelerated resolution and increased coronary microvascular flow as well as reduced reperfusion injury
  14. 14. Dosage and administration  Recommended adult dosage- 10 mg BD ;reduced to 5 mg BD in patients prone to headache  Can be increased to 20 or 20 md BD according to clinical effect  Intravenous dosage- loading dose of 0.2 mg/kg followed by continuous administration of 0.2 mg/kg/hr
  15. 15. Adverse Reactions  Headache-mild to moderate  Gastrointestinal events(nausea and vomiting)  Dizziness ,malaise and fatigue  No significant effect on glucose or lipid metabolism ,weight gain , do not produce any arrythmias
  16. 16. Contraindications  Known or idiosyncratic hypersensitivity to the drug  Cardiogenic shock  Hypotension  Left ventricular failure with low filling pressures  To be used carefully if SBP< 100 mmHg  To be discontinued if mouth ulcerations appear  Combination with PDE-5 inhibitors( sildenafil) to be avoided in view of risk for severe hypotension
  17. 17. Nicorandil-Place in therapy  Angina does significantly impair the qualily of life of the patient  Life style modifications can improve long term outcome  Sublingual nitroglycerin remains the primary intervention for the direct control of symptoms  Nicorandil ,along with beta blockers ,CCBs play a role in backgroung antianginal therapy  The current standard of care is reperfusion of the infarct related artery; thrombolytic therapy remains the cornerstone of management of AMI
  18. 18. Bibliography  Harrison’s textbook of Medicine,18th Ed  Katsung Lange Pharmacology  Nikoran product monograph,Torrent pharmaceuticals

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