Nicorandil-K+channel opener

2. 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.

3. Goals of management of Angina
 Decrease severity and frequency of angina
 Improve prognosis
 Improve patients’ life quality

4. 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)

5. 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

6. 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

7. 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

8.  (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

9. 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

10. 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

11. 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

12.  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

13. Ischaemic Heart Disease

15.  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

16. 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

17. 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

18. 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

19. 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

21. Bibliography
 Harrison’s textbook of Medicine,18th Ed
 Katsung Lange Pharmacology
 Nikoran product monograph,Torrent pharmaceuticals