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
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
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