Nicorandil

Nicorandil is an antianginal agent belonging to the Potassium channel blocker

Nicorandil is used in the symptomatic treatment of stable angina pectoris.

Nicorandil is absorbed well from the GI tract (oral); peak plasma concentrations after 30-60 min with Protein-binding slightly bound. It gets metabolized through Denitration and gets excreted via urine (as metabolites); 1 hr (elimination half-life).

The onset of the Action of Nicorandil is within 30 minutes.

The Duration of Action of Nicorandil is within 12 hours.

The Tmax of Nicorandil was about 30-60 minutes, and Cmax was about300 ng/ml.

The common side effects are dizziness, drowsiness, headache, weakness, Nausea, strong irregular heartbeat, swelling, and dizziness upon standing.

Nicorandil is available in dosage forms, such as tablets and injections.

Nicorandil is available in the Philippines, Japan, South Korea, Italy, and India.

Nicorandil dilates arterioles and large coronary arteries by opening the potassium channels and stimulates guanylate cyclase causing venous vasodilatation. It, therefore, reduces preload and afterload and improves coronary blood flow.

Nicorandil is available in the form of dosage forms, such as tablets and injections.

Nicorandil tablets were taken orally with or without food.

Nicorandil Injection:

• Inject a needle into the person’s vein.
• Push a small plastic catheter over the needle and into the vein.
• Remove the needle, leaving the catheter in place.
• Place an access cap over the catheter, which allows them to administer medications without having to re-inject a needle.

Nicorandil is used in the symptomatic treatment of stable angina pectoris.

Nicorandil mediates its therapeutic efficacy via two main mechanisms. Nicorandil is an activator and opener of ATP-sensitive (ATP-dependent) potassium channels (KATP channels) that are composed of Kir6. x-type subunits and sulfonylurea receptor (SUR) subunits. Nicorandil binding sites are located in the sulfonylurea receptor 2 (SUR2) in the ATP-sensitive potassium channel, which are regulatory subunits of the channel that exhibit an ATPase activity.

Nicorandil is approved for its use in the following clinical indications:

Angina pectoris

Adult: Initially, 10 mg bid. The dose can be increased up to 40 mg bid according to the patient's response and tolerance. Max: 40 mg bid. In patients prone to headache: Initially, 5 mg bid.

Nicorandil is available in various dosage strengths:2.5 mg, 5 mg, 10 mg, 20 mg

Nicorandil is available in the form of a dosage forms, such as tablets, injection.

Nicorandil is approved for the treatment of Angina pectoris

Eat plenty of fruits, vegetables, and whole grains. Choose lean proteins, such as skinless chicken, fish, and beans. Eat non-fat or low-fat dairy products, such as skim milk and low-fat yogurt. Avoid foods that contain high levels of sodium (salt).

Nicorandil may be contraindicated in the following.

Cardiogenic shock; hypotension; left ventricular failure with low filling pressure; lactation.

USFDA pregnancy category B.

Nicorandil may not cause harm to an unborn fetus. Before Nicorandil treatment, the patient should discuss with the physician, if they are planning for a pregnancy.

Salt Substitutes: Those who are taking Nicorandil should avoid sodium, calcium, and magnesium-rich foods. The salts may reduce the blood-pressure-lowering effect of Nicorandil.

The adverse reactions related to the molecule Nicorandil can be categorized as

• Common Adverse Effects: Headache (usually transitory), flushing, dizziness, nausea, vomiting, and weakness.
• Less Common adverse effects: red, itchy, or watery eyes – these can be signs of conjunctivitis or a corneal ulcer, Painful sores (ulcers) on the eyes, skin, or the lining of your mouth
• Rare Adverse effects: Hypotension and reflex tachycardia at high doses.

The clinically relevant drug interactions of Nicorandil are briefly summarized here.

Hypotensive interaction may occur with alcohol, TCAs, antihypertensive, and other vasodilators.

Potentially Fatal: Enhanced hypotensive effect with sildenafil and other phosphodiesterases type-5 inhibitors.

Oral forms: Seek emergency medical treatment or contact the doctor in case of an overdose of this medicine. Injections: Since the injection form of this medicine is administered in the hospital/clinical setting by a qualified healthcare professional, the likelihood of an overdose is very low. However, emergency medical treatment will be initiated by the doctor if an overdose is suspected.

Pharmacodynamics:

Nicorandil is a potassium channel opener with nitrovasodilator (NO donor) actions, making it both an arterial and a venous dilator. It causes sustained dilation of both the arterial resistance and conductive vessels that increases coronary blood flow, however, the effect of the drug on coronary arteries does not involve the coronary steal phenomenon. Activation of potassium channels leads to hyperpolarization of the smooth muscle cells, followed by arterial dilation and afterload reduction. Nicorandil is shown to increase pooling in the capacitance vessels with a decrease in preload through relaxing the venous vascular system. Overall, improved blood flow and reduced infarct size are achieved through the reduction of end-diastolic pressure and decreased extravascular component of vascular resistance. Open studies showed the effectiveness of nicorandil treatment on various types of angina pectoris

Pharmacokinetics:

• Absorption

Following oral administration, nicorandil is well absorbed from the gastrointestinal tract with an oral bioavailability of 75% with the maximum peak plasma concentration (Cmax) reached within 30-60 minutes. The mean Cmax is Cmax then is approximately 300 ng/ml. Steady-state plasma concentrations of nicorandil usually are reached within approximately 96-120 h after twice daily dosing (10 or 20mg)

• Distribution:

After oral (and i.v.) administration of the drug, the apparent volume of distribution is approximately 1.0-1.4 L/kg body weight

• Metabolism:

Nicorandil undergoes extensive hepatic metabolism. The main biotransformation pathways of nicorandil are Denitration, followed by subsequent nicotinamide metabolism. The main pharmacologically inactive denitrated metabolite 2-nicotinamidoethanol can be detected in the urine. The derivatives formed from the nicotinamide metabolism of denitrated products are nicotinic acid, nicotinamide, N-methyl nicotinamide, and nicotinic acid

• Elimination

The main route of elimination is the kidney with more than 60% of the administered dose being eliminated in the urine 24 hours after dosing. Only approximately 1% of nicorandil is excreted unchanged in the urine, and the remaining compounds are mainly the denitrated metabolite (9%) and its derivatives (e.g. nicotinic acid 6%, nicotinamide 1%, N-methyl nicotinamide < 1% and nicotinic acid < 1%). Less than 2% of the administered dose is excreted through the biliary system.

1. https://www.mims.com/india/drug/info/Nicorandil ?type=full&mtype=generic
2. https://go.drugbank.com/drugs/DB00590
3. https://www.rxlist.com/consumer_Nicorandil _cardura/drugs-condition.htm
4. https://reference.medscape.com/drug/cardura-xl-Nicorandil -342343