Nifedipine is a dihydropyridine calcium channel blocking agent. Nifedipine inhibits the transmembrane influx of extracellular calcium ions into myocardial and vascular smooth muscle cells, causing dilatation of the main coronary and systemic arteries and decreasing myocardial contractility. This agent also inhibits the drug efflux pump P-glycoprotein which is overexpressed in some multi-drug resistant tumors and may improve the efficacy of some antineoplastic agents.
It works by relaxing the muscles of your heart and blood vessels. It is a medication used to manage angina, high blood pressure, Raynaud’s phenomenon, and premature labor. It is one of the treatments of choice for Prinzmetal angina. It may be used to treat severe high blood pressure in pregnancy. Its use in preterm labor may allow more time for steroids to improve the baby’s lungs and time to transfer the mother to a well qualified medical facility before delivery. Nifedipine has been formulated as both a long- and short-acting 1,4-dihydropyridine calcium channel blocker. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, nifedipine prevents calcium-dependent myocyte contraction and vasoconstriction.
Mechanism of Action of Nifedipine
Nifedipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through L-type calcium channels. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium inhibits the contractile processes of smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload. The vasodilatory effects of nifedipine result in an overall decrease in blood pressure.
or
The principal physiologic action of nifedipine is to inhibit the transmembrane influx of extracellular calcium ions across the membranes of myocardial cells and vascular smooth muscle cells, without changing serum calcium concentrations. Calcium plays important roles in the excitation-contraction coupling processes of the heart and vascular smooth muscle cells and in the electrical discharge of the specialized conduction cells of the heart. The membranes of these cells contain numerous channels that carry a slow inward current and that are selective for calcium. Activation of these slow calcium channels contributes to the plateau phase (phase 2) of the action potential of cardiac and vascular smooth muscle cells. The exact mechanism whereby nifedipine inhibits calcium ion influx across the slow calcium channels is not known, but the drug is thought to inhibit ion-control gating mechanisms of the channel, deform the slow channel, and/or interfere with release of calcium from the sarcoplasmic reticulum. By inhibiting calcium influx, nifedipine inhibits the contractile processes of cardiac and vascular smooth muscle, thereby dilating the main coronary and systemic arteries.
Indications of Nifedipine
- Chronic stable angina pectoris
- High blood pressure (hypertension)
- Raynaud’s syndrome
- Heart failure
- Angina pectoris prophylaxis
- Hypertensive emergency
- Hypertrophic cardiomyopathy
- Migraine prevention
- Premature labor
- Pulmonary edemas
- Pulmonary hypertension
- Ureteral calculus
- Vasospastic Angina
- Nifedipine has additionally been found to act as an antagonist of the mineralocorticoid receptor, or as an anti mineralocorticoid.
- Also used for the management of vasospastic angina, chronic stable angina, hypertension, and Raynaud’s phenomenon. May be used as a first line agent for left ventricular hypertrophy and isolated systolic hypertension (long-acting agents).
Contra-Indications of Nifedipine
- Porphyria
- Acute syndrome of the heart
- Severe narrowing of the aortic heart valve
- Severe heart failure
- Abnormally low blood pressure
- Kidney disease with reduction in kidney function
- Fluid Retention in the Legs ,arms or hands
- Blood Circulation Failure due to Serious Heart Condition
- Chronic idiopathic constipation
- Stomach or intestine blockage
- Narrowing of the intestines
- Decreased motility function of stomach or intestines
- Heart attack
- Allergies to Calcium Channel Blockers
- Calcium Channel Blocking Agents-Dihydropyridines
Dosage of Nifedipine
Strengths: 10 mg; 20 mg; 30 mg; 60 mg; 90 mg
Hypertension
Extended-release tablets
- Initial dose: 30 to 60 mg orally once a day
- Maintenance dose: 30 to 90 mg orally once a day
- Maximum dose: Up to 120 mg/day
Angina Pectoris Prophylaxis
Immediate-release capsules
- difficulty with moving
- Initial dose: 10 mg orally 3 times a day
- Maintenance dose: 10 to 30 mg orally 3 to 4 times a day
- Maximum dose: 180 mg/day
Extended-release tablets
- Initial dose: 30 to 60 mg orally once a day
- Maintenance dose: 30 to 90 mg orally once a day
- Maximum dose: Up to 120 mg/day
Angina Pectoris
Immediate-release capsules
- Initial dose: 10 mg orally 3 times a day
- Maintenance dose: 10 to 30 mg orally 3 to 4 times a day
- Maximum dose: 180 mg/day
Extended-release tablets
- Initial dose: 30 to 60 mg orally once a day
- Maintenance dose: 30 to 90 mg orally once a day
- Maximum dose: Up to 120 mg/day
Side Effects of Nifedipine
The most common
- severe headache, rapid heartbeat, stiffness in your neck,
- chest pain, fast or slow heart rate;
- swelling, rapid weight gain;
- Xerostomia (dry mouth)
- Headache
- Fatigue
- Skin reactions
- Hypotension
- Anxiety
- Constipation
- Nausea/vomiting
- Weight gain/loss
- Erectile dysfunction
More common
- Abdominal or stomach pain, discomfort, or tenderness
- chills or fever
- difficulty with moving
- headache, severe and throbbing
- joint or back pain
- muscle aching or cramping
- muscle pains or stiffness
- chest pressure or squeezing pain in chest
- discomfort in arms, shoulders, neck or upper back
- excessive sweating
- feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
- sudden tingling or coldness in an arm or leg
- sudden slow or difficult speech
- sudden drowsiness or need to sleep
- fast breathing
- sharp pain when taking a deep breath
- fast or slow heartbeat
- coughing up blood
- rust colored urine
- decreased amount of urine
Rare
- Anxiety
- change in vision
- chest pain or tightness
- confusion
- cough
- Agitation
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- convulsions
- extra heartbeats
- fainting
- hallucinations
- headache
- irritability
- lightheadedness
- mood or mental changes
- muscle pain or cramps
- muscle spasm or jerking of all extremities
- nervousness
Drug Interactions of Nifedipine
Nifedipine may interact with following drug, supplements, & may change the efficacy of the drug
- allopurinol
- alpha blockers (e.g., alfuzosin, doxazosin, tamsulosin)
- alpha agonists (e.g., clonidine, methyldopa)
- angiotensin II receptor blockers (ARBs; e.g., candesartan, losartan)
- antidiabetes medications (e.g., insulin, metformin, glyburide)
- atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine, risperidone)
- azathioprine
- barbiturates (e.g., butalbital, pentobarbital phenobarbital)
- beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- calcium channel blockers (e.g., amlodipine, diltiazem, verapamil)
- canagliflozin
- ciprofloxacin
- calcium supplements (e.g., calcium carbonate, calcium citrate)
- carbamazepine
- clopidogrel
- cyclosporine
- diuretics (water pills; e.g., furosemide, hydrochlorothiazide, triamterene)
- duloxetine
- “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
- guanfacine
- heparin
- levodopa
- medications that increase potassium levels (e.g., potassium supplements, spironolactone, amiloride, and salt substitutes containing potassium)
- metformin
- nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, indomethacin, naproxen)
- other angiotensin-converting-enzyme inhibitors (ACEIs; e.g., captopril, ramipril)
- pentoxifylline
- macrolide antibiotics (e.g., clarithromycin, erythromycin)
- methylphenidate
- monoamine oxidase inhibitors (MAOIs; e.g., moclobemide, phenelzine, rasagiline, selegiline, tranylcypromine)
- phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
- pregabalin
- sodium phosphates
- tizanidine
- trimethoprim
- valproic acid
- warfarin
Pregnancy Category of Nifedipine
FDA Pregnancy Category C
Pregnancy
This medication should not be taken by women who are or may become pregnant, as nifedipine may cause harm to the developing baby if it is taken by the mother during pregnancy. If you become pregnant while taking this medication, contact your doctor immediately.
Lactation
This medication should not be taken by women who are breastfeeding. The safety and effectiveness of using this medication have not been established for children.
References
