Nifedipine


Article Author:
Kashif Khan


Article Editor:
Timothy Schaefer


Editors In Chief:
Jasleen Jhajj
Cliff Caudill
Evan Kaufman


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
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Patrick Le
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Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
1/20/2019 4:27:02 PM

Indications

Nifedipine is a calcium channel blocker in the dihydropyridine subclass. It is primarily used as an antihypertensive and as an anti-anginal medication.

FDA Approved Indications[[1][2][2][3][4][5][6]:

  1. Chronic stable angina - nifedipine reduced the frequency of angina and increased the mean exercise time to 1-mm ST segment depression in the IMAGE trial. Reflex tachycardia may limit its effectiveness; the addition of a beta-blocker can overcome this limitation
  2. Hypertension - nifedipine can be used as monotherapy or in combination with several different medications to manage hypertension or CAD in patients
  3. Severe hypertension during pregnancy and postpartum hypertension

Other Off-label uses[7][8][9][10][11]

  1. Primary and secondary Raynaud's phenomenon
  2. High altitude pulmonary edema
  3. Pulmonary hypertension
  4. Achalasia
  5. Distal ureteric calculi

Mechanism of Action

During the depolarization phase of smooth muscle cells, there is an influx of calcium ions through voltage-gated channels. Nifedipine inhibits the entry of calcium ions by blocking these voltage-dependent L type calcium channels in vascular smooth muscle and myocardial cells. The reduced intracellular calcium, results in a reduction of peripheral arterial vascular resistance and dilatation of coronary arteries, leading to a reduction in systemic blood pressure and increased myocardial oxygen delivery. Nifedipine thus has hypotensive and antianginal properties.

Administration

Nifedipine is available in immediate and extended release preparations. Its initial marketing was in a short-acting, immediate-release formulation that required multiple daily dosing. These preparations caused rapid vasodilation followed by reflex sympathetic activation, resulting in side effects such as headaches, palpitations, and flushing. These side effects led to the launch of extended-release preparations, which have shown to have a sustained 24-hour anti-hypertensive effect and fewer side effects. Extended-release preparations are available in 30, 60, and 90 mg tablets. Dosage adjustments should ideally occur at 7- to 14-day intervals. The same total daily dosage should apply when switching from immediate to sustained-release preparations. Immediate release preparations may be taken without regard to meals. A few specific extended-release preparations require ingestion on an empty stomach. 

Immediate release preparations have an onset of action within 20 minutes with a plasma half-life of about 4 to 7 hours. Extended-release preparations have an approximate duration of action of about 24 hours.  It undergoes hepatic metabolism via CYP3A4 pathway. Extended-release preparations have a bioavailability of up to 89%, relative to immediate release preparations. Bioavailability significantly increases in patients with liver failure necessitating dosage adjustment

Recommended Dosages:

Chronic Stable Angina:

Immediate release: 10mg three times daily; maximum dose of 180 mg per day

Extended-release: 30 or 60mg daily; maximum dose of 120 mg per day

Hypertension:

Extended-release: 30 or 60mg daily; maximum dose of 120 mg per day  

Hypertensive emergency during pregnancy or postpartum period: 

Immediate release: 10 mg; may repeat with a 20 mg dose in 20 minutes  

Adverse Effects

Adverse effects present in about 20-30% of patients prescribed nifedipine. These are primarily because of vasodilatory properties of nifedipine. The most common adverse effects include flushing, peripheral edema, dizziness, headache, flushing, heartburn, and nausea. Tolerance is better with the extended-release preparations than the immediate-release preparations of nifedipine. Hypersensitivity reactions such as pruritus, urticaria, and bronchospasms are rare. Abrupt discontinuance of the drug after prolonged use may lead to withdrawal symptoms such as hypertension or angina. 

Contraindications

Absolute contraindications to nifedipine include patients with known hypersensitivity to nifedipine or its components. Contraindications include patients with ST-elevation myocardial infarction.[12] In patients with unstable angina/non-STEMI, the use of immediate-release nifedipine is not a recommendation except with concomitant beta-blockade.[13] Its use should also be avoided in patients with cardiogenic shock, severe aortic stenosis, unstable angina, hypotension, heart failure, and moderate to severe hepatic impairment. Immediate release preparations of nifedipine (sublingually or orally) in hypertensive emergencies and urgencies is neither safe nor effective.[14] In cardiogenic shock, the heart cannot pump effectively, and this situation is exacerbated by inhibiting the influx of calcium ions into cardiac cells.[13] In severe aortic stenosis, nifedipine can cause ventricular collapse and dysfunction. In unstable angina, nifedipine causes a reflexive increase in cardiac contractility, which increases myocardial oxygen demand and worsens the ischemia. Nifedipine can also worsen hypoperfusion to vital organs in patients with severe hypotension.[13] Furthermore, patients with hepatic impairment may not be able to metabolize nifedipine, leading to a long half-life putting them at an increased risk of toxicity and side effects. Lastly, abrupt withdrawal may cause rebound angina in patients with CAD.

Monitoring

In general, there is no required laboratory monitoring for patients taking nifedipine. Since nifedipine is an antihypertensive medication, clinicians and patients should regularly measure blood pressure to achieve target levels as per the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines. Patients should undergo monitoring for adverse side effects such as peripheral edema, dizziness, flushing among others.

Toxicity

Treatment of overdose varies with the amount taken, duration since ingestion, age and, co-morbidities of the patient. Initial assessment involves securing airway, breathing, circulation, appropriate blood work including testing for co-ingestants. Early consultation with poison control/ toxicology should be a priority. An overdose of nifedipine can lead to vasodilation, severe hypotension, and reflexive tachycardia. Prolonged systemic hypotension can progress to shock and even death. Activated charcoal at a dose of 1g/kg is useful if the patient presents within 1 to 2 hours of ingestion. Whole bowel irrigation should be a consideration with extended-release preparations or large quantity ingestion. Nasogastric lavage is usually ineffective.  Intravenous (IV) fluid resuscitation, calcium salts, and vasopressor therapy with dopamine or norepinephrine usually alleviate the hypotension. Administration of high-dose insulin is an option as it has been shown to lower mortality and improve hemodynamics. Electrocardiographic results, vital signs, kidney function, urine output, and electrolytes require continuous monitoring during an overdose. For intentional ingestion, psychiatric consultation is necessary. Patients presenting with an overdose of immediate release preparations need observation for from 4 to 7 hours. For extended-release preparations 24 hours of telemetry observation is ideal. No specific antidote is available. 

Enhancing Healthcare Team Outcomes

Healthcare workers including nurse practitioners should be familiar with the indications and contraindications of nifedipine. The drug can cause severe hypotension, and thus it is recommended that its dosing undergo titration from an initial low dose. Long-term patient monitoring is necessary to determine its effectiveness. Sublingual preparations are no longer recommended for hypertensive emergencies or urgencies due to lack of efficacy data and numerous severe adverse events such as an uncontrollable decrease in blood pressure, reflex tachycardia, and cerebral ischemia/infarction. 


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Nifedipine - Questions

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Which of the following antihypertensive drugs is associated with gingival hyperplasia?



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A patient is taking the calcium channel blocker nifedipine for the control of moderate hypertension. The patient is experiencing postural hypotension. Interventions will include which of the following?



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What is the antihypertensive medication associated with gingival hyperplasia?



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Which is NOT a property of nifedipine?



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Which of the following is not caused by nifedipine?



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Which is an adverse effect of nifedipine?



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What is the mechanism of nifedipine?



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Which of the following drugs is a calcium channel blocker?



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Which drug is synergistic with nifedipine?



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Where is the primary effect of nifedipine?



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A patient wants his money back because he keeps seeing nifedipine XL pills in his stool. Which of the following do you tell him?



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Procardia is the brand name for which one of the following generics?



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Nifedipine - References

References

Calcium channel blockers for primary and secondary Raynaud's phenomenon., Rirash F,Tingey PC,Harding SE,Maxwell LJ,Tanjong Ghogomu E,Wells GA,Tugwell P,Pope J,, The Cochrane database of systematic reviews, 2017 Dec 13     [PubMed]
Postpartum Hypertension: Etiology, Diagnosis, and Management., Sharma KJ,Kilpatrick SJ,, Obstetrical & gynecological survey, 2017 Apr     [PubMed]
Oral nifedipine versus intravenous labetalol for severe hypertension during pregnancy: a systematic review and meta-analysis., Shekhar S,Gupta N,Kirubakaran R,Pareek P,, BJOG : an international journal of obstetrics and gynaecology, 2016 Jan     [PubMed]
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