Products
Dihydropyridines are commercially available in many countries in the form of film-coated tablets, sustained-release tablets, capsules, and injectables. Nifedipine from Bayer (Adalat) was the first active ingredient from this group to enter the market in the mid-1970s. Today, amlodipine (Norvasc, generics) is most commonly prescribed.
Structure and properties
The name 1,4-dihydropyridines is derived from the basic chemical structure of the active ingredients. A dihydropyridine is a hydrogenated pyridine. Dihydropyridines usually exist as racemates.
Effects
Dihydropyridines (ATC C08CA) have vasodilator, antihypertensive, antianginal, and antiischemic properties. They lower total peripheral resistance (afterload), unload the heart, and improve oxygen delivery to the myocardium. Dihydropyridines dilate coronary arteries, coronary arterioles, and peripheral resistance vessels (arterioles and arteries). The effects are based on inhibition of L-type voltage-gated calcium channels. This reduces calcium influx into cardiac myocytes and vascular smooth muscle cells. Calcium is the trigger for contraction. Unlike other calcium channel blockers and the beta blockers, the dihydropyridines do not affect conduction and contractility of the heart. Therefore, they are referred to as vasoselective and are not suitable for the treatment of cardiac arrhythmias.
Indications
- High blood pressure (arterial hypertension)
- Stable angina pectoris
- Vasospastic angina pectoris
- Acute hypertensive crisis (parenteral)
- For prophylaxis and therapy of ischemic neurologic deficits due to cerebral vasospasm after subarachnoid hemorrhage from aneurysms (parenterally, nimodipine).
Off-label, nifedipine is used as a labor inhibitor. In the form of nifedipine cream, it is used to treat anal fissures.
Dosage
According to the drug label. Dosage depends on the drug. Amlodipine needs to be taken only once daily because of its long half-life. Nifedipine has a short half-life of only about two hours and is therefore also taken in the form of sustained-release tablets.
Active Ingredients
The active ingredients have the suffix -dipine:
- Amlodipine (Norvasc, generic).
- Clevidipine (Cleviprex)
- Felodipine (Plendil, generics)
- Isradipine (Lomir SRO)
- Lercanidipine (Zanidip)
- Nifedipine (Adalat a.H., generic).
- Nimodipine (Nimotop)
Out of commerce in many countries:
- Lacidipine (Motens, out of trade).
- Nitrendipine (Baypress, off label).
Other agents exist that are not approved in many countries.
Contraindications
Full precautions can be found in the drug label.
Interactions
Other antihypertensive agents may result in increased lowering of blood pressure. This may be desirable in the context of combination therapy. Dihydropyridines are usually substrates of CYP3A4. Grapefruit juice is an inhibitor of this isoenzyme and may slightly increase the plasma concentration and AUC of dihydropyridines. Interactions are also possible with other CYP inhibitors and with CYP inducers.
Adverse effects
The most common possible adverse effects include:
- Edema (water retention)
- Dizziness, headache
- Palpable heartbeats (palpitations), high heart rate.
- Sleepiness, fatigue
- Redness of the face (flush)
- Lowering of blood pressure
- Gastrointestinal disorders such as abdominal pain, constipation and nausea.
The side effects are mostly a result of vasodilatation and blood pressure lowering. Numerous other adverse effects are possible, including the rare gingival proliferation.
