Pharmacology
Cardiovascular
Which of the following is a common side effect of nifedipine:
Answer:
Nifedipine relaxes vascular smooth muscle and dilates coronary and peripheral arteries. Nifedipine has less myocardial effects than verapamil and has no antiarrhythmic properties but has more influence on the vessels. Unlike verapamil it rarely precipitates heart failure because any negative inotropic effect is offset by a reduction in left ventricular work. Nifedipine commonly causes vasodilatory adverse effects - flushing, dizziness, headache, postural hypotension, ankle swelling, which often improve with continued use, although ankle swelling often persists.Calcium Channel Blockers
Pharmacology / Cardiovascular
Last Updated: 17th April 2019
Calcium channel blockers are widely used in the treatment of angina (second line to beta-blockers) and also for hypertension, heart failure and arrhythmias.
Type Examples
Calcium channel blockers vary widely in their predilection for the various possible sites of action and in their therapeutic effects and may be divided into the dihydropyridine type (e.g. amlodipine, nifedipine and nimodipine) and the rate-limiting non-dihydropyridine type (e.g. verapamil, diltiazem).
Verapamil: Verapamil is used for the treatment of angina, hypertension, and arrhythmias. Verapamil is highly negatively inotropic and reduces cardiac output, slows the heart rate and may impair atrioventricular conduction. It may precipitate heart failure, exacerbate conduction disorders, and cause hypotension at high doses and should not be used with beta-blockers. Constipation is the most common side effect.
Nifedipine: Nifedipine relaxes vascular smooth muscle and dilates coronary and peripheral arteries. Nifedipine has less myocardial effects than verapamil and has no antiarrhythmic properties but has more influence on the vessels. Unlike verapamil it rarely precipitates heart failure because any negative inotropic effect is offset by a reduction in left ventricular work.
Nimodipine: Nimodipine is related to nifedipine but the smooth muscle relaxant effect preferentially acts on cerebral arteries. It is used solely for the prevention and treatment of vascular spasm following aneurysmal subarachnoid haemorrhage.
Mechanism of Action
Calcium channel blockers inhibit L-type voltage-sensitive calcium channels in arterial smooth muscle, causing relaxation and vasodilation. They also block calcium channels within the myocardium and conducting tissues of the heart which produces a negative inotropic effect by reducing calcium influx during the plateau phase of the action potential.
The dihydropyridines have relatively little effect on the heart because they have a much higher affinity for inactivated channels found more frequently in vascular muscle. Furthermore, at clinical doses, vasodilation results in a reflex increase in sympathetic tone that counteracts the mild negative inotropic effect.
The non-dihydropyridines are rate-limiting calcium-channel blockers that depress the sinus node and slow conduction in the atrioventricular node, causing a mild resting bradycardia.
Contraindications
Verapamil:
- Acute porphyrias
- Atrial flutter or fibrillation associated with accessory conducting pathways (e.g. Wolff-Parkinson-White-syndrome)
- Bradycardia
- Cardiogenic shock
- History of heart failure (even if controlled by therapy)
- History of significantly impaired left ventricular function (even if controlled by therapy)
- Hypotension
- Second- and third-degree AV block
- Sick sinus syndrome
- Sinoatrial block
Nifedipine:
- Acute attacks of angina
- Cardiogenic shock
- Significant aortic stenosis
- Unstable angina
- Within 1 month of myocardial infarction
Nimodipine:
- Unstable angina
Within 1 month of myocardial infarction
Side Effects
- Gastrointestinal adverse effects - constipation, nausea, vomiting, dyspepsia
- Cardiovascular adverse effects - Bradycardia, AV block, reflex tachycardia, palpitations
- Vasodilatory adverse effects - flushing, dizziness, headache, postural hypotension, ankle swelling (more common with dihydropyridine calcium-channel blockers and often improve with continued use, although ankle swelling often persists)
- Lethargy, fatigue
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
