Calcium Channel Blockers
The calcium channel blockers (CCB's) are a heterogeneous group of drugs.
There are nine CCB's currently available on the Canadian market.
Trade name- Generic Name |
Role of Calcium
Calcium ions play a fundamental role in the activation of cells, particularly in neuronal and nuscular tissue.
Within the cardiovascular system, calcium influx results in contraction of cardiac muscle and maintenance of vascular tone in the coronary and peripheral vessels.
Activation of calcium channels in the sinoatrial (SA) and atrioventricular (AV) nodes is responsible for maintenance of normal heart rate and AV conduction.
Excess calcium entry into tissue following certain types of injury is thought to be responsible for activation of various processes which eventually lead to cell death.
All CCB's work by decreasing the inward flow of calcium through calcium channels.
They differ in their relative potency, tissue selectivity, and onset and duration of action resulting in different pharmacologic actions.
| Drug | Trade name | Negative inotropic potential | Effect on heart rate | Vascular selectivity | Cerebral vascular selectivity | Onset | Duration of effect | ||||||||||||||||
| Diltiazem | Cardizem, Cardizem-SR, Cardizem-CD| ++ | decrease | + | n/a | <30 min, 30-60min, 30-60min | 4-8 hrs, 12 hrs, 24hrs |
| ||||||||||||||||
| Verapamil | Isoptin, Isoptin-SR | +++ | decrease | + | n/a | <30 min, <30 min | 8-10 hrs, 24 hrs | ||||||||||||||||
| Nifedipine | Adalat, Adalat-PA, Adalat-XL | ++ | increase, ------, ------ | ++ | n/a | <20 min, <60 min, 2hrs | 6 hrs, 12hrs, 24hrs | ||||||||||||||||
| Felodipine | Plendil, Renedil | +/- | increase/- | ++ | n/a | 120-300 min | 24 hrs | ||||||||||||||||
| Nicardipine | Cardene | +/- | increase/- | +++ | ++ | < 20 min | 8 hrs | ||||||||||||||||
| Amlodipine | Norvasc | +/- | increase/- | +++ | n/a | 90-120 min | 24 hrs | ||||||||||||||||
| Nimodipine | Nimotop | - | increase/- | +++ | ++ | <30 min | 4 hrs | ||||||||||||||||
| Flunarizine | Sibelium | - | - | ++ | ++ | several weeks | half-life: 19 days |
Flunarizine- Sibelium- also has antihistaminic properties
-Used in the prophylaxis of migraine headaches
-Reduces the frequency of attacks and to a lesser extent the severity of migraine attacks.
- Well absorbed with peak levels attained 2-4 hrs post oral administration.
- Plasma levels increase gradually during chronic administration with steady state being
reached after 5-6 weeks.
There is a substantial interindividual variation.
- Flunarizine is 99.1% bound, 90 % to plasma proteins, 9% distributed to blood cells, leaving less than 1% as free drug.
- Elimination half life is 19 days.
- Metabolized by the liver
- The most serious side effects are depression, and extrapyramidal side effects. The extrapyramidal side effects are not improved with antiparkinsonian drugs, but tend to be reversible when the drug is discontinued.
Dose: 10 mg in the evening.
Pinaverium Bromide- Dicetel
Has high selectivity for intestinal smooth muscle
- Indicated for the treatment and relief of symptoms associated with irritable bowel syndrome: abdominal pain, bowel disturbances and intestinal discomfort.
Also indicated for treatment of symptoms related to functional disorder of the billiary tract.
-Adverse effects: minor digestive disorders that may be related to the disease.
May be irritating to esophageal mucosa- take with a glass of water during mealtime.
Dose: 50 mg three times a day
The Controversy
In March of 1995 a paper was presented to the scientific community suggesting that there was a dose-related increase in mortality rate in patients with coronary artery disease who were treated with Nifedipine.
The lay media publicized this report causing a great deal of anxiety among patients who were treated with CCB's. Since then several articles have been published, pointing to defects in the reported study and putting it into context.
- only short acting Nifedipine was implicated
-does not apply to other CCB's, does not apply to Nifedipine PA, or Nifedipine XL.
- We don't know the patient characteristics, those who died may have had very different risk factors from the control group.
- a modest bias was identified in patient selection, i.e. those who were prescribed Nifedipine and those selected to receive other anti-hypertensive agents.
- the report uses previously published studies, those which were chosen for analysis were chosen at random, others were omitted.
- there were several misquotations or errors regarding doses and number of patients.