| Class | Calcium channel blocker |
|---|---|
| Chemistry |
Benzothiazepine |
| Routes of administration |
Oral or IV |
| Absorption |
oral bioavailability 39% |
| Solubility |
pKa 7.5, excellent lipid solubility |
| Distribution |
Highly lipid soluble: octanol/water partition coefficient 2.7, 80-86% protein bound. VOD =5.3 L/kg |
| Metabolism |
Mainly hepatic clearance, by CYP3A4 (which it inhibits) |
| Elimination |
Time to peak effect = 0.5-1.5 hrs; elimination half-life 2-5 hrs |
| Time course of action |
Clinical effects persist for longer than the half life would suggest, because they are mainly determined by drug-receptor affinity |
| Target receptor |
α1c subunit of the L-type calcium channel (non-selective, affecting both myocardial and smooth muscle isoforms) |
| Mechanism of action |
Modulates the opening of voltage-gated calcium channels, which prevents intracellular calcium influx during depolarisation. This decreases the availability of intracellular calcium for vascular smooth muscle cells, decreasing their resting tone. In cardiac myocytes, this decreases contractility as well as the automaticity of pacemaker cells. |
| Clinical effects |
Relaxation of vascular smooth muscle, thereby decreasing peripheral vascular resistance and afterload. Decreased cardiac contractility and decrease heart rate, thereby decreasing myocardial oxygen demand. Side effects include flushing and constipation. |
| Literature reference |
Abernethy & Schwartz (1999) |
| CICM details of understanding | Not specifically listed in the CICM syllabus |
| Mentioned around Deranged Physiology | |
| Related SAQs |