| Class | Calcium channel blocker |
|---|---|
| Chemistry |
1,4-dihydropyridine |
| Routes of administration |
Oral or IV |
| Absorption |
oral bioavailability 11.60% |
| Solubility |
pKa 5.4, excellent lipid solubility |
| Distribution |
Highly lipid soluble: octanol/water partition coefficient 3.8, 98% protein bound. VOD =1.7 L/kg |
| Metabolism |
Mainly hepatic clearance, by CYP3A4 |
| Elimination |
Time to peak effect = 1 hr; elimination half-life 1-2 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 (selective for the smooth muscle isoform) |
| 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. The magnitude of this effect depends on the resting membrane potential of the smooth muscle cells, which makes nimodipine more selective for the cerebral circulation (where the resting membrane potential is lower) |
| Clinical effects |
Relaxation of vascular smooth muscle, thereby decreasing peripheral vascular resistance and afterload. Side effects include flushing and constipation. |
| Literature reference |
Abernethy & Schwartz (1999) |
| CICM details of understanding | Level 2 |
| Mentioned around Deranged Physiology |
Calcium channel blockers; also classification and summary of antihypertensive agent classes. To a lesser extent, evidence for the use of nimodipine in SAH from the Second Part exam sections.
|
| Related SAQs |
Question 8 from the second paper of 2017 Question 17 from the second paper of 2011 (verapamil vs nimodipine) |