Classify calcium channel blockers, and give an example for each classification. (30% of
marks) Describe the pharmacology of verapamil. (70% of marks)
College Answer
Most candidates managed to provide a classification of calcium anatagonists. The
pharmacology of verapamil was less well understood. The structure for answering a
pharmacology question was often poor and there was commonly a lack of precision in
pharmacokinetics. We suggest that candidates look at a general pharmacokinetic structure
when answering these questions. One approach would be a structure that covers drug name
and description, pharmaceutics (chemistry/ ampoule contents), Pharmacokinetics,
Pharmacodynamics (Think CNS/CVS/Resp/GIT etc. if relevant), Dose and Side effects then
Indications and Contraindications can help organize the information
Discussion
Classification of calcium channel blockers:
- Phenylalkylamines:
- Verapamil
- Benzothiazepines:
- Diltiazem
- 1,4-dihydropyridines:
- Nifedipine
- Nimodipine
- Amlodipine
- Lercanidipine
- Clevidipine
Pharmacology of verapamil
| Class | Calcium channel blocker |
| Chemistry | Phenylalkylamine |
| Routes of administration | Oral or IV |
| Absorption | oral bioavailability 24% |
| Solubility | pKa 8.73, excellent lipid solubility |
| Distribution | Highly lipid soluble: octanol/water partition coefficient 67, 84-91% protein bound. VOD =3.8 L/kg |
| Target receptor | α1c subunit of the L-type calcium channel (non-selective, affecting both myocardial and smooth muscle isoforms) |
| Metabolism | Mainly hepatic clearance, by CYP3A4 (which it inhibits) |
| Elimination | Time to peak effect = 0.5-1.0 hrs; elimination half-life 4.5-12 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 |
| 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. |
| Single best reference for further information | Abernethy & Schwartz (1999) |
References
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