Question 8

Classify calcium channel blockers providing examples (15% marks). Describe the pharmacology of verapamil (85% marks).

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College Answer

Answering this question well required the demonstration of understanding of the concept of achieving maximum urinary concentrating ability. Answers required a description of the usual concentrating processes and the changes that would occur in circumstances where maximally concentrated urine would be made. A key concept was the creation of a medullary concentration gradient to allow water reabsorption independent of solute reabsorption. This required an explanation of the contribution of the loop of Henle, the vasa recta, and urea cycling in the creation and maintenance of this gradient, along with the impact of ADH. More detailed explanation of each contribution was required as overarching statements were not sufficient to attract all marks for each section. Answers that focused solely on the counter-current exchange and multiplier process were insufficient on their own to achieve a passing mark. The examiners commented that a significant proportion of candidates excluded the role of urea in their answers.



  • Phenylalkylamines:
    • Verapamil
  • Benzothiazepines:
    • Diltiazem
  • 1,4-dihydropyridines:
    • Nifedipine
    • Nimodipine
    • Amlodipine
    • Lercanidipine
    • Clevidipine

Now, for 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)


Singh, B. N. "The mechanism of action of calcium antagonists relative to their clinical applications." British journal of clinical pharmacology 21.S2 (1986): 109S-121S.

Drapak, Iryna, et al. "Cardiovascular calcium channel blockers: historical overview, development and new approaches in design." Journal of Heterocyclic Chemistry 54.4 (2017): 2117-2128.

Triggle, David J. "Calcium-channel drugs: structure-function relationships and selectivity of action." Journal of cardiovascular pharmacology 18 (1991): S1-S6.

Abernethy, Darrell R., and Janice B. Schwartz. "Calcium-antagonist drugs." New England journal of medicine 341.19 (1999): 1447-1457.