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CHAPTER 12 Vasodilators & the Treatment of Angina Pectoris 203

TABLE 12–4 Properties of several voltage-activated calcium channels.

Properties of the
Type Channel Name Where Found Calcium Current Blocked By
2+
L Ca V 1.1–Ca V 1.4 Cardiac, skeletal, smooth muscle, Long, large, high threshold Verapamil, DHPs, Cd , ω-aga-IIIA
neurons (Ca V 1.4 is found in retina),
endocrine cells, bone
2+
T Ca V 3.1–Ca V 3.3 Heart, neurons Short, small, low threshold sFTX, flunarizine, Ni (Ca V 3.2 only),
mibefradil 1
3
N Ca V 2.2 Neurons, sperm 2 Short, high threshold Ziconotide, gabapentin, 4
ω-CTXGVIA, ω-aga-IIIA, Cd 2+
P/Q Ca V 2.1 Neurons Long, high threshold ω-CTX-MVIIC, ω-aga-IVA
R Ca V 2.3 Neurons, sperm 2 Pacemaking SNX-482, ω-aga-IIIA
1 Antianginal drug withdrawn from market.
2 Channel types associated with sperm flagellar activity may be of the Catsper 1–4 variety.
3 Synthetic snail peptide analgesic (see Chapter 31).
4 Antiseizure agent (see Chapter 24).
DHPs, dihydropyridines (eg, nifedipine); sFTX, synthetic funnel web spider toxin; ω-CTX, conotoxins extracted from several marine snails
of the genus Conus; ω-aga-IIIA and ω-aga-IVA, toxins of the funnel web spider, Agelenopsis aperta; SNX-482, a toxin of the African tarantula,
Hysterocrates gigas.

binding, and extensive metabolism. Verapamil and diltiazem are verapamil and diltiazem appear to bind to closely related but not
also used by the intravenous route. identical receptors in another region of the same subunit. Bind-
ing of a drug to the verapamil or diltiazem receptors allosterically
Pharmacodynamics affects dihydropyridine binding. These receptor regions are stere-
oselective, since marked differences in both stereoisomer-binding
A. Mechanism of Action affinity and pharmacologic potency are observed for enantiomers
The voltage-gated L type is the dominant type of calcium channel of verapamil, diltiazem, and optically active nifedipine congeners.
in cardiac and smooth muscle and is known to contain several Blockade of calcium channels by these drugs resembles that
drug receptors. It consists of α1 (the larger, pore-forming sub- of sodium channel blockade by local anesthetics (see Chapters 14
unit), α2, β, γ, and δ subunits. Four variant α1 subunits have and 26). The drugs act from the inner side of the membrane and
been recognized. Nifedipine and other dihydropyridines have bind more effectively to open channels and inactivated channels.
been demonstrated to bind to one site on the α1 subunit, whereas Binding of the drug reduces the frequency of opening in response

TABLE 12–5 Clinical pharmacology of some calcium channel-blocking drugs.

Oral Half-Life
Drug Bioavailability (%) (hours) Indication Dosage
Dihydropyridines
Amlodipine 65–90 30–50 Angina, hypertension 5–10 mg orally once daily
Felodipine 15–20 11–16 Hypertension, Raynaud’s phenomenon 5–10 mg orally once daily
Isradipine 15–25 8 Hypertension 2.5–10 mg orally twice daily
Nicardipine 35 2–4 Angina, hypertension 20–40 mg orally every 8 hours
Nifedipine 45–70 4 Angina, hypertension, Raynaud’s 3–10 mcg/kg IV; 20–40 mg orally
phenomenon every 8 hours
Nisoldipine <10 6–12 Hypertension 20–40 mg orally once daily
Nitrendipine 10–30 5–12 Investigational 20 mg orally once or twice daily
Miscellaneous
Diltiazem 40–65 3–4 Angina, hypertension, Raynaud’s 75–150 mcg/kg IV; 30–80 mg
phenomenon orally every 6 hours
Verapamil 20–35 6 Angina, hypertension, arrhythmias, 75–150 mcg/kg IV; 80–160 mg
migraine orally every 8 hours