Calcium antagonism

The concept of calcium antagonism as a specific mechanism of drug action was pioneered by Albrecht Fleckenstein and his colleagues, who observed that verapamil and subsequently other drugs of this class mimicked in reversible fashion the effects of Ca++ withdrawal on cardiac excitability. These drugs inhibited the Ca" + component of the ionic currents carried in the cardiac action potential. Because of this activity, these drugs are also referred to as slow channel blockers, calcium channel antagonists, and calcium entry blockers. 

T. Godfraind, R. Miller, M. Wibo (1986). Calcium antagonism and calcinm entry blockade. Pharmacol. Rev. 38 321-416. 

Kiue A, Sano T, Suzuki KI, Inada H, Okumura M, Kikuchi J, Sato SI, Kohno K, Kuwano M (1990) Activities of newly synthesized dihydropyridines in overcoming of vincristine resistance, calcium antagonism, and inhibition of photoaffinity labeling of P-glycoprotein in rodents. Cancer Res 50 310-317... 

Interaction between zinc and calcium has been demonstrated In several animal studies (l- ). It has been shown that calcium antagonizes the biological effects of zinc and that calcium reduces the availability of zinc for absorption. This decrease In zinc absorption resulted In severe malnutrition and parakeratosis (1.-7.) Several studies have conclusively shown that the calclum-zlnc antagonism studied In animals Is due to excess phytic acid In the diet (, 9). However, In the absence of phytic acid, excess dietary calcium per se has also been shown to decrease the Intestinal absorption and the retention of zinc In rats (10). This Inhibitory effect on zinc absorption. Induced by calcium, was further enhanced by the addition of phosphorus to the high calcium Intake (11). 

Godfraind T, Miller R, Wibo M (1986) Calcium antagonism and calcium entry blockade. Pharmacol Rev 38 321 16... 

Early studies showed that curare blockade was increased by tetracychnes (71-73). This effect can be antagonized by calcium ions (74). There was a shortterm increase in muscular weakness in patients with myasthenia gravis after intravenous tetracycline. The mechanism may be a calcium-antagonizing effect of magnesium ions present in the tetracycline solvent, as the... 

Administer calcium gluconate IV. Calcium antagonizes the effect of magnesium. 

Recent studies have suggested that N-terminal-truncated PTH may be biologically active. Synthetic PTH(7-84), used as the available representative of N-terminal-truncated PTH, decreased serum calcium antagonized the calcemic, phosphatemic, and phosphaturic effects of intact PTH in thyroparathyroidectomized animals and was bound by a C-terminal PTH receptor distinct from the PTH/PTHrP receptor. ... 

Fleckenstein A. Calcium Antagonism in Heart and Smooth Muscle. J. Wiley Sons, New York, NY. 1983. 

In symptomatic patients, or in those with severe hyperkalemia (serum potassium >7 mEq/L), emergency care is indicated. Initial therapy in this setting is the administration of intravenous calcium to protect the heart from life-threatening arrhythmias." Calcium antagonizes the cardiac membrane effect of hyperkalemia and reverses ECG changes within minutes. Its duration of action is 30 to 60 minutes, and it can be repeated as needed based on ECG findings. 

Figure 10 Calcium antagonism of the dihydropyridine lactones (6) plot of the angular deviation Aa vs. KI (reproduced from Figure 6 of ref [349] with permission from the copyright owner).

The poisoning effects of foreign metals are often traceable to cation antagonism. Thus lead, a well-known neurotoxin, displaces calcium from several parts of the nervous system, thus hindering release of neurotransmitters (Kober and Cooper, 1976). The widespread contamination by cadmium on the West Coast of Japan, coupled with a low calcium intake, caused the painful disease itai itai , a form of osteomalacia, around 1960. This turned out to be a straightforward case of cadmium—calcium antagonism (Friberg, 1974). 

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