Calcium channel agonists blockers

A large number of diugs interfere with the smooth muscle contraction. These compounds lower blood pressure and are referred to as antihypertensive. In this section, only those coumpounds will be mentioned that have a direct effect on smooth muscle tone. Phenylephrine is an agonist on most smooth muscles and activates ax adrenoceptors. Carbachol is an agonist on some smooth muscles and activates contraction through muscarinic receptors. Blockers of the ax-adrenoceptors such as prazosin and urapidil are competitive inhibitors of the ax-receptor in vascular and bladder smooth muscle. Phenoxybenzamine is an ineversible blocker of ax receptors and phentol-amine blocks ax and a2 receptors. Ca2+ channel blockers such as the dihydropyiidines, phenylalkyla-mines and benzothiazepines lower smooth muscle tone by blocking the L-type calcium channel. 

Drugs most commonly used for acute tocolysis include magnesium sulfate, -adrenergic agonists, NSAIDs, and calcium channel blockers. 

The following drug classes may have a potential drug interaction with nevirapine Antiarrhythmics, anticonvulsants, antifungals, calcium channel blockers, cancer chemotherapy (cyclophosphamide), ergot alkaloids, immunosuppressants, motility agents, opiate agonists. 

Iodinated radiographic contrast media can cause acute renal insufficiency, perhaps as a result of reduced renal blood flow, an intrarenal osmotic effect, or direct tubular toxicity (58). Diuretics, calcium channel blockers, adenosine receptor antagonists, acetylcysteine, low-dose dopamine, the dopamine Di receptor agonist fenoldopam, endothelin receptor antagonists, and captopril have all been used to prevent contrast nephropathy. 

Figure 7.12 Diagrammatic representation of cross section of calcium channel showing various sites that bind drugs and toxins. Bay K 8644, atrotoxin and maitotoxin are agonists (activators) of calcium channels. Nifedipine, verapamil, and diltiazem are antagonists (blockers) of calcium channels. (From Eldefrawi, M.E. and Eldefrawi, A.T., in Safe Insecticides Development and Use, Hodgson, E. and Kuhr, R.J., Eds., Marcel Dekker, New York, 1990, p. 155. With permission.)...

However, the studies on the calcium channel blockers remained centered even today around the l,4-dihydropyridine class. Since this class of compounds can also act as calcium channel activators, attention has always been drawn towards their structure-activity relationship studies. Attempts were made to differentiate in the mechanisms of their agonist and antagonist activities. On the basis of the force field and quantum mechanical calculations, Holtze and Marrer [51] discovered a imique area of the molecular potentials where Ca agonists and antagonists possess potential of opposite sign. These authors demonstrated that the molecular potential of a simple receptor site was reduced by interaction with calciiun channel activators and, on the contrary, increased by interaction with calcium channel blockers. These opposite effects probably could be the basis for the opposite actions of DHP enantiomers at the potential-dependent calcium channel. 

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