Interference with calcium conductance

Class IV anti-arrhythmic drugs usually interfere with calcium conductance such as verapamil hydrochloride. Verapamil inhibits the aetion potential of the upper and middle nodal regions of the heart where the slow inward ealeium-ion-mediated current contributes to depolarisation. This is responsible for the bloekade of slow-ehannel eonduetion in the atrioventricular node. It has been found to inhibit one limb of the re-entry circuit which is assumed to underlie most paroxysmal supraventricular tachycardias, thereby causing the reduction of ventricular rate in atrial flutter and fibrillation. 

The pharmacologic and toxicologic mechanisms of the calcium channel blockers are complex. They include interference with electrical conduction through the atrioventricular node, decreased myocardial contractility, and direct vasodilation. Calcium channel blockers also interfere with pancreatic release of insulin. 

The interference with electrical conduction through the atrioventricular node is caused by interference with the influx of calcium in phase II of the action potential and manifest by bradycardia, lengthening of the PR interval, QRS widening, and QTc prolongation. 

Calcium-channel blockers interfere with the inward movement of calcium ions through the cell membrane channels. This results in reduction of myocardial contractility (hence negative inotropes), reduction of cardiac output and arteriolar vasodilatation. The dihydropyridine group, such as nifedipine and amlodipine, which may be used in the management of hypertension, are very effective as arterial vasodilators, whereas diltiazem and verapamil are very effective in reducing atrioventricular conduction. 

The worker heart muscle cells (as opposed to the cells in the conduction system, which are also specialized muscle cells) are peculiar in using both Na and Ca in the depolarization phase of the action potential (Figure 5.8b, bottom). While they do not normally create action potentials themselves, under pathological conditions some of them may show spontaneous discharge. This depolarization may then spread across the entire heart (or parts of it) and interfere with normal and regular activity. While both calcium and sodium channel blockers have their applications in treating heart arrhythmias, the beauty of the sodium channel blockers is that they will not interfere with the activity of the regular pacemakers (since those essentially don t use sodium channels). Another beneficial feature was pointed out above Lidocaine extends the duration of the inacti-... 

Although they are chemically heterogeneous, many adverse effects are common to all calcium channel blockers, predictable from their pharmacological actions. Calcium plays a role in the functions of contraction and conduction in the heart and in the smooth muscle of arteries drugs that interfere with its availability (of which there are many, the calcium channel blockers being the most specific) will therefore act in all these tissues. A few idiosjmcratic and hypersensitivity reactions have also been reported with individual calcium channel blockers. 

The clinical effects of the calcium channel blockers are primarily cardiovascular in nature. Due to their interference with conduction, they can cause a variety of dysrrhythmias including sinus bradycardia,... 

The digitalis glycosides interfere with the Na, K -ATPase pump with a resultant intracellular loss of potassium and intracellular increases in sodium and calcium. The net effects of this are increased myocardial contractility and decreased cardiac conduction. 

Anorexia, nausea, vomiting, visual disturbances, and the cardiac effects seen in acute toxicity may be seen. In chronic exposures, patients may not demonstrate the classic finding of hyperkalemia, which is frequently seen in acute exposures. Decreased renal function may interfere with clearance of the glycosides. Patients may be more sensitive to the effects of their squill remedies if they are on medication that also slows AV conduction such as quinine, beta blockers, or calcium channel blockers. 

Industrial grade NaCl has a content of 92-98%. The precipitation titration can be conducted using 0.1 N AgNO, as the titrant and 5% K,Ci<) as the indicator (the Mohr method). The sample chloride solution should be buffered with calcium carbonate to a pH between 6.3 and 7.2 in order to avoid any interference from other... 

Drugs that demonstrate calcium inhibitory activity display different cardiac membrane effects dependent upon their structure, physical properties and concentration. Compounds which interfere with Ca + influx are expected to prolong the duration of the action potential. This prediction is supported by evidence that decreased intracellular Ca2+ activity may decrease the late increase in K+ conductance and potentially prolong the duration of repolarization (phase 3) (69). The first substances reported to inhibit I without influencing rapid depolarization (phase 0) were Mn2+, Ni2+ and Co2+ (16,... 

Features of lithium-induced hyperparathyroidism include a) a low urinary calcium excretion and the absence of nephrolithiasis b) normal urinary cyclic adenosine monophosphate excretion and c) normal plasma inorganic phosphate [30]. In lithium-induced hypercalcemia, a higher frequency of conduction defects has been noted [42]. Lithium also inhibits parathyroid hormone-mediated renal reabsorption of Ca and Mg and blunts parathyroid hormone-mediated phos-phaturia [43]. Lithium interferes with the formation of renal cyclic adenosine monophosphate, which is regulated by parathyroid hormone. Levels of minary cy-... 

Cathodic inhibitors in near-neutral solutions interfere with the oxygen reduction reaction by restricting the diffusion of dissolved oxygen to the electrode surface. These substances usually form thick surface layers with poor electronic conductivity (the latter is an important prerequisite to avoid oxygen reduction on the film surface). Examples are phosphates, polyphosphates, silicates, borates, and inorganic inhibitors, such as Zn +, which precipitate as Zn hydroxide, and Ca ", which forms calcium carbonate films in the presence of CO3 [3]. These inhibitors... 

Ammonium is determined in many laboratories in a CF system in which the Berthelot reaction is implemented. In the Berthelot reaction, ammonium reacts with chlorine and phenol in the presence of sodium nitroprusside as catalyst in alkaline medium. EDTA is added to prevent interference of calcium and magnesium. Modern systems have been developed that use macroporous polytetrafluoroethylene (PTFE) membranes. In these systems a sample is introduced into a stream to which sodium hydroxide solution is added. Ammonia diffuses through the PTFE membrane into a stream of de-ionized water and the stream is fed through the flow-through cell of a conductivity meter. In this system a minimum of reagents is required and the only interference is from volatile amines. 

Pumiliotoxin B had no apparent effect on sodium, potassium or chloride conductances or on resting membrane potential 24). The potentiative effects of pumiliotoxin B were fully manifest in preparations in which acetylcholine receptors were blocked by a-bungarotoxin. Dantrolene, an agent which appears to interfere with release of calcium from the sarcoplasmic reticulum and methoxyverapamil, a purported antagonist of calcium channels, only partially prevented the effects of pumiliotoxin B on muscle contractions. 

Bell [526] analyzed transition metals together with magnesium and calcium utilizing ion pair chromatography on a chemically bonded reversed-phase column, which can be combined with both nonsuppressed conductivity detection and photometric detection after derivatization with PAR. Because Bell used predominantly ashed fermentation samples, his chromatograms are free of interferences. Simultaneous separations of alkali and alkaline-earth metals in methanotropic bacterial cultures and other media on surface-sulfonated... 

---