Brain sodium concentration effects

We have also defined both the effect of veratridine concentration on sodium channel activation in this system and the impact of , -DDT on the concentration-effect curve for veratridine-dependent activation (Figure 5). Half-maximal activation by veratridine oc-cured at approximately 50 PM, a value very close to that found for the action of this compound in mouse brain synaptosomes (7. , -... 

Clinical effects of lithium are slow in onset and may not be apparent before a week or two of daily treatment. Lithium is cleared exclusively by the kidney at a rate 20% of that of creatinine. Clearance is influenced by many factors, including renal function, serum sodium concentration, hydration state, pregnancy, and the presence of other drugs. High urinary levels of sodium inhibit renal tubular reabsorption of lithium, thus decreasing its plasma levels. By decreasing blood volume, thiazides may increase lithium plasma levels. Any drug that can cross the blood-brain barrier can cross the placental barrier The answer is (C). 

Tamplin et. al. (54) observed that V. cholerae and A. hydrophila cell extracts contained substances with TTX-like biological activity in tissue culture assay, counteracting the lethal effect of veratridine on ouabain-treated mouse neuroblastoma cells. Concentrations of TTX-like activity ranged from 5 to 100 ng/L of culture when compared to standard TTX. The same bacterial extracts also displaced radiolabelled STX from rat brain membrane sodium channel receptors and inhibited the compound action potential of frog sciatic nerve. However, the same extracts did not show TTX-like blocking events of sodium current when applied to rat sarcolemmal sodium channels in planar lipid bilayers. 

As lithium is an alkaline earth metal which readily exchanges with sodium and potassium, it is actively transported across cell membranes. The penetration of kidney cells is particularly rapid, while that of bone, liver and brain tissue is much slower. The plasma CSE ratio in man has been calculated to be between 2 1 and 3 1, which is similar to that found for the plasma red blood cell (RBC) ratio. This suggests that the plasma RBC ratio might be a useful index of the brain concentration and may be predictive of the onset of side effects, as these appear to correlate well with the intracellular concentration of the drug. 

No histological alterations were observed in the brains of rats exposed for 2 weeks to a dust of 4-nitrophenol sodium salt at concentrations of up to 2,119 mg 4-nitrophenol/m (Smith et al. 1988). Gross and histological examination of the brain, spinal cord, and peripheral nerves of rats exposed to up to 30 mg 4-nitrophenol dust/m for 4 weeks revealed no treatment-related effects (Hazleton 1983). However, since neurological tests were not performed in these studies, reliable NOAELs for neurological effects cannot be determined. 

Lidocaine is structurally similar to cocaine, which was the first clinically useful local anaesthetic (Figure 5.4). The stimulating effect of cocaine, however, is due to its effect on a second, different receptor in the brain that indirectly amplifies the effect of dopamine and norepinephrine (we will deal with this matter in a later lecture). This effect is actually observed at concentrations lower than those required for the blocking of sodium channels. Yet, local application of cocaine will result in very high concentrations that will... 

Cerebral effects can complicate thoracic aortography when excessive doses of concentrated agent are injected, particularly if the catheter is sited so that the major dose of contrast agent is directed into the cerebral circulation. In one case, 10 ml of sodium iotalamate 70% was injected into the carotid artery, being mistaken for methylgluca-mine iotalamate 60% this was followed by an immediate convulsion, with loss of consciousness for 2 minutes. The patient at first appeared to have recovered completely, but hemiparesis followed and persisted for some 24 hours. Such changes are presumably due to cerebral edema after transient damage to the blood-brain barrier. 

---