Lithium nervous system

Isolated seizures that are not epilepsy can be caused by stroke, central nervous system trauma, central nervous system infections, metabolic disturbances (e.g., hyponatremia and hypoglycemia), and hypoxia. If these underlying causes of seizures are not corrected, they may lead to the development of recurrent seizures I or epilepsy. Medications can also cause seizures. Some drugs that are commonly associated with seizures include tramadol, bupropion, theophylline, some antidepressants, some antipsy-chotics, amphetamines, cocaine, imipenem, lithium, excessive doses of penicillins or cephalosporins, and sympathomimetics or stimulants. 

Lithium Neonatal central nervous system and cardiovascular disturbances... 

Nonaka S, Chuang DM. Chronic lithium treatment robustly protects neurons in the central nervous system against excitotoxicity by inhibiting N -methyl-D-aspartate receptor-mediated calcium influx. Proc Natl Acad Sci USA 1998 95 2642-2647. 

Solutions and powders of several lithium salts are very toxic to the human nervous system, thus requiring close observation by a physician when used as antidepressant drugs. 

Concurrent administration of lithium and selective serotonin re-uptake inhibitors, such as paroxetine, results in an increased risk of central nervous system effects and lithium toxicity has been reported. 

Outside its therapeutic range, lithium has a wide range of undesirable effects. Nervous system-related effects include tremor, difficulty walking, seizures, slurred speech, and mental confusion. In addition there can be cardiovascular effects, nausea, vomiting, and kidney damage. 

Bher P, de Montigny C Lack of efficacy of hthium augmentation in obsessive-compulsive disorder the perspective of different regional effects of lithium on serotonin release in the central nervous system. J Chn Psychopharmacol 12 65-66, 1992... 

Hong J-S, Tilson HA, Yoshikawa K Effects of lithium and haloperidol administration on the rat brain levels of Substance P. J Pharmacol Exp Ther 224 590-597, 1983 Honig A, Bartlett JR, Bouras N, et al Amino acid levels in depression a preliminary investigation. J Psychiatr Res 22 159-164, 1989 Honjo H, Ogino Y, Natitoh K, et al In vivo effects by estrone sulphate on the central nervous system on senile dementia [Alzheimer s type). Journal of Steroid Biochemistry 34 521-525, 1989... 

Lee G, lingsch C, Lyle PT, et al Lithium treatment strongly inhibits choline transport in human erythrocytes. Br J Chn Pharmacol 1 365-370, 1974 Lee KF, li E, Huber J, et al Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral nervous system. Cell 69 737-749, 1992... 

Lithium Mechanism of action uncertain suppresses inositol signaling and inhibits glycogen synthase kinase-3 (GSK-3), a multifunctional protein kinase No significant antagonistic actions on autonomic nervous system receptors or specific CNS receptors no sedative effects Bipolar affective disorder-prophylactic use can prevent mood swings between mania and depression Oral absorption, renal elimination half-life 20 h. narrow therapeutic window (monitor blood levels) Toxicity Tremor, edema, hypothyroidism, renal dysfunction, dysrhythmias pregnancy category D Interactions Clearance decreased by thiazides and some NSAIDs... 

Renal lithium excretion sensitive to changes in sodium balance. (Sodium depletion tends to cause lithium retention.) Susceptible to drugs enhancing central nervous system lithium toxicity. 

Methyldopa [NE] Increased likelihood of central nervous system lithium toxicity. 

The tertiary members of these classes (Figure 8-2) are often used for their effects on the eye or the central nervous system. Many antihistaminic (see Chapter 16 Histamine, Serotonin, the Ergot Alkaloids), antipsychotic (see Chapter 29 Antipsychotic Agents Lithium), and antidepressant (see Chapter 30 Antidepressant Agents) drugs have similar structures and, predictably, significant antimuscarinic effects. 

Unlike antipsychotic or antidepressant drugs, which exert several actions on the central or autonomic nervous system, lithium ion at therapeutic concentrations is devoid of autonomic blocking effects and of activating or sedating effects, though it can produce nausea and tremor. 

Katzung PHARMACOLOGY, 9e > Section V. Drugs That Act in the Central Nervous System > Chapter 29, Antipsychotic Agents Lithium > ... 

Lithium ion, Li+, is a central nervous system toxicant that causes dizziness, prostration, anorexia, apathy, and nausea. It can also cause kidney damage and, in large doses, coma and death. 

There seems no reason, therefore, to eschew the description of lithium therapy as the treatment of manic patients by lithium poisoning, in the words of an early critic (Wikler 1957). Anticonvulsants do not share the toxicity profile of lithium, but by virtue of their use to prevent epileptic fits, they all exert depressant effects on the activity of the central nervous system. With this profile of drug-induced effects in mind, let us examine the research on whether lithium or other drugs currently used in manic depression act in a disease-centred way and consider whether they have any real benefits. 

Since the drug s primary action is mediated through the central nervous system, it is not surprising that lithium can cause cognitive... 

Lithium disrupts almost every measurable cellular activity pertaining to nerve transmission as well as many other vital functions. In addition, its distribution is fairly uniform throughout the central nervous system, with no known areas of specific concentration. It produces what Wilson et al. (1975) called a nonselective diminution in neuronal activity. The neurophysiology of lithium, even without supporting clinical data, renders absurd the notion of a specific biochemical treatment for a specific disease and confirms the brain-disabling effect. 

Lithium also impairs the function of the peripheral nervous system, reducing motor nerve conduction velocity (Faravelli et al., 1999). It causes many metabolic adverse effects, resulting in hypothyroidism, hyperthyroidism (rare), hyperparathyroidism, and diabetes insipidus (Livingston et al., 2006). 

Of as yet unknown consequence to the brain and nervous system, there are many studies indicating that valproic acid promotes a variety of potentially dangerous viruses (e.g., Fan et al., 2005). Both valproic acid and carbamazepine cause a small increase in the rate of major congenital malformations in infants (Wide et al., 2004). Acute and potentially fatal pancreatitis has been reported with valproic acid (e.g., Grauso-Eby et al., 2003). Liver failure is a known problem as well. Valproic acid is known to cause hyperammonemia with encephalopathy (e.g., McCall et al., 2004). Severe and even lethal skin disorders can occur with all of the antiseizure medications now used as mood stabilizers. The various adverse effects of valproic acid and other mood stabilizers are not nearly as benign as physicians believe in their eagerness to switch patients from lithium. 

Dawson, E. B., Moore, T. D., McGanity, W. J. (1970). The mathematical relations of drinking water, lithium, and rainfall to mental hospital admissions. Diseases of the Nervous System, 31, 811-820. 

Faravelli, D., Di Bernardo, M., Ricca, V., Benvenuti, P., Bartelli, M., Ronchi, O. (1999). Effects of chronic lithium treatment on the peripheral nervous system. Journal of Clinical Psychiatry, 60, 306-310. 

Juhl, R., Tsuang, M., Perry, P. (1977). Concomitant administration of haloperidol and lithium carbonate in acute mania. Diseases of the Nervous System, 38, 675-676. 

Morrison, S., Erwin, C., Gionturco, D., Gerber, C. (1973). Effect of lithium on combative behavior in humans. Diseases of the Nervous System, 34, 186-189. 

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