1. Furosemide 40 to 240 mg IV over 30 minutes 2. Ethacrynic acid 50 to 100 mg IV over 30 minutes 3. Bumetanide 1 to 8 mg IV over 30 minutes Copyright ©2004 Lippincott Williams & Wilkins Samuels, Martin A. Manual of Neurologic Therapeutics, 7th Edition VITAMIN DEFICIENCY, DEPENDENCY, AND TOXICITY Part of "16 - Toxic and Metabolic Disorders" VITAMIN A BACKGROUND 1. Vitamin A deficiency is an important cause of blindness in large parts of the world but is rare in economically developed countries. 2. Vitamin A intoxication is seen in people who engage in megavitamin therapy. PATHOPHYSIOLOGY In many developing countries, general malnutrition is the major cause of vitamin A deficiency whereas in developed countries it is usually related to malabsorption or an unconventional diet. PROGNOSIS 1. If treated early, the neurologic manifestations are usually completely reversible. 2. Once blindness has occurred, little can be done to reverse the visual loss. DIAGNOSIS 1. Night blindness and dry eyes are probably the earliest symptoms of vitamin A deficiency. 2. Dry pruritic skin is also an early symptom of this deficiency. TREATMENT 1. Vitamin A 1,000 units daily for 6 months and restoration of a normal diet for early disease. 2. Vitamin A up to 100,000 units daily for 6 months with restoration of a normal diet may be needed for moderate or advanced symptoms. Long-term use of vitamin A is not advisable as it may produce hypercoagulable state with consequent increased intracranial pressure (ICP) (pseudotumor cerebri) possibly caused by cerebral venous thrombosis. Treatment consists of discontinuation of the vitamin A. VITAMIN B 1 (THIAMINE) DEFICIENCY BACKGROUND 1. Vitamin B 1 (thiamine) deficiency occurs in parts of the world where polished rice is a major dietary staple or in people who are malnourished for any reason. 2. In developed countries, it is strongly linked to alcoholism. P.485 PATHOPHYSIOLOGY Thiamine is the coenzyme in thiamine pyrophosphate catalysis of decarboxylation of pyruvic acid and α-ketoglutaric acid. PROGNOSIS Treatment of Wernicke encephalopathy [the central nervous system (CNS) disease caused by thiamine deficiency] is usually quite successful, but the longer treatment is delayed the greater the probability of irreversible brain disease. DIAGNOSIS 1. Thiamine deficiency should be assumed to be present in all malnourished people including, but not limited to, those with alcoholism. 2. The full triad of Wernicke encephalopathy (i.e., mental change, ataxia, and eye findings) is present in only a minority of those people later found to have Wernicke encephalopathy by pathologic study. 3. Measurement of 24-hour urine thiamine excretion is available and red blood cell transketolase may be measured. 4. For confirmation of the diagnosis, MRI may show lesions characteristic of Wernicke encephalopathy (i.e., small mamillary bodies and/or hypothalamic peri-third ventricular necrosis). TREATMENT 1. Thiamine 100 mg IV push followed by: 2. Thiamine 25 daily for several months and restoration of a normal diet. P.486 VITAMIN B 2 (RIBOFLAVIN) DEFICIENCY BACKGROUND Riboflavin deficiency is caused by general malnutrition or malabsorption. PATHOPHYSIOLOGY Riboflavin is a coenzyme in the flavoprotein enzyme system. PROGNOSIS Treatment is usually successful unless the disease is far advanced. DIAGNOSIS 1. The clinical syndrome of cheilosis, angular stomatitis, visual loss, night blindness, glossitis, and burning feet in a susceptible person suggests the diagnosis. 2. Urinary 24-hour riboflavin excretion measurements are available (less than 50 µ/24 hours) but are rarely used except in problematic diagnostic dilemmas. TREATMENT 1. Riboflavin 5 mg p.o. three times a day (t.i.d.). 2. Vitamin A replacement may help in relieving riboflavin induced ocular symptoms (see Treatment section of Vitamin A, above). 3. Restoration of a normal diet. NIACIN (NICOTINIC ACID AND NICOTINAMIDE) DEFICIENCY BACKGROUND Niacin deficiency (pellagra) is usually associated with general malnutrition, often with alcoholism. PATHOPHYSIOLOGY Niacin is the coenzyme for nicotinamide dinucleotide codehydrogenase for the metabolism of alcohol, lactate and L-hydroxybutyrate. PROGNOSIS Untreated pellagra is lethal, but if recognized during life will usually respond favorably to therapy. DIAGNOSIS 1. The characteristic triad of dermatitis (sun sensitivity followed by hyperpigmentation), diarrhea, and mental symptoms (usually a disorder of attention and/or mood followed by confusion, drowsiness, stupor, and coma) suggests the diagnosis in the setting of malnutrition. 2. The diagnosis can be confirmed with a 24-hour urinary niacin excretion of less than 3 mg/24 hours. TREATMENT 1. Niacin or nicotinamide 50 mg p.o. ten times daily for 3 weeks. 2. In patients unable to take oral feedings, nicotinamide may be given IV 100 mg/d for 5 to 7 days. 3. Resumption of a normal diet is important for long-term recovery. 4. If pyridoxine deficiency is also deemed to be present (e.g., isoniazid therapy), vitamin B 6 (pyridoxine) must also be replaced as it is required for the normal conversion of tryptophan to niacin. VITAMIN B 6 (PYRIDOXINE) DEFICIENCY, DEPENDENCY, AND TOXICITY BACKGROUND 1. Pyridoxine deficiency is rarely seen in developed countries except in people who are taking isoniazid, an antituberculosis drug that is an antagonist of pyridoxine. 2. Cycloserine, hydralazine, and penicillamine also may lead to pyridoxine deficiency. 3. Pyridoxine toxicity is seen in people who take more than the recommended daily allowance of 2 mg because of perceived health benefits of megavitamin therapy. PATHOPHYSIOLOGY Pyridoxine is a cofactor in the conversion of tryptophan to 5-hydroxytryptophan and the conversion of homocysteine to cystathionine. PROGNOSIS Treatment usually results in complete resolution of the complaints. P.487 DIAGNOSIS 1. Pyridoxine deficiency causes a generalized sensory and motor neuropathy. 2. Pyridoxine dependency is a rare autosomal recessive condition that leads to neonatal seizures. 3. Pyridoxine overuse also causes a peripheral neuropathy. a. Long-term low-dose (about 50 mg/d) exposure to pyridoxine leads to a small-fiber neuropathy. b. Shorter exposure to very high doses (over 100 mg/d) may produce a primary sensory neuronopathy that is less likely to improve with cessation of exposure to the vitamin. TREATMENT 1. Pyridoxine deficiency caused by: a. Malnutrition: 50 mg/d p.o. for several weeks followed by 2 mg/d and resumption of a normal diet. b. Pyridoxine antagonists: 50 mg/d only while taking the antagonist. 2. Pyridoxine dependency: 10 mg IV push to terminate neonatal seizures and then 75 mg/d for life. 3. Pyridoxine toxicity: discontinue pyridoxine supplementation. VITAMIN B 12 (COBALAMIN) DEFICIENCY BACKGROUND 1. Vitamin B 12 deficiency may result from inadequate dietary intake, but this is rare as the daily requirement is small (2 µg/d) and the body stores are high (4 mg or about a 7-year supply). 2. Vegans who assiduously avoid animal protein may become cobalamin-deficient but this process requires many years. 3. More commonly, cobalamin deficiency is caused by failure to mobilize vitamin B 12 from the GI tract because of insufficient intrinsic factor, most often caused by autoimmune gastritis (pernicious anemia). a. Aging alone may lead to enough gastric parietal cell atrophy to cause intrinsic factor deficiency and consequent vitamin B 12 deficiency. b. In rare circumstances, the ingested cobalamin may be consumed before absorption by a parasite (the fish tapeworm Diphyllobothrium latum) or be inaccessible to cells because of a genetically determined deficiency in one of the cobalamin- carrying proteins (transcobalamin I and II). c. Human immunodeficiency virus (HIV) may lead to abnormal cobalamin function by an unknown mechanism, possibly involving abnormal transmethylation. PATHOPHYSIOLOGY 1. Cobalamin is bound to salivary R protein. In the duodenum, pancreatic enzymes digest the R protein allowing cobalamin to be bound to intrinsic factor that is synthesized in gastric parietal cells. The cobalamin-intrinsic factor dimer is absorbed by specific receptors in the microvilli of the distal ileum. The newly absorbed cobalamin enters the portal circulation bound to transcobalamin II. Transcobalamin I is bound to previously absorbed cobalamin. 2. Inside cells, cobalamin is converted to its two active forms, methylcobalamin and adenosylcobalamin. a. Methylcobalamin is the coenzyme for the enzyme methionine synthetase (also known as methyl transferase), which catalyzes the conversion of homocysteine to methionine. Cobalamin is then remethylated to methylcobalamin by a methyl group donated by methyl tetrahydrofolate (serum folate). By this process, the P.488 demethylated folate may participate in the formation of thymidylate, which is required for DNA synthesis. These interlocking reactions account for the fact that many of the clinical manifestations of vitamin B 12 and folate deficiencies are similar. b. Cobalamin also participates in an important metabolic pathway that is independent of folate. In mitochondria, adenosylcobalamin acts as a coenzyme for the enzyme methyl malonyl coenzyme A (CoA) mutase that catalyzes the conversion of methyl malonyl CoA to succinyl CoA. Thus homocysteine and methylmalonic acid act as biologic markers for the intracellular effectiveness of cobalamin's two coenzymes. PROGNOSIS 1. The clinical features of the cobalamin deficiency syndrome are dominated by a demyelinating process of the CNS affecting the lateral and posterior columns of the spinal cord (subacute combined degeneration), the white matter of the brain, and the optic nerves. A peripheral neuropathy may also be present. 2. Patients usually present with upper extremity paresthesias followed by stiffness of the legs, slowness of thinking, and reduced visual acuity. For unknown reasons, the optic neuropathy or mental change may dominate the clinical picture in some patients. 3. Most of the manifestations of the disease are reversible with appropriate therapy, but far-advanced disease may not completely respond. 4. Exposure to nitrous oxide may precipitate an acute presentation of cobalamin deficiency (anesthesia paresthetica) as it is a blocker of methyl transferase, one of the enzymes for which cobalamin is a coenzyme. DIAGNOSIS 1. Hypersegmented (i.e., greater than five lobes) polymorphonuclear leukocytes are often seen on the peripheral blood smear. 2. Bone marrow may show megaloblasts (i.e., red blood cell precursors with a relatively immature nucleus compared to the cytoplasm). 3. Vitamin B 12 levels are usually low: a. When less then 100 pg/mL, cobalamin deficiency is likely. b. When between 100 and 180 pg/mL, cobalamin deficiency is possible. c. When over 180 pg/mL cobalamin deficiency is unlikely. 4. Serum methylmalonic acid is the most specific test for intracellular cobalamin failure. Levels above 0.5 µmol/L suggest intracellular cobalamin failure. 5. The Schilling test may be useful to determine the cause of vitamin B 12 deficiency. a. Phase I is aimed at determining whether the patient can absorb crystalline vitamin B 12 . b. Phase II identifies those who are vitamin B 12 — deficient because of intrinsic factor deficiency. c. The food Schilling test, in which radiolabeled vitamin B 12 is attached to egg albumin, is used to identify those patients who are unable to extract vitamin B 12 from food because of an inadequately acidic environment. 6. Anti—intrinsic factor antibodies are specific but insensitive for autoimmune gastritis. 7. Anti — parietal cell antibodies are sensitive but not specific for autoimmune gastritis. TREATMENT 1. Cyanocobalamin 1,000 µg IM daily for 1 week, followed by weekly injections for 1 month, followed by monthly injections for life. 2. Cyanocobalamin 1 mg/d p.o. may be effective, but methylmalonic acid levels should be monitored to ensure that the treatment is having the expected metabolic effect. 3. Discontinue any exposure to nitrous oxide. P.489 VITAMIN B 9 (FOLATE) BACKGROUND 1. Folate is synthesized by plants and microorganisms. Its major dietary source is green leafy vegetables. 2. The daily requirement is 50 µg except in pregnant and lactating women when it is increased approximately tenfold. 3. Folate is ingested as a polyglutamate, which is metabolized to pteroylmonoglutamate and absorbed in the jejunum. In the bowel mucosal cells, it is reduced to tetrahydrofolate and methylated to methyl-tetrahydrofolate (serum folate). 4. Only about a 12-week supply of folate is stored in the body, so folate deficiency may become rapidly evident with malnutrition. PATHOPHYSIOLOGY 1. Folate interacts intimately with vitamin B 12 (cobalamin). Serum folate (methyl-tetrahydrofolate) is the methyl donor that reconstitutes cobalamin into methylcobalamin in the conversion of homocysteine to methionine. Thus, homocysteine levels are a reflection of the effectiveness of both folate and vitamin B 12 in the methyltransferase (methionine synthetase) reaction. 2. Once demethylated, tetrahydrofolate undergoes polyglutamation and is converted to 5,10-methylene tetrahydrofolate, which, catalyzed by thymidylate synthase, generates deoxythymidine monophosphate for the synthesis of the thymidine needed for DNA synthesis. 3. Vitamin B 12 deficiency causes release of folate from cells and interferes with its utilization, thereby leading to an elevated serum folate level (the folate trap). 4. When vitamin B 12 is repleted, the folate level may precipitously fall, leading to a folate-deficiency state unmasked by the cobalamin therapy. PROGNOSIS 1. Pure folate deficiency is rare as it is usually associated with generalized malnutrition, but it may be seen when folate inhibitors are used (e.g., methotrexate and sulfonamides are inhibitors of dihydrofolate reductase and phenytoin interferes with folate absorption). 2. It is clear that folate deficiency during gestation causes neural tube defects. 3. In adults, pure folate deficiency probably causes a sensory — motor polyneuropathy. In most cases, folate repletion leads to reversal of the neurologic deficits and adequate provision of folate during pregnancy reduces the risk of neural tube defects. DIAGNOSIS 1. The blood and bone marrow changes of folate deficiency are indistinguishable from those caused by vitamin B 12 deficiency. 2. A serum folate level is specific but not particularly sensitive. 3. If the serum folate level is normal, but folate deficiency is suspected on clinical grounds, a red blood cell folate level should be obtained because it reflects the average intracellular folate level over the life span of the red blood cell and therefore is not unduly affected by recent dietary intake. TREATMENT 1. Folic acid 1 mg/d p.o. 2. Resumption of a normal diet. 3. For patients on folate antagonists, folinic acid (leucovorin, citrovorum factor) 15 mg p.o. every 6 hours for 10 doses starting 24 hours after the dose of methotrexate is given. If folate deficiency develops from phenytoin, another antiepileptic drug P.490 should be chosen, because folate replacement may reduce the antiepileptic efficacy of phenytoin. VITAMIN C (ASCORBIC ACID) BACKGROUND Vitamin C deficiency (scurvy) is rare in developed countries, occurring almost exclusively in generally malnourished people who are poor, elderly, alcoholic, or adherents of unusual diets. PATHOLOGY 1. Ascorbic acid is found in citrus fruits, green vegetables, and tomatoes and is absorbed from the small intestine via a transport system. 2. It has multiple functions, including acting as an antioxidant, a promoter of iron absorption, and a cofactor in the conversion of dopamine to norepinephrine and the synthesis of carnitine. 3. Consuming less than 10 mg of ascorbic acid daily will result in deficiency in a few months. PROGNOSIS 1. Vitamin C deficiency (scurvy) is characterized by symptoms and signs of abnormal connective tissue such as perifollicular hemorrhages and bleeding from the gums. Neurologic symptoms include weakness, fatigue, depression, and confusion. 2. Treatment usually results in complete remission of the clinical syndrome. 3. Megadoses of vitamin C (i.e., greater than 2 g/d) may result in GI bleeding and oxalate kidney stones, but no hypervitaminosis C syndrome of the nervous system is known. DIAGNOSIS A plasma level of vitamin C of less than 11 µmol/L is considered abnormal, but most patients with clinical scurvy with neurologic impairment have an undetectable plasma vitamin C level. TREATMENT Vitamin C (ascorbic acid) 100 mg q.i.d. for 1 week followed by 100 mg t.i.d. for 1 month and resumption of a normal diet. VITAMIN D BACKGROUND 1. Vitamin D (1,25-dihydroxycholecalciferal; vitamin D 3 ) is the least classic of the vitamins in that it can be synthesized in the skin in adequate amounts for metabolic needs provided there is adequate sun exposure. 2. Vitamin D deficiency or resistance is the cause of rickets in the growing skeleton and osteomalacia in adults. P.491 PATHOPHYSIOLOGY 1. Ultraviolet radiation converts provitamin D 3 (dihydrocholesterol) to vitamin D 3 in the skin. 2. In the liver, vitamin D 3 is converted to hydroxylated D 3 and then in the liver a final hydroxylation step is performed to yield the biologically active vitamin D (1,25 dihydroxyvitamin D 3 ). PROGNOSIS 1. Vitamin D metabolism is intimately linked with numerous disorders of calcium and phosphate metabolism. The precise prognosis varies depending on the cause of the disorder. 2. In vitamin D deficiency related to intestinal malabsorption in adults, the symptoms may be expected to dramatically improve with vitamin D repletion. DIAGNOSIS 1. Vitamin D deficiency causes a syndrome of pain and proximal muscle weakness. It is suspected when a painful myopathic syndrome is encountered in a patient who is at risk for osteomalacia (e.g., inadequate exposure to sunlight; antiepileptic drug treatment; hepatic and/or renal failure; inadequate dietary vitamin D). 2. Vitamin D levels can be measured in the serum to confirm the diagnosis. TREATMENT 1. For dietary deficiency or inadequate exposure to sunlight: vitamin D 2 (ergocalciferol) or vitamin D 3 (cholecalciferol) 800 to 4,000 IU (0.02 — 0.1 mg) daily for 8 weeks, followed by 400 IU/d until the cause (e.g., inadequate exposure to light or inadequate diet) is resolved. 2. For tetany: calcium gluconate 10% 10 to 20 mg IV. 3. For patients on antiepileptic drugs: add 1,000 IU/d and monitor serum calcium and 1,25-hydroxyvitamin D 3 levels. VITAMIN E (TOCOPHEROL) BACKGROUND 1. Vitamin E is a family of fat-soluble tocopherols, which is never deficient for dietary reasons. 2. All vitamin E deficiency is due to severe malabsorption or genetic disorders that affect the transport or receptors for vitamin E. PATHOPHYSIOLOGY 1. Of the eight naturally occurring tocopherols, RRR-α-tocopherol is the most biologically active. 2. It is taken up by the liver as chylomicrons, incorporated into very-low-density lipoprotein, and stored in brain, fat, and muscle. 3. Abetalipoproteinemia causes severe vitamin E deficiency by reducing both absorption and transport capacity. PROGNOSIS 1. Vitamin E deficiency and resistance is manifested in the nervous system as a spinocerebellar degeneration, sometimes with features of myopathy, progressive external ophthalmoplegia, and pigmentary retinopathy. P.492 2. Response to treatment depends on the precise cause, but early symptoms may respond well to vitamin E treatment. DIAGNOSIS 1. Serum tocopherol may be measured. 2. An α-tocopherol level of less than 5 µg/mL or less than 0.8 mg of tocopherol per gram of total lipid are considered diagnostic abnormalities. TREATMENT 1. For patients with pure vitamin E deficiency: α-tocopherol 800 to 1,200 mg/d 2. For patients with abetalipoproteinemia, α-tocopherol 5,000 to 7,000 mg/d VITAMIN K BACKGROUND Vitamin K is a family of fat-soluble quinones that are involved in the coagulation cascade. PATHOPHYSIOLOGY 1. Vitamin K 1 (phylloquinone) is found in vegetables, particularly leafy vegetables (e.g., spinach), and vitamin K 2 (menaquinone) is synthesized by gut flora. 2. The fat-absorption mechanisms mediated by the pancreas allow for absorption of vitamin K after which it may be stored in the liver and transported bound to lipoproteins. 3. Vitamin K is a cofactor necessary for the binding of calcium to a number of proteins involved with coagulation, including prothrombin. 4. Vitamin K deficiency may lead to bleeding including the predisposition for intracerebral, intraventricular, subarachnoid, subdural, and epidural hemorrhages. PROGNOSIS Treatment with vitamin K will rapidly reverse the coagulation abnormalities, but the prognosis depends on the location and extent of any hemorrhages that occurred prior to treatment. DIAGNOSIS 1. A prolonged prothrombin time in a susceptible person (i.e., a patent with known fat malabsorption, use of antibiotics that sterilize the bowel, use of warfarin, or in infancy) suggest vitamin K deficiency. 2. Vitamin K levels may also be obtained in problematic cases. TREATMENT Vitamin K 10 mg IV followed by 1 to 2 mg/d p.o. or 1 to 2 mg/wk parenterally until the underlying cause is resolved. Copyright ©2004 Lippincott Williams & Wilkins Samuels, Martin A. Manual of Neurologic Therapeutics, 7th Edition HEAVY-METAL POISONING Part of "16 - Toxic and Metabolic Disorders" P.493 LEAD BACKGROUND 1. Lead toxicity is an important cause of intellectual impairment. 2. Despite dramatic lowering of children's blood lead levels in recent years as a result of stringent public health policy in developed countries, low levels of lead toxicity are still a cause of long-term neuropsychological problems. PATHOPHYSIOLOGY 1. The most common cause of lead poisoning in children is residential remodeling. Inorganic lead is present in paints (both interior paints, which still line the walls of many older buildings, and modern exterior paints). 2. The organic lead compound tetraethyl lead is a gasoline additive, which is present in high concentrations in the atmosphere around tanks used to store gasoline and in dirt collected from urban areas near heavily traveled intersections and expressways. PROGNOSIS 1. Encephalopathy: a. Epidemiology: 1. Lead encephalopathy occurs in children who ingest large amounts of lead salts. 2. It occurs only rarely in adults and only in those exposed to tetraethyl lead, which is lipid-soluble and reaches high levels in the CNS. 3. In children, it is usually accompanied by pica, and it is most common between the ages of 1 and 3 years. 4. Lead encephalopathy is more common in summer than in winter. b. Signs and symptoms: 1. The usual symptoms of lead encephalopathy are personality change, lethargy, and irritability progressing to somnolence and ataxia, and finally, seizures, coma, and death. 2. In children, acute episodes of lead encephalopathy may recur, superimposed on a state of chronic lead intoxication. c. Prognosis: The mortality of acute lead encephalopathy is less than 5% in the best of hands, but 40% of victims are left with permanent and significant residual neurologic deficits, which may include dementia, ataxia, spasticity, and seizures. 2. Lead colic is the most common manifestation of lead poisoning in adults. a. The patient is anorectic and constipated, and often has nausea and vomiting. There is abdominal pain but no tenderness. Characteristically, the patient presses on the abdomen to relieve the discomfort. b. Lead colic generally accompanies lead encephalopathy in children. 3. Neuromuscular form: a. Slowing of motor nerve conduction velocity is an early sign of lead poisoning in children, but symptomatic neuropathy is rare. b. In adults, however, symptomatic neuropathy is common in lead poisoning. c. Typically, lead neuropathy is predominantly motor, but paresthesias and sensory changes may occur. d. Extensors are weakened before flexors, and the most used muscle groups (usually the extensors of the wrist) are involved earliest. 4. It is likely that chronic low-level lead exposure in children causes an attention deficit disorder with hyperactivity. P.494 DIAGNOSIS 1. Physical examination: The only characteristic physical finding of lead poisoning is the presence of lead lines around the gum margins. These occur in a minority of patients and only in patients with poor dental hygiene. 2. Blood smear: In chronic lead exposure, there is usually a microcytic anemia that may be superimposed on an iron deficiency anemia. Basophilic stippling is seen in a minority of cases, and the bone marrow may show ringed sideroblasts. [...]... Samuels, Martin A Manual of Neurologic Therapeutics, 7th Edition CARBON MONOXIDE POISONING Part of "16 - Toxic and Metabolic Disorders" P.500 BACKGROUND Carbon monoxide is the most common cause of death by poisoning, either because of accidental exposure (e.g., smoke) or because of intentional exposure for the purpose of murder or suicide PATHOPHYSIOLOGY 1 The acute manifestations of carbon monoxide... time of ingestion b Ethanol is metabolized by the liver, and it is more rapidly metabolized in those who drink regularly and heavily than in occasional drinkers c The rate of ethanol metabolism is approximately 7 to 10 g/h, which represents about 1 oz of 90 -proof spirits or 10 oz of beer per hour d The lethal blood level of alcohol is about 5,000 mg/L In a 70-kg man, this represents about 1 pt of 90 -proof... Samuels, Martin A Manual of Neurologic Therapeutics, 7th Edition BARBITURATE INTOXICATION Part of "16 - Toxic and Metabolic Disorders" BACKGROUND Barbiturates do not occur naturally, so exposure is always due to the use of sedative and antiepileptic drugs PATHOPHYSIOLOGY Barbiturates bind to part of the GABA receptor, which controls a chloride channel, which in turn leads to hyperpolarization of neuronal... than 5 g/kg 2 Profound coma with respiratory failure 3 Severe metabolic acidosis P.517 4 Renal failure 5 Failure to respond to conservative therapy Copyright ©2004 Lippincott Williams & Wilkins Samuels, Martin A Manual of Neurologic Therapeutics, 7th Edition HYPERTHERMIA Part of "16 - Toxic and Metabolic Disorders" BACKGROUND Hyperthermia is a common cause of neurologic dysfunction It is particularly... short-acting compounds The indications for its use are: 1 Renal or hepatic insufficiency severe enough to prevent the elimination of the drug 2 Shock or prolonged coma that does not respond to conservative management 3 Ingestion of a lethal dose of drug (3 g of a short-acting or 5 g of a long-acting barbiturate) 4 A serum drug level predictive of prolonged coma (approximately 3.5 mg/dL for short-acting... Long-term therapy: a A 5-day course of dimercaprol plus EDTA usually removes about 50% of the soft-tissue stores of lead and reduces the serum lead level by a corresponding amount 1 After chelation therapy is stopped, however, lead may be mobilized from bone, again raising the soft-tissue and serum lead concentrations Consequently, the serum lead should be checked every few days after completion of. .. BACKGROUND 1 Alcohol accounts for the most neurologic toxicity of any drug or toxin 2 Since alcoholism is often associated with malnutrition, the neurologic complications of alcoholism are a mixture of those caused by the direct effects of alcohol (and/or its metabolites) and the neurologic complications of malnutrition PATHOPHYSIOLOGY 1 Pharmacokinetics of ethyl alcohol: a Ethanol is completely absorbed from... course of intoxication, the greater its effect It may need to be repeated every 8 to 12 hours d Pralidoxime does not reach CNS AChE, and compounds that do so are not generally available Copyright ©2004 Lippincott Williams & Wilkins Samuels, Martin A Manual of Neurologic Therapeutics, 7th Edition ALCOHOL Part of "16 - Toxic and Metabolic Disorders" BACKGROUND 1 Alcohol accounts for the most neurologic. .. avoided, as they may potentiate the respiratory depressant effects of benzodiazepines used to treat withdrawal symptoms Copyright ©2004 Lippincott Williams & Wilkins Samuels, Martin A Manual of Neurologic Therapeutics, 7th Edition WERNICKE ENCEPHALOPATHY Part of "16 - Toxic and Metabolic Disorders" BACKGROUND Wernicke encephalopathy is a thiamine-deficiency disease that occurs in chronic alcoholics or patients... Wilkins Samuels, Martin A Manual of Neurologic Therapeutics, 7th Edition NEUROLEPTIC MALIGNANT SYNDROME Part of "16 - Toxic and Metabolic Disorders" BACKGROUND 1 Neuroleptic malignant syndrome (NMS) is characterized by hyperthermia, muscle rigidity, and altered mental status 2 It occurs in patients taking neuroleptic medication or, rarely, in association with withdrawal of L-dopa or other dopaminergic . represents about 1 oz of 90 -proof spirits or 10 oz. of beer per hour. d. The lethal blood level of alcohol is about 5,000 mg/L. In a 70-kg man, this represents about 1 pt of 90 -proof spirits distributed. Martin A. Manual of Neurologic Therapeutics, 7th Edition ALCOHOL Part of "16 - Toxic and Metabolic Disorders" BACKGROUND 1. Alcohol accounts for the most neurologic toxicity of any. & Wilkins Samuels, Martin A. Manual of Neurologic Therapeutics, 7th Edition HEAVY-METAL POISONING Part of "16 - Toxic and Metabolic Disorders" P. 493 LEAD BACKGROUND 1. Lead toxicity