Toxicology, Vitamins, and Trace Elements PDF

# TOXICOLOGY - Study of toxic drugs or poisons encountered in households, environment, industries and in the workplace. ## ACUTE TOXICITY - Usually associated with a single, short-term exposure to a substance, the dose of which is sufficient to cause immediate toxic effects. ## CHRONIC TOXICITY -...

# TOXICOLOGY - Study of toxic drugs or poisons encountered in households, environment, industries and in the workplace. ## ACUTE TOXICITY - Usually associated with a single, short-term exposure to a substance, the dose of which is sufficient to cause immediate toxic effects. ## CHRONIC TOXICITY - Caused by repeated frequent exposure for extended periods of time that are insufficient to cause an immediate acute response. ## TOXIC AGENTS/POISONS ### Cyanide - Common suicidal agent - Reversibly binds to cytochrome A3 and inhibits reoxidation - Binds to ferric and ferrous form of iron to produce cyanohemoglobin - Odor of bitter almonds - Fast acting toxin; occurrence of altered mental status and tachypnea - Unexplained metabolic acidosis (with increased anion gap) ### Carbon Monoxide - Most Common gaseous poison - Produces tissue hypoxia - Binds to hemoglobin to form carboxyhemoglobin (CO-Hb) - Induces synthesis of NO (nitric oxide) a potent vasodilator that causes large in systemic BP - CHERRY RED color on the face = acute CO poisoning - Delayed neurologic symptoms (mental deterioration, mutism, memory impairment, gait disturbance and urinary incontinence). ### Arsenic - **KING OF POISONS** - Inorganic arsenicals - sodium arsenate, lead arsenite, and copper arsenite - Organic arsenicals - carbasone and tryparsamide - Poisoning generally occurs in the industrial setting - Occur in 3 oxidation states: elemental, trivalent arsenite, & pentavalent arsenate - Readily absorbed through GI tract and lungs - Can cross the placenta - Odor of garlic breath and metallic taste in patient's mouth - Cyanosis, hypotension, tachycardia, and ventricular arrhythmia may develop - Mees lines in nail beds - Treatment includes: removal of residual arsenic through gastric lavage/emesis & treatment with dimercaprol ### Mercury - Exists in 4 different forms: - (1) elemental/metallic, (2) mercurous (poorly soluble, poorly absorbed), (3) mercuric (readily soluble/absorbed), and (4) alkyl mercury - Major effect on CNS with a half life of 70-90 days. - Inhibits catecholamine-O-methyltransferase - Congenital Minimata disease - Effect of methyl mercury - First described in Japan - children were born with stigmata of cerebral palsy ### Acrodynia - Pink disease/Feer-swift disease and Feer syndrome. - Occurs mainly in children but can also affect adults. - Symptoms include: erythematous rash of palms and soles, hypertension, tachycardia, pruritus, sweating, and weakness of the proximal pelvic girdle. - Poor muscle tone ### Erethism - Complex of neurological symptoms: memory loss, drowsiness, withdrawal, depression, and irritability ### Iron - **Hemochromatosis**: deposition of iron in tissues - **Hemochromatosis**: iron induces tissue damage - Iron absorption is regulated by HFE gene encoded protein - More than 10 transfusions with PRBCs are at risk for acquired hemochromatosis - Signs of intoxication: severe gastroenteritis, melena, abdominal pain, and hematemesis. ### Lead - Largest body compartment: BONE - HALF LIFE: 32 days - Acute manifestations include encephalopathy, convulsions, stupor, and colic. - Chronic toxicity may be manifested by general malaise, weight loss, anorexia, and constipation. - May produce intellectual deficit in children - May also cause peripheral neuropathy with wrist drop or foot drop, lead nephrosis with albuminuria, hematuria, and pyuria and anemia (hypochromic, microcytic, or normocytic) with basophilic stippling. - blocks the action of δ-aminolevulinic acid (ALA) synthetase, δ-ALA dehydratace (ALAD) coproporphyrinogen decarboxylase, and ferrochelatase, producing anemia. ### Organophosphates and Carbamates - Both compounds inhibit the enzyme acetylcholinesterase (AChE), which normally hydrolyzes the neurotransmitter acetylcholine (ACh). - symptoms of organophosphate poisoning include parasympathetic manifestations such as salivation, lacrimation, urination, and defecation. - **AChE** is found primarily in nervous tissue and erythrocytes - **pseudocholinesterase** is found in plasma # VITAMINS AND TRACE ELEMENTS - Adequate intake of vitamins and trace elements is critical for maintaining human health and development. - **Vitamins** are organic compounds that are essential for human health, growth, and reproduction. They must be obtained from the diet. - **Trace elements** are inorganic analytes found in small quantities in body fluids and tissues. - **Ultratrace elements** are similar to trace elements but are found in even smaller quantities. - The terms **avitaminosis** and **hypovitaminosis** both describe a deficiency of a specific vitamin. - **Hypervitaminosis** describes an excess of a particular vitamin in the body. - **Nutrition** refers to the body's status in relation to nutrition, which can be in general or specific to a certain nutrient. ## Fat Soluble Vitamins | VITAMIN | FUNCTION | DEFICIENCY SYNDROME | TOXICITY | |---|---|---|---| | Vitamin A (Retinol) | Component of retinal rod pigment - Dim light vision - Resistance to infection | Squamous metaplasia - xerophthalmia (dry eye) - Night blindness - Vulnerability to infection | ACUTE: drowsiness, headache, stupor, skin peeling, & papilledema CHRONIC: osteoporosis, hepatotoxicity | | Vitamin D (Cholecalciferol) | Promotes absorption of calcium and phosphorus; mineralization of bones and teeth | Rickets (CHILDREN), Osteomalacia (ADULTS) - Hypocalcemia - Tetany | carotenoids = distinct orange-yellow skin color - Hypercalcemia, hypercalciuria - Muscle weakness - Renal calculi | | Vitamin E (Tocopherol) | Antioxidant - Primarily involved in RBC integrity | Spinocerebellar degeneration, Ataxia | Mild GI distress - Coagulopathies (px. Receiving anticonvulsants) | | Vitamin K (Phytomenadione) | Cofactor of procoagulants (factors II, VII, X and proteins C and S). | Defective clotting - Bleeding disorder | ↑ amounts may decrease clotting time | ## Water Soluble Vitamins | VITAMIN | FUNCTIONS | DEFICIENCY SYNDROME | TOXICITY | |---|---|---|---| | VITAMIN B1 (Thiamine) | Enzyme cofactor | Beri-beri - Wernicke-Korsakoff syndrome | ONLY when given parenterally | | VITAMIN B2 (Riboflavin) | Enzyme cofactor in intermediary metabolism | Ariboflavinosis - Angular stomatitis - Corneal vascularization | No known toxicity | | VITAMIN B3 (Niacin) | NAD and NAD phosphate Redox reactions | Pellagra | Vascular dilation - Hepatotoxic | | VITAMIN B5 (Pantothenic acid) | Incorporated in coenzyme A | Depressed immune system - Muscle weakness | Diarrhea | | VITAMIN B6 (Pyridoxine) | Amino acid, phospholipid, and glycogen metabolism | Cheilosis - Glossitis - Peripheral neuropathy | Long term megadose supplementation = ataxia & neuropathy (sensory) | | VITAMIN B7 (Biotin) | Enzyme cofactor | RARE (dermatitis, glossitis, and hypercholesterolemia). | NO KNOWN TOXICITY | | VITAMIN B9 (Folic Acid) | Amino acid synthesis | Megaloblastic anemia - Neural tube defects | NO ADVERSE EFFECTS AT ↑ ORAL DOSES | | VITAMIN B12 (Cobalamin) | Folate metabolism - DNA synthesis - Spinal tract myelinization | Megaloblastic anemia - Peripheral neuropathy | NO KNOWN TOXICITY | | VITAMIN C (Ascorbate) | Hydroxylation of collagen | Scurvy | Kidney stones | ## Trace elements | ELEMENT | FUNCTION | EFFECT OF DEFICIENCY | EFFECT OF TOXICITY | |---|---|---|---| | CHROMIUM (Cr) | Potentiates insulin action, glucose and lipid metabolism - Component of glucose tolerance factor | Impaired glucose tolerance in type 2 DM - Insulin resistance - Hyperglycemia and hyperlipidemia - Peripheral neuropathy | Skin ulcers - Contact dermatitis - Asthma - Hepatic and renal necrosis - Lung cancer | | COBALT (Co) | Hemoglobin synthesis | Anemia | Cardiomyopathy, heart failure | | COPPER (Cu) | Vitamin B12 component - Cellular respiration - Collagen synthesis - Vascular and skeletal structure development | Anorexia - Growth depression - Menke's kinky hair syndrome (congenital failure of Cu absorption) - Iron refractory anemia - Bone fractures, skeletal defects | Goiter - Hypothyroidism - Wilson's disease (failure to excrete Cu in bile) - Kayser-Fleischer (copper deposits in the Descemet membrane of the cornea) | | FLUORINE (F) | Prevents tooth decay | ↑ dental caries | Mottled enamel - Fluorosis | | IODINE (I) | Component of thyroid hormone | Goiter - Hypothyroidism - Cretinism (INFANTS) - Myxedema (ADULTS) | Goiter - Thyrotoxicosis | | IRON (Fe) | Oxygen transport - Component of Hemoglobin, Vitamin A - Bone and connective tissue | Hypochromic, microcytic anemia - Glossitis - Angular stomatitis, cheilosis, and koilonychia - Skeletal and cartilage defects | Hemochromatosis | | MANGANESE (Mn) | Component of metalloenzyme | LEAST TOXIC of all the trace elements | Syndrome resembles Parkinson's and Wilson's disease | | MOLYBDENUM (Mo) | DNA metabolism - Essential for uric acid production | Growth depression - Hypercuprinemia - Goiter - Cretinism - Keshan disease (endemic cardiomyopathy; affects children and women of childbearing age) - Kashin-Beck disease (endemic osteoarthritis; affects pre-adolescents | Anemia - Goiter - Thyrotoxicosis | | SELENIUM (Se) | Protects against oxidative damage of lipid, gene expression, thyroxine deiodinase | | Hypouricemia - Hair and nail loss - Liver failure - Neuropathy - Garlic odor on breath | | ZINC (Zn) | - Protein synthesis, zinc finger proteins - gene expression, immunity, needed for normal skin, bones, and hair - Component of metallothionein ≈ 300 enzymes | and adolescents) - Acrodermatitis enteropathica - In CHILDREN (immune deficits, glossitis, and osteoporosis) | Relatively NON-TOXIC - Causes copper deficiency |