Toxic Substances Chapter 22 PDF

Toxic Substances Chapter 22 Preamble ▪ PowerPoints are a general overview and are provided to help students take notes over the video lecture ONLY. PowerPoints DO NOT cover the details needed for the Unit exam ▪ Each student is responsible for READING the TEXTBOOK for details to answer the UNI...

Toxic Substances Chapter 22 Preamble ▪ PowerPoints are a general overview and are provided to help students take notes over the video lecture ONLY. PowerPoints DO NOT cover the details needed for the Unit exam ▪ Each student is responsible for READING the TEXTBOOK for details to answer the UNIT OBJECTIVES ▪ Unit Objectives are your study guide (not this PowerPoint) ▪ Test questions cover the details of UNIT OBJECTIVES found only in your Textbook! Introduction ▪ Toxicology (toxicos logos) “the science of poisons, including their source, chemical composition, action, tests, and antidotes.” ▪ Poison “any agent which, when introduced into the animal organism, is capable of producing morbid, noxious, or deadly effects upon it.” (Webster’s Dictionary) ▪ Toxicant “an agent or a substance that acts as a poison.” ▪ Poisoning “damaging physiological effects of ingestion, inhalation, or other exposure to a range of pharmaceuticals, illicit drugs, and chemicals, including pesticides, heavy metals, gases/vapors and common household substances, such as bleach and ammonia.” ▪ Clinical laboratories offering toxicology testing at any level have experienced an increased volume of testing. ▪ Demands and pressures by emergency room departments and by mental health facilities have caused clinical laboratories to provide increased toxicology test menus and reduced turnaround times. ▪ See Table 22-3 for examples of Toxic Substances and Their Sources That May Result in Laboratory Test Requests from Hospital Emergency Departments Requirements of Toxicology Testing ▪ Many states require an additional permit to perform toxicology testing. Forensic permit Requires the laboratory to provide chain of custody. From the time a specimen is drawn to the time the results are released to a clinician Requires drug confirmation of all positive screening tests. ▪ Drug abuse screens Tests that qualitatively identify the presence of one or more drugs or classes of drugs Group I Analytes (1) ▪ Acetaminophen Nonsteroidal anti-inflammatory drug (NSAID) Three major effects: Anti-inflammatory effects i.e., modification of the inflammatory reaction Analgesic effects i.e., reduction of certain types of pain Antipyretic effects i.e., lowering of raised body temperature Given orally and is nearly completely absorbed. Side effects with therapeutic doses are few, Toxic doses, described as two to three times the maximum therapeutic dose, cause a serious and potentially fatal hepatotoxicity. Results from saturation of enzymes catalyzing the normal conjugation reaction and results in the drug being metabolized by mixed function oxidases Measurement of serum acetaminophen concentration is important in assessing the severity of intoxication. Group I Analytes (2) ▪ Salicylate Aspirin (acetylsalicylic acid) has analgesic, antipyretic, and anti-inflammatory properties. Interferes with platelet aggregatio Thus prolongs bleeding times Salicylism Syndrome associated with tinnitus (a high- pitched buzzing noise in the ears), vertigo, decreased hearing, and occasionally nausea and vomiting Reye’s syndrome Rare disorder in children Has a 20-40% mortality outcome. Suggested that the drug not be given to children Salicylate poisoning Result of accidental ingestion or knowingly ingesting large amounts of the drug Causes several metabolic changes in the body Most notably in the body’s acid-base balance and electrolyte status Group I Analytes (3) ▪ Ethanol Rapidly absorbed Principally from the stomach Most of it is cleared by first-pass hepatic metabolism. Metabolism of ethanol in the liver involves successive oxidations First to acetaldehyde by the enzyme alcohol dehydrogenase Then to acetic acid by aldehyde dehydrogenase Purely a depressant at the cellular level Though it increases impulse activity in some parts of the CNS. Effects of acute ethanol intoxication in humans include: Slurred speech Uncoordinated body movements Increased self-confidence Euphoria Structure of the o l’s (Alcohols) and their Respective Metabolic Products The Far-Reaching Effects of Ethanol on the Human Body 1. The cardiovascular effects of ethanol produce cutaneous vasodilatation, central in origin, which causes a warm feeling but actually increases heat loss. 2. Salivary and gastric secretion are increased by ethanol consumption. Heavy consumption causes damage directly to the gastric mucosa, resulting in chronic gastritis, which may lead to G I bleeding. 3. Ethanol increases the output of adrenal steroid hormones by stimulating the anterior pituitary gland to secrete adrenocorticotrophic hormone (A C T H). 4. Antidiuretic hormone (A D H) secretion is inhibited by ethanol, and patients develop diuresis. 5. Oxytocin secretion is also inhibited, resulting in delayed parturition at term. 6. Chronic male alcoholics are often impotent and show signs of feminization, which is associated with impaired testicular steroid synthesis. 7. Liver damage is one of the most serious long-term consequences of excessive ethanol consumption. 8. Moderate drinking reduces mortality associated with coronary heart disease; this may be due to its effect on lipoproteins (e.g., raises blood levels of H D L-C). 9. Ethanol may also protect against ischemic heart disease by inhibiting platelet aggregation. 10. Excessive alcohol intake during pregnancy is associated with fetal alcohol syndrome (F A S), which results in a variety of abnormal features exhibited by neonates. Group I Analytes (4) ▪ Carbon monoxide A colorless, odorless, tasteless gas Product of incomplete combustion of carbonaceous material Combines tightly with the heme Fe +2 of hemoglobin to form carboxyhemoglobin Binding affinity is 200 to 240 times greater than that for oxygen. Toxicity arises from impaired oxygen delivery and use and leads to cellular hypoxia, dysfunction, and death. When CO enters tissues such as blood, it replaces oxygen on the hemoglobin molecule. Overall effects on the cardiovascular system are myocardial depression and hypotension. Drugs-of-Abuse Urine (DAU) Screen (1) ▪ Screening methods ▪ Classes of drugs screened in the laboratory Thin-layer chromatography Amphetamines Immunoassays Barbiturates EMIT Benzodiazepines FPIA Cannabinoids ▪ Quantitative analysis Cocaine GC Methadone HPLC Opiates GC-MS Phencyclidine Tricyclic antidepressants Drugs-of-Abuse Urine (DAU) Screen (2) ▪ Most drug screening methods are immunoassays and are calibrated at established cutoff concentrations. ▪ Cutoff values are not the same as assay detection limits. ▪ Immunoassays are not always specific for the drug tested. Tests Cut-off Values (ng/mL) Amphetamines 500 Barbiturates 200 Cocaine 150 Methodone 300 Opiates 300 Phencyclidine 25 Canabinoids 50 Examples of Possible Cutoff Values Used in Urine Drug Abuse Immunoassays Amphetamines ▪ Psychomotor stimulants ▪ Act by releasing monoamines from nerve terminals in the brain ▪ Pharmacological Effects Locomotor stimulation Euphoria and excitement Anorexia ▪ Also have peripheral sympathomimetic actions ▪ Readily absorbed from the GI tract ▪ Freely penetrate the blood–brain barrier ▪ Primary use for amphetamines is in the treatment of attention deficit/hyperactivity disorder (A DHD), principally in children.  Barbiturates ▪ Class of drugs that form the largest group of hypnotics and sedatives Hypnotic drug Produces drowsiness and facilitates the onset and maintenance of a state of sleep Sedatives Decrease activity, moderate excitement, and calm the recipient ▪ Antianxiety properties of barbiturates are inferior to those exerted by the benzodiazepines. ▪ Affects Central nervous system, Respiration, Cardiovascular system, G I tract, Liver and Kidney ▪ Typically administered orally for sedative-hypnotic use ▪ Absorbed rapidly ▪ Overdosing with barbiturates is of great concern along with the fact that they can induce a high degree of tolerance and dependence. ▪ Large doses of barbiturates cause death from respiratory and cardiovascular depression. ▪ See table 22-4 for listing of Frequently Prescribed Barbiturates, Their Respective Half-Lives, and Therapeutic Use(s) Benzodiazepines ▪ Represent the most widely prescribed drugs due to their principal pharmacological effects ▪ Act selectively on G A B A receptors, which mediate fast inhibitory synaptic transmission throughout the C N S ▪ Enhance the response to G A B A. ▪ Pharmacologic effects Reduction of anxiety and aggression Sedation and induction of sleep (hypnotic) Reduction of muscle tone and coordination Anticonvulsant effect Anterograde amnesia ▪ Several unwanted effects In the presence of other CNS depressants, particularly alcohol, benzodiazepines can cause severe, even life-threatening, respiratory depression. Side effects during therapeutic use include drowsiness, confusion, amnesia, and impaired coordination. Tolerance occurs with all benzodiazepines, as does dependence, which are their primary downsides. ▪ See Table 22-5 for Drugs Classified as Benzodiazepines Cannabinoids (1) ▪ The hemp plant, Cannabis sativa, contains the active substance Δ9 – tetrahydrocannabinol (THC) ▪ THC acts mainly on the CNS, producing a mixture of depressant and psychotomimetic effects. ▪ Several effects that can be measured in humans are: Impairment of short-term memory Analgesia Increased appetite Impairment of motor coordination Catalepsy Retention of fixed unnatural postures ▪ Immunoassay urine screening tests are developed to detect metabolites of THC. Cocaine ▪ Cocaine is found in the leaves of a South American shrub, coca. ▪ Pharmacological effects of cocaine lie in its ability to inhibit catecholamine uptake by the noradrenalin and dopamine transporters. ▪ Enhances the peripheral effects of sympathetic nerve activity and produces marked psychomotor stimulant effects. Euphoria, garrulousness, increased motor activity, and a magnification of pleasure Similar to the effects of amphetamine ▪ With excessive dosage, tremors and convulsion may occur, followed by respiratory and vasomotor depression. ▪ Primary adverse effects include cardiac dysrhythmias and coronary or cerebral thrombosis. ▪ Qualitative screening test for cocaine in urine is designed to detect the metabolite benzoylecgonine. Methadone ▪ A long-acting μ-receptor agonist ▪ Pharmacological properties qualitatively similar to those of morphine ▪ Classified as a narcotic analgesic drug or opiate ▪ Effects on the respiratory system can be detected for more than 24 hours after a single dose. ▪ Widely used as a drug to treat morphine and diamorphine addicts.  Opiates (1) ▪ Applies to any substance, whether endogenous or Effects include: synthetic, that produces morphine-like effects Analgesia, that are blocked by antagonists Euphoria, ▪ Opiate Respiratory depression, Synthetic, morphine-like drugs with nonpeptidic Depression of cough reflex, structures Nausea and vomiting ▪ Morphine analogues Pupillary constriction Compounds that structurally resemble morphine and are often synthesized from it Diamorphine (heroin), codeine, nalophine, and naloxone. Opiates (2) ▪ Acute overdose results in coma and respiratory depression; constricted pupils are a sign of overdose. ▪ Treatment for overdose may include administration of naloxone by IV. ▪ Immunoassays for opiates are designed primarily to detect morphine and codeine at a cutoff concentration. ▪ See Table 22-6 A Partial Listing of Opiates and Opiate Agonist Compounds That Are Often Abused Phencyclidine ▪ PCP ▪ Psychotomimetic Also called psychedelic or hallucinogenic drugs Affect thought, perception, and mood without causing marked psychomotor stimulation or depression. Categorized into two broad groups: Drugs with a chemical resemblance to known neurotransmitters Drugs unrelated to monoamine neurotransmitters ▪ Mode of action at the cellular level is not well understood. Tricyclic Antidepressants ▪ Initially produced as possible antipsychotic drugs ▪ Antidepressant drugs serve to alleviate depression. ▪ Primary mechanism of action is to block the uptake of amines by nerve terminals for binding sites on the transport protein. ▪ Immunoassays for quantitative TCAs in serum and urinary TCA qualitative screening are often provided by clinical chemistry laboratories. Lead (1) ▪ Metal found in many industrial processes and products. ▪ Most human exposure to lead occurs through ingestion or inhalation. ▪ Absorbed lead that is not excreted is exchanged primarily among three compartments: Blood Soft tissue Mineralizing tissues ▪ Lead exposure can come from a variety of sources Occupational Lead Exposures Environmental Lead Exposures Hobbies and Related Activities Other Potential Sources See Box 22-4 for a full listing of sources Lead (2) ▪ Clinically relevant BLLs for pediatric and adults are as follows: 0-6 years: 0.0-4.9 μg/dL >7 years: 0.0-9.9 μg/dL See Table 22.7 for lead concentration management ▪ Critical Values Pediatrics (< 15 years): > 20 mg/dL Adults (> 16 years): > 70 mg/dL ▪ Lead can induce two types of anemia. Often accompanied by basophilic stippling of the erythrocytes Acute, high-level lead exposure Associated with hemolytic anemia. Chronic lead exposure Lead induces hypochromic microcytic anemia ▪ Current biomarker for assessment of lead exposure is venous blood lead with or without measured FEP. ▪ Measure total lead and zinc protoporphyrins as FEPs. Group II Analytes (1) ▪ Methanol Also called methyl alcohol or wood alcohol Contained in: Antifreeze solutions (gas line and windshields) Fuel Photocopy fluids Effects on the body Depresses the CNS and like other alcohols Produces vasodilation Causes hypotension Reduces cardiac output Group II Analytes (2) ▪ Ethylene glycol Contained in: De-icing solutions Brake fluid Other fluids used in boats and aircrafts Ingestion of ethylene glycol itself is nontoxic. Metabolites produced can cause tissue destruction and metabolic toxicity. Metabolized to glycoaldehyde, glycolic acid, glyoxylic acid, and ultimately oxalic acid. Clinical laboratory findings Calcium oxalate crystals in the urine Increase in osmolal gap Possible acidosis Group II Analytes (3) ▪ Isopropanol Principal compound in rubbing alcohol Abused like ethylene glycol as an inexpensive ethanol substitute Primarily a CNS depressant Clinical presentation of isopropanol ingestion includes CNS depression and ketonemia without acidemia. Due to isopropanol’s metabolism to acetone ▪ Phenothiazine Tricyclic structure, with two benzene rings linked by sulfur and a nitrogen atom Chemically related to the thioxanthenes Used to treat psychotic disorders, including schizophrenia, the manic phase of bipolar illness, and acute idiopathic psychotic illnesses. Group II Analytes (4) ▪ Organophosphate and Carbamate Compounds Class of compounds referred to as anticholinesterase agents. Function of cholinergic agents is to terminate the action. Compounds that inhibit AChE are anticholinesterase (anti-ChE) agents. Used extensively in agricultural insecticides, in pesticides, and as potential chemical warfare “nerve gas.” Muscarinic symptoms Bronchospasms or laryngeal spasms that may lead to a compromised airway. Nicotinic symptoms Fatigue and generalized weakness, involuntary twitching, and eventually severe weakness and paralysis. Measurement of cholinesterases is appropriate for individuals who have been exposed to insecticides Group II Analytes (5) ▪ Gamma-hydroxybutyrate (GHB) Popular drugs of abuse in adolescents and adults Implicated in several celebrity overdoses Popularized as a “date-rape drug” GHB is a relatively fast-acting CNS depressant. Structurally similar to the inhibitory neurotransmitter γ-aminobutyric acid (GABA) Group II Analytes (6) ▪ Ketamine (Ketalar and Ketaject) An abused drug that can result in death Abusers usually snort the drug, smoke it, inject it, or, on occasion (as with date rape incidents), mix it in drinks. Ketamine is not usually measured in hospital-based clinical chemistry laboratories They are not equipped with GC or GCMS instrumentation. Effects of the drug include: Sedation Immobilization Amnesia Analgesia Trancelike cataleptic feature Short-term anesthetic for painful diagnostic or surgical procedures in children Group II Analytes (7) Signs and symptoms reflect sympathomimetic ▪ Lysergic Acid Diethylamide (LSD) effects. Hallucinogen Mydriasis Ability to produce distortions of reality Flushing Individuals using LSD experience a variety of Tremor clinical effects that vary among users. Hyperthermia Altered visual perception Tachycardia Hypersensitive to sound Increased blood pressure Rapid mood swings Diaphoresis Anxiety Ataxia Despair Severe toxicity can result in coma, seizures, and respiratory arrest. Suicidal thoughts Urine drug abuse screening for L S D is not Panic available in most clinical chemistry laboratories. Group II Analytes (8) ▪ Urine Specimen Validity Specimens submitted for drug screening should be tested for possible adulteration, dilution, or substitution. The validity of DAU screening depends on the integrity of the urine samples. Contaminated or adulterated samples may cause erroneous results leading to significant consequences. Dilute urine specimen Creatinine and specific gravity values that are lower than expected for human urine Substituted urine specimen Creatinine and specific gravity values that are so diminished or so divergent that they are not consistent with normal human urine Group II Analytes (9) ▪ Urine Specimen Validity Urine specimens can be adultered by simply adding common household chemicals. Commercially available drug testing adulterant products Remove unwanted substances from the urine Interfere with the chemical reactions of the urine adulteration test strips ▪ Urine Adulteration Test Strip These products test for combinations of creatinine, nitrite, glutaraladehyde, pH, specific gravity, bleach, pyridinium chloro- chromate, and oxidants. Intect® 7 AdultaCheck® AlereTM Toxicology PLC Trace Metals (1) ▪ Term applies to metals that serve a biological role in humans and animals. ▪ Trace metals refers to low blood concentration of metal Range of µg/dL in body fluids, mg/kg in tissues ▪ Ultratrace metal Blood levels in the range of ng/dL or µg/kg Trace Metals (2) ▪ Classification of trace metals based on the need for their presence in humans. Essential Possibly Nonessential Essential Essential When symptoms that appear when a diet is deficient in the metal Chromium Arsenic Aluminum are uniquely reversed when an adequate supply of the particular Cobalt Boron Antimony trace metal is present Iron Lithium Bismuth Manganese Nickel Germanium Possibly essential Molybdenum Silicon Mercury Do not have clearly definitive biochemical roles, yet signs of Selenium Vanadium Silver deficiency have been documented Zinc Thallium Nonessential trace metals Titanium ▪ Conclusive characterization of trace or ultratrace metals is often difficult. Widespread distribution of these metals in the environment and food supply Only minute amounts are needed to support physiologic processes TABLE 22-9 The Role of Trace Metals and Associated Clinical Disorders (1 of 7) Metal Role(s) Deficiency Toxicity Aluminum Not an essential trace Not significant* May affect bone formation and remodeling metal May be associated with Alzheimer’s disease Not clear Can lead to dialysis encephalopathy or dialysis dementia Antimony Not an essential trace Not significant* Pneumoconiosis metal Affects heart Not clear Dermatitis Spontaneous abortions and premature births Lymphocytosis and reduction in leukocytes and platelets Arsenic Possibly an essential trace Not significant* Known carcinogen metal G I tract involvement Not clear Cardiac effects Encephalopathy Lung injury Renal failure *Not significant: No known clinical symptoms associated with low levels of trace metals in blood or tissues. Table 22-9 The Role of Trace Metals and Associated Clinical Disorders (2 of 7) Metal Role(s) Deficiency Toxicity Beryllium Not necessary for human Not significant* Chronic beryllium (B e) disease health Significant lung involvement Cadmium No known biological role Not significant* Nephrotoxicity Chronic emphysema Cancer Osteomalacia Chromium Metabolism of glucose Impaired glucose Occupational: renal failure, dermatitis, tolerance pulmonary cancer Cobalt Component of vitamin Vitamin B12 deficiency Developmental defects B12 anemia Male sterility Testicular atrophy *Not significant: No known clinical symptoms associated with low levels of trace metals in blood or tissues. Table 22-9 The Role of Trace Metals and Associated Clinical Disorders (3 of 7) Metal Role(s) Deficiency Toxicity Copper Cofactor for oxidase Anemia Nausea and vomiting enzymes Growth retardation Diarrhea Defective keratinization and Hepatic failure pigmentation of hair Tremor Hypothermia Mental deterioration Degenerative changes in aortic elastin Hemolytic anemia Osteopenia Renal dysfunction Mental deterioration Manganese Required for Impaired growth and skeletal General: neurotoxicity, Parkinson-like glycoprotein and development, symptoms proteoglycan synthesis reproduction, lipid and carbohydrate Occupational: encephalitis-like syndrome, metabolism; upper body rash Parkinson-like syndrome, psychosis, pneumoconiosis Mercury None found Not significant Brain involvement Gastroenteritis Interstitial pneumonitis Cardiac problems Renal tubular dysfunction TABLE 22-9 The Role of Trace Metals and Associated Clinical Disorders (4 of 7) Metal Role(s) Deficiency Toxicity Molybdenum Component of sulfite Severe neurologic abnormalities Reproductive and fetal abnormalities and xanthene oxidases Nickel May be essential for Not significant Dermatitis life but Pulmonary, hepatic, and neurologic dysfunction unclear Selenium Component of Cardiomyopathy General: alopecia, nausea, vomiting, abnormal glutathione Heart failure nails, emotional liability, peripheral neuropathy, peroxidase and Striated muscle degeneration lassitude, garlic odor to breath, dermatitis iodothyronine-5’- Occupational: lung and nasal carcinomas, liver deiodinase necrosis, pulmonary inflammation Silver Not clear Not significant Argyria Hemopoiesis Cardiac enlargement Degeneration of the liver and destruction of renal tubules Growth retardation *Not significant: No known clinical symptoms associated with low levels of trace metals in blood or tissues. Table 22-9 The Role of Trace Metals and Associated Clinical Disorders (7 of 7) Metal Role(s) Deficiency Toxicity Thallium Not clear Not significant Alopecia (hair loss) Peripheral neuropathy Renal failure Seizures Zinc Cofactor of more than Growth retardation General: reduced copper absorption, 300 metalloenzymes Reduced taste and smell gastritis, sweating, fever, nausea, vomiting Alopecia Occupational: respiratory distress, Dermatitis pulmonary fibrosis Diarrhea Immune dysfunction Failure to thrive Gonadal atrophy Congenital malformations *Not significant: No known clinical symptoms associated with low levels of trace metals in blood or tissues. Trace Metals (3) ▪ Aluminum Incorporated into antacids and astringents Toxicity has been linked to the following: Oral exposure from aluminum-containing pharmaceutical products such as antacids Alzheimer’s disease resulting from the accumulation of aluminum in the neurofibrillary tangles of patients with the disease Dialysis dementia Hodgkin’s disease ▪ Antimony Acute and chronic exposure to antimony may result in the following effects: Cardiovascular Renal Hematologic Dermatologic Neurologic Clinical assessment of a patient with a history, signs, and symptoms of antimony intoxication may require laboratory measurement of biological specimens. Trace Metals (4) ▪ Arsenic Toxic forms of arsenic (A s) include: As (III) As (V) Most toxic Arsenic metabolites Monomethyl arsine (M M A) Dimethylarsine (D M A) Urine As (III) and (V) peaks ~10 hrs. Urine M M A and D M A peaks ~40-60 hrs. Half-life of inorganic As is 4-6 hours. Serum A s is elevated for only a short time and rapidly disappears into the large body phosphate pool. Abnormal serum A s levels are detected for only ~4 hrs. See Box 22-8 for Sources of Arsenic Trace Metals (5) ▪ Beryllium Humans can be exposed to beryllium via food, drinking water, and industrial processes. A large percentage of absorbed beryllium accumulates in the skeleton. The beryllium lymphocyte proliferation test (BeLPT) uses a sample of blood that measures beryllium sensitization, which represents an “allergic” reaction to beryllium. ▪ Cadmium Cadmium alloys (with zinc and lead) are used extensively in solder and brazing rods. Industrial applications include electroplating and the production of nickel-based rechargeable batteries. The toxicological impact of cadmium in humans manifests itself in four principle tissue sites: Kidney Bone Lung GI tract Trace Metals (6) ▪ Chromium Essential trace element that augments the action of insulin Chromodulin is a low-molecular-weight intracellular octapeptide that binds four Cr3+ ions then moves to sites on the cell membrane near insulin receptors. Chromium deficiency is characterized by: Insulin resistance Glucose intolerance Weight loss Possible neurological deficits See Table 22-10 for the Industrial Uses of Chromium- Containing Compounds Trace Metals (7) ▪ Cobalt An essential element in vitamin B12 Target tissues and systems include: Cardiac Endocrine Hematopoietic GI Neurological systems Chronic exposure results in pulmonary edema, allergy, nausea, vomiting, hemorrhage, and thyroid abnormalities. Trace Metals (8) ▪ Copper In the hepatocytes, copper is bound to enzymes. For example, ceruloplasmin-producing Prion protein (P r P) binds CU2+ and may be involved in copper regulation within the brain. Wilson disease An inherited autosomal recessive trait Characterized by a defect in the metabolism of copper Copper deposits in the liver, brain, kidney, cornea, and other tissues See Table 22-11 for Commercial Uses of Copper-Containing Compounds Trace Metals (9) ▪ Manganese Serves as an important constituent in several metalloenzymes. Pyruvate carboxylase Arginase Glycosyltransferases Patients with severe liver disease may develop signs of neurotoxicity because of a failure to excrete manganese in bile. Trace Metals (10) ▪ Mercury Found naturally in small amounts as a metal silver–colored liquid Mercury compounds are organized into three groups that differ with respect to toxicodynamics and toxicokinetics. Metal Inorganic Organic The relative toxicities of mercury compounds are shown as: Nontoxic - Hg0 < Hg2+ = CH3Hg1+ - Very toxic Trace Metals (11) ▪ Mercury After any form of mercury is absorbed, it distributes widely to all tissues, predominantly the kidneys, liver, spleen, and CNS. Clinical symptoms of acute elemental mercury inhalation include: Symptoms of acute elemental mercury inhalation include chills, fever, cough, and shortness of breath. GI symptoms include nausea, vomiting, and diarrhea. Other symptoms include a metallic taste, dysphasia, salivation, weakness, headaches, and visual disturbance. See Box 22-9 for the Nonoccupational and Occupation Sources of Mercury Compounds Trace Metals (12) ▪ Molybdenum Specific enzymes that require molybdenum as metallo-cofactor include: Sulfite oxidase Xanthine dehydrogenase Aldehyde oxidase Excess intake of molybdenum creates a copper deficiency by inhibiting copper absorption through formation of an insoluble thiomolybdate-copper complex. ▪ Nickel Most common disorder associated with acute exposure to nickel is allergic dermatitis. Symptoms of acute toxicity include: Acute lung injury Intestinal pneumonitis Myocarditis Neurological symptoms Possible leukocytosis Cerebral edema Trace Metals (13) ▪ Selenium Thought to be closely associated with vitamin E in its functions. Selenium-specific selenoproteins abound in humans. Glutathione Selenoprotein P Iodothyronine deiodinase Selenium deficiency is associated with the following: Keshan disease Kashin-Beck disease Nutritional depletion in hospital patients Thyroid function Immune function Trace Metals (14) ▪ Silver A significant effect of silver overexposure or ingestion in humans is the development of argyria. Permanent bluish-gray discoloration of skin, mucous membranes, and nails because of silver deposits in those tissues. Patients can also experience: Growth retardation Product Route of Medicinal Use Hemopoiesis Name Administration Cardiac enlargement Silver nitrate Ophthalmic Prevention of gonorrheal (1%) ophthalmia neonatorum Liver degeneration Silver nitrate Cutaneous In podiatry for corns, calluses, Renal tubule destruction (10%) impetigo vulgaris, plantar warts, and papillomatous growths Silver Cutaneous Antimicrobial treatment for wound sulfadiazine infections for patients with second- and third-degree burns Silver-Containing Products Used for Medicinal Purposes Trace Metals (20 of 21) ▪ Thallium The mechanism of toxicity includes competition with potassium because the two elements have similar ionic radii. Individuals may develop conditions associated with: GI tract Cardiovasculature Respiratory apparatus Kidneys Central and peripheral nervous systems Skin Patients may also develop alopecia. Trace Metals (21 of 21) ▪ Zinc Approximately 300 zinc metalloenzymes span all of the enzyme categories. Examples include: Carbonic anhydrase Alkaline phosphatase RNA and DNA polymerases Alcohol dehydrogenase Thymidine kinase Zinc deficiency is associated with several conditions. Most notably, a reduction in growth Minimal Risk Elements (1) ▪ Boron Exact role of boron in humans has not been clearly elucidated Boron in the form of boric acid is used for medicinal purposes to treat arthritis. Used as an antiseptic and preservative. ▪ Fluorine Used in dentistry for prophylactic therapy to help prevent the formation of dental caries Fluorosis can develop, usually in children, when an excess amount of fluoride is deposited on the teeth. ▪ Platinum Several chemotherapeutic agents contain platinum. These compounds may be nephrotoxic, depending on their relative concentrations in blood. Minimal Risk Elements (2) ▪ Silicon One of the most abundant metals in the environment Two forms of silicon are of medical interest: Amorphous oxides found in asbestos Methylated polymers of silicon ▪ Asbestosis Inhaling asbestos containing dust leads to deposition of asbestos fibers in the pulmonary alveoli. ▪ Silicosis Variety of pulmonary diseases associated with the inhalation of crystalline silica oxide (SiO2), or quartz Postamble ▪ READ the TEXTBOOK for the details to answer the UNIT OBJECTIVES. ▪ USE THE UNIT OBJECTIVES AS A STUDY GUIDE ▪ All test questions come from detailed material found in the TEXTBOOK (Not this PowerPoint) and relate back to the Unit Objectives