Phchem 5L- Finals- Postlab(ACT14) PDF

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PHCHEM5L: CLINICAL TOXICOLOGY LAB POST-LABORATORY DISCUSSION FINALS ACTIVITY 14: HOUSEHOLD HAZARDS (MISCELLANEOUS CHEMICALS) 1. BLEACHING SOULTIONS - 3-6% Sodium Hypochlorite solution in water - Swimming pools: 20% Sodium Hypochlorite POISONOU S INGREDIEN T MECHANIS M OF TOXICITY

TREATMEN T OF POISONING

Sodium Hypochlorite

Sodium hypochlorite is a strong oxidizer. Oxidation reactions are corrosive, solutions burn skin and cause eye damage, especially when used in concentrated forms. In particular, hypochorite (HOCl) is known to cause post-translational modifications to amino acids in proteins, the notable ones being cysteine and methionine oxidation. These oxidation reactions can lead to widespread protein aggregation and denaturation, leading to cell death and tissue damage. (1) Remove bleaching solution from the skin by flooding with water. (2) Dilute and decompose swallowed bleaching solution by giving milk, melted ice cream, or beaten eggs. Antacids such as milk of magnesia or aluminum hydroxide gel is also useful. Do not use emesis, lavage, or acid antidotes. (3) Treat chloramine-T poisoning with nitrite and thiososulfate administrations for cyanide (4) Remove by gastric lavage

2. CHLORINATED LIME POISONOUS Calcium hypochlorite (10–70% available chlorine) INGREDIENT MECHANISM Hypochlorite’s potential to cause toxicity is related to its oxidizing OF TOXICITY capacity and the pH of the solution. Toxicity arises from its corrosive activity upon contact with mucous membranes and skin Emesis; treat as for bleaching solution TREATMENT OF POISONING 3. ABRASIVE CLEANERS POISONOUS INGREDIEN T MECHANIS M OF TOXICITY TREATMENT OF POISONING

Sodium phosphates

Phosphate toxicity is likely due to the disturbance of other electrolytes when phosphate levels are high, producing symptoms including tetany, dehydration, hypotension, tachycardia, hyperpyrexia, cardiac arrest and coma Ingestion (1) Emergency measures – Dilute the alkali by giving water or milk to drink immediately and allow vomiting to occur. Avoid gastric lavage or emetics, which increase the possibility of perforation. Esophagoscopy is the only way to exclude the possibility of corrosion in the upper gastrointestinal tract; if corrosion is suspected, esophagoscopy should usually be performed within 24 hours. (2) Antidote – For hypocalcemia after phosphate ingestion, give calcium gluconate, 5 ml of 10% solution slowly intravenously, to restore ionic calcium to normal level. (3) General measures – Give nothing by mouth until esophagoscopy has COMPILED BY: Ghinelli Anne P. Laygo, RPh SY 2019-2020

been done. Treat perforation with organism-specific chemotherapy. After the acute injury has subsided, esophageal dilation can be done. (4) Specific measures – Button batteries lodged in the esophagus should be removed endoscopically or surgically. Batteries that have passed beyond the esophagus will ordinarily be expelled within 1–3 days; surgical intervention is unnecessary unless the battery lodges in a diverticulum. Catharsis may speed passage of the battery through the intestinal tract. Eye contact (1) Emergency measures – Wash eye for 15 minutes with running water and then irrigate eye for 30–60 min with normal saline solution. (2) General measures – Apply sterile bandages, allay pain by systemic administration of analgesics, and take the patient to an ophthalmologist for evaluation of the injury. Skin contact Wash with running water until skin is free of alkali as indicated by disappearance of soapiness. 4. CLOTH MARKING INKS Aniline POISONOU S INGREDIEN T Aniline induces lipid peroxidation and protein oxidation in the spleen MECHANIS M OF and that oxidative stress plays a role in the splenic toxicity of aniline. Since one of the major functions of the spleen is to remove damaged TOXICITY erythrocytes, aniline-damaged erythrocytes would be expected to be scavenged by the spleen, especially by phagocytes. The deposition and subsequent breakdown of damaged erythrocytes will not only release aniline and/or its metabolites, but, most importantly, will also result in accumulation of iron in the spleen which may catalyze the generation of tissue-damaging oxygen radicals which can subsequently cause oxidation of biomolecules and result in lipid peroxidation and protein oxidation. It is also possible that during the scavenging of damaged erythrocytes, the splenic phagocytes, especially macrophages themselves, can become activated and release reactive oxygen species (ROS) which could further contribute to the oxidation of biomolecules leading to tissue injury. Acute poisoning TREATMEN T OF (1) Emergency measures: (a) Remove poison from skin by washing thoroughly with soap and POISONING water. (b) If poison was swallowed remove by emesis or gastric lavage and consider using activated charcoal (c) Give O2 if respiration is shallow or anoxia is present. (2) Antidote – For severe methemoglobinemia, give methylene blue, 1% solution, 0.1 ml/kg (1 mg/kg) slowly intravenously, to reduce methemoglobin to normal hemoglobin (3) Other measures – If methemoglobinemia does not respond to methylene blue, hemodialysis or exchange transfusion is useful. Chronic poisoning (1) Remove from exposure. (2) Treat liver damage 5. FERTILIZER POISONOU

Ammonium nitrate, phosphate, and metal salt COMPILED BY: Ghinelli Anne P. Laygo, RPh SY 2019-2020

S INGREDIEN T MECHANIS M OF TOXICITY

TREATMEN T OF POISONING 6. FIREWORKS POISONOU S INGREDIEN T MECHANIS M OF TOXICITY

The topical damage caused by ammonia is probably due mainly to its alkaline properties. Its high water solubility allows it to dissolve in moisture on the mucous membranes, skin, and eyes, forming ammonium hydroxide. Ammonium hydroxide causes saponification of cell membrane lipids, resulting in cell disruption and death. Additionally, it extracts water from the cells and initiates an inflammatory response, which further damages the surrounding tissues. Excess circulating levels of ammonia (hyperammonemia) can cause serious neurological effects. This is thought to involve the alteration of glutamate metabolism in the brain and resultant increased activation of NMDA receptors, which causes decreased protein kinase C-mediated phosphorylation of Na+/K+ ATPase, increased activity of Na+/K+ ATPase, and depletion of ATP. Ammonia can chemically interact with an internal thiolester bond of complement 3 (C3). This causes a conformation change in C3, which activates the alternative complement pathway, causing the release of chemoattractants and the assembly of the membrane attack complex of complement. The altered C3 can also bind directly to phagocyte complement receptors, which causes the release of toxic oxygen species. Dilute with milk or water

Arsenic Mercury Antimony Lead Phosphorus ARSENIC: Arsenic and its metabolites disrupt ATP production through several mechanisms. At the level of the citric acid cycle, arsenic inhibits pyruvate dehydrogenase and by competing with phosphate it uncouples oxidative phosphorylation, thus inhibiting energy-linked reduction of NAD+, mitochondrial respiration, and ATP synthesis. Hydrogen peroxide production is also increased, which might form reactive oxygen species and oxidative stress. Arsenic's carcinogenicity is influenced by the arsenical binding of tubulin, which results in aneuploidy, polyploidy and mitotic arrests. The binding of other arsenic protein targets may also cause altered DNA repair enzyme activity, altered DNA methylation patterns and cell proliferation. MERCURY: High-affinity binding of the divalent mercuric ion to thiol or sulfhydryl groups of proteins is believed to be the major mechanism for the activity of mercury. Through alterations in intracellular thiol status, mercury can promote oxidative stress, lipid peroxidation, mitochondrial dysfunction, and changes in heme metabolism. Mercury is known to bind to microsomal and mitochondrial enzymes, resulting in cell injury and death. ANTIMONY: The inhalation data suggests that the myocardium is a target of antimony toxicity. It is possible that antimony affects circulating glucose by interfering with enzymes of the glycogenolysis and gluconeogenesis pathways. The mechanism of action of antimony remains unclear. However, some studies suggest that antimony combines with sulfhydryl COMPILED BY: Ghinelli Anne P. Laygo, RPh SY 2019-2020

groups including those in several enzymes important for tissue respiration. The antidotal action of BAL (2,3-dimercaptopropanol) depends on its ability to prevent or break the union between antimony and vital enzymes. Moreover, the cause of death is believed to be essentially the same as that in acute arsenic poisoning. LEAD: Lead mimics other biologically important metals, such as zinc, calcium, and iron, competing as cofactors for many of their respective enzymatic reactions. For example, lead has been shown to competitively inhibit calcium's binding of calmodulin, interfering with neurotransmitter release. It exhibits similar competitive inhibition at the NMDA receptor and protein kinase C, which impairs brain microvascular formation and function, as well as alters the blood-brain barrier. Lead also affects the nervous system by impairing regulation of dopamine synthesis and blocking evoked release of acetylcholine. However, it's main mechanism of action occurs by inhibiting delta-aminolevulinic acid dehydratase, an enzyme vital in the biosynthesis of heme, which is a necessary cofactor of hemoglobin PHOSPHORUS: A. Phosphorus is highly corrosive and is also a general cellular poison. Cardiovascular collapse occurring after ingestion probably results not only from fluid loss caused by vomiting and diarrhea but also from a direct toxic effect on the heart and vascular tone. B. Yellow/white phosphorus spontaneously combusts in air at room temperature to yield phosphorus oxide, a highly irritating fume. TREATMEN T OF POISONING

ARSENIC Acute poisoning from arsenic (1) Emergency measures – Remove ingested arsenic by gastric lavage or Emesis. Follow with a saline cathartic. (2) Antidote – Give dimercaprol for 2 days, then penicillamine or succimer. Discontinue antidote when the urine arsenic level falls below 500 μg/24 h. (3) General measures: (a) Treat dehydration by giving 5% glucose in normal saline intravenously. (b) Treat shock (c) Treat pulmonary edema (d) Treat anuria (e) Treat liver damage (f) In severe poisoning use hemodialysis after dimercaprol therapy to remove combined dimercaprol and arsenic. Acute poisoning from arsine Treat hemolytic reaction. Exchange transfusions are useful to remove the hemoglobin–arsine complex. Dialysis is necessary during the period of hemoglobinuric renal failure. Antidotes appear to be useless. Chronic poisoning Remove from further exposure and give dimercaprol or penicillamine. Signs of arsenic intoxication disappear slowly. MERCURY Acute poisoning (1) Emergency measures – Remove ingested poison by gastric lavage with tap water or by emesis and catharsis. COMPILED BY: Ghinelli Anne P. Laygo, RPh SY 2019-2020

(2) Antidote – Give dimercaprol. Penicillamine and succimer are also effective. Neither penicillamine nor dimercaprol is effective against the neurologic effects of alkyl mercury compounds but succimer can increase the elimination of methyl mercury from the brain. A chelating agent should be continued until the urine mercury level falls below 50 μg/24 h. (3) General measures: (a) Treat anuria and shock (b) Treat stenotic lesions of the gastrointestinal tract after appropriate endoscopy. Chronic poisoning Remove from further exposure. Give dimercaprol. Maintain nutrition by intravenous or oral feeding.

Treat

oliguria.

ANTIMONY Acute poisoning (1) Emergency measures (a) Remove ingested antimony compounds by gastric lavage or emesis (b) Remove patient from further exposure to stibine. (2) Antidote – None. (3) General measures – Treat hemolysis from stibine Chronic poisoning Remove from further exposure. LEAD Emergency measures Remove ingested soluble lead compounds by gastric lavage with dilute magnesium sulfate or sodium sulfate solution or by emesis. Treat cerebral edema with mannitol and prednisolone or other corticosteroid . Antidotes Dimercaprol and calcium disodium edetate, and later succimer, should be given to all patients with clinical symptoms of lead poisoning and should be considered for asymptomatic patients with blood lead levels over 80– 100 μg/dl or free erythrocyte protoporphyrin levels over 250–300 μg/dl of whole blood. (1) Urine flow – Initiate urine flow first. Give 10% dextrose in water intravenously, 10–20 ml/kg body weight over a period of 1–2 h. If urine flow does not start, give mannitol, 20% solution, 5–10 ml/kg body weight intravenously over 20 minutes. Fluid must be limited to requirements, and catheterization may be necessary in coma. Daily urine output should be 350–500 ml/m2/24 h. Excessive fluids further increase cerebral edema. (2) For children – Give dimercaprol, 4 mg/kg intramuscularly every 4 h for 30 doses. Beginning 4 h later, give calcium disodium edetate at a separate injection site, 12.5 mg/kg intramuscularly every 4 h as 20% solution, with 0.5% procaine added, for a total of 30 doses. If significant improvement has not occurred by the fourth day, increase the number of injections by 10 for each drug. In patients without encephalopathy who respond well, dimercaprol can be discontinued after the third or fourth day and edetate reduced to 50 mg/kg/24 h for the remainder of the 5-day course of injections. Two to 3 weeks after the first course, if the blood lead level is still above 80 μg/dl, give a second course of 30 injections each of both drugs. Courses of calcium disodium edetate should not exceed 500 mg/kg, with at least 1 week between courses. For follow-up COMPILED BY: Ghinelli Anne P. Laygo, RPh SY 2019-2020

care, place the child in a protected environment to make certain that further ingestion of lead does not occur; give penicillamine or succimer orally. Penicillamine dosage: 30 mg/kg daily in 3–4 doses, for 3–6 months or until blood lead level falls below 60 μg/dl. The maximum dose is 500 mg/d. Give penicillamine on an empty stomach 90 minutes before meals. Succimer dosage: 10 mg/kg every 8 h for 5 days then twice daily for 14 days. Repeat course after 14 day interval until blood lead is below 25 μg/dl. (3) For adults – Adults with acute encephalopathy should be given dimercaprol and calcium disodium edetate in the same way as for children. For other symptomatic adults, the course of dimercaprol and calcium disodium edetate can be shortened or calcium disodium edetate only can be given in a dosage of 50 mg/kg intravenously as 0.5% solution in 5% dextrose in water or normal saline by infusion over not less than 8 h for not more than 5 days. Follow with oral penicillamine 500– 750 mg/d orally for 1–2 months or until urine lead level drops below 0.3 mg/24 h. General measures in acute encephalopathy (1) For cerebral edema, give mannitol, 20% solution, 5 ml/kg by intravenous injection at a rate not to exceed 1 ml/min. Give prednisolone,1–2 mg/kg intravenously or intramuscularly, or other corticosteroid in equivalent doses, every 4 h. (2) Do not use catharsis or enemas in the presence of severe symptoms. (3) Control convulsions with cautious administration of phenobarbital, hydantoin anticonvulsants, or diazepam. Associated depression of respiration may increase cerebral edema and can be hazardous in the acute stage. (4) Reduce fever with cooling blanket. (5) Maintain urine output at 350–500 ml/m2/24 h by giving 10% dextrose in water parenterally. Avoid administration of sodium-containing fluids. (6) Withhold oral fluid, food, and medication for at least 3 days. Special problems (1) In the presence of impaired renal function, dialysis is mandatory. (2) Wrists drop and foot drop may be corrected by splinting and passive exercise until function returns. (3) Toxicity from tetraethyl lead and tetramethyl lead does not respond to chelation therapy. Give barbiturates or diazepam to control hyperactivity. PHOSPHORUS Acute poisoning (1) Emergency measures – Remove poison by gastric lavage with 5–10 liters of tap water. If a gastric tube is not immediately available, induce emesis. Remove phosphorus contamination from the skin or eyes by copious irrigation with tap water for at least 15 minutes. (2) General measures – Treat pulmonary edema. Treat shock. Give 10% calcium gluconate, 10 ml intravenously, to maintain serum calcium. Give 1–4 liters of 5% glucose in water or 10% invert sugar (Travert) in water intravenously daily until a high-carbohydrate diet can be given by mouth. Treat hepatic failure. Chronic poisoning Remove from further exposure. Treat jaw necrosis by surgical excision of sequestered bone.

7. FLUORESCENT LAMP COMPILED BY: Ghinelli Anne P. Laygo, RPh SY 2019-2020

POISONOU S INGREDIEN T MECHANIS M OF TOXICITY

Beryllium salts Mercury

BERYLLIUM Once in the body, beryllium acts as a hapten and interacts with human leucocyte antigen (HLA) DP presenting cells in the lungs, becoming physically associated with a major histocompatability (MHC) class II molecule. This MHC class II-beryllium-peptide complex is recognized by the T lymphocyte receptor, triggering CD4+ T lymphocyte activation and proliferation. The resulting inflammatory response is a cell-mediated process orchestrated by cytokines and results in the formation of (usually pulmonary) granulomas. Beryllium's toxicity may be controlled by the iron-storage protein ferritin, which sequesters beryllium by binding it and preventing it from interacting with other enzymes. MERCURY Mechanism of toxicity. Mercury reacts with sulfhydryl (SH) groups, resulting in enzyme inhibition and pathologic alteration of cellular membranes. A. Elemental mercury and methylmercury are particularly toxic to the CNS. Metallic mercury vapor is also a pulmonary irritant. Methylmercury is associated with neurodevelopmental disorders. B. Inorganic mercuric salts are corrosive to the skin, eyes, and GI tract and are nephrotoxic. C. Inorganic and organic mercury compounds may cause contact dermatitis.

TREATMEN T OF POISONING

BERYLLIUM SALTS Acute pneumonitis (1) Emergency measures: (a) Complete bed rest is necessary. (b) If cyanosis is present, give 40–60% O2 by mask or intratracheal tube as necessary to maintain arterial pO2 above 60 mmHg. Ventilatory assistance may be necessary. (2) Antidote – The administration of calcium edetate has been suggested. (3) General measures: (a) Relieve bronchial spasm – Give epinephrine, 0.2 mg (0.2 ml of 1:1000 solution) subcutaneously, or aminophylline, 0.25 g intravenously every 6 h. (b) Treat bronchial pneumonia – Give organism-specific chemotherapy. (c) For right heart failure – Digitalize. (d) Give prednisone or equivalent corticosteroid, 25–50 mg/d orally, to decrease the hypersensitivity reaction to beryllium. These hormones relieve symptoms but are not curative. Chronic granuloma of lungs (berylliosis) Moderate activity is allowable. Maintain arterial pO2 above 60mmHg by intermittent O2 administration – if necessary, by mechanical ventilation. Adequate oxygenation delays the onset of pulmonary hypertension and cor pulmonale. Skin granuloma and ulcers Excise beryllium-contaminated areas of skin surgically. Beryllium dermatitis or conjunctivitis (1) Remove from further exposure. Wash skin and eyes thoroughly (2) Apply local anesthetic ointment to control pain. COMPILED BY: Ghinelli Anne P. Laygo, RPh SY 2019-2020

MERCURY (refer to the one above) 8. MATCH POISONOU S INGREDIEN T

Phosphorus poisoning from watusi • Synonym: Light – carrier, “St. Elmo’s Fire” Three main allotropic forms: A. White Phosphorous - Colorless or white solid with waxy appearance - Darkens on exposure to light - Sometimes called Yellow Phosphorus, color due to impurities or some add ons - Stored under water  handled using forceps - When exposed to air in the dark, it emits a greenish light and gives off white fumes with garlicky odor - It commonly is found in hand grenades, mortar and artillery rounds, and smoke bombs....