Supportive or Symptomatic Treatment 11/4/2011

1. Supportive or Symptomatic Treatment11/4/2011 Management of Poisons in Conscious Patient: 1) Establish and stabilize adequate vital signs of Patient(CV, Respiration, CNS) 2) Clinical evaluation(Lab test, blood chemistry, liver enzymes) 3) Determine the cause for the symptoms (body temperature, pupil size, breath) 4) Removal of unabsorbed or the remaining portion of poison from the site of exposure * immediate action *gastric emptying, (emesis, lavage,cathartics, neutralization,antidotes), * enhance elimination (diuresis, changing urine pH), * artificial & mechanical removal of the remaining poison) 5) Supportive & Symptomatic Treatment 6) Patient Disposition 7) Poison prevention

2. Supportive or Symptomatic Treatment 5) Supportive & Symptomatic Treatment a) General treatment strategy of relieving symptoms without actually treating the cause (at this point, symptoms is treated and not the poison) b) Regular medical treatment of each symptom separately (nausea & vomiting, bleeding, changes in body temperature, CV, seizure, convulsion) c) If the patient is suffers from acidosis, most likely is hyperkalemic ( K) & has an electrolytes imbalance (Na+ & K), Na+ level needs to be adjusted d) Adjust respiratory gases e) If bradycardia develops, an external pacemaker may be necessary f) If sever hypotension develops, an Intra-Aortic Balloon Pumps (IABP) is inserted into the aorta to help maintaining blood pressure g) If hyperthermia develops (ASA & salicylates can produce hyperthermia & may lead to seizers in children), use of Tepid sponging (warm water) to return the child normal temperature (also used for restless, tense patient) h) Ice packs and alcohol sponging should not be used for toxic poisoning

3. Disposition • After released from hospital, patient should follow up with recommended treatment for the specific symptoms • Legal issues should be address: • If toxicity is resulted from suicide or homicide attempted, authorities must be notified • Psychiatric should follow up regularly for the suicide cases • If a child was overdosed, the case should be reported to Social Service • Substances resulted in chronic effects, should be monitored & need follow up: • acetaminophen (APAP) may cause delayed liver damage (liver enzymes must be monitored regularly • Iron overdose, may cause delayed mucosal effects & clotting deficiencies • Any slow in improvement of the condition, patient should be referred to specialist

4. Poisoning Prevention (1) • Storage: medicines & chemicals should be stored safely out of reach & out of sight of children, up high (at least 5-6 ft high) in a locked or child resistant cupboard. Many poisonings occur when a product or medicine is not in its usual storage location, when it is in use and left on a bench top or bedside table, or during transport from shop to home. • Safe use: Use medicines and chemicals safely. Read directions for use carefully. Do not leave them unattended whilst in use. Separate medicines from household products. • Identification: Be sure that all products are properly labeled. Read the label carefully before use. • Regular clean up: Clean out your medicine cupboard every several weeks. Take unwanted and out-of-date medicines to your nearest pharmacy for disposal. • Children tend to imitate adults, so avoid taking medicines in their presence. • Refer to medicines by their proper names. They are not lollies.

5. Poisoning Prevention (2) • Watch the children at home: Visitors' bags may contain medicines. Keep them well out of reach of children. Also, the incidence of poisoning increases when usual household routines are disrupted (moving being on holiday, parties and having visitors). • Use child resistant packaging: always ask for and use household and medicines which are in child resistant packaging (e.g., blister or strip packs or special push and turn lids). • Know what you are taken: Always take medicines in a well lit room, wear yourglasses. Follow the directions for use carefully and accurately. Do not take other peoples medicines. • Use of house cleaning: Use appropriate protection when painting, spraying or oven cleaning. Follow the directions for use. Protect skin and eyes. Ensure there is adequate ventilation, with air circulating continuously. Remove any contaminated clothing immediately. • Rinsing: all empty containers from liquid medications or household products should be rinsed with water before they are thrown out. • Keep everything in original containers and never in cups or soft drink bottles.

6. Agents-induced toxicity • Hypoxia Producing Poisons • Carbon monoxide • Cyanide toxicity • Corrosives and house hold cleaners toxicity • Toxicity of drug of abuse • Toxicity of therapeutic agents and drug overdose • Radiation toxicity • Pesticides/Insecticides and Insect Repellants toxicity • Rodentcidies and Herbicides toxicity • Heavy metals toxicity • Food Poisoning • Natural and other environmental toxins (i.e, Radon)

7. Agents-induced toxicityHypoxia Producing Poisons Carbon monoxide (CO) poison • Endogenous & Environmental sources of CO: • Produced endogenously in human body @ rate of 0.4 %/hr (breakdown of the heme protein) • The level is much higher in smokers (5-10% Carboxyhemoglobin COHb) • CO produced as a result of incomplete combustion • Burning Natural gas water heater, oil, coal, gasoline (garden tools), wood burning stove/fireplace • Faulty gas stoves, faulty space heaters, unclean chimneys, and car exhaust • This has been used for the purpose of suicide (car exhaust) Why CO is so treacherous: It is odorless, colorless, and tasteless know as the silent killer *** CO poisoning cause the death of 500 persons/year & 15,000 visit to the hospital emergency room/year (CDC)

8. Hypoxia Producing PoisonsCarbon monoxide (CO) poison * It has a high affinity for hemoglobin (250 times that of O2) * It will also displace O2 very rapidly & decreases O2 dissociation from hemoglobin (make O2 not readily available to the tissues, causing hypoxia §    * Hypoxic hypoxia (Hypoxia to tissues as a result of hypoxia in the blood) §    * The brain and the heart are most affected -The brain can not perform any anaerobic reactions (depends on O2)        - The final reason CO is so treacherous is because at low levels it produces fainting. §

9. Hypoxia Producing PoisonsCarbon monoxide (CO) poison Symptoms of CO poisoning: * < 10% (%= the amount hemoglobin converted to carboxyhemoglobin, COHg), no serious symptoms • * 20% - headache, tightness across forehead, dilation of blood vessels • * 20-30%, visual disturbances, sever headache (brain function is affected),Tachycardia, Tachypnea, Possible nausea and vomiting * 30-40%, increased Tachycardia and Tachypnea, Syncope (fainting), inability to leave the place where the poisoning is taking place • * 50%, while in syncope, there is an increase in neuronal activity and convulsions result, coma develops due to exhaustion of the CNS • * 60% and higher, DEATH

10. Carbon Monoxide Poisoning

11. Carbon Monoxide Poisoning

12. Carbon Monoxide Poisoning    * Populations with increased sensitivity to CO (at high risk): • oAnemic • oFemales, due to having less hemoglobin • o   Children, due to their high metabolic rate • o   Chronic Obstructive Pulmonary Disease (COPD) • oHyperthyroid sufferers due to  metabolic rate

13. Carbon Monoxide Poisoning • * Treatment and Prevention of CO poisoning: - Resuscitate the patient (ASAP, Sustain respiration, CNS, and circulation ) • - Give pure 100% O2 • - CO has a half-life of 4 hours (Carboxyhemoglobin). If we use 100% O2, we will decrease CO half life to 40 minutes (Decreased chance for brain damage). • - It the patient is placed into a hyperbaric chamber the CO half life will be decreased even more to 20 minutes.

14. Carbon Monoxide Poisoning * * Treatment and Prevention of CO poisoning * To get rid of the cerebral edema • - Use an osmotic diuretic (Mannitol)          - Give a glucocorticoid (Prednisone) to decrease inflammation • - Due to anaerobic metabolism, acidosis may develop • -Can lead to coma (give IV Na HCO3) • -Can also cool the patient to decrease the demand of the CNS • In any case, if one even suspect CO poisoning, do not hesitate to call the National Poisoning Control Center 24/7. Do not wait until is a matter of life and death • Prevention: Install CO detector (every home should have one)

15. Carbon Monoxide Poisoning • * Outcome of CO poisoning • § Impairment of the CNS • § Muscle Weakness • § Depression • § Parkinson’s –like symptoms • § Decreased & blurred vision • § Numbness in the extremities • § Speech impairment • § Paralysis • § various degrees of symptoms may last for up to two years after the incident • § If exposure was the result of car exhaust fumes, then treat the CO poisoning and also for alcohol intoxication.

16. Hypoxia Producing Poisons2) Cyanide Poisoning • Cyanide is 1st isolated in pure form in 1786 by Scheele from the dye Prussian blue • Its sever toxicity was also discovered by Scheele (was killed when inhaling the vapor) • One of the most rapidly acting lethal poisons known to the public • i.e., homicidal disasters as the Jonestown massacre 33 years ago • Cyanide-laced Tylenol in Chicago in 1982

17. Cyanide Poisoning • Cyanide (CN- ) negatively charged ion • It present either in the gas form as Hydrogen Cyanide(HCN), as a liquid or solid forms as Cyanide salts • At physiological pH 7.4 (unbound), in present in the form of HCN • HCN Can be formed when acid added to a Cyanide salt • It is concentrated in the RBC than in plasma (100:1) • In RBC, 92-95% CN- is bound to Hb

18. Cyanide PoisoningSources of exposure 1) Industry: • electroplating (HCN gas or particulates in the air) • Extraction of Ores (gold and silver) • Metal processing • Manufacturing of plastics, pesticide, rodentcidies • Hair removal from hides (in tanning industry) • In pressure-treated wood (lumber) • Acetonitrile: a chemical widely used in laboratories & some cosmetic removal is metabolized to CN when ingested

19. Cyanide PoisoningSources of exposure 2) Plants: (food/dietary supplements) • Many plants (fruit pits of Apricot, Bitter Almond, Peach, Plum) containing Amygdalin a cyanogenic glycoside, a cyanide producing substance (glucose, benzaldehyde + CN) • The enzyme -glucosidase (found in these plants and in human GI tract) will hydrolyze the glycosides  HCN • Amygdalin (active ingredient in Laetrile) is hydrolyzed by the enzyme emulsin (in GI)  HCN • CN poisoning will develop if the kemels (i.e. Almond) is eaten raw • Once the kemels are processed, destroying the emulsin and CN poisoning will notoccur

20. Cyanide PoisoningSources of exposure 3: Combustion: - Small amount is endogenously produced in human body (Vit B12 metabolism) - Polyurethane, a commonly used in modern plastic furniture, release CN on combustion • Silk and wool will release CN during fires • Smoke inhalation, death will be due to both CO & CN • Cigarette smoking (each release 150-200 g of HCN) • Burning pressure treated wood in close place will release HCN gas

21. Cyanide PoisoningMechanism of Action • Toxicity occurs by either respiratory, PO and dermal routes. • Produces cytotoxic hypoxia (interferes with cell metabolism in the presence of normal blood and O2 supply) = metabolic inhibitor. • HCN binds to heme iron in the cytochrome oxidase (a-a3) (has high affinity for Fe+++) forming a complex • This complex inhibits the final step of oxidative phosphorylation where O2 is used for the production of ATP • Aerobic metabolism stops (cells will not be able to use Q2), Patient essentially suffocates

22. Cyanide PoisoningMechanism of Action • Cyanide inhibits mitochondrial cytochrome oxidase , thus blocks electron transport, resulting in decreased oxidative metabolism and oxygen utilization • Lactic acidosis occurs as a consequence of anaerobic metabolism (accumulation of Lactic acid). • Most affected cells are at the heart & CNS

23. Cyanide PoisoningSymptoms • Acute: • Depends on the dose, route of exposure & duration • CNS (most sensitive), headache, nausea, vomiting, confusion, restlessness & anxiety, tachypnea with convulsion (are immediate, within few min) • Severe poisonings progress to tachycardia and tachypnea, comma, fixed dilated pupils and death (occur within minutes)

24. Cyanide PoisoningSymptoms • Acute • Skin/Ocular: • In sever poisoning, skin is cold • Cyanosis may be develop late • Retinal veins and arteries may appears similar in color • CVS: (required higher dose than that of CNS dose) • Tachycardiafollowed bybradycardia • Hypotension followed by peripheral vascular collapse • Abnormal ECG & pulmonary edema

25. Cyanide PoisoningSymptoms • Chronic: • Long-term CN exposure  Occupational –related, heavy smoker will cause headache, dizziness, nausea, or vomiting, psychosis • Tobacco Amblyopia: visual impairment not due to lesion & abnormalities in the optic disk, but due to direct effect of CN on the eye • (Vit B12a) improve visual acuity in some patients)

26. Cyanide PoisoningManagement For prevention: small doses of Na+ Nitrite: (Sequesters CN before it gets into the cells) • * Give a mild nitrite by inhalation (2 pearls of Amyl Nitrite (crushed and rubbed on the face) • * Several drugs are used: • 1) Amyl nitrite (by inhalation), followed by • 2) Na nitrite (by IV), initial dose 300 mg/adult • * these combination will convert Hb to methemoglobin and the formation of Fe+++ heme • * The Fe+++ will bind to CN forming a stable complex Cyanmethemoglobin • * As a result the free CN in circulation will ↓ • Be careful with the Nitrites, massive vasodilation and server hypotension are possible

27. Cyanide PoisoningManagement • * Permanent & irreversible intoxication of CN is by IV injection of Na thiosulfate • -25% Na + Thiosulfate 50ml, IV (Provides Sulfur for the • enzymes Rhodanase) •     - The enzyme Rhodanase converts CN to Thiocyanate (inactive) which is excreted in the urine

28. Cyanide PoisoningLaetrile • * Used to be found in health food stores as a nutritional supplement for malignancy • *Obtained from the kemels of peaches, apricots, and almonds • * Contain amygdalin (a cyanogenetic glycoside), CN is liberated by the enzyme, emulsin (which works better in alkaline pH) • -Used in more than 22 countries for cancer treatment (falsely) • - It kills cancerous and normal cells - Children have a higher incidence of toxicity because they have a more alkaline environment in their GI - 2-3 tablets are lethal

29. Toxicity induced by household chemicals1. Corrosive Alkalis

30. Toxicity induced by household chemicals1. Corrosive Alkalis • *Occurs most often in Toddler’s and children • *Alkalis are present in many household products: • Liquid plumber, Drano, Oven cleaners, Glass cleaners (ammonia), Dishwasher detergents, Lye, Drain openers, Alkaline batteries • *Alkaline batteries are dangerous to children because they are small and easily swallowed. • * Alkaline dissolve tissues • Liquefy membrane by interacting with proteins to form water soluble salts & lipids through saponification • *Solubilized cellular membranes • - Protein, Na, K, Salt • -Very penetrative & cause perforation

31. Toxicity induced by household chemicals1. Corrosive Alkalis • * Penetrating effect: -Least: sticking together of esophagus walls –stricture • - Worst: perforation of membranes if swallowed • ·At high doseAlkalis, can produce either an immediate death to a delayed death ************************ • Acute effects: • - Severe irritation of the eye, skin and other dermatoses • Eye: disintegration and sloughing of the conjunctival and corneal epithelium, corneal opacification, edema, ulceration) • Skin: severe burn, deep skin ulceration, loss of hair • mucous membrane: corrosion of the lips, mouth, tongue and pharynx,

32. Toxicity induced by household chemicals1. Corrosive Alkalis • Chronic effects: • §Esophageal strictures may occur in small doses, which can lead to respiratory distress. • §Burns (can be 1st to 3rd degree burns) causing skin scaring • §Permanent corneal opacification • §Dehydration which can lead to immediate death (From traumatic shock and severe pain that leads to cardiovascular and CNS collapse) • §Delayed death (24-48 hours later), (Due to internal injury caused by perforation) • §If the alkalis ingested is a small amount and make it into the stomach, usually the acid will neutralize the toxin. • §If ingestion occurred, usually bloody emesis will be seen and the patient will be unable to swallow so drooling may result.

33. Toxicity induced by household chemicals1. Corrosive Alkalis • Management • *Removal from exposure ASAP • *Flushing the eyes and skin with lots of water • *Use of an antibiotics ointment to prevent ocular adhesions • *Nothing should be given by mouth to dilute the poison (unless the patient is in the act of swallowing) • *If is already swallowed, give diluted vinegar or fruit juice to balance GI pH, followed by administering eggs or gelatin, followed by stomach emptying where possible • *Stomach intubation’s is not recommended because the possibility of penetrating of the abdomen • * If the alkalis were spilled onto the body, use Morphine to reduce the pain and IV fluids should be given to reduce shock

34. Toxicity induced by household chemicals1. Corrosive Alkalis • * Treatments of esophageal stricture, • §Antibiotics (Penicillin or Ampicllin) • §Prednisolone to decrease inflammation of the esophagus • §Feed with a gastric tube 2-3 days after the ingestion • §Use special catheters (which have Mercury on the end which slide down the esophagus by gravity and do not have to be pushed forcefully).       * Esophageal replacement: • Previously, a portion of the colon was used • Recently, a Reserve (inverted) gastric tube replacement is performed • A portion of the stomach is formed into a tube to act like the esophagus (Continuity is not broken and the blood supply is not interrupted)

35. Toxicity induced by household chemicals1. Corrosive Alkalis • Batteries • ·Alkaline • ·Toddler’s favorite are attracted to their size • ·If swallowed and there is no obstruction, the batteries will not burst and leak their contents • ·If the battery is excreted into the feces, no action should be taken • ·Observe the child for 24-48 hours, if the battery is not passed, then an x-ray should be performed • ·If the battery is obstructed, the alkaline content may leak and perforation may occur. • ·At this point, the battery should be removed by surgery

36. Toxicity induced by household chemicals2)Strong or concentrated Acids • Source of exposure: • -Any acid solutions used for cleaning brick, garage (concrete) or bathroom floor • -Acids will not affect the lipids of the membrane, but will cause coagulation of the proteins • - The penetrative power is much less then the alkalis • - Acids produce more charring (burning) and cause more pain

37. Toxicity induced by household chemicals2)Strong or concentrated Acids Pathology a) Acute Toxicity: • -If ingested: ==►burning in the mouth, esophagus, stomach with pain, nausea & vomiting • -If inhaled: ==► coughing, burning in the throat, inflammation of the nose, eye laryngeal spasms, pulmonary edema • - Dermal: skin burn, dermatitis b) Chronic Toxicity: - Prolong exposure to diluted solutions ==►dermatitis, tooth erosion

38. Toxicity induced by household chemicals2)Strong or concentrated Acids Duration of Symptoms: • -7-14 days depending or the rout of exposure Treatment: • -Flush the skin, eye with H2O • -If inhalation is the rout, use 60-100 % O2 • -For lung inflammation ==► use steroids (i.e.Prednisolone) • -For GI ==► use milk of magnesia (as an antacid and laxative)

39. Toxicity induced by household chemicals3)Phenols Source of Exposure: - Disinfectants, (at homes, hospitals, school,….), cleaning solutions - Occupational exposure (manufactures, packing, distribution, storage or use) - In some skin medication, vaccine, inks

40. Toxicity induced by household chemicals3)Phenols Pathology a). Acute Toxicity: • -dark-colored urine • -mucous membrane whiting • -skin numbness, necrosis • -GI disturbance • -CNS effects b). Chronic Toxicity: - Similar to acute, but resulted from long term and repeated exposure

41. Toxicity induced by household chemicals3)Phenols • Duration of exposure: • - If seizure developed ==► death due to respiratory OR cardiac collapse • - If hepatic & renal failure developed ==►death occurs after several days • Pathology: • -esophagus appears tanned • -cerebral edema • -cardiac dilation • -degeneration of glomerular and tubular cells of the kidney

42. Toxicity induced by household chemicals3)Phenols • Treatment: • -Dermal: wash skin, eye with H2O (for at least 15 minutes) • -If seizure developed ==►control with diazepam or Phenobarbital • - If ingested ==►Do not induce vomiting. Do not dilute (may absorption). Give polyethylene glycol solution or activated charcoal with Sorbitol. wash stomach repeatedly with 25% bicarbonate

43. Radiation Toxicology • Source of Radiation: • 1) Cosmic, radiation present in environment, radio active materials in soil, rocks,…. • 2) X-Ray diagnostics, dental, industry, T.V., industrial X-ray machine, cobalt treatment for cancer, other 238PU 3) Radioactive Pharmaceutics: used for diagnostic purpose and/or treatment (e.g.,131 I), in vivo or in vitro, in RadioImmunoAssay (RIA) kit 4) Reactors: operate on the basis of nuclear fission, in peace time, they produce energy and power

44. Radiation Toxicology Factors affecting toxicity: 1) Depend on the types of particles (α, Causing high degree of cell damage, β or γ ) 2) Dose and frequent of exposure 3) Whole body irradiation vs. partial exposure 4) Type of elements (radium, tritium) 5) t1/2 6) Tissue uptake and concentration 7) Type of tissue exposed Toxic effects: • - Radiation react with H2O to form free radicals • - Free radical interact with cell molecules - The result changing in cell function

45. Radiation Toxicology • Toxic effects: * Radiation react with H2O to form free radicals • * Free radical interact with cell molecules • * The result changing in cell function • Symptoms: •  * Anorexia, nausea, vomiting, diarrhea, apathy, headache, fever, tachycardia, anemia

46. Radiation Toxicology • Delayed effects: • *Mutation • * Sterility • * Carcinogenesis • * Alopecia • * Shorten life expectancy (due to cancer) • *Cataract • Treatment • * Blood transfusions • * Antibiotics • * Supportive

47. Radiation Toxicology • Preventive measures • * Don’t smoke, eat or drink while handling radioactive materials • * Wear protective clothes • * No radiation exposure during pregnancy • * Use Pb shield for X-ray •  * Keep distance from α, β • * Every thing should be prepared under a designated hood, disposed correctly

48. Principle of ToxicologyDecember 2, 2011 Agents-Induced Toxicity I. Natural Substances • Animal source Fish (Puffer fish) • Plant source (Wild Mushroom) II. Heavy Metals • Lead (Pb) III. Drug of Abuse • Amphetamine • MDMA • Cocaine

49. Toxicity induced Natural Substances • Animal Sources (fish) • More than 700 species of marine fishes are toxic (due to injury OR after ingested by human): • Some have tissue that are toxic at all times, • other are toxic at a specific period/areas and • some have specific organs that are toxic • Most potent marine toxin is Tetrodotoxin

50. Toxicity induced Natural Substances1) Fish (Puffer fish) • Fish-induced human poisoning: • Globe fish = puffer fish, contains a potent and deadly toxin called tetrodotoxin. • The toxin is concentrated mainly in the eggs (ovaries), liver and skin. • The organs containing toxins even after careful removal, there are still chances that the flesh of the fish will be contaminated. • The toxin cannot be destroyed by drying, cooking, or freezing. • The toxin can affect a person’s central nervous system, and in extreme cases, can cause death. • There is no specific antidote at present