Toxicology T3

• • ORGANOPHOSPHATES
  • Undergoes bond aging in 24 hours (irreversible)
  • Pesticides and chemical warfare agents
  • Sarin, Soman, Tabun, Parathion, Malathion
  • MOT: Acteylcholinesterase (AChE) inhibitor → increase Ach

  • Signs and symptoms: DUMBBELS (Diarrhea, Diaphoresis;

  Urination; Miosis; Bradycardia,

  Bronchoconstriction; Emesis, Excitation; Lacrimation; Salivation)

  • Treatment: Atropine - anticholinergic
• ORGANOCARBAMATES

  No CNS toxicity (milder effect)

  Short lived → spontaneous hydrolysis of carbamylated AChE (reversible)

  Treatment:: Atropine
• STRYCHNINE

  • Blocks glycine → seizures
  • Signs and symptoms: Rigor Mortis,Spinal Convulsion,Sardonic Smile
  • Treatment: IV Diazepam Phenobarbital Neuromuscular Blockers
• • PHOSPHORUS2 forms:
  • Red: non-poisonous (matches), granular, non-absorbable
  • White: highly poisonous (watusi), waxy, fat-soluble

  + H2O/Acids → phosphine gas (PH3) → hemolysis

  Signs and symptoms:

  Luminous vomit

  Garlic odor breath and stools

  Loose teeth

  • Treatment:

  Gastric lavage (CuSO4)

  Diazepam or Barbiturates (Seizures)

  Ca Gluconate (Hypocalcemia)
• THALLIUM

  • rat, roach and ant killer (now prohibited); in fireworks, in cardiac imaging
  • MOT: Membrane depolarizationSH bindingInduces riboflavin defiency
  • Signs and Symptoms: Gastroenteritis AlopeciaGarlic breath odor (after 2-3 weeks)
  • Treatment: Gl decontamination and gastric lavage Forced diuresis with furosemide and KCI supplements Oral Prussian blue (Ferriferrocyanate) Diphenyldithiocarbamate
• ANTICOAGULANT

  • coumarin derivative (Racoumin - rat killer)
  • internal haemorrhage
• HYDROGEN SULFIDE (HS)

  • sewer gas, stink damp; released from decomposing organic matter and other S-containing compounds
  • Signs and symptoms: Local mucous membrane irritation Respiratory depression Knockdown (collapse within seconds)
  • Treatment: Amyl nitrite (inhalation) & Na nitrite (IV) Hyperbaric 02 (2-3 atm) → used even after hours of exposure
• CARBON MONOXIDE (CO)

  • product of incomplete combustion or second-hand smoke
  • MOT: CO + Hgb → carboxyhemoglobin (lacks 02 carrying capacity) → hypoxia CO + Cytochrome oxidase → inhibit respiratory function. Treatment: 100% 02, Artificial air (80% He, 20% 02) Hyperbaric 02 (at 3 atm)
• SILICA

  • Silicosis → lung fibrosis and bronchogenic cancer
• ASBESTOS

  • Fire retardant, fire proof clothing of fireman
  • Any metal that breaks down into fibers; most common: Chrysolide (Mg silicate with 40% silica)
  • Asbestosis (silicosis) and lung CA
• CARBON TETRACHLORIDE (CCI4)

  • Non-flammable solvent (cleansing fluids and fire extinguisher)
  • Toxic metabolites: Epoxide (most toxic metabolite) + heat/acid → phosgene/ warfare gas (hepatorenal toxin)
• • CHLORAMINE T in milk
  • + H20 releases 12% CI (H2O purifier, mouthwash)
  • In vivo: transformed into CN derivative → cyanosis, respiratory failure, collapse
  • Treatment: Na nitrite (with amyl nitrite; Na2S203)
• TARTRAZINE

  • Food colorant, FD & C #5 (Yellow)
  • Allergies and anaphylacic reacions Cros-sensivity with AS
• MONOSODIUM GLUTAMATE (MSG)

  • Chinese restaurant syndrome
  • Signs and Symptoms: Pressure in headTightens of faceSeizure
• ARTIFICIAL SWEETENERS

  • Saccharin (300x sweeter than sucrose) - urinary bladder metastases in rats and mice (carcinogenic)
  • Aspartame (180-200x sweeter than sucrose) - neurotoxic (decrease serotonin levels, depression), fetotoxic
• CLEANING SUPPLIES

  • Drain cleaners, oven cleaners, lye and toilet bowl cleaners are among the most dangerous of the cleaning supplies at home. Ammonia, bleach and polishers can be poisonous if swallowed. Breathing in fumes or accidental dermal exposure can also cause toxicity.
• PERSONAL CARE

  • False finger nail remover, hand sanitizer, facial cleansers and mouthwashes are extremely dangerous especially for children because of their high alcohol content.
• PAINTS AND PAINT THINNER

  paint thinners and paint chips may cause acute poisoning (by inhaling fumes or swallowing) and as well as chronic toxicity (lead poisoning) due to its lead content. Paint thinner fumes are especially toxic and paint thinner should only be used in a well-ventilated area.
• Metals are typically defined by physical properties of element in solid state.
• Toxic metals, including "heavy metals", are individual metals and metal compounds that negatively affect people's health.
• MIMICRY - acting as mimic of essential metals, they bind to physiological sites that are normally reserved for an essential element as replacements.
• METAL-MEDIATED OXIDATIVE DAMAGE - many metals can directly act as catalytic centers for redox reactions with molecular oxygen or other oxidants producing oxidative modification of biomolecules such as proteins or DNA.
• METALLOTHIONIENS are best known example of metal binding proteins. These thiol ligands provide the basis for high affinity binding of several essential and toxic metal including zinc, cadmium, copper and mercury.
• TRANSFERRIN is a glycoprotein that binds most of the ferric iron in plasma and helps the transport of iron across cell membranes. This protein also transports aluminium and manganese.
• CERULOPLASMIN IS a copper-contaning glycoprotein oxidase in plasma that converts ferrous iron to Ferric lon.

  which then binds to transferrin and also stimulates iron uptake by a transferrin-independent mechanism.
• FERRITIN is a primary storage protein for iron
• ARSENIC

  • The 1s chemotherapeutic agent was derived from organoarsenic compounds

  Lewisite metal in manufacturing of insecticides.

  Ex. Paris green, Fowler's and Donovan solution
• Arsphenamine

  also known as Salvarsan or compound 606,

  is a drug that was introduced at the beginning of the 1910s as the first effective treatment for syphilis. (Obsolete; New: Benzethine Penicillin)
• Napoleon - chronic Arsenic poisoning
• Arsenic poisoning Antidote:

  BAL (British Anti Lewisite), combined with Penicillamine or DMSA if severe
• CADMIUM

  • Found in anti-dandruff shampoo, in smoke and stink bombs
  • Toxicity: Itai-itai
• Signs and symptoms of cadmium poisoning:

  • Fanconi-like syndrome (kidney problem)
  • Renal tubular dysfunction
  • Proteinuria, fractures, gail disturbance
  • Chronic pulmonary diseases
• Treatment For cadmium poisoning:

  EDTA
• LEAD

  • Found in canned goods, automobile exhaust as tetraethyl lead, wine glasses, old pipes, cables, paint, and newspapers.
  • MOA: interfere with heme synthesis and cytochrome production, inhibits ALA dehydrogenase and coproporphyrinogen decarboxylase.
  • Distribution: soft tissues: kidney, liver; hard tissues: teeth, bones
• Signs and symptoms of lead poisoning :

  Acute: milky vomitus - Pb + HCI = PbC/2

  Chronic: known as Plumbism

  CNS: Lead encephalopathy, insomnia, HTN, disorientation, agitation, lead palsy (foot drop or wrist drop) due to degeneration of motor neurons)

  GIT: Anorexia, and persistent metallic taste, black gum lines, black stool Blood: Microcytic anemia, Hypochromic anemia
• Treatment for lead poisoning: Calcium disodium EDTA, BAL, DMSA
• MERCURY

  • "Quick silver", found in thermometers and cosmetics.
  • Source: inhalation, mercuric salts, organic mercurial
  • MOA: binds to sulfhydryl groups
• Signs and symptoms of mercury poisoning:

  Triad of poisoning (gingivitis, excitability and tremors)

  Acute: CV collapse, Anuria (volume of urine is below 3ml)

  Chronic: CNS: tremors, irritability and psychosis

  Eyes: Mercurialentis (brown coloration of the anterior portion of the optic lens)

  Mouth: Stomatitis

  Others: Acrodynial/Pink diseas (pink palms and soles)
• Toxicity of mercury poisoning: Minamata Disease
• Treatment for mercury poisonin:

  • High level exp: Dimercaprol/BAL;
  • Low level exp: Penicillamine

  Na Formaldehyde Sulfoxinates (most useful)