General Toxicology

1. General Toxicology By: RajiaMahmoudHejazy MD CLINICAL TOXICOLOGY Assistant professor of clinical toxicology Faculty Of Pharmacy, & Faculty of Medicine Umm Al-Qura University, KSA Benha University, EGYPT

2. GENERAL TOXICOLOGY • Classification of poisons: • I- According to their mode of action: • a) Poisons with local action: • They act locally producing immediate destruction of the tissues with which they come in contact e.g corrosives (except organic acids). • b) Poisons with remote action: • They act only after absorption without any local effects e.g plant poisons which act mainly on CNS. • c) Poisons with both local and remote actions: • As irritant metallic poisons (lead, Mercury, arsenic,..etc) which have a local irritant action on the tissues they come in contact for sometime and a remote action (on parenchymatous organs) after absorption.

3. II- According to the organs affected: • The poison may be: Hepatotoxic: APAP, phosphorus, CCL4 and arsenic, Cardiotoxic: digitalis, Nephrotoxic:mercury, ASA Neurotoxic: alcohol …. etc. • III- According to the chemical nature: • Acids: like H2SO4, HNO3 and H2CL. • Alkalies: as caustic soda & caustic potash and ammonium hydroxide. • N.B. The source of the poison may be considered as in cases of plant and animal poisons.

4. IV- According to Use • (e.g., pesticide, solvent, food additive) • V- According to Effects - (e.g., cancer, mutation, liver injury) • VI- According to Labeling requirements - (e.g., explosive, flammable, oxidizer) • VII- According to Poisoning potential - (e.g., very or slightly toxic)

5. Factors affecting the severity of toxicity: • Factors related I- to the person II- to the poison • I- 1) Age of the person & individual suscptibility: • Children and old people generally are more susceptible to the toxic agents due to decrease detoxification power. However, children can tolerate the action of atropine, but not morphine.

6. 2) Genetic factors: Persons suffering from glucose-6-phosphate dehydrogenase deficiency are susceptible at therapeutic doses to hemolytic effect of some drugs like vitamin K and sulphonamides. Drug rash

7. 3) Personal hypersensitivity: • Very small harmless doses can produce severe symptoms in sensitive patients e.g. therapeutic dose of penicillin or iodine may produce anaphylaxis in some hypersensitive patients. • 4) Tolerance: • Repeated intake of substances of abuse leading to the development of tolerance where the addicts can stand big dose without ill-effect. So, they have to increase the dose to get the same effect.

8. 5) Idiosyncrasy: • Abnormal response to some drugs e.g. morphine may produce convulsion instead of depression of CNS. • 6) State of health : • Patients suffering from liver or kidney diseases may show signs of increased toxicity of the poisons. • 7) Synergism: • The action of one drug may be increased if given with another drug e.g. alcohol and barbiturate.

9. 8) Condition of the stomach: • - Type of food: • Fatty foods delay the absorption of arsenic while they increase the absorption of some poisons as DDT and phosphorus. • - Gastric secretion: • Poisoning with potassium cyanide may not be fatal in case of achlorhydria as HCL in stomach is important to form the severely toxic hydrocyanic acid. • Empty or full stomach : • A poison taken on full stomach has slower action than the same dose of poison on empty stomach.

10. II- Factors related to the poisons: • 1) State of the poison. • Poisons in gaseous form are more rapidly absorbed followed by liquid poisons, fine powder, then big lumps. • 2) Routes of administration: • The quick.. inhalation followed by IV, IM, SC, ingestion, absorption through mucous membranes, lastly absorption through the intact skin which is minimal except in some poisons as organophosphates, phenol & tetraethyl lead.

11. 3) Dose of the poison: • The bigger the dose, the more toxic the effect. However, this is NOT a general rule as big doses of metallic poison may cause severe vomiting, so eliminate most of the poison. • 4) Cumulation: • After repeated small doses of certain drugs, that are not readily metabolized, the effect of a single large dose is reached leading to poisoning e.g. digitalis.

12. Diagnosis of Poisoning: • 1- History and circumstantial evidences. • 2- Clinical manifestations. • 3- Investigations.

13. 1- History and circumstantial evidences: • - Sudden appearance of toxic manifestations in a healthy person or a group of persons after taking certain food or drink (as food poisoning, methanol and carbon monoxide toxicity). • - History of intake a poison, financial problems, psychiatric troubles, previous attempts at suicide or threatening by somebody. • - Presence of bottle of tablets or insecticide near the victim . • - Patients rescued from fire (CO, cyanide).

14. 2- Clinical manifestations (signs and symptoms): • - Vital signs: • Temp, Pulse, BP,Respiratory rate Breath odour, Pupil, Skin • Recorded in initial evaluation & repeated regularly.

15. Temperature: • *Hyperthermia: a,ss,t • a: anticholinergics. • s: salicylate , sympathomimetics • t: tricyclic antidepressants. • *Hypothermia: in CNS depressants (a,bb,o) • a: alcohols • b: barbiturate+ benzodiazepines. • o: opiates.

16. Pulse: • *Bradycardia:(a,b,c,d,o) • a: atropine (early), • b: beta blockers, • c: cholinergics, calcium channel blockers • d: digitalis, • o: opiates. • *Tachycardia:(It can occur late with any poison) • Anticholinergics. • Sympathomimetics.

17. Blood pressure: • *Hypertension:CNS stimulants (AC) • A:Amphetamine • C:cocaine • *Hypotension & tachycardia:occur late with any poison.+ theophylline and TCA • Respiratory rate: • *Tachypnea:ACT M • A:Aspiration pneumonia ( kerosine). • C:CNS stimulants ( cocaine,amphetamine), • T:Toxic hypoxia ( CO2, CO, cyanide), • M:Methemoglobinemia. • *Bradypnea:CNS depressants.(a bb o)

18. Breath smell: • Cyanide: (bitter almond) • Arsenic, OPC Garlic • Camphor Mothballs • Cyanide Bitter almond • Methyl salicylate Wintergreen • Paraldehyde Pears • Hemlock Carrots • Pupils: • *Miosis:OO, PP, CNE(D.D pontine hemorrhage). • OO: opiates, organophosphates, • PP: phenol (early stage), phenothiazine • C: carbamates • N: nicotine • E: ergot

19. *Mydriasis: • Dilated & reactive: • CNS stimulants • nicotine • opoid withdrawal • Dilated & fixed: • Anticholinergics • late in any poisoning • brain stem lesion

20. Skin: • *Needle tracksin IV drug abuse • *Bullous lesionsin prolonged coma with prolonged pressure and skin hypoxia e.g. sedative hypnotics (especially barbiturates) & CO • *Flushinganticholinergics (flushed & hot), • alcohol (flushed & cold) • *Diaphoresis (CANOS) • C: carbamates • A: alcohol withdrawal • N: nicotine • O:organophosphates, • S: salicylates, • (D.D. hypoglycemia).

21. *Red:CO & cyanide • *Cyanosed:CNS depressants • *Jaundiced: (appi)arsenic, phosphorous, paracetamol, iron • *Petechiae & ecchymosis e.g. salicylates. • *Patches or escharsaround the mouth in corrosives.

22. Clinical examination: 1-Respiratory system: Wheeze, pulmonary edema *Wheezing:(due to bronchospasm) ipcco e.g. irritant gases & fumes, paraquate, carbamates , cholinergics organophosphates. • *Pulmonary edema: cardiogenic or non-cardiogenic • - Cardiogenic: (left ventricular failure) e.g. calcium channel blockers, beta blockers, tricyclic antidepressants. • - Non-cardiogenic: (due to factors increasing the pulmonary capillary permeability) ipcons irritant gases & fumes, prolonged coma of CNS depressants as opiates & barbiturates (due to prolonged hypoxia)carbamates , organophosphates. nicotine, salicy.

23. CNS: • *Coma:abpo • a: alcohols, atropine • b: barbiturates • p :phenol • o:organophosphates, opiates • *Convulsion: • prolonged coma of CNS depressants as opiates & barbiturates (due to prolonged hypoxia) • lead, arsenic (encephalopathy) • oxalic acid (decalcification) • organophosphates (early stage of CNS stimulation) • CNS stimulants: strychnine; nicotine, cocaine. amphetamine • phenol, atropine, ergot, cyanide,

24. Abdomen: • *Adynamicileuse.g. Anticholinergics • *Distened abdomen may indicate GIT perforation from inorganic corrosives.

25. 3- Investigations: • They are done to assess: -base line of the patient -follow up target organs e.g. blood gases, electrolytes, glucose, liver & renal function tests, ECG and X-ray.

26. Common radiopaque medications: (BETA CHIP) B -Barium E -Enteric coated tablets: ASA, theoSR T-Tricyclic antidepressants A-Antihistamines. C-Chloral hydrate, cocaine, calcium, condoms(contains tablets, or Body Packers). H-Heavy metals I- Iodides P-Phenothiazines

27. b) Chemical detection: (Analytical toxicology) The most important evidence of poisoning is by chemical analysis. A) In the living: Samples are taken from vomitus, gastric lavage, blood, urine and stool. B) In the dead: - Bloodfrom femoral , axillary or iliac veins. - Stomach and intestine. - Organ samples • Vitreous humorif there is difficulty in blood sampling particularly in putrefaction. • CSF.

28. General lines of treatment of poisoned patient (6)

29. Good supportive care is the backbone of any successful therapy of poisoned patients: • 1- Prevent further exposure to the poisons. • 2- Emergency and supportive measurements. • 3- Decontamination. • 4- Enhancement of excretion. • 5- Administration of toxin-specific (physiological) antidotes. • 6- Symptomatic treatment.

30. 1-Prevent Further Exposure To The Poisons: *In industrial or agricultural exposure → removed from the polluted area. *In cases of toxic inhalants → removal of the patient to fresh air and giving oxygen. *In suspected suicidal cases → the patient hospitalized and observed to prevent another trials. *During medical treatmentif toxic manifestations appear → the drug should be stopped immediately

31. 2. Emergency and Supportive Measures: ABCD’s

32. 2. Emergency and Supportive Measures:The first step is to recognize and treat life threatening conditions(A, B, C, D):A=Airway.B= Breathing.C= Circulation.D= Disabilityi.e. assess neurological status, level of consciousness and convulsion.

33. A)Airway opening & clearance: • Airway opening: • Triple airway maneuver: • (Head tilt, jaw thrust, Mouth opening) • If there is any suspicion of neck injury: • Place the patient in left lateral position with the head downwards which allows the tongue to fall forwards and vomitus or secretions to drain out of the mouth.

34. Airway clearance: • a- Finger sweep technique to remove any F.B. or denture. • b- Suctioning of the mouth and oropharynx to remove secretions.

35. B) Breathing support: • a)  Airway devices • b)Assist ventillationby giving oxygen c)Active ttt.

36. Airway devices : 1-oropharyngeal or nasopharyngeal airway devices 2-ETT, 3-Tracheostomy 1-Oropharyngeal or nasopharyngeal airway devices: placed in the mouth or to lift the tongue and push it forward

37. Endotracheal intubation (ETT): • In Comatosed patient. • Advantages : • - It protects the airway & prevents aspiration and obstruction. • - It allows for mechanically-assisted ventilation. • Some emergency drugs can be given through it e.g. naloxone, atropine and epinephrine

38. -Cricothyrodotomy or tracheostomy: In upper airway obstruction (ETT can not be INSERTED)

39. b- Assist ventillation: (oxygen) • Indication • PO2 < 60 mmHg & PCO2 > 60 mmHg. Don’t wait until apniec Methods: • 1- Mouth-to-mouth ventilation. • 2- Mouth-to-mask ventilation (this method is more hygienic). • 3- Bag and mask ventilation • 4-Bag and tube ventilation • 5-Mechanical ventilation (used when resuscitative efforts are prolonged).

40. The greatest contributor to death from drug overdose or poisoning is respiratory failure • Toxic causes of respiratory failure: • I Central causes: • such as opiates, barbiturates, alcohols ….. • II Peripheral causes due to • 1-airway obstruction • 2-Neuromuscular block • 3-Paralysis of respiratory muscles

41. c- Active treatment: • Bronchospasm, pneumonia, pulmonary edema, specific antidote. • 1-Administer bronchodilatorsif there is wheezing or ronchi: • - B2- agonists e.g. sulbutamol inhalation. • - Aminophylline slowly IV if the above is not effective. • 2-Treat pneumonia with the following: • - Antibioticsif there is evidence of infection. • - Corticosteroids(if it is a chemical-induced pneumonia). • 3-Treat pulmonary edema with the following: • -Avoid excessive fluid administration. • -Administer supplemental oxygen. • -Diuretics. • 4-Consider specific antidotes e.g. Naloxone can reverse respiratory depression in a patient with opiate overdose.

42. C) Circulatory support:(5) • 1-Check blood pressure and pulse rate and rhythm: • Perform CPR if there is no pulse. • Treat shock and arrhythmia if present. • Hypotension treatment: • Normal saline fluid challenge, 20 mL/kg up to 2 liter or S BLP 100 mm/Hg • Vasopressors if still hypotensive as dopamine or dobutrex • PRBC’s if bleeding or anemic • Hypertension treatment: • Nitroprusside, beta blocker, or nitroglycerin • With tachycardia: do not give BB alone, you can worsen HTN if it is caused by alpha adrenergic stimulation as with cocaine

43. C) Circulatory support:(5) • 2-Begin continuous ECG monitoring: • This is essential for comatosed patients and patients with cardiotoxicity. • 3-Establish an intravenous line . • 4-Draw blood for routine studies. • 5-Foly’s catheteris placed in the bladder if the patient is seriously ill (shocked, convulsing or comatosed). • Obtain urinefor routine and toxicologic testing and measure hourly urine output

44. REASSESS. . . frequently

45. D)Disability • Once ABC are addressed, the neurological status should be assessed, mainly: • level of consciousness & convulsions.  • I-level of consciousness: a)Coma and b)stupor • Stupor: is a grade of unconsciousness in which the patient can be aroused (awakened) only by painful stimuli. • Coma: is a state of prolonged unconsciousness in which the patient can not be aroused by painful stimuli. • The level of consiuosness is evaluated roughly by the responsive scale AVPU: • A=awake and alert. • V= respond to verbal stimuli. • P=respond to pain. • U= unresponsive

46. Reed’s classification of the level of consiousness

47. Causes of coma :(5) *Toxic*Traumatic*Pathologic *Environmental*Hysterical Toxic causes: • Generalized CNS depression(e.g. ethanol, opiates, sedative-hypnotics). • As a postictal phenomenon (after a drug-induced seizure)(e.g. anticholinergics). • Hypoglycemia(e.g. insulin, oral hypoglycemic drugs). • Cellular hypoxia(e.g. CO, cyanide). • Traumatic Causes • head injures. • Pathologic causes: Liver & renal failure. Infections as encephalitis or meningitis .

48. 4.Environmental causes: Hypothermia or hyperthermia. • 4. Hysterical: • No organic cause, normal vital signs, and negative investigations. • Complications of coma: • - Loss of protective airway reflexes, resulting in airway compromise which is a major cause of death. • -Hypotension. • -Hypothermia. • -Rhabdomyolysis.

49. Treatment of coma (7) • 1- Support ABC. • 2- Give coma Coktail: DONT • Administer supplemental O2 • Dextrose, Naloxone and Thiamine:

50.  a)  Dextroseis given to all patients with depressed consciousness. • Child: 25 % (1-2 ml/kg) I.V. • Adolescent/Adult: 50 % (1 ml/kg) I.V. • b)    Naloxoneis given to all patients with depressed respiration. • -      Child: 0.01 mg/kg I.V. • -         Adolescent/Adult: 0.4 mg I.V. (amp= 200µgm/Kg) up to 2 mg I.V. can be repeated max 10 mg. • if no response, repeat the dose every 2 min. till a total dose of 10 mg. • c)    Thiamineis given to malnourished and chronic alcoholic patients. • -       It is not given routinely to children. • 100 mg I.M.