A Concise review of General Clinical Toxicology

1. GENERAL TOXICOLOGY
By
Kerolus E. Shehata
• PGY III IM Resident, Ain Shams University
• ECFMG certified

2. • Clinical Toxicology: The science that deals with nature, action, effects, manifestations,
detection and treatment of poisoning.
• Poison: Any agent that is capable of producing a deleterious response in a biological system.
Factors affecting the toxic response
I- Factors related to the poison
 Amount (dose)  The greater the amount, the more serious are the symptoms and prognosis.
 Route of
administration
 The quickest and most dangerous is the IV injection, followed by inhalation,
IM, absorption through mucus membranes (Rectal or vaginal), and lastly the
skin absorption is rapid in organophosphorus insecticides, carbolic acid and
tetraethyl lead.
 Form of the poison
 The gaseous form is rapidly absorbed through the lungs. Liquid poisons are
more rapidly absorbed than solids. Fine powder is more rapidly absorbed
than big lumps.
 Cumulation
 Repeated small doses of certain drugs that are not metabolized rapidly can
produce an effect similar to a single large dose leading to toxicity e.g.
Digitalis.

3. II- Factors related to the patient
 Stomach
 If the toxin is ingested on empty stomach, it can cause more quicker
and serious action that when taken on full stomach. However, some
poisons are more rapidly absorbed in the presence of fatty meals
e.g. chlorinated insecticides, yellow phosphorus and mercury.
 Age
 Extremes of age are more susceptible to toxicity than adults due to
low detoxification ability of their metabolic systems.
 Disease  Cirrhosis and renal insufficiency lead to diminished toxins excretion.
 Tolerance
 That occurs with repeated intake of addicting drugs e.g. opiates,
BZP, alcohol…etc. The patient can withstand larger doses without
serious effects.
 Hypersensitivity  Can occur even with very small doses in sensitive patients.
 Idiosyncrasy  Genetic variations that affect the body response to a poison.

4. • Plants  e.g. opium, atropine, strychnine and digitalis
• Metals  e.g. Lead, mercury, antimony, arsenic, Iron and phosphorus.
• Animal  e.g. Snake bite, scorpion sting, marine animals and spiders
• Synthetic  e.g. Barbiturates, Tricyclic antidepressants, analgesics…etc.
Origin & source of toxins
• Local  On the skin or GIT causing immediate destructive effects e.g. strong corrosives.
• Remote  Have systemic manifestations after being absorbed.
• Mixed  Has local and systemic effects e.g. Metals, carbolic and oxalic acids.
Site of action of toxins

5. Mode of exposure to toxins
• Acute  Single large dose of the poison.
• Chronic  Repeated cumulating doses of the poison
• Acute on top of chronic  Acute poisoning with a background of chronic exposure to the toxin.
Examples of organ specificity of toxins
• Liver  Paracetamol, arsenic…etc.
• Heart  Digitalis, beta blockers, calcium channel blockers, aconite, antimony…etc.
• Kidney  Mercury, cadmium, phenol…etc.
• Neurotoxins  Convulsants & depressants
• Ocular  Methanol & Nicotine
• Dermal  Corrosives, arsenic and mercury
• Respiratory  Hydrocarbons & irritant gases

6. Circumstances of toxin exposure
 Accidental  Suicidal  Homicidal
 Therapeutic error  Bite  Sting
Outcome of poisoning
 Full recovery  The return to previous health without any sequelae after treatment.
 Delayed recovery  Recovery is delayed without sequelae after treatment of the acute phase.
 Sequelae  A persistent disability after recovery from poisoning.
 Death
 Due to respiratory failure, cardiovascular collapse, seizures, hyperthermia,
and /or other organ dysfunction.
The initial approach to the poisoned patient
1- Resuscitation and stabilization. 2- History and physical examination.
3- Decontamination measures. 4- Investigations (Lab. or imaging studies).
5- Administration of antidotes, if indicated. 6- Enhanced elimination techniques.

7. High-yield definitions
• Antitoxin  Parenteral preparation that contains antibodies to neutralize a specific toxin.
• Antidote  Substance that is given to counteract the specific toxic effects of a poison.
• Decontamination
 A therapeutic intervention employed to decrease exposure to a poison,
prevent local injury and to reduce systemic absorption.
• Enhanced
Elimination
 The use of techniques to accelerate removal of toxic substance from the body
after its systemic absorption.
General rules in poisoning management
 Poisoning is common, but it is rarely deadly if properly managed.
 Clinical history can be everything or nothing (unattainable, misleading or unreliable).
 Vitals (hemodynamic parameters e.g. B.P, pulse rate, R.R, Temp.) are vital.
 We rarely know for sure what has been taken, but it will rarely matter.
 Most poisoned patients require only supportive therapy for recovery.
 The presence of an antidote DOESN’T necessarily mean that you should use it.
 If you don’t know anything about DRUG toxicity, give ACTIVATED CHARCOAL!!

8. Emergency stabilization of poisoned patients
N.B: The components of BLS protocol (ABC) should be applied before any other consideration.
Airway
 Airway must be kept Patent & Clear. In severe coma with GCS < 8, flaccid tongue can fall back obstructing the airway.
“Head tilt chin lift” or “Jaw thrust” maneuvers can be used initially and followed by placement of cuffed endotracheal tube
along with suctioning of any oral secretions.
Breathing
 Assisted ventilation is deployed according to the situation. Patients may have one or more of the following complications:
bradyapnea, ventilatory failure, hypoxia, or bronchospasm. Clinical (Respiratory rate & pattern) and lab. (ABG, SaO2,
paO2, PaCO2) monitoring is crucial.
Circulation
 Check the hemodynamic parameters (B.P & pulse rate) along with cardiac monitoring (ECG). Secure venous access.
Correct any abnormality as indicated (hypotension or arrhythmias) using IV fluids, vasopressors, inotropics or anti-
arrhythmic medications.
Coma
 For patients with altered consciousness or respiratory depression of unknown cause give "coma cocktail” empirically for
diagnostic and therapeutic reasons: Dextrose (Hypoglycemia), Thiamine (Alcohol-induced Wernicke's Encephalopathy),
Naloxone (Opiates) & O2 (Hypoxia).
Seizures
 Should be controlled early with IV BZP e.g. Diazepam. Then search for its cause and administer its specific therapy if
applicable e.g. anticholinergics-induced seizures may respond to physostigmine, INH-induced seizures may respond to
pyridoxine & theophylline-induced seizures that rarely respond to phenytoin alone and often needs a multidrug therapy

9. Hints for history taking
 Keep it well-focused at the important items that will help you explore the real problem(s) and
those which could change your decision regarding the case.
 Most important is to gain the trust of your patient.
 Be skilled enough to discover a fake history!!
 Stress upon important items for more clarification.
 Multi-directional approach: If you still have doubt, ask once more, ask the relatives…etc.
 Could be unattainable from the start.
Hints for physical examination
 General as well as focused.
 If it matches the history, go on for treatment.
 If it doesn’t match the history, ask for more clarification, assure the patient regarding his
concerns and confidentiality before confrontation.
 Trust your objective findings NOT the subjective pt.]’s history and start your
investigations & treatment plan if necessary.

10. Hints for communication and inter-personal skills
 Establish Confidentiality.
 Show your concern toward the patient’s health.
 Respond to all the Pt.’s concerns.
 Never to lie to the patient & never to give a false reassurance.
 Respect the patient’s decision regarding what is going to be done to his/her own body.
Skin decontamination measures
 Remove all contaminated clothing.
 Washing skin gently with soap and running water for at least 30 minutes.
 Forceful washing & hot water may damage the skin and promotes further absorption.
Eye decontamination measures
 Wash the conjunctiva with running water or normal saline for 20 minutes.
 Solid corrosives should be removed by forceps.
N.B. In lachrymatory gas exposure, water can increase the eye irritation.

11. Gastric decontamination measures Intestinal decontamination measures
Induction of emesis  Whole bowel irrigation
Gastric lavage  Cathartics
Activated charcoal  Activated charcoal
Induction of Emesis
N.B. Never to use salty water or saline as it can lead to fatal hypernatremia.
 Agent used: Syrup Ipecac; extracted from the root of Cephalus Ipecachuana.
 Active substances: emetine & cephaline.
 Action: Irritation of gastric mucosa peripherally & stimulation of CTZ centrally.
 Dose: 15 mL for children & 30 mL for adults.
 Recent guidelines recommended AGAINST its use once patient arrived to ED & also it is no longer
recommended for home treatment of poisoning.
Contraindications
Substance wise Patient wise
Corrosives (Alkalis & Acids): perforation  Coma: aspiration pneumonia
Convulsants: can precipitate fits.  Infant < 6 months: weak gag reflex
Hydrocarbons: aspiration pneumonia  Recent surgery
Foaming agents: froth can block the airway  Hemorrhagic tendency
Sharp objects e.g. needle, pin razor  Pregnancy
Severe cardiovascular disease  Severe respiratory distress

12. Gastric lavage
 Can be used if emesis induction is contraindicated or has failed.
 In the 1st hour, it removes 50% of the poison. In the 2nd hour, 15% only is removed.
 Better to be done under coverage of cuffed endotracheal tube to prevent aspiration.
 Technique: Under cardiac monitoring, the patient is positioned on the left side. Tube size is selected
according to the patient age. Dentures, mucous, vomitus should be removed from patient's mouth. An
assistant with suction machine should be available. Tube is lubricated and introduced gently from the
mouth until gastric aspirate flushes out. Continue with the lavage with distilled water till the aspirate is clear.
Contraindications
Absolute Relative
Corrosives  Coma: use cuffed ETT
Foaming agents e.g. shampoo  Convulsions: may precipitate fits
Esophageal varices & peptic ulcer.  Hydrocarbons
Complications
Bradycardia: Vagal stimulation  Laryngospasm
Mechanical gut injury  Faulty passage into the trachea
Aspiration of gastric contents  Hyponatremia: if tap water was used
Stress reaction in conscious patients i.e. tachycardia & hypertension

13. Activated charcoal
 Prepared by destructive distillation of wood pulp. It las large surface area that can adsorb a wide variety of drugs and
chemicals.
 It is not digested; it stays inside the GI tract and eliminates the toxin into the stool.
 Dose: 10 times the amount of ingested poison.
 Substances that are not adsorbed by activated charcoal:
Corrosives  Alcohols  Hydrocarbons
Oils  Metals e.g. Iron, lithium, mercury, lead…etc.
Contraindications
Intestinal obstruction.
Corrosives: Not effective, masks the endoscopy view & worsens perforation.
Hydrocarbons: may precipitates vomiting leading to aspiration.
Complications
Can adsorb other medications of the patients preventing their absorption.
In very large amounts, it can cause constipation or rarely intestinal obstruction.
Multiple dose activated charcoal (MDAC) (Gut dialysis)
Repeated doses of AC are given to enhance poison elimination. It is indicated for:
Drugs that remain in the gut for long time e.g. slow release preparations.
Drugs that form concretions e.g. salicylates
Drugs with active entero-hepatic circulation e.g. Barbiturates, digoxin, TCA, dapsone.
Drugs that diffuse passively from blood to GI lumen e.g. theophylline

14. Whole bowel irrigation (WBI)
 Agent: non-absorbable osmotically balanced polyethylene glycol solution.
 Action: flush out the entire gastrointestinal tract including the ingested toxins.
 Indications
Smugglers who swallow packs of cocaine or heroin “Body packers”.
Drugs that don’t get adsorbed by charcoal e.g. Iron, lithium…etc.
Slow release preparations.
Cathartics
Agents: Osmotic (MgSO4) or Irritant (Castor oil).
Action: decrease contact between the poison and the intestinal wall to decrease its absorption.
Complications of cathartics & WBI:
Dehydration especially in children and the elderly.
Electrolyte imbalance.
Contraindications of Cathartics & WBI:
GIT hemorrhage  Recent bowel surgery
Ileus & intestinal obstruction  Renal failure: Mg+2 overload
Corrosives  Pre-existing electrolyte imbalance
Measures for enhancement of poison excretion
Multiple dose activated charcoal (MDAC)  Forced diuresis
Manipulation of urine pH  Dialysis (Peritoneal & Hemodialysis)
Hemoperfusion  Chelators

15. Forced diuresis
 Efficient for: Renally excreted drugs that has small volume of distribution, low protein binding with low lipophilicity.
 Types: Fluid diuresis (Dextrose 5% & normal saline) & Osmotic diuresis (Mannitol 10%).
Forced alkaline diuresis
 Action: Increasing the urine pH that allows the acidic poison to be more in the ionized form allowing its excretion
and decreasing its re-absorption (Ionic trap phenomenon).
 Agents: Sodium bicarbonate 1-2 mEq/kg, Dextrose 5%, Mannitol 10% & KCl
 Used for: acidic drugs e.g. barbiturates & salicylates and in cases of toxicity associated of hemolysis &
rhabdomyolysis.
What to monitor?
Blood pH & serum K+: for hypokalemia
Renal function tests: Must be normal before the start of diuresis.
Lung auscultation: for pulmonary edema.
Urine pH: keep it between 7.5 – 8.0
Urine output chart: keep output between 300-500 mL/hour.
Contraindications
Old age  Renal failure
Heart failure  Pulmonary edema
Complications
Acid base imbalance  Electrolyte imbalance e.g. hypokalemia
Fluid overload: cerebral edema, pulmonary edema or heart failure.

16. Peritoneal dialysis
The peritoneum acts as the semi-permeable membrane. It is easier but less effective.
Complications
Injury of abdominal organs  Intra-peritoneal hemorrhage
Peritonitis  Dehydration or overhydration
Contraindications
Pregnancy Abdominal hernia Respiratory distress
Hemodialysis
The cellulose bag in the dialysis machine acts as the semi-permeable membrane.
Complications
Hypotension  Bleeding tendency (Heparin effect)
Elimination of therapeutic medications  Air embolism
Infection e.g. hepatitis B,C & HIV  Muscle cramps (decrease Ca+2 & Mg+2)
Electrolyte imbalance
Contraindications
Non-dialyzable drugs e.g. opiates, atropine & antidepressants.
Patients with coagulation disorders.
Patients with uncorrected hypotension.

17. Hemoperfusion
 Principle: the anticoagulated blood passes through columns of activated charcoal to
adsorb toxins in the plasma.
 Indications:
 toxins with high (protein binding, molecular weight) & lipophilic toxins.
 Toxin must be adsorbable by activated charcoal.
 Not effective for toxins that can’t be adsorbed by AC.
 Complications
Trapping of WBCs: leukopenia  Trapping of platelets: thrombocytopenia
Hypomagnesemia & Hypocalcemia  Hypotension
Adsorption of therapeutic medications

18. THANK YOU