Toxicology Flashcards
What is a poison?
Any substance including any drug that can harm a living organism.
Almost all ____ have a ____ beyond which they become ____?
Almost all drugs have a threshold dose beyond which they become poisonous.
Even Excess Carbs - Diabetes
How many serious/fatal adverse drug reaction are there in the US?
2 Million Hospitalized per Year
100, 000 is Fatal.
How many adverse effects due to dosing error per year?
775, 000
What are the types of effects from drugs?
What is pharmacological toxicity?
Pharmacological toxicity: is an extension of therapeutic effect due to an increase in the dose to toxic levels or an increase in duration of treatment. (Type A reactions – expected from pharmacological actions of a drug - 80%)
Type B - Unexpected - 20% - Immune System
What are the examples of Pharmacological Toxicity?
i. CNS depression produced by very high doses of barbiturates such as phenobarbital
ii. A severe fall in blood pressure produced by very high doses of sodium nitroprusside
iii. Extrapyramidal motor disorder (Parkinson-like muscle rigidity) produced by prolonged treatment with certain antipsychotics (blocks dopamine receptor) etc.
What is pathological Toxicity?
The toxic effect of certain drugs is manifested as pathological effects in the body.
What are some examples of Pathological toxicity?
i) A classic example is the liver damage
produced by acetaminophen overdose.
(ii) The antifungal drug amphotericin B
and the antibiotic gentamicin can
cause nephrotoxicity(Kidney Damage)
What is Genotoxicity?
Drugs, chemicals and ionizing radiation damage the DNA and cause genotoxicity.
What are some examples of Genotoxicity?
Many cancer chemotherapeutic drugs are genotoxic. They are designed to damage the DNA of cancer cells and kill them, but they also damage normal body cells.
– E.g. Nitrogen mustards (cyclophosphamide, chlorambucil), nitrosoureas
(carmustine), Alkyl sulfonates (busulfan), cisplatin
Drugs NAMES X
What is the mechanism of “On-target” adverse effects?
The result of drug binding to its intended Receptor.
2 Examples
Sedative side-effect of certain antihistaminics administered for allergy are due to H1 receptor binding in the CNS
Increased prolactin secretion and galactorrhea due to the antipsychotic drug haloperidol is due to inhibition of dopamine D2 receptors in the pituitary) (D2 normally inhibits this secretion)
What is the mechanism of “Off target” adverse effects?
Due to a drug binding to an unintended receptor.
Examples
The cardiac Ikr (hERG) potassium channel (found in heart) is not very specific in its binding to drugs and inhibition of K+ currents by many drugs (e.g. erythromycin, astemizole, terfenadine, cisapride) leads to cardiac arrythmias including torsades de pointes and sudden death. All new drugs are tested for binding to this channel (hERG assay).
Another common example of ‘off-target’ binding is seen with β1 and β2 receptors when their
agonists and antagonists are used for specific organ/tissue stimulation or inhibition
Some antihistamines, antibiotics bound to hERG.
What is the third type of drug toxicity mechanism?
Adverse effects (Type B- idiosyncratic or unexpected) mediated by the immune system – hypersensitivity responses (allergic reactions) and autoimmune reactions
What is type 1 hypersensitivity?
Immediate or Anaphylaxis - Mediate by IgE antibodies - Degranulation of Mast Cells.
Symptom: Bronchoconstriction, Vasodilation, Inflammation.
Penicillin induced Anaphylaxis - Type 1
What is type 2 hypersensitivity?
Cytolytic Reaction - Drug binds to Cell - Recognized by Antibody IgG - Causes Cell Lysis
Heparin-Induced Thrombocytopenia
What is type 3 hypersensitivity?
Antibodies IgG or IgM bind to soluble antigens and form complexes, which are deposited in tissues causing inflammation locally.
Serum Sickness
Any organ can be a target
What is type 4 hypersensitivity?
Delayed Type Hypersensitivity - 48-72 Hours after exposure - Activation of Cytotoxic T Cell
Cell not Antibody Mediated
Examples
Skin rashes following a drug – e.g. Erythema multiforme or the more severe Stevens-Johnson syndrome and toxic epidermal necrolysis, which can be life-threatening (SCARS – severe cutaneous adverse reactions) are type IV reactions.
“Red man syndrome” is due to direct effect of drug on mast cells causing degranulation without
the mediation of IgE antibodies (e.g. i.v. vancomycin infusion) (Pseudoallergy).
Are substances that cause toxicity the same across the globe?
Yes
What are the top 5 most common types of substances involved in poisoning in the US?
What are the top 5 substances that cause poisoning in Canada in all ages?
What are the top 5 substances that cause poisoning in Canada in children?
What are the poisons associated with the largest number of human fatalities?
What is the most likely situation in which toxicity can occur?
What are the “5 rights” of safe medication?
What are the effects of different classes on drugs on pupil size?
What are some common antidotes to different poisons?
What are the diagnostic criteria, signs&symptoms, main pathological features, treatment options, and mechanisms of Organophosphate Poisoning?
Mechanism: OPs bing to and inactivate AChE causing cholinergic crisis. Aging occurs when the phosphorylated cholinesterase undergoes a reaction that irreversibly inactivates it.
Used in: Insecticides/Pesticides, Suicide, Chemical Warfare and Terrorism
Symptoms: Diarrhea, Frothy salivary secretions, incontinence, excess sweating, miosis, bronchospasm, bronchorrhea, lacrimination, tachycardia, and hypotonia(low muscle tone).
Treatment: Atropine (Competitive Antagonist of Muscarinic Receptor), Pralidoxime (Removes OPs from AChE enzymers before aging occurs.
Pediatric patients present with more muscarinic symptoms than nicotinic.
What are the diagnostic criteria, signs&symptoms, main pathological features, treatment options, and mechanisms of Acetaminophen Poisoning?
Diagnosis: Blood acetaminophen level well above the therapeutic range of 66–199 μmol/L. Liver Function Tests Normal: Bilirubin (normal range: 3–17 μmol/L); Glucose Levels (normal range of 4–8 mmol/L); Albumin (normal range: 32–45 g/L). Complete blood count, electrolytes, and renal function tests were all within normal limits.
Pathology: Hepatic Toxicity, Acute Liver Failure, sometimes fatal.
Treatment: Activated Charcoal (Within 1 hour of ingestion - Prevent Drug Absorption by binding to subtance. NAC (N-acetylcysteine) infusion. (Started within 8 hour of ingestion - Reduces Hepatotoxicity to below 10%)
**Mechanism of Treatment (NAC): **
1. Replenish Glutathione Stores
2. Prevent Liver Damage - Neutralize NAPQI by supporting Glucathione Production
**Modes of NAC Administration: **
- Oral - Higher Dose over longer time - Less Side Effects
- IV - Main route in Canada - Possible Anaphylactoid Reaction.
This Toxicity is most caused by incorrect dose and medication error.
What are the diagnostic criteria, signs&symptoms, main pathological features, treatment options, and mechanisms of Mercury Poisoning?
Treatment: DMSA (Dimercaptosuccinic Acid), Diamercaptopropane, Chelating Agents.
Pathology: Mercury is a toxic heavy metal. Methylmercury Fungicide, Peripheral Neuropathy, Cerebellar Ataxia.
Diagnosis: Confirmed History, Blood Work Normal, Cerebellar Ataxia, Peripheral Neuropathy, Raised Serum Alanine Transaminase and Haemoglobin (Deranged Liver Funtion).
Symptoms: Long Term Exposure - Paraeshesia, Headache, Fatigue, Dysarthria, Ataxia, Visual and Hearing Impairment.
Measurement of organic mercury concentration is taken from whole blood while urine is used to
measure inorganic mercury concentrations
Mercury in Tuna Cans
