Toxicology and Drugs of Abuse

Chapter 30 Toxicology and Drugs of Abuse



I. General Principles of Toxicology

A. Definitions

1. Toxicology is the study of the hazardous effects of chemicals, including drugs, on biologic systems.

2. Toxicity is a reflection of how much, how fast, and how long an individual is exposed to a poison.

B. Primary determinants of toxicity

1. Dose and dose rate


Paracelsus, the father of toxicology, wrote: “All things are poison and nothing is without poison, only the dose permits something not to be poisonous.”


2. Duration of exposure

3. Route of exposure

C. Factors that affect toxicity

1. Biotransformation


a. Methanol is transformed to formaldehyde and formic acid (toxic metabolites).

b. Parathion is transformed to paraoxon (toxic cholinesterase inhibitor).

2. Genetic factors


a. Polymorphic metabolism (toxicokinetics)


Large overdoses of chemicals often switch kinetics from first to zero-order because clearance pathways are saturated.


• Individuals are fast or slow acetylators of isoniazid (slow acetylator have increased neurotoxicity).

b. Polymorphic targets (toxicodynamics)

• Increased risk of drug-induced torsades de pointes with mutations in ion channels leading to prolonged QT interval

3. Immune status (hypersensitivity)


a. Penicillin allergies


Hypersensitivity to β-lactam antibiotics demonstrate cross-allergenicity including penicillins, cephalosporins, and carbapenems but not aztreonam.


b. Sulfonamide allergies


Drugs with sulfonamide structures include: sulfonamide antimicrobials; sulfonylurea drugs used to treat diabetes, most diuretics, and celecoxib.


4. Photosensitivity

• Skin photosensitivity due to e.g., demeclocycline, sulfonamides, fluoroquinolones

5. Species differences

• Malathion is rapidly inactivated by humans but not by insects

6. Age


a. Toxicodynamics affected by age

• Elderly more sensitive to benzodiazepines

b. Toxicokinetic parameters vary with age


(1) Decreased renal clearance in elderly

(2) Decreased cytochrome P−450 activity in elderly


Elderly are often much more sensitive to drugs’ adverse effects than young adults.


7. Gender

• Hormonal status affects both toxicodynamic and toxicokinetic parameters.

8. Environmental factors

• Aromatic hydrocarbons induce cytochrome P−450 activities

9. Nutritional status/protein binding


An example is tyramine in foods and drinks can cause a hypertensive action in patients taking monoamine oxidase inhibitors (e.g., phenelzine).


10. Drug interactions

• Interactions between drugs and between drugs and environmental chemicals may occur by both toxicokinetic and toxicodynamic mechanisms


Drug-drug or drug-environmental chemical interactions can lead to marked enhancement of adverse effects.


11. Environmental Pathology (see Chapter 6; Rapid Review Pathology)

II. Symptoms and Treatment of Acute Poisoning (Table 30-1 and Table 30-2)

A. General Approach to the Poisoned Patient

1. Systematic

2. Treatment and diagnostic actions are in parallel

3. Basic goals


a. Rapid stabilization of the patient

b. Categorization of poison class

c. Initiation of general treatment (supportive)


TABLE 30-1 Symptoms and Treatment of Poisoning

image

TABLE 30-2 Specific Antidotes for Selected Drugs and Toxins











































































Antidote Poison
Drugs That Chelate Metals  
Calcium disodium edetate (CA2+,2Na+EDTA) Lead
Deferoxamine Iron
Dimercaprol Arsenic, gold, mercury, lead
Penicillamine Lead, copper, arsenic, gold
Succimer Lead; also used for chronic exposure to arsenic and mercury
Substances That Act Against Specific Drugs or Toxins  
Acetylcysteine Acetaminophen
Amyl nitrite/sodium nitrate Cyanide
Atropine Cholinesterase inhibitor
Digoxin-specific FAB antibodies Cardiac glycosides (e.g., digoxin)
Esmolol Theophylline, caffeine, metaproterenol
Ethanol Methanol or ethylene glycol
Flumazenil Benzodiazepine
Fomepizole Ethylene glycol, methanol
Glucagon Beta blockers
Naloxone Opioids
Oxygen Carbon monoxide
Physostigmine Anticholinergics
Pralidoxime (2-PAM) Organophosphates; contraindicated for carbamates
Pyridoxine Isoniazid
Sodium bicarbonate Cardiac depressants (tricyclic antidepressants, quinidine)
Sodium thiosulfate Cyanide

FAB, fragment antigen binding.




Most poisons do not have a specific antidote.


d. Specific treatment when available

4. Remember that poisonings are often mixed, with multiple drugs/chemicals

5. Treatment often nonspecific

6. Prevent further toxin exposure

7. Enhance toxin elimination

B. ABCDTs of treatment


Treatment requires ABCDTs: Airway, Breathing, Circulation; Drugs, Temperature.


1. Airway should be:


a. Cleared of vomitus or any other obstruction

b. An airway or endotracheal tube inserted

2. Breathing assessed by:


a. Observation

b. Measurements of arterial gases

c. Pulse-oximetry

• Intubate and mechanically ventilate if needed

3. Circulation


a. Monitor


(1) Pulse rate

(2) Blood pressure

(3) Urine output

b. Start IV and draw blood for:


(1) Glucose

(2) Laboratory determination

4. Drugs


a. Dextrose

• Every patient with altered mental status

b. Administer 100 mg of thiamine to alcoholic and malnourished patients

• Prevents Wernicke-Korsakoff syndrome


Thiamine prevents Wernicke-Korsakoff syndrome.


c. Naloxone


Remember multiple doses of naloxone may be required for opioid overdoses.


d. Flumazenil

• May cause seizures


Flumazenil may cause seizures if used improperly.


e. IV lorazepam or diazepam for seizure control


Stop seizures with diazepam or lorazepam.


5. Temperature (cooling)

• Tepid sponge bath or fan

C. Remove stomach contents if indicated

1. Gastric lavage


a. Not recommended after 4 hours of poisoning

• Usually not helpful after 1 hour

b. Contraindications


Contraindications of emesis and gastric lavage include: coma, seizures, corrosives, petroleum solvents.



(1) After 30 minutes of ingestion of corrosive material

(2) Ingestion of hydrocarbon solvents (aspiration pneumonia)

(3) Coma, stupor, delirium, or seizures (present or imminent)

c. Substances used to reduce absorption of poison


(1) Charcoal

(2) Cholestyramine (acidic compounds)

d. Activated charcoal adsorbs many toxins if given immediately before or after lavage.

2. Induced emesis


a. Same contraindications as for gastric lavage

b. Makes use of syrup of ipecac (slow-acting oral emetic)

3. Current changes in emergency treatments


a. Gastrointestinal (GI) decontamination


(1) Ipecac now much less commonly used

Related posts:

  1. Introduction to Autonomic and Neuromuscular Pharmacology
  2. Drugs Used in the Treatment of Parkinson’s Disease
  3. Antiarrhythmic Drugs
  4. Drugs Used in the Treatment of Hypothalamic, Pituitary, Thyroid, and Adrenal Disorders

Stay updated, free articles. Join our Telegram channel
Tags:
Apr 8, 2017 | Posted by in PHARMACY | Comments Off on Toxicology and Drugs of Abuse

Full access? Get Clinical Tree
Get Clinical Tree app for offline access