Toxicology Flashcards
Give examples of the four most common classes of drugs that are frequently monitored and state the rationale for monitoring.
Antibiotics
o Ex: amikacin, gentamicin, tobramycin, vancomycin
o Toxic effects: nephrotoxic, ototoxic
Anti-seizure agents o Ex: carbamazepine, lamotrigine, phenytoin, phenobarbital, primidone, valproic acid o Narrow therapeutic windows • Too low: risk of seizures • Too high: depress CNS → coma
Immunosuppressants
o Ex: azathioprine, cyclosporine, methotrexate, mycophenolate mofetil, sirolimus, tacrolimus
o Ensure adequate immune suppression to prevent transplant rejection
o Some reports of hepatoxicity and nephrotoxicity
Cardiac medications
o Ex: amiodaroen, digoxin, flecainide, lidocaine, procainamide, quinidine
o Cardiac glycosides (digoxin) = narrow therapeutic windows
o Overdose: vomiting, diarrhea, confusion, visual disturbances, cardiac arrhythmias
Some psychiatric drugs
Describe the unique issues regarding cannabis, cocaine and opioid testing.
Cannabis:
o THC persists in urine for many days
o Lipophilic = can reside in fat stores for longer
o Pantoprazole (PPI drug for acid reflux), ibuprofen = can cause false positives
Cocaine o Primary metabolite = benzoylecgonine • Long ½ life compared to parent drug o Result = better marker for abuse • Can be detected in urine 3-5 days later (vs. cocaine only 1 day later)
Opioids
o Many drugs of opioid class can cross-react in screening tests
o Many opioids metabolize to other opioids
o Note: may need to test for opioid use/patient adherence (ensure patient is taking medication before writing new prescription)
Note: only metabolite of heroin = 6-acetyl morphine
Drugs affecting nutrients: steroids
Vit D and Ca2+
Drugs affecting nutrients: Phenytoin
Antiepileptic
Vit D, Ca2+, Folate
Drugs affecting nutrients: sulfasalazine
IBD tx
folate
Drugs affecting nutrients: TMP/sulfa
(if long term use)
folate
Drugs affecting nutrients: INH
(TB prophylaxis)
Vit B6
Drugs affecting nutrients: methotrexate
folate, vit B12
Drugs affecting nutrients: PPI
Vit B12, magnesium, Ca2+, iron
Cholinergic toxidrome
Cholinergic: organophosphates, carbamates
DUMBELS: o Diarrhea, Diaphoresis o Urination o Miosis (Constricted) o Bradycardia, Bronchosecretions o Emesis o Lacrimation o Salivation
Antidote: atropine, pralidoxine
What is the most life threatening effect of cholinergic poisoning?
• Pulmonary edema
Anticholinergic toxidrome
Anticholinergic: antihistamines, TCA’s
Think: • Hot as a hare, red as a beet; dry as a bone; blind as a bat, mad as a hatter o Hyperthermia o Dry Skin o Mydriasis (Dilated) o Delerium, Hallucinations o Tachycardia o Urinary Retention o Seizure
Antidote: physostigmine
How do you differentiate anticholinergic toxicity from sympathomimetic toxicity?
• Anticholinergic = dry skin, urinary retention
• Sympathomimetic = diaphoresis (sweating)
What is the most life threatening effect of anticholinergic toxicity?
• Hyperthermia, seizures
In addition to an antidote, what other medication may be useful?
• Adjunct: benzodiazepine
Sympathomimetic toxidrome
Sympathomimetic: cocaine, amphetamines
o Hyperthermia o Diaphoresis o Mydriasis (Dilated) o Tachycardia o Hypertension o Seizure
Antidote: none
What are the most life threatening effects of sympathomimetic toxicity?
• Seizure, cardiac arrest
What are the key principles underlying management of these patients? Supportive care: o Maintain airway o Active cooling for hyperthermia o Seizure control o Na+HCO3- bolus for dysarrhythmia
Opioid Toxidrome
Opioid: heroin, methadone, oxycodone, hydrocodone
o Miosis (Constricted) o Hypoventilation o Coma o Bradycardia o Hypotension
Antidote: naloxone
What is the most life threatening effect of opioid toxicity?
• Respiratory depression
After treatment with antidotal therapy for opioid overdose, when is a patient safe for discharge?
• About 4 hours
Describe when the following interventions are indicated: syrup of ipecac
Not supported → causes lots of vomit
Describe when the following interventions are indicated: activated charcoal
o Most effective within 1 hour of ingestion
o Only use in alert patients
o Binds toxins in gut: (PHAILS) pesticides, hydrocarbons, acids/akali, iron, lithium, solvents
o Multiple doses = interrupts entero-hepatic circulation: (AABBCD) antimalarials (quinine) and aminophylline (theophylline), barbituates (phenobarbital) and beta blockers (nadolol), carbamazepine, dapsone
Describe when the following interventions are indicated: gastric lavage
o No longer indicated except if within 1 hour of life-threatening ingestion and no alternative
o But = no solid evidence on outcomes
o Complications: aspiration, esophageal perforation
o Contraindications: ingestion of corrosive substance or hydrocarbon
Describe when the following interventions are indicated: whole bowel irrigation.
o Polyethylene glycol via nasogastric tube
o Used for lead ingestion (paint chips)
Describe when the following interventions are indicated: urinary alkalization
(aspirin & phenobarbital overdose)
Describe when the following interventions are indicated:hemodialysis
(acute aspirin, toxic alcohol, lithium toxicity)
Name the antidote(s) for the following poisonings: parathion, diphenhydramine, oxycodone, methanol, acetaminophen, lead.
- Parathion (organophosphate = cholinergic): atropine, pralidoxine
- Diphenhydramine (antihistamine = anticholinergic): physostigmine
- Oxycodone (opioids): naloxone
- Methanol: fomepizole, ethanol
- Acetaminophen: n-acetylcysteine
- Lead: succimer, BAL, CaNa2EDTA
Anion Gap Metabolic Acidosis
How do you calculate an anion gap?
• AG = Na+ - (Cl- + HCO3-)
• Normal: 8-12 mEq/L
What is the differential diagnosis for a patient with a high AGMA? • (MUDPILES) • Methanol (formic acid) • Uremia • Diabetic ketoacidosis • Propylene glycol • Iron tablets or INH • Lactic acidosis • Ethylene glycol (oxalic acid) • Salicylates
When is dialysis indicated for patients with AGMA?
• Life-saving for salicylate and toxic alcohol poisoning
How do you calculate an osmolar gap?
OG = 2(Na+) + (glucose/18) + (BUN/2.8)
Describe the mechanism and features of antifreeze toxicity.
• Antifreeze = ethylene glycol, 1,2-ethanediol
Mechanism of injury o Absorbed in proximal GI tract o Converted to 3 major metabolites (via hepatic alcohol dehydrogenase) • Glycoaldehyde • Glycolic acid • Glyoxylic acid
Treatment = ethyl alcohol
• Slows glycoaldehyde formation by saturating alcohol DH → less toxic metabolites
• Allows time for urinary excretion of ethylene glycol
Toxicity
o Ethylene glycol = not directly toxic
o Metabolites (glycolic acid and oxalic acid) = TOXIC
1) Glycolic acid
• Forms in high amounts
• Causes elevated anion gap metabolic acidosis
2) Oxalic acid
• Relatively small amounts
• Highly reactive and toxic
• Reacts with Ca2+ containing molecules → calcium oxalate crystals → deposit in kidney → can lead to renal failure
Cocaine: metabolism
(p450) –> norcocaine
(EtOH) –> ethylcocaine (stronger biologic activity, longer 1/2 life)
(smoking/crack) –> methylecgonidine
Primary metabolite = benzoylecgonine
