Medical Archive

Epidemiology

Diagnosis

Standard urine drug screen (UDS)

Treatment

Specific toxic syndromes and poisonings

Physiologic condition	Causes	Examples	Mechanism of action	Clinical features	Specific treatments
Stimulated
Sympathetics	Sympathomimetics
	Ergot alkaloids
	Methylxanthines	Caffeine, theophylline	Inhibition of adenosine, Stimulation of E/NE, inhibition of PDE	Tachyarrhythmia, seizures	Activagted charcoal, BZD/barbiturates
	MAO inhibitor
Anticholinergics	Antihistamines	Diphenhydramine, Doxylamine, Pyrilamine			Physostigmine
	Antipsychotics
	Belladonna alkaloids
	Cyclic antidepressants
	Mushrooms and plants	Jimson weed (Datura stramonium)
Depressed
Sympatholytics	α2-adrenergic agonists
	Antipsychotics
	β-Adrenergic blockers			Bradycardia, AV block, hypotension, diffuse wheezing	Glucagon (via Gs)
	Calcium channel blockers
	Cardiac glycosides	Digoxin
	Cyclic antidepressants
Cholinergics	Acetylcholine esterase inhibitors
	Muscarinic agonists
	Nicotinic agonists
Sedative-hypnotics	Anticonvulsants
	Barbiturates
	Benzodiazepines
	GABA precursors
	Muscle relaxants
	Other agents
Discordant
Asphyxiants	Cytochrome oxidase inhibitors	Cyanide Hydrogen sulfide Nitroprusside	Bind ferric iron (Fe3+) Inhibit cytochrome c oxidase	Reddish skin discoloration, N/V, lactic acidosis	Inhaled amyl nitrite, hydroxycobalamin, sodium thiosulfate
	Methemoglobin inducers	Aniline derivatives, dapsone, local anesthetics, nitrates, nitrites, nitrogen oxides, nitro- and nitrosohydrocarbons, phenazopyridine, primaquine-type antimalarials, sulfonamides	Met-Hb cannot bind to O2 → ↓oxygen content, ↓oxygen carrying capacity of the arterial blood, ↓bound fraction of O2, ↓oxygen delivery to the peripheral tissue.	Gray- or blue-colored skin, “chocolate-colored” blood	Methylene blue
	AGMA inducers	Ethylene glycol
		Iron	Non-transferrin bound iron catalyzes formation of free radicals that cause mitochondrial injury, lipid peroxidation, increased capillary permeability, vasodilation, and organ toxicity.	Hematemesis, liver necrosis, shock (distributive d/t systemic vasodilation, cardiogenic d/t iron-induced myocardial injury)	Whole-bowel irrigation for large ingestion; endoscopy and gastrostomy if clinical toxicity and large number of tablets are still visible on x-ray; IV hydration; sodium bicarbonate for acidemia; IV deferoxamine for systemic toxicity, iron level >90 μmol/L (500 μg/dL)
		Methanol
		Salicylate
CNS syndromes	Extrapyramidal reactions
	Isoniazid
	Lithium
	Serotonin syndrome
	Membrane-active agent

Methylxanthines

Theophylline

• Clinical features
  • CNS stimulation – headache, insomnia, seizures
  • GI disturbances – nausea, vomiting
  • Cardiac toxicity – arrhythmia
• Measure serum theophylline levels to assess for toxicity

Anticholinergics

Etiology

Antihistamines, antipsychotics, antispasmodics, TCA

Clinical features

• Classic toxidrome
  • Fever, dry skin and mucous membranes, flushing, mydriasis, and blurred vision (d/t cycloplegia)
• CNS involvement
  • Confusion, visual hallucinations, psychosis, and seizure.
• Coma and respiratory failure.

P2 S7 C51 Acidosis and Alkalosis

?-adrenergic blockers

-> tintinalli

Cardiac glycosides

Digitalis

• ??: QTc ??
• Interaction
  • ?Serum level of digoxin
    • Amiodarone, varapamil, quinidine, propafenone
    • When initiating amiodarone therapy, decrease digoxin dose by 25%-50% with close monitoring of digoxin levels once weekly for the next several weeks.
  • Hypokalemia increases digoxin cardiac sensitivity (ie, ?toxicity)
  • Hypercalcemia
• Toxicity
  • Gastrointestinal (m/c acute toxicity)
    • A/N/V
  • Neurologic (chronic toxicity)
    • Confusion and color vision alterations (eg, yellow vision)
  • Arrhythmia (chronic toxicity)
    • Sinus bradycardia
    • PR ??(??? p? ?? junctional rhythm)
    • QTc shortening, ST depression, T inversion (?? hypokalemia??)
    • Increase ectopy in the atria or ventricles
      • Atrial tachycardia (m/c) ? palpitation
      • VPC & bigeminy. VT & VF are rare.
    • Increase vagal tone, ?conduction through the AV node
      • AV block (not Mobitz type II)
  • Yellow vision
• Diagnosis
  • ???(K, Mg, Ca)
  • BUN/Cr
  • Serum digoxin
    • ECG Serum digoxin >2ng/mL ? ? ?? ??
    • ?? ?? ??? clearance ?? 
• Treatment
  • ?? ??
  • (DC cardioversion? ??? ?? ???! VT/VF ?? ????)
  • Hypokalemia?? ???? KCl ??.
  • ?? – BB, lidocaine or phenytoin (IB), Vfib? defib.
  • ?? – Atropine, temporary pacing
  • ??? purified Fab fragment (artificial anti-digoxin Ab) – “digibind” 10vial, 400mg

Acetylcholine esterase inhibitor

Organophosphates

• Clinical manifestations
  • Muscarinic effects
    • Urination, Miosis, Bronchospasm/bronchorrhea/bradycardia, Emesis, Lacrimation, Salivation
  • Nicotinic effects
    • Muscle weakness, paralysis & fasciculataions
  • CNS (both receptors)
    • Seizures and coma
• Treatment
  • Atropine
    • No effect on nicotinic receptors – patients are still at risk of muscle paralysis.
  • Pralidoxime
    • Cholinesterase-reactivating agent that allows for degradation of excess acetylcholine and treats both the muscarinic and nicotinic effects of organophosphates.
  • Benzodiazepine
    • Organophosphate agent induced seizures should be treated with a benzodiazepine.
    • Prophylactic diazepam has been shown to decrease neurocognitive dysfunction after organophosphate poisoning

Cytochrome oxidase inhibitor

# Carbon monoxide (CO) poisoning

Carbon monoxide prevents oxygen binding
Normal PaO2, SaO2, oxygen content.
-> C36 Hypoxia and Cyanosis

Produced from the combustion of nitrogen-containing synthetic polymers (eg, foam, cotton, paint, silk)

Sodium nitroprusside

• Prolonged infusion (>24 hours) at high rates (5-10 µg/kg/min) can lead to cyanide toxicity, especially in patients with CKD.

Clinical manifestations

Early acute toxicity – neurologic and cardiorespiratory stimulation
Headache, vertigo, dizziness, hyperventilation, tachycardia, N/V

• Skin: flushing (cherry-red color), cyanosis (occurs later)
• CNS: headache, altered mental status, seizures, coma
• Cardiovascular: arrhythmias
• Respiratory: tachypnea followed by respiratory depression, pulmonary edema
• Gastrointestinal: abdominal pain, nausea, vomiting
• Renal: metabolic acidosis (from lactic acidosis)

Treatment strategy

• Inhaled amyl nitrite
  • Promotes methemoglobin formation, which combines with cyanide to form cyanmethemoglobin
  • To increase ferric iron (Fe3+) in circulating hemoglobin.
• Sodium thiosulfate
  • Serves as sulfur donor to promote hepatic rhodanese-mediated conversion of cyanide to thiocyanate, which is excreted in the urine
• Hydroxycobalamin
  • Cobalt moiety binds to intracellular cyanide ions & forms cyanocobalamin, which is excreted in the urine.

Methemoglobin inducers

Etiology

Oxidizing agents.

• Topical anesthetics (eg, benzocaine)
• Dapsone
• Nitrates (in infants)

Pathophysiology

• Cause iron component of hemoglobin to be oxidized (Fe2+ to Fe3+) ? methemoglobin, which cannot bind O2
• Met-Hb cannot bind to O2 ? ?oxygen content, ?oxygen carrying capacity of the arterial blood, ?bound fraction of O2, ?oxygen delivery to the peripheral tissue.
• Large oxygen saturation gap
  • ?Pulse oximetry (~85%)
  • Normal PaO2 (falsely elevated)
  • >5% difference between oxygen saturation on pulse oximetry & AGB

Clinical manifestations

• Methemoglobin ~10% of total hemoglobin
  • Cyanosis can occur
• Methemoglobin 20%~ of total hemoglobin
  • Hypoxic symptoms(eg, headache, lethargy) occur
• Methemoglobin 50%~ of total hemoglobin
  • Severe symptoms (eg, altered mental status, seizures, respiratory depression, coma)

Treatment

• Methylene blue
  • Acts as an electron acceptor for NADPH, which in turn reduces methemoglobin to hemoglobin.
• High-dose ascorbic acid (vitamin C)
  • Acts as a reducing agent and can be used when methylene blue is unavailable or contraindicated (eg, G6PD)

AGMA inducer

Toxic alcohols

• Alcohol ketoacidosis
• Methanol ingestion
• Ethylene glycol 
  • ? Glycolate – cytotoxic to the renal tubules and causes ATN.
  • ? Oxalate – contributes to oliguric renal failure by precipitating in the kidneys and causing tubular obstruction (calcium oxalate crystals)
• Isopropyl alcohol ingestion
  • CNS depression, disconjugate gaze, absent ciliary reflex
  • NO increased anion gap or metabolic acidosis
• Management
  • Ethyl alcohol (fomepizole > ethanol) in conjunction with dialysis 
  • # Ethyl alcohol inhibit alcohol dehydrogenase

Insecticides, herbicides

• • ?? cholinesterase? ????
  atropin ????? ?? ??. ?????!
• • ??
• o ???? ??? ??
• o SLUDGE: Salivation, Lacrimation, Urination, Defication, 

Gastrointestinal cramping, Emesis 

• o ??? ??? ?? – ??

• • ??
• o Atropinization
  • • Muscarinic ??? ????
  • • ??? ???(??)? ??? ??? ??
• o pralidoxime(2-PAM) 
  • • acetylcholinesterase? ?? ??, 
  • • ???? ??? ??? ??. 
  • • atropine? ???? ???.

Isoniazid

• • OTPT>200 ??? jaundice ??? ??
• • ??, ??, rifampin, pyrazinamide? ??? ?

????

Aspirin	???, ??, ??, ??
Acetaminophen	AST/ALT ??, ??
Amphetamine	??, ???, ???, ?? ??
Narcotics	??, ?? ??, ???, ????
Organophosphate	????, ???, ????, ???
Methanol	CNS ??, ????, ????
Opioid	OPH? ???? +??, ?? ??
Paraquate (???)	??/??? ??, cyanosis (???!)
????	Torsa des pointes, ?????

<Antidote>

Acetaminophen

NAC (N-acetylcystein)

# NAC restores hepatic glutathione store, promoting enzyme-based detoxification of the toxic acetaminophen metabolite (NAPQI)

Atropin

Physostigmine (AchI)

Benzo 

Flumazenil

CO 

CO is competitive inhibitor of oxygen

Iron 

Deferoxamine

Lead, mercury

Ca-EDTA, BAL

Opiates 

Naloxone 

Organophosphate

Atropine (muscarinic ????), Pralidoxime (2-PAM, ???)

INH

Pyridoxine 

TCA ? sodium bicarbonate

Ethanol ? conservative

Salicylates ? ??? ??? x

.Caustics ? (endoscopy)

?? ???? ? ???, ???, ????…

Bipyridyl herbicide (paraquat)

?? ???

1. 1. ?? Emesis

1. a. ?? ?? ??, 1?? ??? ??
2. b. ?????? ?? ??????. 6?? ??? ??x
3. c. ??? ??? ipecac syrup ??
4. d. ???(?/?)? ??

1. o ??? ??? ???? ?/??? ??
2. ??? Gastric lavage

1. a. ?? ?? ??, 1?? ??? ??
2. b. ???(?/?)? ?? (or 30? ??? ??)
3. c. ?? ???? ?? ?? ??.
4. 3. ??? Activated charcoal

1. a. 4?? ??? ??. ??? ? ????.
2. b. ?? ??? ??
3. i. ???(?/?), iron, alcohol, ??, ???

1. ii. Iron, lithium, cyanide
2. 4. ?? Cathartics 

1. a. ?? ????. MgS ? ??
2. b. Na, Mg? ??? ??? ??!
3. 5. ????

1. a. ?? ??? ??. ???? or ?? ??/??
2. 6. Whole bowel irrigation
3. a. ????? PEG, ??? ?? ??