Toxidromes Part III Flashcards
What drug control schedule are benzodiazepines in?
C-4
T/F: Death from benzodiazepines overdose is common.
False: death from benzos is rare
What is the greatest concern in a benzodiazepine overdose?
They are synergistic with other CNS depressants –> especially alcohol
Describe the mechanism of action of benzodiazepines and compare them to barbiturates.
They enhance GABA transmission. They are not as potent as barbiturates because GABA must be present for them to work
Describe the clinical presentation associated with a benzodiazepine overdose.
Lethargy, slurred speech, ataxia, respiratory depression
What is the antidote to benzodiazepines and what is its contraindication?
Flumazenil –> contraindicated in patients that ingested TCAs or any patient that is at risk for seizures
What non-TCA drugs in overdose are treated like a TCA overdose?
Carbamazepine (anti-epileptic) and Cyclobenzaprine (muscle relaxant)
Describe the mechanism by which ethyl alcohol (ETOH) is broken down into its metabolites after ingestion.
ETOH (alcohol dehydrogenase) –> acetyl aldehyde (aldehyde dehydrogenase) –> acetyl CoA and CO2
What population under-express alcohol dehydrogenase?
Asians –> results in faster inebriation
What drug previously discussed in class inhibits aldehyde dehydrogenase?
Metronidazole –> causes a disulfiram reaction –> acetyl aldehyde builds up cause severe N/V.
Describe the mechanism by which methanol is broken down into its metabolites after ingestion.
Methanol (alcohol dehydrogenase) –> formaldehyde (aldehyde dehydrogenase) –> formic acid
What is the result of formic acid accumulating in the body?
Metabolic acidosis and it is toxic to the optic nerve (causes blindness)
What common substances contain methanol?
Paint thinner, windshield wiper fluid, and bad moonshine
Describe the mechanism by which ethylene glycol is broken down into its metabolites after ingestion.
Ethylene glycol (alcohol dehydrogenase) –> glycolaldehyde (aldehyde dehydrogenase) –> glycolic acid and calcium oxalate crystals
What pathophysiology results from the accumulation of glycolic acid and calcium oxalate crystals in the body?
Glycolic acid = metabolic acidosis
Ca oxalate = crystalizes in kidneys and causes real failure
What common substance contains ethylene glycol?
Anti-freeze
What is the least toxic and most toxic alcohol?
Least: ETOH
Most: Ethylene Glycol
Name two substances that can be used as an antidote to ethylene glycol or methanol and describe the mechanism of each.
- ETOH: alcohol dehydrogenase prefers to bind ETOH resulting in fewer metabolites from ethylene glycol
- Fomepizole: alcohol dehydrogenase inhibitor that inhibits formation of toxic metabolites without causing inebriation.
Is dialysis effective in treatment of methanol or ethylene glycol overdose?
Yes, dialysis removes ethylene glycol and methanol. But it also removes the antidotes –> must redose antidotes when dialysis is complete.
What is isopropyl alcohol used for?
Rubbing alcohol
What is the clinical result of isopropyl alcohol ingestion?
It is relatively non-toxic but causes bad gastritis.
What type of patients might present with isopropyl alcohol ingestion?
Severe alcohol use disorder
Describe the metabolic pathway of acetaminophen (APAP).
90% conjugated in the liver to glucuronide and sulfate metabolites
5% metabolized by CP-450 into a hepatotoxic metabolite which is then further metabolized and inactivated by glutathione
Describe the mechanism by which APAP overdose causes toxicity.
The conjugation pathway is overwhelmed and more APAP goes down the toxic CP-450 pathway and there is not enough glutathione to inactivate the excess hepatotoxic metabolites
Describe the 4 phases of APAP toxicity.
1: (0-24h): severe GI upset
2: (24-72h): Pt feels better –> LFTs rise and peak at around 72 hours
3: (72h +): liver dysfunction continues –> PT/INR increase s/p decreased production of clotting factors, ammonia increases and may lead to hepatic encephalopathy
4: (5-14 days): death or resolution of hepatic impairment
Describe what is indicated by a rise in LFT enzymes.
They tell you that liver damage has occurred (enzymes released from damaged cells) but they give no true indication of liver function.
What is the antidote for APAP overdose and how does it work?
N-acetylcysteine (NAC): replenishes glutathione stores
At what point after ingestion is the antidote for APAP overdose most effective?
Best when used acutely –> NAC does not reverse liver damage, it only stimulates breakdown of toxic metabolites with glutathione.
Describe the two routes by which NAC may be administered and list the name for each form.
PO: aka mucomyst
IV: aka acetadote
Other than APAP overdose, what can mucomyst be used for?
Used in nebulized form to thin and mobilize mucus that accumulates in CF patients
What are the disadvantages of each form by which NAC can be administered for APAP overdose?
PO: Has a noxious smell, is hard to take and keep down, and requires large volumes to be effective
IV: must be administered in D5W at high volumes (fluid overload and hyperglycemia) and has high risk of allergic reaction
What is used to combat the nausea associated with PO NAC administration?
Ondansetron, Aprepitant (anti-emetic), metoclopramide (prokinetic)
How many doses of PO NAC should the APAP OD patient receive?
17 full doses –> must repeat dose if one is vomited back up
Name and describe the graph used to predict the level of toxicity expected from an APAP overdose.
Rheumac Nomogram –> can only be used 4 hours or more after ingestion.
What two substances should always be tested for in any overdose and why?
APAP and ASA –> because they are readily available
What is the clinical result of ASA (or any NSAID) toxicity?
Metabolic Acidosis
Name the graph used to predict the level of toxicity expected from an ASA overdose.
Dunn Nomogram
Describe the clinical result of cyanide toxicity.
Rapid metabolic acidosis caused by anaerobic metabolism in the cells
What is the mechanism by which cyanide causes anaerobic metabolism?
It binds to Hgb with much higher affinity than oxygen and significantly decreases oxygen carrying capacity of blood.
T/F: Cyanide is a good drug to use for someone that wants to commit suicide.
True: it is quickly lethal
What is a key clinical sign associated with cyanide toxicity?
Skin changes: cherry red early (especially noted in the lips) and cyanotic late
What smell is commonly associated with cyanide in the air?
Smell of bitter almonds
How is a diagnosis of cyanide toxicity commonly made?
Based on clinical presentation –> cyanide blood levels require long turn-around time
What presentations (5) should lead the provider to suspect cyanide toxicity?
- Sudden collapse of a lab or industry worker
- Fire victim with coma and acidosis
- Suicide attempt with acidosis and unexplained coma
- Ingestion of nail polish remover
- ICU patient on sodium nitroprusside with mental status change or unexplained acidemia
What patient population in the ICU is at particular risk for cyanide toxicity from sodium nitroprusside?
Elderly patients with hepatic and renal issues
What three drugs are contained in the Lilly Cyanide Antidote Kit?
- Amyl Nitrite Pearls - forms methemoglobin
- Sodium Nitrite (Nitroglycerine) - forms methemoglobin
- Sodium Thiosulfate - donates sulfa groups to rhodanase
What is the mechanism by which methemoglobin treats cyanide toxicity?
It has half the O2 carrying capacity as regular Hgb but cannot be bound by cyanide
What is the mechanism by which rhodanase treats cyanide toxicity?
Rhodanase detoxifies cyanide but it relies on sulfa groups, which are depleted in cyanide overdose
