Toxicologic Disorders Flashcards
Mechanism of action and clinical effects of clonidine (overdose)
Alpha-2 adrenergic agonist
Stimulation of centrally acting alpha-2 receptors inhibits release of peripheral catecholamines -> decrease HR, contractility, peripheral vascular resistance
Paradoxical hypertension can occur immediately after ingestion due to peripheral alpha-2 adrenergic stimulation, but ultimately manifests in hypotension and bradycardia
Also stimulates mu-receptors causing miotic pupils and lethargy
What type of toxidrome does “paint stripper” cause?
Solvent = methylene chloride or dichloromethane is metabolized by liver to carbon monoxide
What is the problem with tar and asphalt?
Dermal hydrocarbon injuries commonly in construction workers
Apply mineral oil, antibacterial ointments, petroleum jelly to dissolve and remove the substance to ensure proper burn management
INR Reversal Guidelines
*Table from Question 232838
What medication is obtained in oil of wintergreen?
Salicylates
Salicylate toxicity effects on organ systems
***Q174111 pic
Treatment for salicylate toxicity
- Activated charcoal if <2 hours from ingestion
- Urine alkalinization with bicarb gtt (ion-trapping) with pH goal 7.5-8
- K+ prior to alkalinization
- Dialysis
Dialysis indications in salicylate toxicity
- Level >100 mg/dL
- Severe acidosis
- Coma, seizure, AMS
- Rising levels despite alkalinization
- Renal failure
- Pulmonary edema
- Clinical deterioration
Clinical presentation of GHB overdose
Low dose - euphoria; increasing dose - sedation with amnesia; high dose - coma, respiratory depression
- Hypothermia, bradycardia, hypotension
- Agitation, nystagmus, dizziness
- U waves on ECG
- Pupils small and minimally responsive
- Respiratory depression
- Classic presentation is comatose patient requiring intubation then has an abrupt awakening
What is the main complication of GHB other than respiratory depression?
Rhabdomyolysis
Beta-blocker toxicity clinical presentation
- Bradycardia
- Hypotension
- AMS/seizures (propranolol - will also widen QRS)
- Hypothermia
- Hypoglycemia (due to interference with gluconeogenesis and glycogenolysis)
Tx for beta-blocker toxicity
- Glucagon (bypasses antagonized beta-receptors by independently activating myocardial adenylate cyclase, increasing intracellular cAMP, improving myocardial contractility
- Adrenergic receptor agonists (norepi, epi, phenylephrine)
- Calcium
- High-dose insulin
- Sodium bicarb if QRS prolonged
- Lipid emulsion therapy
Which beta-blocker prolongs QTC?
Sotalol due to blockade of potassium channels
What is sarin gas?
Organophosphate nerve agent
Examples of potent cholinesterase inhibitors
Organophosphates: parathion, fenthion, malathion, diazinon
Carbamates: methomyl, aldicarb
Nerve agents: sarin, tabun, soman
Cholinergic toxicity mnemonics
SLUDGE and DUMBBELLS
Salivation; Lacrimation; Urination; Diarrhea; GI cramps; Emesis
Diarrhea; Urination; Miosis; Bradycardia; Bronchospasm; Emesis; Lacrimation; Lethargy; Salivation; Seizures
Also nicotinic effects such as fasciculations, muscle weakness, paralysis
Tx for cholinergic toxicity
- Decontamination
- Atropine (anticholinergic… does not bind nicotinic receptors)
- Pralidoxime - regeneration of cholinesterase -> HAS TO BE GIVEN WITHIN 4-6 HOURS AFTER EXPOSURE
Adverse effects of carbamazepine
- Ataxia
- Diplopia
- Hepatotoxicity
- Blood dyscrasias (aplastic anemia, agranulocytosis)
- SIADH
- SJS
- Teratogenicity
Acute toxicity of carbamazepine
- CNS depression
- Nystagmus
- Ataxia
- Hypertonicity
- Anticholinergic toxidrome
Compounds that can be removed by dialysis
- Amanita mushrooms
- Barbiturates
- Ethylene glycol, methanol, isopropanol
- Isoniazid
- Lithium
- Metformin
- Salicylates
- Theophylline
- Carbamazepine
Indications for dialysis in salicylate toxicity
- AMS
- Seizures
- Pulmonary edema
- New hypoxemia
- pH = 7.2
- Initial salicylate levels >100 mg/dL
Over ingestion of sulfonylureas (chlorpropamide, glyburide, glipizide) causing hypoglycemia can be treated with what agent?
Octreotide
Sulfonylureas have a high affinity to inhibit potassium channels on pancreatic beta cells -> opens voltage-gated calcium channels and influx of Ca = release of endogenous insulin
Octreotide inhibits Ca entry through the voltage-gated Ca channels, prevents further insulin release
What medications ingested by children can result in hypoglycemia?
- Oral hypoglycemics
- Ethanol
- Salicylates
- Beta-blockers
- Pentamidine
Clinical manifestations of hydrogen peroxide ingestion
Small ingestions can liberate large amount of oxygen!
Cardiac and cerebral gas emboli with symptoms similar to those seen in diving related decompression injuries
Treatment for hydrogen peroxide ingestion
Hyperbaric oxygen
Which patients with carbon monoxide toxicity should be treated with hyperbaric oxygen?
- Neurologic abnormalities
- Cardiovascular instability
- COHb level >25% (or 15% in pregnant women)
Classic EKG findings in patients who present with TCA overdose?
Sinus tachycardia
Prolonged PR, QRS and QT
Terminal R wave in aVR
Negative S wave in lead I
What medication should be administered for hypoglycemia if IV access is unavailable?
Glucagon
Vital sign changes with specific calcium channel blocker overdose
Dihydropyridines (“-pines”): hypotension
Non-dihydropyridines (dilt, verapamil): bradycardia
Signs and symptoms of local anesthetic systemic toxicity
CNS:
- Tinnitus
- Circumoral numbness
- Metallic taste
- Agitation
- Dysarthria
- Seizures
- LOC
- Respiratory arrest
CV:
- Hypotension
- Bradycardia
- Ventricular dysrhythmias
- Cardiovascular collapse
Dose for lipid emulsion therapy pin systemic anesthetic toxicity
20% lipid emulsion in adults >70kg -> bolus 100mL IV over 2-3 minutes followed by infusion of 200-250 mL over 15-20mins
In children or adults <70kg -> bolus 1.5mL/kg IBW over 2-3 mins followed by infusion at 0.25mL/kg/min
(Max dose of lipid emulsion approx 12mL/kg IV)
Repeat bolus once or twice and double infusion rate for cardiovascular instability
Continue infusion for at least 10 minutes after hemodynamic stability is achieved
S/S of lead poisoning
- Headache
- Joint pain
- Peripheral neuropathy
- Constipation
- Encephalopathy
Lab/Img findings of lead toxicity
Lab: normocytic, hypochromic anemia and basophilic stippling on peripheral smear
Imaging: hyperdense lines at meatphyses, radioopaque foreign bodies
Tx based on lead levels
5-20 mcg/dL - exposure history, education, continued monitoring of levels
>20 mcg/dL - neurodevelopmental exam, investigation and hazard reduction, lab work, abdominal x-ray
45 mcg/dL - chelation therapy
>70 - hospitalization and immediate chelation
Tx of lead toxicity
Oral succimer or IV EDTA (calcium disodium edetate, given after dimercaprol)
Other clinical effects of opioids
Top 3: CNS depression, respiratory depression, miosis
- Hypothermia
- Bradycardia
- Hypotension
- Noncardiogenic pulmonary edema
- Decreased GI motility
How long do the effects of naloxone last?
Reverses opiate effects for 1-2 hours
Early clinical features of acute salicylate overdose
- N/V
- Tinnitus
- Tachypnea -> resp alkalosis
Clinical effects of TCA overdose and the mechanisms that lead to them
- Dry skin, tachycardia, mydriasis, hot, AMS, urinary retention (anticholinergic)
- Peripheral vasodilation and hypotension (inhibition of central sympathetic reflexes and inhibition of alpha-1 adrenergic receptors)
- Prolonged QRS (Sodium channel blockade)
- Prolonged QT
- Terminal R wave in aVR (Right bundle branch more affected due to longer refractory period)
- Sedation (antihistamine effects)
- GABA receptor antagonism may contribute to seizures
Tx for TCA overdose
Sodium bicarb 1-2mEq/kg IV bolus followed by infusion of 150mEq in 1,000 cc of D5W administered IV at twice maintenance
Treatments contraindicated in TCA overdose
Phenytoin - due to sodium blockade
Physostigmine - lowers seizure threshold
Clinical effects of clonidine overdose
Alpha-2-adrenergic agonist
Initial transient HTN (due to peripheral effects causing release of norepi) -> hypotension and bradycardia
Also with hypoventilation, hypoxia, Cheyne-Stokes respiration, periodic apnea, miosis
Tx for clonidine overdose
Supportive care; naloxone at high doses (4-10mg) sometimes effective
How long does GHB generally last?
<6-8 hours
Why do some athletes and bodybuilders use GHB?
Thought to elevate levels of human growth hormone
Heparin reversal in patients with bleeding is with what?
Protamine sulfate
What kind of risk does protamine sulfate pose?
Hypotension and anaphylaxis
Heparin function?
Reduce thrombin and fibrin formation by binding and activating antithrombin III
- Unfractionated heparin - inhibits factors Xa and IIa in equal proportions
- LMWH - higher ratio of inhibition of Xa as apposed to IIa
What can be administered within 1 hour of ingestion of TCA?
Activated charcoal - if patient awake and cooperative
Indications for sodium bicarb in TCA overdose
- QRS > 100ms
- Terminal right axis deviation greater than 120 degrees
- Brugada pattern
- Ventricular dysrhythmias
What is target when sodium bicarb given for TCA overdose?
Target pH 7.50-7.55
What is initial dose of sodium bicarb for TCA toxicity?
1-2mEq/kg
What is the end point of tx with atropine in patients with organophosphate poisoning?
Dry respiratory secretions and cessation of bronchoconstriction
What type of toxicity can occur in patients who receive large or continuous infusions of benzodiazepines?
Propylene glycol - the diluent used in parenteral formulations of diazepam, lorazepam, phenobarbital, phenytoin, nitroglycerin
Propylene glycol toxicity presentation
- Anion gap metabolic acidosis
- Skin and soft tissue necrosis from extravasation
- Hemolysis
- Cardiac dysrhythmias
- Hypotension
- Lactic acidosis
- Seizure
- Coma
- Multisystem organ failure
Why should you exercise caution when using flumazenil?
It can cause withdrawal seizures
T/F: The use of pralidoxime decreases requirement for atropine?
True
Mnemonic to remember symptoms of NMS
FEVER Fever Encephalopathy Vitals unstable Elevated CK Rigidity
Usually mental status changes and rigidity precede hyperthermia and autonomic instability
Tx for NMS
Aggressive control of hyperthermia
Benzos
Bromocriptine
Jimsonweed overdose presents with what toxidrome
Anticholinergic because of belladonna alkaloids
What are the indications for physostigmine in anticholinergic poisoning?
Tachycardia uncontrolled with standard therapy and agitation uncontrolled with sedatives
Rigid chest syndrome is a noted adverse effect of which medication?
Fentanyl
Which opioid, due to anticholinergic metabolites, can result in seizures, agitation, and psychosis at therapeutic doses?
Meperidine
What can cyanide toxicity smell like?
Bitter almonds
Mild-moderate-severe signs of cyanide toxicity
Mild
- tachycardia, headache, drowsiness, dyspnea, tachypnea
Mod-Severe
- bradycardia, hypotension, CV collapse, asystole, seizures, coma, apnea
Maximum dose of bupivacaine
2 mg/kg or 0.4 mL/kg
What is the first-line antidysrhythmic in a patient with dysrhythmia from systemic lidocaine toxicity?
Amiodarone
What nonopioids can cause a false-positive opioid drug screen?
Poppy seeds and fluoroquinolones
What kind of effect does lithium toxicity have on renal system?
Nephrogenic diabetes insipidus - renal collecting system becomes resistant to antidiuretic hormone
Indications for hemodialysis in lithium toxicity
- Impaired renal function and lithium concentration > 4 mEq/L
- Lithium concentration > 5 mEq/L
- Presence of seizure, dangerous dysrhythmia, altered mental status
- Elevated lithium level in symptomatic patient with contraindication to aggressive hydration (e.g. heart failure)
What medication has been shown to help minimize further accumulation of lithium in patients with mild-moderate nephrogenic diabetes insipidus due to chronic lithium use?
Amiloride
Acute lithium toxicity symptoms
More GI sx early
Delayed neuro symptoms
Cardiovascular symptoms: prolonged QT interval, ST/T wave changes
Leukocytosis
Chronic lithium toxicity symptoms
Early neuro symptoms
CV: myocarditis
Aplastic anemia
Dermatitis, ulcers, edema
What is the mechanism of action of glucagon in the treatment of beta blocker toxicity?
Stimulates production of intracellular cyclic adenosine monophosphate
What type of toxicity produces an osmolal gap with normal anion gap?
Isopropyl alcohol poisoning
Metabolized to acetone by alcohol dehydrogenase
“Ketosis without acidosis”
Calculation for serum osmolarity
2 x Na + (glucose/18) + (BUN/2.8) + (Ethanol/4.6)
Normal = 275-295
Indications for hemodialysis in isopropyl alcohol toxicity
- Refractory hypotension despite conventional therapy
- Comatose
- Isopropyl alcohol levels > 400 mg/dL
For which volatiles can fomepizole be used?
Methanol and ethylene glycol (not isopropyl alcohol)
Medications that can precipitate lithium toxicity
Nephrotoxic - NSAIDs, ACEI, diuretics due to decreased kidney excretion of lithium
What is ergotism?
When Ergot derivatives such as dihydroergotamine increase serotonin activity in CNS and have alpha-adrenergic agonist effects peripherally
Can occur when medications used in excess or drug interactions with macrolide antibiotics and triptans
- Miosis
- Burning sensation in extremities
- Cerebrovascular or cardiac ischemia
- GI disturbances
- Seizures
- Bradycardia
What ancillary lab test can aid in diagnosis of valproic acid poisoning?
Serum ammonia level
Which three anticonvulsant drugs are typically associated with seizure in overdose?
Tigabine
Iamotrigine
Carbamazepine
Lab results in Wilson disease
LOW ceruloplasmin
LOW serum copper
INCREASED urine copper
Tx for Wilson Disease
Chelation with penicillamine
Substances known to cause acquired methemoglobinemia
- Dapsone
- Topical anesthetics, especially mucous membrane use of benzocaine (although also reported with lidocaine, tetracaine, or prilocaine)
- Nitrates
- Antimalarials
What has the odor of fresh hay?
Phosgene
- plastics, textiles, pharmaceuticals
What chemical is liberated when phosgene mixes with the fluid of the epithelial lining of skin?
Hydrochloric acid
What drug commonly causes hyponatremia and associated seizures?
MDMA - increase release of antidiuretic hormone
Effects of MDMA
- Hyperthermia
- Dysrhythmia
- Rhabdomyolysis
- DIC
