UMEM Educational Pearls - Toxicology

Category: Toxicology

Title: AMIODARINE TOXICITIES AND ADVERSE EVENTS

Keywords: amiodarone, torsades, hypothyroidism, toxicity, adverse effects, medication induced (PubMed Search)

Posted: 3/6/2008 by Ellen Lemkin, MD, PharmD (Updated: 12/7/2021)
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 Did you know how many toxicities and adverse effects amiodarone has? Many are severe, and many VERY common.

1. CARDIAC: hypotension with rapid infusion, prolonged QT, torsades

2. NEUROLOGIC problems occur in 20-40%, including malaise, ataxia, and peripheral neuropathies

3. ENDOCRINE: hypothyroidism and hyperthyroidism

4. GI problems occur in 25%

5. OPHTHALMOLOGIC disturbances include optic neuropathy, papilledema, and photosensitivity

6. SKIN: blue grey pigmentation

7. PULMONARY: pulmonary fibrosis


Category: Toxicology

Title: Sleeping Pills

Keywords: zolpidem, benzodiazepines, eszopiclone (PubMed Search)

Posted: 2/28/2008 by Fermin Barrueto, MD (Updated: 12/7/2021)
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Both dealing with the adverse effects from therapeutic administration, like when you order it on the floors or take yourself - to the overdose setting. Here is a brief list of the common sleep aids, MOA and toxicity. (Zolpidem or Ambien gets the award for most entertaining adverse effect of "Sleep Eating")

  • "Unisom": there are multiple formulations, most have diphenhydramine or some derivative. Toxicity is anticholinergic and Na channel blockade in overdose. Be aware that some have doxylamine which causes atraumatic rhabdomyolysis.
  • Zolpidem (Ambien): Nonbenzodiazepine hypnotic, with sedation as the primary effect though the reports of hallucinations, "sleep eating" and "sleep coitus" have been made famous.
  • Eszopiclone(Lunesta): Nonbenzodiazepine hyponitic, mechanism of action unknown. Does not require a controlled substance Rx but is expensive. Toxicity: metallic taste next day, minimal toxicity reported.

Category: Toxicology

Title: Influenza Treatment - Tamilfu Adverse Reactions

Keywords: influenza, tamiflu, oseltamivir (PubMed Search)

Posted: 2/21/2008 by Fermin Barrueto, MD (Updated: 12/7/2021)
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Tamiflu (oseltamivir)

  • Must be administered within 48 hours of onset of symptoms
  • Patient must be 1 year or older
  • Rare cases of anaphylaxis, Stevens-Johnson, TEN and erythema multiforme have been reported.
  • Not proven safe in pregnancy nor harmful.

Here are a couple of herbals touted as aphrodesiac's and the toxcity associated with them (the price of love):

Chan Su or "Love Stone" - A chinese herbal that is suppose to be topically applied, unfortunately all of the instructions are in chinese and those who ingest it will die a digoxin-like death. It has a compound that is essentially a potent digoxin-like substance.

Yohimbine - herbals that contain this can cause priapism -  shocker

 


Category: Toxicology

Title: Scabies - I am itchy!

Keywords: crotimaton, permethrin, lindane (PubMed Search)

Posted: 1/24/2008 by Fermin Barrueto, MD (Emailed: 2/2/2008) (Updated: 12/7/2021)
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We have seen this lovely  bug infect our patients and have to instutitue therapy. But do you know what is the first line drug and which one has now become second line due to its toxicity? Here is the short list:

First Line Therapy: Permethrin (Nix) - least toxic, only causes local irritation

Second Line Therapy: Crotamiton (Eurax) - again local irritation

Third LIne Therapy: Lindane - SEIZURES if you leave it on too long or put on too much. Children were particularly susceptible and relatively contraindicated.

 


Category: Toxicology

Title: Drug-Induced Hyperkalemia

Keywords: hyperkalemia, medications (PubMed Search)

Posted: 1/31/2008 by Fermin Barrueto, MD (Updated: 12/7/2021)
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Here is a list of drugs that can cause hyperkalemia either at therapeutic levels or in overdose:

Amiloride, ACEI, Beta Blockers, Cardiac Glycosides, FLuoride

Heparin, NSAIDS, Penicillin (the Pen VK formulation), Spironolactone

Succinycholine and triamterene


Category: Toxicology

Title: Bisphosphonates - A Recent FDA Warning

Keywords: bisphosphonates (PubMed Search)

Posted: 1/10/2008 by Fermin Barrueto, MD (Updated: 12/7/2021)
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With the aging population, bisphosphonate use will continue to increase. They promote bone growth by inhibiting osteoclast action and resorption of bone. Unfortunately, they have their side effects and the FDA has sent out a recent warning that affects us all:

  • [Posted 01/07/2008] FDA informed healthcare professionals and patients of the possibility of severe and sometimes incapacitating bone, joint, and/or muscle (musculoskeletal) pain in patients taking bisphosphonates.

If a patient presents with severe bone/joint pain, check the med list to see if they are on a bisphosphonate - they may not be faking the pain. This can occur days, weeks or even years after initiation of dose


Category: Toxicology

Title: Levetiracetam (Keppra)

Keywords: anticonvulsant, status epilepticus, keppra (PubMed Search)

Posted: 1/3/2008 by Fermin Barrueto, MD (Updated: 12/7/2021)
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Levetiracetam

  • A new anticonvulsant that is 100% renally eliminated
  • Does not require therapeutic drug monitoring like phenytoin
  • The IV form does not cause skin necrosis or have cardiotoxicity like phenytoin
  • Is being investigated in benzodiazepine-refracory status epilepticus (1)
  • Fairly safe drug even in overdose (Barrueto et al ;) )

 

Knake et al. Intravenous levetriacetam in thetreatment of benzodiazepine-refractory status epilepticus. J Neurol Neurosurg Psychiatry 2007 Sept 26; Epub


Category: Toxicology

Title: Phenytoin: PO vs IV load

Keywords: phenytoin, anticonvulsants, loading dose (PubMed Search)

Posted: 12/27/2007 by Fermin Barrueto, MD (Updated: 12/7/2021)
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                                      Phenytoin po      Phenytoin IV       Fosphenytoin

Time to therapeutic       6.4 hrs                  1.7 hrs                 1.3 hrs

Adverse Events              0.69/pt                   1.86/pt                 1.87/pt

Cost                                   $2.83                   $88.50                $224.09
 
(Swadron et al. Ann Emerg 2002)

Also to take into account  is that the adverse events with IV phenytoin include soft-tissue necrosis if there is extravasation of infusion. The cardiotoxicity seen with phenytoin and fosphenytoin is largely due to the propylene glycol diluent and thus not seen with oral loading or even in oral overdosing.

You decide, at least you have the data to properly evaluate the risk:benefit ratio.


Category: Toxicology

Title: Ketorolac (Toradol) Toxicity - Need to Know

Keywords: NSAID, ketorolac, gastritis, renal failure (PubMed Search)

Posted: 12/20/2007 by Fermin Barrueto, MD (Updated: 12/7/2021)
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Ketorolac: an NSAID that gained popularity since it is not an opioid, has excellent anti-inflammatory/analgesic effects and is given IM or IV. Also has been used in renal colic secondary to smooth muscle relaxation (Prostaglandin mediated) in the ureters. You should know:

  • When given IV or IM still causes PUD and has caused GI perforations.
  • Renal Insufficiency is larger concern with this NSAID than others.
  • Consider misoprostol for GI complications.
  • Use for acute pain, limit the number doses given and don't prescribe for more than 3 days. I generally don't prescribe it at all, use another NSAID for outpatient treatment.

 

Corelli et al. Renal Insufficiency and ketorolac. Ann Pharmacother. 1993; 27(9): 1055-7


Category: Toxicology

Title: Drugs that Alter the Thyroid

Keywords: thyroid, hypothyroid, hyperthyroid (PubMed Search)

Posted: 12/14/2007 by Fermin Barrueto, MD (Updated: 12/7/2021)
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Lithium: Hypothyroidism (5-15% of pts) and goiter (37% of pts), mechanism unclear

Amiodarone (37% Iodine by weight): Hyper or Hypothroidism

Beta-Blockers: by blocking peripheral conversion of T4 to T3 cause hypothyroidism

Corticosteroid: same as beta-blockers but can also cause transient thyrotoxicosis (Jod-Basedow effect)

Iodine, Iodinated contrast, radiactive iodine all can cause hypothyroidism but iodinated contrast material can actually induce thyrotoxicosis and thyroid storm from unknown mechanism.


Category: Toxicology

Title: Anti-Emetics

Keywords: ondansetron,metoclopramide (PubMed Search)

Posted: 12/7/2007 by Fermin Barrueto, MD (Updated: 12/7/2021)
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Everything you need to know about anti-emetics, mechanism of action, potency and toxicity:

1) 5-HT3 Blockers - Ondansetron, Granistron

- The most potent anti-emetic, only toxicity is really cost

2) Dopamine Blockers - Metoclopramide

- Can titrate to high doses, causes dystonia, akathisia and mild QT prolongation

3) Anticholinergic - Promethazine, meclizine, diphenhydramine

- Cannot titrate, most sedating, urinary retention in elderly, mild QT prolongation


Category: Toxicology

Title: Radiocontrast-Induced Nephropathy

Keywords: radiocontrast, nephropathy, renal failure (PubMed Search)

Posted: 11/29/2007 by Fermin Barrueto, MD (Updated: 12/7/2021)
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  • Risk Factors for RCIN: Renal insufficiency, >60 yr old, DM, Renal Transplant, Hypovolemia, EF <30%, concomitant nephrotoxic drugs
  • Consider Prophylaxis with anyone of three methods (no method has been found superior.
    • Normal Saline: 1 ml/kg/h IV pre and post study
    • NaHCO3: 3 ml/kg IV bolus over 1 hr then 1 ml/kg/h pre and post
    • IV Acetylcysteine 150 mg/kg bolus over 1hr then 50 mg/kg over 4h

Category: Toxicology

Title: Food Toxicology Pearls

Keywords: Food Poisoning, tetrodotoxin, ciguatera toxin (PubMed Search)

Posted: 11/22/2007 by Fermin Barrueto, MD (Updated: 12/7/2021)
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A short list of some of the unique food poisonings and the toxicologic effects:

  • Ciguatera toxin (fish): hot-cold sensation reversal
  • Tetrodotoxin (fugu, puffer fish): paresthesias progressing to paralysis and dysrythmias
  • Scrombroid (spoiled fish): flushed face due to histamine ingestion
  • Paralytic Shellfish Poisoning (mussels, clams, etc): acts like curare, toxin is saxitoxin
  • Amnestic shellfish poisoning (mussels): exactly what it says, loss of memory - very cool

Category: Toxicology

Title: Sulfonylureas - What is the antidote?

Keywords: sulfonylureas, octreotide, hypoglycemia (PubMed Search)

Posted: 11/8/2007 by Fermin Barrueto, MD (Updated: 12/7/2021)
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Sulfonylureas

  • Sulfonylureas cause insuline release via cAMP/protein kinase C
  • All sulfonylurea overdoses should be admitted for 24 hrs regardless of symptoms
  • Antidote for recurrent hypoglycemia due to sulfonylureas (overdose or therapeutic misadventure) is octreotide, after your glucose
  • Octreotide, a somatostatin analogue, turns of insulin secretion completely
  • Octreotide 50 mcg SQ q 6 hrs for 24 hrs then observe for hypoglycemia 12-24 hrs

Fasono et al. Comparison of Octreotide and Standard Therapy Versus Standard Therapy Alone for the Treatment of Sulfonylurea-Induced Hypoglycemia. Ann Emerg Med 2007 Aug 29.


Category: Toxicology

Title: Carbamazepine

Keywords: anticonvulsant, carbamazepine, seizure (PubMed Search)

Posted: 11/2/2007 by Fermin Barrueto, MD (Updated: 12/7/2021)
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Carbamazepine

  • Anticonvulsant that can be monitored (you can draw a level)
  • Toxicity resembles a TCA with seizures and cardiac conduction delays
  • > 40 mcg/mL assoc with coma, seizures, respiratory failure and cardiac toxicity
  • Treat widened QRS comples with sodium bicarbonate
  • Adsorbs very well to activated charcoal, multi-dose may be required

Category: Toxicology

Title: Toxicity of SSRIs

Keywords: SSRI, serotonin, toxicity (PubMed Search)

Posted: 10/25/2007 by Fermin Barrueto, MD (Updated: 12/7/2021)
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SSRI Toxicity

Things to watch for in patients that are taking SSRI:

  • Therapeutic administration usually safe
  • Hyponatremia is a common adverse effect (ADH secretion regulated by serotonin)
  • Serotonin Syndrome is a possibilty in combination with other serotnergic drugs
  • One SSRI is more problematic than the rest => Citalopram and Escitalopram
    • The only SSRI that can cause QT prolongation (even 24hrs after OD) and can cause seizures
    • This is the only SSRI with significant toxicity and unfortunately is the most commonly Rx by psych

Category: Toxicology

Title: "Liquid X" or Gamma-Hydroxybutyrate (GHB)

Keywords: Gamma-Hydroxybutyrate, GHB, Liquid X, date rape, overdose (PubMed Search)

Posted: 10/18/2007 by Fermin Barrueto, MD (Updated: 12/7/2021)
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GHB

  • Sedating and amnestic, has become notorious in chemical submission (date rape)
  • Very fast onset and rapid resolution though respiratory depression can occur 
  • Difficult to test for with few labs and quickly eliminated through urine 
  • Best chance to catch it is if the patient's first urine void is collected and tested

Category: Toxicology

Title: Valproic Acid and its Unique Antidote

Keywords: valproic acid, poisoning, carnitine (PubMed Search)

Posted: 10/11/2007 by Fermin Barrueto, MD (Updated: 12/7/2021)
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Valproic Acid (Depakote) - Increased use for both seizure disorder, migraine prophylaxis and bipolar disorder - Causes hyperammonemia with or without hepatic insufficiency (Liver enzymes could be normal!) - Hyperammonemia can occur at therapeutic concentrations and overdose - If the patient is sedated and has hyperammonemia, consider carnitine therapy antidotal - Carnitine IV or PO: 50-100 mg/kg bolus or divided bid, safe to give


Category: Toxicology

Title: Rubbing Alcohol - Dangerous?

Keywords: Isopropanol, toxic alcohol, poisoning (PubMed Search)

Posted: 10/4/2007 by Fermin Barrueto, MD (Updated: 12/7/2021)
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Isopropanol (Commonly Rubbing Alcohol)
  • Rubbing alcohol is 70% isopropanol, like drinking Bacardi 151 (151 proof)
  • This is NOT a toxic alcohol in the traditional sense
  • This causes a large ketosis, large osmol gap but NO anion gap and no acidosis
  • This is because isopropanol is metabolized to acetone (a ketone) not an acid
  • Toxicity: inebriation, hemorrhagic gastritis, sedation to the point of death/intubation