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281-300 of 558 results with category "Toxicology"
There is minimal evidence of cross-reactivity between sulfonamide antibiotics and non-antibiotics [1-4]. Despite this, the U.S. FDA-approved product information for many non-antibiotic sulfonamide drugs contains warnings concerning possible cross-reactions.
Key Findings from a New Review Article [5]:
- An estimated 3-6% of the general population is allergic to sulfonamides.
- Structurally, none of the non-antibiotic sulfonamides exhibit both of the features shown to be responsible for sulfonamide reactions (i.e., an N-containing ring attached to the N1 nitrogen of the sulfonamide group and an arylamine group at the N4 position).
- A comprehensive literature search (1966-December 2011) identified only 9 case reports indicating possible cross-reactivity to sulfonamide medications; however, in most cases, adequate patient testing was not conducted to firmly establish either sulfa allergy or sulfonamide cross-sensitivity.
Bottom line: You can feel safe prescribing furosemide, glyburide, and hydrochlorothiazide to your patient with an allergy to sulfamethoxazole/trimethoprim.
Other blog reference on this topic: http://lifeinthefastlane.com/2011/04/sulfa-drug-discombobulation/
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Naloxone can be administered via pretty much any route. One that has gained popularity in the past several years is nebulized naloxone. Although anecdotal reports tout the benefits of nebulized naloxone, what does the literature say?
- Case report of 46 y/o f with initial oxygen saturation of 61%. Naloxone was administered by nebulizer and within 5 min oxygen saturation was 100% and mental status was normal. [1]
- Retrospective analysis of prehospital adminstration in 105 patients. 22% had "complete response" and 59% had "partial response." Problem is the initial respiratory rate was 14 bpm with GCS of 12. [2]
- Prospective analysis of 26 patients in an inner-city, academic ED. Pre-naloxone respiratory rate was 13 with GCS of 11. Post-naloxone respiratory rate was 16 with GCS of 13. Three patients (12%) experienced moderate-to-severe agitation and 2 (8%) were diaphoretic. [3]
Bottom Line: Many of the studied patients may not have needed naloxone in the first place (initial respiratory rate 13-14), with a few developing withdrawal symptoms. Nebulized naloxone may have a role in the not-too-sick opioid overdose in whom you want to prove your diagnosis and wake the patient up enough to obtain a history. It is not a therapy for the apneic opioid overdose.
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A recent article was published in the Journal of Medical Toxicology reviewing the use of sodium acetate for treatment of overdoses and poisonings.
Acetate is metabolized to bicarbonate, causing a net increase in cations; this increased strong anion difference leads to alkalemia.
It has been used to treat acidosis in uremia, diarrhea, and in trauma patients.
Although no studies have been conducted using sodium acetate as an antidote, if bicarbonate is unavailable this is a viable option for management of salicylate overdose, and for qrs widening or arrhythmias due to overdoses.
Sodium acetate, if given rapidly (in animals and hemodialysis patients), causes myocardial depression, hypotension, and hypopnea.
The bolus dose should be given as 1-2 mEq/L given over 15-20 minutes. For the maintenance infusion, dilute 150 mEq diluted to 1 L in dextrose 5%, infuse at 2X the maintenance rate.
It must be diluted in dextrose 5% and NOT normal saline.
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The internet has become a wealth of information and some books have now gained internet noteriety. A chemist and author of the book - TIKHAL: Tryptamines I Have Known and Loved is an excellent example.
Tryptamines include drugs like LSD and alpha-methyltryptamine (AMT). Vivid visual hallucinations and serotonin agonism, these drugs were glamorized by this author. He would synthesize a tryptamine and then "taste it". Take a look at the link below where he first describes the biochemical synthesis he performed then describes his dose response effect when he tried the drug.
If you run into a drug or slang term in the ED you are not familiar with, the website www.erowid.org will likely have the translation.
http://www.erowid.org/library/books_online/tihkal/tihkal48.shtml
In June 2013 the American College of Medical Toxicology (ACMT) released a Guidance Document on the Management Priorities in Salicylate Toxicity. Here are some key highlights:
- Continuous IV infusion of sodium bicarbonate is indicated even in the presence of mild alkalemia from the early respiratory alkalosis.
- Euvolemia is important.
- If intubation is required, administration of sodium bicarbonate by IV bolus at the time of intubation in a sufficient quantity to maintain a blood pH of 7.45-7.5 over the next 30 minutes is a reasonable management option during this critical juncture.
- Once airway control has been established, it is imperative that the increased minute ventilation and low PCO2 usually seen with salicylate intoxication are maintained.
- A salicylate concentration approaching 100 mg/dL warrants consideration of hemodialysis in the acute toxicity setting (40 mg/dL for chronic toxicity). Consult nephrology well before these threshold levels.
The full document can be accessed here.
The Poison Review blog by Dr. Leon Gussow discusses the guidance document here.
Follow me on Twitter (@PharmERToxGuy)
When reviewing a patient's medication list, there are always some that should catch your eye. Digoxin is one since we can measure it, has a low therapeutic index and elimination is effected when renal function is diminished. Another drug that should catch your eye is SOTALOL. Renally cleared and affected by even a minimally lower than normal magnesium. The toxic effect even at therapeutic levels is torsades de pointes.
One study, in a 736 bed hospital, showed 89% of patients prescribed sotalol were on an inappropriate dose due to renal function and an odds ratio of 3.7 increased re-admission rate at 6 months for the patients on the inappropriate dose of sotalol.
We can catch this in the ED. Involve your pharmacist, ED pharmacist or local toxicologist for dosing calculations.
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In the treatment of acetaminophen poisoning with N-acetylcysteine (NAC), the PT/INR can be slightly elevated even in the absence of hepatotoxicity. Considering Prothombin Time (PT) is one of the criteria used to assess severity of liver damage in this setting, it is important to know how much the PT/INR can be affected by NAC and if it has an actual effect on coagulation factor levels.
- N-acetylcysteine has been shown to slightly increase the PT) by up to 3.5 seconds in healthy volunteers.
- A more recent study by the same authors demonstrated a reduction in vitamin K-dependent clotting factor activity (II, VI, IX, and X) after NAC administration in healthy volunteers.
Clinical Practice Pearls
- The elevation in PT/INR after NAC administration is real, not simply laboratory interference.
- However, the PT/INR elevation and decrease in coagulation factors is modest and not likely clinical signficant.
- Many poison center guidelines allow for an INR up to 2 to be considered 'normal' to account for this phenomenon in this setting.
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- Opioid analgesia can actually INCREASE sensitivity to pain in some cases
- The exact cause is unclear, but may be due to up-regulation of NDMA receptors in spinal cord dorsal horn neurons
- Pain tends to be DIFFERENT and DIFFUSE from the underlying condition for which the narcotics were prescribed
- Switching from shorter acting opiates to methadone may be effective, as it is a weak NDMA antagonist and has only partial cross tolerance with other opioids
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Hyperglycemia in the setting of antipsychotic use has been reported mostly with olanzapine (Zyprexa) but does occur with other antipsychotics. A recent study from the NYC medical examiner's office details 17 deaths of DKA due to antipsychotics and found that (from highest to lowest incidence) quetiapine > olanzapine > risperidone were the atypical antipsychotics found with these deaths.
Remember hyperglycemia occurs with patients on antipsychotics and can lead to hyperglycemia hyperosmolar coma or DKA. Both can be lethal.
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Utilizing 20% lipid emulsion at a dose of 1.5 mL/kg (100 mL Bolus) IV with repeat in 15 minutes in no response is being recommended in patients hemodynamic instabiity due to poisoning.
Probably more effective in lipophilic drugs is a current theory for the mechanism of action - the "lipid sink". The idea is that the lipids envelope the drug pulling it off its receptors or sequestering it in the intravascular space. A recent paper has added another mechanism - direct inotropic and lusiptropic effects.(1)
Also, if you think the therapy is experimental, think again. Another recent paper surveyed Poison Control Centers and found 30/45 Poison Centers in the US have a defined protocol for utilization of lipid emulsion therapy. The PCCs are recommending it more.(2)
What was once considered just a purely experimental therapy only used at the very end of code is becoming more mainstream. Comfort with its safety profile and anectodotal effiicacy continues to mount.
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Strychnine poisoning is still occasionally found in rat poisons and in adulterated street drugs and herbal products. The typical symptoms are involuntary, generalized muscular contractions resulting in neck, back, and limb pain. The contractions are easily triggered by trivial stimuli (such as turning on a light) and each episode usually lasts for 30 seconds to 2 minutes, for 12 to 24 hours. Classic signs include opisthotonus, facial trismus, and risus sardonicus.
Differential diagnosis includes:
- Tetanus: However, the onset of symptoms is more gradual and the duration much longer than in the case of strychnine poisoning.
- Generalized seizures: However, strychnine poisoning presents with a normal sensorium during the period of diffuse convulsions.
- Dystonic reaction: However, dystonic reactions are usually static, whereas strychnine poisoning results in dynamic muscular activity.
- Serotonin syndrome
- Malignant hyperthermia
- Neuroleptic malignant syndrome
- Stimulant use
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If you are working in a community hospital and have an acetaminophen overdose, one of the criteria to transfer the patient to a tertiary care center is presence of the King's College Criteria.
The below is taken from mdcalc.com - http://www.mdcalc.com/kings-college-criteria-for-acetaminophen-toxicity/
Each one is assigned points and can be prognostic for severe toxicity and need for transplant. The lactate and phosphorus are new ones and have modified the criteria. Phosphorus is utilized to create glycogen. If the liver is injured and trying to heal, your phosphorus will be low (good). If the liver is injured and unable to repair itself the phosphorus will be high (bad). This single test has an excellent prognostic ability.
| Lactate > 3.5 mg/dL (0.39 mmol/L) 4 hrs after early fluid resuscitation? | |
| pH < 7.30 or lactate > 3 mg/dL (0.33 mmol/L) after full fluid resuscitation at 12 hours | |
| INR > 6.5 (PTT > 100s) | |
| Creatinine > 3.4 mg/dL (300 µmol/L) | |
| Grade 3 or 4 Hepatic Encephalopathy? | |
| Phosphorus > 3.75 mg/dL (1.2 mmol/L) at 48 hours |
With recent events, a few notes about ricin seems appropriate:
- Easy to make from castor bean though heat labile
- No antidote, though Fab like digibind is in development
- Granule size of the grain of sand can kill
- Inhalation, IM, IV all effective
- After immediate exposure likely no symptoms
- Vomiting and diarrhea initially, acute lung injury and death in 3-5 days
CDC website: http://www.bt.cdc.gov/agent/ricin/
Methods: A large retrospective case series evaluated 121 children under 6 years old with hypoglycemia from a sulfonylurea ingestion.
Results:
- In addition to dextrose, patients who received octreotide had a median of zero hypoglycemic episodes after octreotide (compared to 2 before treatment, p < 0.0001).
- Median blood glucose concentrations after receiving octreotide were also higher (62 mg/dL vs 44, p < 0.001).
- Most required only 1 dose of octreotide with no reported adverse effects.
Authors' Conclusion: Octreotide administration decreases the number of hypoglycemic events and increases blood glucose concentrations in children with sulfonylurea ingestion.
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Cocaine toxicity is characterized by the sympathomimetic toxidrome: tachycardia, hypertension, hyperpyrexia, diaphoresis as well as sodium channel blocking effects that can cause local anesthesia topically, QRS widening and even seizure.
Usual treatment for a cocaine toxic patient is benzodiazepines and cooling. Be wary of end organ damage, trauma and seizures.
There was a recent study that looked at dexmedetomidine to treat the sympathomimetic effects. Placebo-controlled trial used cocaine-addicted volunteer and applied intranasal cocaine. Measuring skin sympathetic nerve activity and skin vascular resistance, this study, unfortunately, showed as the dose increased MAP did not fall further and increased paradoxically in 4 of 12 subjects.
This highlights the incredible physiologic mechanism of catecholamine release from the CNS with cocaine. This mechanism overlaps some with the centrally acting alpha agonist - dexmedetomidine and was shown in the study by Kontak et al.
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In 2013, the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists published a second update to their position statement on gastric lavage for GI decontamination (original 1997, 1st update 2004).
- Gastric lavage should not be performed routinely, if at all, for the treatment of poisoned patients.
- Further, the evidence supporting gastric lavage as a beneficial treatment even in special situations is weak.
- In the rare instances in which gastric lavage is indicated, it should only be performed by individuals with proper training and expertise.
Bottom line: Gastric lavage generally causes more harm than good. It should not be thought of as a viable GI decontamination method.
Bonus: Dr. Leon Gussow (@poisonreview) reviews the position paper on his blog, The Poison Review, here: http://www.thepoisonreview.com/2013/02/23/gastric-lavage-fuggedaboutit/
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Question
A foley is inserted in a fire victim patient. Urine return is in picture. Describe the reason for this colored urine.
Special Thanks to Dr. Doug Sward for the urine picture
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Typical opioid withdrawal include clinical symtpoms of piloerection, nausea, vomiting and diarrhea. If you were to see seizure, another etiology other than opioid withdrawal should be investigated.
Except in the case of neonates borne to women who have been taking opioids chronically such as a methodone patient. Once the child is born, symptoms of withdrawal may take days to weeks to materialize though seizures typically occur <10 days. The child is at increased risk of SIDS as well.
Most antidotes have not been adequately studied in pregancy and hold a Pregnancy Risk Category 'C' by the FDA. However, there are a few antidotes that hold a category 'D' or 'X' rating (contraindicated).
- Ethanol (toxic alcohols) - Category C
- Reproduction studies have not been conducted with alcohol injection. Ethanol crosses the placenta, enters the fetal circulation, and has teratogenic effects in humans. When used as an antidote during the second or third trimester, Fetal Alcohol Syndrome AS is not likely to occur due to the short treatment period; use during the first trimester is controversial.
- Alternative (preferred) antidote: fomepizole.
- Methylene blue (methemoglobinemia) - Category X
- Use during amniocentesis has shown evidence of fetal abnormalities, but it has been used orally without similar adverse events. IV may be ok.
- Lorazepam and diazepam (seizures, nerve agents) - Category D
- Teratogenic effects have been observed in some animal studies and in humans. Lorazepam/diazepam and their metabolite cross the human placenta.
- Potassium iodide (radioactive iodine) - Category D
- Iodide crosses the placenta (may cause hypothyroidism and goiter in fetus/newborn). Use for protection against thyroid cancer secondary to radioactive iodine exposure is considered acceptable based upon risk:benefit, keeping in mind the dose and duration.
- Amyl nitrite (cyanide) - Category C (manufacturer contraindicates)
- Animal reproduction studies have not been conducted. Because amyl nitrate significantly decreases systemic blood pressure and therefore blood flow to the fetus, use is contraindicated in pregnancy (per manufacturer).
- Other options exist to treat cyanide exposure including sodium nitrite, sodium thiosulfate, and hydroxocobalamin.
- Penicillamine (chelator) - Category D
In most cases, the benefits of short-term use probably outweigh the risk, especially when accounting for the health and prognosis of the mother.