Abnormal ocular movement (e.g. nystagmus) can often be observed in select CNS pathology.
Certain drugs/toxin overdose can also induce nystagmus.
In an "unknown" intoxication, physical exam findings such as nystagmus may help narrow the identity of the suspected ingestion/overdose.
Bupropion (Wellbutrin, Zyban) is unique monocyclic antidepressant and smoking cessation agent that is structurally similar to amphetamines. Bupropion blocks dopamine and norepinephrine reuptake and antagonizes acetylcholine at nicotinic receptors.
Bottom line:
Bupropion is a common cause of drug induced seizures but in severe overdose can also cause prolonged QTc and wide complex ventricular dysrhythmia that may be responsive to sodium bicarbonate. All patients with an overdose of bupropion should have an ECG performed and cardiac monitoring to watch for conduction delays and life-threatening arrhythmias.
47 year old woman presents with cough, headache, weakness, and low grade fever. Her symptoms have been present for several days. Vital signs are temperature 99.9 F, HR 96, RR 16, BP 140/88, Pulse Ox 98%. Physical exam is nonfocal. She is Influenza negative. She is treated with Ibuprofen and oral fluids. Upon discharge she mentions she is having difficulty hearing and feels dizzy. Upon further questioning she admits to ringing in her ears. What tests should you order?
Acute liver failure carries a high morbidity without liver transplantation. Liver support systems can act as “bridge” until an organ becomes available for the transplant procedure or until the liver recovers from injury. Artificial liver support systems temporally provide liver detoxification utilizing albumin as scavenger molecule to clear the toxins without providing synthetic functions of the liver (coagulation factors). One of the most widely used devices is the Molecular Adsorbent Recirculating System (MARS).This system has 3 different fluid compartments: blood circuit, albumin with charcoal and anion exchange column, and a dialysate circuit that removes protein bound and water soluble toxins with albumin.
Bottom Line
MARS therapy could be a potentially promising life saving treatment for patients with acute poisoning from drugs that have high protein-binding capacity and are metabolized by the liver, especially when concomitment liver failure. Consider consultation and transfer of patients to liver center.
Acetaminophen (APAP) overdose is the leading cause of liver failure in the U.S. and Europe. Large APAP ingestion can result in hepatotoxicity despite the early initiation of n-acetylcysteine (NAC).
A recently published study from Austrialia investigated the effect of activate charcoal and increasing the NAC dose for large APAP overdose patients (3rd bag: 100 to 200 mg/kg over 16 hours) during first 21 hours of NAC therapy
acetaminophen ratio (first APAP level taken between 4 to 16 hour post ingestion / APAP level on the Rumack nomogram line at that time point) was determined to compare APAP levels at different time points among study sample
e.g.
first APAP level at 4 hour post ingestion = 400
APAP level on the Rumack APAP nomogram at 4 hour post ingestion = 150
APAP ratio = 400/150 = 2.67
Findings:
Conclusion:
Note: Any increase in NAC dosing from the standard 21 hour therapy should be performed after consulting your regional poison center.
Loperamide (Imodium) is a common inexpensive over-the counter antidiarrheal agent. It acts peripherally at the mu opioid receptor to slow gastrointestinal motility and has no CNS effects at therapeutic doses due to it's low bioavailability and limited abillity to cross the blood brain barrier dependent on glycoprotein transport. In the past few years, reports of loperamide abuse causing serious cardio toxicity began to appear in the literature. Abused at daily doses of 25-200 mg to get high or and to treat symptoms of withdrawal. (therapeutic dose: 2-4 mg with a maximun of 8mg for OTC and 16mg for prescription). Loperamide has been called the "poor man's methadone".
At large doses, loperamide effects the cardiac sodium, potassium and calcium channels which prolongs the QRS complex and can lead to ventricular arrhythmias, hypotension, and death. Clinical features includes:
Take Home Point:
Consider loperamide as a possible cause of unexplained cardiac events including QT interval prolongation, QRS widening, Torsades de Pointes, ventricular arrhythmias, syncope, and cardiac arrest. Intravenouse sodium bicarbonate should be utilized to overcome blockade and may temporize cardiotoxic events. Supportive measures necessary may include defibrillation, magnesium, lidocaine, isoproternol, pacing, and extracorporeal life support.
Different chemical, food or pharmaceutical agent exposure can change the color of the urine.
What could cause this patient's urine to turn green?
Lithium salts have been used therapeutically for over a 150 years to sucessfully treat manic depressive symptoms, schizoaffective disorder, and cluster headaches. Lithium has a narrow therapeutic range (0.6-1.5 meq/L) and is 100% eliminated by the kidneys. Multisystem toxicity occurs however CNS toxicity is significant and consist of confusion, lethargy, ataxia, neuromuscular excitability (tremor, fasciculations, myoclonic jerks, hyperreflexia). Since there is a poor relationship between serum concentration and toxicity in the brain, serum blood levels may not reflect extent of toxicity . The goal of enhanced elimination is to prevent irreversible lithium-effectuated neurotoxcity which causes persistant cerebellar dysfunction with prolonged exposure of the CNS to high lithium levels.
Decision for hemodialysis is determined by clinical judgement after considering factors such as lithium concentration, clinical status of patient, pattern of lithium toxicity (acute vs. chronic), concurrent interacting drugs, comorbid illnesses, and kidney function. Strongly consider hemodialysis for the following:
Many medications are discovered from plants (quinine – cinchona trees) or organisms (penicillin – mold [penicillicum]).
Digoxin was isolated from foxglove (Digitalis lanata), a colorful floral plant often found in many gardens. There are other sources of cardioactive steroids (aka cardiac glycosides) that have similar effect as digoxin.
Non-digoxin cardioactive steroid exposure can result in a positive digoxin level due to cross reactivity. This confirms exposure; however, the “digoxin level” does not represent the true extent of the ingested dose or toxicity.
Non-digoxin cardioactive steroid toxicity
The cornerstone treatment of poisoning is removal of the toxin from the patient. This can be accomplished before absorption into the body by decontamination methods (dermal or gastrointestinal) or after absorption by blocking metabolism of parent compound, displacing drugs from receptors, binding toxins with neutralizing agents (chelators, Fab fragments), or enhancing elimination by dialysis. Toxins that are ideal candidates for dialysis include substances that are low molecular weight, have low volume of distribution (stay in the blood stream), or low protein binding. Toxins most commonly treated with dialysis are:
Her first book “The mysterious affair at Styles,” Agatha Christie introduced her lead detective in her novels, Hercule Poirot - the Belgian detective. She also described the death of Mrs. Emily Inglethorp by strychnine.
Strychnine is found in a disc-like seed of strychnos nux-vomica, a tree native to tropical Asia and North Australia.
It is currently used as rodenticide (moles and gophers), in Chinese herbal medicine and a traditional remedy in Cambodia.
Strychnine inhibits binding of glycine (a major inhibitory neurotransmitter in spinal cord) to Cl-channel resulting in identical clinical syndrome – seizure-like generalized muscle contraction with normal mental status – as tetanus toxin. Tetanus toxin inhibits the release of presynaptic glycine in the spinal cord.
Management
Goal: decrease muscle hyperactivity
Agatha Christie is an English crime novelist who frequently used poisons in her books to murder the victims. In her book, Murder is Easy, Ms. Christie uses arsenic/arsenic trioxide to kill several characters.
Primary source of arsenic in general population is contaminated food, water and soil. Arsenic exists in several forms: elemental, gaseous (arsine), organic and inorganic (trivalent or pentavalent).
Arsenic trioxide has also been used to treat acute promyelocytic leukemia in China; it’s use in other leukemia, lymphoma, and other solid tumors are currently being investigated.
Arsenic primarily inhibits the pyruvate dehydrogenase complex and multiple other enzymes involved in the citric cycle/oxidative phosphorylation, resulting in mitochondrial dysfunction.
Acute toxicity of arsenic after ingestion
Management
Cannabinoid hyperemesis is a syndrome (CHS) characterized by severe intractable nausea, cyclical vomiting, and abdominal pain associated with chronic marijuana abuse. It is often a underrecognized cause of cyclic vomiting syndrome. Despite well established anti-emetic properties of marijuana, paradoxical effects on the GI tract exist through cannabinoid receptors which exert their neuromodulatory properties in the central nervous system and the enteric plexus. Multiple theories of mechanism of CHS are in the literature. Diagnosis is based on the following clinical criteria:
Acute care goals are to treat dehydration and terminate nausea and vomiting. Administration of intravenous fluids, dopamine antagonists, topical capsaicin cream, and avoidance of narcotic medications are recommened treatment measures. Benzodiazepines followed by haloperidol and topical capsaicin are reported to be most effective. Capsaicin activates the transient receptor potential vanilloid 1 receptors (TRPV1) which impairs substance P signalling in the area postrema and nucleus tract solitarius similar to noxious stimuli, such as heat.
Hunan hand syndrome is a painful contact dermatitis that frequently presents in cooks and chili pepper workers after preparing or handling chili peppers. Contact with other body parts gives rise to the terms: "Hunan nose" ''Hunan eye",and "Chili Willie". Capsaicin, found in the fruit of plants from the genus Capsicum such as red chili peppers, jalapeños, and habaneros, is a hydrophobic, colorless, odorless compound that binds with pain receptors causing the sensation of intense heat or burning. The "heat" or pungency of a peppers is measured in Scoville heat units (SHU), the number of times a chili extract must be diluted with water to lose heat. Habanero peppers generate 30,000 SHU. Even at low concentrations capsaicin is a skin irritant. It is the primary ingredient in pepper spray used in law enforcement and in personal defense sprays.
Treatment consists of decontamination with water irrigation for opthalmic exposure and milk or antacids for dermal or gastrointestinal exposure. Burning can be recurrent and of of long duration depending on tissue penetration. Topical anesthetic especially for the eye and cool compresses for the skin can relieve pain. Parodoxically capsaicin is used as a topical analgesic medication for local pain relief from muscle pain, itching, and painful neuropathies (diabetic, postherpetic). Capsaicin initially causes neuronal excitation followed by a long-lasting refractory period due to depletion of substance P, during which neurons are no longer responsive to a large range of stimuli and thus are desensitized.
Hyperkalemia is a potentially life threatening problem which can lead to cardiac dysrhythmias and death. Drug interactions inducing hyperkalemia are extremely common such as the combination of ACE inhibitors and spironolactone or ACE inhibitors and trimehoprim sulfamethoxazole. Hyperkalemia can also occur with a single agent and is a relatively common complication of therapy with trimethoprim sulfamethoxazole. The following drugs can cause hyperkalemia:
During the past several years, several new classes of diabetic medications were introduced for clinical use, including SGLT2 inhibitors (canagliflozin, dapagliflozin and empagliflozin).
SGLT2 inhibitors prevent reabsorption of glucose in the proximal convoluted tubules in the kidney and does not alter insulin release.
A recent retrospective study (n=88) of 13 poison center data from January 2013 to December 2016 showed
49 patients were evaluated in a health care facility (HCF) with 18 admissions. Referral to HCF was more common in pediatric patients. This was likely due to unfamiliarity with a new mediation and lack of toxicity data.
Other case reports have shown higher incidence of DKA with the therapeutic use of SGLT2 vs. other classes of DM medications.
Bottom line:
Limit data is available regarding the toxicologic profile of SGLT2 inhibitors.
Based upon this small retrospective study, hypoglycemia may not occur and majority of the patient experience minimal symptoms.
Radiographs studies can be valuable in poisoning diagnosis, management, and prognosis. Radiographic imaging should be utilized for the following toxins:
Container toxins - Body packers
Sustained Released preparations
There have been reports of “intoxication” or adverse effects among first responders and law enforcement due to exposure to a “powder” suspected to be fentanyl or its analog.
This has led to a significant concern among first responders and law enforcement when investigating or handling “powder” at the scene of overdose or drug enforcement related raids. (http://www.foxnews.com/health/2017/08/15/police-department-gets-hazmat-like-protective-gear-for-overdose-calls.html)
American College of Medical Toxicology and American Association of Clinical Toxicology recently published a position statement to help clarify the potential health risk associated with exposure to fentanyl and its analogs.
VX ("venomous agent X")
LD50 expresses the dose at which 50% of exposed population will die as a result of exposure.
Full cohort analysis idarucizumab for dabigatran associated bleeding was recently published in NEJM.
This study evaluated the laboratory correction of elevated ecarin clotting time or diluted thrombin time induced by dabigatran and time to either cessation of bleeding (Group A: patients with GI bleeding, traumatic bleeding, or ICH) or time to surgery (Group B: patients requiring surgical intervention within 8 hours).
Findings
Group A (n=301): Median time to the cessation of bleeding was 2.5 hours in 134 patients.
HOWEVER:
Group B (n=202): Median time to intended surgery after infusion of idarucizumab was 1.6 hours.
Laboratory markers:
100% reversal of abnormal ecarin clotting time or diluted thrombin time within 4 hours after the administration
Mortality
Conclusion
Authors concluded thate idaurcizumab is an "effective" reversal agent for dabigatran.
Overall, the findings are more promising compared to the interim analysis that was published in 2015.
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