UMEM Educational Pearls - Toxicology

Watch out for tradename and generic name's of medications.

They can get the patient and yourself into trouble:

• coumadin: warfarin, jantoven
• diphenhydramine: unisom, benadryl, tylenol PM

Classic example is my own case: Insert a central line in a patient - subclavian - and shortly after completion am alerted the patient's INR is 25. No adverse outcome but when I reviewed the med list, I did not see coumadin or warfarin and assumed I was in the clear. Patient was on jantoven.

Happy Holidays

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The FDA has ruled that Long-Acting Beta Agonists (LABAs) are not worth the risk with increased hospitalization and increased mortality. Serevent has largely been replaced by Advair now. Unfortunately, for the children, it took 3 years to look at the data and finally come to this conclusion. Advair (LABA + fluticasone) has escaped the ruling with lack of evidence.

A search of the toxicology literature will reveal that naloxone has been tried in many different overdose situations.  It is thought that the endogenous opioid system mediates several physiologic and pharmacologic pathways.

• Captopril – naloxone reverses hypotension (Ann Emerg Med 1991;20(10):1125-7)
  • Evidence: One case report.
• Valproic Acid – naloxone reverses CNS depression possibly through GABA attenuation
  • Evidence: Two case reports demonstrated effectiveness in patients with minimally elevated VPA levels.  Other reports showed no effect in patients with much higher concentrations.
• Clonidine – naloxone reverses coma, bradycardia, and hypotension
  • Evidence: Several case reports suggest positive response while others demonstrate no benefit.  Anecdotal experience estimates a response in about 50% of cases.

Bottom line: In none of these instances was improvement as dramatic or consistent as in the reversal of the toxic effects of an opioid.  Naloxone can certainly be tried in non-opioid overdoses but should not be considered a first-line antidote.  The most benefit appears to be with clonidine.

CO is formed from the incomplete combustion of carbon materials, eg. fires, stoves, portable heaters CO reversibly binds hemoglobin, producing carboxyhemoglobin (HbCO). This causes oxygen to bind more tightly to hemoglobin, releasing less in the tissues. Because of this, it affects the organs with the highest oxygen requirements most profoundly (eg. brain and heart).

Symptoms are mainly neurological and cardiovascular, but may include a wide variety of non-specific symptoms. The initial symptoms of CO poisoning may include headache and flu-like illness progressing to confusion, agitation, lethargy, seizures and coma.

Place patients on 100% oxygen to decrease the half-life of HbCO. Though controversial, HBO therapy is thought to decrease the incidence of neurologic sequelae. HBO therapy should be considered for patients with a HbCO level above 20%, severely symptomatic patients with lower levels, and pregnant patients. Remember that pulse oximetry will not be accurate.

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Tryptophan - a precursor to melatonin, it is often blamed for the post prandial coma that many go into after a big turkey dinner. Never mind the 5000 kcals that was consumed during the meal. The supplement really doesn't help with sleeping. Interestingly, turkey isn't even in the top 10 or 20 of foods that contain tryptophan. The top five are:

1) Game meat (Elk): 746 mg of tryptophan

2) Seaweed (Spirulina): 736 mg of tryptophan

3) Spinach: 690 mg of tryptophan

4) Egg White: 673 mg of tryptophan

5) Soy protein: 630 mg of tryptophan

Supplements of L-tryptophan have been contaminated with a compound that has been associated with eosinophilia myalgia syndrome.

 

Local Anesthetic - Bupivacaine (Marcaine) - Sodium channel blocker with duration of action 2-4 hrs (w/epi 3-7 hrs) - Toxic dose is > 2.5 mg/kg or > 175 mg total dose (Infiltrating into SQ) - Bupivacaine 0.25% = 2.5 mg/mL - Inadvertent intravenous injection can result in toxicity - Lethally cardiotoxic with widened QRS, V-tach and neurotoxic with inebriation and seizures - Anesthesia literature reports successful use of Intralipid as an antidote

How many times have you had a patient with an allergy to codeine described as stomach upset?  Or how about a rash with morphine (probably secondary to histamine release)?  True anaphylactic reactions to opioids are very rare (< 1%).  But what happens when you have a patient with a true allergy, but still need to give an opioid?  No problem, you just need to choose one that is structurally different.

• Group 1 (aka opiates) - Naturally occurring agents derived from the opium plant
  • Morphine, codeine, thebaine
• Group 2 - Semi-synthetics
  • Hydrocodone, oxycodone, hydromorphone, oxymorphone, buprenorphine (heroin is also in this group)
• Group 3 - Synthetics
  • Fentanyl (alfentanil, sufentanil, etc.), methadone, tramadol, propoxyphene, meperidine

All of the group 1 and 2 agents are structurally very similar to each other and should not be given if a true allergy exists to any other natural or semi-synthetic derivative.  Group 3 agents have structures different enough that they can be given to a patient intolerant to the natural or semi-synthetics without fear of cross reactivity.  They are also very different from others in this same group.

This is a psychoactive herb which can induce strong dissociative effects by stimulation of the kappa receptor. It has become increasingly well known and available in modern culture, and popularized by YouTube Salvia (also known as Sage, Diviner's Sage, Magic Mint, or Sally D) is usually smoked, but can be chewed or ingested.

The high it produces is very intense, but lasts only approximately 10 minutes. Currently many states have enacted legislation against it, including Fla, IL, KA, MI, MO, ND, OK and VA, but it is available over the internet.

  

The following video demonstrates clinical effects of drug.
Although it is amusing, this is not meant to condone use.

(if you can not view the embeded video here is the link)

http://www.youtube.com/watch?v=w6dgXX0ytSo

Methylenedioxymethamphetamine (MDMA) or "Ecstasy"

A designer club drug that has been classified as a "hallucinogenic" amphetamine though it does not cause visual hallucinations like are reported with LSD. It has many of the sympathomimetic effects like other amphetamines but its main mechanism of action which both causes the euphoria and toxicity is serotonin agonism. Since Anti-diuretic hormone is released by the hypothalamus under the direct regulation of serotonin, there is a transient but dangerous episode of Syndrome of Inappropriate ADH (SIADH). Combined with the club culture and fear of dehydration while taking MDMA, patients ingest MDMA concomitantly with free water through the night further exacerbating the hyponatremia. The time sequence of events for these patient is (women appear genetically predisposed to this phenomena):

• Friday Night: Ingestion of MDMA (even one pill is enough) +/- free water
• Saturday Morning: headache, nausea, vomiting
• Saturday Afternoon: (Realizes its not a hangover) patient becomes confused progressing to unresponsive and eventually seizures
• Saturday Evening: Presents to ED with seizures

Treatment: Fluid restriction - this is the one time that the 1L NS Bolus can kill a patient with cerebral edema. If you must give fluid give 3% NaCl if there is symptomatic hyponatremia. Remember the patient has dropped their sodium in about 24 hours so you can replenish in about the same time quite safely and even faster in severe cases. Treated correctly, patients improve rapidly - within 24-48 hours. Read a great case report in the reference below.

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 Olanzapine (Zyprexa)

This is an atypical antipsychotic that gained popularity because it caused less sedation and fewer extrapyramidal effects. However, there are many other adverse effects that need to be emphasized. Some of these may contribute to a patient's condition in the ED:

• Hyperglycemia: has been reported to even cause hyperglycemic hyperosmolar nonketotic coma as well as DKA in patients that were not diabetic prior to initiation of olanzapine.
• Anticholinergic: one of the most anticholinergic antipsychotics, watch for polypharmacy. Perhaps the patients urinary retention and mild confusion is due to the many anticholinergic medications the patient is taking.
• Serotonin Syndrome: again a problem with polypharmacy and in overdose.

Bisphenol A (BPA) is found in epoxy resins that line common food and beverage materials. There has been concern that this compound, like phthalates, may be causing harm through chronic low exposure. An epidemiologic study was performed and published in JAMA that has raised this question. Amazingly, the study did find that:

• Higher urinary BPA levels correlated with an increase incidence of: NIDDM, CAD and elevated liver enzymes
• Mechanism may be an estrogen effect, disruption of Beta-islet cell function and even obesity promoting effects
• Study was strictly epidemiologic but raises a serious public health concern that you will see in the news more

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Clinical Manifestations in relation to lead level in children:

• > 70 - 100 mcg/dL: Encephalopathy, increased ICP, anemia, vomiting
• 50 - 70 mcg/dL: Irritable, difficult child, abdominal pain, anorexia
• >10 mcg/dL: often asymptomatic, may develop impaired cognition, behavior, impaired fine-motor coordination, hearing and growth

Several antihypertensive agents raise intracranial pressure. Normal cerebral blood flow (CBF) is constant within normal cerebral perfusion pressure (CPP) ranges, recalling that CPP=MAP-ICP.

If CPP is outside the range in which autoregulation occurs, e.g. due to a structural lesion, ischemic stroke, or head trauma, CBF decreases and can adversely affect the patient.

• Nitroprusside
  • Vasodilates both cerebral arteries and veins, increasing ICP
  • Inhibits the normal vasoconstrictive response to hypocapnia
• Nitroglycerin
  • Causes cerebral venodilation, increasing ICP
  • Impairs vasodilatory response to hypercapnia
• Hydralazine (varying effects)
  • Vasodilates cerebral arteries > cerebral veins
  • Impairs cerebral autoregulation
• Nicardipine
  • Other calcium channel blockers increase ICP by vasodilating arteries
  • Has been used to treat vasospasm in SAH
  • Increases cerebral blood flow in patients with SAH and acute stroke

In patients with ischemic stroke or intracerebral pathology, labetalol or esmolol may be used to lower blood pressure without raising ICP. Nicardipine is recommended for use in patients with ischemic stroke or SAH but not in patients with brain injury

If the patient has NO structural abnormalities, but has hypertensive encephalopathy, nitroglycerin, nitroprusside, labetalol, esmolol, or nicardipine may be used.

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 Melamine

• In case you thought the chinese only sent their toxin filled products to the USA, a massive scandal has been occurring with their milk.
• Adding melamine to their milk, companies were able to get falsely elevated readings of protein which is measured by the government to make sure the milk was not watered down.
• 53,000 illnesses, over 12,000 hospitilizations and at least 4 infant deaths have been attributed to their milk supply - 20% of China's milk supply is thought to be contaminated
• Melamine or melamine resin is used to make plastics and involved in other polymeric reactions.
• Toxicity involves the creation of kidney stones - imagine the pain in these poor children
• These children died from renal failure from multiple kidney stones.
• Check the link below to the news article

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 Cheese Heroin: a slang term for the combination of heroin with an over-the-counter antihistamine

• The two are combined and forms a cheesy like powder that is different from pure heroin
• A string of deaths were reported between 2005-2007 in Texas, many adolscents
• This concoction is more often insufflated than smoked or injected
• Combines opioid effect with the anticholinergic confusion and hallucinations
• Scorpion was a heroin that was combined with scopolamine that had similiar effect

Treatment

• Find the anticholinergic toxidrome, place the foley and supportive care are mainstays
• Consider administration of physostigmine 1mg IV slowly over 2-5 minutes (call toxicologist)
• The anticholinergic effects will linger much longer than the heroin effects ( <1hr)

 

 

 Latrodectus sp (Black Widow Spider)

• The only indigenous neurotoxic insect  in the state of Maryland and found through many states in the US
• The "bite" often not visible and does not cause a necrotic lesion like the brown recluse
• Causes Acetycholine release from post-synaptic motor and sensory nerves
• This leads to intense muscle contraction and pain. There have been reports of a black widow spider on the leg and the patient undergoes ex lap surgery for suspected acute abdomen only to find out the abdominal muscles were fasciculating due to envenomation
• Treat with aggresive analgesia and benzodiazepines.
• Not often lethal with approximately 60-70 deaths in the US over 30 years

Take a look at a picture of the black widow on the following attachment

Attachments

black-widow-spider-1.jpg (14 Kb)

Topical Lidocaine for local anesthesia

 

Disclosure: I have no financial or invested interest in the product or the company.

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Buprenorphine (Suboxone)

• Use in opioid maintenance therapy programs, doesn't have QT prolongation and less respiratory depression than methandone
• Patients must been maintained on <40mg of methadone for successful conversion to buprenorphine to take place
• Primary caregivers can prescribe after taking a course
• Partial agonist can actual precipitate withdrawal if patient takes a full opioid (say sneaking a little heroin before appointment)
• Suboxone is buprenorphine+naloxone, since naloxone has poor bioavailability when taken appropriately there is no effect but if the tablet is crushed and injected the patient will go into florid withdrawal.
• Use and abuse has been steadily increasing and death can still occur from overdose.
• Pain is difficult to manage in patient on buprenorphine since opioid effect will be blunted, buprenorphine is potent partial agonist.

 A recent landmark article has cited a connection between non-insulin dependent diabetes and low-level arsenic in our drinking water.

 

• Approximately 13 million in the USA are drinking water that contains Arsenic levels higher than EPA allowable standards
• This study controlled for organic arsenic (found in seafood) and was looking for the effect of inorganic arsenic which is the more toxic compound - don't have to stop eating sushi
• This study essentially found a dose response curve with people with lower arsenic levels having lower incidence of non-insulin dependent diabetes, those with higher levels, higher risk.

 

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