UMEM Educational Pearls - Toxicology

Classical illicit recreational drugs like cocaine, ecstacy, and marajuana are sometimes difficult for teens to acquire. As a result, many are turning to their parents medicine cabinets as a source for recreational drugs.

[From the website drugabuse.gov] In 2008, 15.4 percent of 12th-graders reported using a prescription drug nonmedically within the past year. This category includes:

• amphetamines
• sedatives/barbiturates
• tranquilizers
• opiates other than heroin
  • hydrocodone, oxycodone

When adolescent patient presents to the ED, consider the possibility of a poly-pharmacy overdose. Always query parents about the presence of OTC and Rx medications in their home, and what is within reach of their kids.

While sedatives and analgesics are concerning, be alert for overdoses of more mundane medications like beta blockers and calcium-channel blockers which often pose a much more lethal threat. Consider overdose in adolescent patients with:

• GI or respiratory complaints
• Altered mental status (combative or somnolent)
• Abnormal vital signs
• History of depression or psychiatric illness

---

Monitoring the Future Study: Trends in Prevalence of Various Drugs for 8th-Graders, 10th-Graders, and 12th-Graders

2005-2008 (in percent)*

	8th-Graders				10th-Graders				12th-Graders
	2005	2006	2007	2008	2005	2006	2007	2008	2005	2006	2007	2008
Any Illicit Drug Use
Lifetime Past Year Past Month	21.4 15.5   8.5	20.9 14.8   8.1	[19.0] [13.2]   7.4	19.6 14.1   7.6	38.2 29.8 17.3	36.1 28.7 16.8	35.6 28.1 16.9	34.1 26.9 15.8	50.4 38.4 23.1	48.2 36.5 21.5	46.8 35.9 21.9	47.4 36.6 22.3

Full chart available by clicking link in references.

Show References

Serotonin is a neurotransmitter that has central and peripheral effects. It regulates the secretion of ADH from the hypothalamus and also controls the chemoreceptive trigger zone (CTZ) which induces emesis. Here are a list of medications categorized by the way they affect serotonin. Remember, any combination of these agonists could precipitate serotonin syndrome:

Enhance 5-HT synthesis: L-tryptophan

Direct HT agonists: Ergots, metoclopramide, sumatriptan, buspirone

Increase 5-HT release: amphetamines, cocaine, dextromethorphan, MDMA, L-dopa

Inhibit 5-HT breakdown: MAOIs, Linezolid

Inhibit 5-HT re-uptake: SSRIs (paxil), amphetamines, carbamazapine, tramadol, TCAs, citalopram, trazodone, lamotrigine, meperidine

 

Goldfrank's sniffing bar: no this is not a pub where toxicologist's hang out but rather a bar that assists with teaching the recognition of odors related to toxicology. Certain drugs and compounds have a distinct aroma.

The following is a list odors, see if you can name a medication or compound that has that odor - scroll down further to see the corresponding answers (if you really got all 5 email me and convince me):

1) Bitter Almond

2) Rotten Eggs

3) Wintergreen

4) Garlic

5) Sweet, Fruity (acetone)

 

Answers:

1) Cyanide; 2) N-acetylcysteine or Hydrogen Sulfide; 3) Methylsalicylate (like bengay); 4) Arsenic, organophosphate insecticides; 5) Chloroform, chloral hydrate

Add metoclopramide (Reglan) to the laundry list of medications with black box warnings from the FDA. Why was a black box warning added?

• Long-term metoclopramide use has been linked to tardive dyskinesia (involuntary and repetitive body movements) even after the drug is no longer being taken.
• Risk factors: Long-term or high-dose use, elderly, female gender.
• Recommended that metoclopramide treatment not exceed 3 months.

• None really.
• Just be aware of the dopamine antagonist effects (EPS - dystonic reactions) that are possible whenever you order metoclopramide in the acute setting.
• These effects can be treated effectively with an anticholinergic agent, such as diphenhydramine or benztropine.

Clevidipine

• A new intravenous antihypertensive agent
• Has a very rapid onset (2-4 min) and offset (5-15 min), in contrast to the available IV calcium channel blocker nicardipine, which has a duration of action of 3-6 hours
• Contraindicated in patients with soy or egg allergies, and in those with defective lipid metabolism
• Most common ADR's reported were headache, nausea, and vomiting
• Initiate at 1-2 mg/hr, most respond at doses between 4-6 mg/hr
• Maximum recommended dose is 16 mg/hr
• Costs between $86 to $140 per 50 mg vial

Show References

As the economy worsens and our patients pay for more prescriptions out of pocket, here are some tips that may help you better serve your patients: 1) Ondansetron (zofran) is now off patent. Write generic on your script for zofran - for pediatrics the ODT (dissolving tablets) - are all much cheaper ($0.50 to $1.00 per pill or ODT). IV formulation is now cheaper than phenergan. Reglan is probably still the cheapest in most pharmacies. 2) Typical $4 antibiotics are the following: SMP-TMZ (Bactrim), Cephalexin, Amoxicillin, Penicillin, Ciprofloxacin. 3) Albuterol MDIs are now much more expensive because they have to be CFC free. Unfortunately, after this federal regulation, patients will have difficulty getting these inhalers which can be quite expensive. If you write a script and the patient is self-pay, they are going to have difficulty. Hospitals are beginning to discourage "to go" inhalers and even pills due to the fact that insurance companies DO NOT reimburse these costs - only IV meds.

Rocuronium is fast becoming the agent of choice for RSI in the Emergency Department. Here is a head to head comparison of the two drugs to understand why:

	Rocuronium	Succinycholine
Dose	1-1.2mg/kg	1mg/kg
Onset	1-1.5min	1min
Duration	7-12min	30-40min
Histamine Release	No	Minimal Yes
CVS Effect	Tachycardia rare	Severe Brady rare
Other Adverse Effect	No fasciculations, No ICP effect, No Rhabdo	Fasciculations, increase ICP, rhabdo, movement of displaced Fxs

 

You have a 44 y/o female patient with an arterial line monitoring her blood pressure which is reading 302/156 mm Hg.  Her heart rate is 140 bpm.  Her history reveals she is taking a monoamine oxidase inhibitor (MAOI) and has inadvertantly ingested tyramine at her friend's cheese/wine party.   What do you do?

• Conditions producing hypertensive crisis from catecholamine surges (phenylephrine overdose, cocaine, tyramine interactions, pheochromocytoma) can be treated with phentolamine
• Phentolamine is a nonspecifc alpha blocking agent which produces peripheral vasodilation with a resultant fall in blood pressure in most patients.
• Other uses include extravasation of some vasopressors (e.g. norepineprhine)
• May see an increase in HR after administration (once alpha blockade is established, beta-blocker can be administered)
• Dose: 5-15 mg IV/IM
• Duration: 30-45 minutes

There have been multiple case reports of patients who have had coronary stents who have been on clopidogrel for > 1 year who have developed coronary thrombosis after clopidogrel cessation. There are also reports of patients who have developed DVTs likewise after clopidogrel cessation. In vivo studies in diabetics have demonstrated increased platelet and inflammatory markers after clopidogrel withdrawal. It appears that abrupt discontinuation of clopidogrel may lead to a thrombotic state in susceptible patients.

Show References

Rodenticides have taken many forms. The following is a list of some of the more interesting ones either due to the mechanism of toxicity or how it is lethal. All of these are also toxic to people.

1) Strychnine - Glycine Antagonist at the post-synaptic spinal cord neurons - patient or rat will have convulsion of the extremeties but will be awake, alert and in extreme pain. Essentially look like generalized seizure except awake. Treatment: Benzodiazepines, Analgesia, Supportive

2) Brodifacoum - Long Acting Coumarin - rat eats, later develops elevated INR then tries to run through thin cracks in the wall or takes a little too high of a jump, then boom - subdural or some other internal hemorrhage. In human, they can stay anticoagulated for weeks after an overdose. Treatment: Vitamin K and large padded room

3) Cholecalciferol - Vitamin D precursor - there are big blocks of this drug in the NY and other subway systems. Rat nibbles, gets hypercalcemic, then gets thirsty because of this. Rat runs out into middle of subway to drink out of puddle then - splatt - the M train to Brooklyn comes along. Treatment: IVF, Loop Diuretics, Bisphosphonates

 

Octreotide

• Somatostatin-analog that supresses insulin secretion but also treats acromegaly, esophageal varices and secretory diarrhea
• Sulfonylurea-induced hypoglycemia requires frequent monitoring and administration of intravenous dextrose
• Octreotide is considered antidotal therapy since it turns off insulin secretion that is caused by sulfonylureas
• Recent article by Fasano et al Ann Emerg Med 2008 showed that octreotide 75 mcg SQ one-time in the ED was superior to "traditional" therapy with fewer recurrent hypoglycemic episodes during the patient's hospitalization.
• Excellent article worth reading, even if its just the abstract

Show References

Tetrodotoxin - Sodium Channel blocker - Extremely toxic causes paresthesias, dysrhythmias and paralysis - Found in the sushi called Fugu (From the Pufferfish) - Eating the sushi is considered a delicacy and goal is to get just enough of the toxin to get perioral paresthesias after eating. - Also found in the blue-ringed octopus, angelfish and parrot fish. Enjoy your seafood and take a look at the attached pic of actual fugu.

Attachments

• 0901152329_fugu_0111.jpg (145 Kb)

A few previous pearls have touched on identifying drugs that cause QT prolongation.  In our patient population, methadone is one of the more common causes of drug-induced prolonged QT syndrome.  Of 692 physicians surveyed (35% family practitioners, 25% internests, 22% psychiatrists, and 8% self-identified addiction specialists) only 41% were aware of methadone's QT-prolonging properties and just 24% were aware of methadone's association with torsade de pointes.

 

Now that you know, what do you do when a patient on methadone presents with a QTC of 580 msec and intermittent runs of vtach and torsade de pointes?

 

The answer is... the exact same thing you would do with any other patient who presents this way, regardless of the cause.

• Give magnesium sulfate 2 gm IV for torsade de pointes
• Check magnesium and potassium levels.  If low (which they often are), replete.
• Monitor continuous EKG.

Buprenorphine, an alternative to methadone, is not associated with prolonged QT syndrome.

 

Show References

Although we tend to think of ACS with cocaine use, there are many other serious complications, including:

• Agitation, psychosis, and anxiety
• Hyperthermia
• Vascular headache of withdrawal
• Seizures
• Hemorrhagic stroke (many of these patients have an underlying vascular abnormality)
• Ischemic stroke
• Acute Renal Failure
• Crack Lung: acute pulmonary syndrome that occurs after inhaling freebase cocaine presents as fever, dyspnea, hypoxemia, diffuse alveolar infiltrates, and respiratory failure
• Intestinal perforations

Show References

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

Show References

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.

Show References

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.