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You are here: Home / 14. Toxicology / *General Principles and Random Drugs

*General Principles and Random Drugs

September 6, 2011 by CrashMaster

“All things are poison and nothing is without poison.  Solely the dose determines that a thing is without poison.”

–Paracelsus

 

Tox Links

Vaults of Erowid

www.lycaeum.org

www.householdproducts.nlm.nih.gov

www.ansci.cornell.edu/plants

www.dartmouth.edu/~toxmetal

www.toxed.com

www.microdex.com/products/poisondex

www.clinicalpharmacology-ip.com

 

 

Mnemonics

Do not adsorb to charcoal

PHAILS

Pesticides;

Hydrocarbons;

Acids and alkali;

Iron;

Lithium; and

Solvents

 

Repeat Dose Charcoal

ABCD

Antimalarials (quinine) and aminophylline (theophylline);

Barbiturates (Phenobarbital) and beta-blockers (nadolol);

Carbamazepine

Dapsone

and Dilantin (Phenytoin)

Valproate

Theophylline

 

Toxins Accessible To Hemodialysis

Small Molecule, Low Protein Binding, Water Soluble

I STUMBLE

Isopropyl Alcohol

Salicylates

Theophylline (caffeine)

Uremia

Methanol

Barbiturates, beta-blockers (water soluble, such as atenolol)

Lithium

Ethylene glycol

 

Vital Sign/PE Mnemonic

s

Bradycardia (PACED)

Propranolol or other beta-blockers, poppies (opiates), propafenone, phenylpropanolamine

Anticholinesterase drugs

Clonidine, calcium-channel blockers

Ethanol or other alcohols

Digoxin

 

Tachycardia (FAST)

Free base or other forms of cocaine

Anticholinergics, antihistamines, amphetamines

Sympathomimetics (cocaine, amphetamines), solvent abuse

Theophylline

 

Hypothermia (COOLS)

Carbon monoxide

Opiates

Oral hypoglycemics, insulin

Liquor

Sedative-hypnotics

 

Hyperthermia (NASA)

Neuroleptic malignant syndrome, nicotine

Antihistamines

Salicylates, sympathomimetics

Anticholinergics, antidepressants

 

Hypotension (CRASH)

Clonidine, calcium-channel blockers

Reserpine or other antihypertensive agents

Antidepressants, aminophylline

Sedative-hypnotics

Heroin or other opiates

 

Hypertension (CT SCAN)

Cocaine

Thyroid supplements

Sympathomimetics

Caffeine

Anticholinergics, amphetamines

Nicotine

 

Rapid respiration (PANT)

PCP, paraquat, pneumonitis (chemical)

ASA and other salicylates

Non-cardiogenic pulmonary edema

Toxin-induced metabolic acidosis

 

Slow respiration (SLOW)

Sedative-hypnotics (including GHB)

Liquor

Opiates, sedative-hypnotics

Weed (marijuana)

 

Miosis (COPS)

Cholinergics, clonidine

Opiates, organophosphates

Phenothiazines, pilocarpine

Sedative-hypnotics

 

Mydriasis (AAAS)

Antihistamines

Antidepressants

Atropine and other anticholinergics

Sympathomimetics

 

Drugs Causing Pneumonitis Or Pulmonary Edema

(MOPS)

Meprobamate, methadone

Opiates, organophosphates

Phenobarbital, propoxyphene, phenothiazines

Salicylates, smoke inhalation (including cocaine smoke), solvents

 

Causes of high Osmal Gap

ME DIE

Methanol

Ethylene glycol

Diuretics (osmotic diuretics like mannitol)

Isopropyl alcohol

Ethanol

Also acetone

 

Drugs that cause Seizures

Aspirin

Tramadol (Ultram®, Ultracet™)

Tricyclic antidepressants

Bupropion (Wellbutrin®, Zyban®)

Diphenhydramine (Benadryl®)

Amphetamines/Cocaine

Venlafaxine (Effexor®)

Leon from the Poison Review has this mnemonic:

O – organophosphates
T – tricyclic antidepressants
I – isoniazid, insulin (hypoglycemia)
S – sympathomimetics, synthetic cannabinoids (Spice)

C – cocaine, camphor
A – amphetamines, anticholinergics, atypical antipsychotics
M – methylxanthines (theophylline, caffeine)
P – phencyclidine (PCP)
B – botanicals (e.g., water hemlock), bath salts, benzo withdrawal, bupropion
E – ethanol withdrawal
L – lead, lindane
L – lithium, lidocaine

 

 

Smells of Toxicology (River’s)

Nitrites, Isopropyl alcohol:  fruit like

Phenols:  disinfectant

Cyanide:  bitter almonds

Chloral Hydrate:  pear-like

Arsine, phosphorous, tellerium, organophosphates:  garlic

Turpentine:  violets

Hydrogen Sulfide:  rotten eggs

Camphor, naphthalene:  mothballs

Phosgene:  hay

Methylsalicylate:  wintergreen

Presentations

Brady+Vomiting=Digoxin

Also av or nodal block with atrial or ventricular irritability

Tachy+Vomiting=think theo

Extrapyramidal Toxidrome

TROD seen with zines, haldol, reglan

Tremor, torticollis, trismus

Rigidity

Opisthotonos, Oculogyric Crisis

Dysphonia, dysphagia

Activated Charcoal

AC only helps in tylenol overdose if given within 1 hour of ingestion (J Toxicol Clin Toxicol 2001;39(6):601)

Position Statement Am Acad Toxicol, no AC after 1 hour can be supported by evidence, only give in patients with intact or protected airway

A different opinion on charcoal

Doesn’t adsorb charged ions (potassium, sodium, etc.)

Malignant Hyperthermia

Rare inherited disorder: autosomal dominant with variable expression and incomplete penetrance

May occur up to 24 hours after the use of succinylcholine or inhaled anesthetics

From abnormal calcium channels

AMS, rigidity, hyperthermia, autonomic instability, acidosis

Active Cooling

Benzos

Dantrolene-1 mg/kg IV may repeat to dose of 10 mg/kg.  2 mg/kg PO QID for 2 days after.

 

Malignant HYperthermia Review

Date Rape Drugs

GHB and flunitrazepam

Barbs, benzos, ambien, carisoprodol, chloral hydrate, GHB, THC, Cocaine, methamphetamines, XTC, PCP and Ketamine, Scopolamine

Statins

Cholesterol membrane instability, muscle affected most

Rhabdomyolysis b/c of coenzyme Q inhibition in mitochondria.  Myopathy and hepatotoxicity

.

TB Meds

Isoniazid (INH)

>20 mg/kg needs evaluation

>79 mg/kg can lead to seizures

May be asymptomatic for up to 2 hours post ingestion

N/V, photophobia, hallucinations, dizziness, ataxia, slurred speech, lethargy progressing to grand mal seizures, coma, and death

Blocks GABA formation (active b6 catalyzes glutamate to GABA, INH makes you pee out B6 and decreases enzymatic formation of active B6), also inhibits conversion of lactate to pyruvate, so lactic acidosis

 

Benzos

Pyridoxine (B6) should be administered to match gram for gram dose of INH up to 5 grams.  If dose unknown, give 5 grams empirically

Effects diminish rapidly, so 6 hours observation, then D/C

Side effect is hepatitis:  10% have elevated enzymes, 10% of those get hepatitis, 10% of those die from it.

Can also cause niacin deficiency:  pellagra=diarrhea, dementia, dermatitis

Rifampin

Causes all fluids to turn red

Ethambutol

Optic Neuritis

Pyrazinamide

Hepatic dysfunction

Antimalarial Meds

Mefloquine

gives vivid dreams

Quinine

Cinchoism=n/v, hearing loss, tinnitus, HA.

Also blocks Na and K channels in heart causing QRS/QT prolongation, requiring Bicarb.  TDP as well.  Give MdAC.  Can get blindness from direct retinal toxicity.

Chloroquine

GI Symptoms, Hypokalemia, QRS/QT prolongation, severe hypotension.  Give 2 mg/kg diazepam over 30 min then 1-2 mg/kg/day.  EPI .25 ug/kg/min until systolic > 100.  Validated in France where this used to be a popular suicide med.

May want to supplement K/Mg before giving bicarb to avoid exacerbating K-channel blockade

 

Dapsone

MetHb

Paraphenylenediamine (Para, PPD)

In hair dyes

Respiratory failure, myoglobinuria, vomiting, tongue swelling.  Causes cancer.

Hydrazine

can cause stat epilepticus, contained in jet fuel

Baclofen

Withdrawal

Fever, AMS, rebound spasticity, rhabdo, organ failure

Can be caused by catheter malfunction, empty reservoir, dead batteries

RX:  restart the pump, oral baclofen, benzos

Poisonings in Lab workers

CO, Cyanide, Azides, MetHb inducing chemicals

Fatal inhalations-CO, Hydrogen Sulfide, Asphyxiants, NOs, Smoke, Halogens

Blood Screening-Na Azide, cyanide, CO, sulfide

Sodium Azide (NaN3)

Highly toxic and highly explosive

Used in detonators and as preservative in lab reactions

In vapor form, colorless, pungent.

Sx arise suddenly and dissipate in a few hours

ABD cramps, chest pain, dysphoria, faintness, flushing, headache, incontinence, n/v, palpitations, weakness, agitation, diarrhea, hyperventilation, hypo or hypertension, leukocytosis, pallor, syncope, sweats, tachycardia, and vomiting.  Larger doses can give blindness, dilated pupils, NCPE, myocardial dysfunction, myocarditis, shock, seizures and coma.  Uncouples oxidative phosphorylation.

GI Decon and supportive care

Review Article

Mitochondrial Toxins

propofol

b. cereus toxin

valproate

hiv meds

can see ketoacidosis, lactic acidosis, myopathy

Propofol Infusion Syndrome

Inten Care Med 2003;29:1417

cardiac depressant

infusion syndrome is associated with catecholamine and steroid tretament simultaneous with propofol

consider after >48 hours of infusion

catechols-increased CO causes increased clearance requiring higher doses

Causes cardiac failure and rhabdomyolysis

>5 mg/kg/hr is considered high dose and puts pts at risk

 

Often seen in kiddies, but reported in adults (Burow BK – Anesthesiology – 01-JUL-2004; 101(1): 239-41 followed by editorial comment)

Green Urine is Seen

 

Phase 1. Fast distribution from blood to tissue; half-life, 2 to 3 minutes

 

The desired clinical response can be titrated by either bolus injections of 0.5 mg/kg every 10 seconds to a total dose of 2 to 2.5 mg/kg or by continuous infusion.

 

Although hypotension is the most commonly reported adverse event, volume loading with 12 mg/kg of Ringer’s lactate solution is effective in maintaining hemodynamic stability.18 Interestingly, propofol in high doses has also been rarely reported to cause seizures, but the mechanism is unknown.19,20

Annals EM Dec 2003 42:6; 793.  propofol recovery time is 5-15 minutes with a 30 second onset

strong anti-emetic properties

can cause hypotension, apnea, and pain on injection

Bassett Peds Study-hypoxia in 5%, airway repositioning in 2% and apnea needing BVM in .8%

 

Great review of lit

Propofol (2,6 di-isopropylphenol) is a very short acting non-opioid sedative–hypnotic agent. It is thought to work by potentiating the binding of -amino butyric acid to receptor sites in the central nervous system (CNS).6 It has no analgesic properties and must be used in conjunction with adequate pain relief. Studies vary regarding the extent of amnesic properties compared to benzodiazepines.6,7 but it has recognised antiemetic and euphoric effects. Onset of action is <60 seconds (one arm–brain circulation). Despite a half life of 13–44 hours, duration of action is approximately 10 minutes, owing to rapid redistribution from CNS tissue to muscle and fat. Metabolic clearance equals or exceeds hepatic blood flow, suggesting extrahepatic clearance, possibly pulmonary.6 Pharmacokinetics are unaffected by renal or hepatic disease but dose reduction is required in the elderly,6 as volume of distribution falls with age.

 

Bassett et al19 (table 1) is a further study in the same institution following almost the same protocol. Patients were fasted for 3 hours and 10 litres of oxygen was administered routinely. At least three deviations from protocol were noted when patients were not given oxygen, and all of these patients became hypoxic.

 

(EMJ 2006;23(2):89)

Screening with CPK (<5000 for discontinuation) may be an effective prevention strategy (Injury, Int. J. Care Injured 45 (2014) 245–249)

 

Nail Polish Removers

most contain acetonitrile which is converted to cyanide in vivo.

Dystonic Reactions

buccolingual-protruding or pulling sensation of tongue

Torticollic-neck or facial spasm

Oculogyric-roving or deviated gaze

Tortipelvic-abd rigidity and pain

Opisthotonic-spasm of entire body

 

Give 50 mg of benadryl IV

 

Strychnine

seizure while awake, lift back off bed

muscle spasms

Strychnine poisoning is an unusual but dramatic poisoning in which convulsions are the major threat to life. Convulsions are predominantly at the spinal level, and the key to recognition of this poisoning is observation of convulsive activity in the awake patient without a postictal phase. Successful treatment requires aggressive airway control and treatment of seizures with benzodiazepines or barbiturates. Neuromuscular blockade may be required. Gastrointestinal decontamination is usually indicated in recent acute ingestions but may precipitate convulsions. Recovery from strychnine poisoning is usually complete and rapid if treatment is aggressive. In the absence of trauma, compartment syndrome, rhabdomyolysis, or anoxic central nervous system injury, no neurologic or musculoskeletal sequelae are expected. Confirmation of strychnine poisoning is best obtained by submitting urine or gastric aspirate for analysis utilizing a qualitative test such as thin layer chromatography (TLC).

 

Malignant Hyperthermia

 

 

Dextromethorphan

DXM

skittles, red hots, triple cs

presents with new-onset and otherwise unexplained psychosis. Although the authors don’t mention it, one clue to the diagnosis might be the presence of nystagmus. One other take-home lesson is that DXM will not itself show up on a urine drug screen, but in large amounts can produce a false-positive urine screen for PCP.

 

Reglan

Metoclopramide

Rate of Akasthisia is directly related to rate of infusion. Over 10 minute infusion sig. less side effects than 2 minute IV Bolus (EMJ 2005;22(9):621)

 

Toxin Induced Hyperthermia

Crit Care 2007; 11:236

 

Colchicine

review of toxicity

Methotrexate

Methotrexate (MTX) is a chemotherapeutic drug that is structurally similar to folic acid. MTX inhibits dihydrofolate

reductase, an enzyme that reduces folic acid to tetrahydrofolic acid. This inhibition interferes with DNA

synthesis and cell reproduction. MTX is used in the treatment of a variety of illnesses including cancer, rheumatoid

arthritis, systemic lupus erythematosus, and psoriasis. It is given intravenously, intramuscularly, orally

and intrathecally.

Methotrexate toxicity develops due to increased patient susceptibility during treatment, excessive parenteral

or intrathecal administration, therapeutic errors by patients (e.g. taking MTX orally daily instead of weekly),

self-administration to induce abortion, or intentional oral overdoses. Clinical manifestations of toxicity include

nausea, vomiting, diarrhea, mucositis, stomatitis, esophagitis, elevated hepatic enzymes, renal failure, rash,

myelosuppression (leukopenia, pancytopenia, thrombocytopenia), acute lung injury, tachycardia, hypotension,

and neurologic dysfunction (depression, headache, seizures, motor dysfunction, stroke-like symptoms, encephalopathy,

coma). Toxic effects may occur hours to days to weeks after MTX administration or overdose.

Treatment of MTX toxicity includes the administration of activated charcoal in the event of a recent, oral overdose.

Renal failure may be prevented by adequate hydration and urinary alkalinization with sodium bicarbonate.

There are three antidotes that have been used for MTX toxicity: leucovorin, thymidine and glucarpidase.

Leucovorin (folinic acid) is the reduced and active form of folic acid. It selectively “rescues” normal cells from

the toxic effects caused by MTX’s inhibition of the production of reduced folates. The recommended dosage in

most cases is 100 mg/m

2 intravenously every 3 to 6 hours until the plasma MTX level is less than 0.01

mcmol/L or for 3 days or longer if levels are not available. Thymidine rescues cells from the cytotoxic effects of

MTX. Its use is investigational and is only given along with other therapies. Glucarpidase (carboxypeptidase) is

an antidote that has been used recently for MTX toxicity in combination with leucovorin. It converts MTX to an

inactive form and rapidly lowers MTX blood levels. It is given as a single bolus of 50 units/kg intravenously

over 5 minutes. Leucovorin should be continued for 48 hours after glucarpidase administration. Hemodialysis

and hemoperfusion have been used to lower MTX levels. Intrathecal overdoses require special measures including

cerebrospinal fluid drainage and exchange, steroids, and antidotes. (Maryland ToxTidbits)

 

Dinitrophenol (DNP)

Fatal 2,4-dinitrophenol poisoning . . . coming to a hospital near you. Siegmueller C, Narasimhaish R. Emerg Med J 2010 May 29 [Epub ahead of print]

Abstract

Dinitrophenol (DNP) is an industrial chemical used in the manufacture of explosives, herbicides, dyes, and wood preservatives.  When ingested, DNP uncouples mitochondrial oxidative phosphorylation, interfering with the cells’ ability to store energy as ATP.  Instead, the energy is dissipated as  heat, causing severe hyperthermia that in case reports has proven very difficult if not impossible to control. In addition, the ATP depletion causes release of calcium from the sarcoplasmic reticulum in muscles.  The resulting uncontrolled muscular contraction produces even more heat. Patients with DNP toxicity often die of hyperthermia, multi-organ failure, and cardiovascular collapse. Presenting signs and symptoms of acute DNP toxicity include hyperthermia, diaphoresis, nausea and vomiting, and diarrhea.

In the 1930s, DNP was often used as a diet aid after a clinical pharmacologist found that — by increasing the metabolic weight — controlled doses of DNP could cause an average loss of 1.5 – 2.0 pounds per week.  One laboratory brought out a product called Formula 281, that contained DNP 1.5 grains.  The promotional brochure gushed: “Here, at last, is a reducing remedy that will bring you a figure men admire and women envy, without danger to your health or change in your regular mode of living.” Enthusiasm for these products waned when it became apparent that the gap between the “therapeutic” and toxic doses was extremely narrow, and customers taking even the recommended dose started to go blind from “dinitrophenol cataracts“.

Unfortunately, DNP is being sold again — over the internet — as a weight-loss product.  This fascinating case report from  London describes an adult male who suicidally ingested 14×200 mg DNP tablets purchased from a website.  On arrival at hospital 12 hours after ingestion, he had vomiting and diarrhea, diaphoresis, and dehydration.  His pulse was 150/min, BP 104/64, respiratory rate 28.min, and temperature 38.4°C.  The clinicians instituted  treatment recommended by the U.K. National Poison Information Service guidelines, including fluids, cooling, and sedation. However, the patient’s condition deteriorated and he developed respiratory failure and an asystolic cardiac arrest from which he could not be resuscitated.

The authors make the point that the U.K. NPIS guidelines recommend treating DNP toxicity with dantrolene if the patient’s temperature is greater than 39-40°C.  Although this is based — as far as I can determine — on just a single abstract, the pharmacology makes sense: dantrolene specifically inhibits calcium release from sarcoplasmic reticulum.  The authors argue that the NPIS threshold for administering dantrolene may be set too high, and that giving it earlier in significant DNP toxicity may be beneficial.

 

Drug Stuffers and Body Packers

Mules

The protocol from EMJ

 

Review of Blood Purification

From Adv in Chronic Kidney Dis

Drug-Induced Hyperthermia

Best Review Article of Drug-Induced Hyperthermia

2,4 Dinotrophenol

Too Hot to Handle!

 

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Filed Under: 14. Toxicology


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