The Do’s and Don’ts of Antidotes
© 2010 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
Page 1
Lisa Booze, PharmDCertified Specialist in Poison Information
PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of
continuing pharmacy education
Legal Disclaimer: The material presented here does not necessarily reflect the views of Pharmaceutical Education
Consultants (PharmCon) or the companies that support educational programming. A qualified healthcare professional
should always be consulted before using any therapeutic product discussed. Participants should verify all information and data before treating patients or employing any therapies described in this educational activity.
This program has been brought to you by PharmCon
This program has been brought to you by PharmCon
Accreditation:
Pharmacists: 0798-0000-10-026-L04-P
Pharmacy Technicians: 0798-0000-10-026-L04-P
Nurses: N-593
CE Credits: 1.0 contact hour
Target Audience: Pharmacists, Technicians
& Nurses
Program Overview:
Home is where the poisons are. It's not that we stock them intentionally. It's just that so many things that
we use around the house--medicines, cleaners, painting supplies, perfumes, insecticides, even vitamins--
can be toxic if swallowed or if taken in excess. This program is designed to give pharmacists the do’s and
don’ts of antidotes for many of the common poisonings that can occur in everyday life
Objectives:
• Know the indications, routes and dosages for the use of acetylcysteine in treating acetaminophen
overdoses
• Identify the antidotes used in the treatment of calcium channel blocker, beta blocker and sulfonylurea
overdoses
• Describe the differences between the Cyanide Antidote Kit and hydroxocobalamin
• Review the indications and dosing for fomepizole
• List other antidotes used for poisonings and overdoses and their indications
Speaker: Dr. Lisa Booze is the Clinical Coordinator and a Certified Specialist in Poison Information at the
Maryland Poison Center, a division of the University Of Maryland School Of Pharmacy. She is responsible for
developing and implementing toxicology continuing education programs for health professionals in Maryland. She
is a co-coordinator of the Poison Center Surveillance for Chemical and Bioterrorism and Public Health Program,
supported by the Maryland Department of Health and Mental Hygiene. Dr. Booze is a member of the American
Association of Poison Control Centers, the American Academy of Clinical Toxicology, and the Expert Consensus
Panel that develops Out-of-Hospital Management Guidelines for U.S. poison centers.
Speaker Disclosure: Dr Booze has no actual or potential conflicts of interest in relation to this program
This program has been brought to you by PharmCon
PharmCon is accredited by the Accreditation Council for Pharmacy Education as a provider of
continuing pharmacy education
Legal Disclaimer: The material presented here does not necessarily reflect the views of Pharmaceutical Education
Consultants (PharmCon) or the companies that support educational programming. A qualified healthcare professional
should always be consulted before using any therapeutic product discussed. Participants should verify all information and data before treating patients or employing any therapies described in this educational activity.
“Substances which can counteract a form of poison”.
Few antidotes
Not always indicated
Many pharmacists and physicians are unfamiliar with poisons/drugs and their antidotes
The Do’s and Don’ts of Antidotes
© 2010 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
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available in more than 600 nonprescription and prescription drug products
>150,000 cases reported to poison centers yearly
>25,000 treated with an antidote
Acetaminophen
APAP glucuronide
Unchanged APAP5%
APAP sulfate
40-67%
20-46%
NAPQI Cysteine, mercaptate
conjugates
CYP450
Glutathione
5-15%
Acetaminophen
APAP glucuronide
Unchanged APAP5%
APAP sulfate
40-67%
20-46%
NAPQI Cysteine, mercaptate
conjugates
CYP450
Glutathione
Binds to hepatocellular
proteins
5-15%
Initially, just mild GI symptoms
Delayed symptoms: hepatic dysfunction, metabolic acidosis, encephalopathy, coagulation deficiency, renal failure
Many unintentional overdoses result in liver failure (Larson, et al. Hepatology 2005; 42(6):1364)
APAP - 42% liver transplant patients
48% were unintentional overdoses (> 2 APAP products, APAP/opioid combinations)
The Do’s and Don’ts of Antidotes
© 2010 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
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Oral or intravenous administration
EARLY- prevents hepatotoxicityglutathione precursor/ substitute
increases sulfate conjugation
LATE – decreases morbidity and mortality in patients with hepatic failure
improves microcirculatory blood flow
scavenges oxygen free radicals
Delay > 10 hrs post ingestion decreases effectiveness
FDA approved - 1985
140 mg/kg po load; 70 mg/kg po q4h X 17 doses
• 1330 mg/kg over 72 hours
Dilute to 5% solution
Side effects: nausea, vomiting!!
Must repeat dose and give antiemetics if patient vomits within one hour
FDA approved 2004
Approved for acute overdoses, within 8-10 hours of the ingestion
Available as 20% solution in 30 mL vials (200 mg/mL)
300 mg/kg over 21 hour
Patient weighs >40 kg & < 100 kgLoading dose: 150 mg/kg IV in 200 mL D5W over 1 hour
1st maintenance dose:50 mg/kg IV in 500 mL D5W over 4 hrs
2nd maintenance dose: 100 mg/kg IV in 1000 mL D5W over 16 hrs
>100 kg patient? Pediatrics – amount of IV fluid is decreased
The Do’s and Don’ts of Antidotes
© 2010 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
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Treatment failures in high risk patients with 21 hours of IV acetylcysteine
Recheck labs before the end of the 3rd
infusion
Restart Acetadote (6.25 mg/kg/hr ) if elevated AST or ALT, INR or acetaminophen level
<8% of patients (adults and peds)
Flushing/Urticaria
Pruritus
Angioedema
Respiratory distress, hypotension
Use with caution if the patient has asthma or a history of bronchospasm
Oralgoes directly to liver (1st pass effect); <10% into blooddose is larger than IV
oral in high risk patient (delayed presentation, very high acetaminophen level)
oral if serious adverse effects with IV
70 kg patient treated for 72 hours: <$100 + costs of hospitalization, antiemetics, etc
Intravenous
IV in low risk patients (acute ingestion < 10 hours ago)
IV if inability to tolerate oral
IV if fulminant hepatic failure
may need larger doses
70 kg patient treated for 21 hours: >$500 + hospitalization costs
The Do’s and Don’ts of Antidotes
© 2010 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
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221 patients treated with IV acetylcysteine
84 medication errors in 74 (33%) patients
Lapse in treatment of greater than 1 hour – 18.6%
Giving acetylcysteine when not needed – 13.1%
Rate of infusion – 5%Especially loading dose
Incorrect dose – 1.4%
Hayes, Klein-Schwartz, Doyon. Ann Pharmacother 2008; 42:766-770.
Common overdoses - ~ 20,000 cases yearly reported to poison centers
Capable of producing severe toxicity with small amounts, especially CCBs
Lethargy, seizures, hypotension, bradycardia, AV block (verapamil, diltiazem), asystole
Difficult to treat – requires multiple drug therapy
Reverses hypotension and impaired cardiac conduction with CCB OD’s
Calcium Chloride 10% (13.6 mEq/10 mL)
Adults: 10-20 mL (1-2 grams) slow IVP (over 5 min)
Repeat q15mins X 4
Peds: 0.2-0.3 mL/kg (20-30 mg/kg) slow IVP Repeat q15mins X 4
May not be effective in severe overdoses
Binds to myocardium, increases cAMP levels promotes Ca influx
Increases contractility, blood pressure; may increase heart rate
Adult: 5-10 mg IV over 1-5 minutes, then 5-10 mg/hr
Peds: 50 mcg/kg IV over 1-5 minutes, then 50 mcg/kg/hr
Often not enough glucagon available!
Adverse effects: hyperglycemia, vomiting
The Do’s and Don’ts of Antidotes
© 2010 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
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Insulin enhances cardiac carbohydrate metabolism + inotropic effects, increases BPUsed if severe or persistent hypotension & in conjunction with other drug therapy1 unit/kg regular human insulin bolus; followed by 0.5 unit/kg/hrGive dextrose bolus: 1 amp (25 mL) D50 (peds: 0.25 g/kg D25W); follow with D5W
>8,000 poisonings each year
Ethylene glycol, methanol
Toxic metabolites
Toxic dose of ethylene glycol: > 0.2 mL/kgA mouthful in an adult or child
Toxic dose of methanol: > 0.1 mL/kg
Toxic effects: Initial GI upset and intoxication, then delayed metabolic acidosis, cardiac & pulmonary toxicity, renal failure (EG), blindness (methanol)
Competitive inhibitor of alcohol dehydrogenase; blocks metabolism of EG and methanol
Not FDA-approved
IV or PO
Difficult to dose; requires frequent monitoring of blood ethanol levels
Often need hemodialysis
Adverse effects: intoxication, respiratory depression, hypoglycemia (peds)
Antizol®, 4-MP, 4-methylpyrazole
Competitive inhibitor of alcohol dehydrogenase; blocks metabolism of EG and methanol
FDA-approved 1997 (Antizol®); generic available December 2007
1 gm/mL; 1.5 mL vials
The Do’s and Don’ts of Antidotes
© 2010 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
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Begin immediately upon suspicion of EG/Methanol ingestion (history or symptoms) OR serum level > 20 mg/dl ORosmol gap >20 mOsm
Use with dialysis if renal failure, significant metabolic acidosis, visual disturbances, very high EG or methanol levels
Discontinue when EG/methanol levels are < 20 mg/dl, and no sxs, normal pH
Diluted in 100 ml NS or D5W and infused over 30 minutes
Loading dose: 15 mg/kg
Maintenance doses: 10 mg/kg every 12 hours x 4 doses, then 15 mg/kg every 12 hours until EG/methanol level is <20mg/dl
Give every 4 hours during hemodialysis
Adverse effects: headache (14%), nausea (11%), dizziness (6%), drowsiness (6%), bad taste (6%)
Do not give undiluted or by bolus: venous irritation, phlebosclerosis
Fomepizole metabolites are excreted renally -no info on use in renal or hepatic disease
Few cases with pediatric patients
Hemodialysis and ICU may be unnecessary in some cases
Cyanide salts (sodium cyanide, potassium cyanide)
Photography, research, plastics manuf., metal electroplating, fumigation
Hydrogen cyanide (HCN) produced in closed space fires
Chemical weapon - HCN
Acrylic nail glue remover (acetonitrile)
Bitter almonds, cassava, apricot pits (laetrile)
The Do’s and Don’ts of Antidotes
© 2010 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
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Interferes with oxygen use at the cellular level, causing tissue hypoxia (inhibits cytochrome oxidase a3)Onset within seconds to minutes
Dizziness, nausea, tachypnea, (‘air hunger’), loss of consciousness, seizures, apnea, tachycardia, bradycardia, hypotension, cardiac arrest
Anion gap metabolic acidosis, high lactate, normal O2 saturation
Amyl nitrite, sodium nitrite, sodium thiosulfate
Nitrites + hemoglobin methemoglobin
Cyanide binds to methemoglobin cyanmethemoglobin
Cyanmethemoglobin + thiosulfate thiocyanate + hemoglobin
Amyl nitriteOne ampule inhaled for 30 seconds every minute
Sodium nitriteAdult: 10 mL (300 mg) of a 3% solution administered IV >5 minutes (usually 15-20 minutes)
Pediatric: 0.15-0.33 mL/kg up to 10 mL, administered IV over 15-20 minutes
Sodium thiosulfateAdult: 12.5 g (50 mL of a 25% solution)
Pediatric: 1.65 mL/kg of a 25% solution (412.5 mg/kg)
Dosage calculations
NitritesVasodilation, hypotension, tachycardia
Methemoglobinemia
Sodium ThiosulfateSlow onset
Contraindicated if carbon monoxide poisoning (smoke inhalation)
The Do’s and Don’ts of Antidotes
© 2010 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
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Approved by the FDA on 12/15/2006
Hydroxocobalamin binds to CN cyanocobalamin (excreted in urine)
No methemoglobinemia
Given to smoke inhalation victims; carried by some EMS providers
ContentsTwo-2.5 g vials (lypholized powder)
AdministrationDilute each vial in 100 cc NS (rock, don’t shake for 30 sec)
Adults: 5 g over 15 min
Pediatrics: 70 mg/kg
May repeat dose if not improving
Adverse effects: Hypertension and red discoloration of skin and urine
Colorimetric lab interferences
Co-oximetry hemoglobin & carboxyhemoglobin measurements Uhl W, et al. Clin Toxicol
2006;44:S17-S28.
2006: >165,000 ED visits related to use of oxycodone, hydrocodone & methadone (DAWN)
Opioid analgesics involved in almost 40% of poisonings deaths in 2006 (CDC)
Opioid toxidrome: CNS depression, respiratory depression, constricted pupils
The Do’s and Don’ts of Antidotes
© 2010 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
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IM, IV
0.4-2.0 mg; 0.1 mg/kg in peds
Duration: 90 minutes max
Intranasal
Same dosing and onset
Similar efficacy
Better absorption than IM
Ideal for patients where needle stick is difficult
Eliminates concern for needle stick injury
IndicationsLong-acting opioids
Return of respiratory depression requires repeated bolus doses or a continuous infusion or intubation
DoseGive 2/3 of the bolus dose that resulted in reversal per hour
Titrate as needed
Benzodiazepine-receptor antagonist
Reverses BZD-induced CNS/respiratory depression
IndicationsReversal of procedural sedation with benzodiazepines
Reversal of BZD toxicity in children
Adults: 0.2 mg IV; may repeat doses of 0.2-0.5 mg prn up to 3 mg
Peds: 0.01-0.02 mg/kg IV, max cumulative dose 1 mg
Not recommended for intentional overdoses or those who chronically take benzodiazepines
Flumazenil might precipitate withdrawal seizures
Flumazenil could remove protectant effect of benzodiazepines when other drugs are also taken seizures, arrhythmias
The Do’s and Don’ts of Antidotes
© 2010 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
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Sulfonylureas (glipizide, glyburide…) antagonize the potassium channel on beta islet cells of the pancreas resulting in increased release of insulin
Produce severe and prolonged hypoglycemia
Treatment – dextroseRebound hypoglycemia
Long-acting, synthetic analog of somatostatin
Inhibits pancreatic insulin secretion
Used if patient requires >1 dextrose bolus or a dextrose infusion to maintain normal blood glucose
Dose: 50-100 mcg SC q6h (1 mcg/kg in peds)
Adverse effects are minimal (GI)
Digoxin inhibits the membrane bound Na-K-ATPase transport system positive inotropic effect
Acute ingestions – children, suicide attempts
Chronic overdoses due to change in renal function, drug interactions, dosage errors
Toxicity: GI symptoms, hyper- or hypokalemia, bradycardia, heart block, arrhythmias
Digibind®, Digifab®
Indicated for dysrhythmias, ingested dose > 10 mg (adults) or > 4 mg (peds), K+ > 5 mEq/L, or digoxin level > 10 ng/mL
Dosage based on amount ingested or serum level
One vial Digibind (38 mg) binds 0.5 mg digoxin
If acute ingestion of unknown amount and unknown serum level, give 20 vials; 6 vials if chronic
Allergic reactions rare (<1%)
The Do’s and Don’ts of Antidotes
© 2010 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
Page 12
Rattlesnakes, copperheads, cottonmouths
Pain, edema, hemorrhagic vessicles, weakness, fasciculations, hypotension, coagulopathy
Sheep immunized with snake venoms (Western Diamondback, Eastern Diamondback, Mojave rattlesnakes and Cottonmouth)
Binds and neutralizes venom toxins
4-6 vials initially; repeat with 4-6 vials until control of symptoms
Continue with 2 vials q 6 hours for < 18 hours; additional 2 vial doses prn
Adverse effects: anaphylactoid; much safer than older Wyeth snake antivenom
Antidote Drug/Poison
Atropine, Pralidoxime (2-PAM) Pesticides, nerve agents
Deferoxamine (Desferal®) Iron
Physostigmine Anticholinergics
Sodium Bicarbonate TCA’s
DMSA (Succimer®), BAL, EDTA, d-penicillamine
Heavy metals
Methylene Blue Methemoglobinemia-inducing drugs
Antivenins Snakes, spiders
Vitamin K Warfarin, rodenticides
Potassium iodide Thyroid radioiodine
Intralipids Lipid-soluble drugs
Legalon®SIL Amatoxin mushrooms
Call the local poison center for information on indications, dosing and stocking of antidotes
Dart, et al. Expert consensus guidelines for stocking of antidotes in hospitals that provide emergency care. Ann Emerg Med 2009;54:386-394.