the do’s and don’ts of antidotes · the do’s and don’ts of antidotes ... •list other...

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.

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


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


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

http://harrypotter.wikia.com/wiki/File:Bezoars_(Antidote_to_Poison)_HBP.jpg




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)




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




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




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




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




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)




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)

http://jems.com/news/102411/




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




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




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%)




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.

the do’s and don’ts of antidotes · the do’s and don’ts of antidotes ... •list other...

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