Drugs Poisoning - amscfkuntad.files.wordpress.com · 2/23/2018 · •Clonidine •Cardiac Glycosides (Digitalis) •Benzodiazepines •TA’s •Other Substances •Hyperadrenergic

Drugs Poisoning

Prescription Medication Toxicity

• Scope of the problem• Widely available medications

• Third most common cause of fatal OD in pediatric patients

• Fifth most common cause of fatal OD in Adult patients

Toxicologic Emergencies

• Prescription• Blockers

• Calcium Channel Blockers

• Clonidine

• Cardiac Glycosides (Digitalis)

• Benzodiazepines

• TCA’s

• Other Substances• Hyperadrenergic agents

• Organophosphates

Cardiovascular Drugs

Anticoagulants

Anticoagulants are used medically to inhibit the clotting

mechanism.

Warfarin and a number of chemicals (superwarfarin) with similar,

but much longer, action, including the coumarins and indanedione,

are also used as rodenticides. Single doses of these compounds

are not dangerous.

Fatalities have been recorded following repeated daily doses.

Occurrence

In suicidal cases when there is deliberate overdose of the oral

anticoagulant medication.

In accidental exposure to rodenticide that contains an

anticoagulant (common among young children),

overdosage of heparin due to patient self-administration is rare as

it is available only parenterally, most problems with the use of

heparin are iatrogenic in nature.

Toxicity

The toxic dose is variable.

Chronic ingestion generally produces more toxicity than a simple

acute episode of accidental ingestion.

Clinical Features

• Haemoptysis,

• nosebleeds,

• haematuria,

• bloody stools,

• haemorrhages in organs,

• widespread bruising, and

• bleeding in joint spaces.

Management of Toxicity

In overdoses of anticoagulant, withdraw the medicine.

It is usually prudent to admit patient to the hospital for

close observation of abnormal bleeding.

Conduct physical examination with a check of the

urine and stool for blood at 12- to 24-hour intervals.

In oral ingestions, administer activated charcoal.

Gastric emptying should be avoided in those who are

already anticoagulated or bleeding.

• For patient with a significantly elevated PT (more than

2 times control) but with no evidence of active

abnormal bleeding, administer vitamin K1.

• Give transfusions of fresh blood or plasma if

haemorrhage is severe (PT three or more times

control).

•Absolute bed rest must be maintained

For heparin overdosage, give protamine sulphate, 1% slowly

intravenously (not exceeding 50 mg in 10 min).

For overdosage of coumarin anticoagulants, give Vitamin K1 :

• 0.1 mg/kg parenterally

• 5-10 mg subcutaneously once daily for 2-3 days (for patient with no

abnormal bleeding)

• 5 - 10 mg IV very slowly every 12-24 hours (for patient with active

bleeding, rarely used);

• dosage for children is 1 -5 mg.

Fresh frozen plasma and packed red blood cells is also given during

active bleeding as it gives immediate control since vitamin K will

require 24 hours to be effective.

Repeated doses may be required. Intramuscular injections

are best avoided because of the risk of haematoma formation.

Antidotes:

Analgesics and Antipyretic

Paracetamol is widely used as an analgesic, antipyretic, & in cold

remedies.

It may also be combined with other analgesics such as codeine.

Paracetamol poisoning can cause gastroenteritis within hours and

hepatotoxicity 1 to 3 days after ingestion.

Severity of hepatotoxicity after a single acute overdose is predicted

by serum acetaminophen levels.

Treatment is with N-acetylcysteine to prevent or minimize

hepatotoxicity.

Paracetamol (acetaminophen)

Levels vs time. Cautions for use of this chart: (1) The time coordinates refer to

time of ingestion. (2) Serum levels drawn before 4 h may not represent peak

levels. (3) The graph should be used only in relation to a single acute

ingestion. (4) The lower solid line 25% below the standard nomogram is

included to allow for possible errors in acetaminophen

Acute toxicity:

Acute ingestion of 140 mg/kg in children and 6 g in adult is

potentially toxic.

Children <10 years are less susceptible to hepatotoxicity.

It has been suggested that conjugation of NABQI with glutathione is

more efficient in children than in adults.

Chronic alcoholics and patients with induced cytochrome P450 are

more susceptible to hepatotoxicity since there will be an increase

production of NABQI.

Toxicity

Hepatotoxicity is caused by the reactive metabolite N-acetyl-

pbenzoquinoneimine (NABQI) produced by the cytochrome P450

enzyme.

Normally the NABQI is conjugated with glutathione.

In overdose, the excess NABQI reacts with hepatocytes causing

necrosis.

Chronic toxicity:

Children are more susceptible to chronic toxicity presumably

because they are less able to clear paracetamol by the other

main conjugation pathways due to saturation.

In alcoholics, chronic toxicity has been reported with daily

consumption of 4-6 g.

Chronic overdose:

Symptoms may be absent or may include any of those that

occur with acute overdose.

The Rumack-Matthew nomogram cannot be used, but likelihood

of clinically significant hepatotoxicity can be estimated based on

AST, ALT, and serum acetaminophen

Clinical Features

Early signs: anorexia, nausea, vomiting.

After 24 hours: Increase in prothrombin time (PT) and transaminases

indicating hepatic necrosis, encephalopathy, metabolic acidosis, renal

failure may occur with or without liver failure, myocardial damage, coma.

Stages of Acetaminophen Poisoning

Stage Time Post-

ingestion

Description

I 0 to 24 h Anorexia, nausea, and vomiting

II 24 to 72 h Right upper quadrant abdominal pain

(common); AST, ALT, and, if poisoning is

severe, bilirubin and PT (usually reported as

the INR) sometimes elevated

III 72 to 96 h Vomiting and symptoms of hepatic failure; AST,

ALT, bilirubin, and INR peak; sometimes

renal failure and pancreatitis

IV > 5 days Resolution of hepatotoxicity or progression to

multiple organ failure (sometimes fatal)


• Supportive treatment

• Treat spontaneous vomiting so that activated charcoal may be

administered orally.

• Support hepatic and renal failure, coma if they occur

• Obtain 4-hour post-ingestion serum sample for paracetamol

concentration to assess severity of toxicity

• Gastric decontamination. Administer activated charcoal and

cathartic. Gastric lavage is not necessary if charcoal is given

promptly.

Antidote:

N-acetylcysteine

Intravenous: 150 mg/kg IV in 200 mL 5% dextrose over 15-30

min followed by 50 mg/kg in 500 mL over 4 h then 100 mg/kg

in 1000 mL over 16 h.

OR

Methionine

Oral: 2.5g initially, followed by 2.5g every 4 hours for another

3 doses.

Note: Methionine is NOT the antidote of choice as its efficacy

has not been established.

Nonsteroidal anti-inflammatory agents

Generally, significant symptoms occur after ingestion of > 5 – 10

times the usual therapeutic dose.

Clinical Features

• With most NSAIDs: Anorexia, nausea, vomiting, abdominal pain,

haematemesis, drowsiness, lethargy, ataxia, tinnitus, disorientation.

• With more toxic agents e.g. Phenylbutazone and oxyphenbutazone

mefenamic acid, piroxicam, and massive ibuprofen overdose:

acidosis, hepatic dysfunction, hypoprothrombinaemia, convulsions,

cardiopulmonary arrest, renal failure, coma

Salicylates and their usual contents in dosage forms

Aspirin, salicylic acid, methyl salicylate, glycol salicylates

(2-30% for external use)

Toxicity

Toxic oral dose: 300 - 500 mg/kg (salicylates)

Toxic effects appear at varying plasma levels depending on the

duration of poisoning but are uncommon below 300mg/L.

Toxic blood levels: >500 mg/L in adults >300 mg/L in children

Severe poisoning blood levels:

1. >1000 mg/L in adults

2. >600 mg/L in children

Chronic poisoning: Not well correlated with serum concentrations.

Chronic users of salicylates showing confusion and lethargy and

levels >600 mg/L require haemodialysis.

Clinical Features

Hyperpnoea, acid-base imbalance, mild pain in throat

and stomach, vomiting particularly in infants and

children, sweatiness, hypoprothrombinaemia, tinnitus

(which may sometimes lead to deafness), delirium,

convulsions, oliguria, uraemia, cyanosis, pulmonary

oedema, respiratory failure.

Coma is not uncommon and indicates very severe

poisoning


• Maintain airway,

• Treat seizures, coma, metabolic acidosis and dehydration if they

occur.

• Gastric lavage is not necessary after small ingestions (i.e. <200 –

300 mg/kg) if activated charcoal can be given promptly.

• Administer activated charcoal. Multiple doses of activated charcoal

would be reasonably likely to enhance elimination of a significant

amount of absorbed salicylate.

• In severe poisoning, begin hydration in the first hour with

intravenous fluids 400mL/m2. Maintain acid/base balance.

• Treat metabolic acidosis with IV sodium bicarbonate. Do not allow

pH to fall below 7.4.

• Forced alkaline diuresis can be considered if plasma-salicylate

concentration reaches toxic levels (>500 mg/L). Difficult to achieve in

critically ill patients. There are currently other more efficient methods

of enhancing elimination, such as multi-dose activated charcoal and

haemodialysis.

• Early haemodialysis for rapid removal of salicylates in severe

poisoning (levels >1,200 mg/L, severe acidosis in patients with acute

ingestion; levels > 600 mg/L and any confusion or lethargy in patients

with chronic intoxication)

• Haemoperfusion is also very effective but does not correct acid-base

or fluid disturbances. Especially indicated when plasma salicylate

levels are very high, i.e. >1000mg/L.

Beta Blockers

• Prescribed for• Hypertension

• Angina

• Hyperthyroid

• Migraine

• Glaucoma

• SVT

• Therapeutic effect• 1 Cardiac influence

• 2 Peripheral influence

Beta Blockers

• Pharmacology• Lipophilicity

• Membrane stabilizing effect

• Selective vs non-selective agents

• Propranolol is most common and most dangerous

Beta Blockers

• Toxic Dose • 2-3 times therapeutic dose

• Signs and Symptoms• Bradyarrhythmia

• Hypotension

• Respiratory depression

• Seizure

• Ventricular arrhythmia

Beta Blockers

• Prehospital Management• Aggressive airway management

• Atropine 1mg prn (max 3mg)• Peds 0.02 mg/kg

Atropine often not effective

- Transcutaneous Pacemaker- Do not delay in symptomatic bradycardia

Beta Blockers

• Prehospital Management• Glucagon 5 mg IV bolus

• Peds 0.1 mg/kg IV bolus Increases cyclic AMP

• Fluid resuscitation 200-300 cc BSS (NOT D5!)• Peds 20 cc/kg

• Pressors prn• Dopamine 5-20 mcg/kg/min

• Epinephrine drip 2 mcg/min Titrate to response. May need higher than normal dose

Calcium Channel Blocker

• Prescribed for:• Angina

• Hypertension

• Migraine

• SVT

• Mechanism of Action• Blocks entrance of calcium into

cardiac and smooth muscle cells.


• Pharmacology• Negative inotrope

• Blocks flow of calcium ions through slow channels

• Decreased amount of calcium from sarcoplasmic reticulum

• Negative chronotrope• Decrease automaticity in SA node and AV junction


• Agents• Verapamil

• Significant cardiac depressant • Vasodilation

• AV slowing

• Diltiazem

• Nifedipine

• Felodipine

• Amlodipine


• Toxicity• Hypotension

• Bradycardia

• Arrythmias

• Respiratory depression

• Neurologic disorders• Seizures etc.




Atropine often not effective



• Prehospital Management• Calcium Chloride 250-500 mg IV

• Peds 20 mg/kg

• Glucagon 5 mg IV bolus• Peds 0.1 mg/kg IV bolus

Increases cyclic AMP

• Fluid resuscitation 200-300 cc BSS (NOT D5!)• Peds 20 cc/kg


• Other Management Issues• Pressors prn

• Dopamine 5-20 mcg/kg/min

• Epinephrine drip 2 mcg/min Titrate to response. May need higher than normal dose

• Treat Dysrhythms

• Pediatric Patient• Small doses can be lethal

• Seizures more likely than adult

Case Report:

* 14 mo boy died 3hrs

after ingesting 10 mg of

Nifedipine

Hum Tox 1993;35:345

Clonidine

• Prescribed for • Hypertension

• Withdrawal syndrome

• Migraine

• ADHD

• Tourette’s syndrome

• Mechanism• adrenergic agonist

Clonidine

• Toxic Effects• Cardiovascular

• Bradycardia

• Hypotension (Initial hypertension)

• Arrhythmias

• Neurologic• Miosis

• Respiratory Depression

• Seizures

• Coma

• Signs/symptoms• Mimics Barbiturate/Opiate OD

• Withdrawal• seen after chronic use.

Clonidine

• Treatment• ALS management symptomatic

• Airway, seizures, respiratory depression



• Pressors prn• Dopamine 5-20 mcg/kg/min

• Epinephrine drip 2 mcg/min

Clonidine

• Induction of Emesis• Not indicated due to probability for rapid CNS depression

Digoxin

• Prescribed for• CHF

• Improves cardiac output

• A-fibrilasi

• Mechanism• Cardiac glycoside

• Inhibition of Na/K ATPase• Allows increase in calcium to activate contractile proteins (actin/myosin)

• Increased myocardial contractility

Naturally Occurring Cardiac Glycosides

• Foxglove (Digitalis purpurea)

• Lily of the valley (Convallaria majalis)

• Oleander (Nerium oleander)

• Red squill (Urginea maritima)

• Yellow oleander (Thevetia peruviana)

Digoxin

• Toxicity• Dysrhythmias

• PVC’s

• Slow A-fib, PAT w/ block

• Bradycardia, V-fib, V-tach

• Hypotension

• Hyperkalemia (Renal insufficiency is a risk factor)

• CNS• Delirium, hallucinations, lethargy, agitation

• Ocular disturbances

Digoxin

• Treatment• Basic management (ABC’s etc.)

• Electrolyte disturbances• Hyperkalemia

• NEVER give Calcium

• Atropine/Pacemaker

• Manage dysrhythms

• Digoxin specific antibody

Other Prescriptive Medications

Overdose/Toxidromes

Case Presentation

• 30-year-old woman; brought into ED by

EMS

• Boyfriend reports recent anxiety, stress

• Empty bottles of Ativan (lorazepam) and

bourbon whiskey found

Case Presentation

Primary ABCD Survey

• Airway: open; saliva accumulating; gurgling;

smell of alcoholic beverage on breath

• Breathing: respiration = 8/min; sonorous;

decreased gag reflex

• Circulation: BP = 80/50 mm Hg; sinus

tachycardia 130 bpm

What is your initial Management?

Case Presentation

Secondary ABCD Survey

• Airway: clearly needs intubation performed

• Breathing: ETT placement confirmed 2 ways

• Circulation:– 2 large-bore IVs, begin fluid challenge

• Develop differential diagnosis; note major findings:– RR, and BP

– HR

– Not consistent with benzodiazepine OD!

Benzodiazepine

• Treatment for Overdose• Supportive ABC’s

• Benzodiazepine antagonist• Flumazenil

• Blocks BZD binding to GABA receptor

Benzodiazepine

• Flumazenil (Romazicon)• Benzodiazepine antagonist

• Adverse effects• BZD withdrawal (mild severe)

• Removes masking of seizures by BZDs from coingestants (eg, from TCAs)

• Unmasks ventricular arrhythmias

• Contraindications• History of seizures

• Recent myoclonus or seizure episode

• Known addiction to short-acting BZDs

• Heavy/long-term BZD abuse

• Coingestion of epileptogenic drugs (TCAs most common)

Case Presentation

• 42 yo female resident of a van down by the river. Teenage children moved to Fresno to be with father. Boyfriend recently jailed for Narcotic trafficking

• Took complete bottle of anti-depressant

• Found by fisherman unconscious barely breathing

What is your initial Management?

Case Presentation

Primary ABCD Survey

• Not in full cardiac arrest

• Multiple episodes of nonsustained VT occur

• One shock converts episode of sustained VT

Secondary ABCD Survey

• Needs intubation and hyperventilation

• Oxygen, IV, monitor, fluid challenge

• Continuous grand mal seizures begin

What is the cause of her toxicity?

Tricyclic Antidepressant

• Anticholinergic effects

– Hyperthermia, blurred vision, flushed skin, hallucinations, tachycardia, status seizures

• Quinidine-like effects

– Negative inotrope, prolonged QT, ventricular arrhythmias (eg, torsades de pointes)

• -Adrenergic blockade effects

– Hypotension

• CNS effects

– Seizures, coma


• Clinical Features of Toxicity• Mild-Moderate

• Drowsiness, lethargy

• Hypertension, tachycardia

• Severe• Seizures

• Hypotension

• Arrythmias

• Coma

Rapid progression

of toxic symptoms:

characteristic of

TCAs



• Fluid challenge prn

• NaHCO3 1 mEq/kg + 50 mEq to IV bag• Tachycardia, widened QRS, seizures

• MgSO4 2g slow IV (peds 25-50 mg)• Wide QRS

• May need high dose pressors for refractory hypotension


• Treatment Goal

• Systemic alkalinization (achieve and sustain)

– Target pH: 7.45 to 7.55

– Bicarbonate: superior to hyperventilation

– Complications: indicative of severe toxicity

• Marked conduction disorders (QRS >120 ms)

• Marked tachycardia/bradycardia

• Ventricular arrhythmias

• Significant hypotension

• Seizures or coma Typical Dysrhythm

Case Presentation

• 35 you male c/o crushing chest pain, pt. states he has been partying for 3 days

• Pt appears quite agitated, diaphoretic, speaks in 4-5 word sentences

• HR = 140 bpm, BP = 160/120 mm Hg, RR = 30/min, T = 39°C

What is your initial management for this patient?

Case Presentation

• Primary ABCD SurveyABCD: clear

• Secondary ABCD SurveyA: No intubation required

B: Oxygen given

C: IV fluids, monitor, cool him down

D: Develop a differential diagnosis; decontaminate, define toxidrome, drug-specific therapy

What is your differential diagnosis?

Hyperdynamic/Hyperadrenergic Agents• Cocaine (crack)

• Ketamine/phencyclidine (PCP)

• Amphetamine/methamphetamine (ice, crystal meth)

• Ephedrine and derivatives, 2-agonists

• Caffeine, nicotine, theophylline

• Dextromethorphan

• MDMA (Ecstasy)

Hyperdynamic/Hyperadrenergic Agents• Signs and Symptoms

• Tachycardia, ventricular dysrhythms

• Hypertension, intracranial bleed, aortic dissection

• Hyperthermia

• Agitation

• Delerium

• Cerebral, Myocardial infarction

• Angina

• Seizures

Hyperdynamic/Hyperadrenergic Agents• Prehospital Management

• Airway management• 100% O2

• Lidocaine 1 mg/kg• Ventricular dysrhythmias

• Treat V-fib per protocol• Limit EPI to 1 mg q 5 mins

Hyperdynamic/Hyperadrenergic Agents• Treatment

• Reduce the hyperdynamic state • Monitor/reduce temperature

• Physical cooling: spray and fan• Dantrolene 1 to 10 mg/kg

• Prevent or treat seizures• Restrain to prevent harm

• Chemical restraints preferred over physical restraints• Agents: BZDs, haloperidol, or droperidol

Hyperdynamic/Hyperadrenergic Agents

• Treatment Summary

• Hyperthermia: cooling

• Seizures: BZDs, phenobarbital

• Delirium: BZDs, droperidol

• Drug-induced acute coronary syndrome: BZDs, nitrates, phentolamine

• ST elevation with enzyme release: PTCA preferred over IV thrombolytics

• BP: BZD, nipride, phentolamine, labetalol

• Avoid propranolol

• leaves unopposed -adrenergic stimulation; may BP

Documents

Drugs Poisoning - amscfkuntad.files.wordpress.com · 2/23/2018 · •Clonidine •Cardiac Glycosides (Digitalis) •Benzodiazepines •TA’s •Other Substances •Hyperadrenergic