Drugs Poisoning - amscfkuntad.files.wordpress.com · 2/23/2018 · •Clonidine •Cardiac...
Transcript of Drugs Poisoning - amscfkuntad.files.wordpress.com · 2/23/2018 · •Clonidine •Cardiac...
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)
Management of Toxicity
• 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
Management of Toxicity
• 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.
Calcium Channel Blocker
• 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
Calcium Channel Blocker
• Agents• Verapamil
• Significant cardiac depressant • Vasodilation
• AV slowing
• Diltiazem
• Nifedipine
• Felodipine
• Amlodipine
Calcium Channel Blocker
• Toxicity• Hypotension
• Bradycardia
• Arrythmias
• Respiratory depression
• Neurologic disorders• Seizures etc.
Calcium Channel Blocker
• 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
Calcium Channel Blocker
• 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
Calcium Channel Blocker
• 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
• Atropine 1mg prn (max 3mg)• Peds 0.02 mg/kg
- Transcutaneous Pacemaker- Do not delay in symptomatic bradycardia
• 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
Tricyclic Antidepressant
• Clinical Features of Toxicity• Mild-Moderate
• Drowsiness, lethargy
• Hypertension, tachycardia
• Severe• Seizures
• Hypotension
• Arrythmias
• Coma
Rapid progression
of toxic symptoms:
characteristic of
TCAs
Tricyclic Antidepressant
• Prehospital Management• Aggressive airway management
• 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
Tricyclic Antidepressant
• 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