Transcript Toxicology Common poisonings and Drugs of Abuse

Toxicology
Common poisonings and Drugs of Abuse
Jeffrey W. Fuss
B.Sc.,M.D.,F.R.C.P.c
Toxicology
Common poisonings and Drugs of Abuse
Case 1
Mother calls you . My one year old 10kg
child at bottle of childrens tylenol pills.
(12 pills)
What do you tell her?
Toxicology
Common poisonings and Drugs of Abuse
Acetaminophen
One of the most common analgesicantipyretic medications
More hospitalizations occur after
acetaminophen overdose than after
overdose of any other pharmaceutical
agent
Toxic dose 140mg/kg
Toxicology
Common poisonings and Drugs of Abuse
Acetaminophen
primarily metabolized in the liver through
three routes:
(1) conjugation with glucuronide (40-67%)
(2) conjugation with sulfate (20-46%)
(3) oxidation via the cytochrome P450
(CYP450) mixed-function oxidase system
Toxicology
Common poisonings and Drugs of Abuse
Acetaminophen
Toxicology
Common poisonings and Drugs of Abuse
Acetaminophen
CLINICAL FEATURES : four stages
Stage 1 (preinjury period)
first 24 hours after ingestion. Nonspecific symptoms, including nausea,
vomiting, anorexia, diaphoresis, and malaise, are common in the first 8 hours
after ingestion, usually resolving thereafter. Patients may be asymptomatic
during this stage.
Stage 2 (liver injury)
24 hours after ingestion but possibly 12 to 36 hours after overdose
Signs and symptoms of hepatic injury include nausea, vomiting, and right
upper quadrant and epigastric pain or tenderness.
Stage 3 (maximum liver injury)
3 to 4 days after ingestion,
Fulminant hepatic failure can develop during this stage, with encephalopathy,
coma, and clinical evidence of coagulopathy
hypoglycemia and metabolic acidosis.
Death with hepatic failure can occur from hemorrhage, adult respiratory
distress syndrome, sepsis, multiorgan failure, or cerebral edema.
Stage 4 (recovery period)
Hepatic enzymes return to baseline by 5 to 7
resolution of hepatic insult can take months.
Toxicology
Common poisonings and Drugs of Abuse
Acetaminophen
Risk of hepatotoxicity is best
established by
plotting
acetaminophen
concentration on
the acetaminophen
Modified from Rumack BH, Matthew H:
Acetaminophen poisoning and toxicity.
Pediatrics 55:871, 1975.)
Toxicology
Common poisonings and Drugs of Abuse
Acetaminophen
MANAGEMENT
The goals in managing acetaminophen
overdose are to:
(1) limit gastrointestinal absorption when
appropriate using activated charcoal
(2) initiate NAC in a timely manner, within
8 hours of ingestion;
(3) control symptoms; and
(4) provide supportive and follow-up care
Toxicology
Common poisonings and Drugs of Abuse
Acetaminophen
N-Acetylcysteine
The initial bolus 140 to 150 mg/kg IV
over 1 hour
Then 15 mg/kg/hr for 4 hours followed
by 7.5 mg/kg/hr for 16 hours.
For patients treated more than 8 hours
after exposure, chronic ingestion, or
hepatic failure the continuous infusion is
15 mg/kg/hr for 44 hours
Toxicology
Common poisonings and Drugs of Abuse
20y.o. female
Unknown OD
T 39.5, RR 40, confusion
Increased anion gap on bloodwork
Toxicology
Common poisonings and Drugs of Abuse
ASA
Rapidly absorbed intact from the
gastrointestinal
Two thirds of a therapeutic dose is
absorbed in 1 hour
salicylate is eliminated by renal
excretion
Toxicology
Common poisonings and Drugs of Abuse
ASA
Pathophysiology
Salicylate stimulates the medullary
respiratory center
GI Irritant
Salicylates inhibit the Krebs cycle
Toxicology
Common poisonings and Drugs of Abuse
ASA
Predict clinical features
Initial manifestations include:
Tinnitus
Hyperventilation
Vomiting
Dehydration
Hyperthermia
Shortness of breath 20 pulmonary edema
Confusion 20 cerebral edema
Hepatic failure
Treat dehydration; maintain urine output at 2-3
mL/kg/hr with normal saline.
Correct potassium depletion
Alkalinize urine.
Obtain baseline arterial blood gas values.
Administer 1-2 mEq/kg sodium bicarbonate
initially, then as needed (50 mL bicarbonate
increases serum pH by 0.1).
Infuse intravenous fluids: D5 with 100 mEq
bicarbonate/L.
Monitor serum pH; do not cause systemic
alkalosis.
Do not attempt forced diuresis.
Toxicology
Common poisonings and Drugs of Abuse
ASA
Toxicology
Common poisonings and Drugs of Abuse
ASA
4. Monitor for dialysis indications:
Coma, seizure
Renal hepatic, or pulmonary failure
Pulmonary edema
Severe acid-base imbalance
Deterioration in condition
Toxicology
Common poisonings and Drugs of Abuse
ASA
How do you know who is sick??
careful observation of the patient,
correlation of the serum salicylate
concentrations with blood pH values
repeat determinations of serum salicylate
concentrations every 2-4 hours
until the patient is clinically improving and has
a low salicylate concentration in the presence
of a normal or high blood pH
Toxicology
Common poisonings and Drugs of Abuse
34-year-old male smoker called 911 because
of chest discomfort that had begun about 4
hours earlier
developed midsternal chest pressure that
radiated to the back
worse with exertion
associated with nausea and three episodes of
vomiting.
When emergency medical services (EMS)
technicians arrived they gave him:
oxygen, 162 mg of aspirin
sublingual nitroglycerin spray
Toxicology
Common poisonings and Drugs of Abuse
blood pressure, 145/95 mm Hg
pulse, 114 beats/min
respirations, 20 breaths/min
temperature 37°C
oxygen saturation while breathing room
air was 97% by pulse oxymetry
glucose test was normal
physical examination was remarkable
Toxicology
Common poisonings and Drugs of Abuse
2 hours later the troponin I was reported as
positive
patient was given 325 mg of aspirin
intravenous loading dose of heparin, followed
by a continuous heparin infusion.
2 doses of metoprolol (2.5 mg each) were
administered IV 10 minutes apart, for
persistent tachycardia.
Within 10 minutes of the second dose the
patient complained of severe crushing
substernal chest pain, and became diaphoretic
and nauseated.
Toxicology
Common poisonings and Drugs of Abuse
Cocaine
2000 BC, the leaves of the cocoa plant (Erythroxylon coca) were
chewed for treatment of various ailments
ophthalmologist Karl Koller introduced cocaine as an effective
local anesthetic for eye surgery Sigmund Freud, wrote extensively
on the psychoactive properties of cocaine
Following these revelations, Merck, Europe's main cocaine
producer increased production from less than 0.75 pounds in
1883 to more than 150,000 pounds in 1886.
1914 cocaine in U.S. consumer products was banned
1993 and 1995, 2000 unintentional cocaine-related deaths were
reported in New York City.
Cocaine also is implicated in violent deaths
detected in 25% of autopsies of fatal injuries in adults age 15 to
44
Toxicology
Common poisonings and Drugs of Abuse
Cocaine
Unpurified cocaine paste.
crack cocaine: crystallized freebase of cocaine
alkaloid
inhaled using a special ‘crack pipe’
The high lipid solubility and rapid transport from the
lungs into the brain
water-soluble salts of cocaine (cocaine
hydrochloride and cocaine sulfate)
white crystalline powder that is taken intranasally
or dissolved and injected intravenously.
Gastrointestinal administration is uncommon
except for patients who are smuggling or
concealing drug
Toxicology
Common poisonings and Drugs of Abuse
Cocaine
Acute cocaine
use causes
release of
dopamine,
epinephrine,
norepinephrine,
and serotonin
Toxicology
Common poisonings and Drugs of Abuse
Cocaine
Local anesthetic agent
slows nerve impulses from pain fibers by
blocking the inward movement of sodium
across cell membranes
Antiarrythmic:
Sodium channel blockade across
myocardial cells, similar to the class Ia
antidysrhythmic agents
Toxicology
Common poisonings and Drugs of Abuse
Cocaine
Clinical effects:
Hypertension
Tachycardia
Mydriasis Diaphoresis
Hyperthermia
CNS excitation
MI
Cardiac arrythmias
Hypertensive emergencies
Toxicology
Common poisonings and Drugs of Abuse
Cocaine
Other Complications
prolonged use causes catecholamine depletion,
dehydration, and poor nutrition
crack dancing :
choreoathetoid movement disorder after using cocaine.
Paranoia, and psychological addiction
Inhalation of crack can cause oropharyngeal burns
from the high temperature
Pneumothorax, pneumopericardium, and
pneumomediastinum may occur from inhalational
barotrauma.
Intranasal cocaine use is associated with nasal
perforation and sinusitis.
Complications of IV Use
Toxicology
Common poisonings and Drugs of Abuse
Cocaine
Treatment
Dysrhythmias
Not lidocaine
Cocaine-Related Chest Pain
Cardiac and non cardiac causes
Hypertensive Emergencies
phentolamine
Hyperthermia
Cocaine Body Packers and stuffers
Toxicology
Common poisonings and Drugs of Abuse
OTHER STIMULANTS: Amphetamines
MDMA (Ecstasy, XTC, Adam) is a chemically
modified amphetamine that is an orally
administered drug originally used in all-night
dance parties, or ‘raves
Methamphetamine, known as ‘ Ice’, ‘crank’
and ‘crystal meth,’ is a fat-soluble, smokable,
designer amphetamine
Ephedra, a plant-derived product, also known
as a Chinese herbal product, ma-huang,
Khat is a stimulant agent naturally occurring in
the leaves of the plant Catha edulis
Toxicology
Common poisonings and Drugs of Abuse
OTHER STIMULANTS:
Amphetamines
less likely to cause seizures,
dysrhythmias, and myocardial ischemia
anxious, volatile, aggressive, and may
have life-threatening agitation.
Visual and tactile hallucinations, as well
as psychoses, are common
Toxicology
Common poisonings and Drugs of Abuse
comatose 23-year-old man.
EMS found that the patient was
hypoventilating (2 breaths/min)
cyanotic
miotic pupils
Toxicology
Common poisonings and Drugs of Abuse:
Opioids
dried extract of the poppy plant Papaver somniferum, was first
recorded around 1500
used by the Egyptians medically
narcotic refers to a sleep-inducing agent and initially was used to
connote the opioids
opium smoking was so problematic in China by the 1830s that
the Chinese government attempted to prohibit the importation of
opium by the British East India Company
in 2001, 404,000 Americans age 12 and older had used heroin;
3.7 million have used heroin at least once
euphoric and addictive potential of the opioids is immortalized in
the works of several famous writers, such as
Thomas de Quincey (Confessions of an English Opium Eater, 1821),
Samuel Coleridge (The Rime of the Ancient Mariner, 1798), and
Elizabeth Barrett Browning (Aurora Leigh, 1856).
Toxicology
Common poisonings and Drugs of Abuse:
Opioids
How do they do it?
Shoot it up
Grind up pills
Scrape of patches
Heroin, morphine
Orally
“Hillbilly heroin” oxycontin, percocet are a large
source of illicit drug use particularly in London
Sub cut
Inhalational
“chasing the dragon." inhale a thick, heroin white
paste that is heated on aluminum foil using a handheld flame
Toxicology
Common poisonings and Drugs of Abuse:
Opioids
Toxic Effects
CNS depression
pulmonary edema
Movement Disorders
Chest wall rigidity may have contributed to the
lethality associated with epidemics of fentanyladulterated heroin
Gastrointestinal Effects
Seizures
Miosis
Toxicology
Common poisonings and Drugs of Abuse:
Management
Supportive
Narcan
Opioids
Toxicology
Common poisonings and Drugs of Abuse
Complications of IV drug use
Local
Abscesses
Intraarterial injection
Other skin infections
Local irritation
Missing Vein and damaging other
structures
Toxicology
Common poisonings and Drugs of Abuse
Complications of IV drug use
Infectious
Septic arthtitis
Endocarditis
Epidural Abscess
Complications of shared needles
HIV
MRSA
Hepatitis’
Toxicology
Common poisonings and Drugs of Abuse
Others
Marijuana
Jimson Weed
PCP (Angel dust)
Toxicology
Common poisonings and Drugs of Abuse
Others
Hallucinogens
LSD (“Acid”)
Magic Mushrooms
Toxicology
Common poisonings and Drugs of Abuse
SUMMARY
Specific drug and classes
Acetaminophen
ASA
Cocaine
Amphetamines
Opiates
Remember the pathophysiology
From that predict clinical effects and
treatments
Goldfrank's Toxicologic Emergencies - 8th Ed. (2006), Rosen's Emergency Medicine: Concepts and Clinical Practice