TOXICOLOGY

(Management of the Poisoned Patient)

General Objective:
At the end of the lecture, the students will be able to know about toxicology and
drugs of abuse

Specific Objectives:

I. Approach to patient in clinical

setting of drugs of abuse

A. Your Patient A. Case – your patient

1. A 23 year old Medical Student
2. found by his apartment mate]
3. unconscious at around 7 pm
- no pill bottles on scene
- no family with him
- but apartment mate said, he has taken
some pills

B. You are the ER Physician B. ER Physician

1. You are never going to know exactly what
he took
2. What do I do with him?
- What do I order?
- How do I treat him?
- How do I decontaminate him?
- Di I give him an antidote?
3. Statistics
- Annual statistics in US- 1 Million
cases of acute poisoning with few
fatal cases
a) Adults and adolescence- most
death due to intentional suicidal
overdose
b) Childhood death – accidental
ingestion of a drug or toxic
household product
- In Philippines – UP Poison Center
- year 2000, about 326 reported
Cases of pesticide poisoning
C. Acute Poisoning
1. What to do?
2. Toxico Kinetics
(Absorption, distribution,
excretion and
metabolism of toxins,
toxic doses of
therapeutic agents and
their metabolites)
3. Toxicodynamics
( the injurious effects of
drugs/substances on
vital function)
C. What to do?
a) Few Fatal – most deaths due to
intentional suicidal overdose by an
adolescent or adult
b) Preventive measures to decrease
childhood deaths a. Safety packaging
b.Effective poison prevention education
c) Prompt Medical Attention
d) Good Supportive Care
a) May be absorbed by GIT, lungs and/or
skin.
b) May accumulate to a critical
concentration in the body when the rate
of absorption exceeds the rate of
elimination.
c) Many chemicals are not toxic but have to
be activated by biotransformation into
toxic metabolites.
d) A toxicant may produce toxicity thru:
1. Pharmacologic effect – CNS
depression by barbiturates
2. Pathologic effect – kidney injury
produced by mercury
3. Genotoxic effect – cancer produced
by mustard gas
e) Special aspects of Toxicokinetics
1. volume of distribution
2. clearance
3. Toxicodynamics - What the toxic
substance does to the vital functions of the
body
4. Special Aspects of 4. Special aspects of TK:
Toxico Kinetics
a. Volume of distribution (VD)
- approval volume into which a
substance is distributed.

1. Large Vd
- drug not readily accessible
measures aimed at purifying
the blood such as
hemodialysis.
- extra vascular distribution
o 5 L/kg
- eg. antidepressants,
antipsychotics antimalarials,
narcotics, propanolol,
verapamil.
2. Small Vd
- < 1 L/kg
- -vascular distribution
- salicylate, phenobarbital,
lithium, valporic acid, warfarin,
phenytoin
b. Clearance
- a measure of the volume of
plasma that is cleared of drug
per unit time
- total clearance = kidney + liver
- normal dosage
 Most drugs eliminated at
rate proportionate to
plasma concentration
(first-order kinetics)
- high plasma conc with
saturated normal
- metabolism
- fixed rate of elimination (zero
order-kinetics) prolong serum
half life and inc. toxicity

5. Your Patient 5. – How does the poisoined patient die?

 a 23 yr.old medical
student a. Depress CNS – obtunded, comatose
 found by his b. CVS toxicity
apartment mate a) hypotension, hypovolemia
 results to hyperthermia
b) peripheral vascular collapse
c) cardiac arrhythmias
 unconscious at 7pm : c. Cellular hypoxia
no pill bottles at d. Seizures, muscular hyperactivity,
scene rigidity
 no family with him e. delayed onset
but apartment mate f. behavioral effects causing traumatic
said, he has taken injury
some pills

6. You are the ER A. Start with Basics

Physician a. ABC – Airway, breathing, circulation
a. You are never going b. Get a better history.
to know what he c. Establish a pattern to his symptoms
took… Toxic Syndrome-Toxidrome
b. What do I do with
him? B. Initial Management
What do I order? a. Prompt supportive care-ABCD
How do I treat him? 1. Airway-cleared
How do I 2. Breathing-Asses, observe,
decontaminate him? oximetry, ABG
Do I give him an 3. Circulaton – pulse rate, blood
antidote? pressure, urine output, peripheral
perfusion.
4. Dextrose Challenge
- Altered mental status
- Check bedside blood
glucose
- D50W
- Kids – 0.5 g/Kg
b. Alcoholic or malnourished patient
1. Thiamine 100mg 1M or IV to
prevent Wernicke’s syndrome.
c. Naloxone 0.4 to 2mg IV – reverse
respiratory and CNS depression due
to opioid drugs.
d. History and Physical examination
1. Ask accompanying
2. Circumstances
3. Events
4. Empty bottles
e. Vital signs
 1. Hypertension and tachycardia
a) Amphetamine
b) Cocaine
c) Antimuscarinic drugs
2. Hypotension and Bradycardia
a) Calcium channel blockers
b) Beta blockers
c) Clonidine
d) Sedative
3. Hypotension with tachycardia
a) Tricyclic anti-depressant
b) Vasodilators
c) Theophylline
d) Phenothiazines
4. Tachypnea
a) Salicylates
b) CO
c) Substances producing
metabolic acidosis or cellular
asphyxia
5. Hyperthermia
a) Sympathomimetics
b) Anticholinergics
c) Salicylates
d) Drugs producing seizures or
muscular rigidity
6. Hypothermia CNS Depressants

f. EYES
1. Miosis
a) Opioids
b) Clonidine
c) Phenothiazine
d) Cholinisterase inhibitors
e) Sedatives
2. Mydriasis
a) Amphetamines
b) Cocaines LSD
c) Atropine
d) Anicholinergic drugs
3. Horizontal Nystagmus
a) Phenytoin
b) Alcohol
c) Barbiturates
d) Other sedative drugs
g. MOUTH
 1. Signs of burns
2. Typical odor- Cyanide-bitter
almonds
h. SKIN
1. Flushes, hot, dry
a) Atropine
b) Other antimuscarinic
2. Excessive sweating
a) Organophosphate
b) Nicotine
c) Sympathomimetic drugs
i. ABDOMEN
1. Ileus
a) Antimuscarinic drugs
b) Sedative drugs
2. Hyperactive bowel sounds
a) Organophosphate
b) Iron
c) Arsenic
d) Theophyline
j. NERVOUS SYSTEM
1. Focal seizures and Motor Deficits
often structural lesion
2. Seizures
a) Antidepressants
b) Cocaine
c) Amphetamine, Theophylline
d) INH
e) Diphenhydramine

7. Laboratory and 7. Laboratory and Imaging Procedures

Imaging Pocedure 1. Atrerial blood gaser
2. Electrolytes
- Elevated anion gap
a. Organic acid metabolites-
methanol, ethylene glycol
b. Lactic acidosis – cyanide, CO,
Ibuprofen, INH, Metaformin,
Salicylates, Valproic acid, any
drug-induced seizure, hyperxia,
hypotension
3. Renal function test
4. Serum osmolality
5. ECG
6. X-ray

8. Analysis of our Case
Patient
9. Decontamination I.
process
- Should be taken
simultaneously with
initial stabilization
- Remove from skin or II.
GIT
7. Toxicology screening test
- Tentative diagnosis history, PE,
routine lot
- Time consuming, expensive, often
unreliable.
A. So back to our patient:
a. Agitated, pupils 8mm., sweaty, HR
140’s, BP 230/130 - Sympathomimetic
b. Unarousable, RR 4, pupils pinpoint
opiate.
c. Confused, pupils 8mm., flushed dry
skin, no bowel sounds, 1000 cc
Output w/ Foley Anticholinergic
d. Vomiting, urinating uncontrollably, HR
40, p Oxygen 80% from bronchorrhea,
pupils 2mm.
e. Lethargie, HR 67, BP 105/70, RR 12,
pupils midpoint
- Sedative hypnotic
B. Basic approach:
a. Airway, breathing, circulation
b. Establish IV, Oxygen and Cardiac
Monitor
c. Consider coma cocktail
Thiazamine, D50, Narcan
d. Evaluate history and through physical
exam
1. Look at vital signs, pupils, neuro,
skin, bowel sounds.
2. Gives you hints regarding the
general class of toxins.
3. Guides your supportive care
e. Draw blood/urine for testing
f. Time to consider decontamiation
options.
How do I get the poison out of the body?
a. Induce vomiting – Ipecac
b. Take out pills from the stomach – Lavage
c. Adsorb the toxins in the gut – charcoal
d. Flush out the system- whole bowel
Gastrointestinal tract
a. Emesis
 a. Remove clothing Ipecac syrup
completely Not for suspected corrosive,
b. Wash skin with petroleum distillate, or rapidly
soap and water convulsant
- Emetine and cephaeline:
Ipecac inducesenesis
rarely if ever still recommended
for home use.
b. Gastric Lavage
 Can be a brutal procedure
 Indication: life threatening ingestions
that occurred within 1 hour
 Airway protection is key
 Limited indications
 Lots of complications
c. Charcoal
 Work to adsorb substances to its
matrix: not for metals, caustics.
 Generally safe, few contraindications
aspiration, bowel obstructions.
 Dosing: 1g/kg po dose - ±single dose
of cathartic.
d. Whole bowel
 Isotonic polyethylene glycol,
electrolyte solutions (Golytely)- NSS
 Large volumes ingested “wash” the
substances through the bowel:
essentially useful for metals or other
things not well adsorb by charcoal.
 Avoid in patients with bond
obstruction or ileus.
 Dose in volume sufficient to create
clear rectal effluent.
 Dosing: 1-2 liters/hour
Have to use an NGT(Nasogastric
tube)

10. Methods of enhancing A. Dialysis Procedure

elimination of Toxins
a. Peritonea Dialysis
b. Hemodialysis
1. More efficient than peritoneal
2. Assist in correction of fluid and
electrolyte imbalance
3. Removal of toxic metabolites
 c. Hemoperfusion
B. Forced Diuresis and Urinary ph Manipulation

11. Common Toxic A. Acetaminophen

Syndromes - Most common in suicide attempts and
 No every drug fits accidental poisoning
into a broad based - Acute ingestion- toxic if:
category. > 150-200 mg/kg (children)
 Lots of meds have 7 grams (adults)
unique effects not - Stages of acetaminophen toxicity
easily grouped. 1. Initially asymptomatic or mild GI
 5 Basic Toxidrones symptoms
1. Sympathomimetic 2. After 24 to 24 hours
2. Opiate  evidence of liver injury
3. Anticholinergic  increase SGPT, hypoprothrombinemia
4. Cholinergic 3. Severe
5. Sedative Hypnotic  Liver failure/Renal failure
 Hepatroencephalopathy
 Death
- Measure serum acetaminophen severity:
 150-200 mg/kg at 7 hours after
ingestion
 Increase risk for liver injury
 Chronic alcoholic patients taking P450
enhancers 100mg/L at 4 hours
B. Amphetamines and other stimulants
1. Methamphetamine (crank or crystal)
2. Methylenedioxymethamphetamine
(MDMA, Ecstacy)
3. Cocaine (crack)
4. Pseudoephedrine
5. Ephedrine
 “Metabolic enhancer” or “fat
burner”
 Caffeine + Pseudoephedrine/
ephedrine
B.1 Signs and Symptoms of Stimulant
Abuses
1. Euphoria/wakefulness
2. Sense of power and well-being

B.2 Signs and Symptoms for Higher doses

1. Restlessness, agitation
2. Acute psychosis
3. Hypertension + tachycardia
 4. Seizures
5. Hyperthermia

B.3 Treatment
- Supportive, no specific antidote
C. Anticholinergic agents

1. MOA: inhibit effects of a cetylcholine

2. Classic anti cholinergic syndrome
1- red as a beet (skin fluched)
2- hot as hare (hyperthermia)
3- dry as a bone (no sweating, dry
mucous membranes)
4- blind as a bat (blurred vision)
5- mad as a hater (confusion, delirium)
3. Sinus tachycardia
4. dilated pupils
Treatment:
1. supportive
2. Physostigmine
Antidote for central and peripheral
anticholinergic syndrome

D. Antidepressants
1. Tricylic
2. MAO inhibitors
3. Newer antideprassants

D.1 Tricylic Antidepressants:

 e.g. amitryptyline lethal :  1 gram or
15-20 mg/kg.
 MOA: competitive antagonist at
muscarinic cholinergic receptors
 Signs and symptoms : tachycardia,
dilated pupils, dry mouth
 Quinidine - like depressants effects :
Wide QRS
Treatment : supportive antidote for quinidine
like cardiac toxicity sodium bicarbonate 50-
100 meq. or 1-2 meq./ LIV bolus
Do not use Physostigmine

D.2 MAO inhibitors

- Phenelzine
- Severe hypertensive reaction
 D.3 Antipsychotics
1. CNS depression
2. Seizures
3. Hypotension

E. Asperin (Salicylate)
 Acute intoxication 200 mg/kg
 MOA . Poisoning causes uncoupling of
oxidative phorphorylation and disruption
of normal cellular metabolism.
- Hyperventilation and respiratory
albalosis
- First sign of toxicity
- Followed by metabolic acidosis
Treatment
- Supportive
- GUT decontamination

F. Beta Blockers
 High Dose – loss of selectivity
 Propanolol – most toxic beta blocker
 Treatment: Supportive care, glucagon

G. Calcium channel blockers

 Small dose – toxicity and death
 Treatment
- Supportive
- Whole bowel irrigation
- Activated charcoal
H. Carbon monoxide (CO) and other gases
I. Cholinesterase inhibitors
(Organophosphates)
Carbamate Cholinisterase inhibitors
Organophosphates
+ Muscarinic receptors
- Abdominal cramps
- Diarrhea
- Excessive salivation
- Sweating
- Urinary frequency
- Increase bronchial secretions
+ Nicotinic receptor – generalized gangliric
activation
 DUMBELS
D - Diarrhea
U – Urination
M – Miosis, Muscle weakness
B - Bronchospasm
E - Excitation
L - Lacrination
S - Seizure, sweating, salivation

J. Digoxin – acute overdose of digoxin

accumulation
1. Vomiting
2. Arrhythmias
3. General supportive care
4. May use Atropine for bradycardia and AV
blocks
5. Lidocaine
6. No calcium – lethal arrhythmias
7. Rx: Digoxin antibody
K. Ethanol and Sedative Hypnotic Drugs
1. Euphoric and rowdy
2. Or stuporous or comatose
3. General supportive care
L. Ethylene glycol and Methanol
1. Important toxins because of their
metabolism to higher toxic organic acids
- Formic acid, glycolic, oxalic
- Metabolic acidosis
- Coma, blindness
- Renal failure
2. CNS depression
3. Drunken state –like ethanol overdose
4. Antidote: Ethanol (5%)
Fomepizole – block alcohol
dehydrogenase
M. Iron and Other Metals
N. Opioids – respiratory depression, hypotension
Tx: Naloxone
O. Rattlesnake Envenomation
 Rare fatal
 20% do not involve envenomation
 60% with morbidity due to destructive
digestive enzymes in venom

So back to your patient
1. How do I treat him?
Good supportive care
Good physical exam
2. How do I decontaminate
him?
Charcoal as long as he is
not an aspiration risk
3. What do I order?
Chemical ASA, APAR, EKG
at minimum
4. Do I give him an antidote?
Comacocktail, others as
indicated by labs
5. When can he go to
psychiatrist?
Hemodialysis for serum
cone 100 mg/kg and
instractable service
Observe for 6 hours and re-
evaluate
Signs and Symptoms: pain, swelling, bruising,
hemorrhagic bleb formed nausea, vomiting,
muscle fasciculation, tingling and metallic taste,
shock, systematic congulopathy with prolong
clothing time and decreased platelet count
Treatment: Venous antivenin
P. Theophylline
 Serious/fatal poisoning – 20-30 tablets
 Chronic and subacute theophylline
posoning
 Accidental over medication using
theophylline with another drug that may
interfere with its metabolism
(Ciprofloxacin, Erthromycin)
Signs and symptoms:
Sinus tachycardia, seizure, hypertension,
vomiting, tremor
Treatment:
General supportive care but decontamination –
repeated activated charcoal whole bowel
irrigation
Antidote: propanolol or other beta blockers
Phenobarbital