Clinical Toxicology

Clinical cases
By
Dr. Ahmed Salim Mahmood
 CASE No. I
A 30 & 31 year friends present to the hospital with respiratory depression
(slow deep respiration 2-7/min), pinpoint pupils, seizures,
unconsciousness & hypothermia. After taking history by doctor, it found
that they took an injection of certain medication with high doses. What
kind of medications may cause this poisoning? How would you proceed to
manage those patients?
Opioid over dose (Morphine, Pesthidine)
Treatment: Nalaxone Nalmefene, sodium bicarbonate
‫شرج مفصل عن العالج‬
A 48 year old, white female with a blood pressure of 170/95 on 3 clinical visiting,
Doctor put her on antihypertensive medications. Suddenly she developed dizziness
& fatigue, after that, the symptoms becomes more intense with seizure, cerebral
ischemic events, myocardial depression, bradycardia & pulmonary crackles. She
admitted the emergency department after one hour. What kind of toxicity she
developed and what your expectation about the cause of toxicity. How would you
proceed to manage this patient?
Calcium channel blockers
Treatment: antidote :calcium cholride
Supportive testament, Sodium bicarbonate, Dopamine, phenylephrine,
norepinephrine, epinephrine, Glucagon, insulin , atropine, Milirinone ------ect.
‫شرح مختصر عن العالج‬
Case NO. III
• A 45 year old female presents to the hospital with depressed BP and
respiration, nystagmus on lateral look, ataxia, slurred speech and
confusion. What kind of medications may cause this poisoning? How
would you proceed to manage this patient?
• Barbiturate poisoning
• Treatment:
1. Emergency and supportive measures should be done (As with Benzodiazepam)
2. There is no specific antidote.
3. Administer activated charcoal orally if conditions are appropriate.
4. Enhanced elimination by alkalinization of the urine increases the urinary elimination of
phenobarbital but not other barbiturates. Its value in acute overdose is unproven, and
it may potentially contribute to fluid overload and pulmonary edema.
5. Repeat-dose activated charcoal has been shown to decrease the half-life of
phenobarbital and its metabolites.
6. Continuous venovenous hemodiafiltration has been reported to accelerate elimination.
Case NO. IV
• An twenty five year old female presents to the emergency
department via emergency medical staff after she collapsed outside
a bar. Because she was unresponsive and apenic (comatoz). PMH
(past medical history): Unknown.
• Physical Examination: T: 37.39°C HR: 100 bpm RR: 5 breaths per
minute BP: 75/57 mm Hg
• Pupils miotic but equale.
1. What is the suspected cause of poisoning in the above case?
2. How can you treat the above case?
3. Gastric lavage should be done in above case
Case NO. V
A 21-year-old female with a history of generalized anxiety disorder and major depression presented with
increased depressive symptoms over several months while taking fluoxetine 20 mg daily. The doctor
replace Fluoxetine with paroxetine 10 mg daily. The paroxetine continued to be uptitrated over a 3-week
period to a dose 30 mg due to unremitting depressive symptoms. One month later, the patient
presented with tachycardia, generalized body aches, extreme fatigue, weakness, uncontrollable
twitching, tremor, and hyperreflexia.
1. What are the cause of poisoning?
Answer: Drug- Drug interaction
1. What are the mechanism of toxicity?
Answer: blocking the reuptake of serotonin in the nerve terminals
1. Drugs of choice for treatment of above case
Answer:
cyproheptadine, an antihistaminic drug used as an antiserotonergic agent in this
situation—a dose of 4 to 8 mg orally, repeated every 2 hours until a favorable
response is noted, followed by 4 mg orally every 6 hours for 48 hours.
Case NO. VI
• Patient has the following sings: visual, auditory and tactile
hallucinations; disorientation and confusion, memory loss, dilation
of pupils and seizures referred to the toxicity of?
• Answer: Scopalamine
Case NO. VII
• A 25 year young boy admitted to the hospital with mydriasis & hyperthermia, hyperglycemia,
tachycardia, & hypertension, after 90 min. from ingestion of strange bills, he developed
hallucination & loss of control. What kind of agent may cause this poisoning? How would you
proceed to manage this patient?
• Answer:
• LSD (d-lysergic acid diethyl amide
 Treatment :
 Pre-hospital care should focus on preventing harm and transporting patients to
an appropriate facility for further evaluation.
 It is important to note that patients under the influence of hallucinogens may
exhibit a wide range of behaviors with the potential to rapidly fluctuate from a
relaxed, euphoric state to one of extreme agitation and aggression.
 Diazepam is given if necessary to achieve sedation & in case of convulsion
 Chlorpromazine to treat the bad trips
Important subjects
1. Clinical Symptoms of LSD Intoxication
2. the management phencyclidine toxicity
3. chloral hydrate toxicity
4. flumazenil
5. signs of an overdose of zolpidem
6. barbiturates toxicity
7. Supportive therapy in calcium channel blockers
8. Advantages of intravenous lipid emulsion in treatment of clomipramine toxicity
9. Advantages of intravenous lipid emulsion in calcium channel blocker (nefidipine,
verapamil …ect)
10. Role of Diazepam or chlorpromazine or amphetamine in treatment of
amphetamine poisoning?
11. How can recognized between the signs and symptoms of opioid overdose and
signs and symptoms of opioid withdrawal.
 Case No. 1 ‫مكرر لكن األسئلة مختلفة‬
An twenty five year old female presents to the emergency department via emergency
medical staff after she collapsed outside a bar. Because she was unresponsive and apenic,
a by stander administered CPR. No other history available.
PMH (past medical history): Unknown.
Physical Examination:
T: 37.39°C HR: 100 bpm RR: 5 breaths per minute BP: 75/57 mm Hg
General: Obtunded, well moan to painful stimuli.
HEENT: Normocephalic, atraumatic. Pupils miotic but equal.
Pulmonary: Clear.
CV: Regular rate and rhythm.
Abdomen: Normal
 Questions on case study
1. What medication, if any, would you administer?
Nalaxone
2. What other ingestions should you be concerned about?
These patients should also be evaluated for the possibility of co-ingestants,
including acetaminophen and salicylate, since opiates are commonly mixed
with these agents.
3. What is the classic presentation for this type of ingestion?
The classic presentation of an opiate poisoning usually consists of the triad
of CNS depression, respiratory depression and miosis. Hypotension can also
occur. In suspected cases, the diagnosis may be confirmed by administering
naloxone.
 Case No. 2
A 6-year-old white male presents to the emergency department with his
parents after accidently ingesting one nadolol tablet. One hour following
the ingestion, the child became dizzy and vomited. Because the child
appeared to be very sleepy, the parents brought him in for evaluation.
PMH: None.
Physical Examination:
T: 37 °C HR: 100 bpm RR: 22 breaths per minute BP: 100/60 mm Hg
General: Sleepy, but easily aroused.
HEENT: Normocephalic, pupils equal and reactive to light.
Pulmonary: Clear.
CV: Regular rate and rhythm.
 Questions on case
1. What are the most common clinical effects associated with β-blocker overdoses?
• Bradycardia and hypotension; More severe cases can result in AV block, cardiogenic shock and
asystole.
• Because of their membrane stabilizing activity, propranolol, acebutalol and sotalol may be
associated with QRS widening and resultant ventricular dysrhythmias.
• CNS toxicity, including delirium, drowsiness, coma and seizure can occur with lipophilic beta-
blockers, such as propranolol, carvedilol and nebivolol
2. What management should be instituted if the patient’s heart rate is 40 bpm?
ABC, symptomatic treatment of hypoglycemia, Diazepam (treat seizure) and Activated Charoal
,Atropine and Glucagon. High dose insulin-euglycemia and Calcium
3. What is the mechanism by which β-blockers cause toxicity?
• blockade on cardiac myocytes, which leads to decreased intracellular CAMP.
• This results in negative inotropic, chronotropic and dromotropic effects on the
• heart and peripheral vasoconstriction.
 Case No. 3
History: A 47-year-old female presents to your emergency department 30 minutes after a suicide
attempt in which she ingested 2000 mg of sustained release diltiazem. She insists there were no
other ingested medications.
The patient has experienced no vomiting.
PMH: None.
Physical Examination:
T: 37 °C HR: 90 bpm RR: 17 breaths per minute BP: 120/70 mm Hg
General: Alert and oriented.
Pulmonary: Clear.
CV: Regular rate and rhythm without murmur.
Abdomen: Soft and non-tender.
Skin: Pale with a normal capillary refill.
 Questions on case
1. What are the complications which may be associated with this type of overdose?
• Cardiovascular toxicity predominates as a cause of morbidity and mortality after CCB
overdose. AV block, asystole, nausea and vomiting, altered mental status, metabolic
acidosis (likely secondary to hypotension), hyperglycemia (secondary to blockade of
insulin release), seizures and coma.
• 2. What type of gastrointestinal decontamination, if any, is indicated?
Activated charcoal, Gastric lavage, Whole bowel irrigation
3. What management strategies should be used?
ABC, symptomatic treatment of hypoglycemia, Atropine and Glucagon. High dose
insulin-euglycemia, Calcium chloride. Hypotension treated by Normal saline and
adrenaline. Dopamine may be used to treat AV block.
 Case No.4 ‫ترك غير مطلوب‬
A 33-year-old woman presents with a fever and diarrhea. She is very
tearful and admits to having taken 20 tablets enalapril approximately 30
minutes ago. She claims she is not currently suicidal and ingested no
other medications. She took her father’s medication.
PMH: None.
Physical Examination:
T: 38.22°C HR: 100 bpm RR: 18 breaths per minute BP: 80/40 mm Hg
General: Awake and alert.
Pulmonary: Clear.
CV: Regular rate and rhythm without murmur.
Abdomen: Soft and non-tender.
Questions on case
1. What are signs and symptoms of an angiotensin-converting enzyme
inhibitor overdose?
• Overdoses of ACE inhibitors rarely produce severe toxicity. Symptoms
of poisoning can include hypotension, diarrhea, glomerulopathy,
hyperkalemia, cough, rash, angioedema and drug fever.
2. How should the hypotension be managed?
• The hypotension should be managed with supine positioning,
intravenous fluids. Vasopressors are rarely required.
 Case No. 5 ‫ترك غير مطلوب‬

A 29-year-old comatose male arrives to your Emergency Department via EMS, after having two seizures
at home. The paramedics state that enroute to the hospital he had a generalized tonic clonic seizure
that lasted 25 seconds. According to family members, he has no prior history of seizures.
PMH: Suicide attempt (tried to cut wrists) four days ago.
Physical Examination:
T: 38.38 °C HR: 140 bpm RR: 22 breaths per minute BP: 180/99 mm Hg
General: Comatose.
HEENT: Pupils 6 mm bilaterally and sluggishly reactive to light. No gag reflex.
Pulmonary: Clear.
CV: Regular rhythm, sinus tachycardia.
Abdomen: Hypoactive bowel sounds. Soft, non-tender. Palpable bladder.
Questions on case
1- What immediate diagnostic and therapeutic measures should be indicated at the
bedside?
This patient should have his airway, breathing and circulation secured. Intravenous
access, continuous cardiac monitoring and pulse oximetry should be initiated. A
bedside glucose should be obtained (this patient’s initial blood glucose reading was
134 mg/dL). A trial of naloxone was attempted with no response. The clinician
should consider empiric administration of glucose and thiamine.
2. What is your differential diagnosis in this case?
Physical exam implies autonomic nervous system dysfunction: tachycardia,
mydriasis, hyperpyrexia, dry skin and mucous membranes, ileus and urinary
retention. These symptoms fit a picture of cholinergic blockade. The anticholinergic
toxidrome is differentiated from the sympathomimetic toxidrome by the presence
of dry skin and absence of bowel sounds. The most useful place to check for dry
skin is in the patient’s axilla. The anticholinergic syndrome is a clinical diagnosis.
One must also consider the possibility of head trauma.
Questions on case
3. What substance ingestions should be considered?
Antihistamines; Tricyclic antidepressants; Belladonna alkaloids; Antispasmodics;
Antiparkinsonian drugs; Ophthalmic preparations; Antipsychotics; Various plants (Jimson weed);
Numerous OTC medications (sleep aids, cold preparations); Atropine; Scopolamine; Street drugs
(e.g. heroin “cut” with scopolamine)
4. What therapeutic trial may help confirm the diagnosis?
A therapeutic trial of physostigmine may help to confirm the diagnosis and avoid invasive
diagnostic workup; however benefits are generally outweighed by the risks associated with its
use. Physostigmine is an anti-cholinesterase that antagonizes the enzyme cholinesterase, which
breaks down ACh at the receptor site. Physostigmine therefore helps to overcome the
competitive antagonism of ACh caused by the ingested substance. Physostigmine is lipophilic, so
it crosses the BBB to reverse central and peripheral toxic effects. Its use is controversial and
should be reserved for severe toxicity with both central and peripheral symptoms, such as
severe agitation or refractory seizures. Because there are case reports of asystole when used for
reversal of symptoms caused by TCA poisoning, its use is contraindicated in this condition. If
used in non-TCA related anticholinergic toxicity, an ECG should be obtained to ensure that the
patient has no QRS prolongation and the medication should be given slowly while the patient is
on continuous cardiac monitoring to detect arrhythmias.
 Case No. 6
A 27-year-old woman presents to your emergency department after she was found
in her apartment unresponsive following a call from a concerned friend. She was
“barely” breathing and the paramedics placed her on 100% oxygen and assisted her
ventilations. An intravenous line was started and the patient received glucose,
thiamine and naloxone without response.
PMH: Depression.
Medications: Chloral hydrate.
Physical Examination:
T: 37 °C HR: 150 bpm RR: 24 breaths per minute BP: 130/86 mm Hg
General: She is in a deep coma. The smell of pears is present.
Pulmonary: Clear.
CV: Tachycardic without murmur.
Abdomen: Soft and non-tender. Bowel sounds diminished.
Neurologic: Corneal reflexes are present. Deep tendon reflexes are diminished.
 Questions on case
1- What is the most likely etiology of the symptoms?

Chloral hydrate poisoning

2. What types of symptoms are associated with this type of an overdose?

CNS depression, respiratory arrest, coma, aspiration, drowsiness, ataxia, nystagmus and stupor, Hypothermia can also
occur, which, in combination with deep coma can cause the patient to appear dead or to be suffering from brain death.
Depression of cardiac contractility and decreased venous tone can lead to hypotension and ventricular arrythmia

3. What laboratory studies are indicated?

Laboratory studies should focus on the identification of co-ingestants (acetaminophen, salicylate) and excluding other
conditions that may produce coma such as infection, metabolic derangements, neurologic and psychiatric illness. In
general, quantitative measurement is not useful.
Questions on case

4. What treatment is indicated?

• Support of airway, breathing and circulation should be performed in
the usual manner. Activated charcoal can be administered in the right
clinical setting and Hemodialysis. Due to the potential to induce
tachy-dysrhythmias, patients should undergo continuous cardiac
monitoring for 18-24 hours. Propranolol and esmolol can be used to
treat tachycardia.
 Case No. 7
A 16-year-old female presents to the Emergency Department via private vehicle barely responsive to painful
stimuli. An hour ago, she informed her sister that she had “taken all of Mom's diazepam,” which her sister
estimates to have been about 20 tablets (5 mg), and washed them down with “a bottle of vodka.” The reason for
the delay in arrival was that she refused to be transported, so her sister waited until she “passed out” to put her
into the car and drive her to the Emergency Department.

Physical Examination:

T: 37.39 °C HR: 78 bpm RR: 6 breaths per minute BP: 126/86 mm Hg

General: Groans in response to painful stimuli. There are no signs of trauma.

Pupils are mid-position, equal and sluggishly reactive. She has a diminished gag reflex.

Pulmonary: Clear .

CV: Regular rate and rhythm.

 Questions on case
1. What is most likely responsible for this patient’s respiratory depression?

The patient’s respiratory depression is most likely the result of the ethanol co-

ingestant. Oral benzodiazepine poisoning alone rarely causes respiratory

compromise, and these patients instead often present with CNS depression and

normal vital signs. Most intentional overdoses involve a co-ingestant, with

ethanol being the most common.

 Questions on case
2. Would you administer flumazenil to this patient?

The use of flumazenil in acute overdose is controversial. We should insure that the patient dose not use diazepam chronically (addict).

Flumazenil administration is not contraindicated in the presence of alcohol. So, in this case we can use flumazenil because it consider
from history (acute overdose diazepam toxicity)

Contraindications to flumazenil administration include:

a. History of chronic benzodiazepines use

b. History of seizure disorder

c. Concomitant ingestion of tricyclic antidepressants or other agents known

to have proconvulsant properties.

The most common use of flumazenil is for the reversal of iatrogenic conscious sedation.

3. What is the dose of flumazenil?

It is administered IV with a starting dose of 0.1–0.2 mg, repeated as needed up to amaximum of 3 mg.