Class

Question 1

Enumerate the contra-indications of emesis 7

Answer 1

-Corrosives: for fear of perforation of esophagus or stomach.

-Coma: for fear of suffocation or aspiration pneumonia.

-Convulsions: as vomiting and patient manipulation may stimulate convulsions.

-Kerosene (volatile hydrocarbons) for fear chemical pneumonitis. Chronic poisoning.

-Cardiac and elderly patients and vascular insufficiency.

-Infants below the age of 6 months (immature gag and airway protec­tive reflexes).

Question 2

Enumerate contraindications of gastric lavage

Answer 2

Are the same as for emesis with exception of:

-Coma & volatile hydrocarbons —> Lavage is allowable after inserting a cuffed endotracheal tube to prevent aspiration pneumonia.

-Convulsions—► Lavage can be performed under general anesthesia.

-Cardiac dysrhythmias must be controlled before gastric lavage is initi­ated, as insertion of the tube may create vagal response —► cardiac at­ rest.

Question 3

Enumerate the poisons in which activated charcoal is ineffective (poorly absorbed)

Answer 3

C- Cyanide and Corrosives.

H-Heavy metals (Lead, Arsenic and Mercury).

A-Alcohols.

R-Rapid onset or absorption poisons (Cyanide and Strychnine).

C-Chlorine and iodine.

O-Others insoluble in water (substances in tablet form).

A–Aliphatic and poorly adsorbed hydrocarbons (petroleum distillates).

L—Lithium

Question 4

Multiple dose activated charcoal (MDAC) is indicated in poisons that:

Answer 4

• Show enterohepatic circulation (TCA, Digitalis and Barbiturates)
• Stick to the stomach (Salicylate).
• Slow gut motility (Barbiturates & Morphine)

Question 5

Enumerate the contraindications of whole bowel irrigation 6

Answer 5

a. Unprotected airway or compromised airway.

b. Bowel obstruction or perforation.

c. Clinically significant GIT bleeding.

d. Intractable vomiting.

e. Unstable vital signs.

f. Signs of leakage of illicit drug packets (e.g. tachycardia, hyperten­sion, hyperthermia in a patient who has ingested cocaine packets); surgical consult should be obtained in this circumstance.

Question 6

Discuss Ion trapping

Answer 6

Alteration of the urine pH (Ion Trapping):
Changing PH of urine —> the poison to be ionized ->poison can’t be reab­sorbed through the cells of the renal tubule, as ionized drugs are poorly absorbable through cell membranes —> increase excretion.

Alkalization of urine as in salicylates and Acidification (not used due to SE).

Indicated in severely intoxicated patients, toxic serum drug level and progressive clinical deterioration

Question 7

Enumerate the types of Antidotes 6

Answer 7

I. Physio-mechanical Antidotes e.g. Activated charcoal

II. Chemical Antidotes

III. Physiological or pharmacological antidotes; These produce effects opposite to that of poison e.g.: Glucagon in calcium channel blockers

IV. Competitive antagonist: at receptor site: naloxone in morphine poi­soning

V. Dispositional antidotes: interfere with absorption, distribution ,metab­olism or excretion of the poison .

VI. Chelating agents: These substances combine with metals forming nontoxic compounds that are easily excreted in urine e.g. Deferrioxamine: used for chelation of iron.

Question 8

Enumerate the anti-cholinergic toxidromes

Answer 8

Atropine, hyoscine

Antihistamine (diphenhydramine)

TCAs (Imipramine, amitripyline)

Phenothiazines: Chlorpromazine

Question 9

Give the MOA of Atropine (also hyoscine)

Answer 9

Peripheral: antagonize the muscarinic action of acetylcholine.

Central: stimulation followed by depression of central nervous system.

But, Hyoscine: Peripheral action is weaker & Central action is depression of central nervous system without initial stimulation.

Question 10

Give the MOA of Antihistamines (diphenhydramine)

Answer 10

• Antagonize effects of histamine on H1 receptor.
• Anticholinergic action
• Large diphenhydramine overdose: Prolongation of QRS (sodium channel blockade).

Question 11

Give the MOA of Imipramine (TCAs)

Answer 11

1. Neurotransmitter reuptake inhibition: Norepinephrine, Dopamine and Serotonin.
2. Receptor blockade: Cholinergic, Alpha adrenergic and Histaminic receptors.
3. Cardiovascular effects:
   * Myocardial effects: Direct Quinidine like effect —>conduction defects and arrhythmias.
   * Hypotension due to: direct myocardial depression, peripheral vasodilatation (alpha blocking) and increased capillary permeability.

Question 12

Give the MOA of Amitriptyline (TCAs)

Answer 12

1. Neurotransmitter reuptake inhibition: Norepinephrine, Dopamine and Serotonin.
2. Receptor blockade: Cholinergic, Alpha adrenergic and Histaminic receptors.
3. Cardiovascular effects:
   * Myocardial effects: Direct Quinidine like effect —>conduction defects and arrhythmias.
   * Hypotension due to: direct myocardial depression, peripheral vasodilatation (alpha blocking) and increased capillary permeability.

Question 13

Give the MOA of Chlorpromazine (Phenothiazine)

Answer 13

1. Receptor blockade: Cholinergic, Alpha adrenergic, Histamine and Dopamine receptors.

-Blockade of Dopamine receptors causes Extrapyramidal Manifestations & increased Prolactin (amenorrhea galactorrhea syndrome).

2. CVS effects: the same as TCA
3. CNS effects: Depression of:
   - Cerebral cortex —> Coma and Seizures may occur.
   - Respiratory center -> Respiratory failure.
   - Chemoreceptor trigger zone (CTZ) -»Antiemetic action.
   - Heat regulatory center (HRC) -> Hyperthermia or Hypothermia

Question 14

Discuss the antidotes of anti-cholinergic toxidromes

Answer 14

Physostigmine in case of atropine & antihistamines:

• It reverses the peripheral & central anticholinergic effects.
• It is indicated in severe cases.
• It should be given under cardiac monitoring & should not be given as a constant infusion for a long time.
• It is contraindicated with wide QRS complex, bradycardia, and bowel or bladder obstruction.

Sodium bicarbonate in case of TCAs is indicated for: Conduction defects, Arrhythmias, asthma and Metabolic acidosis.

• Mechanism: Alkalinization: promotes dissociation of the tricyclic antidepressant from sodium channels. Increased plasma sodium to helps to drive sodium through sodium channels.
• Dose: IV bolus dose, followed by continuous IV infusion with dextrose) to maintain alkalinization.

Question 15

Discuss the Opioid toxidromes (CNS depressants)

Answer 15

1- Opium contains more than 20 alkaloids such as morphine & codeine.
-Morphine is only injected & has no smell.
-Codeine is an antitussive

1- Heroin is a semisynthetic derivative of morphine, with analgesic properties superior to morphine and cough-suppressant properties superior to codeine. Heroin is 2-4 times more addictive than morphine; it is neither used medically nor manufactured legally.

2- Fentanyl, meperidine, methadone and tramadol are synthetic opioids.

Fentanyl is 25-50 times more potent than heroin and 50-100 times more potent than morphine.

Question 16

Discuss the MOA of Opioid toxidromes

Answer 16

They exert their effects by interacting with specific opioid receptors.

Opioids interact with [mu, kappa and delta receptors] causing a mixture of stimulations and depressions but mainly depressions.

Tramadol binds to μ-opioid receptors only. It also inhibits the reuptake of noradrenaline and serotonin

Question 17

CNS manifestations of opioid poisoning

Answer 17

-The patient feels euphoria (sense of well being and relief of pains) due to depression of Sensory cortex followed by dysphoria (distress, anxiety and fear).

• Gradual deterioration of consciousness (drowsy, stupor then comatose) due to depression of Consciousness.

-Cyanosis due to depression of respiratory center.

• Circulatory collapse due to depression of vasomotor center.

-Vomiting due to stimulation of vomiting center.

-The pupils are constricted pin pointed pupil (ppp) and non- reactive due to stimulation of Pupillo-constrictor center.

Question 18

Discuss the CVS, respiratory and gastrointestinal manifestations of opioid poisoning

Answer 18

CVS: slow full pulse due to vagal center stimulation

Respiratory: Non-cardiogenic pulmonary edema and slow deep respirations due to stimulation of vagal center

GIT: constipation and diminished bowel sounds

Question 19

Discuss the treatment of Opioid poisoning

Answer 19

1. Supportive measures: ABCs
2. GIT decontamination: Gastric lavage Using cuffed endotracheal tube even if alert (rapid CNS depression), and Even in case of injected morphine (morphine is re-excreted in the stomach). Local charcoal also for adsorption
3. Antidote:
   -Atropine blocks vagal stimulation and increase HR.
   -Naloxone (Narcan): reverses respiratory depression
   -Nalmefene: new opioid antagonist
   -Naltrexone: used in opioid addiction treatment
4. Symptomatic treatment
5. Elimination of poison from blood: Hemodialysis is ineffective due to high volume of distribution

Question 20

Give the MOA of Sedative hypnotic toxidromes (CNS depressants); Barbituates like phenobarbital and Benzodiazepines like diazepam

Answer 20

Both act by enhancing the binding of y-aminobutyric acid (GABA) to GABA receptors. GABA receptors inhibit post-synaptic nerve impulse transmission.

       Barbiturates causing GABA dependent chloride-channels to stay open for a longer period of time,

benzodiazepines causing chloride- channels to open more frequently.

Question 21

Give the clinical CNS manifestations of Sedative hypnotic toxidromes (CNS depressants); Barbituates like phenobarbital and Benzodiazepines like diazepam

Answer 21

1. CNS manifestations: Confusion, memory deficit, poor judgment, vertigo, slurred speech, and ataxia.
   -Mild drowsiness up to coma.

-Barbiturates coma characterized by being deep & prolonged, with slow weak pulse, slow shallow respiration, hypotension and hypothermia, Muscle flaccidity with diminished reflexes and may end in respiratory failure (central asphyxia).

-Benzodiazepines coma is Low-grade coma (in most comatose patients arousal occurs within 12-36 hrs. following an acute overdose).

Question 22

Give the CVS, Respiratory system, skin and renal manifestations of sedative hypnotic toxidromes (CNS depressants); Barbituates like phenobarbital and Benzodiazepines like diazepam

Answer 22

2. CVS manifestations: Hypotension due to direct myocardial depression & vasodilatation.
3. Respiratory manifestations:
   * R.C. depression (in barbiturates only) which results in hypoventilation & apnea.
   * Pneumonia (in barbiturates only) which may occur due to:
   –Prolonged coma.
   –Inhibition of the protective reflexes (cough reflex).
   –Aspiration pneumonia following vomiting of gastric contents.

• Non-cardiogenic pulmonary edema in (barbiturates only): In rare cases respiratory arrest may occur following rapid IV administration in benzodiazepines.

1. Skin manifestations: Blisters “bullae” over pressure points.
2. Renal manifestations in barbiturates only:
   Renal failure due to:
   * Hypotension —► decreased perfusion.
   * Rhabdomyolysis (due to prolonged coma).

Question 23

Investigations in barbiturate and diazepam poising

Answer 23

1. Routine investigations:
   - Renal function test in cases of barbiturates: Acute renal failure.
2. Toxicological screen.
3. CPK in cases of barbiturates: high (due to rhabdomyolysis).
4. Chest X-ray in cases of barbiturates: pneumonia and non- cardiogenic pulmonary edema.

Question 24

Discuss the treatment of sedative hypnotic toxidromes (CNS depressants) poisoning

Answer 24

1. Supportive treatment: ABC.
2. GIT decontamination: Emesis: not recommended since rapid neurologic deterioration is known to occur.
   *Gastric Lavage: with cuffed endotracheal tube up to several hours after the overdose due to decreased GIT motility.
   *Activated charcoal.
   * MDAC: in phenobarbital toxicity only (enterohepatic circulation).
3. Elimination of the poison from blood:
   * Forced alkaline diuresis: for long acting barbiturates only
   * Hemodialysis and hemoperfusion have been successfully utilized in all types of barbiturate overdoses (most effective for long-acting barbiturates)
   * Hemodialysis and hemoperfusion are ineffective in benzodiazepines
   *Charcoal hemoperfusion is more effective than hemodialysis only in barbiturates.
4. Symptomatic treatment:
5. Antidote: Flumazenil (Anexate) in benzodiazepines only:
   *Action: Flumazenil is a competitive BZ receptor antagonist.
   * Dose: IV, over 30 sec, may be repeated at 1-min. interval up to a maximum total dose of 3 mg.

Question 25

Give the contraindications of flumazenil usage

Answer 25

o Hypersensitivity to flumazenil or BZ.

o Co-ingestions especially BZ+ drugs causing seizures,

o Chronic use of BZ as it may induce withdrawal syndromes,

o Patients given BZ for control of a potentially life-threatening condition as status epilepticus.

o History of convulsions.

o Head trauma (seizures may occur).

Question 26

Give the advantages and disadvantages of flumazenil

Answer 26

*Advantages:
Effective within minutes in treating isolated BZ overdose (It is highly lipid-soluble and crosses the blood brain barrier quickly).

*Disadvantages and precautions:
Its half-life is 57 min (which is much shorter than most of oral BZ), and re-sedation commonly occurs after a single dose.

Question 27

Factors affecting severity of corrosive

Answer 27

• Physical form: Solid/liquid.
• Concentration.
• Quantity.
• PH: pH <2 and >11 are more corrosive.
• Duration of contact
• Food: Presence or absence of food in stomach.

Question 28

Complications (causes of death) in corrosive

Answer 28

1) Acute:
Airway obstruction Shock (due to pain)
Vomiting-
dehydration
GIT perforation.

2) Late:
- Stricture leading to cachexia.

3) Remote:
- Carcinoma of esophagus

Question 29

It is CONTRAINDICATED to do the following in GIT corrosives

Answer 29

o Induced emesis: causes reintroduction of the caustic to the upper gastrointestinal tract and airway

o Activated charcoal:
■ It interferes with tissue evaluation by endoscopy.
■ Most caustics are not adsorbed to activated charcoal,

o Gastric lavage: carries the risk of perforation

o Neutralization and dilution:
■ It has the potential to form gas.
■ Generate an exothermic reaction leading to more tissue damage.

Question 30

Compare between alkali and acid corrosives

Answer 30

Question 30

A 21 year old female attempted suicide by drinking Dettol, following her final exams. The smell of phenol is prominent on her mouth

a) what is the causative substance?

b) Give the local clinical presentation

Answer 30

a) Carbolic acid (phenol)

b)
a)Stomach:

• Weak corrosive action:
  Pain and vomiting which has characteristic phenolic smell. Superficial ulcers of gastric mucosa.
• Local anesthetic action —>pain and vomiting disappear after short time.
• Coagulative necrosis-* thickening of gastric wall.

b)Skin:
white eschars with smell of phenol around the mouth or skin, which turns brown on exposure to air due to oxidation.

Question 31

A 21 year old female attempted suicide by drinking Dettol, following her final exams. The smell of phenol is prominent on her mouth

c)

Answer 31

a) Systemic effect:

a) CNS: stimulation followed by depression —> constricted pupil and
convulsions rapidly followed by coma.
b) CVS: myocardial depressant —►hypotension, tachycardia and
arrhythmias.
c) Kidney: Acute renal failure —> oliguria with albumin, blood and casts in urine passing to anuria. The urine turns green on exposure to air due to oxidation of the excretory products of phenol.

d)Acid Base imbalance:
* Respiratory alkalosis due to respiratory center stimulation.
* Metabolic acidosis follows due to uncompensated renal loss of base during stage of alkalosis because of renal damage.

e) Met-hemoglobinemia

Question 32

A 21 year old female attempted suicide by drinking Dettol, following her final exams. The smell of phenol is prominent on her mouth

d) give the cause of death

e) give the investigations needed

Answer 32

a)
1- Early: respiratory failure due to respiratory center depression.
2- Late: renal failure.

b)
1- Routine lab investigation:
* ABG:
o Respiratory alkalosis.
o Metabolic acidosis follows.
* Kidney function test: Acute renal failure.

2- Urine analysis: oliguria with albumin, blood and casts in urine.
3- Met-hemoglobin level.
4- ECG: Arrhythmias

Answer 33

1) Supportive measures: ABCs

2) GIT decontamination:
* Emesis is not recommended due to rapid onset of coma and seizures (within half an hour for significant ingestion).

• Gastric lavage is indicated and essential due to: -
  o Vomiting is temporary (local anesthetic action).
  o Thickening of gastric wall (coagulative necrosis) and superficial ulcers (no expected perforation).
  o Carbolic acid has a systemic effect so lavage is indicated to decrease absorption.
• Local antidote is:
  o Milk & egg white: as phenol will coagulate their protein
  instead of stomach protein.
  o Ethanol 10%: it dissolves phenol then rapidly removed by gastric lavage.
• Eye decontamination: Flush exposed or irritated eyes with copious
  amounts of water or saline for at least 15 minutes.

3) No specific antidotes.

4) Symptomatic: Treatment of met-hemoglobinemia, renal failure, metabolic acidosis and seizures