Toxicology

Question 1

Toxidromes

Answer 1

• Alpha and Beta Adrenergic
• Anticholinergic
• Cholinergic
• Epileptogenic
• Extrapyramidal
• Hallucinogenic
• Narcotic
• Sedative/Hypnotic
• Serotonin
• Sympathomimetic

Question 2

Toxidromes: Anticholinergic

saying to remember pt presentation

Answer 2

• blind as a bat
• hotter than hell
• red as a beet
• dryer than the desert
• mad as a hatter

Question 3

Anion gap

Gap is present if greater than __

cation - anions = gap
(Na+ + K+) – (Cl- + HCO3-)

Answer 3

14

Question 4

Osmolar gap

Presence of additional unmeasured low molecular weight molecules that
are osmotically active (reference range: 285-300 mOSm/kg)

– Gap = Measured - Calculated
– Calculated = ( __ x Na+) + (BUN/ ___ ) + (Glu/ ___ ) + (EtOH/ ___ )
– Gap is present if greater than __

Answer 4

• (2 x Na+) + (BUN/2.8) + (Glu/18) + (EtOH/4.6)
• 10

Question 5

Activated Charcoal

44-95% prevention of absorption

1-2 gm/kg ABW or 50-100 gm in adults

Pros:
- Decreases ___ related problems
- Absorbs most toxins

Cons:
- Difficult administration
- Should NOT be administered if airway is ___

COMMON DECONTAMINATION STRATEGIES

Answer 5

• time
• unprotected

Question 6

Whole Bowel Irrigation: ____
- Sustained-release products, “body packers/stuffers”, ___ , ___
- Patient should remain seated on a bedside toilet
- Continue until presence of clear rectal effluent

COMMON DECONTAMINATION STRATEGIES

Answer 6

• Polyethylene glycol
• iron
• lithium

Question 7

Hemodialysis

Effective for the following medications (4)

COMMON DECONTAMINATION STRATEGIES

Answer 7

• Alcohols
• Lithium
• Salicylates
• Theophylline

Question 8

SALICYLATE TOXICITY - Risk Factors

Salicylate Concentrations
- Mild toxicity: > ___ mg/dL (tinnitus, dizziness)
- Severe toxicity: > ___ mg/dL (CNS effects)

Mixed Acid/Base Disorders
- ↑ anion gap → metabolic ___
- Early respiratory ___ → hyperventilation

Electrolyte Disturbances
- Hypo ___
- Hypo/hypernatremia

Answer 8

• 30
• 80
• acidosis
• alkalosis
• hypokalemia

Question 9

Salicylates: Toxicity Signs and Symptoms

Answer 9

• N/V
• Tinnitus and diaphoresis
• Decreased GI motility
• Altered mental status
• Seizures
• Hyperventilation

Question 10

Salicylates: Antidote

Sodium bicarbonate
MOA: Urine ___

Indications
- Serum salicylate level > __ mg/dL
- Anion gap metabolic ___
- Altered mental status

Dosing
- __ - __ mEq/kg (50 to 100 mEq) IV push over 1 to 2 minutes
- May consider continuous infusion and titrate to effect

Monitoring
- Serum pH
- Electrolytes ( __ , __ )

Answer 10

• alkalinization
• 30
• acidosis
• 1-2
• K, Ca

Question 11

Sedatives: Toxicity Signs and Symptoms

Answer 11

• CNS depression
• Respiratory depression
• Hypotension
• Bradycardia

Question 12

Sedatives: Flumazenil ehhhhhhh

MOA: Competes with BZDs at BZD binding site of ___ complex
- use with caution in patients
with ___ (Can induce activity)
- can induce ___ symptoms (N/V, agitation)

Answer 12

• GABA
• seizures
• withdrawal

Question 13

TCAs: Clinical Practice

Indications
- Bed wetting
- ___
- Insomnia
- Migraines
- ___

Examples
- ___
- Desipramine
- Doxepin
- ___
- Nortriptyline

Answer 13

• Depression
• Neuropathy
• Amitriptyline
• Imipramine

Question 14

TCAs: Pharmacokinetics

Initially, rapidly absorbed from the GI tract
- Anticholinergic effects may ___ GI motility ( ___ rate of absorption)

___ Vd (10-50 L/kg)

Acidemia increases the percentage of
___ TCA

Highly ___

t1/2 = __ - __ hours

Answer 14

• slow, decrease
• large
• unbound
• lipophilic
• 4-93

Question 15

TCAs: Pharmacology

• ___ activity
• ___ receptor blockade
• Serotonin, norepinephrine, and dopamine inhibition
• Sodium and potassium channel blockade
• CNS and respiratory ___

Answer 15

• Anticholinergic
• alpha
• depression

Question 16

TCAs: Toxicity Signs and Symptoms

• Altered mental status
• ___ tension
• ___ cardia
• Prolonged ___
• Seizures
• ___ symptoms

Answer 16

• Hypotension
• Tachycardia
• QRS
• Anticholinergic

Question 17

TCAs: Effects of QRS Prolongation

QRS interval> 100 msec
- Increased risk of ___ activity

QRS interval > 150 msec
- Increased risk of ___

Metabolic acidosis
- Promotes ___ of drug from proteins

Answer 17

• seizure
• arrhythmias
• unbinding

Question 18

TCAs: Antidote

1. Sodium bicarbonate
   MOA: ___ sodium gradient of poisoned sodium channels

Indications
- QRS interval > ___ msec
- TCA induced ___ or ___
- Metabolic ___

Dosing
- __ - __ mEq/kg (50 to 100 mEq) IV push over 1 to 2 minutes
- May consider ___ infusion and titrate to effect

Monitoring
- Serum pH

D/C when
* QRS interval < ___ msec
* Resolution of ___ abnormalities
* Hemodyamically stable

Answer 18

• increases
• 100
• arrhythmias, hypotension
• acidosis
• 1-2
• continuous
• 100
• ECG

Question 19

TCAs: Seizure Management

• ___
• ___
• Phenytoin ?
• Fosphenytoin ?
• Levetiracetam ?

Answer 19

• Benzodiazepines
• Phenobarbital

Question 20

Antipsychotics: Pharmacology

First Generation: ___ antagonism

Second Generation: ___ / ___ antagonism

Answer 20

• D2
• 5HT2A/D2

Question 21

Antipsychotics: Toxicity Signs and Symptoms

• Hypotension
• Tachycardia
• QT/QRS prolongation
• ___ symptoms (EPS)
• ___ ___ syndrome (NMS)
• Sedation

Answer 21

• Extrapyramidal
• Neuroleptic malignant

Question 22

Extrapyramidal Symptoms

___ 2 mg IM
- Onset ~ 15 - 20 minutes
- Longer half life

___ 1- 2 mg/kg IV/IM (up to 50 mg) over several minutes
- Onset ~ 5 minutes
- Continue oral therapy for 3 - 4 days: Diphenhydramine 50 mg PO TID

Answer 22

• Benztropine
• Diphenhydramine

Question 23

Neuroleptic Malignant Syndrome (NMS)

___ up to 42.2C (108F) with altered mental status (delirium or coma) and “lead pipe” muscular ___

Occurs __ - __ days after initiating therapy or after adding a second agent

Often these patients are less than 40 years of age and more often males

Complications continue for 5-10 days
- 84% of cases: Haloperidol, depot fluphenazine, or chlorpromazine use
- Death is secondary to rhabdomyolysis, renal failure, cardiovascular collapse, respiratory failure, arrhythmias, or thromboembolism

Answer 23

• Hyperpyrexia, rigidity
• 3-9

Question 24

NMS: Treatment

• D/C offending agent
• Rapid external cooling
• ___

___ - Initial dose of 2.5 mg/kg to a maximum of 10 mg/kg
- Maintenance dose is 2.5 mg/kg Q6H until resolved

___ has also been utilized
- 2.5 mg BID initially, increasing to 5 mg TID
- Doses as high as 60 mg/day have been used

Answer 24

• Benzodiazepines
• Dantrolene
• Bromocriptine

Question 25

# Serotonin Syndrome Toxic hyperserotonergic state - Excessive stimulation of the post-synaptic receptors in the CNS Triad of symptoms - Altered ___ status - ___ instability - ___ abnormalities Development of serotonin syndrome is rapid - Within 6 hours of an increase in the precipitating medication

Answer 25

- mental - Autonomic - Neuromuscular

Question 26

# Serotonin Syndrome: Pharmacology Direct agonists

Answer 26

Buspirone Lithium LSD Sumatriptan

Question 27

# Serotonin Syndrome: Pharmacology Increased release of serotonin

Answer 27

Amphetamines Cocaine Mirtazapine MDMA (“ecstasy”)

Question 28

# Serotonin Syndrome: Pharmacology Inhibitors of serotonin metabolism

Answer 28

Monoamine oxidase inhibitors Linezolid

Question 29

# Serotonin Syndrome: Pharmacology Reduced uptake of serotonin

Answer 29

Selective serotonin reuptake inhibitors (SSRIs) * Citalopram, fluoxetine, sertraline, paroxetine Tricyclic antidepressants (TCAs) * Amitriptyline, imipramine, nortriptyline Serotonin norepinephrine reuptake inhibitors (SNRIs) * Duloxetine, Venlafaxine Trazodone Dextromethorphan

Question 30

# Serotonin Syndrome: Treatment - D/C offending agent - Benzodiazepines - Aggressive cooling ___ (Periactin®) – 1st generation histamine receptor blocking agent – Non-specific 5-HT1A and 5-HT2A receptor blocking effects * 4 mg PO Q1H * Maximum dose: 16 mg

Answer 30

Cyproheptadine

Question 31

# Serotonin Syndrome vs NMS Serotonin syndrome – Lower fever – Myoclonus, hyperreflexia – Lasting < ___ hours – Responds to ___ – ___ limbs are more affected than upper limbs NMS – ___ fever – Lasting > ___ hours – Responds to bromocriptine – ___ lead pipe rigidity

Answer 31

- 24 - cyproheptadine - lower - higher - 24 - diffuse

Question 32

# Digoxin: Clinical Practice Indicated for the treatment of atrial fibrillation (AF) and heart failure (HF) Monitored with serum concentrations due to narrow therapeutic index - Goal range usually 0.8 to 2 ng/mL - May be 0.5 to 1 ng/mL in HF - Must be drawn at least __ hours after previous dose Digitalis inhibits ___

Answer 32

6 Na/K ATPase

Question 33

# Digoxin: Toxicity Signs/Symptoms Non Cardiac * Nausea/vomiting * Abdominal pain * Anorexia * Confusion * ___ changes Cardiac * ___ cardia * 2nd or 3rd degree heart block * Arrhythmias * ___ kalemia – 5 to 6.4 mEq/L ~ 35% mortality – > 6.4 mEq/L ~ 90% mortality

Answer 33

- Vision - bradycardia - Hyperkalemia

Question 34

# Digoxin: General Management - D/C digoxin - ABC management - Obtain serum digoxin concentration, BMP - Monitor vital signs and ___ changes (arrhythmias, bradycardia) - Administer activated charcoal (if presentation within __ hours of ingestion) - Consider administration of ___ - ___ is NOT effective

Answer 34

- ECG - 2 - Digibind - Hemodialysis

Question 35

# Digoxin: Antidote Digoxin Immune Fab (Digibind®) MOA: Binds free digoxin and tissue bound digoxin released during equilibrium state Indications - Ventricular arrhythmias, bradycardia/2nd or 3rd degree heart block not responsive to atropine - ___ (K > 5.5 mEq/L) with signs/symptoms of toxicity - Serum digoxin concentrations > __ - __ng/mL drawn at least 6 hours after time of ingestion - Ingestion > __ mg in adults, > __ mg in children

Answer 35

- Hyperkalemia - 10-15 - 10, 4

Question 36

# Digibind® Dosing Each vial binds approximately ___ of digoxin Based on acute ingestion of known amount - Total body load (TBL) = mg digoxin ingested x 0.8 - TBL/0.5 mg = # Digibind vials to administer Based on serum digoxin concentrations in adults – # Digibind vials = digoxin concentration (ng/mL) x patient’s weight (kg) / 100

Answer 36

- 0.5 mg

Question 37

# Digoxin: Toxicology Tidbits T or F: Toxicity can occur with acute ingestion and chronic therapy

Answer 37

TRUE

Question 38

T or F: Serum digoxin concentrations are clinically useful after Digibind administration

Answer 38

FALSE useless

Question 39

# Toxicity Signs and Symptoms - CCBs and BBs CCBs - ___ glycemia - metabolic ___ - pulmonary edema - ileus BBs - ___ glycemia - ___ Both - hypotension - bradycardia - ___ - cardiogenic shock - CNS depression

Answer 39

CCBs - hyperglycmeia - acidosis BBs - hypoglycemia - bronchospasms Both - arrythmias

Question 40

# General Management - Monitor vital signs and ECG changes (arrhythmias, bradycardia) - Administer ___ ___ (depending on dosage form and time of presentation) Potential antidotes: - ___ - Calcium - ___ Therapy - Glucagon - High Dose ___ Therapy - Lipid Emulsion Therapy

Answer 40

- activated charcoal - Atropine - Vasopressor - Insulin

Question 41

# Atropine MOA: Blocks ___ activity to ___ heart rate Dosing - 0.5-1 mg IV push - Maximum dose: 3 mg **Readily available, but usually not effective in CCB and BB overdoses**

Answer 41

- parasympathetic, increase

Question 42

# Calcium More effective in ___ overdose MOA: Opens calcium channels and promotes ___ of calcium from sarcoplasmic reticulum resulting in myocardial ___ Dosing (Note: calcium ___ has 3x more elemental calcium than calcium gluconate)

Answer 42

- CCB - release - contractility - chloride

Question 43

# Vasopressor Therapy Binds beta receptors not occupied by BB as well as Gs receptors to eventually stimulate ___ and ___ release to improve ___

Answer 43

cAMP, Ca contractility

Question 44

# Vasopressor Therapy May require higher doses to overcome receptor blockade - Medication selection depends on clinical presentation - Review patient’s ingestion history and monitor vital signs to select appropriate agents Vasodilatory shock → ___ cardiogenic shock → ___

Answer 44

- Norepinephrine - Epinephrine

Question 45

# Glucagon MOA: Stimulates contractility by ___ beta receptors and binding to Gs receptors to activate conversion of ATP to ___ Dosing - Adults: 3-10 mg IV bolus - Children: 50-150 mcg/kg IV bolus - Infusion: initiate infusion at same dose as effective bolus dose (in mg/hr) May need to pre-medicate with ___ and add PRN regimen due to nausea/vomiting with glucagon

Answer 45

bypassing cAMP ondansetron

Question 46

# CCBs and BBs: High Dose Insulin Therapy MOA: Increased ___ and increased intracellular glucose transport Dosing - Insulin drip at 0.5 to 1 unit/kg/hr IV - ___ at 0.5 gm/kg/hr IV - Titrate to ____ > 90 to 100 mm Hg or effect every 30 to 60 minutes (improved contractility, decreased symptoms) Monitoring – Improved contractility within 15 to 60 minutes – Goal glucose: 100 to 250 mg/dL – Serum electrolytes every 1 to 2 hours (glucose, potassium)

Answer 46

- inotropy - Dextrose - SBP

Question 47

# Lipid Emulsion Therapy MOA: Limits ___ of lipophilic medication by creating a “lipid sink” Maximum = ___ mL/kg total dose

Answer 47

bioavailability 10

Question 48

# Toxicology Tidbits - ___ - Not likely to be effective in either CCB or BB overdoses - ___ - More likely to be effective with CCB overdoses vs. BB overdoses. Chloride has 3x more elemental calcium vs. gluconate, but extravasation more likely with chloride form - ___ therapy - Should utilize high doses to overcome beta receptor blockade - ___ May need to pre-medicate with ondansetron and add PRN regimen due to nausea/vomiting - High Dose ___ Therapy - Communicate with healthcare providers to address patient safety - ___ Emulsion Therapy - Depending on infusion pump and dose, may need multiple pumps to administer therapy. Total dose maximum: 10 mL/kg

Answer 48

- atropine - calcium - vasopressor - glucagon - insulin - lipid

Question 49

# Iron: Toxicology Tidbits Toxicity can occur at 10 to 60 mg/kg of elemental iron - Prenatal vitamins contain approximately 65 mg of elemental iron - Children’s vitamins contain approximately 10 to 18 mg of elemental iron Concern is absorption of iron into ___ - Can still experience toxicity with normal serum iron concentrations Human body has no natural mechanism to handle iron overload – Excretion * Male = 1 mg daily * Female = 2 mg daily

Answer 49

tissues

Question 50

T or F: activated charcoal is effective against Fe overdose

Answer 50

FALSE

Question 51

# Iron: Whole Bowel Irrigation Whole Bowel Irrigation: ___ - Procedure usually takes 4 to 6 hours - Patient should remain seated on a bedside toilet - Continue until presence of clear rectal effluent

Answer 51

Polyethylene glycol

Question 52

# Iron: Antidote ___ (Desferal) MOA: ___ iron and enhances ___ elimination Indications - Metabolic acidosis or other signs of shock - Clinical deterioration despite IV fluid administration - Presence of iron tablets on ___ - Serum iron concentration > 500 mcg/mL

Answer 52

Deferoxamine - Chelates, renal - KUB

Question 53

# Deferoxamine Dosing Start at 15 mg/kg/hour - May increase to ___ mg/kg/hour for patients with severe poisoning - Decrease rate if patient experiences ___ Usually continued for __ - __ hours May titrate down based on resolution of symptoms and/or absence of ___ urine

Answer 53

45 hypotension 12-24 vin rose