Toxicology Flashcards
(91 cards)
1
Q
What are the top medication overdoses?
A
analgesics
antidepressants
cadiovascular drugs
dietary supplements/herbals/homeopathic
2
Q
What drugs show up on a urine drug screen?
A
amphetamines, barbiturates, BZDs, cannabinoids, cocaine, opioids, phencyclidine
3
Q
What is the anion gap?
A
– Difference between primary measured cations and primary measured anions
– (Na+ + K+) – (Cl- + HCO3-)
– Gap is present if greater than 14
4
Q
What is the osmolar gap?
A
– Presence of additional unmeasured low molecular weight molecules that are osmotically active (reference range: 285-300 mOSm/kg)
– Gap = Measured - Calculated
– Calculated = (2 x Na+) + (BUN/2.8) + (Glu/18) + (EtOH/4.6)
– Gap is present if greater than 10
5
Q
What are common decontamination strategies?
A
activated charcoal, whole bowel irrigation, hemodialysis
6
Q
Activated charcoal
A
Decreases time related problems
Absorbs most toxins
Difficult administration
Should not be administered if airway is unprotected
7
Q
Whole bowel irrigation
A
polyethylene glycol
* Sustained-release products, “body packers/stuffers”, iron, lithium
* Patient should remain seated on a bedside toilet
* Continue until presence of clear rectal effluent
8
Q
Hemodialysis is effective for what medications?
A
- Effective for the following medications:
– Alcohols
– Lithium
– Salicylates
– Theophylline
9
Q
What are the toxicity risk factors for salicyclates?
A
mixed acid/base disorders
electrolyte disturbances
salicylate concentrations
10
Q
Mixed acid/base disorders
A
- ↑ anion gap → metabolic acidosis
- Early respiratory alkalosis → hyperventilation
11
Q
Electrolyte disturbances
A
- Hypokalemia
- Hypo/hypernatremia
12
Q
Salicylate concentrations
A
- Analgesic properties: 10-15 mg/dL
- Anti-inflammatory properties: 15-20 mg/dL
- Mild toxicity: > 30 mg/dL (tinnitus, dizziness)
- Severe toxicity: > 80 mg/dL (CNS effects)
13
Q
What are signs/symptoms of salicylate toxicity?
A
N/V, tinnitus and diaphoresis, decreased GI motility, altered mental status, seizures, hyperventilation
14
Q
What is the general management for salicyclate toxicity - stabilization?
A
- ABC management
- Oxygenation
- Vital signs
- IV access
- CNS/respiratory depression
15
Q
What is the general management for salicyclate toxicity - exposure?
A
Medications/illicit substances
Dose(s)
Time of ingestion
Family/EMS report
Pill count
16
Q
What is the general management for salicyclate toxicity - assessment?
A
- Physical exam
- Labs (BMP, ABG)
- Salicylate/APAP concentrations
- Activated charcoal (?)
- Fluids with KCl
- Sodium bicarbonate
- Hemodialysis (?)
17
Q
What is the antidote for salicylate toxicity? What is its MOA?
A
sodium bicarbonate
MOA: Urine alkalinization
18
Q
What are the indications for sodium bicarbonate for salicylate toxicity?
A
- Serum salicylate level > 30 mg/dL
- Anion gap metabolic acidosis
- Altered mental status
19
Q
What is the monitoring for sodium bicarbonate?
A
- Serum pH 7.5-8
- Electrolytes (potassium, calcium)
20
Q
What are the signs/symptoms of sedative toxicity?
A
CNS depression, respiratory depression, hypotension, bradycardia
21
Q
What is the general management of sedative toxicity - stabilization?
A
- ABC management
- Vital signs
- IV access
- Oxygenation
- CNS/respiratory depression
22
Q
What is the general management of sedative toxicity - exposure?
A
- Medications/illicit substances
- Dose(s)
- Time of ingestion
- Family/EMS report
- Pill count
23
Q
What is the general management of sedative toxicity - assessment?
A
- Physical exam
- Labs
- APAP/salicylate concentrations
- EtOH/toxic alcohol panel
- Activated charcoal (?)
- Flumazenil (?)
24
Q
What is the antidote for sedative toxicity? What is the MOA?
A
flumazenil
MOA: Competes with BZDs at BZD binding site of GABA complex
25
Who should you use flumazenil with caution in?
Use with caution in patients with seizures
* Can induce seizure activity
Can induce withdrawal symptoms
* Nausea/vomiting, agitation
26
What are the indications for tricyclic antidepressants?
* Bed wetting
* Depression
* Insomnia
* Migraines
* Neuropathy
Ex: amutriptyline, desipramine, doxepin, imipramine, nortriptyline
27
What are the pharmacokinetics for tricyclic antidepressants?
* Initially, rapidly absorbed from the GI tract
– Anticholinergic effects may slow GI motility
– Decrease rate of absorption
* Large Vd (10-50 L/kg)
* Acidemia increases the percentage of unbound TCA
* Highly lipophilic
* t1/2 = 4-93 hours
28
What is the pharmacology for tricyclic antidepressants?
anticholinergic activity, alpha receptor blockade, serotonin, norepinephrine, and dopamine inhibition, sodium and potassium channel blockade, CNS and respiratory depression
29
What are the signs and symptoms of antidepressant toxicity?
altered mental status, hypotension, tachycardia, prolonged QRS, seizures, anticholinergic symptoms
30
TCAs: What are the effects of QRS prolongation?
QRS interval > 100 msec: Increased risk of seizure activity
QRS interval > 150 msec: Increased risk of cardiac arrhythmias
Metabolic acidosis: Promotes unbinding of drug from proteins
31
What is the general management for antidepressants and antipsychotic toxicity - stabilization?
* ABC management
* Vital signs
* IV access
* Oxygenation
* CNS/respiratory depression
32
What is the general management for antidepressants and antipsychotic toxicity - exposure?
* Medications/illicit substances
* Dose(s)
* Time of ingestion
* Family/EMS report
* Pill count
33
What is the general management for antidepressants and antipsychotic toxicity - assessment?
* Physical exam
* Labs
* Activated charcoal (?)
* Fluids
* Vasopressors
* Seizure management
* Sodium bicarbonate
34
What is the antidote for TCA toxicity? What is its MOA?
sodium bicarbonate
MOA: Increases sodium gradient of poisoned sodium channels
35
What are the indications for sodium bicarbonate for TCA toxicity?
* QRS interval > 100 msec
* TCA induced arrhythmias or hypotension
* Metabolic acidosis
36
What is the monitoring for sodium bicarbonate for TCA toxicity?
* Serum pH 7.45-7.55
* D/C when: QRS interval < 100 msec; Resolution of ECG abnormalities; Hemodyamically stable
37
What is seizure management for TCA toxicity?
BZDz, phenobarbital, phenytoin, fosphenytoin, levetiractem
38
What is the pharmacology of antipsychotics?
first gen: D2 antagonism
second gen: 5HT2A/D2 antagonism
39
What are examples of antipsychotics?
typical: haloperidol, fluphenazine, chlorpromazine, thioridazine, perphanazine
atypical: aripiprazole, clozapine, olanzapine, paliperidone, ziprasidone
40
What are signs and symptoms of antipsychotic toxicity?
hypotension, tachycardia, QT/QRS prolongation, extrapyramidal symptoms, neuroleptic malignant syndrome, sedation
41
What is the treatment for extrapyramidal symptoms?
* Benztropine 2 mg IM
– Onset ~ 15 - 20 minutes
– Longer half life
* Diphenhydramine 1- 2 mg/kg IV/IM (up to 50 mg) over several minutes
– Onset ~ 5 minutes
– Continue with oral therapy for 3 - 4 days: Diphenhydramine 50 mg PO TID
42
What is neuroleptic malignant syndrome?
* Hyperpyrexia up to 42.2C (108F) with altered mental status (delirium or coma) and “lead pipe” muscular rigidity
* Occurs 3-9 days after initiating therapy or after adding a second agent
* Death is secondary to rhabdomyolysis, renal failure, cardiovascular collapse, respiratory failure, arrhythmias, or thromboembolism
most cases it's from: haloperidol, depot fluphenazine, or chlorpromazine use
43
What is the treatment for neuroleptic malignant syndrome?
* D/C offending agent
* Rapid external cooling
* Benzodiazepines
* Dantrolene
* Bromocriptine has also been utilized
44
What is serotonin syndrome?
* Toxic hyperserotonergic state
– Excessive stimulation of the post-synaptic receptors in the CNS
* Triad of symptoms
– Altered mental status
– Autonomic instability
– Neuromuscular abnormalities
* Development of serotonin syndrome is rapid
45
Which drugs are direct agonists that cause serotonin syndrome?
– Buspirone
– Lithium
– Lysergic acid diethylamide (LSD)
– Sumatriptan
46
Which drugs increase the release of serotonin, leading to serotonin syndrome?
– Amphetamines
– Cocaine
– Mirtazapine
– MDMA (“ecstasy”)
47
Which drugs are inhibitors of serotonin metabolism, leading to serotonin syndrome?
– Monoamine oxidase inhibitors
– Linezolid
48
Which drugs reduce the uptake of serotonin, leading to serotonin syndrome?
SSRIs (citalopram, fluoxetine, sertraline, paroxetine), TCAs (amitriptyline, imipramine, nortriptyline), SNRIs (duloxetine, venlafaxine), trazodone, dextromethorphan
49
What is the treatment for serotonin syndrome?
* D/C offending agent
* Benzodiazepines
* Aggressive cooling
* Cyproheptadine (Periactin®)
– 1st generation histamine receptor blocking agent
– Non-specific 5-HT1A and 5-HT2A receptor blocking effects
50
What are the differences in serotonin syndrome vs NMS?
serotonin syndrome:
– Lower fever
– Myoclonus, hyperreflexia
– Lasting < 24 hours
– Responds to
cyproheptadine
– Lower limbs are more affected than upper limbs
NMS:
– Higher fever
– Lasting > 24 hours
– Responds to bromocriptine
– Diffuse lead pipe rigidity
51
What is digoxin used for?
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 6 hours after previous dose
52
What are the signs/symptoms of non cardiac toxicity of digoxin?
* Nausea/vomiting
* Abdominal pain
* Anorexia
* Confusion
* Visionchanges
53
What are the signs/symptoms of cardiac toxicity of digoxin?
* Bradycardia
* 2nd or 3rd degree heart block
* Arrhythmias
* Hyperkalemia
54
What is the general managment for digoxin?
* D/Cdigoxin
* ABC management
* Obtain serum digoxin concentration, BMP
* Monitor vital signs and ECG changes (arrhythmias, bradycardia)
* Administer activated charcoal (if presentation within 2 hours of ingestion)
* Consider administration of Digibind®
* Hemodialysis is not effective!
55
What is the antidote for digoxin? What is the MOA?
digoxin immune Fab (digibind)
MOA: Binds free digoxin and tissue bound digoxin released during equilibrium state
56
What are the indications for digibind?
* Ventricular arrhythmias, bradycardia/2nd or 3rd degree heart block not responsive to atropine
* Hyperkalemia (K > 5.5 mEq/L) with signs/symptoms of toxicity
* Serum digoxin concentrations > 10-15 ng/mL drawn at least 6 hours after time of ingestion
* Ingestion > 10 mg in adults, > 4 mg in children
57
What is the dosing of digibind?
* Each vial binds approximately 0.5 mg 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
58
When can toxicity occur from digoxin?
Toxicity can occur with acute ingestion and
chronic therapy
Serum digoxin concentrations are clinically useless after Digibind® administration
59
What are the signs/symptoms of toxicity of CCBs?
* Hyperglycemia
* Metabolic acidosis
* Pulmonary edema
* Ileus (SR)
* Hypotension
* Bradycardia
* Arrhythmias
* Cardiogenic shock
* CNS depression
60
What are the signs/symptoms of beta blocker toxicity?
* Hypotension
* Hypoglycemia
* Bradycardia
* Bronchospasms
* Arrhythmias
* Cardiogenic shock
* CNS depression
61
What is the general management for CCB and BB toxicities?
* ABC management
* Monitor vital signs and ECG changes (arrhythmias, bradycardia)
* Administer activated charcoal (depending on dosage form and time of presentation)
62
What are potential antidotes for CCB and BB toxicity?
atropine, calcium, vasopressor therapy, glucagon, high dose insulin therapy, lipid emulsion therapy
63
What is the MOA of atropine? What is it more effective in?
Blocks parasympathetic activity to increase heart rate
usually not effective in CCB and BB overdoses
64
What is the MOA of calcium? What is it more effective in?
Opens calcium channels and promotes release of calcium from sarcoplasmic reticulum resulting in myocardial contractility
More effective in CCB overdose vs. BB overdose
65
What is the MOA of vasopressor therapy?
Binds beta receptors not occupied by BB as well as Gs receptors to eventually stimulate cAMP and calcium release to improve contractility
66
What to use for vasodilatory shock?
norepinephrine
67
What to use for cardiogenic shock?
epinephrine
68
What is the MOA of glucagon?
Stimulates contractility by bypassing beta receptors and binding to Gs receptors to activate conversion of ATP to cAMP
69
What might you have to premedicate with when giving glucagon?
May need to pre-medicate with ondansetron and add PRN regimen due to nausea/vomiting with glucagon
70
What is the MOA of high dose insulin therapy?
Increased inotropy and increased intracellular glucose transport
71
What is monitoring for high dose insulin therapy?
– Improved contractility within 15 to 60 minutes
– Goal glucose: 100 to 250 mg/dL
– Serum electrolytes every 1 to 2 hours (glucose, potassium)
72
What is the MOA of lipid emulsion therapy?
Limits bioavailability of lipophilic medication by creating a “lipid sink”
73
What is the maximum total dose of lipid emulsion therapy?
Maximum = 10 mL/kg total dose
74
Toxicology tidbits: atropine
Not likely to be effective in either CCB or BB overdoses
75
Toxicology tidbits: calcium
*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
76
Toxicology tidbits: vasopressor therapy
Should utilize high doses to overcome beta receptor blockade
77
Toxicology tidbits: glucagon
May need to pre-medicate with ondansetron and add PRN regimen due to nausea/vomiting with glucagon
78
Toxicology tidbits: high dose insulin therapy
Communicate with healthcare providers to address patient safety
79
Toxicology tidbits: lipid emulsion therapy
*Depending on infusion pump and dose, may need multiple pumps to administer therapy
*Total dose maximum: 10 mL/kg
80
What is the use of iron in clinical practice?
* Most commonly used for the treatment of iron deficiency anemia
* Component of prenatal vitamins and children’s vitamins
81
At what dose can iron toxicology occur?
* 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 tissue
– 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
82
What is the first stage of iron toxicity?
* 0.5 to 2 hours post ingestion
* GI upset, abdominal pain, hematemesis, hematochezia
83
What is the second stage of iron toxicity?
* 6 to 24 hours post ingestion
* Latent phase resembling recovery; continue to monitor
84
What is the third stage of iron toxicity?
* 2 to 24 hours post phase 1
* Shock stage (acidosis, hypotension, hypovolemia, poor cardiac output)
85
What is the fourth stage of iron toxicity?
* 48 to 96 hours post ingestion
* Hepatoxicity
86
What is the fifth stage of iron toxicity?
* Days to weeks post ingestion
* GI scarring, obstructions, strictures
87
What is the general management of iron toxicity?
* ABC management
* Monitor vital signs
* Fluid hydration
* Serum iron concentration 4 hours post ingestion
* Activated charcoal is not effective
* KUB (kidneys, ureter, and bladder) scan
* Whole bowel irrigation
* Consider administration of deferoxamine for chelation
88
What is whole bowel irrigation for iron toxicity?
polyethylene glycol
* Procedure usually takes 4 to 6 hours
* Patient should remain seated on a bedside toilet
* Continue until presence of clear rectal effluent
89
What is the antidote for iron toxicity? What is the MOA?
Deferoxamine (Desferal®)
Mechanism of action: Chelates iron and enhances renal elimination
90
What are the indications for deferoxamine?
* Metabolic acidosis or other signs of shock
* Clinical deterioration despite IV fluid administration
* Presence of iron tablets on KUB
* Serum iron concentration > 500 mcg/mL
91
What is the dosing for deferoxamine?
* Start at 15 mg/kg/hour
– May increase to 45 mg/kg/hour for patients with severe poisoning
– Decrease rate if patient experiences hypotension
May titrate down based on resolution of symptoms and/or absence of vin rose urine
