2. 1. Which of the following poisoningantidote therapeutic pairings is
correct?
A.Anticholinergic-atropine
A.Beta-blocker- octreotide
A.Calcium-channel blocker-insulin
A.Digoxin-Calcium
3. 2. A 70 year-old patient with a history of CHF on digoxin
presents with weakness. Which is correct with regard to
her EKG?
A. EKG findings suggest the emergent need for
digiFAB
B. EKG findings are most likely due to ischemia
C. EKG findings are expected with therapeutic
digoxin levels.
D. EKG findings are diagnostic of chronic vs. acute
digoxin toxicity
4. 3. A 29 year old patient is brought in to the ED
by EMS in full cardiac arrest. The medics found
an empty bottle of digoxin next to his bed.
What is the most appropriate initial dose of
DigiFab for this patient?
A. 2 Vials
B. 4-6 Vials
C. 10 Vials
D. 20 Vials
E. It needs to be calculated
based on the digoxin level.
5. 4. Which of the following is correct
regarding Beta Blocker overdose?
A. Beta blocker overdose universally causes
AV block.
B. Seizures and obtundation are seen more
often with propanolol compared to
metroprolol.
C. Octreotide is an important component of
treatment
D. Unlike calcium channel blocker toxicity,
high-dose insulin/glucose is not effective for
beta-blocker toxicity.
6. 5. High dose insulin treatment in
beta-blocker overdose increases
cardiac output primarily by increasing
heart rate.
• A. True
• B. False
7. 6. Which is correct regarding the EKG?
• A. This EKG shows a common finding in acute digoxin
toxicity.
• B. Salvage treatment should include administering of
intravenous lipid emulsion (ILE).
• C. This EKG is highly suggestive of Class I sodium channel
blockade (TCA, beta blocker (sotalol)
• D. This EKG is diagnostic for Digoxin Toxicity
8. 7. Which statement is not correct with regard
to the theoretical mechanism-of-action of
intravenous lipid emulsion (ILE) therapy for
beta blocker overdose?
A. Directly activates cardiac calcium
channels.
B. Acts as a “sink” for lipid-soluble beta
blockers
C. Provides a substrate for cardiac myocytes.
D. Activates Adenyl cyclase by a C-AMP
process.
E. It would be appropriate to use in a massive
propanolol overdose.
9. 8. Which calcium channel blocker has
the highest fatality rate after
overdose?
•
•
•
•
•
A. Diltiazem
B. Verapamil
C. Nifedipine
D. Nicardipine
E. Bepridil
10. 9. Which is correct regarding the clinical
endpoint for atropine administration in
Organophosphate toxicity?
A. Pupillary dilatation @ 10mm is the best
endpoint.
B. Heart rates exceeding 140 are a relative
contraindication to continued atropine
administration.
C. Drying of airway secretions is always the best
clinical endpoint.
D. Total bolus dosing should never exceed 200 mg .
11. 10. Which is true with regard to
intubation of a patient with a significant
organophosphate exposure?
• A. Succinylcholine in OGP is associated with
malignant hyperthermia.
• B. Succinylcholine will cause a worsening of
airway secretion production.
• C. Succinylcholine is contraindicated in OGP.
• D. Succinylcholine’s activity lasts longer than
that of rocuronium.
• E. There is little risk of exposure to ED staff
during airway management.
13. 1. Which of the following
poisoning-antidote therapeutic
pairings is correct?
A.Anticholinergic-atropine
A.Beta-blocker- octreotide
A.Calcium-channel blocker-insulin
A.Digoxin-Calcium
14. 1. Which of the following
poisoning-antidote therapeutic
pairings is correct?
A.Anticholinergic-atropine
A.Beta-blocker- octreotide
A.Calcium-channel blocker-insulin
A.Digoxin-Calcium
17. Digoxin Toxicity
• Derived from Digitalis lanata (Foxglove plant)
• Drug looking for an indication
– 1797
• Most common cause of preventable
iatrogenic cardiac arrests
19. Pharmacologic Effects
• Inotrope
– Increased contractility due to increase
intracellular calcium concentrations
• Parasympathomimetic
– Decreased AV Conduction
– Due to increased vagal efferent activity
– Slowed ventricular rate in afib
20. Digoxin at Toxic levels
• Paralysis of Na/K ATPase
– Hyperkalemia
• SA Nodal blockade
• AV nodal blockade
• Increased sensitivity of SA node to
catecholamines
21. Digoxin effects on Pukinje fibers
• Decreased resting potential (slowed phase 0)
• Decreased action potential duration
– Increased sensitivity to electrical stimuli
• Enhanced automaticity (increased phase 4
repolarization)
Most common manifestation of
Digoxin toxicity= Increased PVC’s
24. Digoxin Toxicity
• Elimination half-life
– Digoxin=36 hours; multi-dose charcoal not
effective
– Digitoxin=7 days; multi-dose charcoal very
effective
• Highly protein bound
– Dialysis is not effective
25. 2. A 70 year-old patient with a history of CHF on digoxin
presents with weakness. Which is correct with regard to
her EKG?
A. EKG findings suggest the emergent need for
digiFAB
B. EKG findings are most likely due to ischemia
C. EKG findings are expected with therapeutic
digoxin levels.
D. EKG findings are diagnostic of chronic vs.
acute digoxin toxicity
26. 2. A 70 year-old patient with a history of CHF on digoxin
presents with weakness. Which is correct with regard to
her EKG?
A. EKG findings suggest the emergent need for
digiFAB
B. EKG findings are most likely due to ischemia
C. EKG findings are expected with therapeutic
digoxin levels.
D. EKG findings are diagnostic of chronic vs.
acute digoxin toxicity
27.
28. EKG - Digoxin
• Causes increased automaticity with
conduction block (PAT with block)
• Therapeutic levels may cause
– T wave depression
– ST down sloping (Salvador Dali moustache)
– QT shortened
• Toxic levels
– PVCs (most common dysrhythmia)
– Sinus / AV node blocks
– AV dissociation
– SVT (especially with blocks)
– Sinus bradycardia
32. Clinical Manifestations
• Acute Toxicity:
–
–
–
–
GI: Nausea and vomiting
CNS: Headache, dizziness, confusion, coma
Cardiac: bradyarrhythmias SVT with block
Electrolytes- potassium elevated
• Chronic Toxicity
– Hx: elderly patients taking diuretics
– GI: nausea and vomiting
– Cardiac: Almost any arrhythmia, Ventricular are
common.
– Potassium normal or low
33. Elderly patient with altered mental
status and cardiac arrhythmia
• Think Digoxin toxicity
34.
35.
36. Putting it all together
http://manicgrandiosity.blogspot.com
37. NB! Indications for Fab Fragments
• Ventricular dysrhythmias (beyond PVC’s)
• Hemodynamically significant bradycardia
unresponsive to atropine
• Potassium >5.0
• Worsening rhythm disturbances/rapidly
rising K+
38. 3. A 29 year old patient is brought in to the ED
by EMS in full cardiac arrest. The medics found
an empty bottle of digoxin next to his bed.
What is the most appropriate initial dose of
DigiFab for this patient?
A. 2 Vials
B. 4-6 Vials
C. 10 Vials
D. 20 Vials
E. It needs to be calculated
based on the digoxin level.
39. 3. A 29 year old patient is brought in to the ED
by EMS in full cardiac arrest. The medics found
an empty bottle of digoxin next to his bed.
What is the most appropriate initial dose of
DigiFab for this patient?
A. 2 Vials
B. 4-6 Vials
C. 10 Vials
D. 20 Vials
E. It needs to be calculated
based on the digoxin level.
40. Calculation of DigiFab dosing
• Step 1: Calculate total body-load (TBL)
– TBL= amt ingested (mg) x 0.80
– TBL= dig level (ng/ml)x 5.6 x wt (kg)
1,000
Step 2: Calculate # vials of DigFab
1 vial=40 mg DigFab
Number of vials= TBL/0.5
44. Summary
• Think of dig toxicity in any patient with GI or
visual disturbances and new onset
dysrhythmia or conduction abnormality
• Use DigFab before pacing or other
antidysrhythmics
• Hyperkalemia best definitively treated with
digfab
45. 4. Which of the following is
correct regarding Beta Blocker
overdose?
A. Beta blocker overdose universally causes
AV block.
B. Seizures and obtundation are seen more
often with propanolol compared to
metroprolol.
C. Octreotide is an important component of
treatment
D. Unlike calcium channel blocker toxicity,
high-dose insulin/glucose is not effective for
beta-blocker toxicity.
46. 4. Which of the following is
correct regarding Beta Blocker
overdose?
A. Beta blocker overdose universally causes
AV block.
B. Seizures and obtundation are seen more
often with propanolol compared to
metroprolol.
C. Octreotide is an important component of
treatment
D. Unlike calcium channel blocker toxicity,
high-dose insulin/glucose is not effective for
beta-blocker toxicity.
47. Beta Blocker toxicity
• Initially used to treat dysrhythmias
• Antihypertensive effects discovered later
• Used for
– SV dysrhythmias
– HTN
– Angina
– Thyrotoxicosis
– Migraine
– Glaucoma
53. NB!
Propanolol
• Non-selective
• Most fatalities
• Lipophilic and readily crosses BB barrier
– Altered mental status
– Seizures
• Hypoglycemia common in children
54. Sotalol
• Class III (K ch) and Class II (beta blockers)
antidysrhythmic
• Torsades de pointes
• Dialyzable (Remember ANTS)
• QT prolongation
– Sotalol
– Acebutolol
56. Glucagon
• Inotropic and chronotropic effects not
dependent on beta receptors
– Stimulates C-AMP
• Helps counteract hypoglycemia
• Dose: 5-10 mg IV bolus (0.1 mg/kg)
– Followed by response dosing (over 1 hour)
– Short half-life (20 minutes)
• Less effective than insulin-glucose
57. 5. High dose insulin treatment in
beta-blocker overdose increases
cardiac output primarily by increasing
Heart rate.
• A. True
• B. False
58. 5. High dose insulin treatment in
beta-blocker overdose increases
cardiac output primarily by increasing
Heart rate.
• A. True
• B. False
59. 5. High dose insulin treatment in
beta-blocker overdose increases
cardiac output primarily by increasing
Heart rate.
• A. True
• B. False
60. High Dose Insulin-Glucose
• HDI is a potent inotrope
– Optimizing of the use of carbohydrates
– And modulation of IC calcium
• NB! Improve in CO due more to increase in
stroke volume vs. HR
• 1U/kg Bolus
• 1 -10 U/kg/hr drip
• Preceded with amp D50 and followed by D10
or D25 drip.
61. Adjuncts for specific agents
• Sodium Bicarb
– Use for QRS widening
• Propanolol
• Sotalol
• Magnesium
– Prolonged QT interval
• Sotalol
• Acebutelol
62. 6. Which is correct regarding the EKG?
• A. This EKG shows a common finding in acute digoxin
toxicity.
• B. Salvage treatment should include administering of
intravenous lipid emulsion (ILE).
• C. This EKG is highly suggestive of Class I sodium channel
blockade (TCA, beta blocker (sotalol)
• D. This EKG is diagnostic for Digoxin Toxicity
63. 6. Which is correct regarding the EKG?
• A. This EKG shows a common finding in acute digoxin
toxicity.
• B. Salvage treatment should include administering of
intravenous lipid emulsion (ILE).
• C. This EKG is highly suggestive of Class I sodium channel
blockade (TCA, beta blocker (sotalol)
• D. This EKG is diagnostic for Digoxin Toxicity
65. 7. Which statement is not correct with regard
to the theoretical mechanism-of-action of
intravenous lipid emulsion (ILE) therapy for
beta blocker overdose?
A. Directly activates cardiac calcium
channels.
B. Acts as a “sink” for lipid-soluble beta
blockers
C. Provides a substrate for cardiac myocytes.
D. Activates Adenyl cyclase by a C-AMP
process.
E. It would be appropriate to use in a massive
propanolol overdose.
66. 7. Which statement is not correct with regard
to the theoretical mechanism-of-action of
intravenous lipid emulsion (ILE) therapy for
beta blocker overdose?
A. Directly activates cardiac calcium
channels.
B. Acts as a “sink” for lipid-soluble beta
blockers
C. Provides a substrate for cardiac myocytes.
D. Activates Adenyl cyclase by a C-AMP
process.
E. It would be appropriate to use in a massive
propanolol overdose.
67. Intravenous Fat emulsion
• Lipid sink
• Optimization of cardiac metabolism
– Provides substrate for myocytes
– Free fatty acids
• Direct activation of cardiac calcium channels
• Dose: 1.5 ml/kg 20% solution over 3 minutes,
then drip at 0.25ml/kg/min
69. Calcium channel blockers
• Rapidly absorbed
• Peak effect earliest with nifedipine
• Highly protein bound not conducive to
dialysis
70. 8. Which calcium channel blocker has
the highest fatality rate after
overdose?
•
•
•
•
•
A. Diltiazem
B. Verapamil
C. Nifedipine
D. Nicardipine
E. Bepridil
71. 8. Which calcium channel blocker has
the highest fatality rate after
overdose?
•
•
•
•
•
A. Diltiazem
B. Verapamil
C. Nifedipine
D. Nicardipine
E. Bepridil
72. Pathophysiology
• Block slow L-type calcium channels
– Coronary and peripheral vasodilation
– Reduction of contractility
– Slow AV conduction
• NB! Verapamil
– Deadliest, severe vasodilation and myocardial
depression
73. Calcium channel blocker toxicity
•
•
•
•
Hypotension
Bradycardia
All degrees of AV block
Nifedipine (Dihydropyridines)
– Reflex tachycardia
•
•
•
•
NB!
No QRS widening is seen.
Pulmonary edema
Lethargy, confusion, seizures
Metabolic: hyperglycemia, lactic acidosis, mild
hyperkalemia.
75. Ca Channel blocker toxitiy
Pediatric PEARLS
•
•
•
•
Seizures are more common
Death is rare
Refractory shock can be treated with IABP
Verapamil IV is contraindicated for SVT in
infants.
76. Know these two
• Nifedipine
– Single pill can kill a child
– Shortest onset
– Has Reflex tachycardia
• Verapamil
– Highest fatality rates
77. Nitrates/Nitrites
• Know
– Nitroprusside (renal failure patients)
– PDI contraindication
• Viagra et al
– Found in rural well water
– Patients with G-6PD deficiency= hemolysis
• Methemoglobinemia
– Treatment methylene blue 1-2 mg IV over 5
minutes
78. 9. Which is correct regarding the clinical
endpoint for atropine administration in
Organophosphate toxicity?
A. Pupillary dilatation @ 10mm is the best
endpoint.
B. Heart rates exceeding 140 are a relative
contraindication to continued atropine
administration.
C. Drying of airway secretions is always the best
clinical endpoint.
D. Total bolus dosing should never exceed 200 mg .
79. 9. Which is correct regarding the clinical
endpoint for atropine administration in
Organophosphate toxicity?
A. Pupillary dilatation @ 10mm is the best
endpoint.
B. Heart rates exceeding 140 are a relative
contraindication to continued atropine
administration.
C. Drying of airway secretions is always the best
clinical endpoint.
D. Total bolus dosing should never exceed 200 mg .
82. Muscarinic vs. Nicotinic
• Muscarinic
–
–
–
–
Not an ion channel
G-protein-coupled receptor
Activate ion channels via second messenger system.
Blocked by atropine
• Nicotinic
–
–
–
–
Ion gated channel
Post-synaptic neuromuscular junction
Ach causes Na entry and leads to depolorization.
Stimulation (tremor, seizures, temp, etc)
85. Cholinesterase inhibitors can result in
:
• Tachycardia, bradyardia
• Hypertension or hypotension
• Mydriasis, miosis
86. OGP Aging
• Irreversible conformational change when
OGP bound to cholinesterase enzyme
• Becomes irreversible
• Varies with agent
• Importance of 2PAM
87. OGP Aging
• Irreversible conformational change when
OGP bound to cholinesterase enzyme
• Becomes irreversible
• Varies with agent
• Importance of 2-PAM (give regardless of time
from ingestion)
88. Diagnosis
• Clinical syndrome
• Cholinesterase levels
– RBC
– Plasma-these decrease first
• RBC cholinesterase levels correlate best with
ACH activity at nerve terminal.
• RBC cholinesterase recovers slowly
89. 10. Which is true with regard to
intubation of a patient with a significant
organophosphate exposure?
• A. Succinylcholine in OGP is associated with
malignant hyperthermia.
• B. Succinylcholine will cause a worsening of
airway secretion production.
• C. Succinylcholine is contraindicated in OGP.
• D. Succinylcholine’s activity lasts longer than
that of rocuronium.
• E. There is little risk of exposure to ED staff
during airway management.
90. 10. Which is true with regard to
intubation of a patient with a significant
organophosphate exposure?
• A. Succinylcholine in OGP is associated with
malignant hyperthermia.
• B. Succinylcholine will cause a worsening of
airway secretion production.
• C. Succinylcholine is contraindicated in OGP.
• D. Succinylcholine’s activity lasts longer than
that of rocuronium.
• E. There is little risk of exposure to ED staff
during airway management.
91. Management
• 1. Decontamination
– Remove clothes, soap and water
• 2. Supportive Care
– Airway management (rocuronium better choice)
• 3. Reversal of ACH excess at muscarinic sites
• 4. reversal of toxin binding at active sites on
the ACH molecule
92. Treatment
• Atropine 1-2 mg IV and double dose q 5
minutes until secretions dry
• Patients may need 200-300 mg
• Follow with continuous infusion:
• 5-100 mg/hr
93. 2-PAM
• Pralidoxime
• Regenerates ACHesterase complex and
restores ACHesterase activity at nicotinic and
muscarinic sites.
• Dose: 1-2 g IV over 30 minutes repeat q 4
hours
• Benzodiazepines for seizures
94. Carbamates
•
•
•
•
Differentiated from OGP by short half-life
Reversible inhibition
Lasts ~48 hours
Symptoms
– Twitching, hyperdynamic, rhabdo, altered MS
• Treatment
– Decontamination
– Cooling measures
– Benzos
96. Summary
•
•
•
•
Decon all!
Patients die from airway compromise
V/S and pupil findings variable
2-PAM should be given if you are giving
atropine
• Rapid cooling and glucose the most
important therapies for phenol toxicity
Editor's Notes
Cardiac myocytes, as well as many other cells, have a Na+-Ca++ exchanger (not an active energy-requiring pump) that is essential for maintaining sodium and calcium homeostasis. The exact mechanism by which this exchanger works is unclear. It is known that calcium and sodium can move in either direction across the sarcolemma. Furthermore, three sodium ions are exchanged for each calcium, therefore an electrogenic potential is generated by this exchanger. The direction of movement of these ions (either inward or outward) depends upon the membrane potential and the chemical gradient for the ions. We also know that an increase in intracellular sodium concentration competes for calcium through this exchange mechanism leading to an increase in intracellular calcium concentration. As intracellular sodium increases, the concentration gradient driving sodium into the cell across the exchanger is reduced, thereby reducing the activity of the exchanger, which decreases the movement of calcium out of the cell. Therefore, mechanisms that lead to an accumulation of intracellular sodium cause a subsequent accumulation of intracellular calcium because of decreased exchange pump activity.By inhibiting the Na+/K+-ATPase, cardiac glycosides cause intracellular sodium concentration to increase. This then leads to an accumulation of intracellular calcium via the Na+-Ca++ exchange system. In the heart, increased intracellular calcium causes more calcium to be released by the sarcoplasmic reticulum, thereby making more calcium available to bind to troponin-C, which increases contractility (inotropy). Inhibition of the Na+/K+-ATPase in vascular smooth muscle causes depolarization, which causes smooth muscle contraction and vasoconstriction.By mechanisms that are not fully understood, digitalis compounds also increase vagal efferent activity to the heart. This parasympathomimetic action of digitalis reduces sinoatrial firing rate (decreases heart rate; negative chronotropy) and reduces conduction velocity of electrical impulses through the atrioventricular node (negative dromotropy).
Note cardioselectivity is lost in overdose. Cardioselectivity portends a lower mortality rate compared to propanolol
