Theophylline toxicity: Difference between revisions

No edit summary
 
(10 intermediate revisions by 3 users not shown)
Line 1: Line 1:
''See [[theophylline]] for general drug information''
''See [[theophylline]] for general drug information.''
==Background==
==Background==
*Still used in patients with debilitating brochospastic disease
*Primarily used as a bronchodilator, however rarely used now due to better available options
*Studied for treatment of [[Acute Mountain Sickness]] and [[Contrast-Induced Nephropathy]]
*Also studied for treatment of [[Acute Mountain Sickness]] and [[Contrast-Induced Nephropathy]]
*PO in elixir, extended release, or controlled release forms but absorption erratic
*PO available as elixer and capsule (12 or 24-hour extended release)
*IV as aminophylline
*IV as aminophylline (shorter acting than PO)
*Adenosine antagonism, Increase catecholamines, and Phosphodiesterase inhibition
*Mechanism of action<ref name="Fisher">Fisher, J., & Graudins, A. (2015). Intermittent haemodialysis and sustained low-efficiency dialysis (SLED) for acute theophylline toxicity. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 11(3), 359-63.</ref>:
**Release of endogenous catecholamines → β2 agonism → bronchodilation
**PDE inhibition → increases cAMP
**Adenosine antagonist


==Clinical Features==
==Clinical Features==
*Neurologic
**Tremor
**Agitation
**[[Seizure]]
*Cardiovascular
*Cardiovascular
**[[Sinus Tachycardia]]
**[[Sinus Tachycardia]]
**Atrial/Ventricular [[arrhythmias]]
**Atrial/Ventricular [[arrhythmias]]
**[[Hypotension]]
**[[Hypotension]] (due to β2-mediated vasodilation)
*Metabolic
*Metabolic
**[[Hypokalemia]]
**[[Hypokalemia]]
**[[Metabolic Acidosis]]
**[[Metabolic Acidosis]]
**[[Hyperthermia]]
**[[Hyperthermia]]
**[[Rhabdomyolysis]]
**[[Hyperglycemia]]
**[[Hyperglycemia]]
*Neurologic
**Tremor
**Agitation
**[[Seizure]]
*GI
*GI
**[[Nausea/Vomiting]]
**[[Nausea/Vomiting]]


==Differential Diagnosis==
==Differential Diagnosis==
*[[Beta-2 agonist]] toxicity
*[[Sympathomimetic toxicity]]
*[[Iron toxicity]]
*[[Salicylate toxicity]]


==Evaluation==
==Evaluation==
*Theophylline level<ref name="Aggelopoulou">Aggelopoulou, E., Tzortzis, S., Tsiourantani, F., Agrios, I., & Lazaridis, K. (2018). Atrial Fibrillation and Shock: Unmasking Theophylline Toxicity. Medical principles and practice : international journal of the Kuwait University, Health Science Centre, 27(4), 387-391.</ref>
**10–20 μg/mL - Therapeutic
**20-80 μg/mL - Toxic level
**80-100 μg/mL - Severe toxicity or death
*[[ECG]]
*[[ECG]]
*Chem
*Metabolic panel
*Lactic acid level
*CK
*CK
*Theophylline level
*Evaluate for co-ingestion


==Management==
==Management==
*Supportive care is the mainstay of treatment
*Cardiovascular
**Norepinephrine (alpha-agonist) for hypotension resistant to IVF
**Refractory hypotension may respond to non-selective beta-blockers<ref name="Fisher" />
**Beta-blockers (esmolol preferred due to short half-life) for tachydysrhythmias
*GI decontamination ([[Multidose Activated Charcoal]], [[Whole Bowel Irrigation]])
*GI decontamination ([[Multidose Activated Charcoal]], [[Whole Bowel Irrigation]])
**Considered in life-threatening overdose
**Consider in recent severe overdose
***contraindications: unsecured airway, [[nausea]], [[vomiting]], ileus, [[Bowel Obstruction]], or need for emergent endoscopy
**Contraindications: unsecured airway, [[nausea]]/[[vomiting]], ileus, [[Bowel Obstruction]], or need for emergent endoscopy
*[[Seizures]]
*[[Seizures]]
**[[Lorazepam]] (Ativan) 1st line
**[[Lorazepam]] (Ativan) 1st line
**Phenobarbital if [[lorazepam]] ineffective
**Phenobarbital if [[lorazepam]] ineffective
**Phenytoin (Dilantin) contraindicated as increases seizure in animal studies
**Phenytoin (Dilantin) contraindicated as increases seizure in animal studies
*Cardiovascular
*Dialysis or plasmapheresis
**[[IV Fluids]] for [[hypotension]]
**Indicated in [[seizures]], severe [[arrhythmias]], hypotension, serum level >90 μg/mL (>40 μg/mL in chronic ingestion)
**Beta blockers for [[tachyarrhymias]]
***Controversial, involve a toxicologist
*Dialysis
**Indicated in [[seizures]], severe [[arrhythmias]]
**Theophylline level >90mcg/ml in acute ingestion
**Theophylline level >40mcg/ml in chronic ingestion
*Supportive care
**Cardiac monitoring
**Ondansetron (Zofran) for antiemetic
**EEG for sedated and paralyzed patients


==Disposition==
==Disposition==
===Immediate release===
*Almost all patients will require admission
*Home after 6 hours if:
*Can consider discharge with close followup (in conjunction with toxicology) if unintentional overdose, asymptomatic, and normal vital signs
**nontoxic
**asymptomatic
**and, normal vital sign
 
===Sustained release===
*Home after 12 hours if:
**nontoxic
**asymptomatic
**and, normal vital sign


==See Also==
==See Also==
Line 71: Line 68:


==External Links==
==External Links==


==References==
==References==
<references/>


[[Category:Toxicology]]
[[Category:Toxicology]]

Latest revision as of 23:51, 15 November 2018

See theophylline for general drug information.

Background

  • Primarily used as a bronchodilator, however rarely used now due to better available options
  • Also studied for treatment of Acute Mountain Sickness and Contrast-Induced Nephropathy
  • PO available as elixer and capsule (12 or 24-hour extended release)
  • IV as aminophylline (shorter acting than PO)
  • Mechanism of action[1]:
    • Release of endogenous catecholamines → β2 agonism → bronchodilation
    • PDE inhibition → increases cAMP
    • Adenosine antagonist

Clinical Features

Differential Diagnosis

Evaluation

  • Theophylline level[2]
    • 10–20 μg/mL - Therapeutic
    • 20-80 μg/mL - Toxic level
    • 80-100 μg/mL - Severe toxicity or death
  • ECG
  • Metabolic panel
  • Lactic acid level
  • CK
  • Evaluate for co-ingestion

Management

  • Supportive care is the mainstay of treatment
  • Cardiovascular
    • Norepinephrine (alpha-agonist) for hypotension resistant to IVF
    • Refractory hypotension may respond to non-selective beta-blockers[1]
    • Beta-blockers (esmolol preferred due to short half-life) for tachydysrhythmias
  • GI decontamination (Multidose Activated Charcoal, Whole Bowel Irrigation)
  • Seizures
    • Lorazepam (Ativan) 1st line
    • Phenobarbital if lorazepam ineffective
    • Phenytoin (Dilantin) contraindicated as increases seizure in animal studies
  • Dialysis or plasmapheresis
    • Indicated in seizures, severe arrhythmias, hypotension, serum level >90 μg/mL (>40 μg/mL in chronic ingestion)

Disposition

  • Almost all patients will require admission
  • Can consider discharge with close followup (in conjunction with toxicology) if unintentional overdose, asymptomatic, and normal vital signs

See Also

External Links

References

  1. 1.0 1.1 Fisher, J., & Graudins, A. (2015). Intermittent haemodialysis and sustained low-efficiency dialysis (SLED) for acute theophylline toxicity. Journal of medical toxicology : official journal of the American College of Medical Toxicology, 11(3), 359-63.
  2. Aggelopoulou, E., Tzortzis, S., Tsiourantani, F., Agrios, I., & Lazaridis, K. (2018). Atrial Fibrillation and Shock: Unmasking Theophylline Toxicity. Medical principles and practice : international journal of the Kuwait University, Health Science Centre, 27(4), 387-391.