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How long after ingestion do TCA levels reach peak plasma concentrations? Why is absorption prolonged in TCA overdose?
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Peak levels occur 2-4 hours post-ingestion. Due to their anticholinergic side effect of delayed gastric motility, absorption is prolonged in overdose.
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What are the seven major pharmacodynamic effects of TCA's?
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1)Fast sodium channel blockade 2)Alpha-1 receptor blockade 3)Inhibition of norepi. and serotonin reuptake 4)Muscarinic receptor blockade 5)Histamine receptor blockade 6)Potassium efflux blockade 7)Indirect GABA-A antagonism
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What are the first two symptoms of TCA toxicity? How do you treat them?
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The first two symptoms are hypertension and sinus tachycardia. No treatment is necessary at this time.
These are due to the anticholinergic vagolytic effects of TCAs, as well as the increase in circulating catecholamines.
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List the anticholinergic symptoms of TCA toxicity.
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Tachycardia, hyperthermia, mydriasis, anhidrosis, flushed skin, urinary retention, ileus
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List the CNS effects of TCA toxicity.
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Agitation, delirium, myoclonus, clonus, hyper-reflexia, seizures, hyperthermia, sedation, coma
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What are the cardiac complications of TCA toxicity?
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Sinus tachycardia and hypertension initially. This is followed by hypotension and ventricular dysrhytmias.
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What are the classic ecg findings in TCA overdose?
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1)Sinus tachycardia 2)QRS widening (>100 msec) 3)Right axis deviation 4)Right deviation of terminal 40 msec vector in limb leads and prominent R wave in aVR 5)Ventricular bigeminy 6)QTc prolongation 7)PR lengthening 8)Bradydysrhytmias (late and rare)
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What are the indications for use of NaHCO3 in TCA toxicity?
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After beginning volume resuscitation with IV NS, NaHCO3 is indicated if; QRS>100 msec and the patient is symptomatic, or if there is acidemia or dysrhythmia.
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Explain how to dose bicarbonate in TCA toxicity, and what endpoints you use to monitor therapy?
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Begin with NaHCO3 boluses of 1-2 mEq/kg until the QRS narrows or serum pH reaches 7.50-7.55. After reaching your endpoint, you can run a continuous infusion of NaHCO3.
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When should a cholinergic stimulant such as physostigmine be used in the treatment of TCA toxicity?
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NEVER! Can lead to cardiac arrest, seizure and death.
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Other than physostigmine, what other drugs are not recommended as treatments for TCA overdose?
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Beta-blockers and Type Ia and Ic antidysrhythmics are also contraindicated. The antidysrhythmics also block fast sodium channels, which will only worsen the situation.
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A complication of TCA toxicity is seizure. Which of the common drugs used for status epilepticus should not be used in TCA overdose? Why?
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Phenytoin (Dilantin) should not be used, as it may increase both the frequency and length of episodes of ventricular tachycardia. Use benzodiazepines, phenobarbital, or propofol.
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How long should patients with TCA toxicity be monitored if there is good historical evidence of ingestion, but no objective signs and symptoms?
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6 hours. If there are still no major signs of poisoning and bowel sounds are present, you can consult psychiatry and discharge the patient.
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