Pharm - Salicylate and TCA OD Tx Flashcards
Clinical features of acute salicylate OD
- onset of sx: 1-2 hrs after acute ingestion
- vital signs: increased RR and depth, increased body temperature, tachycardia
- tinnitus: very common even at therapeutic concentrations
- n/v
- acid base abnormalities
- altered mental status: agitation, confusion, restlessness, seizures
- pulmonary edema
pathophysiology of the vital sign changes in a salicylate overdose
Increased repiratory rate and depth
• Salicylates stimulate respiratory center in the medulla
• Pts become tachypnic and hyperventilate
Increased body temp
• Salicylates uncouple mitochondrial oxidative phosphorylation
• Heat generated – body temp increases
Increased HR – tachycardia
• May be d/t agitation, distress, hypovolemia
pathophysiology of n/v in a salicylate overdose
o Direct irritation of the gastric mucosa
o Decreased production of prostaglandins
o Direct stimulation of the chemoreceptor trigger zone in the medulla
o Vomiting can be severe and lead to volume loss
o Hemorrhagic gastritis, though uncommon, can also occur
pathophysiology of acid-base abnormality in a salicylate overdose
o Increased respiration can lead to decrease in PaCO2 leading to a respiratory alkalosis
o Anion gap metabolic acidosis occurs d/t accumulation of organic acids
pathophysiology of altered mental status in a salicylate overdose
- Direct toxicity to the CNS:
• Salicylic acid is a weak acid
• Exists as charged and uncharged forms
• Uncharged form can enter the CNS
• The acidosis increases the uncharged form - Neuroglycopenia: salicylates lower CNS glucose concentrations (can occur even if serum glucose concentration is nl)
- Cerebral edema
early symptoms associated with a salicylate overdose
i. Tinnitus
ii. Vertigo
iii. N/v/d
late symptoms associated with a salicylate overdose
i. Altered mental status
ii. Increased temp
iii. Pulmonary edema
iv. Coma
serum salicylate concentration associated with toxicity
- Values above 40 mg/dL associated w/ toxicity
- Measure every 2 hrs until 2 consecutive levels show a decline from the peak concentration also monitoring other sx and RR
- Levels above 100 mg/dL are an absolute indication for hemodialysis
lab values and imaging studies that should be obtained in a salicylate overdose
- creatinine
- K
- coag studies
- lactate
- anion gap
- imaging: CXR; head CT
Creatinine in salicylate OD
- ASA is eliminated by kidneys so check to assess rnal statue
- Renal failure is an indication for hemodialysis
K in salicylate OD
- If hypokalemic, tx aggressively
- In metabolic acidosis, K moves from intra to extracellular space and is removed by the kidneys so: a low serum K in light of a metabolic acidosis represents a significant reduction in total body K
Coag studies in salicylate OD
- Large salicylate OD can cause hepatoxicity, interfere w/ vit. K metabolism and cause a coagulopathy
- May see increase in PT
- Clinically significant bleeding is unusual
lactate in salicylate OD
- Uncoupling of oxidative metabolism lead to increase in anaerobic metabolism
- Lactate accumulates
anion gap in salicylate OD
usu elevated
imaging in salicylate OD
- CXR – pulmonary edema
- Head CT – altered mental status not contributable to noncerebral causes
role of activated charcoal in a salicylate overdose
GI decontamination w/ activated charcoal – some experts recommend multi-dose activated charcoal for management after ABCs
State the reasons for administering supplemental glucose in a salicylate overdose
- Administer supplemental glucose if patient has altered mental status even if serum glucose is WNL
- Salicylates decrease glucose concentrations in the brain
State the reasons for alkalinizing the serum in a salicylate overdose
- Salicylic acid (HSal) is a weak acid
- Increasing the serum pH by adding sodium bicarbonate moves the equation to the left
- Higher serum pH will cause plasma levels to fall which will cause [ HSal] to fall in the CNS as salicylate moves from brain to plasma. This will decrease the toxic effects of salicylate on the brain
H+ + Sal- HSal
State the reasons for alkalinizing the urine in a salicylate overdose
- Moves the equation to the left
- Urinary HSal is converted to Sal- preventing back diffusion of HSal, trapping it in the urine and enhancing elimination
indications for hemodialysis in a salicylate overdose
- Altered mental status
- Pulmonary edema
- c. Cerebral edema
- Serum creatinine 2 mg/dL or GFR < 45 mL/min
- Inability to administer sodium bicarb
- Markedly elevated serum salicylate levels (depend on renal function) > 100 but can use dialysis at lower levels
- Severe academia pH < or = to 7.2
- Pt continues to deteriorate clinically despite supportive care
pharmacologic effects of tricyclic antidepressants in an overdose
- Blockage of cardiac fast sodium channels
- Antagonism of:
1. Central and peripheral muscarinic Ach receptors
2. Alpha-1 adrenergic receptors
3. H1 receptors
4. CNS GABA A receptors - And therefore:
1. Delayed absorption d/t anticholinergic effects
2. Bioavailability may be increased
3. Decreased rate of metabolism
4. Increased amount of free drug
5. Delayed excretion
Identify the cardiac toxicity associated with a TCA overdose
- Conduction abnormalities d/t inhibition of fast Na channels in the His-Purkinje system and myocardium
- Conduction velocity decreases, duration of repolarization increases, and absolute refractory period increases
- Ventricular tachycardia and v. fib – more common in severe poisonings and when there is extreme QRS prolongation
- Hypotension: decreased contractility and peripheral hypotension d/t blockade of alpha 1 adrenergic receptor; can be refractory and a cause of mortality
- Sinus tachycardia: anticholinergic effect and compensatory mechanism d/t peripheral hypotension
Identify the CNS toxicity associated with a TCA overdose
i. Decreased level of consciousness (antihistamine properties)
ii. Delirium (anticholinergic)
iii. Seizures (GABA-A antagonism) – can be associated w/ arrhythmias and/or hypotension
Identify the anticholinergic effects associated with a TCA overdose
i. Elevated temp
ii. Flushing
iii. Dilated pupils
iv. Delirium
v. Intestinal ileum
vi. Urinary retention
Identify EKG changes associated with cardiotoxicity due to TCA overdose
- Arrhythmias are common and can develop quickly
- Signs of cardiotoxicity:
QRS prolongation > 100 ms
Most prominent ECG manifestation
Increases risk of seizures and/or ventricular arrhythmia - Indication for bicarb treatment
1. Abnl morphology of the QRS (deep, slurred S waves in lead I and AVL): associated w/ an increased risk of seizures and/or ventricular arrhythmia
2. Abnl size and ratio of the R and S wave in lead AVR
indications for sodium bicarbonate in a TCA OD
- Sodium bicarb is the standard initial therapy for hypotension or arrhythmia d/t TCA toxicity
- Indicated in pts w/ TCA poisoning who develop widening of QRS interval > 100 ms or a ventricular arrhythmia
the expected response to sodium bicarb in a TCA overdose
- QRS narrows
- Decrease in R wave
What is used to treated seizure secondary to TCA overdose
-Benzos: IV diazepam or lorazepam
interventions used to treated hypotension refractory to traditional treatments in a TCA overdose
- Vasopressors: indicated when BP doesn’t respond to sodium bicarb. Use IV NE or phenylephrine to counteract alpha adrenergic antagonist effect
- Hypertonic saline (3%): Used when pt has be unresponsive to other interventions to increase blood pressure
