Antidepressants Toxicology Flashcards
Alterations in the balance/function of neurotransmitters (in depression) include: (3)
- Impaired synthesis of neurotransmitters
- Increased breakdown or metabolism of neurotransmitters
- Increased pump re-uptake of neurotransmitters.
What 3 neurotransmitters are involved in depression?
- Serotonin
- Norepinephrine
- Dopamine
What anatomic brain system is affected in depression?
Limbic system
A ________ in the __________ _______ of these neurotransmitters causes certain types of depression
decrease; functional balance
What are 5 classes of antidepressant drugs?
- SSRI
- SNRI
- TCA
- MAOI
- Atypical antidepressants
With atypical antidepressants, the key neurotransmitter is?
dopamine
What is the MOA of bupropion? (2)
- Inhibits DAT and NET
- Enhances both noradrenergic and dopaminergic neurotransmission via reuptake inhibition of the norepinephrine/noradrenaline and dopamine
Discuss bupropion toxicity (3)
- Structurally similar to amphetamine (ADHD)
- Narrow therapeutic margin
- Associated with seizures and cardiac toxicity
What are the advantages of SSRIs over TCAs and MAOIs? (2)
- Fewer significant adverse effects and less problematic
- Wide therapeutic window
Tmax of SSRIs is?
~4-8 hours
SSRIs are metabolized by?
CYP2D6
What is the Vd and PPB of SSRIs?
- Vd = ~10-40L/kg
- PPB = 80-98%
Why might citalopram and escitalopram be more toxic in overdose?
They are structurally different from other SSRIs
What are the common ADEs of SSRIs? (4)
- Drowsiness
- Tremor
- Nausea
- Vomiting
Infrequent ADEs of SSRIs are? (2)
- CNS depression
- Sinus tachycardia
________ and ___ _______ are rare in SSRI toxicity
Seizures; ECG changes
What are the symptoms of serotonin syndrome? (5)
- Diaphoresis
- Diarrhea
- Hyperthermia
- Mental status changes
- Myoclonus
When does serotonin toxicity occur most frequently?
After use of combinations of serotonergic xenobiotics
What are the 3 lab/diagnostic options for serotonin syndrome?
- ECG in the case of citalopram, escitalopram, SSRI + coingestions
- Neuromuscular findings
- Creatinine kinase (tissue damage)
- Myoglobin for Rhabdomyolysis
- Serum creatine for kidney function and other LFTs - Investigations to rule out other toxicities
The main management option for SSRI toxicity is?
Symptomatic and supportive care
SSRI Toxicity:
How to manage seizure
BZDs
SSRI Toxicity:
How to manage cardiac abnormalities?
Sodium bicarb
SSRI Toxicity:
How to manage TdP?
Magnesium sulfate
SSRI Toxicity:
How to manage serotonin syndrome?
Cyproheptadine (serotonin antagonist)
Yay or nay? SDAC and gastric lavage in SSRI toxicity?
- ?SDAC yay
- Most benefit within 1-2 hours
- May use up to 4 hours - Nay gastric lavage
Yay or nay? MDAC and hemodialysis in SSRI toxicity?
Nay to both
Hemodialysis ineffective due to high PPB and Vd
What are the symptoms of venlafaxine toxicity? (4)
- Seizure
- Tachycardia
- ECG abnormalities
- Serotonin toxicity
Venlafaxine vs. desvenlafaxine, which is safer?
Desvenlafaxine
What is the one TCA med we need to know for this class?
Amitriptyline
The key to successful management of TCA toxicity is? What is the first thing to do
Early identification
- First thing to do is an ECG (and do blood glucose level)
How are TCAs distributed? Know the Vd
Highly lipophilic and widely distributed
- Vd = 10-50L/kg so large
What is the PPB of TCAs?
85-98% (very high)
TCAs good for hemodialysis?
No
What 2 SSRIs does she want us to know?
- Citalopram
- Escitalopram
Which SNRI does she want us to know?
Venlafaxine
Which TCA does she want us to know?
Amitriptyline
Which MAOI does she want us to know?
Isocarboxazid
Dopamine is a ____-____ hormone and is released in cases of ____ _____ or _______
feel-good; drug abuse or smoking
How are SSRIs excreted?
Renally (mostly)
True or False? SNRIs such as venlafaxine are associated with a lower risk of toxicity and mortality in overdose
False - greater risk of significant toxicity and mortality in overdose
TCAs absorbed poorly or well?
Well absorbed
What important gastric effect does amitriptyline have?
Anticholinergic effect on gastric emptying (delay emptying)
How is amitriptyline metabolized?
Multiple CYPs
Poor predictor of outcome in amitriptyline overdose is?
Dose ingested and plasma concentration –> non consensus on toxic concentration
Amitriptyline metabolism is highly variable because?
Genetic polymorphisms in CYP2D6
How rapid are cardiotoxic symptoms in amitriptyline overdose?
Rapid progression - onset often within 2 hours of ingestion
What is the symptom of cardiotoxicity that amitriptyline causes?
QRS prolongation
What are the respiratory signs/symptoms of amitriptyline toxicity? (2)
- Aspiration (protect airways – intubation)
- Acute respiratory distress syndrome (ARDS)
Severity of amitriptyline toxicity is best reflected by ___, not _____ ______
ECG, serum levels
QRS >___ms is cardiotoxic
100
What do we give to manage dysrhythmias caused by amitriptyline?
Sodium bicarb
What is the MOA of sodium bicarb for dysrhythmias? (2)
- Helps overcome Na+ channel blockade
- Alkalinization of arterial blood pH: inhibits binding of TCA to myocardial Na+ channel as drug is not ionised
- If given 12-24h after ECG resolution ➔good call –> redistribution of TCA from tissues into the plasma
If dysrhythmias continue after giving sodium bicarb, what else can be given? (3)
- Lidocaine
- Hypertonic saline
- Magnesium sulfate
What to give for seizures caused by amitriptyline? (2)
- BZDs
- Sodium bicarb may help manage/prevent seizures if QRS complex is shortened
Yay or nay? Gastric lavage and SDAC for amitriptyline decontamination
- Gastric lavage = ?/yes - reasonable in adults with intentional OD - risk of aspiration
- SDAC = yay - also a risk of aspiration though
What is the antidote for amitriptyline toxicity?
Intravenous lipid emulsion (ILE)
