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)