Antidepressants Flashcards
What is the monoamine hypothesis of depression?
Proposes that depression is due to a functional deficit of monoamine neurotransmitters like norepinephrine and serotonin at certain sites in the brain
Name the major classes of antidepressant drugs.
Tricyclic antidepressants (TCA) SSRIs SNRIs NRIs NDRIs MAO inhibitors Atypical antidepressants
What are SSRIs used for?
First-line treatment for depression and anxiety disorders
Name some common SSRIs.
Fluoxetine Fluvoxamine Paroxetine Sertraline Citalopram Escitalopram
What is the therapeutic lag for antidepressants?
2-4 weeks before a measurable therapeutic response is evident
Describe the neurotrophic hypothesis of depression.
Depression results from decreased neurotrophic support leading to neuronal atrophy decreased hippocampal neurogenesis and loss of glia
What is the role of BDNF in depression?
Brain-Derived Neurotrophic Factor (BDNF) is decreased in depression contributing to neuronal atrophy and reduced neurogenesis
List adverse effects common to SSRIs.
GI symptoms headache insomnia anxiety sexual dysfunction increased risk of GI bleeding serotonin syndrome discontinuation syndrome
What is serotonin syndrome?
A potentially life-threatening condition due to excessive serotonin causing symptoms like agitation confusion rapid heart rate and high blood pressure
What is the role of MAO inhibitors in treating depression?
Inhibit monoamine oxidase preventing the breakdown of monoamine neurotransmitters thus increasing their availability
Name some adverse effects of tricyclic antidepressants (TCAs).
Sedation weight gain dry mouth constipation urinary retention blurred vision tachycardia orthostatic hypotension
What is the role of norepinephrine reuptake inhibitors (NRIs)?
Increase norepinephrine levels by inhibiting its reuptake thus enhancing mood
What is the mechanism of action of SNRIs?
Inhibit the reuptake of both serotonin and norepinephrine
What is an important pharmacokinetic consideration for fluoxetine?
Fluoxetine has the longest half-life among SSRIs and must be discontinued 4 weeks before starting an MAOI
What is the role of neuroendocrine interactions in depression?
Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and the role of stress response can contribute to depression
Name some drugs classified as atypical antidepressants.
Bupropion trazodone nefazodone mirtazapine mianserin agomelatine vortioxetine
What is the significance of active metabolites in antidepressants?
Active metabolites can affect the duration of drug action and influence switching from one medication to another
What is the role of glutamate in depression?
The glutamate hypothesis suggests that rapid actions of drugs like ketamine may be due to their effects on glutamate neurotransmission
Name the primary cellular targets for tricyclic antidepressants (TCAs).
Inhibit the reuptake of norepinephrine and serotonin
What is the main mechanism of action for SSRIs?
Selective inhibition of serotonin reuptake
Describe the pharmacokinetics of most SSRIs.
Good absorption significant liver metabolism (CYP450) and variable half-lives
What is a common adverse effect specific to paroxetine?
Increased risk of teratogenic effects (cardiac) in the first trimester of pregnancy
What are the therapeutic uses of SNRIs beyond depression?
Used for generalized anxiety disorder (GAD) panic disorder (PD) social anxiety disorder and chronic pain conditions
Describe the “switch” phenomenon in bipolar disorder treatment with antidepressants.
Antidepressants can induce a switch from a depressed episode to a manic or hypomanic episode in bipolar patients
What is the relationship between dietary sodium and lithium pharmacokinetics?
Alterations in dietary sodium can affect lithium levels as sodium depletion increases lithium reabsorption
How does exercise affect lithium levels?
Exercise can alter sodium levels impacting lithium reabsorption and potentially causing toxicity or subtherapeutic levels
What are the signs of lithium toxicity?
Nausea vomiting diarrhea tremor confusion seizures and potentially coma
Why is lithium contraindicated in patients with renal impairment?
Reduced renal function can lead to lithium accumulation and toxicity
What is the role of bupropion in depression treatment?
Acts as a norepinephrine-dopamine reuptake inhibitor (NDRI) and is also used for smoking cessation
What is the importance of CYP450 interactions in antidepressant pharmacology?
Many antidepressants are metabolized by CYP450 enzymes and drug interactions can affect their levels and efficacy
What is the mechanism of action of monoamine oxidase inhibitors (MAOIs)?
Inhibit the enzyme monoamine oxidase increasing levels of neurotransmitters like serotonin and norepinephrine
What is the role of serotonin in the neurobiology of depression?
Serotonin deficits are associated with mood disorders and enhancing its levels can improve depressive symptoms
What is the importance of neurogenesis in treating depression?
Increased neurogenesis particularly in the hippocampus is thought to correlate with the therapeutic effects of antidepressants
How does fluvoxamine differ from other SSRIs in terms of enzyme inhibition?
Fluvoxamine is a potent inhibitor of CYP3A4
What is the role of psychotropic medication in treating severe depression with suicidal risk?
Medications like ECT are used when rapid response is needed and delay in antidepressant effects is hazardous
Describe the discontinuation syndrome associated with antidepressants.
Symptoms can include flu-like symptoms insomnia nausea imbalance sensory disturbances and hyperarousal
What is the primary use of mirtazapine in depression treatment?
An atypical antidepressant with noradrenergic and specific serotonergic activity
How do MAOIs interact with dietary tyramine?
MAOIs can cause hypertensive crisis when taken with tyramine-rich foods due to increased levels of tyramine
What are the most common adverse effects of lithium?
Tremor hypothyroidism weight gain renal dysfunction and polyuria
What is the clinical use of agomelatine?
Atypical antidepressant that acts as a melatonin receptor agonist and 5-HT2C antagonist
What is the main therapeutic action of tricyclic antidepressants?
Inhibit the reuptake of norepinephrine and serotonin enhancing mood
What is the pharmacological action of vortioxetine?
Atypical antidepressant that modulates serotonin receptor activity and inhibits serotonin reuptake
How does nefazodone differ from trazodone?
Both are atypical antidepressants but nefazodone has a higher risk of hepatotoxicity
What are the effects of antidepressants on anxiety during early treatment?
May increase anxiety agitation and suicidal ideation during the first few weeks
What is the clinical significance of escitalopram?
S-enantiomer of citalopram with improved efficacy and fewer side effects
Describe the cytokine hypothesis of depression.
Proposes that increased levels of pro-inflammatory cytokines contribute to depressive symptoms
How do SNRIs differ from SSRIs in terms of neurotransmitter targets?
SNRIs inhibit the reuptake of both serotonin and norepinephrine while SSRIs are selective for serotonin
What is the role of electroconvulsive therapy (ECT) in depression?
Used for severe depression especially when rapid treatment response is needed or other treatments have failed
What are the most common side effects of tricyclic antidepressants?
Sedation anticholinergic effects orthostatic hypotension and cardiotoxicity
What is the role of St. John’s wort in treating depression?
Herbal antidepressant that may interact with various drugs and has a risk of inducing serotonin syndrome
How is bipolar disorder treated with anticonvulsants?
Anticonvulsants like valproate and lamotrigine are used for mood stabilization and to prevent manic episodes
What are the potential interactions between SSRIs and NSAIDs?
Increased risk of gastrointestinal bleeding
How does serotonin receptor antagonism contribute to antidepressant effects?
Blocking certain serotonin receptors can help alleviate depressive symptoms and improve mood
What is the role of atypical antipsychotics in treating bipolar disorder?
Used for mood stabilization and treatment of acute manic episodes
What are the implications of CYP450 polymorphism in antidepressant therapy?
Genetic variations can lead to differences in drug metabolism and response among individuals
How does ketamine work as a rapid-acting antidepressant?
Acts on the glutamate system particularly NMDA receptors to produce quick antidepressant effects
What is the clinical use of tricyclic antidepressants in neuropathic pain?
TCAs are effective in treating chronic neuropathic pain due to their analgesic properties
What is the significance of serotonin-norepinephrine reuptake inhibition?
Provides a dual mechanism of action enhancing both serotonin and norepinephrine neurotransmission for improved efficacy in depression
How does the inhibition of MAO contribute to the antidepressant effect?
Prevents the breakdown of monoamine neurotransmitters increasing their availability in the brain
What are the therapeutic effects of bupropion?
Antidepressant and smoking cessation aid with a favorable side effect profile including minimal sexual dysfunction
