Mood Disorders Flashcards
What are the known neurochemical effects of monoamine oxidase inhibitors (MAOIs)?
Irreversibly blocks oxidative deamination of monoamines
Block both MOA a and MOA b
Occurs within 24-48hrs, clinically takes 3+ weeks to begin
What are the known neurochemical effects of tricyclic antidepressants?
Block reuptake of NE and/or 5-HT
OTHER:
- Block H1 receptor (weight gain, drowsy)
- block muscarinic receptor (dry mouth, constipat)
- block alpha 1 receptor (low BP, light headedness)
- Block Na channels (arrhythmias, cardiac arrest and seizures)
What are the known neurochemical effects of second generation antidepressants?
Increase NE, 5-HT and possible DA
What are the major adverse effects associated with MAOIs?
Mess with SSRIs
Serotonin syndrome
What are the main adverse effect associated with tyramine?
Tyramine is completely metabolized by MAO hepatic
- Accumulation induces NE and Epinephrine release
- -> increase BP dangerously –> crisis
What are potential advantages of some of the newer antidepressant drugs?
Less effects Cholinergic receptors
What are the clinical uses of using lithium to treat mood disorders?
- manic phases of bipolar disorder
- prevention of mood swings
- antidepressant in some patients
- effective in 60-80% of treated Pxs
What are the neurochemical effects of lithium?
- unsure
- most likely postsynaptic
- IP3 release and production and DAG
- inhib NEnsensitive ardenylyl cyclase
- uncouple receptor recognition site from GTP-binding protein by competing with Mg
- alters gene expression implicated in long-term neuroplastic events that could underlie long-term mood stabilization
What is the toxicity of lithium?
- 95% excreted by kidneys! therefore effected by water and electrolyte balance
- fatigue, muscle weakness, slurred speech, ataxia, fine tremor of the hands at therapeutic doses
- coma, muscle rigidity, hyperactive deep reflexes, tremor, muscle fasciculations, symptomatic treatment, at toxic levels
What other drugs besides lithium are used to treat bipolar mood disorder?
Anticonvulsants: valproic acid, carbamazepine
Why should SSRIs not be given to bipolar patients who do not receive a mood stabilizer?
Because rapid onset of mania may occur
What is key in distinguishing depressive disorder from bipolar disorder?
Mania
What is the rate of suicides for depression and bipolar disorder?
~15% in depression
~25% in bipolar disorder
When does unipolar depression occur?
Once, everyday at least 2 weeks
Recurrent episodes separated by periods of euthymia
What do Pxs with bipolar disorder alternate between?
Depression, mania, either separated by euthymia or rapid cycles
What is depression?
- Heterogenous disease
- depressed mood and/or anhedonia (no interest in pleasure)
- disruptions in sleep, weight gain or loss, psychomotor retardation, fatigue, indecisiveness, and or suicidal thoughts
What areas of the brain are linked to depression?
- Monoaminergic brain areas
- dorsal raphe nucleus in midbrain
- other limbic structures
What is the monoamine hypothesis?
- depression associated with changes in serotonin or NE signaling in he brain (or both) with significant downstream effects
- other neurochemicals associated downstream
- depression occurs if receptors are insensitive or if amine synthesis, storage, or release is deficient
- mania occurs of excess amines
What is the problem with the amine theory of depression?
Mismatch between time course
What is the neurotrophic hypothesis of mood disorders?
- Nerve growth factors (BDNF) are critical for function
- Depression is associated with the loss of neurotrophic support
- increase this support in cortical areas such as the hippocampus
- antidepressants are associated with an increase in BDNF in animal models
What are the drug classes for mood disorders?
- antidepressants
1. Tricyclic antidepressants
2. MAOIs
3. SSRIs
4. Dual mechanism drugs - mood stabilizers
1. Lithium carbonate
2. Anticonvulsants
3. Atypical antipsychotics
What are the clinical effects of TCAs?
Normal Pxs: no mood effects, antimuscarinic effects, sleepiness and light headedness
Depressed Pxs: elevation on mood after 2-3 weeks
Used always
What TCA blocks NE reuptake selectively?
Desipramine
What TCA blocks NE/5-HT reuptake?
Imipramine
