Pharmacology of Mood Disorders Flashcards
Outline how DA and NE is synthesized
Tyrosine → DOPA via tyrosine hydroxylase, DOPA → dopamine via dopamine decarboxylase, and dopamine → norepinephrine via beta hydroxylase.
Key area of synthesis of NE
locus coeruleus
Locus coeruleus in rostral pons has NE projections to the brain and spinal cord, resulting in:
§ Cerebral cortex: promotes cognitive enhancement
§ Nucleus accumbens: increases motivation
§ HPA: increases cortisol
§ Spinal cord: increases sympathetic tone
After reuptake from the synaptic cleft, monoamines can be destroyed via monoamine oxidase or stored in vesicles
There are different types of adrenergic receptors
Presynaptic __ II ___-receptors: ___ release of norepinephrine
Postsynaptic __ II: projection to __ cortex for attention and cognition
Postsynaptic __ I: projection to prefrontal cortex mediates __
There are different types of adrenergic receptors
Presynaptic Alpha II auto-receptors: inhibit release of norepinephrine
Postsynaptic Alpha II: projection to prefrontal cortex for attention and cognition
Postsynaptic Beta I: projection to prefrontal cortex mediates mood
*__ __ degrades NE or DA/monoamines in the __ cleft. The monoamines can also go through a __ channel and get reabsorbed back into the __.
*monoamine oxidase degrades NE or DA/monoamines in the synaptic cleft. The monoamines can also go through a reuptake channel and get reabsorbed back into the soma.
outline the synthesis pathway for 5HT
Tryptophan → 5-hydroxytryptophan via __ __, 5-hydroxytryptophan → serotonin (5HT) via __ __ __ decarboxylase
Tryptophan → 5-hydroxytryptophan via tryptophan hydroxylase, 5-hydroxytryptophan → serotonin (5HT) via aromatic amino acid decarboxylase
key area of synthesis for 5HT
Raphe nuclei in medulla, pons and midbrain project to various brain regions
After reuptake from the synaptic cleft, monoamines can be destroyed via monoamine oxidase or stored in vesicles
Serotonin receptors on both presynaptic and postsynaptic neurons
Increased norepinephrine binding on a hetero-receptor of a serotonergic neuron will lead to increased serotonin (at the axon terminal and the dendrite)
Depressed Synaptic Activity
Defined as low synaptic __ and __ due to either ___ __ __-__, or loss of dendritic branching due to decreased ___
Monoamine signal transduction → increased __ (this is why we want to keep a patient on anti-depressants for 6-12 months to promote dendritic growth)
Monoamine signal transduction is critical for synthesis of __
- Under stress, a __ in expression of genes for BDNF (and other neuriotrophic factors)
- Low levels of BDNF result in __ of neurons, specifically in the ___.
Depressed Synaptic Activity
Defined as low synaptic serotonin and NE due to either upregulated inhibitory auto-receptors, or loss of dendritic branching due to decreased BDNF
Monoamine signal transduction → increased BDNF (this is why we want to keep a patient on anti-depressants for 6-12 months to promote dendritic growth)
Monoamine signal transduction is critical for synthesis of BDNF
- Under stress, a decrase in expression of genes for BDNF (and other neuriotrophic factors)
- Low levels of BDNF result in apoptosis of neurons, specifically in the hippocampus.
SSRIs Side effects:
• Due to serotonin block in…
o Basal ganglia→___ __ (Parkinsonism, akathisia)
o Limbic cortex→___
o Spinal cord→ delayed __
o Mesocortical pleasure centers→ low __
o Hypothalamus→ __
o GI→__ motility (__)
SSRIs
Side effects:
• Due to serotonin block in…
o Basal ganglia→movement disorders (Parkinsonism, akathisia)
o Limbic cortex→agitation
o Spinal cord→ delayed orgasm
o Mesocortical pleasure centers→ low libido
o Hypothalamus→ nausea
o GI→increase motility (diarrhea)
NDRI (Norepinephrine and DA reuptake inhibitor)
NDRI Only one available is ___ (___). NO sexual side effects, can reverse sexual side effects
Side effects: anxiety, activating, reduction in seizure threshold
NDRI (Norepinephrine and DA reuptake inhibitor)
NDRI Only one available is bupropion (Wellbutrin). NO sexual side effects, can reverse sexual side effects
Side effects: anxiety, activating, reduction in seizure threshold
MAO Inhibitors (MOAI)
Types:
- MAO A: metabolizes __ and __ (focus in __)
- MAO B: metabolize __ (focus in __)
- __: both MAO A and B (irreversible)
- __: MAO A (reversible)
MAO Inhibitors (MOAI)
Types:
- MAO A: metabolizes serotonin and norepinephrine (focus in depression)
- MAO B: metabolize dopamine (focus in Parkinson’s)
- Phenelzine: both MAO A and B (irreversible)
- Moclobemide: MAO A (reversible)
what can cause serotonin syndrome?
- overdose of TCA
- adding an SSRI/SNRI to an MAOI
- adding any serotongergic agent to MAOI
side effect that is a medical emrgency for MAOIS
Side effects:
• Tyramine is found in food and is absorbed/metabolized by MAO. When you are given MAOI and eat tyramine → increased NE → hypertensive crisis
Tyramine is found in processed, cured and pickled foods
Generally:
A2 antagonism releases __
A2 antagonism releases __
A1 agonism (from NE) releases __
Generally:
A2 antagonism releases norepinephrine
A2 antagonism releases serotonin
A1 agonism (from NE) releases serotonin
Common in pregnancy (5-12%); most antidepressants are category __- except ___ which is category D
Bipolar disorder in pregnancy: relapse risk is >__% off medications, and __% on medications
Major malformation rate of 8% with Epival, less if taking 5mg folic acid 1 month prior to conception and during 1st trimester
__ anomaly 0.01% with __ (displaced tricuspid valve allows blood back into right atrium)
Major depressive disorder in pregnancy: 5-12% of women, 30% of whom report suicidal ideation. Multiple meta-analyses do not provide a clear direction.
Common in pregnancy (5-12%); most antidepressants are category C- except Paxil which is category D
Bipolar disorder in pregnancy: relapse risk is >85% off medications, and 37% on medications
Major malformation rate of 8% with Epival, less if taking 5mg folic acid 1 month prior to conception and during 1st trimester
Ebstein’s anomaly 0.01% with lithium (displaced tricuspid valve allows blood back into right atrium)
Major depressive disorder in pregnancy: 5-12% of women, 30% of whom report suicidal ideation. Multiple meta-analyses do not provide a clear direction.
