Mood disorder Flashcards
(27 cards)
Mechanism TCAs
block reuptake of NE and/or 5HT by nerve terminals –> results in higher concentrations at receptors
NE selective TCA
Desipramine (Norpramin)
NE/5HT mixed action TCA
Imipramine (Tofranil)
Adverse effects of TCAs
Orthostatic hypotension blockade of α adrenoceptors Antimuscarinic effects - may be severe in elderly patients Acute confusional state Constipation Glaucoma Weight gain Tachycardia and increased tendency for arrhythmias with high doses
SSRIs examples
Fluoxetine (Prozac) * Sertraline (Zoloft)* Paroxetine (Paxil) Fluvoxamine (Luvox) Citalopram (Celexa) Escitalopram (Lexapro)
SSRIs mechanism
Selective inhibition of serotonin reuptake by CNS neurons
amine hypothesis of mood disorders
Certain levels of amine neurotransmitters and receptor sensitivity are necessary for normal mood
Norepinephrine
Serotonin
Dopamine
Depression occurs if receptors are insensitive or if amine synthesis, storage or release is deficient
Mania occurs if there is an excess
problems with amine hypothesis
mismatch between time course, no evidence in decrease of brain levels of NE or 5HT, most AD cause downregulation of amine receptors, some AD don’t affect NE or 5HT
neurotrophic hypothesis of mood disorders
Nerve growth factors such as brain-derived neurotrophic factor (BDNF) are critical in the regulation of neural plasticity, resilience, and neurogenesis.
Depression is associated with the loss of neurotrophic support
TCAs metabolized by ______ and interact with ________
CYP2D6, inhibited by fluoxetine - do not give together –> TCA toxicity
glutamine hypothesis for depression, drug associated
elevated glutamine –> depression
Ketamine - NMDA receptor antagonist
MAOI
phenelzine
mechanism phenelzine
Irreversibly blocks the oxidative deamination of monoamines
Nonselectively inhibit both MAO-A and MAO-B ( A - NE and 5HT)
Why SSRIs not starts until at least 14 days after MAOI
irreversibly block MAO - need to wait for protein synthesis
Serotonin syndrome
MAOIs
hyperthermia, muscle rigidity, tremors, autonomic instability, confusion, irritability, and agitation
Overactivation of subset of 5-HT receptors
Can progress toward coma and death
Administer nonselective serotonin antagonists (Cyproheptadine, etc.)
Also caused by MDMA (Ecstasy)
MAOIs drug interactions
Potentiate sympathomimetic amines - such as tyramine, completely metabolized by hepatic MAO –> tyramine enters systemic circulation –> Accumulation of tyramine in adrenergic nerve endings and neurotransmitter vesicles and induces norepinephrine and epinephrine release –> stimulate postsynaptic receptors in the periphery, increasing blood pressure to dangerous levels.
SSRIs
Fluoxetine (Prozac)
Sertraline (Zoloft)
SSRIs mechanism
Selective inhibition of serotonin reuptake by CNS neurons
Adverse effects SSRIs
Nausea, diarrhea and weight loss
Stimulation - anxiety, nervousness, insomnia, sufficient to discontinue treatment
Sexual dysfunction
Suicidal ideation
atypical antidepressants
venlafaxine
mirtazapine
venlafaxine mechanism
Serotonin-norepinephrine reuptake inhibitor (SNRI)
Blocks serotonin reuptake like SSRIs
Also blocks NE reuptake
how venlafaxine differ from tcas
Venlafaxine does NOT affect Adrenergic receptors Histaminergic receptors Cholinergic receptors Action of the TCAs on these receptors trigger majority of adverse effects
venlafaxine contraindicated in patients on
MAOIs (and vice versa)
Raising dose of ________ changes efficacy
Raising the dose of venlafaxine can improve efficacy, likely due to secondary mechanisms of action
