18) Depression Flashcards
(39 cards)
Major depressive disorder (MDD)
- Depression of mood without any obvious medical or situational causes
- Manifested by an inability to cope with ordinary events or experience pleasure
The drugs used in MDD are of varied chemical structures; many have effects that enhance the CNS actions of
- Norepinephrine, serotonin, or both
Theamine hypothesis of moodpostulates that
- Brain amines, particularly norepinephrine (NE) and serotonin (5-HT), are neurotransmitters in pathways that function in the expression of mood
Classes of antidepressants
- MAO inhibitors
- Tricyclic antidepressants
- Heterocyclic antidepressants
- 5-HT-NE reuptake inhibitors
- 5-HT antagonists
- SSRIs
TCA site of action
- Inhibit more norepinephrine reuptake more than serotonin reuptake
SSRI site of action
- Selectively inhibits serotonin reuptake (SERT)
- Used for hypertensive patients
Nefazodone and trazodone are inhibitors of
- NE and 5-HT transporters
- Antagonism of the 5-HT2Areceptor
Inhibition of neuronal uptake of norepinephrine (NE) and serotonin (5-HT) increases
- Synaptic activities of these neurotransmitters
Inhibition of monoamine oxidase increases
- Presynaptic stores of both NE and 5-HT
- Leads to increased neurotransmitter effects
Blockade of the presynaptic α2autoreceptor prevents
- Feedback inhibition of the release of NE
TCA mechanism of action
- Inhibit the reuptake transporters responsible for the termination of the synaptic actions of mainly NE and less 5-HT in the brain
SSRI mechanism of action
- Highly selective action on the serotonin transporter (SERT)
- SNRIs bind to transporters for serotonin and NE
- Lack significant blocking effects on peripheral receptors (unlike TCAs)
Serotonin 5-HT2receptor antagonists mechanism of action
- Nefazodone and trazodone appear to result from block of the 5-HT2Areceptor (a G-protein-coupled receptor located in several CNS regions)
Other heterocyclic antidepressants mechanisms of action
- Mirtazapine antagonize presynaptic α2adrenoceptors involved in feedback inhibition (also antagonist at serotonin 5-HT2receptors)
- Bupropion MOA is unknown (drug has no effect on either 5-HT or NE receptors or on amine transporters)
MAO inhibitors mechanism of action
- Increase brain amine levels by interfering with their metabolism in the nerve endings
- Results in an increase in the vesicular stores of NE and 5-HT
Effects of amine uptake blockade
- The drugs that block NE transporters in the CNS also inhibit the reuptake of NE at nerve endings in ANS
- MAOIs increase NE in sympathetic nerve terminals
- In both cases = peripheral autonomic sympathomimetic effects
Sedation effects of antidepressants
- Common CNS effect of tricyclic drugs and some heterocyclic agents (especially mirtazapine and the 5-HT2receptor antagonists nefazodone and trazodone)
Trazodone is commonly prescribed for both the purpose of sedation and as a
- Sleeping aid
MAOIs, SSRIs, and bupropion are more likely to cause
- CNS-stimulating effects
Effects of muscarinic receptor blockade
- Antagonism of muscarinic receptors occurs with all tricyclics (more with amitriptyline and doxepin)
- Atropine-like adverse effects may also occur with nefazodone, amoxapine, and maprotiline
Cardiovascular effects of antidepressants
- Most commonly with tricyclics
- Hypotension from α-adrenoceptor blockade
- Depression of cardiac conduction that may lead to arrhythmias
Seizures associated with antidepressents
- Convulsive threshold is lowered by TCAs and MAOIs
- Seizures may occur with overdoses of these agents
Symptoms of overdose with tricyclics
(1) agitation, delirium, neuromuscular irritability, convulsions, and coma
(2) respiratory depression and circulatory collapse
(3) hyperpyrexia
(4) cardiac conduction defects and severe arrhythmias
- The “3 Cs” (coma, convulsions, and cardiotoxicity) are characteristic
Tricyclic drug interactions
- Additive depression of the CNS with central depressants (including ethanol, barbiturates, benzodiazepines, and opioids)
