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Pharmacology > 18) Depression > Flashcards

18) Depression Flashcards

1
Q

Major depressive disorder (MDD)

A
  • Depression of mood without any obvious medical or situational causes
  • Manifested by an inability to cope with ordinary events or experience pleasure
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2
Q

The drugs used in MDD are of varied chemical structures; many have effects that enhance the CNS actions of

A
  • Norepinephrine, serotonin, or both
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3
Q

Theamine hypothesis of moodpostulates that

A
  • Brain amines, particularly norepinephrine (NE) and serotonin (5-HT), are neurotransmitters in pathways that function in the expression of mood
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4
Q

Classes of antidepressants

A
  • MAO inhibitors
  • Tricyclic antidepressants
  • Heterocyclic antidepressants
  • 5-HT-NE reuptake inhibitors
  • 5-HT antagonists
  • SSRIs
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5
Q

TCA site of action

A
  • Inhibit more norepinephrine reuptake more than serotonin reuptake
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6
Q

SSRI site of action

A
  • Selectively inhibits serotonin reuptake (SERT)

- Used for hypertensive patients

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7
Q

Nefazodone and trazodone are inhibitors of

A
  • NE and 5-HT transporters

- Antagonism of the 5-HT2Areceptor

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8
Q

Inhibition of neuronal uptake of norepinephrine (NE) and serotonin (5-HT) increases

A
  • Synaptic activities of these neurotransmitters
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9
Q

Inhibition of monoamine oxidase increases

A
  • Presynaptic stores of both NE and 5-HT

- Leads to increased neurotransmitter effects

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10
Q

Blockade of the presynaptic α2autoreceptor prevents

A
  • Feedback inhibition of the release of NE
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11
Q

TCA mechanism of action

A
  • Inhibit the reuptake transporters responsible for the termination of the synaptic actions of mainly NE and less 5-HT in the brain
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12
Q

SSRI mechanism of action

A
  • 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)
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13
Q

Serotonin 5-HT2receptor antagonists mechanism of action

A
  • Nefazodone and trazodone appear to result from block of the 5-HT2Areceptor (a G-protein-coupled receptor located in several CNS regions)
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14
Q

Other heterocyclic antidepressants mechanisms of action

A
  • 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)
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15
Q

MAO inhibitors mechanism of action

A
  • 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
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16
Q

Effects of amine uptake blockade

A
  • 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
17
Q

Sedation effects of antidepressants

A
  • Common CNS effect of tricyclic drugs and some heterocyclic agents (especially mirtazapine and the 5-HT2receptor antagonists nefazodone and trazodone)
18
Q

Trazodone is commonly prescribed for both the purpose of sedation and as a

A
  • Sleeping aid
19
Q

MAOIs, SSRIs, and bupropion are more likely to cause

A
  • CNS-stimulating effects
20
Q

Effects of muscarinic receptor blockade

A
  • 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
21
Q

Cardiovascular effects of antidepressants

A
  • Most commonly with tricyclics
  • Hypotension from α-adrenoceptor blockade
  • Depression of cardiac conduction that may lead to arrhythmias
22
Q

Seizures associated with antidepressents

A
  • Convulsive threshold is lowered by TCAs and MAOIs

- Seizures may occur with overdoses of these agents

23
Q

Symptoms of overdose with tricyclics

A

(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

24
Q

Tricyclic drug interactions

A
  • Additive depression of the CNS with central depressants (including ethanol, barbiturates, benzodiazepines, and opioids)
25
Q

Adverse effects of the traditional MAOIs

A
  • Hypertensive crisis in patients taking MAOIs who consume food that contains high concentrations of the indirect sympathomimetic tyramine (aged cheese, wine)
26
Q

MAOIs administered together with SSRIs have resulted in

A
  • Serotonin syndrome
27
Q

SSRI toxicity symptoms

A
  • Nausea, headache
  • Anxiety, agitation, insomnia
  • Sexual dysfunction
  • Extrapyramidal effects and seizures are a consequence of gross overdosage
28
Q

A withdrawal syndrome has been described for SSRIs which includes

A
  • Nausea
  • Dizziness
  • Anxiety
  • Tremor
  • Palpitations
29
Q

Serotonin syndrome

A
  • Life-threatening
  • Severe muscle rigidity
  • Myoclonus
  • Hyperthermia
  • Cardiovascular instability
  • Marked CNS stimulatory effects (including seizures)
30
Q

Drugs implicated in serotonin syndrome

A
  • MAOIs

- TCAs

31
Q

Mirtazapine and trazodone toxic effects

A
  • Weight gain

- Markedly sedating

32
Q

Amoxapine, maprotiline, mirtazapine and trazodone cause some

A
  • Autonomic effects
33
Q

Amoxapine is also a dopamine receptor blocker and may cause

A
  • Akathisia
  • Parkinsonism
  • Amenorrhea-galactorrhea syndrome
34
Q

Adverse effects of bupropion

A
  • Anxiety, agitation
  • Dizziness
  • Dry mouth
  • Aggravation of psychosis
  • Seizures (at high doses)
35
Q

Seizures and cardiotoxicity are prominent features of overdosage with

A
  • Amoxapine

- Maprotiline

36
Q

Venlafaxine causes a dose-dependent increase in

A
  • Blood pressure

- Also has CNS stimulant effects similar to those of the SSRIs

37
Q

Both nefazodone and venlafaxine are inhibitors of

A
  • Cytochrome P450 isozymes
38
Q

Through its inhibitory action on CYP3A4, nefazodone enhances the actions of several drugs including

A
  • Carbamazepine
  • Clozapine
  • HMG-CoA reductase inhibitors (statins)
  • TCAs
39
Q

Though rare, nefazodone has caused life-threatening

A
  • Hepatotoxicity requiring liver transplantation

- Duloxetine is also reported to cause liver dysfunction

Pharmacology (27 decks)

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