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MT 6314 2nd Shift > 7.4: Antidepressant Agents > Flashcards

7.4: Antidepressant Agents Flashcards

1
Q

True or False:

Major depressive disorder is a depressed mood most of the time for at least 2 week or loss of interest or pleasure in most activities.

A

True

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2
Q

True or False:

Other characteristics of major depressive disorder are disturbance in sleep and appetite, deficits in cognition and energy, and thoughts of guilt, worthlessness, and suicide.

A

True

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3
Q

What are the 3 pathophysiology of major depression?

A
  1. Monoamine hypothesis
  2. Neurotrophic hypothesis
  3. Neuroendocrine factors
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4
Q

Determine what kind pathophysiology:

  • Norepineprine (NE) and serotonin (5-HT)
  • Functional decrease in the activity (depression)
  • Functional increase in the activity (mood elevation)
A

Monoamine hypothesis

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4
Q

Determine what kind pathophysiology:

  • Regulation of neural plasticity, resilience, and neurogenesis
  • Exert its influence on neuronal survival and growth effects by activating tyrosine kinase receptor B in both neurons and glia
A

Neurotrophic hypothesis

Brain derived neurotrophic factor (BDNF)

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5
Q

Determine what kind pathophysiology:

It affects
1. Hippocampus
2. Anterior cingulate gyrus
3. Medial frontal cortex

A

Neurotrophic hypothesis

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5
Q

Determine what kind pathophysiology:

Adrenocorticotropic hormone
* Nonsuppression of adrenocorticotropic hormone (ACTH) release in the dexamethasone suppression test
* Dysregulation of the stress hormone axis

A

Neuroendocrine factors

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5
Q

Determine what kind pathophysiology:

  • Thyroid hormone
  • Thyroid dysregulation in depressed patients
  • Blunting of response of thyrotropin to thyrotropin-releasing hormone, and elevations in circulating thyroxine during depressed states
A

Neuroendocrine factors

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6
Q

Determine what kind pathophysiology:

Sex steroids
* Estrogen deficiency states, which occur in the postpartum and postmenopausal periods, are thought to play a role in the etiology of depression in some women
* Severe testosterone deficiency in men is sometimes associated with depressive symptom

A

Neuroendocrine factors

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7
Q

What is the primary action of Selective Serotonin Reuptake Inhibitors (SSRIs)?

A

Inhibition of serotonin transporter (SERT)

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8
Q

What are the 6 major approved SSRIs?

A
  1. Fluoxetine
  2. Sertraline
  3. Citalopram
  4. Paroxetine
  5. Fluvoxamine
  6. Escitalopram

FluSerCiPFE !!! >:(

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9
Q

True or False:

The MOA of SSRIs is Serotonin transporter (SERT) is a glycoprotein with 12 transmembrane regions embedded in the axon terminal and cell body membranes of serotonergic neurons.

A

True

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10
Q

What are the other indications of SSRIs?

A
  1. Generalized Anxiety Disorder (GAD)
  2. Post-traumatic stress disorder (PTSD)
  3. Obsessive Complusive Disorder (OCD)
  4. Panic Disorder
  5. Premenstrual Dysphoric Disorder (PMDD) and Bulimia
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11
Q

What is the half-live of SSRIs?

A

18-24 hours

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12
Q

Identify the drug interactions of SSRIs:

  • Interaction between fluoxetine and a MAOI
  • Life-threatening
  • Reason: Fluoxetine has to be discontinued 4 weeks or longer before an MAOI can be administered
A

Serotonin syndrome

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13
Q

Identify the drug interaction of SSRIs:

  • Severe muscle rigidity
  • Myoclonus
  • Hyperthermia
  • Cardiovascular instability
  • CNS stimulatory effects-seizures
A

Serotonin syndrome

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14
Q

What are the drugs included in Serotonin syndrome?

A
  • MAOIs
  • TCAs
  • Meperidine
  • MDMA (ecstasy)
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15
Q

In serotonin syndrome, what is the antidepressant drug that blocks the 5-HT receptors?

A

Cyproheptadine

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16
Q

What are the 3 antidepressants of SNRIs?

A
  • Venlafaxine and Duloxetine
  • Tricyclic Antidepressants
  • 5HT2A Antagonists
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17
Q

Identify this antidepressant of SNRIs:

  • Metabolized in the liver to Desvenlafaxine
  • Lowest protein binding amongst all anti-depressant (27-30%)
  • Similar half lives of 11 hours (once daily dosing)
  • 45% are excreted unchanged in the urine
A

Venlafaxine

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18
Q

Identify this antidepressant of SNRIs:

  • Well-absorbed
  • Half-life: 12 hours
  • Tightly bound to protein
A

Duloxetine

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19
Q

Identify this antidepressant of SNRIs:

  • NET is structurally very similar to the 5-HT transporter
  • 12-transmembrane domain complex that allosterically binds norepinephrine
  • NET also has a moderate affinity for dopamine
A

Venlafaxine

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20
Q

True or False:

Venlafaxine is a strong inhibitor of NET.

A

False

Weak dapat.

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21
Q

True or False:

Desvenlafaxine, duloxetine, and milnacipran are more balanced inhibitors of both SERT and NET.

A

True

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22
Q

True or False:

Nonetheless, the affinity of most SNRIs tends to be much greater for SERT than for NET.

A

True

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23
Q

True or False:

The SNRIs differ from the TCAs in that they lack the potent antihistamine, -adrenergic blocking, and anticholinergic effects of the TCAs.

24
Q

True or False:

SNRIs tend to be favored over the TCAs in the treatment of MDD and pain syndromes because of their better tolerability.

25
Q

Identify this antidepressant:

  • Imipramine, amitriptyline
  • Structurally related to the phenothiazine antipsychotics
  • Well absorbed orally
  • May undergo first-pass metabolism
  • High volume of distribution
  • Not readily dialyzable
A

Tricyclic antidepressants (TCAs)

26
Q

Identify this antidepressant:

  • Extensive hepatic metabolism is required before elimination
  • Plasma half-lives of 8-36 hours
  • Once-daily dosing
  • Wide therapeutic window
  • Serum are reliable in predicting response and toxicity
  • Nortriptyline, desipramine
A

Tricyclic antidepressants (TCAs)

27
Q

Identify this antidepressant (Mode of transmission):

  • Inhibit the reuptake mechanisms (transporters) responsible for the termination of the synaptic actions of both NE and 5-HT
  • Potentiation of NTA actions at postsynaptic receptors
A

Tricyclic antidepressants (TCAs)

28
Q

Identify this antidepressants of SNRIs on its pharmacologic effects:

  • Inhibits the reuptake of NE at nerve endings in the ANS
  • Peripheral autonomic sympathomimetic effects
  • Sedation is common
  • Antagonism of muscarinic receptors
  • Marked with amitriptyline
A

Tricyclic antidepressants (TCAs)

29
Q

Identify this antidepressants based on pharmacologic effects:

  • Cardiovascular effects
  • Hypotension from alpha-adrenoceptorblockade
  • Arrhythmias
  • Convulsions
  • Overdosage
A

Tricyclic antidepressants (TCAs)

30
Q

Identify this antidepressants based on its clinical uses:

  • Major depressive disorders
  • Alternative agent
  • Psychomotor retardation
  • Sleep disturbances
  • Poor appetite
  • Weight loss
A

Tricyclic antidepressants (TCAs)

31
Q

Identify this antidepressant based on its toxicities:

  1. Pharmacodynamic actions
  2. Sympathomimetic effects
  3. Atropine-like effects
  4. Orthostatic hypotension, ECG abnormalities, and cardiomyopathies
  5. Tremor and paresthesias
  6. Weight gain
A

Tricyclic antidepressants (TCAs)

32
Q

Identify this antidepressants:

  • Trazodone and Nefazodone
  • Rapidly absorbed and undergoes extensive hepatic metabolism
  • Short half loves thus requires split dosing
  • Trazodone prescribed as singe dose at night as a hypnotic in lower doses than are when used for depression
  • Active metabolites
  • Nefazodone are potent inhibtor of CYP3A4
A

5-HT2 antagonists

33
Q

What are the other drugs that do not fit into the other categories of Tetracyclic and Unicyclic Antidepressants?

A
  • Bupropion
  • Mirtazapine
  • Amoxapine
  • Maprotiline
34
Q

Identify this antidepressant of Tetracyclic and Unicyclic:

  • unicyclic aminoketone structure
  • resembles amphetamine in chemical structure AND has central nervous system (CNS) activating properties
  • rapidly absorbed and has a mean protein binding of 85%
  • has three active metabolites one of which is being developed as an anti depressant.
35
Q

What is the biphasic elimination of bupropion in 1st phase and 2nd phase?

A

1 hour; 14 hours

36
Q

Identify this antidepressant of Tetracyclic and Unicyclic:

  • not commonly associated with sexual side effects.
  • tetracyclic chemical structure
  • belongs to the piperazino-azepine group
  • demethylated followed by hydroxylation and
    glucuronide conjugation
  • half-life: 20–40 hours, dosed once in evening
A

Mirtazapine

37
Q

Identify this antidepressant of Heterocyclic Antagonists:

  • MOA: complex pharmacology
  • An antagonist of the presynaptic 2 autoreceptor and enhances the release of both Norepinephrine and 5-HT
  • Antagonist of 5-HT2 and 5-HT3receptors
  • Potent H1 antagonist (drug’s sedative effects)
A

Mirtazapine

38
Q

Identify this antidepressant of Tetracyclic and Unicyclic:

  • N-methylated metabolite of loxapine
  • Share structural similarities with Maprotiline
  • Rapidly absorbed with protein binding of about 85%.
  • Half-life: variable, divided doses
  • 7- hydroxyamoxapine: potent D2 blocker, associated with antipsychotic effects
39
Q

Identify this antidepressant of Tetracyclic and Unicyclic:

  • MOA: potent NET inhibitors and less potent SERT inhibitors.
  • Both possess anticholinergic properties
  • A moderate inhibitor of the postsynaptic D2 receptor
A

Amoxapine and Maprotiline

40
Q

Identify this antidepressant of MAOIs:

  • C-N-N moiety
  • Phenelzine, isocarboxazid
  • No longer marketed
  • Combine irreversibly with MAO
A

Hydrazides

41
Q

Identify this antidepressant of MAOIs:

  • Lack the C-N-N moiety
  • Tranylcypromine
  • Combine reversibly with MAO
A

Nonhydrazides

42
Q

This is structurally related to amphetamines, orally active, and has a nonselective inhibitors.

A

Monoamine oxidase inhibitors (MAOIs)

43
Q

What are the two selective inhibitors of MAOIs?

A
  1. MAO-A
  2. MAO-B
44
Q

Identify if MAO-A or MAO-B:

Metabolizes NE, 5-HT and tyramine

45
Q

Identify if MAO-A or MAO-B:

Metabolizes dopamine.

46
Q

It is the selective inhibitor of MAOIs and is used in parkinson’s disease, selectively inhibits MAO-b at low dose, and is less selective at higher doses.

A

Selegiline

47
Q

Identify this drug of MAOIs:

  • Fastest onset of effect
  • Shorter duration of action (about 1 week)
A

Tranylcypromine

48
Q

True or False:

MAOIs are given daily, and persists even after these drugs are no longer detectable in plasma.

49
Q

True or False:

The MOA of MAOIs increases in brain amine levels by interfering with their metabolism in the nerve endings, and increase vesicular stores of NE and 5-HT.

50
Q

True or False:

When the neuronal activity of MAOIs discharges the vesicles, it increases the amount of amines released.

51
Q

True or False:

MAOIs enhances the action of NTAs.

52
Q

Identify the antidepressant based on its pharmacologic effects:

  • Increase NE in sympathetic nerve terminals
  • Peripheral sympathomimetic effects
  • Long-term use can decrease BP
  • CNS stimulating effects
  • Seizures may occur with overdosage
A

Monoamine oxidase inhibitors (MAOIs)

53
Q

What are the clinical uses of MAOIs?

A
  • Major depressive disorders
  • Anxiety
  • Phobic features
  • Hypochondriasis
54
Q

What are the toxicities of MAOIs?

A
  • Hyperthermia
  • CNS stimulation, agitation and convulsions
  • Shock
55
Q

Identify this antidepressants based on drug interaction:

  • Inhibitors of hepatic drug-metabolizing enzymes
  • Hypertensive crisis
  • Occur in patients who consume food with high concentration of indirect sympathomimetic tyramine
  • Administration with SSRIs have resulted to serotonin syndrome
A

Monoamine oxidase inhibitors (MAOIs)

56
Q

Enumerate the MAO inhibitors:

A
  • Phenelzine
  • Selegiline
  • Tranylcypromine

PST MAO! >:(

57
Q

Enumerate the TCAs

A
  • Amitriptyline
  • Clomipramine
  • Imipramine

TCA ACI

58
Q

Enumerate the heterocyclic antidepressants:

A
  • Bupropion
  • Amoxapine
  • Mirtazepine
59
Q

Enumerate the SNRI inhibitors:

A
  • Duloxetine
  • Venlafaxine
60
Q

Enumerate the 5-HT antagonists:

A
  • Nefazodone
  • Trazodone
61
Q

Enumerate the SSRIs:

A
  • Escitalopram
  • Fluoxetine
  • Fluvoxamine
  • Paroxatine
  • Sertraline

MT 6314 2nd Shift (8 decks)

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