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Neuro B5 - WLB > Antidepressants/Drugs for Manic Disorders - Slattery > Flashcards

Antidepressants/Drugs for Manic Disorders - Slattery Flashcards

1
Q

What is the MOA of Tricyclic Antidepressants?

A
  • Block the reuptake of NE and/or 5-HT by pre-synaptic nerve terminals
    • blocked reuptake increases amount of NT in synaptic space –> downstream effects
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2
Q

What drug class does Desipramine (Norpramin) belong in?

A

NE-selective TCA

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3
Q

What drug class does Imipramine (Tofranil) belong in?

A

NE/5HT mixed action TCA

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4
Q

What are adverse symptoms of TCAs?

A
  • Orthostatic hypotension
  • Weight gain
  • Tachycardia and increased tendency for arrhythmias with high doses
  • Drowsiness
  • Dry mouth
  • Blurred vision
  • Constipation
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5
Q

Why do TCAs cause drowsiness?

A
  • Block histamine receptor
  • Block muscarinic receptor
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6
Q

Why to TCAs cause weight gain?

A

Block histamine receptor (H1)

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7
Q

Why do TCAs cause orthostatic hypotension, light-headedness, and decreased blood pressure?

A

Block alpha-1 receptors

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8
Q

Why do TCAs cause dry mouth, blurred vision, and constipation?

A

block muscarinic receptors

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9
Q

Why do TCAs cause arrhythmias, cardiac arrest, and seizures?

A

Block Na+channels

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10
Q

What is the MOA of Monoamine Oxidase Inhibitors (MAOIs)?

A
  • Irreversibly blocks the oxidative deamination of monoamines
    • Nonselectively inhibit both MAO-A and MAO-B
      • MAO-A = metabolizes NE & 5HT
      • MAO-B = metabolizes DA
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11
Q

What drug class does Phenelzine (Nardil) belong in?

A

MAOIs

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12
Q

Why do you have to wait 14 days to start an SSRI after stopping use of MAOI, and 14 days to start an MAOI after stopping use of an SSRI?

A
  • allow for new synthesis of MAO
  • allow excretion of SSRI’s
  • avoid Serotonin Syndrome
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13
Q

What is Serotonin Syndrome?

A
  • Overactivation of 5HT-2A (also 5HT-1A)
  • Causes:
    • hyperthermia,
    • muscle rigidity,
    • tremors,
    • autonomic instability,
    • confusion,
    • irritability,
    • agitation
    • can progress toward coma & death
  • Also caused by MDMA (Ecstacy)
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14
Q

How do you treat Serotonin Syndrome?

A

Administer nonselective serotonin antagonists (Cyproheptadine, etc.)

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15
Q

What drug interaction is most worriesome when treating with MAOIs?

A

Tyramine

  • Sympathomimetic amine potentiated by MAOIs
  • Metabolized by hepatic MAO
  • If patient has taken MAO inhibitor, tyramine enters systemic circulation
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16
Q

What happens when Tyramine enters systemic circulation?

A
  • Combined effect of tyramine and MAO inhibitor
    • Massive adrenergic stimulation (Epi/NE release)
    • Released catecholamines stimulate postsynaptic receptors in the periphery, increasing blood pressure to dangerous levels
    • May result in a hypertensive crisis
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17
Q

What three foods must people on MOAIs avoid? Why?

A
  • Foods rich in Tyramine
    • Aged cheese
    • Red wine
    • Beer
18
Q

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

A

Inhibits pre-synaptic serotonin reuptake pumps

  • inhibits feedback loop, so release continues
  • allows additional release of 5HT
19
Q

What drug class does Fluoxetine (Prozac) belong in?

A

SSRIs

20
Q

What drug class does Sertraline (Zoloft) belong in?

A

SSRIs

21
Q

What drug class does Escitalopram (Lexapro) belong in?

A

SSRIs

22
Q

What are adverse effects of SSRIs?

A
  • Nausea
  • Diarrhea
  • Weight loss
  • Stimulation:
    • Anxiety
    • Nervousness
    • Insomnia
  • Sexual dysfunction
  • Increased risk for suicidal thoughts & behavior
23
Q

What disorder should SSRIs not be the sole treatment of?

A

Bipolar disorder!

(can switch from depressed right into manic phase)

24
Q

What specific serotonin receptor contributes to the clinical improvement seen in SSRI treatments?

A

5-HT2A

25
Q

What is the MOA of Venlafaxine (Effexor, Effexor XR)?

A
  • Serotonin-Norepinephrine reuptake inhibitor (SNRI)
    • Blocks 5-HT reuptake like SSRIs
    • Also blocks NE reuptake
26
Q

What does Venlafaxine (Effexor, Effexor XR) NOT effect?

A
  • Adrenergic receptors
  • Histaminergic receptors
  • Cholinergic receptors

(TCA effect on these receptors causes its adverse side effects)

27
Q

Why does raising the dose of Venlafaxine improve efficacy?

A

Secondary mechanisms of action:

  • low dose only affects 5HT
  • medium dose affects 5HT/NE
  • high dose affects DA
28
Q

What is the MOA of <!--StartFragment-->Mirtazapine (Remeron)?<!--EndFragment-->

A
  • Blocks pre-synaptic alpha-2 receptors on:
    • adrenergic neurons (autoreceptors)
    • serotonergic neurons (heteroceptors)
    • causes increased NE & 5HT levels
      • (blocks negative feedback loop)
29
Q

What is MOA of Lithium carbonate (<!--StartFragment-->Lithobid, <!--EndFragment-->Eskalith)?

A
  • Mechanism of action is unknown
    • Most likely involves effect on postsynaptic rather than presynaptic neuron
    • Interferes with the production and release of IP3 (phosphatdylinositol-4,5-bisphosphate) and DAG (diacyl glycerol)
    • Can inhibit norepinephrine-sensitive adenylyl cyclase
    • May uncouple receptor recognition site from GTP-binding protein (G-protein) by competing with Mg2+
    • May affect several cell or nuclear regulatory factors
    • Working hypothesis: alters gene expression implicated in long-term neuroplastic events that could underlie long-term mood stabilization
30
Q

What are adverse effects of Lithium carbonate?

A
  • Fatigue
  • muscular weakness
  • slurred speech
  • ataxia
  • fine tremor of the hands
  • excessive thirst and urination
31
Q

What are the clinical/therapeutic uses of Lithium carbonate?

A
  • Manic phases of bipolar disorder
  • Prevention of mood swings in patients prone to bipolar disorder
  • Antidepressant effect in some patients
32
Q

What happens in Lithium toxicity?

A
  • CNS primarily affected
    • consciousness is impaired
    • coma may result
  • Muscular rigidity
  • hyperactive deep reflexes
  • marked tremor and muscle fasciculations
33
Q

Whys is Lithium toxicity easy to acheive?

A

Therapeutic dose (0.8 - 1.4 mEq/l) is very close to toxic range (>2 mEq/l).

34
Q

How do you treat Lithium toxicity?

A

Symptomatic

35
Q

What is Valproic acid (Depakene) used to treat?

A

Rapid-cycling bipolar disorder

(appropriate first-line treatment for some)

36
Q

What drug class does Valproic acid (Depakene) belong in?

A

Anticonvulsant

37
Q

What is Carbamazepine (Tegretol) used for?

A

Prophylaxis of bipolar disorder

38
Q

What drug class does Carbamazepine (Tegretol) belong in?

A

Anticonvulsants

39
Q

Why should SSRIs/SNRIs never be used as monotherapy in patients with bipolar disorder?

A
  • May cause rapid onset of mania
  • Patients should be receiving prophylactic mood stabilizer therapy to prevent this from occurring
40
Q

What new drug was just approved in 2013 to treat bipolar disorder and presumably works through central dopamine (D2) and serotonin (5-HT2A) receptor antagonism, but the precise mechanism is unknown?

A

Lurasidone (Latuda)

Atypical Antipsychotic

Neuro B5 - WLB (19 decks)

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