Lecture 76: Antidepressants Flashcards

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1
Q

MAOIs (key, 3)

A

Phenelzine, tranylcypromine, selegiline

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2
Q

What is special about selegline?

A

Patch delivery

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3
Q

Are MAOIs first line? What population might they be used?

A

No–after trying other anti-depressants first; atypical depression: sleep/eat a lot

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4
Q

MAOI mechanism

A

MAO located in presynaptic neuron and degrades monoamines –> MAOIs inhibit enzyme, inhibiting degradation of monoamines

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5
Q

Important MAOI mechanism notes

A

More NT in both presynaptic neuron AND cleft; irreversible (MAOIs take 2 weeks to recover)

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6
Q

Describe types of MAOs and targeted catecholamines. Which one is in the gut? Which one degrades tyramine? Which are targeted by MAOIs?

A

MAOa: 5-HT, NE, Epi, DA; MAOb: DA; MAOa; both; both

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7
Q

2 MAIN (scary) side effects of MAOI and mechanism

A
  1. Also inhibit breakdown of Tyramine –> NE release (hypertensive crisis) if combined with tyramine diet or adrenergic agonists; 2. Serotonin syndrome if combined with other serotonergic drugs
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8
Q

Other SEs of MAOIs (5)

A

Orthostatic hypotension, weight gain, insomnia, sexual dysfunction, rare hepatoxicity

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9
Q

Describe symptoms serotonin syndrome (11)

A

Abdominal pain, diarrhea, sweating, hyperthermia, tachycardia, hypertension, myoclonus, tremor, irritability, delirium, death

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10
Q

What can you NOT take with MAOIs because of serotonin syndrome (3)

A

Other antidepressants, dextromethorphan (cough medicine) and opiates

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11
Q

What else can you NOT take with MAOIs? Why?

A

Decongestants, stimulants because they can cause hypertensive crisis (BP > 120 mm Hg) due adrenergic agonists

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12
Q

What food items must be avoided with MAOIs? Why?

A

Tyramine inhibition in GUT via MAOa but if tyramine gets access to NE sympa neurons, these MAOa are ALSO blocked leading to NE release; soy, beer, red wine, aged cheese, dried sausage, liver, smoked fish, sauerkraut

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13
Q

How long must a patient wait to resume normal diet after stopping MAOI?

A

2 weeks

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14
Q

Describe Selegiline’s hope

A

At low doses only inhibits MAOb, but turns out at antidepressant levels, also inhibits MAOa so STILL requires dietary restriction

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15
Q

TCAs (key, 1) and secondary amines (key, 2)

A

Amitriptyine; nortriptyline, desipramine

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16
Q

Mechanism of TCAs (?)

A

Inhibit re-uptake of NE and 5-HT

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17
Q

TCA therapeutic uses (4)

A

Depression, neuropathic pain, anixety, migraine

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18
Q

How are tertiary amines different?

A

Also inhibit 5-HT reuptake

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19
Q

TCA SEs via receptor

A

H1 blocker: sedation, weight gain; Alpha1 blockers: orthostatic hypotension; M1 blocker (anticholinergic) constipation/urinary retention, dry mouth, blurred vision; Na channel blockers: type 1 antiarrythmic effects; Serotonin Reuptake inhibitors (same as SSRIs)

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20
Q

Problem with TCAs being a NA channel blocker (2)

A
  1. If you have bad ischemic heart disease, TCA can CAUSE arrythmias; 2. Can lead to overdose
21
Q

Which TCAs are the LEAST anticholinergic and alpha1 blockers

A

Secondary amines

22
Q

TCA: avoid in…

A

People with narrow angle glaucoma, recent cardiac events, children, elderly (orthostatic hypotension –> falling)

23
Q

TCA is active in what liver system?

A

Metabolized BY cytochrome p450

24
Q

SSRIs (key, 5)

A

Fluoxetine, sertraline, paroxetine, citalopram, escitalopram

25
Q

SSRIs major indications (4)

A

MDD, anxiety, OCD, bulimia

26
Q

SSRI mechanism (main)

A

Inhibit reuptake of 5-HT into presynaptic neuron –> more 5-HT in synapse

27
Q

SSRI secondary effects. Important?

A

Some NE and DA reuptake effects; potential SEs

28
Q

Paroxetine secondarily

A

Inhibits NE reuptake

29
Q

Sertraline secondarily; why important

A

Inhibits DA reuptake –> activating good for tired patients

30
Q

SSRIs common SE

A

GI, weight gain, tremor, headache, sweating, sexual

31
Q

SSRIs less common SE

A

Dry mouth, bruising/bleeding (important for surgery), hyponatremia, vivid dreams, serotonin syndrome, mania if underlying BP disorder

32
Q

Fluoxetine has the most…What else is special about this drug (2)?

A

Drug:drug interactions due to p450 inhibition; longest half-life (once weekly formula, best for people who don’t take drugs daily); “activating” –> insomnia

33
Q

Citalopram and Escitalopram has the fewest…importance?

A

Drug:drug interactions; perhaps fewest SEs

34
Q

Paroxetine half-life is…causing…What else is noteworthy about this drug?

A

Short; withdrawal symptoms; NE reuptake blockade and anticholinergic activity; more sedation, dry mouth, weight gain

35
Q

Describe SSRI withdrawal and how long. Drug least and most likely

A

Abrupt discontinution of SSRI –> dizziness, nausea, paresthesias, flu-like, muscle aches, headaches; 3 weeks; fluoxetine = least and paroxetine = most

36
Q

SSRI advantages

A

Standard dosing, clinical response at starting dose, not lethal in OD, no arhythmias, no changes in BP, no seizures, fewer drug-drug interactions

37
Q

Problem with SSRIs and new drugs?

A

Perhaps SSRIs are not effective enough because of the lost of NE, but trying to be less dirty (= SNRIs)

38
Q

SNRIs (key, 2)

A

Venlafaxine, duloxetine

39
Q

SNRI therapeutic use (3)

A

Neuropathic pain, depression, anxiety

40
Q

SNRI SEs

A

Increases diastolic BP at higher doses, otherwise similar to SSRIs

41
Q

Duloxetine (describe and 2 SEs)

A

Affinity for 5HT and NE at all doses with many pain and psych indiactions; small amount get hepatoxicity and elevated BP is possible

42
Q

Advantage of Buproprion and therapeutic use. Mechanism? Avoid in what 3 patients?

A

No weight gain/sex issues; MDD, smoking cessation, ADHD; weak NE and DA inhibitor AND inhibits nACh but NOT 5-HT; avoid in anxious patients, alcoholics (seizure), eating disordered

43
Q

Buproprion SEs (scary one and others)

A

Seizures at high doses; anxiety, rare psychosis

44
Q

Mirtazapine mechanism. Avoids what SEs but not?

A

Alpha2 antagonist (presynaptic) –> more NE and 5-HT NT but blocks 5-HT subtypes that causes SEs (GI, sexual); avoids sexual and GI SEs but STILL causes sedation/weight gain

45
Q

Mirtazapine should be used in what patients…

A

People who are NOT eating or sleeping

46
Q

Trazadone is too…so now just used for? SEs?

A

Sedating; insomnia; priapism

47
Q

Anti-depressant response rate (%)

A

60%

48
Q

Four theories for antidepressant action

A
  1. Therapeutic delay –> downregulation of receptors; 2. Enhance neuronal regeneration; 3. Restore cortical dendrites; 4. Increase expression of neurotrophic factors
49
Q

Comorbid pain, think…

A

SNRIs