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Summer pharm 4 > Antidepressants > Flashcards

Antidepressants Flashcards

1
Q

What is the hypothesis behind mood

A

major depressive disorders result from a functional deficiency of NE or 5-HT at synapses in CNS
Neurotropic and endocrine components

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2
Q

Neurotropic hypothesis of major depression is

A

Changes in tropic factors and hormones play a major role
Successful treatment results in changes in:
CREB (cAMP response element binding)
BDNF (brain derived neurotrophic factor

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3
Q

What do monoamine NT do and how do antidepressants take advantage

A

Carry messages between cells
Initiate cascade of events
Reabsorbed back into nerve cells
-Most antidepressants inhibit transporter reuptake molecules so the NT stay in the synapse longer

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4
Q

What is the amine hypothesis of major depression and how do antidepressants use this

A

Depression is associated with changes in serotonin or NE

Many antidepressants cause changes in amine signaling!

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5
Q

What neuroendocrine factors are associated with depression

A

Thyroid dysregulation
Estrogen deficiency
Testosterone deficiency
More severe depression: Abnormal HPA axis, elevated cortisol

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6
Q

What are the phases of MDD treatment

A

Acute: 6-12 weeks. goal is remission (eliminate Sx)
Continuation: 4-9 months after remission. goal is prevent relapse and eliminate residual Sx
Maintenance: 12-36 months. goal is prevent recurrence

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7
Q

What meds are associated with inducing depressive Sx

A 
Isotretinoin 
Anticonvulsants 
Triptans 
BB, clonidine, methyldopa, reserpine
Hormone therapy 
interferons 
varenicline (smoking cessation)
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8
Q

What drugs are used as antidepressants

A 
TCA
MAOI
SSRI
SNRI
5HT2
heterocyclic antidepressants
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9
Q

What is the PK of antidepressants (general overview)

A 
Rapid oral absorption 
Peak plasma in 2-3 hours 
Tightly bound to plasma proteins 
Hepatic metabolism 
Renally cleared
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10
Q

Antidepressants can be used to Tx

A 
MDD
panic disorder 
GAD
PTSD
OCD 
Neuropathic pain, fibromyalgia, PMDD, menopause vasomotor Sx, stress incontinence
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11
Q

What are TCA

A

Block re-uptake transporters of NE and 5-HT
Used in MDD, *chronic pain, *enuresis, and insomnia
-Amitriptyline, Imipramine, Desipramine, Doxepin, Nortriptyline

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12
Q

What are ADE of TCA

A

muscarinic block (anticholinergic)
sedation
weight gain
OD: arrhythmia, seizure

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13
Q

What are the most potent TCA’s

A

Most potent 5-HT blockers: Ami, Imi
Most potent NE blocker: Desi, Nor
-highest potency drugs have the most ADE!

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14
Q

What are MAO inhibitors

A

Inhibit monoamine oxidases that normally metabolize NE and serotonin (type A) and dopamine (type B)
Used in unresponsive MDD, anxiety, panic d/o
Selegiline in parkinson’s (MAO-B)
-Phenelzine, Tranylcypromine, selegeline

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15
Q

MAOI interact with what drugs

A

Tyramine and sympathomimetics: cause HTN

SSRI: cause serotonin syndrome

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16
Q

Toxicities of MAOI are

A

Hypotension

Insomnia

17
Q

Those on MAOI should avoid these foods (only a few big ones)

A 
dairy 
beer 
wine 
canned aged meat 
sardines 
liver 
yeast 
pod beans 
chocolate 
coffee
licorice  
soy sauce
18
Q

What are SSRIs

A

Selectively inhibit 5-HT transporters w/ modest effects on other NT (fluoxetine and paroxetine mildly block NE)
Used for MDD, GAD, PTSD, OCD, panic d/o, PMDD, bulimia
-Citalopram, Escitalopram, Fluoxetine*, Paroxetnie, Sertraline

19
Q

SSRI interact with

A

Warfarin*: alprazolam and theophylline increase blood levels
lithium
TCA

20
Q

ADE of SSRI are

A

anxiety, insomnia, nausea, serotonin syndrome, sexual dysfunction

citalopram: QT prolongation
fluoxetine: anorexia
fluvoxetine: somnolence
paroxetine: anticholinergic ADE (mildly blocks NE)

21
Q

Bolded dosing info on SSRI’s

A

Citalopram: do not dose >40mg/d to avoid QT prolongation risk
Escitalopram: can increase to max dose after 1 week

22
Q

What ADE is common to all antidepressants

A

Suicidality; Increased risk if <24, Decreased risk if >65

Monitor for behavioral changes and mental status

23
Q

What are SNRI

A

heterocyclic drugs that block NE and 5HT transporters but LACK alpha blocking, anticholinergic, and antihistaminic actions of TCA
Used for MDD, FAD, neuropathies, fibromyalgia, SUI, and menopause vasomotor Sx
-Venlafaxine*, duloxetine, levomilnacipran

24
Q

ADE of SNRI are

A 
HTN/tachy , insomnia, nausea, serotonin syndrome, sexual dysfunction
dose dependent HTN: venlafaxine
orthostatic hypotension: Duloxetine
HLD: desvenlafaxine 
Seizures (venlafaxine, desvenlafaxine)
25
Q

Bolded dosing info on SNRI newer generation

A

Desvenlafaxine ADE are increased with higher dose, but benefits do not increase with dose
Venlafaxine: reduce dose if sustained HTN occurs

26
Q

What are mixed 5-HT2 antagonists/5-HT1a enhancers

A

Block 5-HT2 receptors with minor effects on amine transporters
Used for MDD and hypnotics
-Trazodone, Nefazodone, Vilazodone, Vortioxetine

27
Q

ADE of mixed serotonergics are

A 
Nef: hepatic toxicity 
Traz: sedation, orthostatic hypotension 
Vila: serotonin syndrome, decreased male libido
Vori: GI and sexual dysfunction 
Depression and anxiety 
Depression with cognitive difficulties
28
Q

What is Buproprion

A

NE and dopamine reuptake inhibitor
Used in smoking cessation and MDD
May cause seizures (dose related, and increased w/ alcohol withdrawal, head trauma, CNS tumor)

29
Q

What is Miratazepine

A

Presynaptic a2 blocker w/ some effect on 5-HT
Used for sedation
May cause sedation and weight gain

30
Q

Choose an antidepressant based on

A 
indication 
cost
availability
ADE
potential drug interactions
Pt Hx 
Pt preference 
age and gender 
medical status
31
Q

What are non-med options in treating depression

A

Electorconvulsive therapy

Repetitive Transcranial Magnetic Stimulation

32
Q

What supplements an help Tx depression

A

Omega 3 fatty acids (EPA +/- DHA): used to augment Tx of MDD
St john’s wort: mild-mod MDD. induces hepatic metabolic enzymes
SAMe: under review by task force
Folate: involved in synthesis of new NT, like 5-HT. Reasonable to augment MDD Tx with the 3 compounds

33
Q

What are the 3 folate compounds used in augmenting Tx of MDD

A

Folic acid
Folinic acid
5-Methyltetrahydrofolate

34
Q

Does exercise play a role in treating depression

A

Yes! a recent study even confirmed the benefit of exercise on depression
16 kcal/kg/wk exercise associated with greater remission rates in conjunction with an SSRI
Task force says to include exercise in Tx of MDD!

Summer pharm 4 (14 decks)

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