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Therapeutics II (Spring) > Antidepressants > Flashcards

Antidepressants Flashcards

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1
Q

Types of depression

A

-reactive
-major
-bipolar affective

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2
Q

Physiological features of depression

A

-dec sleep
-appetite changes
-fatigue
-psychomotor dysfunction
-menstrual irreg, palpiations, constipation, headaches, nonspecific body aches

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3
Q

Psychological features of depression

A

-dysphoric mood
-worthlessness
-quilt
-apathy
-dec concentration
-suicide

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4
Q

Drug-induced depression

A

-antihypertensive and CV
-sedative/hypnotics
-anti-inflammaroy/analgesics
-steroids
-others

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5
Q

AntiHTN and CV drug-induced depression

A

reserpine
-methyldopa
-propranolol
-metoprolol
-prazosin
-clonidine
-digitalis

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6
Q

Sedative-hypnotic drug-induced depression

A

-alc
-benzos
-barbituates
-meprobamate

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7
Q

anti-inflammatoy and analgesic drug-induced depression

A

-indomethacin
-phenylbutazone
-opiates
-pentazocine

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8
Q

Steroid drug-induced depression

A

-corticosteroids
-oral contraceptive
-estrogen withdrawal

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9
Q

misc drug-induced depression

A

-anti-PD
-anti-neoplastic
-neurleptics

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10
Q

Biogeenic amine hypothesis of depression

A

-risperidine causes depression by depleting NE and 5HT from vesivles
-tx w agents that inc 5HT and NE
-genetic polymorphisms in SERT promoter
-alerations in 5HT1A/2C and a2 receptors

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11
Q

Neuroendocrine hypothesis of depression

A

-changes in hypothalamic-pituitary Adrenal (HPA) axis
-stress causes hypothalamus to release CRF, CRF promotes ACTH release fro pituitary, ACTH promotes release of cortisol from adrenal
-overactivity of HPA and elevated CRF in almost all depressed pt
-elevated CRF causes insomnia, aanxiety, dec appetite, libido
-antidepressants and ECT reduce CRF levels

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12
Q

HPA

A
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13
Q

CRF

A
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14
Q

Neurotrophic hypothesis of depression

A

-Brain-derived neurotrophic factor (BDNF) critical in neural plasticity, resilience, neurogenesis
-stress and pain dec BDNF
-dec in volume of hippocampus (memory and HPA regulation)
-BDNF has antidepressant activity
-antidepressants inc BDNF levels and maybe hippocampal volume
-some animal studies might not support)

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15
Q

BDNF

A
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16
Q

Dendritic sprouts

A
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17
Q

Effect of BDNF on neuronal growth

A

-maintain complexity of neurons (branching)

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18
Q

Integration hypothesis of depression (most preferred) (combo)

A

-HPA and steroid abnormalities regulate BDNF levels
-hippocampal glucocorticoid receptors activated by cortisol during stress (dec BDNF)
-chronic activation of monoamine receptors inc BDNF signaling
-chronic activation of monoamine receptors leads to downregulation of HPA axis

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19
Q

Main classes of antidepressants

A

-MAOIs
-TCAs
-SSRI
-SNRI
-5HT2 antagonists
-tetracyclic and unicyclic

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20
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24
Why does therapy take 4-8 weeks?
-no one knows -maybe neuroadaptive response -delay due to: activation of presynaptic? pre or post synaptic adaptation?
25
MAOI MOA
-prevent degradation of NE and serotonin by monoamine oxidase (MAO) =moreNE and 5HT released into synapse
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Non-selective MAO
-phenelzine -tranylcypromine
27
MAO-B selective
-selegiline -Safinamide
28
MAO-A selective
-moclobemide
29
MOA inhibitor side effects
-headache -drowsiness -dry mouth -weight gain -orthostatic hypotension -sexual dysfunction -HTN crisis! -limited use
30
MAOI interactions
-OTCs: cold meds, diet pills -Rx: TCAs, SSRIs, L-DOPA -St. John's Wort (also blocks MAO) -AVOID Tyramine (cheese, processed meat, avo, beer, tofu)
31
Tricyclic antidepressant use
-major depression -panic disorders -chronic pain -enuresis
32
TCA overdose/toxicity
-extremely dangeous -depressed pt are more likely to be suicidal
33
Tertiary amines MOA
-inhibit NE and 5HT uptake via NET and SERT -antihistamine (H1) -antimuscarinic -antiadgrenergic (a1)
34
Tertiary amine side effects
-most sedation, autonomic, weight gain -heart conduction disturbances
35
Tertiary amine drugs
-Imipramine -Amitriptyline -Trimipramine/Clomipramine -Doxepin
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Secondary amine drugs
-desipramine -nortriptyline -protriptyline -maprotilline (NET inhibitor) (tetracyclic reduced side effects)
43
secondary amine side effects
-less than tertiary
44
All TCA side effects
-anticholinergic -CV in elderly -neurological -wt gain -suicidal
45
SSRI MOA
-block serotonin transporters -5HT stays in synapse longer
46
SSRI drugs
-fluoxetine -fluvoxamine -paroxetine -sertraline -citalopram -escitalopram
47
Use of SSRI
-depression -alcoholism -OCD -Enuresis -PTSD -eating disorders -social phobias -anxiety -PMDD
48
SSRI side effects
-N/V -headache -sexual dysfunction -anxiety -insomnia -tremor
49
SSRI dc syndrome
-brain zaps -dizziness -sweating -nausea -insomnia -tremor -confusion -vertigo
50
Serotonin syndrome interactions
-when given w MAOI, TCA,metoclopramide, tramadol, triptans, st johns
51
Serotonin syndrome sx
-hyperthermia -muscle rigidity -restlessness -myoclonus -hyperreflexia -sweating -shivering -seizure -comas
52
serotonin syndrome treatment
-dc meds and manage sx -admin serotonin anatagonist (cyprohepatidine or methysergide) -benzos to control myoclonus
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SSRI + 5TH1A partial agonists
-Vilazodone (reduced sex side effects, similar to apiprazole and buspirone) -Vortioxetine
54
SNRI drugs
-venlafaxine -Desvenlafaxine -Duloxetine -Milnacipran -Levomilacipram
55
Venlafaxine
-NET and SERT inhibitor (SNRI) -treat GAD and panic -maybe neuropathy and migraine prevention
56
Desvenlafaxine
-NET and SERT inhibitor (SNRI) -tx vasomotor sx associated w menopaus
57
Duloxetine
-NET/SERT inhibitor (SNRI) -tx GAD and peripheral neuropathy
58
Milnacipran
-NET/SERT inhibitor (SNRI) -tx fibromyalgia
59
Levominacipran
-active enantiomer of milnacipran -NET/SERT inhibitor (SNRI)
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Norepinephrine selective reuptake inhibitors (NSRIs) drugs
-Reboxetine -Atomoxetine
61
Reboxetine
-less side effects than prozac -not used in USA tho -NSRI
62
Atomoxetine
-og meant for depression -use for ADHD now -NSRI
63
selectivity profiles?
64
Serotonin-NE-DA reuptake inhibitors (SNDRIs)
-triple blockers or triple reuptake inhibitors -Tesofensine and brasofensine -NS2359 (GSK) and dov216303 (Merck)
65
Tesofensine and brasofensine
-SNDRIs -maybe parkinsons -tesofensine as appetite suppressant
66
NMDA antagonists
-rapid acting -ketamine subanesthetic dose -scoplamine -lanicemine -GLYx-13 parital
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Low trapping NMDA antagonists
-
68
Clinically used NMDA antagonists
-ketamine -esketamine adj w oral antidepressant -CNS depression, drug interaction -restricted program only (REMS) -intranasal
69
Postpartum Depression (PPD)
-SSRIs (fluoxetine and paroxetine) and venlafaxine -others: CBT and counseling -maybe brexanolone
70
Brexanolone
-newer GABA-A drug -resensitizes GABA-A receptors to inc then dec of allopregnanolone levels after birth -REMS -60h infusion -$$$$$
71
New agents
-psychedelics (MDMA, psilocybin, LSD) -5HT2C ANTAgonists -metabotropic glutamate receptor agonists -reversible inhibitors of MAO-A (RIMAs)
72
RIMAs
-reversible inhibitors of MAO-A -moclobemide -brofaromine -as effective as TCAs and better tolerated
73
nonpharm
-electroconvulsive therapy -psychotherapy -hospitalization
74
considerations
-severity, endo vs exogenous -onset of drug action -uni vs bipolar -drug selection -dosing -duration of therapy -compliance
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Antidepression and Pain transmission
-
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Therapeutics II (Spring) (57 decks)

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