Antidepressants Flashcards
Types of depression
-reactive
-major
-bipolar affective
Physiological features of depression
-dec sleep
-appetite changes
-fatigue
-psychomotor dysfunction
-menstrual irreg, palpiations, constipation, headaches, nonspecific body aches
Psychological features of depression
-dysphoric mood
-worthlessness
-quilt
-apathy
-dec concentration
-suicide
Drug-induced depression
-antihypertensive and CV
-sedative/hypnotics
-anti-inflammaroy/analgesics
-steroids
-others
AntiHTN and CV drug-induced depression
reserpine
-methyldopa
-propranolol
-metoprolol
-prazosin
-clonidine
-digitalis
Sedative-hypnotic drug-induced depression
-alc
-benzos
-barbituates
-meprobamate
anti-inflammatoy and analgesic drug-induced depression
-indomethacin
-phenylbutazone
-opiates
-pentazocine
Steroid drug-induced depression
-corticosteroids
-oral contraceptive
-estrogen withdrawal
misc drug-induced depression
-anti-PD
-anti-neoplastic
-neurleptics
Biogeenic amine hypothesis of depression
-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
Neuroendocrine hypothesis of depression
-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
HPA
CRF
Neurotrophic hypothesis of depression
-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)
BDNF
Dendritic sprouts
Effect of BDNF on neuronal growth
-maintain complexity of neurons (branching)
Integration hypothesis of depression (most preferred) (combo)
-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
Main classes of antidepressants
-MAOIs
-TCAs
-SSRI
-SNRI
-5HT2 antagonists
-tetracyclic and unicyclic
Why does therapy take 4-8 weeks?
-no one knows
-maybe neuroadaptive response
-delay due to: activation of presynaptic? pre or post synaptic adaptation?
MAOI MOA
-prevent degradation of NE and serotonin by monoamine oxidase (MAO)
=moreNE and 5HT released into synapse
Non-selective MAO
-phenelzine
-tranylcypromine
MAO-B selective
-selegiline
-Safinamide
MAO-A selective
-moclobemide
MOA inhibitor side effects
-headache
-drowsiness
-dry mouth
-weight gain
-orthostatic hypotension
-sexual dysfunction
-HTN crisis!
-limited use
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)
Tricyclic antidepressant use
-major depression
-panic disorders
-chronic pain
-enuresis
TCA overdose/toxicity
-extremely dangeous
-depressed pt are more likely to be suicidal
Tertiary amines MOA
-inhibit NE and 5HT uptake via NET and SERT
-antihistamine (H1)
-antimuscarinic
-antiadgrenergic (a1)
Tertiary amine side effects
-most sedation, autonomic, weight gain
-heart conduction disturbances
Tertiary amine drugs
-Imipramine
-Amitriptyline
-Trimipramine/Clomipramine
-Doxepin
Secondary amine drugs
-desipramine
-nortriptyline
-protriptyline
-maprotilline (NET inhibitor) (tetracyclic reduced side effects)
secondary amine side effects
-less than tertiary
All TCA side effects
-anticholinergic
-CV in elderly
-neurological
-wt gain
-suicidal
SSRI MOA
-block serotonin transporters
-5HT stays in synapse longer
SSRI drugs
-fluoxetine
-fluvoxamine
-paroxetine
-sertraline
-citalopram
-escitalopram
Use of SSRI
-depression
-alcoholism
-OCD
-Enuresis
-PTSD
-eating disorders
-social phobias
-anxiety
-PMDD
SSRI side effects
-N/V
-headache
-sexual dysfunction
-anxiety
-insomnia
-tremor
SSRI dc syndrome
-brain zaps
-dizziness
-sweating
-nausea
-insomnia
-tremor
-confusion
-vertigo
Serotonin syndrome interactions
-when given w MAOI, TCA,metoclopramide, tramadol, triptans, st johns
Serotonin syndrome sx
-hyperthermia
-muscle rigidity
-restlessness
-myoclonus
-hyperreflexia
-sweating
-shivering
-seizure
-comas
serotonin syndrome treatment
-dc meds and manage sx
-admin serotonin anatagonist (cyprohepatidine or methysergide)
-benzos to control myoclonus
SSRI + 5TH1A partial agonists
-Vilazodone (reduced sex side effects, similar to apiprazole and buspirone)
-Vortioxetine
SNRI drugs
-venlafaxine
-Desvenlafaxine
-Duloxetine
-Milnacipran
-Levomilacipram
Venlafaxine
-NET and SERT inhibitor (SNRI)
-treat GAD and panic
-maybe neuropathy and migraine prevention
Desvenlafaxine
-NET and SERT inhibitor (SNRI)
-tx vasomotor sx associated w menopaus
Duloxetine
-NET/SERT inhibitor (SNRI)
-tx GAD and peripheral neuropathy
Milnacipran
-NET/SERT inhibitor (SNRI)
-tx fibromyalgia
Levominacipran
-active enantiomer of milnacipran
-NET/SERT inhibitor (SNRI)
Norepinephrine selective reuptake inhibitors (NSRIs) drugs
-Reboxetine
-Atomoxetine
Reboxetine
-less side effects than prozac
-not used in USA tho
-NSRI
Atomoxetine
-og meant for depression
-use for ADHD now
-NSRI
selectivity profiles?
Serotonin-NE-DA reuptake inhibitors (SNDRIs)
-triple blockers or triple reuptake inhibitors
-Tesofensine and brasofensine
-NS2359 (GSK) and dov216303 (Merck)
Tesofensine and brasofensine
-SNDRIs
-maybe parkinsons
-tesofensine as appetite suppressant
NMDA antagonists
-rapid acting
-ketamine subanesthetic dose
-scoplamine
-lanicemine
-GLYx-13 parital
Low trapping NMDA antagonists
-
Clinically used NMDA antagonists
-ketamine
-esketamine adj w oral antidepressant
-CNS depression, drug interaction
-restricted program only (REMS)
-intranasal
Postpartum Depression (PPD)
-SSRIs (fluoxetine and paroxetine) and venlafaxine
-others: CBT and counseling
-maybe brexanolone
Brexanolone
-newer GABA-A drug
-resensitizes GABA-A receptors to inc then dec of allopregnanolone levels after birth
-REMS
-60h infusion
-$$$$$
New agents
-psychedelics (MDMA, psilocybin, LSD)
-5HT2C ANTAgonists
-metabotropic glutamate receptor agonists
-reversible inhibitors of MAO-A (RIMAs)
RIMAs
-reversible inhibitors of MAO-A
-moclobemide
-brofaromine
-as effective as TCAs and better tolerated
nonpharm
-electroconvulsive therapy
-psychotherapy
-hospitalization
considerations
-severity, endo vs exogenous
-onset of drug action
-uni vs bipolar
-drug selection
-dosing
-duration of therapy
-compliance
Antidepression and Pain transmission
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