Santos Flashcards
main excitatory NT
glutamate -> depolarization
main inhibitory NT
GABA and glycine -> hyper polarization
Ion channels (ionotropic)
- FAST neurotransmission
- ligand or voltage gated
GPCR (metabotropic)
- SLOW neurotransmission
- Gq, Gs, Gi
GABAa receptors
- ionotropic -> FAST transmission
- where most drugs bind
GABAb receptors
-metabotropic -> SLOW transmission
glutamate decarboxylase
- converts glutamate to GABA
- requires vit. B6 cofactor
low vit. B6
decrease GABA synthesis -> seizures
ACh NT
- alpha-1 or beta receptors -> excitatory
- alpha-2 receptors -> inhibitory
Serotonin NT
- synthesized from Tryptophan
- 5-HT3R -> ionotropic -> FAST excitatory
- 5-HT1A -> metabotropic -> SLOW inhibitory
- 5-HT2 or 5-HT4 -> metabotropic -> SLOW excitatory
D1-class - D1, D5 receptors
increase AC -> excitatory (Gs)
D2-class: D2, D3, D4 receptors
decrease AC -> inhibitory (Gi)
Histamine: H1, H2 receptors
- metabotropic -> slow EXCITATORY
- H1R -> Gq (PLC)
- H2R -> Gs (AC)
Histamine: H3, H4 receptors
-metabotropic -> slow INHIBITORY
bipolar effective disorder
-high risk of SUICIDE
Lithium
- prophylaxis for mania and depression in bipolar
- REDUCE SUICIDE RISK
- Neuroprotective (increase BDNF, bcl-2)
- not used in renal failure
- NARROW therapeutic window (0.6-1.5 mEq/L)
- AE: tremor, hypothyroidism, DI, TERATOGEN (Ebsteins)
other drugs for bipolar disorder
Valproic acid, Carbamezapine, Lamotrigine
- Carbamezapine -> induce CYP3A4 and not used w/ other drugs
- Lamotrigene -> maintenance only
Schizophrenia
- most common psychotic disorder
- Pos Sx: hallucinations, delusions, disorganized thoughts
- Neg Sx: avolition, apathy, alogia
Monamine hypothesis
-Schizophrenia due to HIGH dopamine D2R, 5-HT2, or Glutamate neurotransmission
1st Gen (typical) antipsychotics
Chlorpromazine, Haloperidol
- D2R antagonists -> MORE EPS effects
- treat only positive Sx
2nd Gen (atypical) antipsychotics
Clozapine, Risperidone, Olanzapine, Quetiapine, Ziprasidone, Aripiprazole
- 5-HT2AR antagonists (some D2R blocking) -> LESS EPS effects
- INVERSE AGONISTS -> block 5-HTA2 and 5-HT2C receptors
- treat positive and negative Sx
Quetiapine
- 2nd gen
- block D1R > 5-HT2AR
Aripiprazole
- 2nd gen
- PARTIAL D2 AGONIST
side effects of antipsychotics
- EPS due to D2R blockade
- NEUROLEPTIC MALIGNANT SYNDROME
- hyperprolactinemia
- QT prolongation (torsades) -> block Ikr rectifier K+ channels
major depressive disorder (MDD)
- recurrent depressive episodes WITHOUT mania ( >2wks)
- SUICIDE RISK
SSRIs
Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Citalopram, Escitalopram, Vilazodone
MOA: inhibit SERT and stimulate 5-HT1A, 5-HT7 auto receptors
Fluoxetine and Paroxetine
- inhibit CYP2D6 -> drug interactions
- fluvoxamine -> inhibit CYP3A4
SNRIs
Duloxetine, Venlafaxine, Desvenlafaxine, Milnacipran, Levomilnacipran
-MOA: inhibit both SERT and NET and stimulate 5-HT1A, 5-HT1D, 5-HT7 auto receptors
TCA
Imipramine**, Desipramine, Clomipramine, Trimipramine, Amitriptyline, Protriptyline, Doxepin
- MOA: inhibit SERT and NET; antimuscarinic, antihistaminic, alpha-blockade
- AE: LETHAL OVERDOSE*** -> CARDIOTOXICITY
5-HT2 Antagonists
Trazodone, Nifazodone, Vortioxetine
- MOA: 5-HT2R antagonist; antimuscarinic, antihistaminic, alpha-blockade
- AE: sedation, orthostatic hypotension, PRIAPISM
MOA inhibitors
Phenelzine, Tranylcypromine, Selegiline
MOA: IRREVERSIBLE inhibitors of MAO-A and MAO-B -> decrease metabolism of 5-HT, NE, DA, and tyramine
-AE: TYRAMINE TOXICITY -> HTN crisis (and tachycardia/stroke) due to tyramine induced NE release
which drug is specific for blocking MAO-B?
Selegiline
Atypical antidepressants
Buproprion, Mirtazapine, Buspirone
- Buproprion -> inhibit NET and DAT
- Mirtazapine -> cause sedation & treat insomnia
what is associated with ALL antidepressants?
RISK OF SUICIDE
