-blocks the neuronal reuptake of NE or NE and 5HT

-binds to NET, SERT, DAT (not that important)

-It takes about 4-6 weeks to see clinical effects of these drug.

-this is due to the complex secondary adaptations to blockade

-activation at the alpha 2 receptors on the presynapse

-decrease in NE release

-densensitization

-NE returns to normal

-the expression of tyrosine hydroxylase and NET is decreased overtime

-change in sensitivity of NMDA, GABA B, 5HT 1 and 2, beta-2, alpha-1, D2

-increase in CREB and BDNF

Glucocorticoids decrease the levels of BDNF. When this occurs, there is a reduction in dentritic branching and a decrease in synapses between the neurons

-TCAs allow the nerves and synapses to grow, therefore an increase in branching and connections

-low therapeutic index

-antimuscarnic

-weight gain

-sedation through antihistamine effects: trazodone and mirtaxapine; potentiate other sedatives

-sexual dysfunction

-reduction in seizure threshold

-hypotention: orthostatic due to alpha 1: tacycardia

-cardiac effects: slowed conduction times leading to arrhythmias like class I

agitation, nausa/vomiting, sucidal tendencies in adolescents, sexual dysfunction, akathisia

-compared to TCAs, they are much safer, and have lesser risk of AEs of TCAs

-no antihistamine effect

-SSRIs are substrates and inhibitors for cyp450s: mostly for 2D6

-(fluvoxamine, fluoxetine, paroxetine > sertraline > citalopram)

-activation at the post synapse of 5-HT receptors

-autoreceptor activation at the 5HT1 receptor on the presynapse

-desensitize of autoreceptors over weeks: serotonin returns to normal

-downregulation of post synapse

-increase in CREB and BDNF

loss of appetite, sexual s/e, sleep disturbances

We see no muscarinic effects

effexor: dose dependant inhibition of SERT, NE, and DA (low doses it is an SSRI)

-minacipran: good for fibromyalgia

-cymbalta: can cause hepatotoxicity; can also be used for neuropathic pain

-good for smoking sensation

-can cause agitation and seizures

-affects DA (increase)

-amphetamine like metabolites increase DA and NE

-affects the 5HT reuptake and receptors

-sedation and hepatotoxicity 

-affects 5HT reuptake

-sedation

-priapism 

***usually given at bedtime

deaminates NE, DA, 5HT, E and tyramine

-thought to be a housekeeping enzyme that prevents any leaky vesicles that would cause monoamines into the synapse

metabolizes DA and tyramine

-thought to be a housekeeping enzyme that clears out any monoamines that might go to the synapse due to leaky vesicles

-indirect acting sympathomimetics: hypertension and intrancranial bleeding

-amphetamines

-Tyramine containing foods: HTN

-take weeks to see clinical effects

-metabolized faster in children than younger adults

-slight dependance and withdrawal

-TCAs cause myalgia and sedation

-SSRIs: myalgia, GI, paresthesias, irritability

MAOIs: psycosis, convulsions

-wont see any effects on nondepressants

-MAOi

-SSRI

-TCA

-Tryptophan 

-tramadol

-meperidine

-amphetamine

serotonin agonists: buspirone, triptans 

-OTC dextromeophan

-Zyvox

cyproheptadine (5HT2 blocking activity) 

-it is also an antihistamine

(Zyprexa also has 5HT2 blocking activity)

MILD SYMPTOMS

-akathisia

-tremors

-altered mental status

-clonus (inducible): hyperflexive

-clonus: sustained

-muscular hypertonicity (increase body movements)

- hyperthermia

SEVERE SYMPTOMS

***We will see HTN throughout this pathway

-treatment for mania (bipolar-mania and depression): caused by increase in Monoamines in the synapse

-MOA is unknown but thought to inhibit NE and DA release, and Increase 5HT

-also inhibits PKC and PI pathway

-low therapeutic index (we can check serum levels to predict efficacy and adverse effects)

-hyponatremia can cause lithium retention (diuresis, diarrhea, NSAIDs ACEi)

-abdominal pain, polyuria, fine tremors, skin rashes (acquired diabetes insipidus, vasopression resistance)

-coma, serizures, confusion, death

-thyroid enlargement but decrease in thyroid function