Schizophrenia- Joshi

What are examples of positive, negative, and cognitive symptoms?

• pos: hallucinations, delusions, exaggeration/distortion of normal fxn

• neg: loss of motivation, alogia (loss of words), anhedonia (decreased pleasure)

• cog: decreased attention and working memory

What is the result of each of the following:

• ↑ activity of mesolimbic tract

• ↓ activity of mesocortical tract

• ↓ activity of nigrostriatal tract

• ↓ activity of tuberoinfundibular tract

• ↑ activity of mesolimbic tract= pos sym

• ↓ activity of mesocortical tract= neg and cognitive sym

• ↓ activity of nigrostriatal tract= movement disorders (EPS)

• ↓ activity of tuberoinfundibular tract= hyperprolactinemia

Dopamine is synthesized from what AA?

tyrosine

Once synthesized, dopamine is stored in vesicles via _______.

VMAT

How is dopamine reuptake in the pre and postsynaptic receptor?

• pre: DAT, NET

• post: OCT

The D1 receptor is what G protein and does cAMP?

a. Gs, increase cAMP

b. Gi, increase cAMP

c. Gs, decrease cAMP

d. Gi, decrease cAMP

a.

The D2 receptor is what G protein and does cAMP?

a. Gs, increase cAMP

b. Gi, increase cAMP

c. Gs, decrease cAMP

d. Gi, decrease cAMP

d.

Glutamate is an excitatory NT and leads to what kind of symptoms?

pos and neg symptoms

What drugs block NMDA receptors, affects glutamate and can result in schizophrenia like symptoms?

ketamine and phencyclidine

How does serotonin effect the mesocortical and mesolimbic tracts?

• mesocortical: ↓ DA activity

• mesolimbic: ↑ DA activity (why SGAs block this)

Haloperidol is what kind of FGA?

butyrophenone

MOA of FGAs

• results?

D2 receptor antagonism= ↑ cAMP = alleviates (+) symptoms

What is the required SAR of phenotiazines (FGAs)?

• what group would ↑ potency?

1. e- neg atom at position 2 - required

   • IF FLUORINE AT GROUP 2= ↑ POTENCY

2. 3C chain btwn nitrogen atoms= required

Do FGAs or SGAs have a higher risk of EPS?

FGAs= ↑ risk

Which FGA has a long half-life of 48-60h?

pimozide

In addition to D2 antagonism, what other receptors are antagonized by FGAs? What side effects result from this?

antagonizes:

• M1: anticholinergic

• H1: sedation, weight gain

• a1: heme

ADRs of FGAs:

• EPS

• Hyperprolactinemia (bc of tube tract)

• Tardive dyskinesia (w/ long term use) (bc of nigro pathway)

BBW of FGAs:

• increase mortality in elderly pts. w/ dementia related psychosis

• Thioridazine—> QT prolongation

MOA of SGAs:

• D2 receptor antagonism (weak)

• 5-HT2 antagonist and 5-HT2A inverse agonist

ADRs of SGAs

• metabolic (weight gain, increase glucose and lipids)

• antagonist of a1, a2, M1, M2—> refer to each SGA for those side effects

BBW of SGAs

• which deals with post-injection?

• which ones have a suicide risk?

• which has a CV risk?

• increase mortality in elderly pts. w/ dementia related psychosis

• Olanzapine ER injection—> post injection delirium and sedation syndrome

• Quetiapine, Lurasidone, Aripiprazole, Brexipiprazole—> suicide

• Clozapine—> orthostatic hypotension, decrease HR, syncope, seizures, myocarditis, cardiomyopathy, mitral valve incompetence

What drug is a muscarinic receptor activator? MOA?

Xanomeline—> activates M1 and M4

NMS is a condition due to what?

rapid block of dopamine receptors