They are either positive or negative symptoms. Positive is something that we can easily identify, and negative symptoms are symptoms that cant be easily seen (withdrawal, poor memory, pleasure from life)

-we may also see hyperviglance: this is when the body has the inability to filter out their surroundings. They take everything in!

-May be involved with hypervigalance

-GABA interneurons have the ability to inhibit sensory input to the cortex

-schitz have a reduced number of GABA interneurons, allowing more sensory input to reach cortex

-Dopamine inhibits the interneuron activity whereas glutamate activates interneuron activity

Ionotropic glutamate receptors: 

AMPA, NMDA, and kinase receptors :ion receptors

-Metabotropic glutamate receptors:

mGluR5:directly interacts with NMDA receptor; activation increases NMDA receptor activity

mGluR2: presynaptic: activation causes a decrease in glutamate release, as well as a dopamine release from dopaminergic neuron

D1/D5:

D1 is found on the cardiac tissue

activates adenylyl cyclase, increases cAMP

increase in glumeral filtration, and cardiac contractility

D2/D3/D4:

inhibits adenylyl cyclase, reduces cAMP

opens K channels: hyperpolarization

presynaptic D3 receptors: activation causes a reduction in DA synthesis and release

Overlapping brain locations

CTZ

D2: causes n/v: use antagonists 

Corpus Striatum (basal ganglia)

D1 and D2: control of posture and movement: use for parkinsons agents as agonists

Limbic system

D1,D2,D3,D4: hypervigilance, hallucinations, agitation, aggression: we use antagonists for psychosis

Pituitary gland:

decrease in prolactin release and increase in GH release: use agonists for amenorrhea or to reduce breast milk

-D2 antagonists

-improve positive symptoms, a little effect on negative symptoms

-takes weeks to months to see maximal benefit

sedation is immediate: sometimes used in patients with positive symptoms to calm them down, but actual decrease in symptoms takes some time

****upregulation in 4-8 weeks

Which two antipsycotics are used for anti-emetics?

-due to antagonism of the D2 in the stiratum

-dystonias: abnormal contractions of muscles in the face and neck

-pseudoparkinsonism

akinesia: difficult to initiate movement

bradykinesia: slow movement

tremors: pill rolling

rigidity: not moving harms while walking

THESE CAN BE TREATED WITH BENZTROPINE: balances the levels of Ach and DA; we can also discontinue the drugs

Akathisia:

contant motion: treat with propanolol: discontinued: reversible

NMS:

course tremors, cationic state, unstable respiration, unstable blood pressure, hpyerthermia, myoglobinemia, nephrotoxicity, musucle rigidity (T>104)

Rare; if occurs its a quick onset and rapid production 10 % mortaility rate

TREAT WITH DANTROLENE along with cooling blankets

Tradive dyskinesia:

lip smacking, twisted psoture, tongue moving back and forth: irreversible; can get off the drug bc it will make symptoms worse; have to decrease levels to the least amount in which we can see efficacy DOSE AND DURATION DEPENDANT; may have a chance to switch if caught early enough

D2 antagonists in the pituitary can also increase the release of prolactin, which can cause gynecomastia, galactorrhea, amenorrhea, and male sexual dysfunction

-Can also bind to muscarinic receptors, alpha 1 receptors, and H1 receptors

-blocked rectifier current :can prolong QT and can get torsades de Pointes and sudden death (thioridazine)

-can decrease the threshold for seizures

-sedations

arganulocytosis, leukopenia(reversible)

-photosensitivity, juandice, dermititis (chlorpromazine)

-retinopathies (thioridazine at high doses)

-overall have a high therapeutic index

has little affinity for the D2 receptors, but has high affinity for the 5HT2a receptors

-for positive AND negative symptoms 

-less risk of movement disorders and prolactin effects

-lower risk of getting tardive dyskinesia (clozapine)

-blocade of the rectifier current: prolong QT: torsades de Pontes: death (geodon)

-decrease in seizure threshold

-weight gain(thru the 5HT2a antagonism)

-cholesterol and diabetes (black box warning) INSULIN RESISTANCE

-doesnt block as much of muscarnic and alpha 

most: clozapine and olanzapine

least: aripiprazole and ziprasidone

Binds to D1, D4, alpha and muscarinic recpetors

-mycoarditis

-bone marrow suppression and agranulocytosis:

-sore throat, fever

1% of patients every year

-4-18 weeks of development and not dose and duration dependant

-need to have a clozapine patient management system in which specific pharmacies only dispense it and WBC has to be done every week for first 6 weeks then every 2weeks: the pharmacy needs to get results

***REDUCTION IN RISKS FOR SUICIDAL TENDENCIES!

-limited effectiveness

-30% of patients be treatment resistant

-cross tapering

-atypical preferred

-no correlation between plasma concentrations and clinical effects

-co administration really just increases S/E but cant take a patient off of both it they say thier doing better with both

-nonompliant patients: IM depot formulation: prolixin, Haldol, Risperdal Consta (q2-4w)