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27 Cards in this Set

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What are (+)Sx of Schizophrenia?


-What are (-)Sx of Schizophrenia?

(+) include delusions, hallucinations, disorganized speech, and catatonic behavior.


(development of abnormal fxn)



(-) include:


afffective flattening (pt. isn't engaged in w/e going on/gives dull responses),


alogia- loss of speech


avolition- loss of motivation


social withdrawl.

difference b/w (+) and (-) sx


-when do sx develop

things a pt can report and is easy to spot.


mid to late teens

What are the three NTs we think are involved w/ schizophrenic behavior

DA, serotonin and PCP (phencyclidine)

Evidence for DA's involvement w/ schizophrenia

chlorpromazine (a drug used to reverse sx) blocks DA receptors



drugs like amphetamines, cocaine, apomorphine can cause schizophrenic like state at high doses and all these are known to ^ DA levels.



hallucinations are a known side effect of levodopa (L-dopa) therapy which is used for parkinson's disease treatment



urinary HVA levels have been correlated w/ clinical improvement

What is PCP's possible role to schizophrenia?

it is an antagonist at NMDA glutamate receptors and it causes similar sx to schizophrenia

How is DA synthesized?

Tyrosine ---tyrosine hydroxylase--->L-DOPA ----Aromatic L-amino acid decarboxylase----> DA




DOPA stands for dihydroxyphenylalinine

How is DA catabolized?

either DA can be acted on by catecholomethyltransferase (COMT) becoming 3-methoxytyramine which then actes acted on by MAO/Aldehyde dehydrogenase resulting in homovanillic acid (HVA)



or


MAO/AD acts first and you get dihydroxyphenylacetic acid (DOPAC) and then you have COMT acting on it causing it to become HVA



HVA is what's excreted in urine

DA and the nigrostriatal tract


-where is the nigrostriatal tract


-how much DA does it contain


-where does it project to


-what is it involved in


-what does damage here do

it is located around the corpus collosum (near middle of brain)


-it contains 80% of DA in the brain


-it projects from substantia niagra to terminals that innervate the cudate and putamen (which is the striatum)


-it's involved in regulating purposeful movement


-damage to DA receptors here results in Parkinson's

DA and ventral tegmental area: mesolimbic system


-where does it project to


-what is it involved in


-what does damage here do

-it projects from VTA (near brainstem) to nucleus accumbens, ventral striatum, and parts of the amygdala and hippocampus (located to the area left of the hypothalamus.)


-it is involved w/ development of emotions and memory


-it can be responsible for (+) schizophrenic sx

DA and the Ventral tegmental area: mesocortical system


-where does it project to


-what is it responsible for


-what does damage here do

-it projects from VTA (near brainstem) to regions of cortex (esp. prefrontal)


-it is responsible for attention, planning, and motivated behavior


-it can be possibly responsible for (-)schizophrenic sx

DA and tubuloinfundibular pathway


-what does it do and where does it act

DA released here by neurons in hypothalamus go to pit gland and inhibit release of prolactin

DA and Area Postrema


-where is the area postrema


-what happens here

this is an area on the floor of the 4th ventricle of brain (near cerebellum and brain stem)


it isn't protected by BBB



D2 receptors are present here and when stimulated they cause N/V

What are the 2 types of antipsych drugs?

Typical: which are relatively potent antagonists of D2 receptors



Atypical which are antagonists of D2 receptors AND other receptors like 5HT 2a serotonin receptors

what do these antipsych. drug binding tables tell us?


-how do you read the tables


-what are the receptors antipsychotics bind to?


-what are some typical antipsych drugs


it helps us to determine the potency of the antipsych. drugs and their side effects



the smaller the number present, the higher the affinity for that receptor.



the receptors bound are D2, D1, M1, Alpha1, and H1



ex. Cholpromazine, thiothixene, haloperidol

what kind of effect do all antipsych. drugs have on musc. receptors. what does this mean?

most antipsych drugs have anti musc. effects which causes: blurred vision, inability to contract pupils, xerstomia, increased HR, constipation, lack of urine production

What do the H1 receptors affect?


-what do Alpha 1 receptors affect

they have a role in sleep cycles and eating behavior. if these are blocked, you'll be sleepy and eat more



-alpha 1 receptors being blocked decreases BP, causes possible orthostatic hypotension, and general vasodilation

DA receptor subtypes


-how many receptors subtypes


-How many families


-distinctions b/w families


-what subtypes are part of what fam.

there are 5 subtypes


there are 2 families. D1 fam has long C-terminal tail and short cytoplasmic loop. D2 has short C-terminal tail and long cytoplasmic loop.


D1 is excitatory group that ^ cAMP and intracellular Ca lvl and activates PKC


D2 is inhibitory and \/ cAMP and intracellular Ca lvls. it also ^K and \/voltage gated Ca channels which hyperpolarize cell.



D1 and D5 are part of D1 fam


D2 D3 and D4 are a part of D2

What are the actions of typical antipsych. drugs?

can relieve (+) sx of schizophrenia but not great w/ (-) sx



Haloperidol can relieve tourette's syndrome



Chlorpromazine can be used as an antiemetic and antipruritic

Side effects of typical antipsych drugs?

autonomic: musc. blocker w/ assoc. sx. and alpha AR blocker w/ associated sx (ortho hypo., tachycardia, impotence, failure to ejaculate)



CNS:


akathisia (non purposeful movement) and dystonia -->dev. in wks


parkinson--> dev. in mo.


tardive dyskinesia-->dev. in yrs


sedation


toxic/confused state



endocrine:


hyperprolactinema, amenorrhea, galactorrhea, infertility in women, gynecomastia, decreased libido and infertility in men



metabolic


weight gain

Peculiar side effects of typical antipsych drugs.

neuroleptic malignant syndrome: muscle rigidtiy, catatonia, stupor, fever, bp all over place, myoglobinemia, and possible death. This occurs w/ drugs that have higher affinity to D2 receptor



hyperprolactinemia



thioridazine causes cardiac arrhythmia due to prolongation of QT interval

side effect comparison- Chlorpromazine vs haloperidol


-more antimusc. more H1 receptor blocker more alpha AR blocker, more extra pyridimal effects

Chlorpromazine is more antimusc. more H1



haloperidol is more extra pyridimal



they're both equal in alpha AR blocker

Pharmacokinetics of typical antipsych drugs

All highly lipophilic, extensively metabolized, high first pass metab. and have sig. protein binding, and they have long have lives.



haloperidol can be given every 3-4 wks

What kind of drug interactions can typical antipsych drugs have with others

reverse the beneficial actions of antiparkinson drugs



antiparkinson's drug could worsen sx of schizophrenia



potentiate sedative effects of benzodiazepens and other centrally acting antihistamines

what can atypical antipsych drugs do

alleviate both (+) and (-) sx of schizophrenia


better at alleviating (+) than typical ones



less extrapyridimal effect risk

Receptor bindings tables for atypical antipsych drugs


-how to read them


-receptors targeted


still smaller number = greater affinities



same as typical but it also affects serotonin


D2, 5HT 2a, alpha 1, H1, M1

What are atypical antipsych drug examples


and what kind of side effects do they produce

Clozapine- sedation, hypotension, agranulocytosis (not making WBC), weight gain



risperidone- not as much sedation, some extrapyridimal effects, hypotension, weight gain, and QT interval prolongation



aripiprazole - maybe slight sedation and hypotension

Specialty of Aripiprazole

t is a partial agonist at D2 receptor


when low DA levels, it will act as an agonist (in mesolimbic sys it will decrease (+) sx)


when high DA levels, it will act as an antagonist (in mesocortical sys it will decrease (-) sx)



a surge release in striatum would displace most of the drug