Antipsychotics Flashcards

1
Q

DA Hypothesis of schizo

A

Efficacy of pharma corresponds to drugs affinity for dopamine receptors

Drugs that increase dopamine can preceipitate psychotics symtpoms

Unmedicated schizo will have more dopamine receptors and higher levels

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2
Q

Negative schizo symtpoms

A

From dopamine deficits in HC and select cortical strcutrue

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3
Q

Mesolimbic/mesocortical tract
Nigrostriatal
Tuberoinfundibular
Medullary-periventricular

A

VTA to NA and frontal cortex…pos and neg of schizo

SN to striatal nuclei…extrapyrmaidal motor dysfunction from antipsychotics

Artcutew and periventricular neuros to pituiatyr portal…increased prolactin from anti[sychotics

Motor of vagus,a area postrema, and other BS nuclei…antiemetic effects, changes in eating behavior associated with antipsyhchotics

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4
Q

Most antipsychotics are

A

DA receptor antagonists…excpet aripirazole which is D2 partial agonist

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5
Q

D1 vs. D2

A

D1 - stimukation of cAMP and PKA dep pathways

D2 like - inhibition

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6
Q

Antipsychotics use

A

Schizo
Sedation
pReventtion of vomiting and nausea

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7
Q

Route of delivery of antiosychotics

A

Oral disintegrating

Short acting injectables (for uncoop or rapid sedation)

Long acting injectables (history of non0-adhenense)

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8
Q

PK of antipsychotics

A

Accumulate in lipid storage and released slowly
Steady state in 4 to 7 days

Long half life
CYP450s

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9
Q

Phenothiazines

A

Chlorpromazine (aliphatic) - oronal
Fluphenazine (piperazine derive)

Least potent of the typicals

Lots of sedation and weight gain

Typcal

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10
Q

Butyrophenones

A

Haloperidol

Far more potent with fewer sedation and weight gain

More extrapyramidal SEs

Most widely used

Typical

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11
Q

Typical antipsychotics

A

Good at relieving positive but not negative

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12
Q

Clozapine

A

Both pos and neg symptoms

Life threatening agranulocytosis so only use for suicide

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13
Q

Olanzipine, quetiapine, aripiprazole, risperidone, ziprasidone

A

Newer atypicals

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14
Q

Atypical vs typical

A

Atypical tx both pos and neg
Lower absolute affinity for D2 receptors relative to typical agents
Equal to greater potenc at 5-HT receptors
Fewer extrapyramidal motor symptoms

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15
Q

Adverse effects of antipsychotics

A
EPS
Akathisia
Tardive dyskinesia
NMS 
Cardiac toxicity 
Wegith gain
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16
Q

EPS

Akathisia

A

Parkinson like syndrome…tx with anti-muscarinic drugs but NOT L-dopa

Restlessness, pacing, rocking…tx with propranolo

17
Q

Tradive dyskinesia

NMS

A

Usually milt…intolerable TD is usually the limiting factor for antipsychotic therapy

Rigidity, fever, cog changes (neroleptic malignant syndrome)
Begin within first 2 eeeks
Tx with dantrolene

18
Q

All adverse effects of antipsychotics associated with

A

Hypoactiviation of D2 receptors

19
Q

Cardiac toxocity

Weight gain

A

QT prolongation (esp thiroridazine and ziprasionde)

Risk of weight gain more with atypicals like olanzapine and cloazapine

20
Q

Hypotension and high resting HR

Muscarinic effects

A

alphra receptor blockade

mACh receptor blockade (anti-effects)

21
Q

Confusion, attnetion porobs

Sedation

A

mACh blockade in brain

Histamine receptor blockade

22
Q

Amenorrhea-galactorrhea syndrome and infertility

Blunt affect, lack of pleasure, dysphroia,

Antiemetic

A

In women, hyperlaction and infertility…in men loss of libido and infertiility…due to D2 blockade

DA blockade in nucleus accumbens

DA blockade in area postrema

23
Q

D2 receptor signifiacne

A

Propentisty for alleviating positive symptoms AND causing extrapyrimdal disturbances is proportional to affinity for D2

Drugs in typical class have greater absolute affinty

24
Q

Which is better and why

A

Depends

Atypical - fewer EP side effects but cause weight gain and variable responsiveness

Typical - less expensive

25
Q

Other concenrs of antipsychotics

A

CYP450 problems

Compliance low

Close monnitoring

Drug abuse could exacerbate symtpms

26
Q

Adjunctive therapy

A

Benzos
Lithium
Anticonvulsants
Prpranolo

27
Q

Benzos

lithium

A

alleviate anxiety…side effects

Mood stabilizer

28
Q

Anticonvulsatns

Propranolol

A

alleviate anxiety and stabilize mood..valproate preferred bc of carbamazepine intx)

Tx aggressive behaviors