Thomas Kuhn- normal science

-biochemical paradigm (psychopharmacology)

Assumptions

-mental disorders are organic and reducible

-mental disorders have a biochemical basis

-mental disorders can be treated by manipulation of brain chemistry

Methylphenidate

drug stimulates release of NT

Drugs block postsynaptic receptors

Chlorpromazine Haloperidol

Catecholamines

-dopamine

-norepinephrine (noradrenaline)

-epinephrine (adrenaline) 

Indolamine

-seratonin

Chlorpromazine (most imp thing that ever happend in psychiatry) - started psychopharmacology revolutions

Reserpine

Phenothiazines- used in methylene blue from coal tar

Methylene blue tried in mental patients to stimulate oxygen in cells (didn't work)

Ehrlich discovered new dyes stain bacteria- first antibiotic used for syphillis

Phenothiazine synthesized as an antiparasitics

Routine screening found antihistamine activity used for allergic reactions and shock

Laborit

-sustained activation of autonomic NS responsible for shock w/ vasuclar damage and histamine release

Lytic coctail to mediate stress from shock

Promethazine- antihistamine in cocktail bc histamine was a mediator for shock reaction

-used as antihistamine in lytic cocktaile

Side-effects

-hypnotic (weak and reversible, sleep but not too deep) 

-no clouding of consciousness

-indifference

-analgesic

-hypothermic

-Preoperative sedative

-analgesic

-psychiatric sedative

-Anesthetic potentiator

(artifical hibernation) 

-promethasine lowers body temp

-state potentiates the effects of anesthetics

-thought less anesthetic could be given

-tryed with dogs but they died, didn't catch on

-Synthesized from promathezine

-lab test showed exceptional CNS activity

-psychiatric application by Delay & Deniker

Deniker tried artificial hibernation w/ med and ice, one time ice ran out and the patient was still calm, decided it might be due to the drug

-transformed ward environment, calmer

-other somatic therapies decline

-population of mental hospitals decline for 1st time in 150 years (catalyst for deinstitutionalization NOT a panacea)

Extrapyramidal

-Dystonia: muscle spasms (ocular gyro crysis)

-Akathesia: motor restlessness, agitation, causes suicide

-Parkinsoism: tremor, rigidity, akinesia

-Tardive dyskinesia- from LT tx, face and mouth distortions, lose ctrl of facial muscles

plant- rauwolfia serpentina

-antihypertensive and antipsychotic action

Kline: 1st to use it as psychiatric sedative

Schizophrenia caused by hyperdopaminergia

Van Rossum

-caused by the treatment

-increase in DA receptors caused by antipsychotics

-Chlorpromazine (Thorazine)

-Haloperidol (Haldol)

Clozapine (Clozaril)

reduced extrapyramidal side effects (less effect on D2 receptors)

Kline

Iproniazid

-tuberculostatic action of isoniazid led to iproniazid, saw patients were happier after

-not used much bc its dangerous (hepatotoxicity, bad combo w/ foods and other meds)

Everett & Toman

theory for depression

Roland Kuhn

-imipramine: derivative of CPZ, lost antipsychotic effect but had a mood effect

-led to antidepressants

-drugs acting on NE better for motor activating effects

-drugs acting on 5-HT better for depressed mood

(led to SSRIs)

-Prozac (Fluoxetine)

-Zoloft

-Paxil

-Celexa

-Lexapro

Kramer's "Listening to Prozac"- accounts of drastic transformations, for the gen public

cosmetic psychopharmacology- "better than well"

Healy- main proponent of the view

-accused drug companies of trying to hide it

-Suicides decrease when SSRIs introduced, autopsies also decrease so ill-defined deaths increase, could be a lack of identified suicides

-suicides increase when black box labeld decreases SSRIs, same time that they switched to antipsychotics

Bieberman- 1st to say it could be diagnosed in children

-use atypical antipsychotics for kids originally thought to be ADHD

Natural substance

-used to treat gout

John Cade: rediscovereed mood stabilizing effect, really toxic so hard to catch on 

Schou- found safe way to do it allowing it to be gradually accepted

mephenesin as antibiotic- found muscle relaxant effects

Miltown- 1st anxiolytic marketed as not having any side-effects (not true) 

Miltown replaced by Benzodiazepines

1st was libium followed by valium

Xanax, Halcion, Ativan

Freud- "uber coca"

Bradley- 1st to use Benazadrine (amphetamine) w/ childhood behavior disorders

-used during spinal taps to make x-ray better, thought it would increase spinal fluid production and make them less sick, teachers said good at math

- create demand where there is no need

-market drug for specific indication

-support patient advocacy groups

-direct advertising to public

-continuing medical education

-influencing prescription practices

-repurposing

-reformulating

-marking for "off-label" use

- marketed specifically for panic disorders

-repurposing 

-isoniazid and iproniazid (anti tuberculosis agents)

-iproniazid elevates monoamines 

led to MAOIs

Keller or zeller

1. iproniazid elevates monoamines (increases MAO)

2. depressogenic action of reserpine (depletes MAO)

Proposed by Everett and Toman