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33 Cards in this Set
- Front
- Back
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First generation anti-psychotics
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Treat acute episode of psychosis and maintenance treatment prevents relapse. Treats positive symptoms only.
Low potency drugs: chlorpromazine (Thorazine) thioridazine (Mellaril) perphenazine (Trilafon) "THIs Clip is low" - Thioridazine and Chlorpromazine are low-potency FGAs High potency drugs: fluphenazine (Prolixin) trifluoperazine (Stelazine) haloperidol (Haldol) First Generation Anti-psychotics (FGA's) Color The Triple Halogens (chlorpromazine, thioridazine, trifluoperazine, haloperidol) (The order is increasing potency and increasing EPS) |
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Biological basis for psychosis
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Hyperactivity of dopamine systems in the subcortical regions of the brain, specifically the mesolimbic dopamine system. Possibly related to the D2 receptor
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2nd generatoin anti-psychotics
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Treats psychosis
May treat positive and negative symptoms of schizoprenia Clozapine (Clozaril) Risperidone (Risperdal) Olanzapine (Zyprexa) Ziprasidone (Geodon) Quetiapine (Seroquel) Aripiprazole (Abilify) Paliperidone (Invega) |
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LY2140023
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Activates mGlu2/3 receptors
Treats positive and negative symptoms of schizophrenia |
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4 important dopaminergic pathways in the brain
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1. Nigrostriatal system: involved in extrapyramidal disorders
2. Tuberoinfundibular system: involved in neuroendocrine control 3. Mesolimbic system: ? involved in schizophrenia 4. Mesocortical system: ? involved in schizophrenia The many dopamine pathways lead to the many side effects associated with anti-psychotics |
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Nigrostriatal pathway
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Project from substantia nigra to caudate nucleus and putamen. Involved in the coordination of voluntary movements and fine control of motor movement.
Blocking D2 Rc causes extrapyramidal symptoms: - Parkinsonism like symptoms. Drugs which have stronger anticholinergic effects (chlorpromazine) have fewer extrapyramidal side effects than drugs which have weaker anticholinergic effects (haloperidol). These are treated by blocking central muscarinic receptors (benztropine or Cogentin). -Akathisia; subjective sense of motor restlessness (urge to keep moving). This is treated with beta blockers. -Tardive dyskinesia |
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The tuberoinfundibular system
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Connects arcuate nuclei and periventricular neurons to the hypothalamus and posterior pituitary.
Dopamine released from these neurons inhibits prolactin secretion. Block of dopamine (D2) receptors in this region by FGA (and some SGA i.e. risperdal) antipsychotic drugs causes excessive prolactin secretion (hyperprolactinemia). Causes a wide range of other endocrine abnormalities |
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The mesolimbic-mesocortical pathways
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Project from cell bodies near the substantia nigra to the limbic system and neocortex.
A hyperactivity of dopaminergic neurons in the mesolimbic pathways is thought to be involved in the positive symptoms of schizophrenia and psychosis. The antipsychotic effects of the drugs (for positive symptoms) are thought to be exerted in this region (D2 receptor block). A hypoactive state of dopaminergic neurons in the mesocortical pathway is thought to be involved in the negative symptoms. Therefore, blocking D2 receptors does not alleviate these symptoms and probably worsens them. D1 receptor agonists are now being considered for treatment of negative symptoms. |
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D2 Receptors
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D2 receptors are located in all the important dopaminergic pathways. The FGA’s block these receptors. Their binding affinity to these, receptors is strongly correlated with clinical antipsychotic and extrapyramidal potency (Parkinson-like symptoms).
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D4 receptors
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D4 receptors are found at highest levels in the mesolimbic and mesocortical arms of the dopaminergic system and may not be important in other pathways.
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D1 receptors
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D1 receptor is currently being explored as a target for improving cognitive dysfunction and negative symptoms in schizophrenia
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Characteristics of first generation anti-psychotics
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The major classes of FGA’s are phenothiazines (e.g., chlorpromazine), and butyrophenones (e.g., haloperidol).
These drugs act to decrease dopamine activity in the mesolimbic system by blocking D2 receptors. |
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Phenothiazines
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Class of first generation anti-psychotic.
Competitive dopamine receptor (D2) antagonists. The phenothiazines, chlorpromazine in particular, are useful in abolishing or diminishing the intensity or incidence of emesis, controlling intractable hiccoughs, or managing the abnormal motor movements in Huntington's chorea. |
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Side effects of Low potency FGAs
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The low potency FGAs have fewer extrapyramidal side effects than the high potency drugs.
The low potency antipsychotics cause other adverse effects more than the high potency drugs such as sedation, alpha1 receptor blockade leading to hypotension, and anticholinergic effects leading to dry mouth and constipation Low potency drugs: chlorpromazine (Thorazine) thioridazine (Mellaril) perphenazine (Trilafon) |
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Side effects of High potency FGAs
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The high potency FGA drugs, because of their strong blocking effect on D2 receptors, cause extrapyramidal side effects (EPS) (dystonias; Parkinsonian symptoms; akathisia). EPS may lead to tardive dyskinesia (TD)
The high potency drugs are not as sedating and do not cause as severe blood pressure impairment. High potency drugs: fluphenazine (Prolixin) trifluoperazine (Stelazine) haloperidol (Haldol) |
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Second generation anti-psychotics
"Atypical" antipsychotics |
All drugs in this class have much less D2 receptor blocking activity and much more 5HT2 (serotonin) receptor blocking activity than the typical drugs. 5HT2 neurons (serotonergic) in the brain modulate dopaminergic transmission at a number of locations, possibly relating to their mechanism of action. All drugs have higher affinity for D4 receptors which are present in mesocortical and mesolimbic areas only. They are not present in tuberoinfundibular or nigrostriatal pathways possibly accounting for low incidence of neurological side effects.
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Causes agranulocytosis
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Clozapine
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Second generation anti-psychotics
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Virtually all atypical antipsychotic drugs (except one, which we don't need to know) end in -apine or idone
I know it's ATYPICAL, but all I need is A PINE and I DONE with schizophrenia Clozapine (Clozaril) Risperidone (Risperdal) Olanzapine (Zyprexa) Seroquel (Quetiapine) Abilify (aripiprazole) Ziprasidone (Geodon) Paliperidone (Invega) LY2140023 (mGlu Rc agonists) |
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chlorpromazine (Thorazine)
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Anti-psychotic drug
FGA - phenothiazine - low potency |
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thioridazine (Mellaril)
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Anti-psychotic drug
FGA - phenothiazine - low potency Noted for its side effect of impairment of ejaculation and prolonged QT interval |
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trifluoperazine (Stelazine)
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Anti-psychotic drug
FGA - phenothiazine - high potency I hate OPERA (trifluOPERAzine), makes me want to grimace and stick out my tongue (TD). At least the OPERA doesn't put me to sleep! (low sedation) This one TRIES (starts with "tri") really hard and is thus high potency |
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haloperidol (Haldol)
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Anti-psychotic drug
FGA - butyrophenones - high potency Competitive dopamine (D2) receptor antagonists. Also used in the treatment of Tourette's syndrome My friend HAL also hates opera (see above), so he grimaces too (TD); he also has Tourette's (effective for this) |
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clozapine (Clozaril)
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Anti-psychotic drug
Atypical - blocks D3, D4, 5HT2 Rcs Other: anticholinergic, H1, a1 Agranulocytosis. Also high incidence of seizure (treat with valproic acid), serious gastric and cardiac side effects It's atypical to stay in the Clozet these days especially without your granulocytes (1% agranulocytosis) |
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risperidone (Risperdal)
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Anti-psychotic drug
Atypical - blocks D2 (medium affinity), 5HT2 Rcs Other - a1, a2 |
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olanzapine (Zyprexa)
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Anti-psychotic drug
Atypical - blocks D2 (less affinity than typical), D4. 5HT2 Rcs Other: M1, H1, A1 O-lanzapine makes you O-bese O-no! You're pregnant! (Forgot to tell you that since you're no longer hyperprolactinemic, you can get knocked up) |
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paliperidone (Invega)
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Anti-psychotic drug
Atypical - blocks D2, 5HT2A Otra: a1, a2, histaminic Side effects similar to respiradone |
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LY2140023
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Anti-psychotic drug
Atypical - mGlu Rc agonists (no effect on dopamine system) Whoever named this was crazy (anti-psychotic) and had probably sniffed glu (mGlu antagonist) No prolactin elevation, extrapyramidal symptoms or weight gain Imrpoved positive and negative symptoms by week 4 |
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Treatment for Neuroleptic Malignant Syndrome
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Caused by anti-psychotics
Characterized by acute changes in mental status, high spiking fevers, muscular rigidity, autonomic instability Hydration, Dantrolene, Bromocriptine |
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Chlorpromazine
DDI |
Potentiates the effects of all central nervous system depressants.
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Extrapyramidal symptoms of a dopamine receptor blockade from FGAs
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-Parkinsonism-like syndrome (treat with anticholinergic drugs)
-Akathisia - restless leg syndrome (treat with clonidine or benzodiazepines or beta blockers) -Tardive dyskinesia |
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Neuroleptic malignant syndrome (NMS)
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NMS resembles a severe form of Parkinsonism with catatonia, fluctuations in the intensity of course tremor, and autonomic instability (labile pulse and blood pressure, hyperthermia). Mortality is 10%. Serum muscle enzymes are elevated typically (e.g. CPK).
All antipsychotics can cause NMS. |
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risperidone (Risperdal)
Metabolism |
Risperidone is administered orally and is completely absorbed from the GI tract. It is metabolized by cytochrome P450IID in the liver (about 10% of an oral dose). The metabolite and the unaltered drug are excreted in the urine. Reduction of dosage level is indicated in patients with hepatic or renal disease.
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Olanzapine
Side effect |
Weight gain (of note because negative symptoms are alleviated as well and the patient may be more social)
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