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Pharmacology Test #6 > Antipsychotics > Flashcards

Flashcards in Antipsychotics Deck (66)
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1

Late onset schizophrenia affects

post-menopausal women

2

Positive symptoms of schizophrenia (psychosis)

auditory/visual hallucinations, delusions

3

Negative symptoms of schizophrenia

withdrawal, reduced speech, interest, drive, attention, and pleasure

4

cognitive deficits with schizophrenia

attention, memory, executive function

5

Onset of schizophrenia

late adolescence (males earlier than females)

6

Core symptom of schizophrenia

cognitive dysfunction

7

Etiology of schizophrenia

complex interactions between genetic predisposition and environmental risk

8

Specific genes associated with schizophrenia

COMT - catecholine metabolism;
DISCI - cell morphology, migration;
DTNBPI - axon stability;
GABRB2 - GABA system;
NRGI - cell growth and differentiation

9

Environmental risks for schizophrenia

1. obstetrical complications (hemorrhage, pre-term, nutrtion, maternal stress)
2. infections and/or inflammation (more schizo for winter pregnancies and flu epidemics)
3. cannabis (COMT mutations
4. immigration (stress?)
5 smoking rates

10

What percentage of schizophrenics are smokers?

75-90%

11

Dopamine hypothesis of schizophrenia

psychosis or psychotic symptoms are due to a hyperactive DA system/signaling

12

5 pieces of evidence for the DA hypothesis

1. Correlation between clinical effectiveness and affinity at D2
2. PRO-DA agents in Parkinson's can produce psychosis
3. Increased D2 density in schizophrenia
4. Increased DA release in schizophrenia and increased DA receptor occupancy
5. Odd changes in DA metabolism following administration of D2-directed antipsychotics

13

Evidence against the dopamine hypothesis

1. D2 antagonists are not universally effective
2. Atypicals - lower D2 affinity and added serotonin pharmacology
3. Blocking NMDA receptors produces psychosis
4. Widespread anatomical abnormalities

14

What does smoking alter?

Smoking alters DA transmission

15

First antipsychotic that worked well

Chlorpromazine

16

First atypical antipsychotic

Clozapine

17

General progression from typicals to atypicals reflects

1. Better affinity at D2 receptors
2. Addition of activity at 5HT2A and others
3. Better control over negative and cognitive Sx
4. Fewer EPS

18

Selectivity of Chlorpromazine

hits multiple targets that are not desirable

19

Haldol selectivity

more selective blocker for D2 than chlorpromazine

20

Difference between D1-like and D2-like receptors

D1-like (D1 and D5) are Gs-coupled (increased cAMP) whereas D2-like (D2, D3, and D4) receptors are Gi-coupled

21

Dopamine system comprises

dopamine-producing cells in the VTA and substantia nigra pars compacta

22

DA circuits involved in the therapeutic and cognitive activities of D2 antagonists

the mesocortical and mesolimbic pathways

23

Basal ganglia pathway important for motor control

nigrostriatal DA pathway from SNc to dorsal striatum

24

Circuit that extrapyramidal symptoms arise from

the nigrostriatal DA pathway from SNC to the dorsal striatum

25

Manipulation of the dopamine pathway in the hypothalamus causes

hyperprolactinemia

26

Manipulation of the dopamine pathway in the medulla is involved in

the anti-emetic properties of some antipsychotics

27

Efficacy of drugs is likely a combination of

direct antagonism and some long term adaptive changes

28

Adaptive changes known to occur with dopamine antagonists

upregulation of D2 receptors

29

1st generation antipsychotics

Phenothiazines and haloperidol

30

Features of 1st generation antipsychotics

1. Strong D2 antagonism
2. Variable off-target effects
3. Long half life
4. Only (+) symptom control