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Flashcards in Antipsychotic Agents Deck (40):
1

Clinical Features of Schizophrenia

Positive symptoms

overactivity of dopamine neurons in the limbic system (mesolimbic pathway)

2

Clinical Features of Schizophrenia
Psychotic Symptoms

Delusions: false belief, often paranoid in nature

Hallucinations: false perception, usually voices

3

Clinical Features of Schizophrenia
Disorganized symptoms

Thought disorders--> wild trains of thought with irrational conclusions (inserted by an outside agency)

4

Clinical Features of Schizophrenia
Negative symptoms

hypoactivity of dopamine neurons in the prefrontal cortex (mesocortical pathway)

-Withdrawal from social contact
-Flattening of emotional responses
-Decreased motivation
-Poverty of speech

5

Clinical Features of Schizophrenia

Cognitive symptoms

Decreased attention span-executive function

Poor working memory

6

Abnormality of brain function in schizophrenics is due to overactivity in brain dopaminergic pathways, especially in the mesolimbic pathway

Dopamine Hypothesis of Schizophrenia

7

Virtually all antipsychotic drugs block __________ receptors

dopamine D2

8

Evidence exists for role of _______ (3) systems in SK

glutamate and serotonin and acetylcholine

9

↑ DA -->

Positive Symptoms
Delusions
Hallucinations
Disordered thoughts

10

↓ DA -->

Negative Symptoms
Blunted affect-anhedonia
Alogia - Asociality

11

Subserve the integration of sensory input and motor responses with affective or emotional data
 

Mesolimbic pathway

12

Involved in communication and social abilities

Mesocortical pathway

13

Part of basal ganglia (aka extrapyramidal tract) plays a central role in planned, coordinated movement

Nigrostriatal pathway

14

Hypothalamic neurons release DA in pituitary to inhibit prolactin release

Tuberoinfinduibular pathway

15

5HT2A receptors on DA neurons in the PFC decrease DA release. Block of these receptors by atypical agents results in _______ resulting in alleviation of negative symptoms of schizophrenia

Serotonin Hypothesis - 5HT2A Receptors

increased DA release

16

Activation of _______ was found to be basis of hallucinatory effects of drugs like LSD and mescaline

Serotonin Hypothesis - 5HT2A Receptors

5HT2A

17

________ on DA neurons in the PFC decrease DA release. Block of these receptors by atypical agents results in increased DA release resulting in alleviation of negative symptoms of schizophrenia

Serotonin Hypothesis - 5HT2A Receptors


5HT2A receptors

18

Glutamate Hypofunction Hypothesis

Cortical Glu --> GABA--> cortical Glu --> ↑ mesolimbic DA

Hypofunction in cortical NMDA-Glu neurons -remove GABA inhibition-activate DA Neurons -positive symptoms of schizophrenia

19

Positive symptoms of schizophrenia (delusions, hallucinations) are believed to result from:

Overactivity of cholinergic neurons in the cortex

Overactivity of dopamine neurons in the mesolimbic system

20

Cortical Glu --> GABA --> Glu --> GABA --> ↓ mesocortical DA

Glutamate Hypofunction Hypothesis

Hypofunction in cortical NMDA-Glu neurons remove inhibition of VTA GABA inhibit mesocortical DA negative symptoms of schizophrenia

21

TYPICAL VS ATYPICAL

Typical Agents [1st generation] – high D2 / 5HT2A blocking ratio

Atypical Agents [2nd generation] - low D2/5HT2A blocking ratio

22

Typical Agents [1st generation] – high D2 / 5HT2A blocking ratio

Good D2 block - good efficacy against positive symptoms

Good D2 block - high incidence of extrapyramidal toxicity

23

Atypical Agents [2nd generation] - low D2/5HT2A blocking ratio

Poor D2 block yet good antipsychotic efficacy (atypical)

Good 5HT2A block good efficacy against negative symptoms

Poor D2 block + good 5HT2A block reduced incidence of EPSE

24

Haloperidol

High potency ↑ D2 side effects (EPSE) but less ADRs via M-H1-α1 block

25

Chlorpromazine

↓ EPSE, but ↑ ADRs from M-H1-α1 block

Low potency

26

Atypical Agents (2nd generation)

#42: Quetiapine (Seroquel®)
#79: Aripiprazole (Abilify®)
#84: Risperidone (Risperdal®)
#145: Olanzapine (Zyprexa®)
Ziprasidone (Geodon®)
Clozapine (Clozaril®)

27

Typical Agents (1st generation)

Haloperidol (Haldol®)
Chlorpromazine (Thorazine®)

28

Olanzapine

Atypical Agents (2nd generation)

29

Haloperidol

Typical Agents (1st generation)

30

Risperidone

Atypical Agents (2nd generation)

31

Aripiprazole

Atypical Agents (2nd generation)

32

Quetiapine

Atypical Agents (2nd generation)

33

Chlorpromazine

Typical Agents (1st generation)

34

Atypical antipsychotic agents such as clozapine or olanzapine are distinguished from typical agents such as haloperidol because they are associated with a lower incidence of:


Extrapyramidal side effects

Defines them, makes them atypical


35

Adverse Reactions
Muscarinic block – ↑ with typical-low potency

Dry mouth

Blurred vision

Urination difficulty

Constipation

Tachycardia

Sedation

36

Alpha-1 adrenergic block
↑ with typical-low potency

Orthostatic hypotension

37

H1 Histamine block
↑ with typical-low potency

Sedation

**Weight gain --> risk of Type 2 diabetes**

38

D2 Block – _______________- ↑ with typical-high potency

Extrapyramidal Side Effects

39

D2 Block
Extrapyramidal Side Effects early

*Acute dystonia (onset 1-5 days)
--Torticollis, trismus, opisthotonos
--rx: anticholinergic agents [diphenhydramine-benztropine]

*Akathisia (onset 6-60 days)
--Motor restlessness – “can’t sit still”
--rx: reduce dose – change drug – try anticholinergic, β blocker or benzodiazepine

40

D2 Block – Extrapyramidal Side Effects late

*Pseudoparkinsonism (onset 5-90 days)

-Tremor, bradykinesia, rigidity, shuffling gait
-Rx: anticholinergic agents

*Tardive dyskinesia (onset 3-6 months or longer, 20-40% incidence in elderly females)

-D2 receptor supersensitivity?
-Involuntary movements of orofacial muscles, choreathetoid* movements
-rx: rarely effective, prevention best strategy