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Mo-Neuro 4 > Antipsychotic Agents > Flashcards

Antipsychotic Agents Flashcards

1
Q

Clinical Features of Schizophrenia

Positive symptoms

A

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

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2
Q

Clinical Features of Schizophrenia

Psychotic Symptoms

A

Delusions: false belief, often paranoid in nature

Hallucinations: false perception, usually voices

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3
Q

Clinical Features of Schizophrenia

Disorganized symptoms

A

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

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4
Q

Clinical Features of Schizophrenia

Negative symptoms

A

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

  • Withdrawal from social contact
  • Flattening of emotional responses
  • Decreased motivation
  • Poverty of speech
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5
Q

Clinical Features of Schizophrenia

Cognitive symptoms

A

Decreased attention span-executive function

Poor working memory

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6
Q

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

A

Dopamine Hypothesis of Schizophrenia

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7
Q

Virtually all antipsychotic drugs block __________ receptors

A

dopamine D2

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8
Q

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

A

glutamate and serotonin and acetylcholine

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9
Q

↑ DA –>

A

Positive Symptoms
Delusions
Hallucinations
Disordered thoughts

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10
Q

↓ DA –>

A

Negative Symptoms
Blunted affect-anhedonia
Alogia - Asociality

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11
Q

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

A

Mesolimbic pathway

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12
Q

Involved in communication and social abilities

A

Mesocortical pathway

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13
Q

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

A

Nigrostriatal pathway

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14
Q

Hypothalamic neurons release DA in pituitary to inhibit prolactin release

A

Tuberoinfinduibular pathway

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15
Q

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

A

Serotonin Hypothesis - 5HT2A Receptors

increased DA release

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16
Q

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

A

Serotonin Hypothesis - 5HT2A Receptors

5HT2A

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17
Q

________ 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

A

Serotonin Hypothesis - 5HT2A Receptors

5HT2A receptors

18
Q

Glutamate Hypofunction Hypothesis

A

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

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

19
Q

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

A

Overactivity of cholinergic neurons in the cortex

Overactivity of dopamine neurons in the mesolimbic system

20
Q

Cortical Glu –> GABA –> Glu –> GABA –> ↓ mesocortical DA

A

Glutamate Hypofunction Hypothesis

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

21
Q

TYPICAL VS ATYPICAL

A

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

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

22
Q

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

A

Good D2 block - good efficacy against positive symptoms

Good D2 block - high incidence of extrapyramidal toxicity

23
Q

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

A

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
Q

Haloperidol

A

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

25
Q

Chlorpromazine

A

↓ EPSE, but ↑ ADRs from M-H1-α1 block

Low potency

26
Q

Atypical Agents (2nd generation)

A 
#42: Quetiapine (Seroquel®)
#79: Aripiprazole (Abilify®)
#84: Risperidone (Risperdal®)
#145: Olanzapine (Zyprexa®)
Ziprasidone (Geodon®)
Clozapine (Clozaril®)
27
Q

Typical Agents (1st generation)

A

Haloperidol (Haldol®)

Chlorpromazine (Thorazine®)

28
Q

Olanzapine

A

Atypical Agents (2nd generation)

29
Q

Haloperidol

A

Typical Agents (1st generation)

30
Q

Risperidone

A

Atypical Agents (2nd generation)

31
Q

Aripiprazole

A

Atypical Agents (2nd generation)

32
Q

Quetiapine

A

Atypical Agents (2nd generation)

33
Q

Chlorpromazine

A

Typical Agents (1st generation)

34
Q

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:

A

Extrapyramidal side effects

Defines them, makes them atypical

35
Q

Adverse Reactions

Muscarinic block – ↑ with typical-low potency

A

Dry mouth

Blurred vision

Urination difficulty

Constipation

Tachycardia

Sedation

36
Q

Alpha-1 adrenergic block

↑ with typical-low potency

A

Orthostatic hypotension

37
Q

H1 Histamine block

↑ with typical-low potency

A

Sedation

Weight gain –> risk of Type 2 diabetes

38
Q

D2 Block – _______________- ↑ with typical-high potency

A

Extrapyramidal Side Effects

39
Q

D2 Block

Extrapyramidal Side Effects early

A
  • 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
Q

D2 Block – Extrapyramidal Side Effects late

A

*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

Mo-Neuro 4 (37 decks)

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