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Pharmacology > AntiPsychotics > Flashcards

AntiPsychotics Flashcards

1
Q

Dopamine pathways

A

Mesolimbic pathway
Mesocortical pathway
Nigrostriatal pathway
Tuberoinfundibular pathway

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2
Q

Mesolimbic pathway

A

which is thought to be hyperactive in schizophrenia and to mediate positive symptoms of psychosis such as delusions and hallucinations, from Vta to Nac

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3
Q

Mesocortical pathway

A

which is thought to be underactive in schizophrenia and thus mediate negative psychotic symptoms such as loss of motivation and social withdrawal, from Vta to PFC.

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4
Q

Nigrostriatal pathway

A

Which is part of the extrapyramidal nervous system and controls motor functions and movements. Deficiency of dopamine in this pathway can lead to dystonia and parkinsonism disease symptoms, while excess of dopamine can lead to hyperkinetic movements such as tics and dyskinesias, From substantia nigra to basal ganglia.

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5
Q

Tuberoinfundibular pathway

A

Which controls prolactin secretion specifically dopamine in this pathway inhibits prolactin release and as a reminder prolactin is a hormone that enables milk production and is also involved in the control of sexual desire and regulation of the immune symptom. From hypothalamus arcuate nucleus to the hypothalamus median eminence.

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6
Q

Forms of psychosis

A
  1. Simple
  2. Catatonic
  3. Hebephrenic 4. Paranoid
  4. Residual
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7
Q

1st. generation typical antipsychotics: (classical neuroleptics)
EXAMPLES

A

Chlorpromazine Fluphenazine Thioridazine Thiothixene Haloperidol

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7
Q

1st. generation typical antipsychotics: (classical neuroleptics)
EXAMPLES

A 
Chlorpromazine
Fluphenazine 
Thioridazine 
Thiothixene 
Haloperidol 
PROCHLORPERAZINE 
TRIFLUOPERAZINE
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8
Q

1st. generation typical antipsychotics: (classical neuroleptics)
MOA

A

● competitive blockade of dopamine D2 receptors on postsynaptic neurons. also blocks alpha receptors, cholinergic receptors and histamine receptors
● First-generation antipsychotics are more likely to be associated with movement disorders
– > known as extrapyramidal symptoms (EPS)
● EPS = Dystonia, Akathisia, pseudoparkinsonism, tardive dyskinesia
● Less likely to have any metabolic abnormalities.
● not selective for any of the four dopamine pathways

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9
Q

1st. generation typical antipsychotics: (classical neuroleptics)

SIDE EFFECTS

A 
EPS symptoms 
Hyperprolactinemia
sedation 
weight gain 
ABCDs 
hypotension
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10
Q

1st. generation typical antipsychotics: (classical neuroleptics)
CONTRAINDICATIONS

A

Hypersensitivity
Parkinsons
Dementia w/ Lewy bodies
Drinking

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11
Q

2nd generation atypical antipsychotics (atypical neuroleptics)

EXAMPLES

A

CLOZAPINE
OLANZAPINE
QUETIAPINE
RISPERIDONE

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12
Q

2nd generation atypical antipsychotics (atypical neuroleptics)
USE

A

Schizo pos. symptoms and neg.

symptoms (Mesocortical)

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13
Q

2nd generation atypical antipsychotics (atypical neuroleptics)
MOA

A

blocks D2 activity and 5HT-2a on postsynaptic neurons. also blocks alpha receptors, cholinergic receptors and histamine receptors

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14
Q

2nd generation atypical antipsychotics (atypical neuroleptics)

SIDE EFFECTS

A 
EPS
prolactin levels 
increased weight gain sedation hyperglycemia 
hypotension 
Agranulocytosis
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15
Q

2nd generation atypical antipsychotics (atypical neuroleptics)
CONTRAINDCATION

A

Hypersensitivity Myeloproliferative disorders

Epilepsy

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16
Q

BUPROPION

MOA

A

Inhibits DA and NE reuptake. SE: Tachycardia and insomnia.

17
Q

MIRTAZAPINE

A

α2 antagonist, increased NE & serotonin release. H1 antagonist. SE: Sedation, increased appetite and increased weight.

18
Q

TRAZODONE

A

Blocks serotonin receptors, α1, H1 and Serotonin reuptake. SE: Sedation, priapism.

19
Q

VARENICLINE

A

Nicotinic partial agonist, used for smoking cessation.

20
Q

VILAZODONE

A

inhibits serotonin reuptake and serotonin partial agonist.

21
Q

1st. generation typical antipsychotics: (classical neuroleptics)
USES

A

● Schizophrenia
● Bipolar disorder (manic phase)
● Antiemesis
● Preop sedation

22
Q

Phenothiazines

EXAMPLES

A

Chlorpromazine
Fluphenazine
Thioridazine
Thioxanthene

23
Q

Chlorpromazine
Fluphenazine
Thioridazine
Thioxanthene

MOA

A

● Blocks D2 receptor

● Also blocks alpha, muscarinic, and H1 receptors

24
Q

Chlorpromazine
Fluphenazine
Thioridazine
Thioxanthene

USE

A

● Schizophrenia
● Bipolar disorder (manic phase)
● Antiemesis
● Preop sedation

25
Q

Chlorpromazine
Fluphenazine
Thioridazine
Thioxanthene

ADVERSE EFFECTS

A

● Extensions of alpha and muscarinic receptor blocking action.
● Extrapyramidal dysfunctions ( Dystonia, Akathisia, pseudoparkinsonism, tardive
dyskinesia)
● Hyperprolactinemia

26
Q

What type of drug is haloperidol

A

Butyrophenone

27
Q

Haloperidol

MOA

A

● Blocks D2 receptors
● Blocks few alpha receptors compared to phenothiazines
● Blocks few muscarinic receptors compared to phenothiazines
● Less sedation compared to phenothiazines

28
Q

Haloperidol

USE

A

● Schizophrenia
● Bipolar disorder (manic phase)
● Huntington’s chorea
● Tourette syndrome

29
Q

Haloperidol

SIDE EFFECT

A

● Extrapyramidal dysfunction (Dystonia, Akathisia, pseudoparkinsonism, tardive dyskinesia)

30
Q

list the atypical neuroleptics

A 
Aripiprazole
Brexpiprazole
Clozapine ( note most important side effect - agranulocytosis )
Olanzapine
Quetiapine
Risperidone
Ziprasidone
31
Q

Aripiprazole

MOA

A

● partial agonists at D2 and 5-HT1A receptors, as well as antagonists of 5-HT2A receptors.

● All of the first-generation and most of the second-generation antipsychotic drugs block D2 dopamine receptors in the brain and the periphery
● The second-generation agents exert part of their action through inhibition of serotonin receptors (5-HT), particularly 5-HT2A receptors.

32
Q

Brexpiprazole: MOA

A

● Newer 2nd gen drugs
● partial agonists at D2 and 5-HT1A receptors, as well as antagonists of 5-HT2A
receptors

● All of the first-generation and most of the second-generation antipsychotic drugs block D2 dopamine receptors in the brain and the periphery
● The second-generation agents exert part of their action through inhibition of serotonin receptors (5-HT), particularly 5-HT2A receptors.

33
Q

MOST IMPORTANT SIDE EFFECT OF CLOZAPINE

A

agranulocytosis

34
Q

Clozapine

MOA

A

● high affinity for D1, D4, 5-HT2, muscarinic, and α-adrenergic
● Weak D2 receptor antagonist

● All of the first-generation and most of the second-generation antipsychotic drugs block D2 dopamine receptors in the brain and the periphery
● The second-generation agents exert part of their action through inhibition of serotonin receptors (5-HT), particularly 5-HT2A receptors.

35
Q

Olanzapine

MOA

A

● blocks 5-HT2A receptors to a greater extent than it does D2 receptors

● All of the first-generation and most of the second-generation antipsychotic drugs block D2 dopamine receptors in the brain and the periphery
● The second-generation agents exert part of their action through inhibition of serotonin receptors (5-HT), particularly 5-HT2A receptors.

36
Q

Quetiapine MOA & SEs

A

relatively weak at blockade of D2 and 5-HT2A receptors
● low risk for EPS

Side effects:
● dizziness, feeling unsteady, or having trouble keeping your balance.
● pain in the joints, back, neck, or ears.
● weakness.
● dry mouth.
● vomiting.
● indigestion.
● constipation.
37
Q

Risperidone MOA

A

blocks 5-HT2A receptors to a greater extent than it does D2 receptors

38
Q

Clinical applications of atypical neuroleptics (1)

A

Actions:
● The clinical effects of antipsychotic drugs reflect a blockade at dopamine and/or serotonin receptors
● They also block cholinergic, adrenergic, and histaminergic receptors
1. Antipsychotic effects:
● reduce hallucinations and delusions associated with schizophrenia (known as “positive”
symptoms) by blocking D2 receptors in the mesolimbic system of the brain
● Many second-generation agents, such as clozapine, can reduce the negative symptoms
to some extent.
2. Extrapyramidal effects:
● Dystonias, Parkinson-like symptoms, akathisia, and tardive dyskinesia can occur with
both acute and chronic treatment
● The second-generation antipsychotics exhibit a lower incidence of EPS.

39
Q

Clinical applications of atypical neuroleptics (2)

A
  1. Antiemetic effects:
    ● The antipsychotic drugs have antiemetic effects that are mediated by blocking D2
    receptors of the chemoreceptor trigger zone of the medulla
  2. Anticholinergic effects:
    ● Some of the antipsychotics, particularly thioridazine, chlorpromazine, clozapine, and
    olanzapine, produce anticholinergic effects.
    ● The anticholinergic effects may actually assist in reducing the risk of EPS with these
    agents.
  3. Other effects:
    ● Blockade of α-adrenergic receptors causes orthostatic hypotension and
    light-headedness.
    ● alter temperature-regulating mechanisms and can produce poikilothermia
    ● In the pituitary, antipsychotics that block D2 receptors may cause an increase in prolactin
    release.
    ● Sedation
    ● Sexual dysfunction
40
Q

USE of atypical neuroleptics

A

● Schizophrenia (positive and negative symptoms)
● Bipolar disorder
● Major depression
● Agitation (seen in alzheimers and parkinsons)
● Prevention of nausea and vomiting
● treat intractable hiccups
● treatment of the motor and phonic tics of Tourette disorder
● tic disorder
● management of disruptive behavior and irritability secondary to autism.

41
Q

Side effects of atypical neuroleptics

A 
● Urinary retention
● Weight gain (clozapine, olanzapine)
● Seizure
● Sedation
● Extrapyramidal symptoms
● Postural hypotension
● Sexual dysfunction
● Arrhythmias
● Sudden cardiac death
● Dry mouth
● Agranulocytosis (clozapine)
● Diabetes (clozapine, olanzapine)
● Hyperprolactinemia (risperidone)
● Qt prolongation (ziprasidone)
● Tardive dyskinesia
● Neuroleptic malignant syndrome

Pharmacology (22 decks)

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