53 - Pharmacology of antipsychotic drugs

Question 1

Drug-Induced Movement Disorders D2 Antagonism

Extrapramidal Symptoms (EPS) 30-50%
- occur early, days/weeks, ___

Symptoms
- dystonia - ___ muscle tone
- pseudoparkinsonism - muscle ___
- tremor
- akathisia - ___

unfortunately most patients will experience EPS as a results of ___ antipsychotic drug therapy

Answer 1

• reversible
• increased
• rigidity
• restlessness

long-term

Question 2

Drug therapy for EPS

• Anticholinergic agents: ___ (Cogentin), ___ (Artane), or ___ (Biperiden)
• Antihistamine - ___ (Benadryl)
• dopamine releasing agent - ___ (Symmetrel)
• ___ - used for akathisia

Answer 2

• benztropine, trihexyphenidyl, akineton
• diphenhydramine
• amantadine
• propranolol

Question 3

Drug-Induced Movement Disorders D2 Antagonism

Tardive Dyskinesia (20-40%)
- occur late, months to a year and is ____
- mouth - rhythmic involuntary movements
- choreiform- irregular purposelessness
- athetoid - worm like
- axial hyperkinesias - to and fro movements

Monitoring: ____ (Abnormal Involuntary Movement Scale), check every 6 months

Treatment: prevention! use the least risky agent at the ___ dose possible and monitor
- reduce dose of current agent
- change to a different drug (possibily a newer agent)
- eliminate ____ drugs
- ___ inhibitors

Answer 3

• irreverisble
  AIMS
  lowest
  anticholinergic
  VMAT

Question 4

Drug-Induced Movement Disorders D2 Antagonism

Tardive Dyskinesia (20-40%)
- occur late, months to a year, and ____
- mouth - rhythmic involuntary movements
- choreiform - irregular purposelessness
- athetoid - worm like
- axial hyperkinesias - to and fro movements

unknown MOA: antagonist ___ of receptors to dopamine (?)

Answer 4

• irreversible
• supersensitivity

Question 5

Tardive Dyskinesia

newer drug therapies for TD: ___ inhibitors
- ____ (Xenazine) for Huntington’s chorea
- ____ (Ingrezza) for TD
- ___ (Austedo) for TD and Huntington’s chorea

Answer 5

VMAT2
- tetrabenazine
- valbenazine
- deutetrabenazine

Question 6

Drug-Induced Movement Disorders D2 Antagonism

TD (cont.)
monitoring: ___ (abnormal involuntary movement scale); check rating scale every 6 months

treatment: ___ ! use the least risky agent at the lowest dose possible and monitor
- reduce dose
- change to different (newer) drug
- eliminate ___ drugs
- ___ inhibitors

Answer 6

AIMS
prevention
- anticholinergic
- VMAT

Question 8

Drug-Induced Movement Disorders D2 Antagonism

newer drug therapies for TD:
- ___ (Xenazine) for Huntington’s chorea
- ___ (Ingrezza) for TD
- ___ (Austedo) for TD and Huntington’s chorea

Answer 8

tetrabenazine
valbenazine
deutetrabenazine

Question 9

Drug-Induced Movement Disorders D2 Antagonism

Neuroleptic Malignant Syndrome (NMS)
- serious and ___ ; 10% fatality

symptoms
- EPS with fever
- impaired cognition
- muscle rigidity

treatment: restore ___ balance
- d/c drug
- DA ___ , diazepam, or dantrolene (skeletal muscle relaxant)

Answer 9

• fatal
• dopamine
• agonist

Question 10

MSC use

Tourette’s syndrome
- tics/vocalizations
- ___ (Orap)

Answer 10

Pimozide

Question 11

MSC use

Huntington’s chorea
- ___ (Xenazine)
- ___ (Austedo)

Answer 11

• tetrabenazine
• deutetrabenazine

Question 12

MSC use

alcohol withdrawal (Hallucinations)
- ___ (Haldol)

Answer 12

Haloperidol

Question 13

MSC use

N/V
- ___ (Reglan)
- ___ (Phenergan)

Answer 13

• metoclopramide
• promethazine

Question 14

MSC use

potentiation of opiates/sedatives
- ___ (Inapsine)

Answer 14

droperidol

Question 15

PCOL effects of antipsychotic drugs

behavioral effects: reversal of signs and symptoms of ___ in affected individuals

neuroleptic syndrome: ___ emotions, reduce interest, may resemble ___ symptoms

decreased spontaneous activity, aggressive, and impulsive behavior

Answer 15

• psychosis
• suppress, negative

Question 16

AE - autonomic

• loss of accomodation, dry mouth, difficulty urinating, constipation = ____ receptor blockade
• orthostatic hypotension, impotence, failure to ejaculate = ___ receptor blockade

Answer 16

• cholinergic
• alpha

Question 17

AE - CNS

• Parkinson’s syndrome, akathisia, dystonias = ___ receptor blockade
• tardive dyskinesia = ___ of dopamine receptors
• toxic-confusional state = ___ blockade
• sedation = ___ receptor blockade

Answer 17

• dopamine
• supersensitivity
• cholinergic
• histamine

Question 18

AE - endocrine system

amenorrhea, galactorrhea, infertility, impotence = dopamine receptor blockade resulting in ___

Answer 18

hyperprolactinemia

Question 19

AE - other

weight gain = possibly combines ___ and ___ blockade

Answer 19

H1, 5HT 2C

Question 20

precautions and contraindications

• CV
• PD
• epilepsy ( ___ will lower seizure threshold)
• ___ (newer agents)

Answer 20

clozapine
diabetes

Question 21

1st Gen antipsyschotics

• more ___ problems
• increased EPS and TD due to strong ___ block

Answer 21

movement
D2

Question 22

1st Gen antipsyschotics

1st antipsychotic: ___

Answer 22

chlorpromazine

Question 23

1st Gen antipsychotics - phenothiazine nucleus

aliphatic phenothiazines
- ___ (Thorazine) - no longer 1st line therapy
- promezine (Sparine)
- Triflupromazine (Vesprin)

used for H1 antagonist properties
- ___ (Phenergan) - indicated for N/V
- trimeprazine (Temaril)

Answer 23

• chlorpromazine
• promethazine

Question 24

1st Gen antipsychotics - phenothiazine nucleus

piperidine phenothiazines
- ___ (Mellaril) - sedation, hypotension, anticholinergic, many SE
- mesoridazine (Serentil)

Answer 24

thioridazine

Question 25

# 1st Gen antipsychotics - phenothiazine nucleus piperazine phenothiazines - **___ (Permitil, Prolixin) - EPS** - trifluoperazine (Stelazine) - EPS - **___ (Compazine) - antiemetic** - thiethylperazine (Torecan) - antiemetic - **___ (Trilafon) - CATIE studies**

Answer 25

- fluphenazine - prochlorperazine - perphenazine

Question 26

# 1st Gen antipsychotics thioxanthines - **___ (Navane) - modest EPS** - chlorprothizene (Taratan)

Answer 26

- thiothixene

Question 27

# 1st Gen antipsychotics Butyrophenones - **___ (Haldol) - EPS** - droperidol (Inapsine) - highly ___ , anxiolytic - droperidol with fentanyl (Innovar)

Answer 27

- haloperidol - sedative

Question 28

# Miscellaneous Antipsychotics **___ (Moban)** - moderate EPS **___ (Orap)** - Tourette's disease-tics, vocalizations

Answer 28

molindone pimozide

Question 29

Answer 29

Question 30

# atypical/2nd Gen antipsychotics reduced EPS - efficacy for ___ symptoms (?) - similar or enhanced ___ receptor antagonism vs D2 more metabolic problems - linked to ___ (greater risk in patients < 50) - ___ and ___ (less evidence in quetiapine and risperidone)

Answer 30

- negatove - 5HT2A - diabetes - olanzapine, clozapine

Question 31

# atypical/2nd Gen antipsychotics **___ (Clozaril)** - 1st atypical - very effective agranulocytosis - occurs in 1-2% within 6 months (weekly blood monitoring) - 2nd or 3rd line therapy SE: anticholinergic, antihistamine - reduced ___ potency = ___ movement disorders - risk of ___

Answer 31

clozapine D2, decreased diabetes

Question 32

# atypical/2nd Gen antipsychotics **___ (Zyprexa)** - weight ___ - less likely to cause N/V - less likely to cause ___ disorders - risk of ___

Answer 32

olanzapine - gain - movement - diabetes

Question 33

# atypical/2nd Gen antipsychotics **___ (Loxitane)** - older agent - metabolite = ___ (Ascendin) - inhibits ___ = antidepressant

Answer 33

loxapine amoxipine NET

Question 34

# atypical/2nd Gen antipsychotics **____ (Seroquel)** - metabolite with ___ activity - 5HT2A and D2 (low ___ activity) - low EPS - ___ (a1) - ___ (H1) - risk of ___

Answer 34

Quetiapine - antidepressant - antimuscarinic - hypotension - sedation - diabetes

Question 35

# atypical/2nd Gen antipsychotics **___ (Risperidol)** - specifically and structurally designed to be both a ___ and ___ receptor antagonist! - relatively low EPS with < 8 mg/day - weight ___ ; some ___

Answer 35

risperidone - 5HT2A, D2 - gain, sedation

Question 36

# atypical/2nd Gen antipsychotics **___ (Invega)** - 9-hydroxy ____ **___ (Fanapt)** - structurally related to ___ - very potent at ___ receptors - 0.5 nM vs 5 nm at 5HT2A and D2

Answer 36

paliperidone - 9-hydroxyrisperidone iloperidone - risperidone - a1

Question 37

# atypical/2nd Gen antipsychotics **___ (Geodon/Zeldox)** - affinity for ___ , ___ , and ___ - prolongs ___ interval

Answer 37

ziprasidone - 5HT2A, D2, a1 - QTc

Question 38

# atypical/2nd Gen antipsychotics **___ (Saphris)** - ___ and ___ (nM affinity at most 5HT, a, DA, and histamine receptor)

Answer 38

asenapine - 5HT2A, D2

Question 39

# atypical/2nd Gen antipsychotics **___ (Latuda)** - ___ and ___ - less weight gain and metabolic effects compared to ___ - ___ onset (days without titration) - low doses have similar effectiveness to high doses

Answer 39

lurasidone - 5HT2A, D2 - olanzapine - fast

Question 40

# atypical/2nd Gen antipsychotics **___ (Nuplazid)** - inverse agonist 5HT2A (40x more than 5HT2C) - used for ___ disease psychosis

Answer 40

pimavanserin Parkinson

Question 41

# atypical/2nd Gen antipsychotics **___ (Abilify)** - high affinity for ___ and ___ (D2 actions are dopaminergic-state dependent and/or it is functionally selective) - partial agonist at ___ receptors (being used for depression) - moderate affinity for ___, ___, and ___ receptors - side effects: weight ___ , low risk for D2 effects - prodrug: ___ , given q 4-8 weeks

Answer 41

aripiprazole - 5HT2, D2 - 5HT1A - D4, a, histamine - gain - aripiprazole lauroxil

Question 42

# dopaminergic activity - aripiprazole dependent actions (partial agonism)

Answer 42

D2 actions are dopaminergic-state dependent and/or it is functionally selective

Question 43

# D2/D3 receptor partial agonists **___ (Rexulti)** - D2/D3 partial agonist with supposedly less ___ vs aripiprazole - indicated for schizophrenia and adjunct to antidepressants for major depression - partial agonist activity at ___ and ___ receptors, and antagonist activity at ___ receptors

Answer 43

brexpiprazole akathisia 5HT1A, D2, 5HT2A

Question 44

# D2/D3 receptor partial agonists **___ (Vraylar)** - greater affinity for ___ - weak partial agonist activity at ___ - ___ is high - for schizophrenia, mania, bipolar disorder

Answer 44

cariprazine - D3 - 5HT1A - akathisia

Question 45

# D2/D3 receptor partial agonists **___ (Caplyta)** - partial ___ agonist at presynaptic receptors - antagonist at postsynaptic receptors ( ____ antagonist)

Answer 45

lumateperone - D2 - 5HT2A

Question 46

Answer 46