53 - Pharmacology of antipsychotic drugs Flashcards
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
- reversible
- increased
- rigidity
- restlessness
long-term
Drug therapy for EPS
- Anticholinergic agents: ___ (Cogentin), ___ (Artane), or ___ (Biperiden)
- Antihistamine - ___ (Benadryl)
- dopamine releasing agent - ___ (Symmetrel)
- ___ - used for akathisia
- benztropine, trihexyphenidyl, akineton
- diphenhydramine
- amantadine
- propranolol
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
- irreverisble
AIMS
lowest
anticholinergic
VMAT
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 (?)
- irreversible
- supersensitivity
Tardive Dyskinesia
newer drug therapies for TD: ___ inhibitors
- ____ (Xenazine) for Huntington’s chorea
- ____ (Ingrezza) for TD
- ___ (Austedo) for TD and Huntington’s chorea
VMAT2
- tetrabenazine
- valbenazine
- deutetrabenazine
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
AIMS
prevention
- anticholinergic
- VMAT
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
tetrabenazine
valbenazine
deutetrabenazine
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)
- fatal
- dopamine
- agonist
MSC use
Tourette’s syndrome
- tics/vocalizations
- ___ (Orap)
Pimozide
MSC use
Huntington’s chorea
- ___ (Xenazine)
- ___ (Austedo)
- tetrabenazine
- deutetrabenazine
MSC use
alcohol withdrawal (Hallucinations)
- ___ (Haldol)
Haloperidol
MSC use
N/V
- ___ (Reglan)
- ___ (Phenergan)
- metoclopramide
- promethazine
MSC use
potentiation of opiates/sedatives
- ___ (Inapsine)
droperidol
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
- psychosis
- suppress, negative
AE - autonomic
- loss of accomodation, dry mouth, difficulty urinating, constipation = ____ receptor blockade
- orthostatic hypotension, impotence, failure to ejaculate = ___ receptor blockade
- cholinergic
- alpha
AE - CNS
- Parkinson’s syndrome, akathisia, dystonias = ___ receptor blockade
- tardive dyskinesia = ___ of dopamine receptors
- toxic-confusional state = ___ blockade
- sedation = ___ receptor blockade
- dopamine
- supersensitivity
- cholinergic
- histamine
AE - endocrine system
amenorrhea, galactorrhea, infertility, impotence = dopamine receptor blockade resulting in ___
hyperprolactinemia
AE - other
weight gain = possibly combines ___ and ___ blockade
H1, 5HT 2C
precautions and contraindications
- CV
- PD
- epilepsy ( ___ will lower seizure threshold)
- ___ (newer agents)
clozapine
diabetes
1st Gen antipsyschotics
- more ___ problems
- increased EPS and TD due to strong ___ block
movement
D2
1st Gen antipsyschotics
1st antipsychotic: ___
chlorpromazine
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)
- chlorpromazine
- promethazine
1st Gen antipsychotics - phenothiazine nucleus
piperidine phenothiazines
- ___ (Mellaril) - sedation, hypotension, anticholinergic, many SE
- mesoridazine (Serentil)
thioridazine
1st Gen antipsychotics - phenothiazine nucleus
piperazine phenothiazines
- ___ (Permitil, Prolixin) - EPS
- trifluoperazine (Stelazine) - EPS
- ___ (Compazine) - antiemetic
- thiethylperazine (Torecan) - antiemetic
- ___ (Trilafon) - CATIE studies
- fluphenazine
- prochlorperazine
- perphenazine
1st Gen antipsychotics
thioxanthines
- ___ (Navane) - modest EPS
- chlorprothizene (Taratan)
- thiothixene
1st Gen antipsychotics
Butyrophenones
- ___ (Haldol) - EPS
- droperidol (Inapsine) - highly ___ , anxiolytic
- droperidol with fentanyl (Innovar)
- haloperidol
- sedative
Miscellaneous Antipsychotics
___ (Moban)
- moderate EPS
___ (Orap)
- Tourette’s disease-tics, vocalizations
molindone
pimozide
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)
- negatove
- 5HT2A
- diabetes
- olanzapine, clozapine
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 ___
clozapine
D2, decreased
diabetes
atypical/2nd Gen antipsychotics
___ (Zyprexa)
- weight ___
- less likely to cause N/V
- less likely to cause ___ disorders
- risk of ___
olanzapine
- gain
- movement
- diabetes
atypical/2nd Gen antipsychotics
___ (Loxitane)
- older agent
- metabolite = ___ (Ascendin)
- inhibits ___ = antidepressant
loxapine
amoxipine
NET
atypical/2nd Gen antipsychotics
____ (Seroquel)
- metabolite with ___ activity
- 5HT2A and D2 (low ___ activity)
- low EPS
- ___ (a1)
- ___ (H1)
- risk of ___
Quetiapine
- antidepressant
- antimuscarinic
- hypotension
- sedation
- diabetes
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 ___
risperidone
- 5HT2A, D2
- gain, sedation
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
paliperidone
- 9-hydroxyrisperidone
iloperidone
- risperidone
- a1
atypical/2nd Gen antipsychotics
___ (Geodon/Zeldox)
- affinity for ___ , ___ , and ___
- prolongs ___ interval
ziprasidone
- 5HT2A, D2, a1
- QTc
atypical/2nd Gen antipsychotics
___ (Saphris)
- ___ and ___ (nM affinity at most 5HT, a, DA, and histamine receptor)
asenapine
- 5HT2A, D2
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
lurasidone
- 5HT2A, D2
- olanzapine
- fast
atypical/2nd Gen antipsychotics
___ (Nuplazid)
- inverse agonist 5HT2A (40x more than 5HT2C)
- used for ___ disease psychosis
pimavanserin
Parkinson
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
aripiprazole
- 5HT2, D2
- 5HT1A
- D4, a, histamine
- gain
- aripiprazole lauroxil
dopaminergic activity - aripiprazole
dependent actions (partial agonism)
D2 actions are dopaminergic-state dependent and/or it is functionally selective
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
brexpiprazole
akathisia
5HT1A, D2, 5HT2A
D2/D3 receptor partial agonists
___ (Vraylar)
- greater affinity for ___
- weak partial agonist activity at ___
- ___ is high
- for schizophrenia, mania, bipolar disorder
cariprazine
- D3
- 5HT1A
- akathisia
D2/D3 receptor partial agonists
___ (Caplyta)
- partial ___ agonist at presynaptic receptors
- antagonist at postsynaptic receptors ( ____ antagonist)
lumateperone
- D2
- 5HT2A
