anti-psychotic drugs Flashcards
what is schizo?
- thinking, behavior, perception disorder
- onset at early adult life
- fluctuation
- 50% attempt suicide
positive symptoms of schizo
- delusions
- hallucinations
- speech
- thought disorder
- catatonia (mental numbness)
- mesolimbic too MUCH dopamine
negative symptoms of schizo
- alogia (inability to speak)
- affect flat
- anhedonia (absence of pleasure)
- avolition (lack of motivation to goals)
- mesocortical too LITTLE dopamine
aetiology of schizophrenia
- genetic
- environment (virus infection and cannabis use)
- social dysfunction
- inflammation
- oxidative stress
- neuroplasticity
explain genetic factor
- 50% monozygotic twins
- 10% siblings
- NMDA receptor dysfunction
- glutamergic transmission
expain social dysfunction factor
- cognition social neuro
- positive symptoms
- negative symptoms
- mood disorder
- substance abuse
differential psychotic behaviour
- delirium (temporary mental confusion)
- dementia
- autism
- depression
- personality disorder
- encephalitis
what is the dopamine hypothesis?
- amphetamine reproduce positive symptoms
- L dopa and agonists increase symptoms
- reserpine decrease symptoms
what is the glutamate hypothesis?
- decrease NMDA receptor function
- ketamine, phencyclidine reproduce positive and negative symptoms
what is the GABA hypothesis?
decrease GABAnergic inhibition
what is the serotonin hypothesis?
5HT 2 antagonism help negative symptoms
what nigrostriate pathway for?
motor function
what mesocortical pathway for?
emotion and reward
what mesolimbic pathway for?
emotion and reward (positive symptoms)
what tuberoinfundibular pathway for?
endocrine function
old terms for anti-psychotic drugs
- neuroleptics
- major tranquillisers
- antischizoprenics
what CAPS (conventional) do?
- first generation
- block D2 mesolimbic
- block MUSCARINIC receptors
- block ADRENERGIC receptors
- histamine 1 give sedation
what AAPS (atypical) do?
- 2nd generation
- block D2 mesolimbic
- block MUSCARINIC receptors
- block ADRENERGIC receptors
- 5HT2 antagonists
- 5HT1 agonists
what are the initial treatment?
- orally at lowest dose
- treat as early as diagnosis
- increase after 2 weeks if poor response
- treat at least 4-6 weeks
- avoid combinations
- treat at least 1 year
- watch for tolerance
general characteristics of CAPS
- oral absorption
- depot IM
- variable efficacy
- lipophilic
- large volume distribution
- first pass metabolism
examples of butyrophenones (CAPS)
- haloperidol
- benperidol
examples of thioxanthines (CAPS)
- flupenthixol
- zuclopenthixol
example of benzamides (CAPS)
sulpiride (reduce EPS)
example of butylpiperidines (CAPS)
pimozide (reduce EPS)
characteristics of aliphatic 1 (phenothiazine) and examples of drugs
- low potency
- sedating
- moderate EPD
- CHLORPROMAZINE and PROMAZINE
characteristics of piperidine 2 (phenothiazine) and examples of drugs
- moderate potency
- moderate sedating
- low EPD
- PIPOTIAZINE and PERICYAZINE
characteristics of piperizine 3 (phenothizine) and examples of drugs
- most potent
- least sedating
- high EPD
- FLUPHENAZINE and PERPHENAZINE
CAPS motor side effects
- dystonia (reversible)
- parkinsonism (reversible)
- dyskinesia (irreversible)
- akathisia (inability to remain motionless)
- neuroleptic malignant syndrome
what 5HT 2A antagonism AAP do?
- indirectly increases dopamine transmission
- negative symptoms improve
what 5HT 2C antagonism AAP results?
- weight gain
- eg: CLOZAPINE and OLANZEPINE
examples of drugs of AAP
- aripiprazole
- risperidone (oral, liquid, long IV)
- olanzepine (oral, short, long IV)
- ziprasidone (short- acting IV)
benefits of AAP
- better tolerated (1st line)
- less EPD
- better for negative symptoms
concerns when giving AAP
- cardiac disease
- parkinson’s disease
- epilepsy
- elderly
- liver disease
side effects of AAP
- severe weight gain
- metabolic syndrome
- hyperglycemia
- postural hypotension prolonged QTs
- sexual dysfunction
drugs to treat neuroleptic malignant syndrome
bromocriptine or dantrolene
main drugs for AAP
clozapine
diagnostic criteria of neuroleptic malignant syndrome
at least 2 of the following
- diaphoresis (sweating)
- dysphagia
- tremor
- incontinence
- mutism
- tachycardia
