2012
others
SCHIZOPHRENIA
Definition:
Etiology unclear
SCHIZOPHRENIA -PATHOPHYSIOLOGY
Morphological changes
Neurotransmitter changes
Glutamate theory
Serotonin theory
DOPAMINE THEORY:
DOPAMINERGIC SYSTEMS IN CNS
Dopamine tract Innervation Function
D-antagonist
effects
Mesolimbic
Limbic areas
(amygdala)
Arousal, memory,
stimulus processing,
behavior, spontaneity,
motivation,
assertively, selfconfidence
Mesocortical
Cortex
frontal and
prefrontal
Communication,
cognition, social
functions and stress
response
Nigro-striatal
Caudate nucl.,
Putamen
Extrapyramidal
system and movement
coordination
Movement
disorders
Tuberoinfundibular
Pituitary
gland
Prolactin secretion
regulation
Hyperprolactinea
mia, galactorhea,
gynecomastia
Psychosis relief
Psychosis relief
Akathisia?
Dopamine receptors D1 type (D1 and D5) and D2-type (D2, D3, D4)
D2-receptors
Are evidently involved
correlation between D2-antagonistic effects and antipsychotic action
Clinical response in occupancy of 60-80% of D2 receptors
for atypical drugs 30-50% is enough
PHARMACOTHERAPY OF SCHISOPHRENIA
GENERAL ASPECTS
Monotherapy is preferable
PHARMACOTHERAPY OF SCHISOPHRENIA
GENERAL ASPECTS
Long-term treatment
PHARMACOKINETICS OF ANTIPSYCHOTICS
Route of administration
oral or by i.m. injection
once or twice a day.
b) incisive:
- haloperidol (typical example, a butyrophenone structure)
- fluphenazine, flupenthixol, clopenthixol
CLASSIFICATION OF ANTIPSYCHOTICS
Acute (reversible)
Parkinson-like symptoms (further details on next seminar)
Tremor
Rigidity
Bradykinesia/akinesia:
Acute dystonias
- severe muscle spasms, very painful (occur within initial 24-96h)
Orofacial muscles (e.g., blepharospasm - eye lid spasm, oculogyric crisis
turning of eye bulbi upward),
Neck muscle spasms (torticollis wry neck)
Tongue protrusion
Can be life-threatening pharyngeal-laryngeal forms
Akathasia
motor restlessness (restless leg syndrome)
inner restlessness
Mechanisms of EPS
Dopamine (-)
cholinergic
pathway (+)
S. NIGRA
CORPUS
STRIATUM
GABA (-)
Adverse effects
B type unpredictable
ADVERSE EFFECTS
OTHERS
- urticarial skin reactions
mainly phenothiazines
- depositions
Chlorpromazine
1st classic neuroleptic drug, inexpensive
Strong autonomic effects (blocks also ,M, H1)
Route: p.o., i.m., i.v.
Ind.:
schizophrenia (against positive symptoms)
Bipolar disorder (against mania)
Not to be used: in patients with dementia, treated by IMAO
Slow discontinuation after longer treatment
Be careful about combination with: sedative drugs, QT-prolonging drugs,
hypotensives
Haloperidol
Prototype incisive neuroleptic drug
Butyrophenone (not phenothiazine)
- Ind.:
Schizophrenia (both acute and chronic)
Korsakov syndrome (in alcoholics acute amnesia, confusion, delusions,
apathy)
Delusional disorders (like paranoid disorders)
Psychomotoric calm-down
Antiemetics
-
Olanzapine
IND
Schizophrenia
Manic phase of bipolar disorder (acute treatment and prophylaxis)
Clozapine
Developed in 70s, but not introduced into clinical practice