Anti-Psychotics Flashcards
Main neurotransmitters in schizophrenia
Serotonin
Dopamine
Psychosis
Inability to think or comprehend reality
Schizophrenia
Withdrawal, disordered thought process, delusions, auditory hallucinations
Schiz positive s/s
Hallucinations
Delusions
Behavioral disorg
Thought disorder
Schiz neg s/s
Alogia Affective blunting Avolition Asociality Anhedonia Attention impairment
Schiz
DA hypothesis
- All antipsycs block D2 receptor
- up synaptic DA= psychosis (amphetamine, L-DOPA)
- DA receptor changes
- successful Tx increases DA metablites
Amphetamine DA release
Up via reversal of transporter
Serotonin
- new Rx block 5HT recepotor
* clin correlation poor
Glutamate
- NMDA receptor
- can induce psychosis with this
- no Rxs
Acute psychotic episode
Antispyc in ER (haloperidol?)
*long term tx 4-6 weeks (depolarization inactivation)
Depolarization Inactivation
After overfiring DA neuron due to presynaptic receptor stimulation, whole neuron wears out in 4-6 weeks
Acute tx
Block post synaptic receptor
Presynaptic sees less, fires more
Frontal cortex in Schiz
Too LITTLE DA = negative symptoms
VTA to cortex degraded (prefrontal neurons),
no feedback mech to Accumbens,
Accumbens ramps up dopamine release
W too much acivity in accumbens
D2 blockers = blocking in nigrostriatal pathway
Parkinson’s s/s
EPS symptoms = extra-pyramidal
Prolonged treatment w/ D2 blockers
D2 post synaptic receptors up regulate =
Tardive Dyskinesia (activity)
- Short-term = movement poverty (EPS)
- Long-term = too much movement
Where = Endocrinological S.E.
Arcuate nucleus (hypothalamus) –> pituitary
DA suppresses PRL release
UP PRoLactin = gynecomastia
Neuroleptic
“Clamp the neuron” = EPS s/s
Don’t say this, old term
Schiz tx
1st generation
Butyrophenones (haloperidol)
2nd gen
Rxs
Clozapine Risperidone Olanzapine Ziprasidone Aripiprazole
Clorpromazine (thorazine)
- anethesia
- d2 blocker
- sometimes in acute
Butyrophenones
Haloperidol
Lower sedation + less alpha block than phenothiazines
Atypical Rxs/ 2nd gen
More 5HT receptor blocking (serotonin)
2nd gen
Clozapine
- 1st
- NO EPS
- DPI ONLY in mesolimbic pathway (NOT striatum, NOT frontal cortex)= no neg/ EPS symptoms
2nd Gen
Clozapine
S.E.
*Agranulocytosis risk (bone marrow/blood)
(Compliancy/cost)
**DM risk
Blocking serotonin
Facilitate Dopamine release in FRONTAL CORTEX
*serotinin blocking dopa neuron ONLY in FRONTAL CORTEX
2nd gen
Risperidone
*low dose = low EPS
(Dose-dependent atypical)
*NO agranulocytosis risk
2nd gen
Olanzepine
- NO agranulocytosis
- *DM risk/weight gain risk
- LESS serum prolactin release than haloperidol
2nd gen
Ziprasidone
*QT interval widening
2nd gen
Aripiprazole
- partial agonist at D2 receptor (block where high, increase where low)
- modest 5HT2 block
- partial 5HT1A agonist
- no DM
Partial D2 agonist
- down dopa in accumbens
* UP dopa in frontal cortex
Anti-psych
Neuro S.E. Early
- ACUTE DYSTONIA = Spastic retrocollis/torticollis
- AKATHISIA = reduce rx/benzo/propanolol
- EPS. = bradykinesia, rigidity, gait
- NMS Neuroleptic Malignant Syndrome
- can be fatal, stop Rx NOW
- Sedation
- Lower seizure threshold (older Rx, clozapine, epileptic)
REVIEW SLIDE
Anti-psych
Neuro S.E. Later
- Perioral syndrome (rabbit syndrome)
- D2 blocked
- give anti-Parkison Rx - anticholinergic
- ***Tarditive dyskinesia
- D2 super-sensitivity
- NO ANTICHOLINGERGICs
MUST PREVENT THESE
Anti-Psycs : Autonomic S.E.
- Ortho HypoHTN (a1 block)
- Altered sexual function
- Anticholinergic
Anti-psych. S.E.
Endocrine
*Up prolactin (D2 block in pituitary)
Other Anti-psych S.E.
- Blood dyscrasias (clozapine-agranulocytosis)
- Metabolic - up weight gain, DM/Hyperlipid
*Skin
*Cardio toxicity
Thioridazine - T wave
Ziprasidone QT prolong
Anti-psychs
ADME
A = erratic, down w/ food , antacid, anticholinergic
- goes in fat (brain)
- hepatic metab, glucuronic acid conjugation
Anti-psychs
Rx interaction
- up CNS depressants
- Quinidine-effect bad w/ Digitalis
- no w/ antiHTN
- barbituates = up metab
- Musc block = confusion
DM risk
Olanzapine
Clozapine
Where = Weight gain S.E.
Motor nucleus (vagus) –> area around ventricles
D2 block = hunger
Where = anti-emetic S.E.
Chemotrigger zone (CTZ)
1st gen S.E.
ASK teacher
2nd gen
DM risk
- Clozapine
- Olanzapine
- Risperidone
- Ziprasidone
2nd gen
EPS s/s
Risperidone
2nd Gen
QT prolongation
Ziprasidone
2nd gen
PRL s/s
Risperidone
2nd gen
Weight gain S/s
Clozapine
Olanzapine
Risperidone
Ach block
Clozapine
Olanzapine
Anti-psycs
Other uses
- Organic brain syndrome
- Acute mania
- Tourette’s Syndrome
- Bipolar
- NO DEMENTIA in ELDERLY
