Treatment Of Schizophrenia Flashcards
(22 cards)
What is the dopamine hypothesis?
- caused by increased and dysregulated levels of dopamine neurotransmission in the brain
- has been observed that treatment with dopamine receptor antagonists, specifically D2 antagonists relieves a number of symptoms
What is the function of the Mesolimbic system?
- involved in development of emotions and memory
- mesolimbic hyperactivity is responsible for positive symptoms of schizophrenia
What is the function of the mesocortical system?
Prefrontal cortex is responsible for attention, planning and motivated behaviors
- mesocortical system plays role in negative symptoms of schizophrenia
What is the glutamate theory?
- glutamate NMDA receptor antagonists- e.g. phencyclidine, produces psychotic symptoms in humans
- decrease in glutamate concentrations and glutamate receptor densities in postmortem brains of schizophrenics
Describe the treatment of acute phase in schizophrenia
- higher doses might be necessary in order to treat psychotic symptoms
Describe the maintenance phase of treatment of Schizophrenia
- dosage gradually decreased to minimum required to prevent further episodes and control inter-episode symptoms
- if symptoms reappear/ worsen on lower dosage, then increased dosage may be necessary to help prevent further relapse
What are the classes of typical antipsychotics?
Phenothiazines- “-azines”
Thioxanthenes- “-thixols or -thixene”
Butyrophenones- “-peridols”
What are the atypical antipsychotics?
Clozapine (prototype) and Risperidone
“-zapines”
“-peridone”
Describe the mechanism of action of antipsychotics
Antagonists or partial agonists at D2 dopamine receptors, but most block a variety of other receptors as well
There is activity at muscarinic, H1 and alpha receptors
Block receptors in the mesolimbic tract (overactivity in this location is responsible or positive schizophrenia symptoms- modulates arousal, memory, behaviour
Blockage of remaining dopamine tracts causes adverse effects rather than therapeutic benefit
Describe the function of the mesocortical, nigrostriatal and tuberoinfundibular tracts and how drugs affect them.
Mesocortical tract- responsible for higher order thinking and executive functions
— dopamine hypofunction in this area may be responsible for negative symptoms
Nigrostriatal tracts- modulates body movement
—antipsychotic blockade- EPSE
Tuberoinfundibular tract
- blockade- hyperprolactinemia
What is the difference between typical and atypical antipsychotics?
Typical- affect all 4 dopamine tracts with varying degrees of potency
Atypical- primarily affect dopamine tracts in limbic system and are limbic specific
- have little or no D2 blocking effects in the mesocortical, nigrostriatal and tuberoinfundibular tracts
Describe Chlorpromazine
- administration
- elimination
- side effects
- clinical uses
Phenothiazine, low potency antipsychotic and cross reacts at many receptors
Given p.o, i.v./i.m.
T1/2 30 hrs
Excretion via urine
ADVERSE EFFECTS
Cholinergic blockade- dry mouth, constipation,urinary retention,blurred vision
Alpha adrenergic blockade- postural hypotension
Histamine blockade- sedation
Epileptogenic
Dopamine blockade (nigrostriatal), extrapyramidal dysfunction: Parkinsonism,akathisia, dystopia, tardive dyskinesia (personal tremor, choreoathetosis), neuroleptic malignant syndrome (hyperpyrexia, catatonic, rigidity)
Dopamine blockade (tuberoinfundibulnar)- increase in prolactin, amenorrhea, galactorrhea, infertility
CLINICAL USES
- schizophrenia
- Mania
- Schizoaffective disorders
- Tourette’s syndrome- tic disorder. A tic is a involuntary, repetitive movement or vocalisation
- antiemetic
- antipruritic for intractable itching (due to H1 blockade)
Describe Haloperidol
- administration
- elimination
- clinical uses
- adverse effects
High potency dopamine blocker, exhibits minimal cross activity at other receptors
Given p.o. I.m (lactate), i.m. decanoate (long acting)i.v.
T1/2- 18 hours, 3 weeks (decanoate)
Excretion- urine (30%), faeces (15%)
CLINICAL USES
- schizophrenia— decrease hyperactivity, decrease hallucinations and decrease delusions
- mania
- schizoaffective disorders
- Tourette’s syndrome
ADVERSE EFFECTS
- relatively free of cholinergic, alpha adrenergic, histamine blocking side effects caused by dopamine blockade
- same as chlorpromazine
Describe atypical antipsychotics (ATA)
- ATA generally NOT associated with extra pyramidal side effects
- low affinity for D2 receptors
- affinity for D2 receptors does not correlate with clinical effective dose
What is the 5 HT2 hypothesis?
- associated with atypical antipsychotics
- based on the finding that ATA are all high affinity 5HT2 receptor antagonists (not clear how 5 HT2 receptor antagonism contributes to antipsychotic effect)
What is the D4 hypothesis?
Associated its atypical antipsychotics
- many ATA also are D4 antagonists
- hypothesis suggests that selective D4 receptor antagonism or a combination of D2 and D4 antagonism is critical to the MOA of the ATA
Describe clozapine
- administration
- elimination
- noteworthy side effects
- monitoring
Potent blockade of 5HT2 receptors along with dopamine blockade, effective in treating negative symptoms of schizophrenia
P.o
Hepatic metabolism
T1/2- 12 hours
Monitoring- prior to initiating, obtain CBC w/ differential: regularly monitor ANC and WBC
Less common effects
- leukopenia
- neutropenia
- thrombocytosis
- agranulocytosis
Describe Risperidone
- Effective for both positive and negative symptoms
- prolong QT interval- use with caution in patients with abnormal QT intervals
- p.o, i.m.
What are the drugs used to treat Parkinsonism and akathisia?
ANTICHOLINERGIC
- benztropine
- trihexyphenidyl
- diphenhydramine
DOPAMINERGIC
- amatadine
GABAMINERGIC
- diazepam
- clonazepam
- lorazepam
NORADRENERGIC BLOCKERS
- propranolol
What are the symptoms of mania?
- pressure of speech
- motor hyperactivity
- reduced need for sleep
- flight of ideas
- grandiosity
- elation
- poor judgement
- aggressiveness
- possible hostility
What are the drugs used in the treatment of bipolar affective disorder?
- lithium
- valproic acid
- carbamazepine
- lamotrigine
- gabapentin
- topiramate
Describe lithium
- MOA
- metabolism
- interactions
- adverse effects
MOA- not clearly understood
- inhibits recycling of neuronal membrane phosphoinositides involved in generation of 2nd messengers in both alpha adrenergic receptors and muscarinic neurotransmission— bluntly hyperactive neurotransmission using these pathways
Lithium helps inhibit the GSK3 enzyme, which affects tau protein phosphorylation
Phosphorylated tau proteins can contribute to age-related cognitive decline and memory health
- ?? Use in maintenance of memory, cognitive health support
Well absorbed orally
Renal excretion
T1/2- 20-24 hours
INTERACTIONS
Thiazides and NSAIDS interfere with renal clearance which leads to increase serum lithium levels
Antipsychotics increases EPSE
ADVERSE EFFECTS
- mild decrease in thyroid function (monitor for lithium induced hypothyroidism)
- teratogen
- reversible nephrogenic diabetes insipidus (blocks effect of ADH on kidney)
- leukocytosis
- tremor, hyperactivity, seizures, at toxic levels confusion, weight gain, vomiting, abdominal cramps, diarrhea,
