16-Drugs for Psychoses and Degenerative Diseases of the CNS Flashcards
Dopaminergic system’s neurotransmitter.
Dopamine. Both an excitatory and inhibitory neurotransmitter. Dopamine is the precursor of norepinephrine.
The four tracts of the dopaminergic system and where they travel.
- nigrostriatal tract (substantia nigra to striatum)
- mesolimbic tract (VTA to limbic system)
- mesocortical tract (VTA to prefrontal cortex)
- tuberoinfundibular tract (hypothalamus to pituitary)
Which dopaminergic pathway is significant in the pathophysiology of Parkinson’s and why?
The nigrostriatal tract. It is implicated in motion and motor control.
Increased activity in which dopaminergic pathway is associated with positive symptoms of schizophrenia?
The mesolimbic tract.
Which dopaminergic pathway is implicated in the negative symptoms of schizophrenia?
The mesocortical tract.
What are the two types of dopamine receptor classes and which G proteins are associated with each?
- D1-like dopamine receptors (D1,D5 - Gs protein associated)
- D2-like dopamine receptors (D2, D3, D4 - Gi protein associated)
True or False: Increase in dopaminergic activity is associated with psychosis.
True
True or False: Increase in dopaminergic activity is associated with neurodegenerative diseases.
False.
Schizophrenia: onset & symptoms
- Onset typically occurs during late adolescence
- Positive symptoms: delusion, disorganized behaviour, agitation, disorganized speech & thinking, hallucinations, paranoia, illusions
- Negative symptoms: anhedonia, lack of motivation, blunted affect, social withdrawal, poverty of speech, poor social skills & hygiene
- Cognitive symptoms: deficits in long-term memory, inability to focus attention, diminished “working memory”, difficulty following instructions, difficulty following the thread of a conversation, difficulty identifying the steps needed to complete a task and placing in sequence
What drug class can induce psychotic symptoms?
Dopamine agonists. Therefore dopamine antagonists have anti-psychotic activity.
What change in dopamine activity is associated with schizophrenia? At which receptors
An increased dopaminergic activity at dopamine D2 receptors (associated with the mesolimbic tract).
What is an alternate name for an antipsychotic drug?
neuroleptic drug
All antipsychotic drugs are _____________ receptor antagonists?
dopamine D2 receptor antagonists.
Does the use of antipsychotic drugs in schizophrenia manage both the positive and the negative symptoms?
Antipsychotic drugs reduce positive symptoms by decreasing dopaminergic activity. However, some do also exhibit an affinity for serotonin receptors to bring up lows of the depression. These are atypical antipsychotics.
What is an example of one of the more common typical (conventional) antipsychotics? When is it used?
Haloperidol (Haldol), a non-phenothiazine drug. Used for acute psychosis to calm someone down or in the case of dementia and delirium.
Are typical antipsychotic drugs used for the treatment of schizophrenia? Why or why not.
Not anymore. There are negligible effects on the negative symptoms. There are also Extrapyramidal effects (EPS) of acute dystonia, pseudo-parkinsonism, akathisia and tardive dyskinesia.
What is the mechanism of action of conventional antipsychotics? What is the therapeutic effect?
- effect mediated via the blockade of dopamine D2 receptors in the mesolimbic and mesocortical tracts
- effective in treating the positive symptoms of schizophrenia (hallucinations & delusion diminish within days; other symptoms may take 7-8 weeks to improve)
Why do the EPS of conventional antipsychotics result in pseudo-parkinsonism?
These drugs are associated with blockade of dopamine D2 receptors in the nigrostriatal tract which induces motor deficits as in Parkinson’s.
True or False: Only non-phenothiazine typical neuroleptic drugs can cause extrapyramidal signs.
False. Both phenothiazine and non-phenothiazine typical neuroleptic drugs can cause extrapyramidal signs.
What is the difference between the adverse effects associated with phenothiazine drugs vs. non-phenothiazine drugs.
Non-phenothiazine drugs are associated with extra pyramidal signs such as acute dystonia, akathisia, pseudo-parkinsonism and tardive dyskinesia. Phenothiazine drugs are associated with greater anticholinergic effects (dry mouth, tachycardia and blurred vision) and increased sedation.
Other than EPS, anticholinergic effects and sedation, what are some other adverse effects of conventional antipsychotic drugs?
Hypotension, sexual dysfunction and neuroleptic malignant syndrome (high fever, confusion, muscle rigidity, and high serum creatine kinase - can be fatal)
What is the first line therapy for both the positive and the negative symptoms of schizophrenia?
Atypical antipsychotic drugs.