What are extrapyramidal symptoms (EPS)?
Motor side effects due to blocking dopamine (D2) receptors
- Dystonia (continuous spasms and muscle contractions)
- Akathisia (motor reslessness)
- Parkinsonism (characteristic symptoms susch as rigidity, bradykinesia, and tremor)
- Tardive dyskinesia (irregular, jerky movements)
What is a general rule for determining if a drug causes EPS (neurologic motor) symproms or metabolic symptoms?
- -pines: Metabolic risk
- -dones/-oles" EPS (motor neurologic)
What are the four dopaminegeric pathways?
- Mesocortical (VTA → cortex)
- Nigrostriatal (substantia nigra → striatum) - Control of movement
- Mesolimbic (VTA → limbic system)
- Tuberoinfundibular (hypothalamus → pituitary) - Inhibits prolactin release
Antipsychotic medications are clinically indicated for use in what three situations?
- Schizophrenic psychosis
What results in negative symptoms in Schizophrenia?
Hypoactivity of the mesocortical pathway
What causes positive symptoms in Schizophrenia?
Hyperactivity of the mesolimbic system
- Main target for antipsychotics
Blockade of the nigrostriatal pathway results in what?
Extra-pyramidal symtoms (EPS)
Blockade of the mesolimbic system results in what?
Antipsychotic effect (main target)
Blockade of the mesocortical pathway may result in what?
May worsen negative symptoms
What receptor is the main target for antipsychotics?
Blockade of the dopamine D2 receptor
Blockade of the tuberoinfundibular pathway results in what?
(Thioridazine/Chlorpromazine/Fluphenazine) is capable of stopping intractable hiccups.
Blockade of the chemoreceptor trigger zone/area postrema results in what?
Blockade reduces vomiting
What percentage of D2 receptors need to be blocked to see an antipsychotic effect?
60 - 80 %
Which antipsychotics have a "fast-off" (short acting) property?
Quetiapine (doesn't occupy 60% of D2 receptors)
Works as antipsychotic with little to no EPS
Which antipsychotic acts as a partial agonist at low concentrations but an antagonist at high concentrations?
What are some unique feature of aripiprazole?
- Actually has increased nausea (via D2 agonism)
- Can lower prolactin
- Very expensive
Resistant OCD with or without tourette's can be treated with whcih antipsychotic?
What is the most effective drug for schizophrenia?
Clozapine (by far, just has adverse side effects)
What are some advantages of clozapine?
Very efficatious for Schizophrenia
- Some efficacy against negative symptoms
- Does NOT cause EPS at all (can even be used in Parkinson's patients with psychosis
- Does NOT cause tardive dyskinesia (and may even improve)
- Social stimulus improves
Which adverse motor effects typically occur early in treatment with antipsychotics?
- Acute dystonia (1-5 days)
- Akathisia (5-60 days)
- Parkinsonian syndrome (5-30 days)
Which adverse motor effects typically occur late in treatment with antipsychotics, sometimes taking months or years to develop?
- Tardive dyskinesia
- Perioral tremors (tremors around the mouth; Rabbit syndrome)
What are the adverse effects of clozapine?
- DKA, cadriomyopathy, pulmonary embolism, bowel obstuction
- Weight gain
Worst metabolic symptoms
Which antipsychotics cause the most weight gain?
Cloz Olaz of metabolic symptoms
Whic antipyschotics have the greatest increase of prolactin?
Results in decrease of GnRH, LH, and FSH (casuing irregular menstation and fertility issues)
Increased prolactin can cause gynecomastia, glactorrhea
How is acute dystonia treated?
Acute dystonia - Torticollis (wry neck), oculogyric crisis (upward elevation of eyes), really painful muscle spasms
How is Parkinsonism treated?
Parkinsonism - TRAPS (Tremor (at rest), cogwheel Rigidity, Akinesia (bradykinesia), Postural instability, Shuffling gait)
What is the difference between idiopathic Parkinson's and Parkinsonism?
Idiopathic Parkinson's - Unilateral
Parkinsonism - Bilateral
What is the treatment for akathisia?
Akathisia - Uncomfortable resltlessness
What is the treatment for tardive dyskinesia?
Tardive Dyskinesia - Involvuntary movements: Tongue thrusting and chewing movements, face coiling, chorieform movemetns, etc.
- Not much can be done for treatment (prevention is best)