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47 Cards in this Set
- Front
- Back
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What percentage of patients maintained on conventional D2 blocking antipsychotics will develop TD each year? |
5%, i.e. 25% in 5 years |
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What is the theorized mechanism of resolution of early TD 2/2 d/cing the conventional antipsychotic? |
TD theoretically caused by D2 receptors becoming supersensitive or upregulated, but early d/c of conventional antipsychotic believed to "reset" them. Eventually, they can't be reset. |
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Predictors of likelihood of development of TD? |
1. Early EPS 2. Genetic risk factors (absence of which can be hypothesized in those who haven't developed TD after 15 years of conventional antipsychotic use. Presumably they don't have the genetic risk and will likely never develop TD) |
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Sequelae of hyperprolactinemia |
1. galactorrhea 2. Amenorrhea --> infertility 3. More rapid demineralization of bones, esp. in postmoenopausal women not on HRT 4. Sexual dysfunction 5. Weight gain |
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What's the relationship between DA and Ach in the nigrostriatal pathway? What's the SE of D2 blockade in this situation? |
DA action on cholinergic interneurons inhibits their release of Ach --> less M1 stimulation
D2 blockade leads to more Ach release --> more M1 stimulation --> EPS
An anticholinergic or antipsychotic with high M1 blockade can block this Ach release/binding and relieve/prevent EPS |
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Other names for atypical antipsychotics? |
Second-generation Serotonin-dopamine antagonists |
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What relationship does the cortical 5HT2A receptor have with DA release, and where? |
5HT2A receptors are brakes on DA release in striatum: Serotonin binds to 5HT2A receptor in cortex on Glutamatergic neuron with end bulb in brainstem Glu neuron releases GABA, which acts on nearby DA neuron, inhibiting it DA neuron projects to striatum, where less DA is released |
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What does blocking the cortical 5HT2A receptor do to DA release in the striatum |
5HT2A antagonism cuts the brake cable on DA release in the striatum. No Glu stimulation in cortex --> no GABA inhibition of DA neuron in brainstem --> no inhibition of DA release in striatum = stimulation of DA release in striatum |
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What clinical significance is there for 5HT2A antagonism in antipsychotics? |
5HT2A antagonism --> increased DA release in striatum --> <80% D2 receptors blocked, alleviating EPS SEs |
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What percentage of striatum D2 receptors have to be blocked to cause EPS? |
80% |
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What effects do 5HT and DA have on prolactin release and through which receptors? |
5HT acting on 5HT2A receptors stimulates prolactin release
DA acting on D2 receptors inhibits it |
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What does blockade of both 5HT and DA receptors by an antipsychotic mean for prolactin levels? |
Blocking D2 --> loss of DA inhibition of prolactin release, but blocking 5HT2A --> inability of 5HT to stimulate prolactin release.
Theoretically, this means less hyperprolactinemia with these (atypical) antipsychotics, though it varies, and some agents don't reduce prolactin elevations at all |
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What makes the "pines" and the "dones" atypicals? |
5HT2A affinity is greater than D2 affinity, leading to the beneficial/modulating effects of blocking that receptor |
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What does 5HT1A stimulation by 5HT do to DA release? Where? How? What other beneficial effect might this have? |
5HT1A = accelerator for DA release in striatum 5HT1A binding by 5HT in PFC --> decreased glut release in brainstem --> decreased GABA inhibition of DA neurons in brainstem --> decreased inhibition of DA release at their end bulbs in striatum 5HT1A stimulation might also have an antidepressant effect |
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What effect do antipsychotics that act on 5HT1A receptors have through that mechanism, and how? |
5HT1A partial agonism presses the accelerator by disinhibiting DA release in striatum, leading to decreased EPS |
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What role does stimulation of presynaptic 5HT1A autoreceptors have in antipsychotic use, and where on the neuron and in the brain are they? |
Accelerator of DA release in striatum 5HT1A autoreceptors at the somatodendritic end of 5HT neurons in the raphe lead to decreased 5HT release at the end bulb --> decreased glut at midbrain --> decreased GABA inhibition of DA neurons in midbrain --> disinhibition of DA release in striatum = decreased EPS |
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What receptor activity makes the two pips and a rip atypical? What two pines have similar activity? What done has similar activity and what two other dones have it to a lesser extent? |
They have 5HT1A partial agonism on the order of D2 activity, decreasing EPS by increased DA release in the striatum Pines: clozapine, quetiapine Dones: iloperidone, ziprasidone, and, especially, lurasidone |
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Which 5HT autoreceptor is found at the terminal end? What does it do? Which atypicals have high or low potency at this receptor? |
5HT1B/D receptors, when occupied by 5HT, lead to decreased 5HT release. Antagonism by atypicals leads to increased 5HT release and, hypothetically, antidepressant effects High: iloperidone, ziprasidone, asenapine (unproven antidepressants) Low: olanzapine, quetiapine, aripiprazole (proven antidepressants) |
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Where on neurons are 5HT2C receptors? What does stimulating them do? What does blocking them do? |
Postsynaptic Stimulating - suppresses DA release, mesolimbic > nigrostriatal (so antipsychotic w/o EPS); also weight loss Blocking - stimulates DA and NE release in PFC --> procognition, antidepression. |
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Name two examples of 5HT2C synergy in antipsychotics |
Synergy for Olanzapine/fluoxetine (both block it), leading to improvement of antidepressant effects Quetiapine blocks NE reuptake AND has 5HT2C antagonism, increasing NE levels further in PFC, increasing antidepressant effects |
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What does 5HT3 antagonism do? What drug that's proven in this [psych] function acts in this way? |
5HT3 are postsynaptic receptors which regulate GABA interneurons that regulate the release a number of other NTs. 5HT3 antagonism in the chemoreceptor trigger zone can decrease nausea in chemoTx pts. Blocking it in GABA interneurons increases release of 5HT, DA, NE, Ach, and His in cortex, thus anti-depres./pro-cognition; i.e. mirtazapine |
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5HT6 receptors are found where and are implicated in what processes? |
Postsynaptic Release of Ach, cognitive processes
5HT6 antagonism proposed action in antipsychotics to decrease cognitive Sx of Schz. |
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5HT7 receptors are found where? What does their antagonism do? |
Postsynaptic Blocking them disinhibits 5HT release, especially in combination w/ 5HT reuptake inhibition Moderate to potent in amoxapine, desipramine, imipramine, mianserin, fluoxetine Potent: cloz, quetia, asena, risperi, paliperi, zipras, luras Moderate: olanz, iloperi, 2pips and a rip |
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What makes the two pips and a rip, and similar drugs, atypical antipsychotics? What happens if they're "too" atypical in this way? |
They are D2 partial agonists Less D2 antagonism means less EPS and less negative Sx, but also can cause more activation and N/V |
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Name 3 antipsychotics that have 5HT and/or NE reuptake inhibition 1 potent 2 weak |
Potent: quetiapine Weak: ziprasidone, zotepine |
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Name some antipsychotics with Alpha-2 antagonism |
Essentially all the pines, especially quetiapine and clozapine and dones (higher for risperidone) as well as aripiprazole |
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What properties make antipsychotics good for even nonpsychotic mania? |
D2 antagonism/partial agonism combined with 5HT2A antagonism Potent 5HT1A partial agonism may also be effective |
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What properties of antipsychotics may make them useful as primary or adjunctive measures in anxiety disorders or PTSD? |
Patients may find the anti-his and anti-Ach sedative properties calming and anxiolytic. The greatest evidence exists for quetiapine |
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What properties of antipsychotics make them sedating? |
Blocking of HAM receptors H1 Alpha-1 (central; peripheral alpha1 antagonism --> orthostatic hypotension) M1 |
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Which antipsychotics have potent or moderate H1 antagonism? Which has essentially none? |
Potent: Clozapine, quetiapine, olanzapine, iloperidone Moderate: essentially all others None: lurasidone |
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Which atypical antipsychotics have potent M1 antagonism? Which don't? |
Clozapine, quetiapine, and olanzapine have high potency for M1 receptors All other atypicals have essentially no M1 binding |
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Which atypicals have potent alpha1 antagonism |
All have at least moderate binding potency Most potent are clozapine, quetiapine, risperidone, iloperidone |
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What level of metabolic risk does clozapine carry? |
High metabolic risk - clozapine, olanzapine Moderate - risperidone, paliperidone, quetiapine, iloperidone (weight only) Low - ziprasidone, aripiprazole, lurasidone, iloperidone (low for dyslipidemia), asenapine |
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What level of metabolic risk does olanzapine carry? |
High metabolic risk - clozapine, olanzapine Moderate - risperidone, paliperidone, quetiapine, iloperidone (weight only) Low - ziprasidone, aripiprazole, lurasidone, iloperidone (low for dyslipidemia), asenapine |
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What level of metabolic risk does risperidone carry? |
High metabolic risk - clozapine, olanzapine Moderate - risperidone, paliperidone, quetiapine, iloperidone (weight only) Low - ziprasidone, aripiprazole, lurasidone, iloperidone (low for dyslipidemia), asenapine |
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What level of metabolic risk does paliperidone carry? |
High metabolic risk - clozapine, olanzapine Moderate - risperidone, paliperidone, quetiapine, iloperidone (weight only) Low - ziprasidone, aripiprazole, lurasidone, iloperidone (low for dyslipidemia), asenapine |
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What level of metabolic risk does quetiapine carry? |
High metabolic risk - clozapine, olanzapine Moderate - risperidone, paliperidone, quetiapine, iloperidone (weight only) Low - ziprasidone, aripiprazole, lurasidone, iloperidone (low for dyslipidemia), asenapine |
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What level of metabolic risk does iloperidone carry? |
High metabolic risk - clozapine, olanzapine Moderate - risperidone, paliperidone, quetiapine, iloperidone (weight only) Low - ziprasidone, aripiprazole, lurasidone, iloperidone (low for dyslipidemia), asenapine |
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What level of metabolic risk does ziprasidone carry? |
High metabolic risk - clozapine, olanzapine Moderate - risperidone, paliperidone, quetiapine, iloperidone (weight only) Low - ziprasidone, aripiprazole, lurasidone, iloperidone (low for dyslipidemia), asenapine |
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What level of metabolic risk does aripiprazole carry? |
High metabolic risk - clozapine, olanzapine Moderate - risperidone, paliperidone, quetiapine, iloperidone (weight only) Low - ziprasidone, aripiprazole, lurasidone, iloperidone (low for dyslipidemia), asenapine |
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What level of metabolic risk does lurasidone carry? |
High metabolic risk - clozapine, olanzapine Moderate - risperidone, paliperidone, quetiapine, iloperidone (weight only) Low - ziprasidone, aripiprazole, lurasidone, iloperidone (low for dyslipidemia), asenapine |
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What level of metabolic risk does iloperidone carry? |
High metabolic risk - clozapine, olanzapine Moderate - risperidone, paliperidone, quetiapine, iloperidone (weight only) Low - ziprasidone, aripiprazole, lurasidone, iloperidone (low for dyslipidemia), asenapine |
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What level of metabolic risk does asenapine carry? |
High metabolic risk - clozapine, olanzapine Moderate - risperidone, paliperidone, quetiapine, iloperidone (weight only) Low - ziprasidone, aripiprazole, lurasidone, iloperidone (low for dyslipidemia), asenapine |
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Why do atypical antipsychotics pose metabolic risks? |
Weight gain (2/2 or independent of appetite increase) --> DM --> CAD; mostly true of those w/ 5HT2C antagonism, notably clozapine, olanzapine, quetiapine, and antidepressant mirtazapine Also, though, these cause dyslipidemia and insulin resistance independent of weight gain |
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What is the only antipsychotic documented to reduce the risk of suicide in schizophrenia? |
Clozapine |
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Which antipsychotic may reduce the severity of tardive dyskinesia in some patients, especially over long term treatment? |
Clozapine |
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What is quetiapine's active metabolite? How does its properties differ? |
Norquetiapine It inhibits Norepinephrine Transporter (NET) as w ........ |
