Antipsychotics, Mood Stabilizers, ADD Drugs

jmanderson's version from 2016-03-12 16:18

PowerPoint Objectives


Question Answer
Give two symptoms that must exist before a diagnosis of psychosis will occur.delusions, prominent hallucinations (auditory > visual), incoherence (loosening of associations), catatonia, flat or inappropriate affect.
Positive Sx of psychosiscombativeness, agitation, acute hallucinations/delusions
Negative Sx of psychosisavolition, asocial, lack of affect, alogia, autistic lifestyle, loss of insight, loss of motivation
Give the arguments in favor of the dopamine hypothesis of psychosis.1) Anti-psychotic drugs block post-synaptic D2 receptors, especially in the meso-limbic-frontal system; 2) drugs that increase dopamine, e.g. levodopa or amphetamines, either aggravate schizophrenia or produce it; 3) non-treated schizophrenic brains have increased DA receptor density; 4) PET scans have shown increased DA receptor density in both treated and non-treated schizophrenics; 5) Successful treatment of schizophrenia results in reduced levels of homovanillic acid in the CSF, urine and plasma.
Give the dopamine pathway most commonly associated with psychosis.MESOLIMBIC-MESOCORTICAL (A10 nucleus Dopamine system (likely to be involved in anti-psychotic actions) cells near the Substantia Nigra → send processes to the limbus and neocortex)
antipsychotic Motor AEsEXTRAPYRAMIDAL effects, such as acute dystonia (facial grimacing and ocular problems); akathisia (constant movement due to leg discomfort); parkinsonian syndrome (slowing of volitional movement), TARDIVE DYSKINESIA as a late effect
antipsychotic Endocrine AEsPROLACTIN increases (all associated with this one), infertility, amenorrhea-galactorrhea
Give the definitions of atypical anti-psychotics.Fewer extrapyramidal side effects; Efficacy on negative symptoms; Increased efficacy in treatment-resistant pts; No elevation of Prolactin levels (?); Low incidence of tardive dyskinesia; Ability to improve cognitive functioning.
Give the ratio of two neurotransmitter receptors that some researchers think is important in determining anti-psychotic efficacy.5-HT2/DA2 ratio
Explain whether there is concern about cardiac problems in relation to anti-psychotic use.1) There have been cases of SUDDEN CARDIAC DEATH with use of anti-psychotics; 2) There are changes in QT-INTERVAL with several anti-psychotics including atypicals (clozapine, olanzapine)
List 3 dynamic systems upon which lithium is capable of acting.1) Some evidence that lithium enhances 5-HT action; 2) May decrease DA and NE release (needs study) which agrees with increased NE synaptic levels in mania; 3) Blocks DA receptor supersensitivity that develops with anti-psychotics.
Describe the advantage of giving lithium with anti-psychotics.Adding Li to anti-psychotics may salvage otherwise TREATMENT-RESISTANT SCHIZOPHRENIA
two metabolic steps in it that are inhibited by lithium.Lithium blocks conversion of IP2 → IP1 and IP → inositol which depletes PIP2.
general lithium and anti-psychotic dosing for initial manic episodesLithium used in combination with anti-psychotics to BEGIN the treatment regimen → when the mania is under control, the anti-psychotic is REMOVED.
Describe what must be monitored during initial and maintained lithium treatment.Complete blood count, urinalysis and blood tests, ECG in older pts as baseline measures (sinus node effect).
Describe what criteria are required for maintenance therapy with lithium.1) If pt has had only one cycle or is unreliable stop Lithium after one course with gradual discontinuation; 2) If CYCLES ARE WORSENING OR MORE FREQUENT or > once per year then maintain them on Lithium after remission, with approval of patient.
use of CARBEMAZEPINE (anticonvulsant, mood stabilizer) along with lithium for mania, including dosingCarbemazepine is used alone for mania or in refractory pts with lithium as a mood stabilizer. Begin with 200 mg TWICE A DAY and increase as needed.
the patient population in whom CLONAZEPAM (benzodiazepine) is usefulUseful prophylactic value in patients NOT COMPLETELY CONTROLLED BY LITHIUM

HandOut Objectives


Question Answer
Dopamine-2-like ReceptorsDA2, DA3, DA4 binding potency is correlated with antipsychotic potency
○ DA2inhibits cAMP (chromosome 11) blocks Ca++ channels but opens K+ channels found pre- and post-synaptically in the striatum and olf. tubercle.
○ DA3 and DA4in same family, decrease cAMP, G-protein linked. DA3 in cortex, medulla and midbrain.
An anti-dopamine neuroleptic drug’s effectiveness in blocking dopamine synapses is almost perfectly correlated with….its ability to clinically control schizophrenia.
Give one thing that is true of withdrawing anti-psychotics from a patient who has developed tardive dyskinesia and what this means for its treatment. (Hint: see table of EPS symptoms)Tardive dyskinesia = is an adverse effect of anti-psychotics.
Features of tardive dyskinesiaoral-facial dyskinesia; widespread choreo-athetosis or dystonia.
Time of risk of tardive dyskinesiaafter months or years of treatment (worse on withdrawal)
Mechanism of tardive dyskinesiaexcess function of dopamine hypothesized.
Treatment of tardive dyskinesiaprevention is crucial (avoid antipsychotic withdrawal) because treatment is unsatisfactory
Endocrine AE’s of Anti-psychoticsincreased prolactin, infertility, amenorrhea, galactorrhea
Characterize the level of movement side-effects from SERTINDOLE (atypical antipsychotic) in the study cited.The level of extrapyramidal side effects from sertindole is equal to placebo.
OLANZAPINE (atypical antipsychotic) AE’sweight gain, some extrapyramidal side effects and tardive dyskinesia, no agranulocytosis, some elevation of prolactin
Typical anti-psychotics wt-gain/sugarless incidence of glucose intolerance and weight gain
Atypical anti-psychotics wt-gain/sugarmore incidence of glucose intolerance (hyperglycemia, glucosuria, diabetes) and weight gain (except risperidone)
Give the four ways to avoid weight gain problems in patients receiving anti-psychotics according to the Melkersson and Dahl article.1) monitor weight, fasting blood glucose, and serum concentrations of lipids and insulin; 2) Where possible use atypical antipsychotics with lower levels of weight gain (see above); 3) Use lowest effective dose of anti-psychotic; 4) regularly ask patients taking atypicals with higher incidence of weight gain about diabetic symptoms, weight, lethargy, polydipsia etc.
Give the two anti-psychotics that when given long-term demonstrate dangerous changes in the QT interval according to the Goodnick et al. paper.Clozapine, olanzapine
Give the advantage of using lithium in treatment of mood disorders in alcoholics.Alcoholism is often associated with bipolar, and lithium reduces drinking when the conditions coexist.
Explain what must be done in cases of lithium overdose.1) Stop the Lithium and monitor serum levels; 2) Use hemodialysis to remove.
Explain why lithium is contraindicated in cases of “sick sinus”.Bradycardia-tachyardia (“sick sinus”) syndrome is a definite contraindication to use of lithium because Lithium FURTHER DEPRESSION OF THE SINUS NODE

ADD drugs Powerpoint Objectives


Question Answer
Explain whether the diagnosis of adhd is appropriate in non-pediatric populations.According to DSM-V, ADD is now thought to continue in adolescents and adults; in adults called ADHD partial or just ADD
Methylphenidate MOAblocks DA and NE uptake transporters increasing these in synaptic cleft
Atomoxetine MOAReuptake inhibitor of norepinephrine, but with surprisingly few peripheral effects
Dextroamphetamine MOALike amphetamine, its effect is mediated through stimulated release of norepinephrine > dopamine (frontal lobe?)
Other than ADHD, what is another indication for methylphenidate and dextroamphetamine.Narcolepsy
Give three adverse effects of dextroamphetamine.Valvulopathy, pulmonary hypertension, nervousness, insomnia, changes in libido, mydriasis
Give an adverse effect of atomoxetine that requires monitoring and what must be monitored.Severe hepatotoxicity, so monitoring of liver enzymes and checking for jaundice is recommended.