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78 Cards in this Set

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  • Back
what disorders are among the most severe psychiatric disorders?
Psychosis disorders all exhibit major disturbances in what?
1.Reasoning , often with delusions and hallucinations
2.Behavior (disorganized or irrational )
3.Mood (excited agitation to severe emotional withdrawal).
Psychosis is a common disorder that affects what % of the population? What stages of life does it often present?
affecting 1% of the population at some age.
Often presents in late adolescence/early adulthood
What are 5 psychotic disorders?
2.Manic phase of bipolar illness (manic-depressive)
3.Acute idiopathic psychotic illnesses
4.Delusional disorder
What is Schizophrenia?
Chronic disordered thoughts, disorganized irrational behavior, “voices”
Schizophrenia is thought to be a group of what? Are there any tests for it?
Schizophrenia is thought to be a group of related brain disorders
There are currently no biological tests for schizophrenia
what are 3 clear biological links to the onset of schizophrenia exist?
Disrupted neurobiochemistry
Altered neuroanatomy
What is altered in patients with schizophrenia?
Brain anatomy
Overall alterations in brain anatomy from schizophrenia include what 2 components?
Significant loss of gray matter
Enlarged ventricles
What does gray matter =? This means that higher functioning will what?
Gray matter = cortex cell loss! This means that higher functioning will decrease
what are 5 Specific Brain Anomolies in Schizophrenia? What happens to the limbic system, Wernicke's area, Occipital lobe, frontal lobal and basal ganglia?
1.Brain areas making up the limbic system are affected (regulation of emotion) 2. Wernicke’s area in the auditory cortex is overactive (auditory hallucinations) 3.Occipital lobe dysfunction leads to difficulty in interpreting complex images 4.Frontal lobe dysfunction leads to difficulty in planning ahead, higher cognitive functions like reasoning 5.The basal ganglia in schizophrenics appear to be dysfunctional (leads to paranoia, hallucinations)
What are the basal ganglia involved in?
The basal ganglia are involved in the integration of sensory info; emotions; the regulation of movement
Schizophrenia have what % shorter life expectancy?
Antipsychotic drugs are what kind of family?
diverse chemical family w/different potencies and side effect profiles
Psychoses involves what?
multiple neurotransmitter anomalies (e.g. dopamine, glutamate)
What is a a common mechanism of antipsychotic drugs?
Blunting of dopamine action
First generation antipsychotics “neuroleptics” have what kind of side effects?
Parkinson-like side effects
Atypical Antipsychotics (2nd Generation) have fewer what? What is there a significant risk of?
Fewer extra-pyramidal side effects (Parkinson-like symptoms)

Significant metabolic syndrome risk
3rd Generation Antipsychotics have fewer what?
Fewer metabolic side effects (perhaps)
What was the antipsycotic rugs in global sales in 2008?
$22 billion
What is Neuroleptic syndrome? What components are kept intact?
Suppression of spontaneous movements and complex behaviors

Spinal reflexes and unconditioned nociceptive-avoidance behaviors intact
Neuroleptics decrease what 3 characteristics?
interest in environment
Neuroleptics are considered to be what?
Can patients on these drugs answer questions and retain intact cognition?
“tranquilizers” : initial drowsiness and slowness to respond to stimuli

What are side effects of neuroleptics?
Parkinson’s like symptoms: tremor, restlessness, rigidity, bradykinesia
Neuroleptic Rx reduce what? Is it a cure?
Gradual (days) reduction in psychotic symptoms
BUT not a cure
What is Nociperception?
the neural processes of encoding and processing noxious stimuli.
What is Bradykinesia?
slowed movement with inability to appropriately adjust body position
1st Generation Antipsychotics “Neuroleptics” are very ___drugs? They have effects on what receptors?
Very “dirty” drugs → effects on many receptors

H1, alpha2 adrenergic, serotonin, muscarinic-cholinergic
1st Generation Antipsychotics “Neuroleptics” have Antipsychotic efficacy via what?
mesolimbic and mesofrontal D2 receptors (antagonists)
What is Haloperidol? What is it more potent than?
Haloperidol is potent dopamine receptor competitive antagonist (D1, D2, D3, D4). More potent than chlorpromazine.
For 1st generation neuroleptics, Extrapyramidal/neuroleptic side effects (Parkinsonian movement disorders) via what? What can it cause?
via binding/antagonism of D2 receptors in basal ganglia

Can cause irreversible tardive dyskinesia (uncontrolled hyperkinetic movements; e.g. fluphenazine)
What are side effects of 1st Generation Antipsychotics “Neuroleptics”?
Side effects: Tachycardia, dizziness and impotence via alpha2 adrenergic receptor, and drowsiness
What are 2, 1st Generation Antipsychotics “Neuroleptics”?
Chlorpromazine and Haloperidol
A D2 receptor antagonist prevents the activation of what? The D2 receptor is coupled to what? What does it dissociate from? What does it inhibit? This causes inhibition of what? What inhibits this usual process?what does it result in?
1. dopamine D2 receptor 2.inhibitory G-proteins, which dissociate from the receptor on agonist binding and inhibit secondary messenger signaling mechanisms 3. This causes inhibition of down-stream signaling mechanisms. 4. Antagonist binding inhibits this usual process, resulting in cell depolarization
What are the Currently the most frequently used antipsychotic Rx?
“Atypical” Antipsychotics- 2nd Generation
“Atypical” Antipsychotics- 2nd Generation are generally more ___ compared to 1st gen?
“Atypical” Antipsychotics- 2nd Generation have what kind of binding affinties?Some appear to have > affinity for ___ than ___?
Variable receptor binding affinities
Some appear to have > affinity for D4 vs. D2 (e.g. clozapine)
“Atypical” Antipsychotics- 2nd Generation have what kind of potent receptors?
Potent 5-HT2 receptor antagonists
“Atypical” Antipsychotics- 2nd Generation compared to neuroleptics are less potentat what site?
Less potent at D1 receptors
“Atypical” Antipsychotics- 2nd Generation have what kind of severe metabolic side effects ?
including rapid weight gain, hypertension, hyperglycemia, hyperlipidemia, insulin resistance → “metabolic syndrome”
September 18, 2003: The FDA stated that all atypical antipsychotic drugs, across all chemical classes, should have what?
warning labels stating increased risk of diabetes and related disorders.
What are 3 "Atypical” Antipsychotics- 2nd Generation drugs?
Olanzapine (Zyprexa)
Ziprasidone (GEODON)
Quetiapine (seroquel)
Olanzapine, Ziprasidone and quetiapine FDA approved for schizophrenia and bipolar disorder in what age group?
Second generation antipsychotics are increasingly prescribed to children and adolescents in the US as what?
first line treatment for psychotic disorders, bipolar disorder and non-psychotic metal disorders
What percent of atypical use in kids off-label for non-psychotic conditions like ADHD?
Second-Generation Antipsychotic Medications During First-Time Use in Children and Adolescents gain how much weight in 11 weeks?
19.7-18.7 lb weight gain following 11 weeks of drug treatment
1 in 10 MaineCare members under 19 years of age is on how many mental health drugs in the course of 1 year?
4 or more
How many foster children are on anti-psychotics? How is this compared to usage in non-foster children?
1 in 5 foster children are on anti-psychotics, 4x the rate of usage in non-foster children
In addition to schizophrenia, the FDA approved 3rd generation antipsychotics: Aripiprazole for what? In what age group?
FDA approved for manic and mixed episodes in adults and children (age 10-17), clinical depression and treat irritability in children with autistic disorder.
3rd generation antipsychotics: Aripiprazole, are involved with what receptor? What could these receptors be responsible for?
D2 receptor partial agonist:Partial agonist at 5-HT1A and 5-HT2c receptors and antagonist at 5-HT2A receptor.

May be reason for less weight gain vs. 2nd generation drugs.
3rd generation antipsychotics: Aripiprazole have moderate affinity for what?

What activity don't they have?
Moderate affinity for H1 and α-adrenergic receptors and SERT. No muscarinic activity.
Antipsychotics: Absorption and metabolism--> Have what kind of absorption? Readily across what? What are they bound to? What size is the Vd? What substrates are involved? What kind of t1/2? What formulations are available?
1. Variable Absorption
2. Readily cross BBB
3. Bound to plasma proteins
4. Large Vd
5. Hepatic CYP substrates (2D6, 1A2, 3A4)
6.Large variation in t1/2
7. Slow or extended release formulations avaliable.
Antipsychotic Medications: Summary
Considered to be powerful what, with that effects? Serious side effect profiles include?When can withdrawal symptoms be severe?
1.Powerful tranquilizers with effects at multiple CNS targets
2.Serious side effect profiles including permanent chemical dependence, diabetes, and reduced life expectancy
3.Withdrawal symptoms can be severe upon cessation of Rx, dose reduction or change in Rx
First generation antipsychotics are efficacious in tx of what? What formulations are they avaliable in? What kind of side effect profile?
1.Efficacious in treatment of psychotic symptoms
2.Available in slow-release depot formulations
3.Significant “parkinsonian” side effect profile
Atypical (2nd Generation) Antipsychotics are used in tx of what? What kind of side effect profile? Significant risk of severe what? Increasing use in what age group?
1.Used in treatment of schizophrenia, bipolar illness and in some cases, autism
2.Low risk of Parkinsonian side effects
3.Significant risk of severe weight gain and adverse metabolic syndrome side effects for several drugs in this class
4.Increasing use in children
3rd Generation Antipsychotics have different what? What kind of cost? Do they have less risk for severe metabolic side effects?
2. cost
3. Not enough data
What is mania? what disorder is it often associated with?
A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary). Often associated with bipolar disorder.
Mania: During the period of mood disturbance, what are three (or more) of the following characteristics that have persisted?
1) inflated self-esteem or grandiosity (2) decreased need for sleep (e.g., feels rested after only 3 hours of sleep) (3) more talkative than usual or pressure to keep talking (4) flight of ideas or subjective experience that thoughts are racing (5) distractibility (attention too easily drawn to unimportant or irrelevant external stimuli) (6) increase in goal-directed activity or psychomotor agitation (7) excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions)
Mania: The mood disturbance is sufficiently severe to cause marked what?
impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features.
Mania:The symptoms are not due to what?
the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatments) or a general medical condition (e.g., hyperthyroidism).
what are drugs for the treatment of mania and bipolar disorder
2. anti-epilepsy-FDA approved as “mood stabilizers” for treatment of bipolar disorder (Valproic acid, carbamazepine, lamotrigine)
3.Antipsychotics (risperidone, olazapine, ziprasidone, aripiprazole) FDA approved for mania Rx
4.Benzodiazepines (for acute stabilization of mania)
Lithium salts are effective in treating what % of patients presenting mania and hypomania?
Lithium salts, at therapeutic concentrations, have no what?
discernible psychotropic effects in normal individuals
Lithium salts are not what 3 things?
It was an ingredient in what soda in the 1950's?
1) Not a sedative, euphoriant or depressant

2) 7-up
What does lithium salts require?
Requires chronic dosing to achieve clinical efficacy
When lithium has a slow onset of action, what does it mean? How long for efficacy? It is a Long term what?
means it is seldom solo Rx (acutely)

2-3 weeks

Mood stabilizer
what Rx is best for long-term prevention of recurring manic episodes?
What is the MOA underlying mood stabilization in lithium? What kind of pharmacology?
1.Not clearly understood 2.Broad spectrum, complex pharmacology
What does lithium alter?
Alters cation distribution in neurons.
Small concentration gradient across membranes (unlike Na+ and K+) → cannot maintain membrane potentials (not substrate for Na+ pump)
What does lithium inhibit?
Inhibits release of norepinephrine and dopamine but not serotonin from nerve terminals
What does pathways does lithium impact?
Impacts myriad intracellular signaling pathways
lithium Impacts myriad intracellular signaling pathways including what?
1.Inhibits inositolmonophosphatase → involved in recycling of PIP2→ depletion of PIP2 inhibits signaling via PLC.
2.Inhibits D2 receptor signaling via altering β-arrestin-GSK-3 interactions
3.Can modify the abundance and function of G-proteins and effector molecules including protein kinases→ impacting myriad signaling pathways and altering gene expression
4.Complex, profound effects on neuron function
Lithium is a small ___ that is ___ , and distributes_____ in body water replacing ______.
Lithium is not bound to what proteins?
Lithium is secreted from where?
1.Lithium is a small cation that is completely absorbed, and distributes uniformly in body water replacing normal cations.
2. plasma proteins
3.Secreted from the kidney intact
What are general side effects of lithium? What kind of intake should increase and what should be monitored?
1.sedation, fine tremor, dehydration (Na+ and water homeostasis effects) nausea and headache.
2.Increase water intake and monitor electrolyte balance
What will the plasma conc levels be at for a lithium overdose? What are toxic effects?
1.plasma concentrations > 1.5 mmol Li+/liter may be fatal.
2.tremor, convulsions, renal failure, ataxia
Toxicity exacerbated by dehydration; diuretic Rx should be avoided
What size is Lithiums therapeutic index? What kind of monitoring is essential?
Very low therapeutic index
Plasma drug monitoring essential
Lithium can lead to what 2 dysfunctions/?
Hypothyroidism and kidney dysfunction
Diabetes insipidus
Altered renal tubule ion transport
Monitor thyroid and renal function
What is diabetes insipidus (DI)
a condition characterized by excessive thirst and excretion of large amounts of severely diluted urine, with reduction of fluid intake having no effect on the latter