Pharmacotherapy Of Psychosis And Mania

Front 1

what disorders are among the most severe psychiatric disorders?

Back 1

Psychosis

Front 2

Psychosis disorders all exhibit major disturbances in what?

Back 2

1.Reasoning , often with delusions and hallucinations
2.Behavior (disorganized or irrational )
3.Mood (excited agitation to severe emotional withdrawal).

Front 3

Psychosis is a common disorder that affects what % of the population? What stages of life does it often present?

Back 3

affecting 1% of the population at some age.
Often presents in late adolescence/early adulthood

Front 4

What are 5 psychotic disorders?

Back 4

1.Schizophrenia
2.Manic phase of bipolar illness (manic-depressive)
3.Acute idiopathic psychotic illnesses
4.Delusional disorder
5.Paranoia

Front 5

What is Schizophrenia?

Back 5

Chronic disordered thoughts, disorganized irrational behavior, “voices”

Front 6

Schizophrenia is thought to be a group of what? Are there any tests for it?

Back 6

Schizophrenia is thought to be a group of related brain disorders
There are currently no biological tests for schizophrenia

Front 7

what are 3 clear biological links to the onset of schizophrenia exist?

Back 7

Disrupted neurobiochemistry
Altered neuroanatomy
Genetics

Front 8

What is altered in patients with schizophrenia?

Back 8

Brain anatomy

Front 9

Overall alterations in brain anatomy from schizophrenia include what 2 components?

Back 9

Significant loss of gray matter
Enlarged ventricles

Front 10

What does gray matter =? This means that higher functioning will what?

Back 10

Gray matter = cortex cell loss! This means that higher functioning will decrease

Front 11

what are 5 Specific Brain Anomolies in Schizophrenia? What happens to the limbic system, Wernicke's area, Occipital lobe, frontal lobal and basal ganglia?

Back 11

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)

Front 12

What are the basal ganglia involved in?

Back 12

The basal ganglia are involved in the integration of sensory info; emotions; the regulation of movement

Front 13

Schizophrenia have what % shorter life expectancy?

Back 13

20%

Front 14

Antipsychotic drugs are what kind of family?

Back 14

diverse chemical family w/different potencies and side effect profiles

Front 15

Psychoses involves what?

Back 15

multiple neurotransmitter anomalies (e.g. dopamine, glutamate)

Front 16

What is a a common mechanism of antipsychotic drugs?

Back 16

Blunting of dopamine action

Front 17

First generation antipsychotics “neuroleptics” have what kind of side effects?

Back 17

Parkinson-like side effects

Front 18

Atypical Antipsychotics (2nd Generation) have fewer what? What is there a significant risk of?

Back 18

Fewer extra-pyramidal side effects (Parkinson-like symptoms)

Significant metabolic syndrome risk

Front 19

3rd Generation Antipsychotics have fewer what?

Back 19

Fewer metabolic side effects (perhaps)

Front 20

What was the antipsycotic rugs in global sales in 2008?

Back 20

$22 billion

Front 21

What is Neuroleptic syndrome? What components are kept intact?

Back 21

Suppression of spontaneous movements and complex behaviors

Spinal reflexes and unconditioned nociceptive-avoidance behaviors intact

Front 22

Neuroleptics decrease what 3 characteristics?

Back 22

initiative
interest in environment
emotion

Front 23

Neuroleptics are considered to be what?
Can patients on these drugs answer questions and retain intact cognition?

Back 23

“tranquilizers” : initial drowsiness and slowness to respond to stimuli

yes

Front 24

What are side effects of neuroleptics?

Back 24

Parkinson’s like symptoms: tremor, restlessness, rigidity, bradykinesia

Front 25

Neuroleptic Rx reduce what? Is it a cure?

Back 25

Gradual (days) reduction in psychotic symptoms
BUT not a cure

Front 26

What is Nociperception?

Back 26

the neural processes of encoding and processing noxious stimuli.

Front 27

What is Bradykinesia?

Back 27

slowed movement with inability to appropriately adjust body position

Front 28

1st Generation Antipsychotics “Neuroleptics” are very ___drugs? They have effects on what receptors?

Back 28

Very “dirty” drugs → effects on many receptors

H1, alpha2 adrenergic, serotonin, muscarinic-cholinergic

Front 29

1st Generation Antipsychotics “Neuroleptics” have Antipsychotic efficacy via what?

Back 29

mesolimbic and mesofrontal D2 receptors (antagonists)

Front 30

What is Haloperidol? What is it more potent than?

Back 30

Haloperidol is potent dopamine receptor competitive antagonist (D1, D2, D3, D4). More potent than chlorpromazine.

Front 31

For 1st generation neuroleptics, Extrapyramidal/neuroleptic side effects (Parkinsonian movement disorders) via what? What can it cause?

Back 31

via binding/antagonism of D2 receptors in basal ganglia

Can cause irreversible tardive dyskinesia (uncontrolled hyperkinetic movements; e.g. fluphenazine)

Front 32

What are side effects of 1st Generation Antipsychotics “Neuroleptics”?

Back 32

Side effects: Tachycardia, dizziness and impotence via alpha2 adrenergic receptor, and drowsiness

Front 33

What are 2, 1st Generation Antipsychotics “Neuroleptics”?

Back 33

Chlorpromazine and Haloperidol

Front 34

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?

Back 34

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

Front 35

What are the Currently the most frequently used antipsychotic Rx?

Back 35

“Atypical” Antipsychotics- 2nd Generation

Front 36

“Atypical” Antipsychotics- 2nd Generation are generally more ___ compared to 1st gen?

Back 36

selective

Front 37

“Atypical” Antipsychotics- 2nd Generation have what kind of binding affinties?Some appear to have > affinity for ___ than ___?

Back 37

Variable receptor binding affinities
Some appear to have > affinity for D4 vs. D2 (e.g. clozapine)

Front 38

“Atypical” Antipsychotics- 2nd Generation have what kind of potent receptors?

Back 38

Potent 5-HT2 receptor antagonists

Front 39

“Atypical” Antipsychotics- 2nd Generation compared to neuroleptics are less potentat what site?

Back 39

Less potent at D1 receptors

Front 40

“Atypical” Antipsychotics- 2nd Generation have what kind of severe metabolic side effects ?

Back 40

including rapid weight gain, hypertension, hyperglycemia, hyperlipidemia, insulin resistance → “metabolic syndrome”

Front 41

September 18, 2003: The FDA stated that all atypical antipsychotic drugs, across all chemical classes, should have what?

Back 41

warning labels stating increased risk of diabetes and related disorders.

Front 42

What are 3 "Atypical” Antipsychotics- 2nd Generation drugs?

Back 42

Olanzapine (Zyprexa)
Ziprasidone (GEODON)
Quetiapine (seroquel)

Front 43

Olanzapine, Ziprasidone and quetiapine FDA approved for schizophrenia and bipolar disorder in what age group?

Back 43

children

Front 44

Second generation antipsychotics are increasingly prescribed to children and adolescents in the US as what?

Back 44

first line treatment for psychotic disorders, bipolar disorder and non-psychotic metal disorders

Front 45

What percent of atypical use in kids off-label for non-psychotic conditions like ADHD?

Back 45

70%

Front 46

Second-GenerationAntipsychotic Medications During First-TimeUse in Children and Adolescents gain how much weight in 11 weeks?

Back 46

19.7-18.7 lb weight gain following 11 weeks of drug treatment

Front 47

1 in 10 MaineCare members under 19 years of age is on how many mental health drugs in the course of 1 year?

Back 47

4 or more

Front 48

How many foster children are on anti-psychotics? How is this compared to usage in non-foster children?

Back 48

1 in 5 foster children are on anti-psychotics, 4x the rate of usage in non-foster children

Front 49

In addition to schizophrenia, the FDA approved 3rd generation antipsychotics: Aripiprazole for what? In what age group?

Back 49

FDA approved for manic and mixed episodes in adults and children (age 10-17), clinical depression and treat irritability in children with autistic disorder.

Front 50

3rd generation antipsychotics: Aripiprazole, are involved with what receptor? What could these receptors be responsible for?

Back 50

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.

Front 51

3rd generation antipsychotics: Aripiprazole have moderate affinity for what?

What activity don't they have?

Back 51

Moderate affinity for H1 and α-adrenergic receptors and SERT. No muscarinic activity.

Front 52

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?

Back 52

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.

Front 53

Antipsychotic Medications: Summary
Considered to be powerful what, with that effects? Serious side effect profiles include?When can withdrawal symptoms be severe?

Back 53

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

Front 54

First generation antipsychotics are efficacious in tx of what? What formulations are they avaliable in? What kind of side effect profile?

Back 54

1.Efficacious in treatment of psychotic symptoms
2.Available in slow-release depot formulations
3.Significant “parkinsonian” side effect profile

Front 55

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?

Back 55

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

Front 56

3rd Generation Antipsychotics have different what? What kind of cost? Do they have less risk for severe metabolic side effects?

Back 56

1.Pharmacology
2. cost
3. Not enough data

Front 57

What is mania? what disorder is it often associated with?

Back 57

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.

Front 58

Mania: During the period of mood disturbance, what are three (or more) of the following characteristics that have persisted?

Back 58

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)

Front 59

Mania: The mood disturbance is sufficiently severe to cause marked what?

Back 59

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.

Front 60

Mania:The symptoms are not due to what?

Back 60

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).

Front 61

what are drugs for the treatment of mania and bipolar disorder

Back 61

1.Lithium
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)

Front 62

Lithium salts are effective in treating what % of patients presenting mania and hypomania?

Back 62

60-80%

Front 63

Lithium salts, at therapeutic concentrations, have no what?

Back 63

discernible psychotropic effects in normal individuals

Front 64

Lithium salts are not what 3 things?
It was an ingredient in what soda in the 1950's?

Back 64

1) Not a sedative, euphoriant or depressant

2) 7-up

Front 65

What does lithium salts require?

Back 65

Requires chronic dosing to achieve clinical efficacy

Front 66

When lithium has a slow onset of action, what does it mean? How long for efficacy? It is a Long term what?

Back 66

means it is seldom solo Rx (acutely)

2-3 weeks

Mood stabilizer

Front 67

what Rx is best for long-term prevention of recurring manic episodes?

Back 67

Li+

Front 68

What is the MOA underlying mood stabilization in lithium? What kind of pharmacology?

Back 68

1.Not clearly understood 2.Broad spectrum, complex pharmacology

Front 69

What does lithium alter?

Back 69

Alters cation distribution in neurons.
Small concentration gradient across membranes (unlike Na+ and K+) → cannot maintain membrane potentials (not substrate for Na+ pump)

Front 70

What does lithium inhibit?

Back 70

Inhibits release of norepinephrine and dopamine but not serotonin from nerve terminals

Front 71

What does pathways does lithium impact?

Back 71

Impacts myriad intracellular signaling pathways

Front 72

lithium Impacts myriad intracellular signaling pathways including what?

Back 72

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

Front 73

Lithium is a small ___ that is ___ , and distributes_____ in body water replacing ______.
Lithium is not bound to what proteins?
Lithium is secreted from where?

Back 73

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

Front 74

What are general side effects of lithium? What kind of intake should increase and what should be monitored?

Back 74

1.sedation, fine tremor, dehydration (Na+ and water homeostasis effects) nausea and headache.
2.Increase water intake and monitor electrolyte balance

Front 75

What will the plasma conc levels be at for a lithium overdose? What are toxic effects?

Back 75

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

Front 76

What size is Lithiums therapeutic index? What kind of monitoring is essential?

Back 76

Very low therapeutic index
Plasma drug monitoring essential

Front 77

Lithium can lead to what 2 dysfunctions/?

Back 77

Hypothyroidism and kidney dysfunction
Diabetes insipidus
Altered renal tubule ion transport
Monitor thyroid and renal function

Front 78

What is diabetes insipidus (DI)

Back 78

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