Antipsychotic Agents

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What types of symptoms do you find in schizophrenia?: Positive and negative
What are the positive symptoms in schizophrenia?: Delusions
hallucinations
disorganized speech
catatonic behavior
What are the negative symptoms in schizophrenia?: Flattened affect
alogia
avolition
don't initiate behaviors
What is schizophrenia?: A disorder in which though processes diverge from reality. May manifest d/o of perception, thinking, speech, emotion or physical activity.
What is the drugs used to treat psychotic (schizophrenia)?: Antipsychotics:
Phenothiazines
Butryphenones
Atypicals
What are the signs and symptoms of a neurotic disorder?: Anxiety, dissatisfaction, feelins of inferiority and frustration, apathy or agitation and hostility
What are the drugs used for treatment of neurotic d/o's?: Anxiolytics: Benzodiazepines, Buspirone, SSRI
What are the signs and symptoms of the depressive affective d/o?: Disturbances of mood (low self-esteem and guilt), loss of feeling, low level of motivation
What is the treatment for depression?: SSRI's, TCA
Monoamine oxidase inhibitors: atypical antidepressants
What are the signs and symptoms of the manic affective d/o?: Hyperactivity, ease of enjoyment, unrealistic optimism with acting out, aggressiveness
What is the treatment for mania?: Lithium, valproate, carbamezepine, antipsychotics
What are biological theories?: Theories which postulate neurochemcial defect as the basis of mental d/o.
What is the biogenic amine hypothesis?: Innappropriate amounts of amine neurotransmitters (NE, dopamine, serotonin) in CNS leads to inappropriate behavior.
What is the biogenic amine hypothesis based on?: Drug effects
What do antidepressants do to receptors?: It increases levels of NE, 5HT (serotonin)
What is depression caused by?: Too little NE, 5HT
What happens if dopamine is increased and unregulated?: Causes pychosis
What does antipsychotics do to the receptors?: Blocks dopamine receptors
What are the "typical" agents used to treat psychoses?: Chlorpromazine (Thorazine)
Thioridazine (Mellaril)
Fluphenazine (Permitil, Prolixin)
Thiothixen (Navane)
Haloperidol (Haldol)
What are the "atypical" agents used to treat psychoses?: Loxapine (Loxitane)
Clozapine (Clozaril)
Risperidone (Risperdal)
Olanzapine (Zyprexa)
Quetapine (Seroquel)
Ziprasidone (Geodon)
Aripiperazole (Abilify)
What does it mean if it is "atypical"?: Their mechanism of action is not typical (or binding to receptor) and it will produce different side effects from the typical drugs.
What is the advantages and disadvantages of chlorpromazine?: Adv.-Generic and inexpensive
Disadv.-many adverse effects, esecially autonomic
What is the adv/disad of Thioridazine?: Adv. slight EPS, generic
Disadv.-800 mg/d limit; no parenteral form, cardiotoxic
What is the adv./diadv. of Fluphenazine?: Adv.-Depot form also avialable
Disadv.-Increases tardive dyskinesia
What is the adv/disad of Thiothixen?: Parenteral form also available; decreased tardive dyskenesia
What is the adv/disad of Halperidol?: Adv.-Parental form also available;generic
Disadv-Severe EPS
What is the adv/disad of Loxapine?: Adv.-no weight gain
Disadv.-Uncertain
What is the adv/disad of Clozapine?: Adv.-May benefit treatment-resistant patients; little EPS toxicity
Disadv.-May cause agranulocytosis; wt gain, hyperglycemia, diabetes, dyslipidemia
What is the adv/disad of Risperidone?: Adv.-broad efficacy; little or no EPS dysfunction at low doses
Disadv.-may cause EPS or hypotension with higher doses; wt gain, hyerglycemia, diabetes, dyslipidemaia
What is the adv/disad of Olanzapine?: Adv.-effective against neg. as well as pos. symptoms; little or no EPS
Disadv.-wt gain, hyperglycemia, diabetes, dyslipidemai, cataracts (?)
What is the adv/disad of Queitapine (Seroquel)?: Adv.-little or no EPS
Disadv.-Wt gain, hyperglycemia, diabetes, dyslipidemia, cataracts?
What is the adv/disad of Ziprasidone?: Adv.-less et gain than other atyipicals
Disadv.-Prolongs QT interval, but no arrhythmias reported yet, somnolence, some EPS
What is the adv/disad of Aripiperazole?: Adv.-little or no EPS, less wt gain, or QT changes
Disadv-Akathesia, insomnia, anxiety; cautin in patient siwth epilepsy or Alz.
What are the receptor interactions of antipsychotic drugs?: All block D2 but the importance of this in relation to other receptor actions varies from drug to drug. Many receptors are involved.
What is the receptor binding profile of Chlorpromazine?: A1 = 5HT2 > D2 > D1
What is the receptor binding profile of haloperidol?: D2 > D1 = D4 > A1 > 5 HT2
What is the receptor binding profile of Clozapine?: D4 = A1 > 5HT2 > D2 = D1
What is the difference between atypicals and typicals in regards to potency and receptors?: Atypicals tend to be less potent at D2 receptors and much more potent at 5 HT2 and D4 receptors
What is Aripiprazole?: partial agonist at D2 and 5HT1a, claimed to be a new generation of antipsychotics
What happens if you block the D2 receptors in a schizophrenic patient?: Allevites positive symptoms (tension, hostility, hyperactivity, combativeness, hallucinations, delusions, insomnia, and anorexia)
What happens if you block D4 nd 5HT2 receptors in a schizophrenic patient?: Alleviate the negative symptoms (apathy, withdrawal, unresponsivesness)
What are the 2 dopamine pathways that are important in relieving psychotic symptoms?: Mesolimbic
Mesocorticol
Which 2 pathways contribute to the side effects of antipsychotics?: Nigrostriatal
Tuberoinfundibular
What are the neurological side effects of antipyschotic agents?: Acute dystonia
Akathisia
Parkinsonism
What are some of the important side offects of antipsychotics?: Neurological
Neurological Malignant Syndrome
Late onset (can't treat)
CNS Effects
What are the features of acute dystonia?: Spasm of muscles of tongue, face, neck, back; may mimic seizures; not hysteria
How do you treat acute dystonia?: Antiparkinsonian agents are diagnostic and curative
What are the features of akathisia?: Motor restlessness; not anxiety or agiatation
What is the treatment of akathisia?: Antiparkinsonian agents, diphenhydramine, benzodiapines, or propranolol
What are the features of the side effect Parkinsonism?: Bradykinesia, rigidity, variable tremor, mask facies, shuffling gait
What are the features of neurologic malignant syndrome (NMS)?: Catatonia, stupor, fever, unstable BP, myoglobinemia: can be fatal
Treatment of NMS?: Stop antipsychotic immmediately: dantrolene or bromcriptinemay help; antiparkinsonian agents NOT effective
What is late onset side effects?: Perioral tremor "rabbit syndrome" and Tardive dyskinesia
How do you treat perioral tremor?: Antiparkinsonian agents sometimes help
What are the features of tardive dyskinesia?: Oral-facial dyskinesia; widespread choreoathetosis or dystonia
Treatment of tardive dyskinesia?: Prevention is crucial; clozapinen or olanzapine may help
What areas of the CNS are affected with side effects from antipsychotics?: Basal ganglia
Hypothalamus
Medullary chemoreceptor trigger zone (CTZ)
What do you see from the basal ganglia SE?: Parkinson-like extrapyramidal effects which is caused by blocking D2
What do you see from hypothalamus?: Increased prolactin secretion; temperature regulation (usually cold)
What do you see from the CTZ?: antiemetic action; DMV-increased eating from vagus nerve stimulation; weight gain
Do you see weight gain with typicals or atypicals?: Atypicals
What effects do you see in the autonomic nervous system from antipsychotics?: Peripheral cholinergic block, alpha adrenergic block
What changes do you see in endocrine system?: Alterations in secretion of many hormones
What effects do you see in the CVS?: Direct depressant effect on the heart, direct vasodilation plus indirect effects due to ANS effects --> decreased BP
How are antipsychotics metabolized?: Liver--oxidation and glucruonide conjugation; some active metabolites formed
How are antipsychotics eliminated?: Reneal excretion
T 1/2 is 10-20 hours and biological effects last 24 hours or more
How is antipsychotics absorbed?: Absorption after oral administraion tends to be erratic and unpredictable
What are the most serious adverse reactions to antipsychotic drugs?: EPS and orthostatic hypotension
What are the early onset adverse reactions?: Parkinson syndrome
Akathisia
Acute dystonic reactions
What are the late onset adverse reactions?: Tardive dyskinesia
Perioral tremor
Why do you see orthostatic hypotension in antipsychotic agents?: Peripheral alpha blockade
What blood disorders are adverse reactions?: Leukopenia
Agranulocytosis (particualry clozapine)
What is Neuroleptic Malignant Syndrome (NMS)?: severe muscular hypertonicity, akinesia, dysarthria, fever and cardiovascular changes
What are some other adverse effects of antipsychotic agents?: Cholestatic jaundice
Rashes and photosensitivity
Seizures
Cataracts?--examine eyes every 6 months
What are some other autonomic side effects of antipsychotics?: Sedation, nasal stuffiness, dry mouth, constipation, palpitation, skin reactions, arrhythmias (ziprasidone, thioridazine), weight gain, diabetes (atypicals), a risk of stroke in patients with dementia (risperidone and olanzapine)
What are the therapeutic uses of antipsychotic drugs?: Psychoses
All agents improve positive symptoms
Atypicals will improve negative symptoms
NV
Hiccough
Other neuropsychiatric diseases (Tourette's-Haloperidol or pimozide) and agitation associated with Alzheimer's Disease

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