17) Psychosis Flashcards
Schizophrenia
- Mental illness that causespsychosis (hallucinations and delusions),and other symptoms
Schizophrenia is characterized by
- Thoughts/experiences that seem out of touch with reality
- Disorganized speech or behavior
- Decreased participation in daily activities
- Difficulty with concentration and memory may also be present
Bipolar disorder
- Generally alternatebetweenperiods of low and high moods
Drugs used to treat psychosis (antipsychotics)
- Classic drugs (D2 receptor affinity)
- Newer agents (5HT2 receptor affinity)
Antipsychotic classic drugs (D2 receptor affinity) names
- Chlorpromazine
- Fluphenazine
- Haloperidol
- Thioridazine
- Triffluoperazine
Newer antipsychotic agents (5HT2 receptor affinity) names
- Clozapine
- Olanzapine
- Quetiapine
- Risperidone
- Ziprasidone
- Others
Classic bipolar drug name
- Lithium
Newer bipolar agents
- Carbamazepine
- Clonazepam
- Olanzapine
- Valporic acid
- Others
Hyperactivation of the dopaminergic mesolimbic pathway induces
- Positive symptoms of schizophrenia
- Via increased D2 receptor stim in limbic areas
Hypoactivation of dopaminergic mesocortical pathway causes
- Negative and cognitive symptoms of schizophrenia
- Decreased D1 receptor activation in cortical areas
Ideal treatment regimen
- Decrease mesolimbic activation
- Increase cortical stimulation
Changing in other pathways’ activity (tuberoinfindibular and nigrostriatal pathways) are responsible for
- Side effect of current antipsychotics
The antipsychotic drugs are well absorbed when given orally because they are
- Lipid soluble
- Readily enter CNS and most tissues
Many antipsychotics are bound extensively to
- Plasma proteins
Antipsychotics require metabolism by _____ before elimination
- Liver enzymes
- Long plasma half-lives permit once-daily dosing
There is a correlation between blockade of D2receptors and
- Extrapyramidal dysfunction
Most of the second generation (atypical) antipsychotic agents have higher affinities for
- Other receptors than for the D2receptor
First vs. second generation antipsychotic naming
- First = typical
- Second = atypical
Most of the atypical drugs cause less _____ than the first-generation agents
- Extrapyramidal dysfunction
With the exception of haloperidol, all antipsychotic drugs block
- H1receptors to some degree
Clozapine affinity
- D4and 5-HT2blocking
- Virtually no D2affinity
Many of the atypical drugs (eg,olanzapine, quetiapine,andrisperidone) also have high affinity for
- 5-HT2Areceptors
- May also interact with D2and others
Ziprasidoneagonist/antagonist activity
- Antagonist: D2, 5-HT2A, 5-HT1D
- Agonist: 5-HT1A
Aripiprazole agonist/antagonist activity
- Partial agonist: D2, 5-HT1A
- Strong antagonist: 5-HT2A
Invega blocks _____ receptors
- Alpha-2
Extrapyramidal toxicity occurs most frequently with
- Haloperidol
- Piperazine (more potent) side-chain phenothiazines
Side effects of antipsychotics
- Reversible neurological events (extrapyramidal toxixity)
- Tardive dyskinesia (lips and buccal cavity)
- Autonomic effects
- Atropine-like effects
- Endocrine/metabolic effects
- Weight gain and hyperglycemia
Autonomic side effects of antipsychotics result from blocking
- Peripheral muscarinic receptors and α adrenoceptors
- Leads to postural hypotension
Atropine-like side effects of antipsychotics
- Dry mouth, constipation, urinary retention, visual problems
- Pronounced with thioridazine and phenothiazines with aliphatic side chains (eg, chlorpromazine)
Endocrine and metabolic side effects of antipsychotics
- Hyperprolactinemia, gynecomastia, amenorrhea-galactorrhea syndrome, and infertility
- Most are predictable manifestations of dopamine D2receptor blockade in the pituitary (dopamine is the normal inhibitory regulator of prolactin secretion)
Significant weight gain and hyperglycemia occur as antipsychotic side effects due to
- Diabetogenic action with several of the second- generation agents (especially clozapine and olanzapine)
- Aripiprazole and ziprasidone have little or no tendency to cause hyperglycemia, hyperprolactinemia, or weight gain
Malignant hyperthermic syndrome symptoms
- Muscle rigidity
- Impairment of
sweating - Hyperpyrexia
- Autonomic instability, which may be life threatening
Sedation as an antipsychotic side effect is more marked with
- Phenothiazines (especially chlorpromazine)
Miscellaneous toxicities associated with antipsychotics
- Visual impairment caused by retinal deposits (thioridazine)
- Conduction defects/fatal ventricular arrhythmias (thioridazine @ high doses)
- Prolonged QT interval (atypicals)
- Agranulocytosis (clozapine)
- Seizures also seen with clozapine @ high doses
Lithium is effective in treatment of
- Manic phase of bipolar disorder
Lithium is distributed throughout the body water and cleared by
- Kidneys
- Half-life is about 20 h
- MOA not well defined
Plasma lithium levels should be monitored (therapeutic levels vs. maintenance)
- Target therapeutic plasma concentration (for acute symptoms) = 0.8–1.2 mEq/L
- Maintenance = 0.4–0.7 mEq/L
Lithium side effects
- Tremor, sedation, ataxia, and aphasia
- Thyroid enlargement
- Reversible nephrogenic diabetes insipidus (occurs commonly at therapeutic drug levels)
- Edema
- Acneiform skin eruptions
- Leukocytosis
- Teratogenic
