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18. Antipsychotics and Mood Stabilizers (18)

Terms in this set (51)

Typical Antipsychotics (High and Low Potency)
Low Potency
-Chlorpromazine (Thorazine)
-Prochlorperazine (Compazine)
-Thioridazine (Mellaril)

High Potency
-Haloperidol
Atypical Antipsychotics
-Aripiprazole (Abilify)
-Clozapine (Clozaril)
-Olanzapine (Zyprexa)
Mood Stabilizers
-Lithium carbonate (Li+) (generic, Eskalith)
-Valproic Acid (Depakene)
-Divalproex (Depakote)
-Carbamazepine (Tegretol)
-Lamotrigine (Lamictal)
False beliefs, a person's version of reality is different than others
Delusion
A person's objective reality is different from what the person is sensing
Hallucinations
Three classes of symptoms for schizophrenia
Positive
-Delusions
-Hallucinations

Negative
-Affective flattening
-Anhedonia (inability to find pleasure)
-Avolition (inability to make choices)

Cognitive symptoms
-Disorganized speech and behavior, poor attention
Inability to find pleasure
Anhedonia
Inability to make choices
Avolition
What are the positive symptoms of schizophrenia related to?

-What pathways are involved?
-Excess amount of dopamine in the mesolimbic system

-Mesocortical and mesolimbic system
What are the negative symptoms of schizophrenia related to?

-What other neurotransmitter is involved?
-Lack of dopamine in the pre-frontal cortex and mesolimbic system

-Serotonin
What chemical does sexual function deal with?
Prolactin
General effects of antipsychotics
-Control bizarre behavior and calm agitation

-Cause psychomotor slowing
-Decreased agitation, aggression, impulsivity
-Produce emotional quieting
Which type of symptoms are harder to treat?

-What type of antipsychotics should be used to treat these symptoms?
-Negative symptoms

-Atypical antipsychotics
In basal ganglia, when you have an inadequate amount of dopamine, there is an excess of what neurotransmitter?

-What does this result in?
Acetylcholine

-Extrapyramidal symptoms
Dopamine Hypothesis of schizophrenia

-What causes schizophrenia?

-What fixes it?

-What are extrapyrimical effects mediated by?

-What are antipsychotic effects mediated by?
-There is an imbalance in the brain that leads to over stimulation of postsynaptic dopamine receptors

-Receptor over-stimulation can be attenuated by dopamine receptor antagonists (antipsychotics)

-The extrapyramidal effects of antipsychotics are mediated by the basal ganglia

-The antipsychotic effects are mediated by the mesolimbic and prefrontal cortex systems.
If dopamine antagonist fix the over stimulation of dopamine receptors, what makes the problem worse?
Dopamine agonists (PCP, cocaine)
How do antipsychotics work?
Antipsychotics block the dopamine receptor, particularly the D2 receptor
Phenothiazines
-Chlorpromazine (Thorazine)
-Fluphenazine (Prolixin)
-Prochlorperazine and promethazine

-end in -ine
Butrophenones
-Haloperidol
-Droperidol (Inapsine)

-end in -idol
Droperidol is used for?

-What did it receive a black box warning for?
Antiemetic effects, not used as an antipsychotic

-QT prolongation
How does haloperidol work?

-Does it have more of an effect on the positive or negative symptoms?

-What type of side effects does it cause?
D2 antagonism

-Positive symptoms

-Greater potential for extrapyramidal motor side-effects
Types of dystonias
-Torticollis
-Facial distortion
-Tongue protrusion
-Dysarthria
-Opisthotonus
-Scoliosis
-Oculogyric crisis
-Akathisia
Muscle contractions leading to twisting of the neck with an unnatural position of the head
Torticollis
Imperfect articulation of speech
Dysarthria
Whole body spasm
Opisthotonus
Rapid eye movements
Oculogyric crisis
Inability to sit; patient is constantly pacing, restlessness. Most common after about a week of treatment.
Akathisia
Treatment of extrapyramidal symptoms
-Reduce dose

-Do not give dopamine agonists

-Use anticholinergics (benadryl)
-This syndrome occurs in 0.5-1.0% of patients.

-Resembles a severe form of Parkinsonism
Muscle rigidity, catatonia, tremors
and instability of the autonomic system
alterations in blood pressure and pulse rate,
cardiac arrhythmias

-Altered mental status

-In severe cases impairment of sweating, and high fever can ensue with a 10% mortality rate

-Potentially fatal
Neuroleptic Malignant Syndrome
Treatment of neuroleptic malignant syndrome
-Stop antipsychotic and anticholinergics

-Antipyretics

-Dopamine agonist (e.g. bromocriptine)

-Diazepam (muscle relaxant)

-Dantrolene (helps with extreme rigidity of the limbs)
Antipsychotics can lead to an increase in _____.

-What will this cause in males and females?
-Prolactin

-Galactorrhea in females, gyncomastia in males
What are some additional side effects of antipsychotics related to weight and affect?
-Weight gain
-Akathisia (agitaiton, restlessness)
What is a major long-term (after 10+ years of treatment) side effect of chronic treatment with antipsychotics?
Tardive dyskinesia (delayed movement)

-Lateral jaw movements
-Lip smacking
-Twisting and protrusion of the tongue
-Purposeless movements of the extremities
Therapy for tardive dyskinesia
-Decrease the antipsychotic dose
What is the mechanism of tardive dyskinesia?
-Up-regulation of dopamine receptors
-How do typical antipsychotics work?

-How to atypical antipsychotics work?
-D2 antagonism

-Work on serotonin
Are atypical better for positive or negative symptoms of schizophrenia?

-Are they more or less likely to cause tar dive dyskinesia?
-Negative symptoms

-Less likely
-This is the original atypical antipsychotic

-Causes agranulocytosis in some patients (blood levels should be monitored)

-This is used almost as a last resort
Clozapine (Clozaril)
-This drug is rapidly becoming the standard atypical antipsychotic

-What is the major issue with this drug
Olanzapine (Zyprexa)

-Weight gain (30-40 lbs)
This atypical antipsychotic works well, but has greater potential for EPS, hyperprolacinemia, and weight gain
Risperidone (Risperdal)
This atypical antipsychotic works well.

-Has some alpha1 binding (hypotension)

-Limited weight gain
Quetiapine (Seroquel)
This drug is a

-Partial dopamine agonist
-Partial 5Ht1a agonist
-Partial 5HT2 antagonist
Aripiprazole (Abilify)
What is the major benefit of aripiprazole (Abilify)
Less weight gain than olanzapine
How does lithium work?
-Works by blocking a phosphate that prevents the conversion of IP2 to IP1 and IP1 to inositol

-With chronic lithium treatment there is a depletion of PIP2 (the source of IP3 and DAG)
Adverse effects of lithium
-Tremor (main side-effect)
-Hypothyroidism
-Renal dysfunction (polydipsia & polyuria)
-Cardiac conduction problems
-Gastric distress
-Mild cognitive impairment
-Edema
-Weight gain
Does lithium have a wide or narrow therapeutic window?
Extremely narrow
-Wider therapeutic window and faster onset than lithium (4-5 days)

-May act through increasing GABA levels

-GI (N&V) & hepatic problems

-Congenital neural tube defects

-Alopecia (hair loss)
Valproic Acid + Sodium Valproate = Divalproex Sodium (Depakote)
-Most probably act through blockade of voltage dependent sodium channels

-Aplastic anemia and agranulocytosis (more with _____)

-Pharmacokinetic tolerance through autoinduction of metabolism

-Hyponatremia (~3%), diplopia, ataxia, GI upset, sedation, wt gain
Carbamazepine
-Not effective in acute mania, used for maintenance therapy

-Blocks sodium and/or calcium channels.

-Can be used as a potentiating agent for antidepressants.

-Helps prevent switches to mania in bipolar patients treated with antidepressants dizziness, headache diplopia, GI upset, somnolence, skin rash
Lamotrigene
Which drug doubles concentration of lamotrigene?
Valproic acid
Which drug halves concentration of lamotrigene?
Carbamazepine
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