Ch 12 - Antipsychotics - DONE Flashcards
What are antipsychotic drugs?
Antipsychotics are drugs used primarily to treat psychotic states
Antipsychotics =
neuroleptics
Give examples of psychotic states:
- Schizophrenia
- Delusional disorders
- Other hallucinatory states
What is the mechanism of action of antipsychotic drugs?
- Antipsychotics blocks various receptors including cholinergic, adrenergic, seretonergic, muscarinic, and histamine receptors.
- However, their antipsychotic actions are primarily thought to be due to blocking of dopamine receptors in the CNS, particularly the D2 receptors in the mesocortical and the mesolimbal system of the brain
Do antipsychotic agents differ in potency?
Yes- a drug´s potency parallells its affinity for the D2 receptors.
Give examples of high-potency antipsychotic drugs:
Haloperidol and Thiothixene are high-potency drugs because they have high affinity for the D2 receptors
Give examples of low-potency antipsychotic drugs:
Chlorpromazine and Thioridazine are low-potency drugs because they have low affinity for the D2 receptors.
Do antipsychotic differ in efficacy?
No. The traditional antipsychotics are all considered to be equivalent in efficacy
How are the antipsychotic usually administered?
- orally (most cases)
- IM (if the patient is noncompliant)
Describe the absorption and metabolism of the traditional antipsychotics:
They are variably absorbed orally but they pass into the brain easily and have a large volume of distribution. Metabolism occurs by the cytochrome P-450 system in the liver
What is the onset of action of antipsychotics?
- Antipsychotics may not become effective for several weeks to months.
- However sedation and other side effects can occur rapidly
Can the antipsychotic drugs cure illnesses such as schizophrenia?
No! Antipsychotics only reduce the symptoms of the illness; they cannot cure the illness.
How are the antipsychotics classified?
- Classification is base on the structural differences.
The major classes of antipsychotics include:
- Phenothiazines
- Butyrophenones
- Dibenzoxazepines
- Thioxanthine
- Benzioxazole
Give examples of phenothiazines:
- Chlorpromazine
- Fluphenazine
- Trifluoperazine
- Perphenazine
What distinctive side effects does thioridazine cause?
- pigmentary retinopathy
- may cause cardiac arrhythmias and conduction block
Name two Butyrophenones:
- haloperidol
- droperidol
Other than psychotic states, for what can haloperidol be used for?
- Tourette´s syndrome
- Huntington´s disease
- Phencyclidine overdose-DOC
What type of side effects is especially pronounced with haloperidol?
Extrapyramidal side effects
Name a dibenzoxazepine:
loxapine
Name a thioxanthenes:
thiothixene
What are the clinical application of traditional antipsychotic agents?
- treatment of any agitated or psychotic state
- antiemetic therapy
- treatment of Tourette´s syndrome
- treatment of intractable hiccups
- antipruritic therapy
Treatment of any agitated or psychotic state:
Treatment of any agitated or psychotic state, such as bipolar disease or schizophrenia
(These drugs are especially effective for the positive symptoms of schizophrenia, such as delusions, thought disorders, and hallucinations)
Antiemetic therapy:
Phenothiazines with the exception of thioridazine
Treatment of Tourette´s syndrome:
Haloperidol
Treatment of intractable hiccups:
Chlorpomazine
Antipruritic therapy:
Promethazine (because of histamine blockade)
What is an easy way of remembering the side effects of traditional antipsychotics?
With a few exceptions, all of the traditional antipsychotics have similar toxicities:
- sedation
- extrapyramidal effects
- anticholinergic effects
- α-adrenergic effect (hypotension)
Do all traditional antipsychotics produce the same degree of each type side effect?
No. The severity of each adverse effect varies among the classes of antipsychotics drugs
Give examples of high-potency drugs:
- haloperidol
- fluphenazine
How are the side effect for high-potency drugs such as haloperidol and fluphenazine?
high-potency drugs produce the greatest extrapyramidal effects
Give examples of low-potency drugs:
- thioridazine
- chlorpromazine
How are the side effect for low-potency drugs such as thioridazine and chlorpromazine?
low-potency drugs produce the greatest anticholinergic effects
Describe the toxicities of traditional antipsychotic agents:
- CNS sedation
- Endocrine alteration
- Anticholinergic effects
- Antiadrenergic effect
- Extrapyramidal side effects
In which antipsychotic drug is CNS sedation seen markedly?
Phenothiazine
Endocrine alteration:
antipsychotic drug
- galactorrhea
- amenorrhea
- infertility, likely of blockade of dopamine release from the pituitary
Anticholinergic effects:
antipsychotic drug
- dry mouth
- constipation
- urinary retention
- blurry vision
Antiadrenergic effect:
antipsychotic drug
- watch for light-headedness and orthostatic hypotension secondary to α- adrenergic blockade.
- Phenothiazines can cause sexual dysfunction (failure to ejaculate)
Extrapyramidal side effects:
antipsychotic drug
- akathisia (motor restlessness)
- parkinsonian syndrome (bradykinic rigidity tremor)
- acute dystonic reactions
- neuroleptic malignant syndrome
. tardive dyskinesia
What antipsychotic drug can cause sexual dysfunction (failure to ejaculate)?
Phenothiazines
What is tardive dyskinesia?
Tardive dyskinesia is a symptome that may occur after prolonged therapy with neuroleptic (4 months to 1 year).
What characterizes tardive dyskinesia?
- Tardive dyskinesia is characterized by rhythmic involuntary movements of the tongue, lips, or jaw.
- Patient may also demonstrate puckering of the mouth or even chewing movements
Is tardive dyskinesia reversible?
There is no treatment ofr established cases of tardive dyskinesia.
- The syndrome may remit partially or completely of neuroleptic treatment is withdrawn, although in many cases it is irreversible.
- Anticholinergic agents actually increase the severity of tardive dyskinesia
What is an acute dystonic reaction?
Prolonged muscle spasm of tongue, neck, or face
How are the acute dystonic reactions treated?
Patients are given diphenhydramine (Benadryl) or an injection of benztropine
What is neuroleptic malignant syndrome?
Patients who receive neuroleptics for long-term treatment may experience:
- rigidity
- altered mental status
- cardiac arrhythmia
- hypertension
- life-threatening hyperpyrexia
What is the therapy of neuroleptic malignant syndrome?
This disorder is treated with Dantrolene, a skeletal muscle relaxant
What is Dantrolene?
a skeletal muscle relaxant
Name six examples of atypical antipsychotic drugs:
- Clozapine
- Risperidone
- Olanzapine
- Aripiprazole
- Quetiapine
- Ziprasidone
Why are these drugs considered “atypical”?
- They are newer and in addition to blocking dopamine receptors, atypical antipsychotics also produce significant therapeutic effects through the blockade of serotonin (5-HT2) receptors.
- They are also rarely associated with extrapyramidal side effects.
Are the atypical antipsychotic drugs more effective than the traditional antipsychotics?
Most physicians consider the atypical antipsychotics a better choice of therapy because of their decreased side effects
Describe the actions of clozapine:
- This agent is a Dibenzodiazepine derivative
- it differs from traditional antipsychotics in its potent blockade of serotonin (5-HT2) receptors, along with the usual dopamine blockade
What is clozapine used for?
- clozapine has been effective in treating cases of schizophrenia that are refractory to other neuroleptic drugs.
- it is especially effective in treating negative symptoms of schizophrenia (blunted emotion, withdrawal, reduced ability to form releationship)
What are the side effects of clozapine?
- causes fewer extrapyramidal side effects than traditional neuroleptics
- clozapine does cause seizures and a very dangerous agranulocytosis in 1% ti 2% of patients
- weekly blood tests are required for patients receiving clozapine therapy
- although weight gain can occur with extended treatment of most antipsychotics, it is especially prominent with clozapine
- this can lead to hypertension and other diseases
Describe the actions of risperidone:
- risperidone (risperdal) in a bezoxazole drug that, like clonazepine, has a very high affinity for 5-HT2 receptors
- it also has antidopaminergic (D2) activity
- however, risperidone exhibits no anticholinergic effects and diminished extrapyramidal effects
- risperidone is a first-line agent for the treatment of schizophrenia, since it is effective for both positive and negative symptoms of the disease
- the drug is also known to prolong QT intervals and therefore should be used with caution in patients who have abnormal QT interval
Describe the actions of olanzapine:
- like risperidone and clozapine, olanzapine blocks both dopamine and serotonin receptors
- effective in treatment of both positive and negative symptoms of schizophrenia, depression, or obsessive-compulsive disorder (OCD)
Describe the action of aripiprazole, quetiapine, and ziprasidone:
- These three drugs are the newer atypical antipsychotics.
- They cause very little extrapyramidal side effects.
- Aripiprazole is unique in that it is the only drug that is a partial agonist at D2 receptors.
