Therapy of Schizophrenia Flashcards
Antipsychotics are similar regarding:
The beneficial effect
_____ are important for appropriate selection of an antipsychotic drug for an individual patient.
Adverse effect profiles
Pharmacotherapy guidelines emphasize antipsychotics:
Monotherapies with adequate benefit/risk ratios
When should antipsychotic combination regimens be used?
In the most treatment-resistant patients
Long-term maintenance antipsychotic treatment is needed for the vast majority of patients in order to:
Prevent relapse
______ should be used in combination with antipsychotic treatment to be effective.
Psychosocial rehabilitation programs
Most deterioration in psychosocial functioning occurs during:
The first 5 years after the initial psychotic episode
Patients with schizophrenia who continue to abuse alcohol or drugs usually have a __(good/poor) response to medications and a __(good/poor) prognosis.
Poor; Poor
Which drugs can induce psychosis?
1) Cannabis, Marijuana
2) Cocaine
3) Amphetamines: ecstasy (MDMA), methamphetamine, methylphenidate
4) LSD
5) Phencyclidine and ketamine
6) Alcohol
What are some medical causes of psychosis?
1) HIV (AIDS)
2) Malaria
3) Syphilis
4) Alzheimer’s disease
5) Parkinson’s disease
6) Hypoglycemia
7) SLE
8) Multiple sclerosis
What are the desired outcomes of schizophrenia therapy?
1) Avoiding unwanted adverse effects of therapy
2) Integrating the patient back into the community
3) Increasing adaptive functioning
4) Preventing relapse
Which drugs are First-Generation Antipsychotics (FGAs)?
1) Chlorpromazine
2) Haloperidol
3) Thiothixene
4) Loxapine
Which drugs are Second-Generation Antipsychotics (SGAs)?
1) Aripiprazole
2) Clozapine
3) Olanzapine
4) Quetiapine
5) Risperidone
6) Ziprasidone
First-Generation Antipsychotics (FGAs) mechanism of action?
1) Block dopaminergic neurotransmission
2) Block noradrenergic, cholinergic, and histaminergic action
Second-Generation Antipsychotics (SGAs) mechanism of action?
1) Block D2 dopamine receptors
2) Block 5-HT2A serotonin receptors
The major advantage of SGAs is:
Lower risk of neurologic adverse effects, particularly motor effects.
In first-episode psychotic patients, typical dosing ranges are about __% of the doses used in chronically ill individuals.
50%
The goals during the first 7 days of schizophrenia treatment should be:
1) Reduction of symptoms
2) Normalization of sleep and eating patterns
Some SGAs have increased risk of:
Metabolic adverse effects:
1) Weight gain
2) Hyperlipidemias
3) Diabetes mellitus
Why do we use lower doses in first-episode psychotic patients?
Because of increased susceptibility to extrapyramidal symptoms.
Which antipsychotic drugs have increased susceptibility to extrapyramidal symptoms?
1) Aripiprazole
2) Risperidone
3) Ziprasidone
In previously treated patients, use any antipsychotic EXCEPT:
1) Clozapine
2) Antipsychotics that were not effective or poorly tolerated by the patient
When can we try Clozapine?
1) Patients who were not responsive with 2 antipsychotic trials
2) Patients who were severely suicidal
If the patient begins to show adequate response at a particular dose, then the patient should ___(up/lower/continue) the dose.
Continue
Improvement is usually a slow but steady process over __-__ weeks or longer.
6-12
Increased socialization and improvement in self-care habits and mood take - weeks to occur.
2-3
Improvement in formal thought disorder can take an additional - weeks to occur.
6-8
What changes in patients taking antipsychotics take 2-3 weeks to occur?
1) Increased socialization
2) Improvement in self-care habits and mood
Chronically ill patients may need - months to improve.
3-6
What changes in patients taking antipsychotics take 6-8 weeks to occur?
Improvement in formal thought disorder
Before changing medications in a poorly responding schizophrenic patient, the
following should be considered:
1) Confirm the diagnosis of schizophrenia, or exclude a different diagnosis, a long-standing behavioral problem, a substance abuse disorder, or a general medical condition.
2) Check whether the patient has treatment-resistant schizophrenia.
Medications for schizophrenia
are __(palliative/curative).
Palliative
Maintenance drug therapy for schizophrenia prevents ___.
Relapse
After treatment of the first psychotic episode, medication should be continued for ____ after remission.
1-5 years
When starting a patient on multiple schizophrenia drugs, what should you do?
Antipsychotics should be tapered slowly over at least 1-2 weeks while the second antipsychotic is initiated and the dose titrated up.
Antipsychotic tapering needs to occur more slowly with ___.
Clozapine
Abrupt discontinuation, especially for clozapine, can result in ___.
Withdrawal symptoms
Abrupt discontinuation, especially for clozapine, can result in withdrawal symptoms such as:
1) Insomnia
2) Nightmares
3) Headaches
4) GI symptoms (abdominal cramps, stomach pain, nausea, vomiting, and diarrhea)
5) Restlessness
6) Increased salivation
7) Sweating
Long-Acting Injectable (LAI) Antipsychotics are used for:
Patients who are unreliable in taking oral medication on a daily basis
If medication nonadherence is due to adverse effects, what should you do?
Try an alternative medication with a more favorable adverse effect profile BEFORE a long-acting injectable antipsychotic is given
What is Paliperidone palmitate?
A long-acting injectable antipsychotic (once-monthly IM injection).
___ is available as once monthly injection that requires 2-3 weeks of oral antipsychotic overlap.
Aripiprazole
___ can be used as LAI administered every 2 - 4 weeks, but it may be associated with a post-injection delirium/sedation syndrome in 2% of patients.
Olanzapine
Olanzapine can be used as LAI administered every 2 - 4 weeks, but it may be associated with:
A post-injection delirium/sedation syndrome in 2% of patients.
What should you do after giving a patient Olanzapine injection?
1) Observe the patient for at least 3 hours after administration
2) Inform them they must not drive or operate machinery for that day
“Treatment Resistant” describes a patient who:
Has had inadequate response from multiple antipsychotic trials
What should you do in patients failing ≥ 2 pharmacotherapy trials?
1) Re-examine diagnosis
2) Exclude substance abuse
3) Medication non-adherence
4) Psychosocial stressors
Which drug may be effective in the management of treatment-resistant schizophrenia?
Clozapine
Clozapine has been effective in patients with:
1) Severe suicidality
2) Aggressive behavior
3) Those who cannot tolerate neurologic adverse effects of even low doses of other antipsychotics
Clozapine is monitored by:
1) Absolute Neutrophil Count (ANC)
2) Serum drug level
3) Norclozapine concentration
Because of the risk of _____, Clozapine is usually titrated more slowly than other antipsychotics, particularly on an outpatient basis.
Orthostatic hypotension
Clozapine dose should not exceed ___ daily.
900 mg
The Norclozapine level under normal circumstances is expected to be around ___ of the clozapine level.
Two-thirds
Antipsychotics are highly lipo(phobic/philic).
Lipophillic
Antipsychotics are highly bound to membranes and plasma proteins, and have __(low/large) volumes of distribution.
Large
Most antipsychotics are largely metabolized by ___.
CYPs
For antipsychotics metabolized by ___, metabolism is polymorphic as patients may be poor, intermediate, rapid, or ultrarapid metabolizers.
CYP2D6
Most antipsychotics have long elimination half-lives ≥ 24 hours, with the exception of __ and ___, which have shorter half-lives (2-10 hours).
Quetiapine and Ziprasidone
Antipsychotics cause weight (gain/loss).
Gain
Why do antipsychotics cause weight gain?
They’re associated with:
1) Antihistaminic effects
2) Antimuscarinic effects
3) Blockade of 5-HT2C receptors
Anti-Psychotics cause Hyperprolactinemia due to:
Dopamine blockade in the
tuberoinfundibular system.
Endocrine effects of antipsychotics are:
1) Gynecomastia
2) Galactorrhea
3) Menstrual irregularities
4) Decreased libido
5) Sexual dysfunction
Cardiovascular system effects of antipsychotics are:
1) Orthostatic Hypotension (α-adrenergic blockade).
2) Sudden cardiac death
3) Elevation of serum triglycerides and cholesterol
4) Sinus tachycardia from anticholinergic effects
5) Reflex tachycardia from α-adrenergic blockade
6) Prolongation of QTc, which may be associated with polymorphic ventricular arrhythmias, including torsade de pointes syndrome.
Which antipsychotic most commonly causes QT prolongation?
Thioridazine
Anticholinergic effects of antipsychotics are:
1) Dry mouth
2) Constipation
3) Tachycardia
4) Blurred vision
5) Impairment of erection
6) Urinary retention
7) Impaired memory
8) Paralytic ileus
9) Necrotizing enterocolitis
What are Extrapyramidal Symptoms?
Movement disorders due to excess dopamine blockade in the nigrostriatal pathway
CNS effects of antipsychotics are:
1) Extrapyramidal Symptoms
2) Sedation
3) Seizures
4) Neuroleptic Malignant Syndrome (NMS)
Which extrapyramidal symptoms are associated with antipsychotics?
1) Dystonia
2) Akathisia
3) Pseudoparkinsonism
4) Tardive Dyskinesia (TD)
What is dystonia?
Prolonged tonic contractions
When does dystonia occur with antipsychotics?
Usually within 1-4 days of initiating or increasing the dose of an antipsychotic
Which type of dystonias are life-threatening?
Pharyngeal–laryngeal dystonias
Are dystonias a reason for medication non-adherence?
YES
What are the types of dystonias?
1) Trismus
2) Glossospasm
3) Tongue protrusion
4) Pharyngeal– laryngeal dystonia
5) Blepharospasm
6) Oculogyric crisis
7) Torticollis
8) Retrocollis
What is oculogyric crisis?
Spasmodic movements of the eyeballs into a fixed position, usually upwards
The risk of dystonia is greatly reduced with:
Second Generation Antipsychotics (SGAs)
Dystonia may be treated with:
1) IM or IV anticholinergics
2) Benzodiazepines
What is Akathisia?
The inability to sit still associated with functional motor restlessness (pacing, shifting, shuffling, or tapping feet)
Akathisia is common with some ___, frequently accompanied
by dysphoria.
First Generation Antipsychotics (FGAs)
Which antipsychotics appear to have the lowest risk of producing akathisia?
1) Quetiapine
2) Clozapine
How is akathisia treated?
1) Benzodiazopines
2) Beta-Blockers
3) 5-HT2 receptor antagonist
Which drugs can be used as protection against akathisia?
5-HT2 receptor antagonists:
1) Cyproheptadine
2) Mirtazapine
3) Trazodone
Which Beta-Blockers can be used as treatment for akathisia?
1) Propranolol
2) Nadolol
3) Metoprolol
When does Pseudoparkinsonism begin when taking antipsychotics?
Typically 1 - 2 weeks after initiation or a dose increase
Pseudoparkinsonism can be treated with:
1) Anticholinergic drugs, but may produce euphoria.
2) Rotigotine
Pseudoparkinsonism can be treated with which anticholinergic drugs?
1) Trihexyphenidyl
2) Benztropine
3) Orphenadrine
Pseudoparkinsonism can be treated with which specific drug that has less effect on memory?
Amantadine
What is the main cause of pseudoparkinsonism?
Due to D2 blockade in the nigrostriatum
What is Rotigotine?
A dopamine agonist
The risk of pseudoparkinsonism with SGAs is low, but may occur with ___ at relatively large doses.
Risperidone
Which antipsychotics are reasonable alternatives in a patient experiencing extrapyramidal symptoms with other Second Gen. Antipsychotics?
1) Quetiapine
2) Aripiprazole
3) Clozapine
What is Tardive Dyskinesia (TD)?
A syndrome characterized by abnormal involuntary movements buccal–lingual masticatory, or orofacial.
Is the onset of tardive dyskinesia gradual or sudden?
Gradual
The first detectable signs of tardive dyskinesia are:
Mild forward, backward, or lateral movements of the tongue
Which extrapyramidal symptom is associated with higher overall morbidity and mortality?
Tardive dyskinesia
Tardive dyskinesia is more prevalent with ___(FGAs/SGAs).
FGAs
Short-term treatment of TD with which drugs may be effective?
1) Clonazepam
2) Ginkgo biloba
3) Clozapine
What are the most sedating antipsychotics?
1) Chlorpromazine
2) Thioridazine
3) Clozapine
4) Olanzapine
5) Quetiapine
Antipsychotics __(increase/decrease) the seizure threshold.
Decrease
Sedation occurs __(early/late) in antipsychotic treatment and can __(increase/decrease) over time
Early; Decrease
Which antipsychotics have the
highest seizure risk?
1) Clozapine
2) Chlorpromazine
Which antipsychotics have the
lowest seizure risk?
1) Risperidone
2) Thioridazine
3) Haloperidol
4) Pimozide
5) Trifluoperazine
6) Fluphenazine
Neuroleptic Malignant Syndrome (NMS) develops __(slowly/rapidly).
Rapidly
True or False: Neuroleptic Malignant Syndrome (NMS) does not occur after stopping antipsychotics.
False; it can occur
Possible mechanisms of Neuroleptic Malignant Syndrome (NMS) include:
1) Disruption of the central thermoregulatory process
2) Excess production of heat secondary to skeletal muscle contractions
What are the signs and symptoms of Neuroleptic Malignant Syndrome (NMS)?
1) Temperature > 38°C
2) Loss of consciousness
3) Muscle rigidity
4) Autonomic dysfunction
a) Tachycardia
b) Labile blood pressure
c) Diaphoresis
d) Tachypnea
e) Urinary or fecal incontinence
Which labs are associated with Neuroleptic Malignant Syndrome (NMS)?
Increased:
1) WBCs (Leukocytosis)
2) Creatine kinase (CK)
3) AST
4) ALT
5) LDH
6) Myoglobinuria
How do you treat Neuroleptic Malignant Syndrome (NMS)?
First: Antipsychotic discontinuation and supportive care.
Second: Medications
Which medications are used to treat Neuroleptic Malignant Syndrome (NMS)?
1) Bromocriptine
2) Amantadine
3) Dantrolene
What is Dantrolene?
Skeletal muscle relaxant
Ophthalmologic effects of antipsychotics are:
1) Exacerbation of narrow-angle (angle-closure) glaucoma
2) Opaque deposits in the cornea and lens
3) Cataract
4) Retinitis pigmentosa, due to
melanin deposits and can result in permanent visual impairment or blindness.
Which antipsychotic causes opaque deposits in the cornea and lens?
Chlorpromazine
Which antipsychotics cause cataracts?
1) Risperidone
2) Quetiapine
Which antipsychotic causes retinitis pigmentosa?
Thioridazine doses > 800 mg daily
Genitourinary System effects of antipsychotics are:
1) Urinary hesitancy and retention
2) Urinary incontinence
3) Sexual dysfunction
4) Priapism
Which antipsychotic causes Urinary incontinence and why?
Clozapine; Due to α-blockade
Which antipsychotics cause Urinary hesitancy and retention?
1) FGAs
2) Clozapine
Why might antipsychotics cause Priapism?
Due to α1-adrenergic receptor blockade, leading to intracavernosal blood stasis
Which antipsychotics typically cause agranulocytosis?
1) Clozapine (0.8%)
2) Chlorpromazine
3) Olanzapine
The onset of agranulocytosis is usually within ____ of antipsychotic therapy.
The first 8 weeks
If the absolute neutrophil count (ANC) is < ___, the antipsychotic should be discontinued and the ANC monitored closely until it returns to normal and also monitored closely for the development of infections.
500/μL
The baseline ANC must be at least __/μL in order to start
clozapine.
1,500
Weekly ANC monitoring for the first ___ of Clozapine therapy is
required.
6 months
Effects of antipsychotics on the skin are:
1) Contact dermatitis
2) Skin reaction with Eosinophilia
3) Photosensitivity
4) Blue-gray or purplish skin coloration in areas exposed to sunlight (chlorpromazine), concurrent with corneal or lens pigmentation.
Which antipsychotic can cause Skin reaction with Eosinophilia?
Ziprasidone
All antipsychotics are known to cause photosensitivity, ESPECIALLY:
Chloropromazine
Why should exposure to sunlight be limited (blocking sunscreen, hats, protective clothing, and sunglasses) when taking antipsychotics, such as Chlorpromazine?
It can cause blue-gray or purplish skin coloration in areas exposed to sunlight, concurrent with corneal or lens pigmentation.
What is another miscellaneous effect of Clozapine?
Sialorrhea (drooling) in 54% of patients
Sialorrhea (drooling) when taking Clozapine may happen due to:
Antagonistic effect on both α1- and α2-adrenergic receptors at the salivary glands = vasodilation and increased blood flow
Which drugs may be used to treat clozapine-related
sialorrhea?
1) Anticholinergics (Benztropine and Atropine)
2) α2-agonists (Clonidine)
___ is the best studied of all antipsychotics, and no relationship between its use and teratogenicity has been found.
Haloperidol
Birth defects occur more often with __(FGAs/SGAs).
FGAs
What are the postnatal and gestational complications of antipsychotics?
1) Weight gain
2) Increased risk of gestational diabetes
3) Risk of neonatal EPS (FGAs), with effects lasting for 3 - 12 months after birth
4) Increased risk of hypertension and VTEs
Which antipsychotics cause weight gain?
1) Olanzapine
2) Clozapine
Which antipsychotics cause increased risk of gestational diabetes?
1) Olanzapine
2) Clozapine
The FDA issued a safety announcement that the pregnancy risk applies for which antipsychotics?
The entire antipsychotic class
What risks are seen in newborns whose mothers were treated with antipsychotics during their third trimester?
1) EPS
2) Withdrawal symptoms
Do antipsychotics appear in breast milk?
Yes
Antipsychotics appear in breast milk with milk-to-plasma ratios of:
0.5:1
1 week after delivery, ___ milk concentrations may reach 3X the plasma concentrations.
Clozapine
Clozapine use during breast-feeding is NOT recommended due to:
The risk of bone marrow suppression
Which antipsychotics are generally considered safe during breastfeeding?
1) Aripiprazole
2) Quetiapine
Infants exposed to ___ through breast milk may become drowsy and lethargic.
Chlorpromazine
Infants exposed to Chlorpromazine through breast milk may become:
1) Drowsy
2) Lethargic
The co-administration of which 2 antipsychotics result in developmental delays at 12 - 18 months of age?
1) Chlorpromazine
2) Haloperidol
What happens when antipsychotics are used with other sedatives?
Excess sedation
What happens when antipsychotics are used with other antimuscarinic drugs?
Additive antimuscarinic effects
Both combined sedative and anticholinergic effects from multiple medications can result in ____, particularly in the elderly.
Impaired cognition
What happens when antipsychotics are used with other drugs that cause orthostasis?
More orthostatic hypotension
What happens when antipsychotics are used with Metoclopramide?
1) Akathisia
2) Other EPS
Careful monitoring is required when giving antipsychotics with diuretics that cause ___.
Hypokalemia
Antipsychotics can __(shorten/prolong) the QT interval.
Prolong
___ can precipitate akathisia or EPS when added to a patient stabilized on an antipsychotic.
SSRIs
5-HT2 (Serotonin) receptor activation leads to:
Decreased dopamine release
Antipsychotic drugs are metabolized by:
1) CYP2D6
2) CYP3A4
3) CYP1A2
