Anti-psychotics and Lithium Flashcards
Presence of delusions, hallucinations, and grossly disorganized thinking in a clear sensorium (i.e grandiosity and paranoia)
Psychosis
States that stimulation of 5-HT receptors cause hallucinogenic effects
Serotonin hypothesis of schizophrenia
States that there is increased dopamine in schizophrenic patients
Dopamine Hypothesis of Schizophrenia
States that hypofunction of NMDA receptors on GABAergic interneurons leads to diminished inhibitory influences on neuronal function, inducing disinhibition of downstream glutamatergic activity and hyperstimulation of cortical neurons through non-NMDA receptors
Glutamate hypothesis of schizophrenia
T/F Antipsychotics are specific for schizophrenia
False
Antipsychotics are NOT specific for schizophrenia
They are also effective in conditions where psychosis is present, such as schizoaffective disorder, mood disorder, dementia, personality disorder.
Three main psychopathological dimensions of Schizophrenia and examples of each
Positive Sx: psychosis (delusion, hallucination)
Negative Sx: social withdrawal, anhedonia, apathy
Cognitive Sx: attention, memory, executive function
Enumerate the four main dopamine pathways important in schizophrenia and their role
– The mesolimbic pathway (positive symptoms)
– The mesocortical pathway (negative symptoms and cognitive symptoms)
– The nigrostriatal pathway (extrapyramidal symptoms and tardive dyskinesia)
– The tuberoinfundibular pathway (hyperprolactinemia)
Dopamine pathway relevant to positive symptoms of schizophrenia
mesolimbic pathway
T/F: All antipsychotic drugs have the ability to reduce dopaminergic neurotransmission.
True. All antipsychotics are dopamine antagonists and therefore address positive Sx of schizophrenia
Negative and cognitive symptoms of schizophrenia are associated with hypofunction of the
mesocortical pathway
This pathway is related to neurological effects caused by D2 antagonists, such as EPS.
nigrostriatal pathway
Dopaminergic projections in the this pathway influence prolactin release.
tuberoinfundibular pathway
T/F First generation AP affects positive and negative symptoms
F; It only affects positive symptoms
T/F Second generation AP affects positive, negative and cognitive symptoms
T
SE of First generation AP
EPS
First generation AP is aka
Typical
Conventional
Neuroleptic
Second generation AP is aka
Atypical
Serotonin-dopamine antagonists
SE Second generation AP
Less EPS; but more metabolic SE (hyperglycemia, weight gain, dyslipidemia)
MOA of First Gen AP
D2 antagonist
But they can also block H1, M1, and alpha-1 receptors
MOA of Second Gen AP
D2 antagonist
5-HT2A antagonist
5-HT1A agonits
Some are 5-HT1A agonists (ziprasidone, quetiapine, clozapine): causes release in dopamine thereby reducing glutamate release
Acute SE of first gen anti-psychotics
Akathisia
Dystonia
Parkinsonism
Inability to sit still
akathisia
Management of akathisia
beta blockers (propranolol)
sustained contraction of tongue, face, back
acute dystonia
Management of dystonia
antiparkinsonian medication
Clinical features of parkinsonism
Masklike facies, resting tremor, bradykinesia, cogwheel rigidity, shuffling gait, psychomotor retardation
Management of anti-psychotic induced parkinsonsism
Anticholinergic agents
benztropine, biperiden, trihexyphenidyl
Give examples of first generation AP classified based on potency (high, mid, low)
High-potency: haloperidol, fluphenazine
Mid-potency: perphenazine, loxapine
Low-potency: chlorpromazine
Most widely used typical AP
haloperidol
Used for emergency psychotic patients
haloperidol
Prototype atypical AP
clozapine
T/F AP are highly lipid soluble and protein bound
T (able to traverse BBB)
Metabolism of AP
CYP (hepatic) metabolism
SE of AP due to blockade of alpha receptors
orhostatic hypotension
tachycardia
SE of AP due to blockade of muscarinic receptors
mouth dryness
blurring of vision
constipation
urinary retention
SE of AP due to blockade of histamine receptors
sedation
Only drug that is Partial agonist of D2 receptor
aripiprazole
Typical AP Must be given in sufficient doses to achieve at least ___% occupancy of D2 receptors
60%
EPS expected when occupancy reaches ____% or higher
80%
Aripiprazole achieves 80% occupancy but DOES NOT cause EPS (Why?)
** Because it is a partial agonist of your dopamine receptor (D2) not capable of achieving of maximum effect.
Endocrine SE of typical AP
Hyperprolactinemia: amenorrhea, galactorrhea, infertility, impotence
QT prolongation is seen in use of
thioridazine
ziprasidone
SE due to chronic use of AP
Tardive dyskinesia
most important unwanted effect of antipsychotic drugs
tardive dyskinesia
Mx of tardive dyskinesia
discontinue medication, reduce dose or switch to antipsychotics which are least likely to cause this syndrome (quetiapine or clozapine)
Impaired Ejaculation is seen in use of
chlorpromazine or mesoridazine
Metabolic SE of Second gen AP
Weight gain
Hyperglycemia
Hyperlipidemia
Weight gain is seen in use of which second gen AP?
clozapine
olanzapine
Agranulocytosis is seen in use of
clozapine
- *pts receiving this drug should have weekly blood counts for the 1st 6 mos and every 3 weeks thereafter
- *Potentially fatal effects develop between 6th and 18th weeks of therapy
Corneal and lens deposits are seen in use of
chlorpromazine
Retinal deposits are seen in use of
thioridazine
Can cause abnormal T waves
thioridazine
Myocarditis is associated with
clozapine
SE of thioridazine
QT prolongation
abnormal T wave
Retinal deposits
Life-threatening disorder that Occur in pts who are extremely sensitive to pyramidal effects of antipsychotic agents
Neuroleptic Malignant Syndrome
Two phases of bipolar affective disorder
Manic phase
Depression
DOC for bipolar disorder
Lithium
Lithium is excreted via
kidneys
Effect of lithium on thyroid
decreased thyroid function (hypothyroidism)
SE of lithium in kidneys
Nephrogenic DI
Treatment of lithium-induced nephrogenic DI =
amiloride
vasopressin does not respond
Effect of lithium on heart ECG
Bradycardia-tachycardia “sick sinus” syndrome
T-wave flattening
Risk in pregnancy in taking lithium
Ebstein anomaly
Ebstein anomaly is a rare heart defect in which parts of the tricuspid valve are abnormal. The tricuspid valve separates the right lower heart chamber (right ventricle) from the right upper heart chamber (right atrium). In Ebstein anomaly, the positioning of the tricuspid valve and how it functions to separate the 2 chambers is abnormal.
How to treat overdosage of lithium?
dialysis (peritoneal and hemodialysis)
Effective in some patients who have failed to respond to lithium
Valproic Acid
Used to treat acute mania and for prophylactic therapy
Used as mood stabilizer is similar to its use as anticonvulsant
Carbamazepine
used in preventing depression that follows the manic phase
lamotrigine
An adolescent male is newly diagnosed with schizophrenia.Which of the following neuroleptic agents may improve his apathy and blunted affect? A. Chlorpromazine. B. Fluphenazine. C. Haloperidol. D. Risperidone. E. Thioridazine
D. Risperidone is the only neuroleptic on the list that has some benefit in improving the negative symptoms of schizophrenia.
Which one of the following neuroleptics has been shown to be a partial agonist at the D2 receptor? A. Aripiprazole. B. Clozapine. C. Haloperidol. D. Risperidone. E. Thioridazine.
A. Aripiprazole is the agent that acts as a partial agonist at D2 receptors.
A 28-year-old woman with schizoid affective disorder and difficulty sleeping would be most benefited by which of the following drugs?
A. Aripiprazole. B. Chlorpromazine. C. Haloperidol. D. Risperidone. E. Ziprasidone.
B. Chlorpromazine has significant sedative activity as well as antipsychotic properties. Of the choices, it is the drug most likely to alleviate this patient’s major complaints, including her insomnia.
