Anti-psychotics and Lithium

Question 1

Presence of delusions, hallucinations, and grossly disorganized thinking in a clear sensorium (i.e grandiosity and paranoia)

Answer 1

Psychosis

Question 2

States that stimulation of 5-HT receptors cause hallucinogenic effects

Answer 2

Serotonin hypothesis of schizophrenia

Question 3

States that there is increased dopamine in schizophrenic patients

Answer 3

Dopamine Hypothesis of Schizophrenia

Question 4

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

Answer 4

Glutamate hypothesis of schizophrenia

Question 5

T/F Antipsychotics are specific for schizophrenia

Answer 5

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.

Question 6

Three main psychopathological dimensions of Schizophrenia and examples of each

Answer 6

Positive Sx: psychosis (delusion, hallucination)
Negative Sx: social withdrawal, anhedonia, apathy
Cognitive Sx: attention, memory, executive function

Question 7

Enumerate the four main dopamine pathways important in schizophrenia and their role

Answer 7

– 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)

Question 8

Dopamine pathway relevant to positive symptoms of schizophrenia

Answer 8

mesolimbic pathway

Question 9

T/F: All antipsychotic drugs have the ability to reduce dopaminergic neurotransmission.

Answer 9

True. All antipsychotics are dopamine antagonists and therefore address positive Sx of schizophrenia

Question 10

Negative and cognitive symptoms of schizophrenia are associated with hypofunction of the

Answer 10

mesocortical pathway

Question 11

This pathway is related to neurological effects caused by D2 antagonists, such as EPS.

Answer 11

nigrostriatal pathway

Question 12

Dopaminergic projections in the this pathway influence prolactin release.

Answer 12

tuberoinfundibular pathway

Question 13

T/F First generation AP affects positive and negative symptoms

Answer 13

F; It only affects positive symptoms

Question 14

T/F Second generation AP affects positive, negative and cognitive symptoms

Answer 14

T

Question 15

SE of First generation AP

Answer 15

EPS

Question 16

First generation AP is aka

Answer 16

Typical
Conventional
Neuroleptic

Question 17

Second generation AP is aka

Answer 17

Atypical

Serotonin-dopamine antagonists

Question 18

SE Second generation AP

Answer 18

Less EPS; but more metabolic SE (hyperglycemia, weight gain, dyslipidemia)

Question 19

MOA of First Gen AP

Answer 19

D2 antagonist

But they can also block H1, M1, and alpha-1 receptors

Question 20

MOA of Second Gen AP

Answer 20

D2 antagonist
5-HT2A antagonist
5-HT1A agonits

Some are 5-HT1A agonists (ziprasidone, quetiapine, clozapine): causes release in dopamine thereby reducing glutamate release

Question 21

Acute SE of first gen anti-psychotics

Answer 21

Akathisia
Dystonia
Parkinsonism

Question 22

Inability to sit still

Answer 22

akathisia

Question 23

Management of akathisia

Answer 23

beta blockers (propranolol)

Question 24

sustained contraction of tongue, face, back

Answer 24

acute dystonia

Question 25

Management of dystonia

Answer 25

antiparkinsonian medication

Question 26

Clinical features of parkinsonism

Answer 26

Masklike facies, resting tremor, bradykinesia, cogwheel rigidity, shuffling gait, psychomotor retardation

Question 27

Management of anti-psychotic induced parkinsonsism

Answer 27

Anticholinergic agents | benztropine, biperiden, trihexyphenidyl

Question 28

Give examples of first generation AP classified based on potency (high, mid, low)

Answer 28

High-potency: haloperidol, fluphenazine Mid-potency: perphenazine, loxapine Low-potency: chlorpromazine

Question 29

Most widely used typical AP

Answer 29

haloperidol

Question 30

Used for emergency psychotic patients

Answer 30

haloperidol

Question 31

Prototype atypical AP

Answer 31

clozapine

Question 32

T/F AP are highly lipid soluble and protein bound

Answer 32

T (able to traverse BBB)

Question 33

Metabolism of AP

Answer 33

CYP (hepatic) metabolism

Question 34

SE of AP due to blockade of alpha receptors

Answer 34

orhostatic hypotension | tachycardia

Question 35

SE of AP due to blockade of muscarinic receptors

Answer 35

mouth dryness blurring of vision constipation urinary retention

Question 36

SE of AP due to blockade of histamine receptors

Answer 36

sedation

Question 37

Only drug that is Partial agonist of D2 receptor

Answer 37

aripiprazole

Question 38

Typical AP Must be given in sufficient doses to achieve at least ___% occupancy of D2 receptors

Answer 38

60%

Question 39

EPS expected when occupancy reaches ____% or higher

Answer 39

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.

Question 40

Endocrine SE of typical AP

Answer 40

Hyperprolactinemia: amenorrhea, galactorrhea, infertility, impotence

Question 41

QT prolongation is seen in use of

Answer 41

thioridazine | ziprasidone

Question 42

SE due to chronic use of AP

Answer 42

Tardive dyskinesia

Question 43

most important unwanted effect of antipsychotic drugs

Answer 43

tardive dyskinesia

Question 44

Mx of tardive dyskinesia

Answer 44

discontinue medication, reduce dose or switch to antipsychotics which are least likely to cause this syndrome (quetiapine or clozapine)

Question 45

Impaired Ejaculation is seen in use of

Answer 45

chlorpromazine or mesoridazine

Question 46

Metabolic SE of Second gen AP

Answer 46

Weight gain Hyperglycemia Hyperlipidemia

Question 47

Weight gain is seen in use of which second gen AP?

Answer 47

clozapine | olanzapine

Question 48

Agranulocytosis is seen in use of

Answer 48

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

Question 49

Corneal and lens deposits are seen in use of

Answer 49

chlorpromazine

Question 50

Retinal deposits are seen in use of

Answer 50

thioridazine

Question 51

Can cause abnormal T waves

Answer 51

thioridazine

Question 52

Myocarditis is associated with

Answer 52

clozapine

Question 53

SE of thioridazine

Answer 53

QT prolongation abnormal T wave Retinal deposits

Question 54

Life-threatening disorder that Occur in pts who are extremely sensitive to pyramidal effects of antipsychotic agents

Answer 54

Neuroleptic Malignant Syndrome

Question 55

Two phases of bipolar affective disorder

Answer 55

Manic phase | Depression

Question 56

DOC for bipolar disorder

Answer 56

Lithium

Question 57

Lithium is excreted via

Answer 57

kidneys

Question 58

Effect of lithium on thyroid

Answer 58

decreased thyroid function (hypothyroidism)

Question 59

SE of lithium in kidneys

Answer 59

Nephrogenic DI

Question 60

Treatment of lithium-induced nephrogenic DI =

Answer 60

amiloride | vasopressin does not respond

Question 61

Effect of lithium on heart ECG

Answer 61

Bradycardia-tachycardia “sick sinus” syndrome | T-wave flattening

Question 62

Risk in pregnancy in taking lithium

Answer 62

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.

Question 63

How to treat overdosage of lithium?

Answer 63

dialysis (peritoneal and hemodialysis)

Question 64

Effective in some patients who have failed to respond to lithium

Answer 64

Valproic Acid

Question 65

Used to treat acute mania and for prophylactic therapy | Used as mood stabilizer is similar to its use as anticonvulsant

Answer 65

Carbamazepine

Question 66

used in preventing depression that follows the manic phase

Answer 66

lamotrigine

Question 67

``` 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 ```

Answer 67

D. Risperidone is the only neuroleptic on the list that has some benefit in improving the negative symptoms of schizophrenia.

Question 68

``` 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. ```

Answer 68

A. Aripiprazole is the agent that acts as a partial agonist at D2 receptors.

Question 69

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. ```

Answer 69

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.