Lithium + Antipsychotics B&B

Question 1

what psychological disorder is lithium used to treat, and what is its MOA?

Answer 1

bipolar disorder - not common anymore due to narrow TI

inhibits inositol monophosphate (IMPase), which regenerates inositol —> depleted inositol causes decrease in 2nd messenger levels (PIP2, IP3, DAG)

Question 2

what are the risk factors for lithium toxicity? why does this make sense?

Answer 2

excreted renally, reabsorbed in PCT (like Na+)

therefore, risk factors for toxicity = renal insufficiency, volume depletion, elderly (low GFR)

Question 3

which drugs increase vs decrease lithium levels in the body?

Answer 3

increase: thiazide diuretics, NSAIDS, ACE inhibitors

decrease: K+ sparing diuretics (Amiloride)

varying: loop diuretics

Question 4

what are the acute, long-term, and fetal adverse effects of lithium?

Answer 4

acute: tremor (symmetric, usually limited to arms/hands)

long-term: hypothyroidism (goiter), nephrogenic diabetes insipidus, cardiac dysfunction (suppression of sinus node - bradycardia)

fetal: Ebstein’s anomaly (RV atrialization)

Question 5

Pt w PMH of bipolar disorder presents with polyuria and polydipsia. Blood chemistry shows normal serum Na+. Urine labs show low osmolarity. Vasopressin is given by a resident to no effect. What drug should be started instead (and give MOA), and which drug should be discontinued?

Answer 5

dx: diabetes insipidus (tubules do not respond to ADH) due to lithium toxicity (tx bipolar)

discontinue lithium, give amiloride (K+ sparing diuretic)

amiloride: inhibits ENaC of principal cells —> this also blocks lithium entry into renal cells (blocks reabsorption)

Question 6

baby born with Ebstein’s anomaly was most likely exposed to ____ in utero

Answer 6

lithium - completely equilibrates across the placenta

Question 7

what is the result of D1 vs D2 receptor activation?

Answer 7

D1 receptors activate adenylyl cyclase —> increased cAMP

D2 receptors inhibit adenylyl cyclase —> decreased cAMP

Question 8

what is the MOA of first gen (typical) antipsychotics?

ex: haloperidol, chlorpromazine, trifluoperazine, fluphenazine, thioridazine, pimozide

Answer 8

aka “neuroleptics”, depress CNS activity via D2 receptor blockade on post-synaptic neurons

D2 normally inhibits adenylyl cyclase (decrease cAMP); therefore, blocking D2 leads to increase cAMP

Question 9

what are the side effects of first generation (typical) antipsychotics? 4

ex: haloperidol, chlorpromazine, trifluoperazine, fluphenazine, thioridazine, pimozide

Answer 9

1. D2 blockade —> extrapyramidal Parkinsonism, hyperprolactinemia, amenorrhea, galactorrhea, gynecomastia, anti-emetic
2. histamine blockade —> sedation, constipation
3. ACh blockade —> dry mouth, constipation
4. alpha1 blockade —> hypotension, ED

Question 10

contrast the following extrapyramidal symptoms that occur with dopamine receptor blockage by first gen. antipsychotics, including when they occur:
a. dystonia
b. akathisia
c. bradykinesia
d. tardive dyskinesia

Answer 10

a. dystonia (hours/days): spasms/stiffness, tx w/ benztropine (blocks M1)

b. akathisia (days, most common): restlessness, tx w/ lower dose or benzos or propranolol

c. bradykinesia (weeks): Parkinson-like, tx w/ benztropine

d. tardive dyskinesia (months, years): choreoathetosis (smacking lips, grimacing), irreversible

Question 11

what is the difference between high potency and low potency first generation (typical) antipsychotics?

name 3 high potency and 2 low potency

Answer 11

high potency have extrapyramidal side effects, ex: haloperidol, trifluoperazine, fluphenazine

low potency have more histamine/muscarinic side effects (sedative, dry mouth), ex: thioridazine, chlorpromazine

Question 12

sort the following into high potency vs low potency first generation antipsychotics:
a. haloperidol
b. trifluoperazine
c. thioridazine
d. chlorpromazine
e. fluphenazine

Answer 12

high potency have extrapyramidal side effects, ex: haloperidol, trifluoperazine, fluphenazine

low potency have more histamine/muscarinic side effects (sedative, dry mouth), ex: thioridazine, chlorpromazine

Question 13

which of the following antipsychotics is most likely to cause sedation?
a. trifluoperazine
b. fluphenazine
c. thioridazine

Answer 13

c. thioridazine - low potency

high potency have extrapyramidal side effects, ex: haloperidol, trifluoperazine, fluphenazine

low potency have more histamine/muscarinic side effects (sedative, dry mouth), ex: thioridazine, chlorpromazine

Question 14

how does neuroleptic malignant syndrome (NMS) present? how is it treated?

Answer 14

[neuroleptics = first gen. antipsychotics]

occurs 7-10 days after tx starts w/ fever and rigid muscles, encephalopathy (mental status changes), elevated CK, myoglobinuria (rhabdomyolysis, acute renal failure)

tx: dantrolene (muscle relaxant) + bromocriptine (dopamine agonist)

Question 15

which antipsychotic is most strongly associated with prolonged QT interval? what is the reason this occurs?

Answer 15

haloperidol

blocked cardiac K+ channels —> prolonged QT interval —> may cause Torsade de Pointes

Question 16

which 2 first generation (typical) antipsychotics are associated with ocular side effects? what are the side effects, specifically?

Answer 16

Chlorpromazine —> Corneal deposits

thioRidazine —> Retinal deposits (“browning” vision, resembles retinitis pigmentosa)

Question 17

which first generation (typical) antipsychotic is associated with corneal deposits?

Answer 17

Chlorpromazine —> Corneal deposits

Question 18

first generation (typical) antipsychotic is associated with retinal deposits?

Answer 18

thioRidazine —> Retinal deposits (“browning” vision, resembles retinitis pigmentosa)

Question 19

what is the difference between first generation (typical) vs second generation (atypical) antipsychotics?

Answer 19

second generation have fewer extrapyramidal and anti-cholinergic adverse effects

Question 20

which 2 antipsychotics are most associated with metabolic syndrome?

Answer 20

1. clozapine
2. olanzapine

both are second generation (atypical)

[metabolic syndrome = weight gain + hyperglycemia + hyperlipidemia]

Question 21

what are the unique side effects (2) of clozapine among second gen. antipsychotics?

Answer 21

1. agranulocytosis - must monitor WBCs
2. seizures - dose related

Question 22

which antipsychotic is associated with bone marrow toxicity?

Answer 22

clozapine - may cause agranulocytosis, must monitor WBCs

Question 23

what is the most common cause of drug-induced hyperprolactinemia?

Answer 23

antipsychotics - esp. risperidone, paliperidone, haloperidol, fluphenazine

dopamine blockade —> increased prolactin (disinhibited) —> amenorrhea/ gynecomastia/ galactorrhea

Question 24

which antipsychotics (2) are most closely associated with drug-induced hyperprolactinemia?

Answer 24

[dopamine blockade —> increased prolactin]

1. risperidone
2. paliperidone

[also haloperidol + fluphenazine, but these are 1st gen and not chronically used anymore]

Question 25

what is the MOA of aripiprazole?

Answer 25

antipsychotic that is D2 partial agonist - causes less dopamine blockade adverse effects

most common side effect = akathisia (restlessness)

Question 26

which antipsychotic may cause agranulocytosis?

Answer 26

clozapine: 2nd gen (atypical), antagonist at D2 and serotonin receptors

Question 27

what is the box warning on atypical antipsychotics?

ex: clozapine, lurasidone, olanzapine, quetiapine, risperidone, ziprasidone

Answer 27

increased risk of death in elderly patients with dementia-related psychosis

Question 28

how is aripiprazole different than other second generation (atypical) antipsychotics?

Answer 28

partial agonist at D2 receptors —> blocks binding but sustains signaling at a lower level

Question 29

which of the following is NOT a second-generation antipsychotic?
a. clozapine
b. lurasidone
c. olanzapine
d. quetiapine
e. chlorpromazine
f. ziprasidone

Answer 29

e. chlorpromazine - first generation (typical)