Ch 3: Neurobiology and Pharmacotherapy

What is considered the gold standard mood stabilizer for bipolar disorder?

lithium (Eskalith, Lithobid).

What is the proposed mechanism of lithium in mood stabilization?

Affects neuronal electrical conductivity, may reduce glutamate activity, inhibits inositol monophosphatase, and enhances serotonergic transmission.

What unique property of lithium makes blood level monitoring essential?

It has a narrow therapeutic index.

Name 3 medications that can increase lithium levels.

Hydrochlorothiazide, ACE inhibitors (e.g., lisinopril), NSAIDs (e.g., ibuprofen).

What substance can decrease lithium levels?

caffeine

What are potential dangers when lithium levels become too high?

Lithium toxicity, which can be life-threatening.

What mood stabilizing anticonvulsant is recommended for rapid cycling and mixed episodes in bipolar disorder?

Valproate (Depakote, Depakene).

What are serious side effects of valproate?

Thrombocytopenia, pancreatitis, hepatic failure, hyperammonemia.

What monitoring is required when using valproate?

Liver function tests (LFTs), CBC, pregnancy test, and therapeutic blood levels.

What is carbamazepine (Equetro, Tegretol) FDA approved to treat in bipolar disorder?

Manic or mixed episodes.

What dangerous side effect is associated with carbamazepine, especially in people of Asian descent?

Stevens-Johnson syndrome

Why is carbamazepine considered a second-line agent in bipolar disorder?

Due to its side effect profile and drug interaction potential.

What is lamotrigine (Lamictal) primarily used for in bipolar disorder?

Maintenance therapy and treatment of bipolar depression (not effective for acute mania).

Why must lamotrigine be titrated slowly?

To prevent serious rash, including Stevens-Johnson syndrome.

What happens to lamotrigine levels if valproate is added?

Valproate increases lamotrigine levels and rash risk; lamotrigine dose must be reduced.

What labs are necessary to monitor for all anticonvulsant mood stabilizers?

LFTs, CBC, and medication-specific drug levels.

What birth defects are associated with valproate and carbamazepine?

Neural tube defects (e.g., spina bifida)

What are common dermatologic adverse effects of lithium?

Acne, alopecia, psoriasis.

What are common digestive (GI) adverse effects of lithium?

Diarrhea, nausea, vomiting.

What are common endocrine adverse effects of lithium?

Hypothyroidism and weight gain.

What fluid and electrolyte disturbances can lithium cause?

edema, polydipsia, polyuria

What nervous and musculoskeletal side effects are associated with lithium use?

ataxia, sedation, fine motor tremor

What is the primary mechanism of action for first-generation antipsychotics?

decreases dopamine activity in the mesolimbic pathway to reduce positive symptoms of schizophrenia.

What symptoms of schizophrenia do first-generation antipsychotics primarily treat?

positive symptoms

What rare but life-threatening reaction can result from dopamine depletion by antipsychotics?

Neuroleptic malignant syndrome (NMS): rigidity, hyperthermia, autonomic instability.

What additional receptors are blocked by first-generation antipsychotics, and what side effects result?

• H1: Sedation, weight gain

• M1: Anticholinergic effects (dry mouth, constipation, etc.)

• α1: Orthostatic hypotension, dizziness

Why do second-generation antipsychotics have a lower risk of EPS?

antagonism increases dopamine release in the nigrostriatal pathway.

What types of schizophrenia symptoms do second-generation antipsychotics target?

positive and negative symptoms

What metabolic side effects are associated with second-generation antipsychotics?

Weight gain, hyperglycemia, dyslipidemia → metabolic syndrome.

What mechanism contributes to metabolic effects in second-generation antipsychotics?

appetite stimulation; insulin resistance

What are key features of clozapine?

Most effective for treatment-resistant schizophrenia; minimal EPS; high risk for agranulocytosis, seizures, metabolic effects. Requires ANC monitoring.

What are key side effects of risperidone?

High EPS and prolactin elevation; moderate metabolic effects; orthostatic hypotension.

Why does quetiapine cause sedation?

Strong H1 antagonism.

What cardiac risk is associated with ziprasidone?

QT interval prolongation → contraindicated in heart failure or recent MI.

How should ziprasidone and lurasidone be taken?

With food to ensure absorption

What is a unique side effect of aripiprazole?

Rare impulse-control disorders (e.g., gambling, shopping)

What distinguishes paliperidone from risperidone?

Paliperidone is the active metabolite of risperidone; similar profile, less hepatic metabolism.

What is important to know about iloperidone titration?

Must be slowly titrated to reduce risk of orthostatic hypotension.

What side effect requires slow titration of lamotrigine?

Stevens-Johnson syndrome (serious rash).