Pharmacology Flashcards: Antipsychotics, Benzodiazepines, Anticonvulsants, Mood Stabilizers

Typical, or first-generation, antipsychotics like haloperidol and chlorpromazine primarily block dopamine D2 receptors and are effective for positive symptoms of schizophrenia such as hallucinations and delusions but frequently cause extrapyramidal symptoms. Atypical, or second-generation, antipsychotics like risperidone, olanzapine, quetiapine, and clozapine block both dopamine and serotonin receptors, treating both positive and negative symptoms with fewer movement side effects.

Extrapyramidal symptoms, or EPS, are movement disorders caused by dopamine blockade in the basal ganglia, most commonly from typical antipsychotics. They include acute dystonia presenting as sustained muscle contractions, akathisia presenting as restlessness and inability to sit still, parkinsonism presenting as tremor, rigidity, and bradykinesia, and tardive dyskinesia presenting as involuntary repetitive movements of the face and tongue. Acute dystonia and akathisia appear early in treatment, while tardive dyskinesia develops after months to years of use and may be irreversible.

Tardive dyskinesia is a potentially irreversible movement disorder characterized by involuntary, repetitive movements of the face, tongue, jaw, and limbs, such as lip smacking, tongue protrusion, and grimacing. It develops after prolonged use of dopamine-blocking medications, primarily typical antipsychotics, and results from dopamine receptor supersensitivity after chronic blockade. Once established, tardive dyskinesia may persist even after discontinuing the offending medication. Newer treatments including valbenazine and deutetrabenazine can reduce symptoms.

Benzodiazepines enhance the effect of gamma-aminobutyric acid, or GABA, the brain's primary inhibitory neurotransmitter, by binding to GABA-A receptors and increasing the frequency of chloride channel opening. This produces sedation, anxiolysis, muscle relaxation, and anticonvulsant effects. Common benzodiazepines include lorazepam, diazepam, alprazolam, and clonazepam. Major risks include dependence with daily use beyond two to four weeks, respiratory depression especially when combined with opioids, falls in elderly patients, and paradoxical agitation.

Combining benzodiazepines with opioids dramatically increases the risk of fatal respiratory depression because both drug classes depress the central nervous system through different mechanisms. Benzodiazepines enhance GABA inhibition while opioids depress the brainstem respiratory center. Together they suppress breathing more than either alone. The FDA issued a black box warning in 2016 requiring labels on both drug classes to warn about this interaction.

Lithium is a mood stabilizer and first-line treatment for bipolar disorder, effective for acute mania and long-term prevention of manic and depressive episodes. It has a very narrow therapeutic index with a therapeutic range of 0.6 to 1.2 milliequivalents per liter. Lithium levels, kidney function, and thyroid function must be monitored regularly because lithium is excreted by the kidneys and can cause hypothyroidism and nephrogenic diabetes insipidus. Signs of lithium toxicity include tremor, nausea, diarrhea, confusion, and seizures.

Valproic acid, also called divalproex, and carbamazepine are anticonvulsants commonly used as mood stabilizers for bipolar disorder. Valproic acid is effective for acute mania and maintenance treatment, with side effects including weight gain, tremor, hair loss, and rare but serious hepatotoxicity and pancreatitis. It is teratogenic and must be avoided in pregnancy due to neural tube defect risk. Carbamazepine is used for bipolar disorder and trigeminal neuralgia but carries risks of aplastic anemia and agranulocytosis.

Neuroleptic malignant syndrome, or NMS, is a rare but life-threatening reaction to antipsychotic medications characterized by four cardinal features: high fever often exceeding 40 degrees Celsius, severe muscle rigidity described as "lead pipe," autonomic instability with tachycardia and blood pressure fluctuations, and altered mental status. Laboratory findings include markedly elevated creatine kinase from muscle breakdown. NMS can occur with any dopamine-blocking medication, though typical antipsychotics carry the highest risk.

Flumazenil is the specific reversal agent for benzodiazepine overdose. It works by competitively binding to the GABA-A receptor at the benzodiazepine binding site, displacing the benzodiazepine and reversing its sedative and respiratory depressant effects. Flumazenil is administered intravenously with effects beginning within one to two minutes. However, its duration of action is shorter than most benzodiazepines, so resedation can occur and repeat doses may be needed. ---