Mechanism of Lorazepam in Treating Extrapyramidal Side Effects of Prochlorperazine
Lorazepam effectively treats prochlorperazine-induced extrapyramidal symptoms (EPS) primarily through its GABA-receptor agonist activity, which helps restore neurotransmitter balance disrupted by dopamine blockade. 1
Pathophysiology of Prochlorperazine-Induced EPS
- Prochlorperazine, a phenothiazine antiemetic, acts as a dopamine receptor antagonist that can disrupt the balance between dopaminergic and cholinergic neurotransmission in the nigrostriatal pathway 2
- This dopamine blockade in the nigrostriatal pathways leads to various extrapyramidal symptoms, including acute dystonia, drug-induced parkinsonism, and akathisia 2
- These symptoms can manifest as muscle spasms, abnormal postures, tremors, rigidity, and subjective feelings of restlessness 3
Mechanism of Action of Lorazepam
- Lorazepam, a benzodiazepine, exerts its central nervous system (CNS) depressant effect by binding to presynaptic γ-aminobutyric acid (GABA) receptors 3
- GABA is the primary CNS inhibitory neurotransmitter that decreases neuronal excitability 3
- By enhancing GABA activity, lorazepam helps counteract the excessive excitatory neurotransmission that occurs when dopamine is blocked by prochlorperazine 1
- This action helps restore the balance between inhibitory and excitatory pathways disrupted by dopamine receptor blockade 2
Clinical Application and Dosing
- Lorazepam can be used at doses of 0.5-2 mg every 4-6 hours for treating extrapyramidal symptoms caused by prochlorperazine 1
- It is particularly useful in acute settings where rapid relief of EPS is needed 3
- Lorazepam has advantages of fast onset of action, rapid and complete absorption, and no active metabolites, making it suitable for acute management of EPS 3
Comparative Effectiveness
- While anticholinergic medications like benztropine are often considered first-line for treating dystonic reactions, lorazepam provides an effective alternative 1
- The combination of a benzodiazepine with an antipsychotic has been shown to reduce the incidence of extrapyramidal symptoms compared to antipsychotics alone (NNH 2, CI 1 to 5) 4
- Benzodiazepines alone have been shown to cause significantly fewer extrapyramidal symptoms compared to antipsychotics (NNT 6, CI 2 to 17) 4
Clinical Considerations and Cautions
- Lorazepam may cause CNS depression, anterograde amnesia, and has potential for paradoxical aggression in older adults 3
- Caution should be exercised in pregnancy and in patients with a history of substance abuse 3
- Monitor patients closely after administration for respiratory depression and excessive sedation 3
- For patients requiring ongoing antiemetic therapy who have experienced EPS with prochlorperazine, consider alternative antiemetics such as ondansetron, though be aware that even 5-HT3 antagonists can occasionally cause EPS 1, 5
Prevention Strategy
- For patients with risk factors for developing EPS (young males, children, adolescents, and elderly patients), consider using alternative antiemetics with lower EPS risk 2, 6
- If prochlorperazine must be used in high-risk patients, prophylactic administration of lorazepam may be considered to prevent EPS 7