Amlodipine and quetiapine are two commonly used medications that are generally well-tolerated when taken at the prescribed therapeutic doses. However, in cases of overdose, these medications can lead to severe and life-threatening cardiovascular effects, including refractory vasoplegia. Refractory vasoplegia is a condition characterized by a severe drop in blood pressure that does not respond to traditional treatments. The management of overdoses involving multiple substances, also known as poly-ingestion overdoses, can be particularly challenging. This is because the treatment approach often needs to be aggressive and multimodal, involving various therapies to counteract the effects of the unknown substances. In a recent case report, a 38-year-old male intentionally ingested a large amount of amlodipine and quetiapine, resulting in refractory shock. Despite receiving high doses of vasopressors, calcium, and insulin therapy, the patient's condition did not improve. In fact, the patient's blood pressure remained persistently low, requiring the use of multiple vasopressors to maintain adequate circulation. However, after conventional therapies failed to yield the desired results, the administration of exogenous angiotensin II (Ang II) led to a marked improvement in the patient's blood pressure and stabilization of hemodynamics. Angiotensin II is a vasoconstrictor that is traditionally used to treat septic shock, but in this case, it proved to be an effective salvage therapy for the patient. Within 60 minutes of initiating Ang II therapy, the patient's mean arterial pressure (MAP) improved significantly, allowing for the weaning of other vasopressors and a gradual reduction in insulin therapy. This case highlights the potential role of Ang II as a salvage therapy in cases of polysubstance ingestions where other treatments have failed, and it underscores the importance of considering alternative approaches when managing complex and refractory cases. Link: https://pubmed.ncbi.nlm.nih.gov/40445505/