No abstract

Donepezil is an acetylcholinesterase inhibitor (AChEI) that prevents the breakdown of acetylcholine, a neurotransmitter, which is depleted in patients with Alzheimer's disease and dementia. 1 There are few reports showcasing donepezil toxicity in the literature and even less that display a coinciding beta-blocker toxicity. 2-8 This case highlights symptoms representative of a donepezil toxicity and risks that may occur even at the manufacturer's recommended doses. The American Geriatrics Society's Beer's list recognizes donepezil as a high-risk medication in older adults due to increased rates of orthostatic hypotension and bradycardia within this population. 9 Some common (>10%) adverse reactions of donepezil include nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue, and anorexia. Other less common (1%-10%) adverse effects are insomnia, emesis, gastritis, hypertension, syncope, bradycardia, chills, generalized coldness, pain, dizziness, abnormal gait, confusion, fatigue, diaphoresis, abdominal pain, bloating, and constipation and were reported to occur more often in females of advancing age. 10 Toxicity symptoms reported in other case reports included: nausea, vomiting, confusion, somnolence, diaphoresis and bradycardia with greater prominence at higher donepezil doses. 2-8 In addition, postmarketing data have revealed hyperglycemia and hypothermia reported in less than 1% of patients. 10 One of the dose-related signs of toxicity in animals was lower body surface temperature. Like donepezil toxicity, altered mental status and bradycardia commonly occur with beta-blocker toxicity. Hypothermia can occur with both agents; however, it is less prevalent in beta-blocker toxicity. Other effects seen with beta-blocker toxicity include hypotension, respiratory depression, seizure, hypoglycemia, and bronchospasm. 11,12 When AChEIs are co-administered with heart rate-lowering agents like beta-blockers, a theoretical risk of enhanced bradycardia exists. 12 Beta-blockers lower the heart rate by blocking beta-1 receptors and impeding the action of epinephrine and norepinephrine. 13 AChEIs increase acetylcholine at the synapses and affect the parasympathetic innervation of the heart, resulting in decreased sinoatrial-and atrioventricular node conduction and decreased heart rate. 14

No abstract

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a disease characterized by high pressures within the pulmonary arteries leading to right sided heart failure and often premature death [1]. Here, we present a case of PAH in which we examine the role of advanced pharmacological management, specifically intravenous prostacyclin [PC] therapy, during the transition of a patient's goals of care.CASE PRESENTATION: 64-year-old male with recently diagnosed Sjogren's disease presented with acute, decompensated right ventricular failure. He was effectively diuresed and right heart catheterization showed pulmonary arterial pressure of 71/26 mmHg (mean 42 mmHg) and pulmonary capillary wedge pressure 5 mmHg. By Fick calculations, cardiac index was 1.7 and pulmonary vascular resistance of 2.88 Wood units. He was diagnosed with Group 1 PAH related to underlying Sjogren's disease and given his low cardiac index and severely elevated mean pulmonary artery pressure, intravenous treprostinil was initiated.Unfortunately, the patient's disease progression was refractory to advanced therapy. Despite reaching a dose of 28 ng/kg/m of intravenous treprostinil, as well as Tadalafil 40mg and Ambrisentan 10mg daily, the patient's diseased right ventricle was unable to be salvaged. In the subsequent 4 months, he spent only a total of 16 days outside of the hospital. During his last hospitalization, the patient began suffering from severe malnutrition and acute metabolic encephalopathy. Unable to tolerate parenteral feeding, the family decided to transition to palliation. At the time of transition, the patient's vitals were: BP 95/70 (on norepinephrine at 12 mcg/min and dobutamine 2.5 mcg/kg/m), HR 105, afebrile, and saturating 99% on 2L NC. He was started on Dilaudid and Ativan infusion, up titrated to optimize comfort. The norepinephrine and dobutamine were stopped, and the Treprostinil remained at a dose of 28 ng/kg/m. The patient passed comfortably 10 hours after transitioning to palliative measures. DISCUSSION: At our institution, there was no protocol for titration of PC therapy during transitions to comfort measures. PC medications, unlike vasopressors, cannot be rapidly titrated as this could potentially result in severe cardiopulmonary compromise, i.e. sudden cardiac death, and thus would not be in line with a palliative care philosophy. As a result of this case, our institution developed a novel protocol for prostacyclin dosing adjustments during end-of-life care with the underlying philosophy that active monitoring of a patient's richmond agitation sedation scale can provide a valuable roadmap on prostacyclin titration. CONCLUSIONS:There is minimal evidence regarding the use of PC therapy during palliation for patients with advanced PAH. Following the implementation of a Prostacyclin End of Life Titration Protocol, we hope to provide optimal comfort and pain control for end of life PAH patients.

No abstract