Drug Treatment of Acute Ischemic Stroke

Abstract

Acute ischemic stroke (AIS) is the fourth leading cause of death and the leading cause of adult disability in the USA. AIS most commonly occurs when a blood vessel is obstructed leading to irreversible brain injury and subsequent focal neurologic deficits. Drug treatment of AIS involves intravenous thrombolysis with alteplase (recombinant tissue plasminogen activator [rtPA]). Intravenous alteplase promotes thrombolysis by hydrolyzing plasminogen to form the proteolytic enzyme plasmin. Plasmin targets the blood clot with limited systemic thrombolytic effects. Alteplase must be administered within a short time window to appropriate patients to optimize its therapeutic efficacy. Recent trials have shown this time window may be extended from 3 to 4.5 hours in select patients. Other acute supportive interventions for AIS include maintaining normoglycemia, euthermia and treating severe hypertension. Urgent anticoagulation for AIS has generally not shown benefits that exceed the hemorrhage risks in the acute setting. Urgent antiplatelet use for AIS has limited benefits and should only promptly be initiated if alteplase was not administered, or after 24 hours if alteplase was administered. The majority of AIS patients do not receive thrombolytic therapy due to late arrival to emergency departments and currently there is a paucity of acute interventions for them. Ongoing clinical trials may lead to further medical breakthroughs to limit the damage inflicted by this devastating disease.

Hepcidin Levels Are Increased in Patients with Acute Ischemic Stroke: Preliminary Report

“…The currently available and approved by US Food and Drug Administration therapeutic strategy for ischemic stroke is limited to rtPA (alteplase). 29 The present study revealed that patients who received thrombolysis had significantly higher levels of hepcidin on the seventh day after stroke diagnosis, as compared with the seventh day's levels in the nonthrombolysis patients. It is noteworthy that 11 of 19 (58%) stroke victims who were not treated with alteplase received a once-daily or a twicedaily injection of the LMWH enoxaparin sodium.…”

Available Therapeutics after a Stroke: Current and Promising Options

“…At present and still after decades, the FDA only approves the use of recombinant tissue plasminogen activator (rTPA), also known as alteplase, as the sole pharmacological option for recanalization [35,39]. Alteplase initiates local fibrinolysis when administered intravenously by hydrolyzing the peptide bond in plasminogen to form plasmin [40]. The standard IV dosage is 0.9 mg/kg for 60 min, with a 10% bolus over 1 min within 4.5 h of AIS onset [31].…”

Effects of resveratrol postconditioning on cerebral ischemia in mice: role of the sirtuin-1 pathway

“…Various cerebroprotective preconditioning procedures like pharmacological or ischemic preconditioning have been proved to be effective in animal studies (Gidday 2006;Vijaykumar et al 2016). However, the anticipation of ischemic episodes is often not possible in clinical set up; therefore, practicality of these preconditioning procedures is particularly limited (Bansal et al 2013). Ischemic postconditioning has also been shown to render protection against cerebral IR injury, however, it is difficult to initiate it in clinical settings (Ledger et al 2015).…”