Pharmacodynamics and Pharmacokinetics of Stroke Therapy

Stroke is a complex disorder that includes several different pathophysiological entities, and therefore requires a personalized approach to therapy. Pharmacological acute stroke therapy includes fibrinolytics such as alteplase (rt-PA) or tenecteplase which has a more favorable pharmacokinetic profile. Hemorrhagic adverse events are the main risks of these therapies, and clinical, laboratorial, and genetic factors may influence the risk of severe bleeding. After the acute time window, prevention is paramount in order to avoid recurrent stroke. Antiplatelet drugs (aspirin, clopidogrel, dipyridamole) are the default secondary prevention therapies. In some patients, such as those with cardioembolic stroke, anticoagulants are the preferred preventive treatment. These include vitamin K antagonists (warfarin) and direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, edoxaban). With some drugs, such as clopidogrel and warfarin, significant heterogeneity of the magnitude of effect and side effect profile exists between subjects. In addition to environmental factors and drug-drug interactions, genetic polymorphisms contribute to intersubject variability, whether through drug receptor or metabolic pathway variations. Knowledge of the precise pharmacodynamic, pharmacokinetic, and pharmacogenetic details of drugs used in stroke care enables the selection of the most appropriate option for each individual patient. Precision medicine and pharmacogenetic-guided drug algorithms may become the standard of care in the future.