Choosing the safest acute therapy during chronic migraine prophylactic treatment: pharmacokinetic and pharmacodynamic considerations

Abstract

The interactions between different drugs might be accurately predicted by the huge and detailed knowledge about the molecular pathways involved in pharmacodynamics and pharmacokinetics. Pharmacogenomic research has shed further light onto the mechanisms involved in the inter-individual variation in drug response and DDIs. Based on this knowledge, this paper will provide suggestions to improve the appropriateness of the drug choice in the prescription of preventative and acute migraine medications.

Chronic migraine treatment: from OnabotulinumtoxinA onwards

“…In addition, safety might be difficult to manage due to the side effects and contraindications and, in case of comorbidities, also the drug-drug interactions [12]. Major migraine comorbidities are the psychiatric and cardiovascular diseases, various forms of visceral pain, fibromyalgia or myofascial pain syndromes [13][14][15][16][17].…”

Effects of Lasmiditan on Cardiovascular Parameters and Pharmacokinetics in Healthy Subjects Receiving Oral Doses of Propranolol

“…It is important to understand how these cardiovascular changes may interact with drugs such as propranolol that are commonly prescribed in this patient population. 7,15 Propranolol is a β-adrenergic receptor antagonist, commonly prescribed for migraine prophylaxis, that is known to decrease heart rate by approximately 17% to 18%. 16 Therefore, understanding the cardiovascular impact of lasmiditan and propranolol coadministration is of particular clinical relevance.…”

How do you choose the appropriate migraine pharmacotherapy for an elderly person?

“…Therefore, one of the most important safety factors in frail geriatric patients is the preemptive identification of DDIs. The combination of a migraine preventive and acute drugs itself might lead to clinically significant DDIs, affecting both PKs and PDs drugs profile, responsible for altered response and development of ADRs [10]. PK interactions usually involve the modulation of specific CYP450 isozymes by coadministered drugs that inhibit or induce cytochromes activity and change their substrates metabolism.…”

“…DDIs can also arise from PD interactions occurring when concomitant drugs share the same molecular targets. Serotonin syndrome risk is higher when TCAs and triptans/ergot-derivatives are coadministrated due to their additive effect on the serotonin system and beta-blockers hypotensive effects might be diminished by NSAIDs inhibition of prostaglandin synthesis [10].…”