Pharmacology of Migraine Medications

Introduction

• Overview of migraine pathophysiology
• Importance of understanding mechanisms of action
• Support by subscribing, liking, and commenting on the video

Pathophysiology of Migraines

• Neurotransmitters and Molecules Involved
  • Vasoactive peptide
  • Substance P
  • Calcitonin Gene-Related Peptide (CGRP)
  • Histamines and prostaglandins
• Mechanism of Migraine Initiation
  • Activation of trigeminal nerves and nociceptors in the meninges
  • Release of neurotransmitters causing vasodilation and increased capillary permeability
  • Connection to trigeminal nerve (Cranial Nerve V)
• Trigeminal Nerve Pathway
  • Afferent fibers send signals to the trigeminal nucleus
  • Information relayed to thalamus and then to the sensory cortex
  • Pain is perceived in regions supplied by trigeminal nerve (orbital, frontal, temporal)

Migraine Presentation

• Classic Headache
  • Pain in specific regions supplied by the trigeminal nerve
• Auras
  • Cortical Spreading Depression Theory
  • Involves visual abnormalities, potential link to serotonin levels
  • Higher serotonin levels linked to vasoconstriction and auras

Treatment Strategies

Acute Therapy

• Targeting Inflammatory Molecules
  • NSAIDs for inflammation reduction
  • Tryptans for increasing serotonin concentration
  • Ergots as second-line treatment
  • Steroids for reducing inflammation

Prophylactic Therapy

• Beta Blockers
  • Propranolol and Metoprolol
  • Work by causing vasoconstriction
• Anticonvulsants
  • Topiramate and Valproate
  • Theory: Sodium channel blockers reducing neurotransmitter release
• CGRP Antagonists
  • Inhibit activation of nociceptors and vasodilation
• Botox Injections
  • Block pain sensations in the trigeminal nerve

Drug Mechanisms and Examples

• Tryptans
  • Sumatriptan and Zolmitriptan
  • Bind to 5-HT1B and 5-HT1D receptors
  • Inhibit peptide release and cause vasoconstriction
• Ergots
  • Dihydroergotamine
  • Bind to various 5-HT receptors and alpha-1 receptors
  • Cause vasoconstriction and may affect peripheral vessels

Adverse Effects and Contraindications

• Tryptans
  • Cause vasoconstriction, risk in patients with coronary artery disease
  • Contraindicated in pregnancy
  • Paresthesias and cold extremities
• Ergots
  • Similar risks as tryptans
  • Hepatotoxicity, paresthesias, nausea, vomiting
  • Risk of serotonin syndrome when combined with SSRIs or TCAs

Serotonin Syndrome

• Results from excess serotonin
• Symptoms: Agitation, delirium, hyperthermia, tachycardia, hyperreflexia
• Risk increased when combining tryptans with other serotonergic drugs

Ergot Toxicity

• Overdose can lead to convulsions and gangrenous necrosis
• Treatment includes anticoagulants and vasodilators

CGRP Antagonists

• Few side effects, mainly pain at injection site
• Risk of anaphylaxis

Conclusion

• Covered pathophysiology, acute/prophylactic therapy, mechanisms, adverse effects
• Importance of understanding migraine pharmacology

Keep this as a reference for understanding and treating migraines effectively.