Headache Medications PDF Spring 2025 - Augsburg University

Headache Medications PA 522 PHA RMACOTHERAPY SPRING 2025 MARAH C ZA JA , PA- C Session Objectives 1. Review the characteristics, pathophysiology, and general approach to the treatment of headaches based on type and severity (Table 25.1 and 25.2). 2. Summarize the Key Prescribing Considerations f...

Headache Medications PA 522 PHA RMACOTHERAPY SPRING 2025 MARAH C ZA JA , PA- C Session Objectives 1. Review the characteristics, pathophysiology, and general approach to the treatment of headaches based on type and severity (Table 25.1 and 25.2). 2. Summarize the Key Prescribing Considerations for Serotonin Receptor Agonists (Triptans) and Ergot Alkaloids. 3. Discuss the indications and drug classes used in preventive migraine therapy. 4. Differentiate between the presentation and treatment of migraines versus cluster headaches (both acute and prophylaxis). 5. Provide patient education for a person experiencing medication overuse headache. Session Objectives For each medication class listed in the “PA522_Medication Table_Spring 2025” know the representative drug names, mechanism of action, indications/therapeutic uses, adverse effects (ADRs), contraindications/cautions, major interactions (drugs or food), lab monitoring/follow-up, patient education, and formulations available. o NSAID, Triptan, Ergot, Beta-Blocker, antiepileptic, TCS, Hormone, CGRP Inhibitors Memorize the initial dosing for the following representative drugs: ◦ Sumatriptan, propranolol, aspirin  Types of Headaches Migraine Cluster Tension Headache Recurrent severe, unilateral headaches Recurrent moderate to severe headaches often waking patients from sleep. Usually episodic, can become chronic if History associated with aura in some cases. Associated with autonomic symptoms. daily. Triggered by specific factors in some cases. History of episodic pattern. May have neurological signs during attacks. May have ipsilateral autonomic symptoms Photophobia, phonophobia, nausea, such as rhinorrhea, lacrimation, ptosis, Exam Findings vomiting, and aura (visual, sensory) in some miosis. Restlessness and agitation are Typically normal exam findings. cases. common. Abortive Triptans, NSAIDs, antiemetics. High-flow oxygen therapy, sumatriptan NSAIDs, acetaminophen, muscle relaxants, Treatments nasal spray, intranasal lidocaine. biofeedback, cognitive-behavioral therapy. Tricyclic antidepressants, selective serotonin Preventive Beta-blockers, antiepileptic drugs, Verapamil, lithium carbonate, prednisone, reuptake inhibitors, botulinum toxin Treatments antidepressants, CGRP inhibitors. topiramate. injections, stress management techniques. Migraine Neurovascular disorder that involves dilation and inflammation of intracranial blood vessels. Headache generation begins with neural events that trigger vasodilation. Vasodilation then leads to pain, which leads to further neural activation, thereby amplifying pain-generating signals. Neurons of the trigeminal vascular system, which innervate intracranial blood vessels, are key components. Precipitating factors include ◦ anxiety, fatigue, stress, menstruation, alcohol, weather changes, and tyramine- containing foods. 70% have migraine without aura  Theory: Cortical Spreading Depression (CSD) Neurophysiological correlation of migraine aura Slow waves of neuronal and glial depolarization Massive increases in both extracellular K+ and glutamate Rises in intracellular Na+ and Ca2+ Triggers activation of trigeminal system and release of “calcitonin gene-related peptide” -> vasodilation Patrick J. Linch, medical illustrator and C. Carl Jeffe, MD, cardiologist.  Opioids (butorphanol Triptans nasal spray) Ergot NSAIDS Abortive Alkaloids Migraine Treatment Beta- Antiepileptics Preventive blockers CGRP Tricyclic receptor Antidepressants antagonists Abortive Therapy Pearls Limit use to 1 or 2 days a week, to avoid medication overuse headache (MOH) Antiemetics indicated for use in migraine: metoclopramide (Reglan) and prochlorperazine Abortive Migraine Treatments: NSAIDS Acetaminophen can be used but with another drug… why? NSAID Class, Indications and Adverse Effects Abortive Treatments: Aspirin MOA: ASA blocks cyclooxygenase (COX), the enzyme that converts arachidonic acid into prostaglandins At sites of tissue injury, COX catalyzes the synthesis of prostaglandins, which promote inflammation and sensitize receptors to painful stimuli. In the brain, COX-derived prostaglandins Used in combination with metocloperamide, it is just as effective and less expensive than sumatriptan (Imitrex)  Abortive Treatment: Serotonin Receptor Agonists (Triptans and Ergot Alkaloids) 1. Plasma levels of 5-HT drop by 50% during a migraine attack. 2. Administration of 5-HT or a triptan can abort an ongoing attack. Triptans are FIRST LINE for ABORTIVE Treatment  Triptans: MOA and Pharmaco-kinetics MOA: analog of 5-HT, causes selective activation of 5-HT1B and 5-HT1D receptors (5-HT1B/1D receptors). ◦ Binds to 5-HT1B/1D receptors ◦ on intracranial blood vessels causing vasoconstriction. ◦ on sensory nerves of the trigeminal vascular system suppresses the release of CGRP Onset: ◦ 15 minutes after subQ or intranasal dosing (complete relief in 2hrs) ◦ 97% bioavailability ◦ 30 to 60 minutes after PO (complete relief after 4hrs) ◦ 15% bioavailability ◦ Headache returns in about 40% of patients within 24 hours. Metabolism: In the liver (MAO), excreted in urine. The half- life is about 2.5 hours. Also approved for cluster headaches. Triptans: Adverse Effects About 50 have unpleasant chest symptoms (Not Dangerous) ◦ “heavy arms” or “chest pressure” rather than pain. ◦ transient and not related to ischemic heart disease. ◦ ?Due to pulmonary vasoconstriction, esophageal spasm, intercostal muscle spasm, and bronchoconstriction. BUT… Coronary Vasospasm: ◦ Avoid with risk factors for CAD until CAD has been ruled out. ◦ (Postmenopausal women, men older than 40 years, smokers, and patients with hypertension, hypercholesterolemia, diabetes, or a family history of CAD). ◦ Contraindicated for patients with a history of ischemic heart disease, myocardial infarction (MI), uncontrolled hypertension, or other heart disease. Avoid during pregnancy. Triptans: Drug Interactions Ergots and other triptans- vasoconstriction, don’t take within 24hrs of each other MAOs: hepatic breakdown suppressed = increased levels SSRI/SNRIs: serotonin syndrome  Ergot Alkaloids: Ergotamine MOA and Pharmaco-kinetics MOA: alters transmission at serotonergic, dopaminergic, and α- adrenergic junctions; blocks inflammation associated with the trigeminal vascular system (block release of CGRP) Bioavailability with rectal administration is higher than oral. ◦ half-life of 2 hours, pharmacologic effects can still last 24 hours Metabolism by CYP3A4 and excreted in the bile. Ergot Alkaloids: Ergotamine Adverse Effects stimulate the chemoreceptor trigger zone, causing nausea and vomiting in about 10% of patients, ◦ metoclopramide or prochlorperazine can help. Others: weakness in the legs, myalgia, numbness and tingling in the fingers and toes, angina-like pain, and tachycardia or bradycardia. Serious toxicity referred to as ergotism. Overdose can cause ischemia secondary to constriction of peripheral arteries and arterioles: ◦ the extremities become cold, pale, and numb; ◦ muscle pain develops; ◦ Gangrene, sepsis… Avoid in vascular disease and renal or hepatic impairment. Ergot Alkaloids: Ergotamine Problems, Drug Interactions, Cautions Not with Triptans (serotonin syndrome) Physical dependence Contraindications: hepatic or renal impairment, sepsis (gangrene has resulted), CAD, peripheral vascular disease, and uncontrolled hypertension, and for those taking potent inhibitors of CYP3A4. Should not be taken during pregnancy because it can promote uterine contractions and hence might cause fetal harm or abortion. Dihydro-ergotamine (2 -line) nd Parenteral dihydroergotamine (D.H.E. 45, Migranal) intramuscular (IM), intravenous (IV), intranasal, or subQ route MOA: similar to ergotamine but causes little nausea and vomiting, no physical dependence, and minimal peripheral vasoconstriction (when used alone). diarrhea is prominent. Pharmacokinetics: Extensive first-pass and metabolized by CYP3A4 in the liver. The half-life plus the active metabolite is about 21 hours. ◦ The 24-hour recurrence rate with dihydroergotamine is only 14%. Preventive Migraine Therapy 1. Reduces the frequency, intensity, and duration of migraine attacks 2. Improve response to abortive drugs 3. Indicated for three or more migraines a month, if attacks are severe, or do not respond adequately to abortive agents 4. Preferred drugs take 2 to 6 weeks to work: 1. propranolol, divalproex, and amitriptyline. First-line Prevention: β blockers Propranolol most commonly used ◦ Metoprolol just as effective ◦ Timolol, atenolol, and nadolol also used 70% see a reduction in the number and intensity of attacks  Antiepileptics divalproex (Depakote ER) –form of valproate/valproic acid reduces the incidence of attacks by 50% in 30% to 50% of patients. BUT intensity and duration are not diminished. Side effects: fatigue, weight gain, tremor, bone loss, and reversible hair loss. BLACK BOX: Potentially fatal pancreatitis and hepatitis can occur. In addition, divalproex can cause neural tube defects in the developing fetus, and hence is contraindicated during pregnancy. topiramate (Topamax) Reduced migraine frequency by at least 50% in 83% of adolescents and about 50% of adults. Side effects: paresthesias, fatigue, and psychomotor slowing, word-finding difficulty, and impairment of concentration and memory, metabolic acidosis and moderate weight loss (owing to anorexia, nausea, and diarrhea). Costly +/- proof for Gabapentin (Neurontin) and tiagabine (Gabitril) although appear promising and are used Tricyclic Anti-depressants Can work for both migraine and tension type HA through theorized inhibition of serotonin reuptake Amitriptyline most commonly used Side effects: hypotension and anticholinergic effects (dry mouth, constipation, urinary retention, blurred vision, tachycardia). Excessive doses can cause dysrhythmias. Menstrually Associated Migraine Migraine that routinely occurs within 2 days of the onset of menses. MOA: Triggered by decline in estrogen levels that precede menstruation. Treatment Approaches: ◦ Topical estrogen preparations—estrogen gel and estrogen patches (e.g., Divigel, Climara) ◦ Perimenstrual frovatriptan, naratriptan, and zolmitriptan can reduce the frequency, intensity, and duration ◦ Dose for 6 days each month, beginning 2 days before the expected onset of menses. ◦ Naproxen sodium 550 mg twice daily, given 6 days before to 7 days after menses Calcitonin Gene-Related Peptide Receptor Antagonists Human immunoglobulin G2 monoclonal antibody binds to and antagonizes the function of the CGRP receptors ◦ Rimegepant (Nurtec ODT) ◦ Ubrogepant (Ubrelvy) Administered once monthly, the half-life is long—about 28 days. Side Effects: Constipation and muscle cramping and risk of antibody formation to the treatment. Botulinum Toxin Multiple injections into muscles of the scalp, neck, and upper back. Expensive On average, patients experience about two fewer headache days a month. Lasts 6-12 weeks  Cluster Headaches 15 minutes to 2 hours and is characterized by severe, throbbing, unilateral pain in the orbital- temporal area (i.e., near the eye). ◦ A typical cluster consists of one or two attacks every day for 2 to 3 months then a break of months to years between. ◦ Associated symptoms: lacrimation, conjunctival redness, nasal congestion, rhinorrhea, ptosis, and miosis on the same side as the headache. ◦ NO aura, NO nausea and vomiting, More debilitating, Less common, M:F 5 : 1 ratio, NO family history component  Cluster Headache Prophylaxis Suboccipital steroid injections (prednisone and dexamethasone) Lithium is considered a second-line drug for prophylaxis. https://headachejournal.onlinelibrary.wiley.com/doi/epdf/10.1111/head.12866 Cluster Headache Abortive Treatment Sumatriptan (6 mg subQ) is the treatment of choice for cluster headaches. Inhaling 100% oxygen (7 to 10 L/min for 15 to 20 minutes) is also highly effective and has virtually no adverse effects. ◦ Who has readily available oxygen?  Medication Overuse Headaches Cause: frequent use of headache medicines (too much, too often) ◦ analgesics (aspirin-like drugs, opioids), triptans, ergotamine (but not dihydroergotamine), and caffeine. Takes days to weeks after the overused drug is withdrawn to go away ◦ Triptans & ergots take ~2 days to resolve ◦ Analgesics (aspirin-like drugs, opioids), take ~2 weeks to resolve Patient Education ◦ take abortive drugs no more than 2 or 3 times a week ◦ Alternate headache medicines ◦ Prophylactic therapy if more than two or three headaches a month ◦ Nondrug measures—stress reduction, avoidance of triggers, getting sufficient sleep, relaxation techniques, and biofeedback—