Pharmacology Case 5 Headache PDF

PHARMACOLOGY: HEADACHE Dr. Adam Gratton NMT200 MSc ND November 20, 2023 LECTURE COMPETENCIES 1. Compare and contrast the mechanisms of action, indications, and adverse effects of drugs used for symptomatic treatment of headache A. Analgesics - ibuprofen, naproxen, acetaminophen...

PHARMACOLOGY: HEADACHE Dr. Adam Gratton NMT200 MSc ND November 20, 2023 LECTURE COMPETENCIES 1. Compare and contrast the mechanisms of action, indications, and adverse effects of drugs used for symptomatic treatment of headache A. Analgesics - ibuprofen, naproxen, acetaminophen B. Antiemetics - metoclopramide C. Ergot derivatives - dihydroergotamine D. Triptans - sumatriptan 2. Discuss indications, adverse effects, and drug interactions for drugs used for migraine prophylaxis A. Angiotensin II receptor antagonists - candesartan B. Antiepileptics – topiramate, divalproex, valproic acid, gabapentin C. Beta1-adrenergic antagonists - propranolol D. Calcitonin gene-related peptide monoclonal antibodies (CGRP) - erenumab E. Tricyclic antidepressants - amitriptyline LECTURE COMPETENCIES 3. Describe medication-overuse headache and the limitations for the number of days per month drugs can be used 4. Discuss treatment options for the pharmacological management of headaches during pregnancy and breastfeeding 5. Discuss treatment options for the pharmacological management of migraine headaches in children and adolescents 6. Prescribe appropriate medications for people with headache based on patient history INTRODUCTION The three most common headache disorders are tension-type headache, migraine, and medication-overuse headache There are a staggering number of other headache disorders Headaches are a common presenting concern in naturopathic practice and several red flags to be aware of Going to approach acute/abortive therapy separately from preventative/prophylactic therapy GOALS OF THERAPY Relieve or abolish pain and associated symptoms - Nausea and vomiting, for example Prevent recurrence Diagnose and manage serious causes of headaches - Tumour, arteritis, infection, etc. Prevent complications of medication usage Choose appropriate therapy that is safe with coexisting condition ACUTE/ABORTIVE THERAPY GOALS OF THERAPY - ACUTE Rapid and consistent freedom from pain and associated symptoms without recurrence (pain-free at 2 hours, headache relief at 2 hours, 24- hour sustained headache relief) Restored ability to function Minimal need for repeat dosing or rescue medications Optimal self-care and reduced subsequent use of resources (e.g., emergency room visits, diagnostic imaging, health-care provider and ambulatory infusion centre visits) Minimal or no adverse effects from medications ANTIEMETICS Antinauseants (like dimenhydrinate) and antiemetic agents (like metoclopramide) are useful adjunctive therapy when nausea and vomiting accompany headaches Use can also facilitate the absorption of medications in some patients The best evidence exists for metoclopramide ANALGESICS Consider ASA and NSAIDs (naproxen, ibuprofen, etc.) as first-line as they may have greater efficacy due to their anti-inflammatory properties over acetaminophen Many do not achieve adequate pain relief by relying exclusively on analgesics Opioid analgesic use of any sort is discouraged due to lack of evidence of superiority over NSAIDs, the potential for dependency, medication-induced headache, and withdrawal syndrome ADVERSE EFFECTS Depend on specific drug used Acetaminophen is generally better tolerated but may potentially cause hepatotoxicity with chronic use NSAIDs increase the risk of cardiovascular disease and mortality, especially with chronic use and may cause GI upset and ulceration ADVERSE EFFECTS NSAIDs and acetaminophen should be used less than 15 days/month to minimize the development of medication- overuse headache ERGOT DERIVATIVES Really only one option - Dihydroergotamine mesylate (DHE) Similar to a triptan but has an additional affinity for dopamine and adrenergic receptors Increases side effect potential Comes in an injectable or nasal spray formulation Can be used to treat medication-overuse headache if not currently being used ADVERSE EFFECTS Chest pain, tingling, nausea, vomiting, paresthesias, cramps and/or vasoconstriction occur infrequently and are of short duration May cause hypotension in rare instances ADVERSE EFFECTS Does not cause dependence, but can cause medication- overuse headache if used 10 days per month or more CONTRAINDICATIONS Pregnancy Cardiac disorders, hypertension, peripheral vascular disorders Sepsis Liver disease Peptic ulcer disease Renal disease TRIPTANS There are several options in this class Exemplar drug: Sumatriptan Need to be taken as early as possible during a migraine attack Different routes of administration available - Injection, nasal spray, oral disintegrating tablets/wafers, etc. SUMATRIPTAN The most effective of all triptans Subcutaneous injection has the fastest onset of action followed by nasal spray Second dose not likely to be effective if the first dose provided no relief TRIPTANS For migraines that build rapidly and/or are accompanied by early vomiting or present full-blown upon waking - Subcutaneous injection - Also has the greatest efficacy among all options Nausea and vomiting - Nasal spray Exacerbated with water - Orally disintegrating options ADVERSE EFFECTS Chest discomfort, fatigue, dizziness, paresthesias, drowsiness, nausea, throat symptoms Use less than 10 days/month to avoid medication- overuse headache CONTRAINDICATIONS All triptans are contraindicated in patients with cardiac disorders, sustained hypertension, basilar and hemiplegic migraine. Basilar migraines originate in the brainstem and usually have an aura with dizziness, double vision, lack of coordination prior to the onset of pain Hemiplegic migraines are rare and mimic strokes (one-sided weakness) CONTRAINDICATIONS Do not use with ergotamine-containing products Do not use a triptan within 24 hours after another triptan Caution with serotonergic medications (small increased risk of serotonin syndrome) Do not use with MAOIs. CALCITONIN GENE-RELATED PEPTIDE RECEPTOR ANTAGONISTS (CGRP -RA) New drug class Ubrogepant was approved by Health Canada in April 2023 Reserved for the treatment of acute migraine when other drug options have failed CGRP-RA CGRP is a vasodilatory neuropeptide involved in pain transmission and modulation pathways Plays a particular role in the pathogenesis and evolution of migraine-related pain ADVERSE EFFECTS Nausea, somnolence, dry mouth Suppression of CGRP may theoretically increase the risk of serious cardiovascular or cerebrovascular ischemic events Contraindicated with concomitant use of strong CYP3A4 inhibitors MEDICATION-OVERUSE HEADACHE Typically improves in weeks to months after discontinuation of medication May require tapering of offending agent(s) and starting a prophylactic therapy PREVENTATIVE/PROPHYLACTIC THERAPY GOALS OF THERAPY - PREVENTION Reduce attack frequency, severity, duration and disability Improve responsiveness to and avoid escalation in the use of acute treatment Improve function and reduce disability Reduce reliance on poorly tolerated, ineffective, or unwanted acute treatments Reduce overall cost associated with migraine treatment Enable patients to manage their own disease to enhance a sense of personal control Improve health-related quality of life Reduce headache-related distress and psychological symptoms, PROPHYLACTIC THERAPY Potentially useful when migraines have a significant impact on quality despite use of abortive therapy or if the frequency of attacks puts the patient at risk of medication overuse headache Wait 2 months before assessing benefit PROPHYLACTIC THERAPY Success is defined as 50% or more reduction in headache frequency or days with headache If not benefit after 2 months switch to another drug If benefit continue for 6-12 months before tapering to assess ongoing need Choice of drug depends on comorbidities and patient preference DRUG OPTIONS Beta blockers Propranolol, metoprolol and nadolol Most evidence exists for propranolol Adverse effects include fatigue, impotence, bradycardia and hypotension, GI symptoms, bronchospasm, heart failure, depression Contraindicated in asthma, insulin dependent-diabetes, or heart block DRUG OPTIONS TCAs Amitriptyline Best for tension-type headache Analgesic doses are lower than those used to treat affective disorders Contraindicated with significant cardiac disease, glaucoma, prostate disease, or hypotension DRUG OPTIONS Angiotensin receptor blockers Candesartan Efficacy in migraine prophylaxis may be due to blocking the direct vasoconstriction, increased sympathetic discharge, and/or adrenal medullary catecholamine release mediated by angiotensin II Lower risk of adverse effects, but can include hypotension, hyperkalemia, renal insufficiency, headache, dizziness DRUG OPTIONS Antiepileptics Includes the drugs valproic acid, divalproex sodium, topiramate, and gabapentin Valproic acid and divalproex sodium may work by modulating GABA receptors in the trigeminovascular system and are effective in migraine prophylaxis Adverse effects include nausea, alopecia, tremor, weight gain, and increased hepatic enzymes. DRUG OPTIONS Topiramate Adverse effects include CNS effects (e.g., dizziness, ataxia, tremor, sedation, cognitive impairment), GI symptoms (e.g., nausea, dyspepsia, constipation), weight loss (can be beneficial in some patients) May increase risk of nephrolithiasis Cognitive side effects if the dose is escalated too quickly DRUG OPTIONS Gabapentin Generally well tolerated. Sedation is the most common adverse effect and it may be helpful for comorbid insomnia Adverse effects include sedation, ataxia, tremor; less commonly, GI upset, peripheral edema, vision changes, weight gain, respiratory depression DRUG OPTIONS CGRP Monoclonal Antibodies Erenumab (there are others) Administered by monthly subcutaneous injection Associated with a 50% reduction in headache days compared to placebo First-line preventative agents must have failed before qualifying for use Adverse effects include injection site reactions, constipation, muscle spasms, pruritus, constipation, hypersensitivity reactions (may occur within minutes or more than 1 week after treatment), hypertension PREGNANCY/BREASTFEEDING The occurrence of migraine during pregnancy does not appear to increase the risk of preterm labour, low birth weight, or congenital abnormalities It may be associated with a higher risk of maternal complications such as gestational hypertension, pre-eclampsia. Preventive and acute headache medications should be discontinued prior to attempting to conceive PREGNANCY/BREASTFEEDING Acetaminophen can be used during pregnancy but is often not suitably beneficial For patients with frequency disabling headaches treatment may outweigh the risks All preventative medications have potential teratogenic effects PREGNANCY/BREASTFEEDING Lactation may have a positive effect on migraine activity and is encouraged Acetaminophen the preferred agent for acute treatment Ibuprofen is the NSAID of choice Sumatriptan is considered compatible with breastfeeding Metoclopramide is considered safe if needed adjunctively HEADACHE IN CHILDREN/ADOLESCENTS Intermittent oral analgesics given as early in the course of headache as feasible are the drug option of choice Ibuprofen has stronger evidence than acetaminophen Avoid using ASA in those under 15 years of age due to the risk of Reye’s syndrome HEADACHE IN CHILDREN/ADOLESCENTS Nausea and vomiting occurs more often than with adults (up to 90% of young migraine sufferers) Antiemetics alone can be effective for both nausea and migraine relief- metoclopramide Triptans can be used, but almotriptan is the only one approved by Health Canada for use in children aged 12 – 18 No triptans are approved for use in children under 12 HEADACHE IN CHILDREN/ADOLESCENTS Preventatively, only propranolol, topiramate, and amitriptyline demonstrate sufficient evidence for recommendation PREGNANCY/BREASTFEEDING Propranolol does not appreciably pass into breast milk Valproic acid, divalproex sodium, and topiramate are considered compatible CASE #1 38-year-old patient with a chief concern of frequent migraines Headache diary shows approximately 12 headache days per month with most occurring in the evening disrupting sleep Patient reports this has been going on for 8 months Current medications include PRN extra-strength ibuprofen (400 mg) 2 caplets every 4 – 6 hours when headaches occur CASE #1 CONSIDERATIONS Class discussion SAMPLE QUESTION Which of the following medications can be used prophylactically to prevent migraine occurrence? A. Sumatriptan B. Dihydroergotamine C. Gabapentin D. Ibuprofen