Neurology PDF - ACCP Updates in Therapeutics 2023

Neurology c. Clopidogrel (Plavix) i. Inhibits adenosine diphosphate–induced platelet aggregation ii. Dose: 75 mg/day orally iii. Very low incidence of neutropenia (0.04% severe) iv. Rarely, thrombotic thrombocytopenic purpura has been reported. v. Partly metabolized by C...

Neurology c. Clopidogrel (Plavix) i. Inhibits adenosine diphosphate–induced platelet aggregation ii. Dose: 75 mg/day orally iii. Very low incidence of neutropenia (0.04% severe) iv. Rarely, thrombotic thrombocytopenic purpura has been reported. v. Partly metabolized by CYP2C19; interactions may occur with inhibitors of CYP2C19, notably proton pump inhibitors, or with genetic polymorphisms of this enzyme. The FDA has issued an alert on this topic (www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformation forPatientsandProviders/DrugSafetyInformationforHealthcareProfessionals/ucm190787.htm). d. Cilostazol (Pletal) i.  Inhibits cyclic adenosine monophosphate phosphodiesterase type 3–induced platelet aggregation ii. Dose: 100 mg orally twice daily on an empty stomach iii. Metabolized extensively by CYP3A4 and CYP2C19 iv. Adverse effects: Headache, palpitation, diarrhea, and dizziness; rarely, thrombocytopenia or agranulocytosis v. Contraindicated in patients with congestive heart failure vi. Monitoring: CBC with differential every 2 weeks for 3 months; periodically thereafter. Thus, used infrequently 5. A nticoagulation: Warfarin (Athrombin-K, Coumadin, Jantoven, Panwarfin) or direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, edoxaban) a. Prevention of second ischemic event, if patient has atrial fibrillation (warfarin or direct oral anticoagulants), rheumatic mitral valve disease (warfarin), mechanical prosthetic heart valves (warfarin), bioprosthetic heart valves (warfarin), or left ventricular mural thrombus formation (warfarin) b. Target INR: 2–3 for nonvalvular atrial fibrillation; 2.5–3.5 for mechanical prosthetic heart valves Patient Cases Questions 11–15 pertain to the following case. L.R. is a 78-year-old woman who presents to the ED for symptoms of right-sided paralysis. She states these symptoms began about 6 hours ago and have not improved. She also has hypertension, breast cancer, diabetes, minimal cognitive impairment, and osteoarthritis. L.R. is diagnosed with a minor stroke by the neurology team. 11. Which is the most accurate list of L.R.’s risk factors for stroke? A. Breast cancer, age, osteoarthritis. B. Sex, diabetes, osteoarthritis. C. Minimal cognitive impairment, diabetes, age, sex. D. Age, diabetes, hypertension. 12. Which best describes whether L.R. is a candidate for tissue plasminogen activator (Alteplase) for the treatment of stroke? A. Yes. B. No, because of advanced age. C. No, her stroke symptoms began too long ago. D. No, her breast cancer is a contraindication for tissue plasminogen activator. ACCP Updates in Therapeutics® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 1-507 Neurology Patient Cases (Cont’d) 13. L.R. previously took no home medications. Which is the best treatment at this time for her? A. Metformin and aspirin. B. Celecoxib and clopidogrel. C. Aspirin and clopidogrel. D. Warfarin. 14. L  .R. presents to her community pharmacy to pick up her medication refills (lisinopril, aspirin, clopidogrel, atorvastatin) 2 months after her discharge from the hospital. Which best assesses her dual antiplatelet therapy (DAPT)? A. Appropriate, continue for 90 days after stroke. B. Appropriate, continue as chronic therapy. C. Inappropriate, single antiplatelet therapy should be initiated for 90 days. D. Inappropriate, single antiplatelet therapy should be initiated indefinitely. 15. L.S. is a 42-year-old woman with a medical history of hypertension, type 2 diabetes, renal failure, and mitral valve replacement. She presents to the anticoagulation clinic for her initial visit. Which best reflects her target INR? A. 1.5. B. 2.0. C. 2.5. D. 3.0. III. PARKINSON DISEASE A. Epidemiology 1. Prevalence is 1 million in the United States. 2. Onset is usually at 40–70 years of age, with peak onset in the sixth decade. 3. Slightly more common in men 4. Observed in all countries, ethnic groups, and socioeconomic classes B. Signs and Symptoms 1. Cardinal signs a. Akinesia or hypokinesia b. Rigidity c. Tremor d. Posture or gait abnormalities 2. Secondary signs a. Cognitive dysfunction b. Autonomic dysfunction c. Speech disturbances d. Micrographia e. Masked facies ACCP Updates in Therapeutics® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 1-508 Neurology C. Treatment 1. General treatment principles a. No treatment has unequivocally been shown to prevent the progression of Parkinson disease; therefore, treatment is based on symptoms. b. In patients who need the initiation of dopaminergic treatment, either levodopa or a dopamine agonist may be used. Choice depends on the relative impact of improving motor disability (better with levodopa) compared with the lessening of motor complications (better with dopamine agonists) for each patient. c. Treatment may be initiated with rasagiline as well, but the effects are not robust. d. Treatment with several different classes of medications simultaneously is common. e. General framework for Parkinson symptoms and treatments i. Tremor (a) Carbidopa/levodopa (b) Dopamine agonists (c) Anticholinergics ii. Bradykinesia (a) Carbidopa/levodopa (b) Dopamine agonists iii. Rigidity (a) Carbidopa/levodopa (b) Dopamine agonists iv. Gait disturbances: No treatment at this time 2. Medications a. Monoamine oxidase type B (MAO-B) inhibitors i. Inhibition of MAO-B allows more dopamine to be available in the brain, thus helping with Parkinson disease movement symptoms. ii. Selegiline (Eldepryl, Zelapar) (a) Loses selectivity for MAO-B at doses greater than 10 mg/day (b) Contraindicated with meperidine because of serotonin syndrome risk (c) Do not administer with tramadol, methadone, dextromethorphan, sympathomimetics, fluoxetine, or fluvoxamine because of serotonin syndrome risk. (d) Dose: 5 mg orally twice daily (tablets; usually morning and noon); 1.25–2.5 mg/day (orally disintegrating tablets) (e) Adverse effects: Nausea, hallucinations, orthostatic hypotension, insomnia (metabolized to amphetamine) (f) Dosage forms: Tablets, orally dissolving tablets, and patches. The patches are FDA indicated for depression; they should not usually be used for Parkinson disease. iii. Rasagiline (Azilect) (a) Selectivity for MAO-B has not been definitively established. (1) Contraindicated with meperidine because of serotonin syndrome risk (2) Do not administer with tramadol, methadone, dextromethorphan, sympathomimetics, fluoxetine, or fluvoxamine because of serotonin syndrome risk. (3) Ciprofloxacin can double the concentration of rasagiline (through CYP1A2 inhibition). (b) Dose: 0.5–1 mg/day orally iv. Safinamide (Xadago) (a) Highly selective MAO-B inhibitor (b) Dose: 50–100 mg daily (c) Reduce dose in hepatic failure (Child-Pugh class C). (d) Adverse effects and drug interactions similar to other MAO-B inhibitors ACCP Updates in Therapeutics® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 1-509 Neurology b. Istradefylline (Nourianz) i. Adenosine receptor antagonist ii. Adjunct to carbidopa/levodopa iii. Treats off-episodes iv. Dose: 20 mg daily; may increase to maximum of 40 mg daily v. Those who smoke tobacco (20 or more cigarettes/day) have decreased systemic exposure and thus require a higher dose of istradefylline (40 mg once daily). vi. Adverse effects: Dyskinesia, dizziness, constipation, nausea, hallucinations, insomnia vii. Drug interactions: CYP3A4 substrate; avoid use with CYP3A4 inducers; maximum dose is 20 mg daily with CYP3A4 inhibitors c. Levodopa inhalation powder (Inbrija) i. Treats off-episodes ii. Dose: 2 capsules (84 mg) inhaled as needed, up to five times daily iii. Adverse effects: Cough, nausea, discolored sputum d. Carbidopa i. Combined in fixed ratios with levodopa ii. Prevents some of the peripheral conversion of levodopa to dopamine by inhibiting peripheral dopamine decarboxylase; therefore, levodopa is available to cross the blood-brain barrier iii. 75 mg/day is usually needed to inhibit peripheral decarboxylase activity. e. Carbidopa/levodopa (Parcopa, Sinemet, Duopa, Rytary) i. Pharmacokinetic considerations (a) High-protein diets and iron supplements decrease absorption. (b) Immediate-release half-life 60–90 minutes (c) Orally disintegrating tablet available; not absorbed sublingually (d) Slow-release considerations: Fewer daily doses; less plasma fluctuations; delay to effect; cannot crush; can divide. No measurable effect on “freezing.” Freezing is typically described as the sudden inability to move for several seconds to minutes. Freezing can also affect speech or repetitive fine-motor skills, but usually only affects certain parts of the body. In an off-episode/period, the patient can not move at all. ii. Acute adverse effects: Nausea and vomiting, orthostatic hypotension, cardiac arrhythmias, confusion, agitation, hallucinations, peak-dose dyskinesia iii.  Long-term adverse effects: Wearing-off and on-off phenomena, involuntary movements (dyskinesias) (a) Wearing-off phenomenon is the return of Parkinson disease symptoms before the next dose. Treatment of wearing-off includes adding a dopamine agonist, adding a MAO-B inhibitor, adding a catechol-O-methyltransferase (COMT) inhibitor, or increasing the frequency or dose of levodopa. (b) On-off phenomenon is a profound, unpredictable return of Parkinson disease symptoms without respect to the dosing interval. Treatment of on-off includes adding entacapone, rasagiline, pramipexole, ropinirole, apomorphine, or selegiline or redistributing dietary protein. (c) Dyskinesias are drug-induced involuntary movements, including chorea and dystonia. Treatment of dyskinesias includes decreasing the levodopa dose or adding amantadine as an antidyskinetic drug. iv. Therapy initiation (a) Standard formulation: 25 mg/100 mg 1 tablet orally three times daily; also available as orally disintegrating tablet (b) Controlled-release formulation: 1 tablet orally two or three times daily ACCP Updates in Therapeutics® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 1-510 Neurology (c)  Titration is always necessary. (d) A combination of formulations may be needed (e.g., ½ tablet of Sinemet 25 mg/100 mg on awakening and 1 tablet of Sinemet CR 25/100 three times daily). v. Levodopa may improve disability and mortality. vi. Greatest benefit for rigidity and bradykinesia, less benefit for tremor and postural instability f. Direct dopamine agonists i. Drugs: Apomorphine (Apokyn), bromocriptine (Parlodel), pramipexole (Mirapex), ropinirole (Requip), rotigotine (Neupro) ii. Bromocriptine is an ergot-derived product: Very rarely, adverse effects such as retroperitoneal, pleuropulmonary, or cardiac fibrosis have been attributed to it; regular ECG monitoring is recommended. iii. Rotigotine is a transdermal system. With the initial formulation, problems occurred with crystallization of the medication. The product was withdrawn from the market and has since been reformulated. Rotigotine is currently available. iv. Dosing: Always titrate to final dose (Table 6). Table 6. Usual Dosage Range for Dopamine Agonists Agent Bromocriptine Pramipexole Ropinirole Rotigotine Usual Dosage Range (mg/day) 5–40 1.5–4.5 0.75–24 6–8 v. Adverse effects: Nausea, vomiting, postural hypotension, hallucinations, impulsive behaviors (e.g., hypersexuality, gambling, shopping, eating), falling asleep during activities of daily living vi. Pramipexole and ropinirole also have FDA indications for restless legs syndrome. vii. Ropinirole and pramipexole are available as extended-release formulations. viii. Apomorphine: Short-acting dopamine receptor agonist (a)  Indication: Acute, intermittent treatment of off-episodes associated with advanced Parkinson disease (b) Contraindications: Use with 5-hydroxytryptamine-3 antagonists (ondansetron, granisetron, dolasetron, palonosetron, and alosetron) causes profound hypotension, sulfite sensitivity, or allergy. (c) Pharmacokinetics: When administered orally, poorly bioavailable and extensive first-pass metabolism; used as subcutaneous injection in a pen self-injector (d) Adverse effects (1) Severe nausea and vomiting (A) Treat with trimethobenzamide 300 mg three times daily for 3 days before initiating treatment and for at least 6 weeks during treatment. (B) About 50% of patients can discontinue trimethobenzamide after 2 months. (C)  Thirty-one percent of patients had nausea and 11% had vomiting with trimethobenzamide. (2) Hypotension (3) Hallucinations (4) Injection site reactions (5) Dyskinesias ACCP Updates in Therapeutics® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 1-511 Neurology (e) Dosing (1) Must be titrated in a setting where blood pressure can be monitored (2) In the “off” state, the patient should be administered a 0.2-mL (2 mg) test dose. (3) Supine and standing blood pressure taken before dose; 20, 40, and 60 minutes after dose (4) If tolerated, begin with a 0.2-mL dose as needed; increase by 0.1 mL, if necessary. (5) Doses greater than 0.6 mL, more than five times daily, or greater than 20 mg/day have limited experience. (6) If first dose is ineffective, do not re-dose. (7) If patients do not dose for more than 1 week, reinitiate at a 0.2-mL dose. g. Anticholinergics i. Drugs: Trihexyphenidyl (Artane), benztropine (Cogentin) ii. Useful only for tremor iii. Initial dosing (a) Trihexyphenidyl 0.5 mg 1 tablet orally twice daily (b) Benztropine 0.5 mg 1 tablet orally twice daily iv. Adverse effects: Dry mouth, urinary retention, dry eyes, constipation, confusion h. Amantadine (Symmetrel) i. Has symptomatic benefits and may reduce dyskinesias caused by levodopa or dopamine agonists ii. Dosing: 100 mg 1 tablet orally two or three times daily; caution in renal dysfunction iii. Adverse effects: Dizziness, insomnia, anxiety, livedo reticularis, nausea, nightmares i. COMT inhibitors i. Prevent breakdown of dopamine, more levodopa available to cross blood-brain barrier ii. Tolcapone (Tasmar): Severely restricted because of hepatotoxicity; must sign consent form iii. Entacapone (Comtan) (a) Increased AUC, increased half-life; no change in Cmax or Tmax of levodopa (b) Dosing: 1 tablet with each carbidopa/levodopa dose; maximum of eight times daily; one dosage form (Stalevo) includes carbidopa, levodopa, and entacapone 200 mg (c) Must use with carbidopa/levodopa (d) Adverse effects: Dyskinesias, nausea, diarrhea (may be delayed for up to 2 weeks after initiation or dose increase), urine discoloration (orange), hallucinations or vivid dreams iv. Opicapone (Ongentys) (a) Dosing: 50 mg daily at bedtime (b) Take doses 1 hour before or after eating. (c) Reduce dose by 50% with moderate hepatic failure. Avoid use in severe hepatic failure. 3. Surgery: Several types of surgery are done for Parkinson disease. a. Thalamotomy: Ablation of portions of the thalamus to control tremor b. Pallidotomy: Ablation of structures in the globus pallidus for the treatment of Parkinson disease c. Fetal transplants: Transplantation of dopaminergic tissue into the striatum; considered experimental d. Trophic factors: Glial-derived nerve growth factor and neurturin have been delivered directly to the striatum or substantia nigra; considered experimental e. Deep brain stimulation i. Most common surgery for Parkinson disease ii. Thought to stimulate areas of the basal ganglia to reversibly block the neuronal activity in the area iii. Patient selection focuses on patients with: (a) Motor fluctuations or dyskinesias that are inadequately controlled with optimized medical therapy (b)  Medication-refractory tremor (c)  Intolerance of medical therapy (d) Some centers will not do the surgery in patients older than 70. ACCP Updates in Therapeutics® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 1-512 Neurology iv. Two areas are targeted. (a)  Globus pallidum (1) Reduces off-time (2) Reduces dyskinesias (3) Thought to have fewer cognitive adverse effects than subthalamic nucleus stimulation (b) Subthalamic nucleus (1) Reduces off-time (2) Reduces dyskinesias (3) Thought to be more effective than globus pallidum stimulation 4. Special situations a. Hallucinations or psychosis may be caused by either Parkinson disease or treatment. i. Discontinue or reduce Parkinson disease medications as tolerated. Reduce antiparkinson medications to minimum the therapeutic dose or discontinue. Start with anticholinergics; then use MAO-B inhibitors, amantadine, dopamine agonists, COMT inhibitors; finally, use carbidopa/ levodopa ii. Pimavanserin (Nuplazid): FDA approved for Parkinson disease psychotic disorder iii. If an antipsychotic is needed, use quetiapine or clozapine as the first choice. iv. Avoid typical antipsychotics, risperidone, and olanzapine because they may worsen motor features associated with Parkinson disease. b. Cognitive disorders i. Discontinue or reduce Parkinson disease medications as tolerated. ii. Rivastigmine (Exelon) has an FDA indication for treatment; other cholinesterase inhibitors may have efficacy. iii. Memantine lacks data to recommend it for cognitive disorders associated with Parkinson disease. c. Sleep disorders, depression, agitation, anxiety, constipation, orthostatic hypotension, seborrhea, blepharitis, and restless legs syndrome can occur in Parkinson disease; treat as usual. Patient Cases Questions 16 and 17 pertain to the following case. L.T. takes carbidopa/levodopa 25 mg/100 mg orally four times daily and trihexyphenidyl 2 mg orally three times daily for Parkinson disease. L.T.’s wife reports that his movements are very slow and that he is having trouble walking. 16. Given these symptoms, which change seems most reasonable? A. Increase carbidopa/levodopa, discontinue trihexyphenidyl. B. Continue carbidopa/levodopa, increase trihexyphenidyl. C. Decrease carbidopa/levodopa, continue trihexyphenidyl. D. Decrease carbidopa/levodopa, increase trihexyphenidyl. 17. Six months later, L.T. returns to the clinic concerned that his carbidopa/levodopa dose is wearing off before his next dose is due, because his tremor and slow movements are worse before the next dose of carbidopa/ levodopa. Which recommendation is best? A. Increase the carbidopa/levodopa dose. B. Decrease the carbidopa/levodopa dose. C. Increase the dosing interval. D. Decrease the dosing interval. ACCP Updates in Therapeutics® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 1-513 Neurology Patient Cases (Cont’d) 18. P.J. is a 57-year-old man with an 8-year history of Parkinson disease. His current medications include carbidopa/levodopa 50 mg/200 mg orally four times daily, entacapone 200 mg orally four times daily, and amantadine 100 mg three times daily. He presents to the clinic with concerns of reddish orange urine. He fears he has blood in his urine. Which most likely caused this condition? A. Carbidopa/levodopa. B. Entacapone. C. Amantadine. D. Hemorrhagic cystitis. 19. L.L. is a 47-year-old man with Parkinson disease. He takes carbidopa/levodopa 50 mg/200 mg orally four times daily. His wife states that he cannot sit still during the day. He is constantly moving, and she fears his disease is worsening. Which is the best therapy for L.L.? A. Add ropinirole. B. Add selegiline. C. Increase the carbidopa/levodopa dose. D. Decrease the carbidopa/levodopa dose. 20. C.A. is a 70-year-old man with tremors in his right hand that have progressively worsened for the past 6 months. He has difficulty walking. He also has backaches and no longer plays golf. In addition, he is losing his sense of taste. His wife notes that he is moving more slowly and that his handwriting has deteriorated. He is diagnosed with Parkinson disease. Which is the best treatment for C.A.? A. Trihexyphenidyl. B. Apomorphine. C. Carbidopa/levodopa. D. Istradefylline. IV. HEADACHE A. Definitions 1. Migraine with aura: At least two attacks with at least three of the following: One or more fully reversible aura symptoms, at least one aura symptom for more than 4 minutes, or two or more symptoms occurring in succession; no single aura symptom lasts more than 60 minutes; headache follows aura within 60 minutes 2. Migraine without aura: At least five attacks of headache lasting 4–72 hours with at least two of the following: Unilateral location, pulsating quality, intensity moderate or severe, aggravation by walking stairs or similar routine physical activity. During headache, at least one of the following: Nausea or vomiting, photophobia, phonophobia 3. Status migrainosus: Attack of migraine, with headache phase lasting more than 72 hours despite treatment. Headache-free intervals of less than 4 hours (sleep not included) may occur. 4. Tension: At least 10 previous headaches, each lasting from 30 minutes to 7 days, with at least two of the following: Pressing or tightening (nonpulsating) quality, intensity mild to moderate, bilateral location, no aggravation with physical activity ACCP Updates in Therapeutics® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 1-514 Neurology 5. Cluster: Several episodes, short-lived but severe, of unilateral, orbital, supraorbital, or temporal pain. At least one of the following must occur: conjunctival injection, lacrimation, nasal congestion, rhinorrhea, facial sweating, miosis, ptosis, or eyelid edema. 6. Medication overuse headache: If patients use analgesics often (usually defined as more than three times weekly), they may develop medication overuse headache. Patients with this condition usually present with a chronic daily headache, for which they take simple or narcotic analgesics. Treatment consists of the withdrawal of all analgesics (but not prophylactic medications). B. Epidemiology 1. Migraine: 15%–17% of women, 5% of men 2. Tension: 88% of women, 69% of men 3. Cluster: 0.01%–1.5% of population; ratio of men to women is 6:1 C. Treatment 1. Migraine a. Prophylaxis should be considered if any of the following criteria are met: Migraines are recurrent and interfere with daily routine, migraines are frequent, patient has inefficacy with or inability to use acute therapy, patient prefers prophylaxis as therapy, cost of acute medications is problematic, adverse effects or contraindications with acute therapies occur, or migraine presentation is uncommon i. General principles (a) Use lowest effective dose. (b) Give adequate trial (2–3 months). (c) If the patient has a coexisting condition, consider prophylaxis choice (e.g., β-blockers are contraindicated in patients with asthma but beneficial in patients with hypertension). ii. Medications with established efficacy for migraine prevention (a) Atogepant (b) Candesartan (c) Eptinezumab (d) Erenumab-aooe (e) Fremanezumab-vfrm (f) Frovatriptan (for menstrually associated migraine, short-term prophylaxis only) (g) Galcanezumab-gnlm (h) Metoprolol (i) OnabotulinumtoxinA (j) Propranolol (k) Rimegepant (l) Timolol (m) Topiramate (n) Valproate iii. Medications with probable efficacy (a) Amitriptyline (b) Atenolol (c) Ibuprofen (d) Ketoprofen (e) Lisinopril (f) Magnesium (recommend magnesium citrate for better absorption) (g) Memantine ACCP Updates in Therapeutics® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 1-515 Neurology (h) Nadolol (i) Naproxen/naproxen sodium (j) Naratriptan (for menstrually associated migraine, short-term prophylaxis only) (k) Venlafaxine (l) Zolmitriptan (for menstrually associated migraine, short-term prophylaxis only) iv. Calcitonin gene-related peptide antagonists are highly effective in refractory migraine headache prophylaxis. (a) Parenteral options: (1) Erenumab-aooe (Aimovig): Dose: 70–140 mg subcutaneously monthly (2) Fremanezumab-vfrm (Ajovy): Dose: 225 mg subcutaneously monthly or 675 mg subcutaneously quarterly (administered as three separate injections) (3) Galcanezumab-gnlm (Emgality): Dose: Two consecutive doses of 120 mg subcutaneously for a total of a 240-mg loading dose, followed by doses of 120 mg subcutaneously monthly (4) Eptinezumab (Vyepti): Dose: 100 mg intravenously every 3 months. Adverse effects with parenteral calcitonin gene-related peptide antagonists: Injection site reactions; severe constipation (erenumab only) (b) Oral options: (1) Atogepant (Qulipta): Dose 10 mg, 30 mg, or 60 mg orally once daily (2) Rimegepant (Nurtec ODT): Dose 75 mg orally every other day b. Acute treatment i. Triptans (Table 7) (a)  Sumatriptan and zolmitriptan have nonoral administration routes (subcutaneous [sumatriptan], intranasal [sumatriptan and zolmitriptan]) that should be considered for patients with nausea or vomiting. (b) Orally disintegrating tablets are available for zolmitriptan and rizatriptan if patients do not have access to water; however, they do not work faster than oral tablets and are not absorbed sublingually. (c) All are contraindicated in patients with or at risk of coronary artery disease, stroke, uncontrolled hypertension, peripheral vascular disease, ischemic bowel disease, and pregnancy (sumatriptan and rizatriptan may be considered in pregnancy); they should not be used in patients with hemiplegic or basilar migraines. (d) Drug interactions: Contraindicated within 2 weeks of MAO inhibitors; do not use within 24 hours of ergotamines; caution with other serotonin-active medications. Propranolol increases serum concentrations of rizatriptan; thus, a maximum 5-mg dose should be used with propranolol, and the dose should not exceed 15 mg/day. ii. Ergots (a) Dihydroergotamine has nonoral administration routes (subcutaneous, intravenous, and intranasal) that can be considered for patients with nausea or vomiting. (b) All are contraindicated in patients with, or at risk of, coronary artery disease, stroke, uncontrolled hypertension, peripheral vascular disease, ischemic bowel disease, and pregnancy; they should not be used in patients with hemiplegic or basilar migraines. iii. Lasmiditan (Reyvow) (a) Mechanism of action: Serotonin-1F receptor agonist (b) Dose: 50–200 mg at start of headache, may only take one dose per 24 hours (c) Adverse effects: Dizziness, fatigue, paresthesia, sedation (d) Avoid driving for at least 8 hours after dose. (e)  Controlled substance: Schedule V ACCP Updates in Therapeutics® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 1-516 Neurology iv. Ubrogepant (Ubrelvy) (a) Mechanism of action: Calcitonin gene-related peptide receptor antagonist (b) Dose: 50–100 mg at start of headache, may repeat once after 2 hours (c)  Adverse effects: Nausea, somnolence (d) Drug interactions: Avoid use with strong CYP3A4 inducers. Dose adjustments may be needed with moderate or weak CYP3A4 inhibitors or inducers and/or P-glycoprotein (P-gp) inhibitors. v. Rimegepant (Nurtec) (a) Mechanism of action: Calcitonin gene-related peptide receptor antagonist (b) Dose: 75 mg at start of headache; should not exceed 15 doses in 30 days (c)  Adverse effects: Nausea (d) Drug interactions: Avoid use with strong CYP3A4 inhibitors, strong or moderate inducers, or P-gp and breast cancer resistance protein (BCRP) inhibitors; with moderate CYP3A4 inhibitors, avoid a second dose within 48 hours. vi. NSAIDs: Usually effective for only mild to moderate headache pain vii. Opioids: Butorphanol has a nonoral administration route (intranasal) that may be considered for patients with nausea or vomiting. viii. Isometheptene combination products: Conflicting evidence about efficacy ix. Antiemetics: Prochlorperazine, metoclopramide, and chlorpromazine are most commonly used; they may have independent antimigraine action; all are available in nonoral forms. Often used in combination with acute migraine treatments to reduce nausea and vomiting 2. Status migrainosus treatments a. Corticosteroids: Either intravenous or oral dosing b. Dihydroergotamine: Intravenous dosing c. Sodium valproate: Intravenous loading d. NSAIDs: Ketorolac intravenous dosing 3. Tension a. Prophylaxis i. Tricyclic antidepressants ii. Botulinum toxin b. Acute treatment i. Simple analgesics (alone or with caffeine) and NSAIDs: Acetaminophen, aspirin, ibuprofen, naproxen, ketoprofen, and ketorolac ii. Used for mild to moderate tension-type headache iii. Do not use more than 2 days/week to prevent the development of chronic tension-type headache. iv. Failure of OTC agents warrants prescription therapy or analgesics with caffeine with: (a) High-dose NSAIDs, combinations with aspirin or acetaminophen with butalbital (b) Acetaminophen 250 mg/aspirin 250 mg/caffeine 65 mg (c) Acetaminophen 500 mg/caffeine 65 mg v. No evidence to support muscle relaxant use 4. Cluster a. Prophylaxis i. Verapamil ii. Melatonin iii. Suboccipital injection of betamethasone iv. Lithium: May be efficacious at serum concentrations as low as 0.3 mmol/L v. Warfarin ACCP Updates in Therapeutics® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 1-517 Neurology vi. Galcanezumab-gnlm (Emgality): Two consecutive doses of 120 mg subcutaneously for a total of a 240-mg loading dose, followed by doses of 120 mg subcutaneously monthly vii. Corticosteroids (a) Consider in patients for whom all other preventive agents for cluster headache have failed. (b) Prednisone 40–60 mg/day, tapered over 3 weeks (c) Relief in 1 or 2 days b. Acute treatment i. Oxygen: 100% oxygen at 6–12 L/minute relieves pain in 50%–85% of patients. ii. Subcutaneous and intranasal routes are safe and effective. (a) Sumatriptan is available as subcutaneous and intranasal routes. (b) Zolmitriptan is available as intranasal route. iii. Subcutaneous route is the most effective. iv. Intranasal route is less effective but is better tolerated. v. Oral route has limited use because of relatively slow onset of action. vi. Intranasal lidocaine: 20–60 mg as a nasal drop or spray (must be compounded) vii. Octreotide and 10% cocaine have been used with some effect. viii. Dihydroergotamine intravenously/intramuscularly/subcutaneously: 1 mg as a single dose; maximum 2 mg/day and 6 mg/week Table 7. Selected Agents for Acute Treatment of Migraine Headache Triptans Almotriptan (Axert) Eletriptan (Relpax) Frovatriptan (Frova) Naratriptan (Amerge) Rizatriptan (Maxalt) Sumatriptan (Alsuma, Imitrex, Sumavel, Zecuity) Zolmitriptan (Zomig) Dose Maximal Dose/ 24 Hr (mg) Dosage Forms Tmax HalfLife (hr) Tablets 6.25 mg, 12.5 mg Tablets 20 mg, 40 mg Tablets 2.5 mg Tablets 1 mg, 2.5 mg Tablets 5 mg, 10 mg Orally disintegrating tablets 5 mg, 10 mg SC injection 4 mg, 6 mg Intranasal 5 mg, 20 mg 1–3 hr 1 hr 2–4 hr 2–3 hr 1–1.5 hr 1.6–2.5 hr 2–4 4–5 26 6 1.8 1.8 1 tablet, may repeat in 2 hr 1 tablet, may repeat in 2 hr 1 tablet, may repeat in 2 hr 1 tablet, may repeat in 4 hr 1 tablet, may repeat in 2 hr 1 tablet, may repeat in 2 hr 25 80 7.5 5 30 30 12 min 30 min 1.9 2 12 40 Tablets 25 mg, 50 mg, 100 mg Tablets 2.5 mg, 5 mg Orally disintegrating tablets 2.5 mg, 5 mg Intranasal 2.5 mg, 5 mg 2 hr 2.5 1 injection, may repeat in 1 hr 1 spray in one nostril, may repeat in 2 hr 1 tablet, may repeat in 2 hr 1.5 hr 3 hr 3.75 3.75 1 tablet, may repeat in 2 hr 1 tablet, may repeat in 2 hr 10 10 3 hr 3 1 spray in one nostril, may repeat in 2 hr 10 2/19 1 tablet, may repeat in 2 hr 170/1000 11 1 tablet, may be taken in 24 hr 75 5–7 1 tablet, may repeat in 2 hr 200 Triptan/NSAID combination Sumatriptan/naproxen Tablets 85 mg/500 mg 1 hr/5 hr sodium (Treximet) Calcitonin gene-related peptide antagonist (CGRP) Rimegepant (Nurtec Orally disintegrating 1.5 hr ODT) tablets 75 mg Ubrogepant (Ubrelvy) Tablets 50 mg, 100 mg 1.5 hr 200 ACCP Updates in Therapeutics® 2023: The Pharmacotherapy Preparatory Review and Recertification Course 1-518