Migraine Medications Flashcards
1
Q
Migraine Treatment
Overview
A
- Older agents that abort an attack work primarily by ⊗ release of peptides and neurotransmitters at indicated sites
- Newer agents antagonize actions of peptides such as CGRP
- Prophylactic agents may work by preventing cortical spreading
2
Q
Migraine
Acute Therapy
A
- NSAIDS ⇒ acetaminophen, naproxen, diclofenac, ibuprofen
-
Combination analgesics
- Excedrin–Migraine ⇒ acetaminophen/aspirin/caffeine
- Triptans ⇒ sumatriptan, rizatriptan, zolmitriptan, naratriptan
- Ergots ⇒ ergotamine and dihydroergotamine
- Antipsychotics ⇒ metoclopramide, prochlorperazine
3
Q
Triptans
Mechanism of Action
A
⊗ release of vasoactive peptides from perivascular trigeminal neurons by acting on presynaptic 5-HT1B/D receptors
- Bind presynaptic receptors in the brain stem ⇒ ⊗ release of neurotransmitters that activate second-order neurons ascending to the thalamus
- Originally thought to provide relief by causing cranial vasoconstriction
- 5-HT1B/D receptors on smooth muscle cells
4
Q
Triptans
Pharmacokinetics
A
- Most effective when given early in the attack
-
Sumatriptan available as tablet, nasal spray, subQ injection
- Peak plasma levels achieved most rapidly w/ SC and least rapidly w/ PO
- Relieves 85% of attacks and is slightly superior to DHE
- Most other agents are oral
- Zolmitriptan comes in a nasal spray
- Newer agents are more lipophilic ⇒ higher oral bioavailability
- 10-20% greater efficacy than sumatriptan and rates of headache recurrence are lower
5
Q
Triptans
Adverse Effects
A
- Nausea
- Dizziness
- Paresthesias
- Somnolence
- Chest tightness
- Excessive dosing can cause cerebral vasoconstriction and rebound headache
6
Q
Triptans
Drug Interactions
A
Should not be used w/ MAO inhibitors ⇒ serotonin syndrome
Should not be used within 24 hours of an ergot ⇒ ↑ vasoconstriction
7
Q
Dihydroergotamine
Mechanism of Action
A
- Ergots are structurally similar to D-lysergic acid
- 5-HT1D agonist > 5-HT2 A/B/C agonist, dopamine and NE α receptor agonist
- Considered broad spectrum or “dirty” triptan
- MOA in migraine similar to triptans
8
Q
Dihydroergotamine
Pharmacokinetics
A
- Most effective when given early in the attack
- Available in parental (SC, IM, IV), intranasal preparations, and rectal formulations (ergotamine/caffeine)
- Injections usually more rapid acting
- Rectal formulations for pts w/ nausea, but stimulation of dopamine receptors may cause nausea
- Parental admin w/ metoclopramide (Reglan) to prevent vomiting
- Some oral and rectal preparations contain caffeine ⇒ ± ↑ absorption
9
Q
Dihydroergotamine
Adverse Effects
A
- Some similarities to the triptans: nausea, dizziness, paresthesias
- Also vomiting, diarrhea, muscle cramps, cold skin
- Cause vasoconstriction through α receptors as well as 5-HT receptors
- Similar contraindications to the triptans ⇒ coronary artery disease and peripheral vascular disease
- Excessive dosing can cause cerebral vasoconstriction and rebound headache
10
Q
Dihydroergotamine
Drug Interactions
A
- Should not be used w/ β-blockers because α-adrenergic vasoconstriction unopposed by β2 vasodilation can cause peripheral ischemia
-
Cytochrome p450 interaction w/ protease inhibitors and macrolide abx
- Combination may cause excessive vasoconstriction
11
Q
Acute Migraine Treatment
Summary
A
- Triptans less toxic and slightly more effective than ergots
- Dihydroergotamine w/ longer duration of action (intranasal preparations)
- Use reasonable restrictions on drug use to prevent toxicity and habituation
- First try NSAIDS, then if they are ineffective try triptans or DHE
- Some pts may go straight to the triptans
12
Q
Migraine Prophylaxis
Indications
A
- Attacks that significantly interfere w/ daily routine despite appropriate acute treatment
- Failure of, contraindication to, or adverse effects from acute medications
- More than two headaches per week
- Patient request
- Hemiplegic migraine
13
Q
Migraine
Prophylactic Therapy
A
- Antibodies to CGRP receptor (erenumab) or CGRP (coming out soon)
- Cardiac medications ⇒ β-blockers, calcium channel blockers, candesartan
- Antidepressants ⇒ TCAs, SSRIs
- Anti-seizure medications
- Serotonin receptor antagonist ⇒ cyproheptadine (Periactin)
- Botox injections
14
Q
Erenumab
A
- Ab vs CGRP receptor
- First drug designed specifically for migraine prophylaxis
- Once-a-month subQ injection w/ minimal adverse effects
- Approved for both episodic (less than 15 a month) and chronic headache (more than 15 a month)
- Initial studies indicated it ↓ episodic headaches day by 2-4 a month, and chronic headache days by 6-8 month
15
Q
Beta Blockers
Migraine Prophylaxis
A
- Only propranolol and timolol are FDA approved for migraine prophylaxis
- MOA in migraine not known
- Indications: migraineurs w/ HTN and/or angina, migraineurs w/ performance anxiety or aggressive behavior
- Contraindications: Asthma or pulmonary disease, significant depression
- Common adverse effects: fatigue, exercise intolerance, cold extremities, diarrhea, constipation, dizziness, worsening of depression
