pharmacology of headache

Question 1

List drugs for abortive therapy of migraine

Answer 1

Dihydroergotamine, ergotamine, isometheptene, NSAIDs, tramadol, triptans

Question 2

List drugs for preventing migraine

Answer 2

b-blockers, anticonvulsants, antidepressants, calcium channel blockers, NSAIDs, 5-HT2 receptor antagonists

Question 3

List drugs for abortive therapy ofcluster headaches

Answer 3

DHE, ergotamine, glucocorticoids, lidocaine, oxygen, sumatriptan

Question 4

List drugs for preventing cluster headaches

Answer 4

Lithium, methysergide, and verapamil

Question 5

List drugs for abortive therapy of tension headaches

Answer 5

NSAIDs-Acetaminophen

Question 6

List drugs for preventing tension headaches

Answer 6

TCADs (amitriptyline) - SSRIs

Question 7

Which medications lead to overuse headaches

Answer 7

high risk [butalbital combinations, aspirin-acetaminophen-caffeine, opioids], moderate risk [triptans, ergots], low risk [NSAIDs]

Question 8

Two phases of migraine attacks

Answer 8

• First phase is characterized by cerebral vasoconstriction and ischemia. Serotonin release (5HT) from neurons and platelets (PERIPHERAL MECHANISMS) that acts on 5-HT2 receptors contributes to this phase.
• Second phase is characterized by cerebral vasodilation and pain. Neurons in the trigeminal complex release the vasoactive peptides substance P [SP] and calcitonin gene-related peptide [CGRP] that trigger vasodilation and neuroinflammation of pial and dural vessels (sensory nerve discharge). This in turn stimulates nociceptive fibers of the trigeminal nerve that causes pain• First phase is characterized by cerebral vasoconstriction and ischemia. Serotonin release (5HT) from neurons and platelets (PERIPHERAL MECHANISMS) that acts on 5-HT2 receptors contributes to this phase.
• Second phase is characterized by cerebral vasodilation and pain. Neurons in the trigeminal complex release the vasoactive peptides substance P [SP] and calcitonin gene-related peptide [CGRP] that trigger vasodilation and neuroinflammation of pial and dural vessels (sensory nerve discharge). This in turn stimulates nociceptive fibers of the trigeminal nerve that causes pain

Question 9

What is the initiating event of the first phase of a migraine

Answer 9

may be an abnormal discharge, set off by emotional or biochemical disturbances (CENTRAL MECHANISMS).

Question 10

Importance of drug route in migraine meds

Answer 10

Effect of oral meds can be delayed by migraine-related decrease in GI motility and / or nausea-vomiting (consider use of anti-emetics [metoclopramide]). Onset is fastest via parenteral route (SC > NASAL > PO).

Question 11

Use of NSAIDs/acetaminophen for migraine and MOA

Answer 11

mild to moderate episodes of migraine without nausea. Inhibit COX-2 which interrupts inflammatory pathway initiated by release of CGRP

Question 12

Triptans- use, examples and MOA

Answer 12

Used as first line agents for moderate to severe migraine. Sumatriptan, zolmitriptan. Agonist of 5HT 1B/1D receptors causing vasoconstriction (1D), inhibition of vasoactive peptides (1B)

Question 13

Triptans - absorption, distribution and duration

Answer 13

All available orally, sumatriptan and zolmatriptan available nasally, S given SC. Lipophilic, good brain penetration except for sumatriptan. Short half life

Question 14

Triptans- adverse drug reactions and drug-drug interactions

Answer 14

Pregnancy category C, may cause Paresthesias, flushing, dizziness, drowsiness, chest tightness and rarely coronary vasospasm, angina, MI, stroke, death. Additive vasoconstriction with ergot alkaloids. Increased risk of seretonin syndrome with MAOIs (clonus, ANS changes, mental status change)

Question 15

Examples of ergot alkaloids

Answer 15

Dihydroergotamine , ergotamine

Question 16

Ergot alkaloids MOA

Answer 16

5HT 1B/D Agonist (less effective than triptans). More toxic (not first line). Only used if no response to triptans.

Question 17

Ergot alkaloids routes, duration/onset

Answer 17

Ergotamine: Oral (increased absorption w/caffeine, otherwise poor availability) - sublingual - rectal; long duration

Dihydroergotamine: Intranasal-parenteral; rapid and reliable onset

Question 18

Ergot alkaloids adverse reactions and DDIs

Answer 18

Can cause vascular occlusion and gangrene (via a-1 adrenergic vasoconstriction). May cause severe peripheral ischemia if used with non selective beta blockers

Question 19

When is prophylactic treatment for migraines used

Answer 19

If severe, frequent (> 4/month), long lasting (> 12 h), or disabling

Question 20

List prophylactic drugs use for migraines, examples

Answer 20

migraine prophylaxis: 1. Beta blockers (propranolol, first line). 2. Ca channel blockers (Verapamil, third line). 3. ACEIs (lisinopril) or ARBs.are second or third line. 4. Antidepressants (amitripyline, second line). 5. anticonvulsants (valproate first line and topiramate). 6. Botox (second line agent) 7. NSAIDS (short term). 8. Methysergide (serotonin receptor antagonist- 5HT2 blocker blocks serotonin mediated vasoconstriction that initiates the attack)

Question 21

Dietary supplements used for migraine prophylaxis

Answer 21

riboflavin and feverfew