Exam 3 - Migraines L30

Question 1

Classes of drugs used for abortive therapy

Answer 1

1) Serotonin receptor agonists
2) Ergot alkaloids
3) Dopamine Receptor antagonists
4) Calcitonin gene-related peptide receptor antagonists
5) Analgesics

Question 2

Classes of drugs used for prophylactic therapy

Answer 2

1) beta-blockers
2) antidepressants
3) anticonvulsant drugs
4) calcitonin gene-related peptide ligand inhibitor
5) botulinum toxin type a
6) calcium channel blockers

Question 3

Migraine background information

Answer 3

-about 44.5 million Americans suffer from migraines
-more women than men
-genetically linked
-costs American economy due to lost productiveness and healthcare costs

Question 4

what are the GI aspects of migraines?

Answer 4

-decreased GI motility and nausea/vomiting symptoms slow the oral absorption of drugs during a migraine
-parental routes of administration should be used

Question 5

Due to the high variability of individual response to migraine drugs…

Answer 5

therapeutic strategies must be customized to each patient

Question 6

what are the phases of a migraine?

Answer 6

1) prodrome
2) aura
3) headache
4) postdrome

Question 7

describe the prodrome phase

Answer 7

-present in less than 60% of patients
- changes in mood and appetite (cravings) that occur hours to days before migraine

Question 8

describe the aura phase

Answer 8

-aura classified as visual disturbances (fortification spectrum)
-occurs in less than 25% of people
-migraine without aura called common migraine
-migraine with aura called classic migraine

Question 9

describe the headache phase

Answer 9

-progression from dull ache to intense pulsations
-accompanied by GI symptoms (nausea and vomiting)
-photophobia and phonophobia sometimes present
-lasts 4-72 hours

Question 10

describe postdrome phase

Answer 10

characteristics of this phase differ among all people with migraines

Question 11

what are some other less common types of migraines?

Answer 11

-menstrual migraine
-tension type headache (not as bad as migraine, less symptoms)
-cluster headaches (very rare, intense pain, more common in males)

Question 12

what are the proposed mechanisms of migrains

Answer 12

-vascular theory
-spreading depression
-serotonergic abnormalities
-p/q calcium channel mutations

Question 13

describe the vascular theory

Answer 13

aura is caused by vasoconstriction of vessels, and pain is caused by the vasodilation

Question 14

describe the spreading depression theory

Answer 14

migraines caused by the spreading decrease in cortical electrical activity

Question 15

describe the serotonergic abnormalities mechanism

Answer 15

-mechanism not known, however it is known that IV injection of serotonin can abort a spontaneous or drug induced migraine
-some drugs work at serotonin receptors

Question 16

what are rebound headaches?

Answer 16

-migraines that are actually caused by increase use of drugs meant to treat migraines
-to avoid, abortive therapy drugs should only be used 2 times a week
-botox is only medication that can relieve these

Question 17

what are the analgesics drugs used in migraine treatment

Answer 17

-NSAIDS (aspirin, acetamenophen, ibuprofen)
-opiates (butorphanol)

Question 18

describe NSAID use in migraine treatment

Answer 18

-over the counter
-efficacy not clearly established
-mechanism of action appears to be related to blocking of prostaglandin synthesis and preventing inflammation
-use with caution in patients with renal problems and ulcers

Question 19

which symptoms is acetaminophen very effective in treating?

Answer 19

photophobia and phonophobia

Question 20

describe opiates in migraine treatment

Answer 20

-not often used, high abuse potential
-many adverse affects

Question 21

describe ergot alkaloids

Answer 21

-naturally occurring compounds found in grains contaminated by fungus
-historically the drug of choice for treatment
-oral, sublingual, suppository dosage form
-half life is 2 hours, but duration of action (vasoconstriction) is 24 hours
-sometimes mixed with caffeine or other alkaloids to avoid side effects

Question 22

what are the pharmacodynamics of ergot alkaloids

Answer 22

-activation of 5-HT1b receptors cause vasoconstriction
-activation of 5-HT1d reduces inflammation by decreasing release of substance P, neurokinin A, CGRP

Question 23

contraindications of ergot alkaloids

Answer 23

-cant be used in pregnant women or patients with peripheral vascular disease
-vasoconstriction can be potentiated by beta blockers in patients taking ergot alkaloids

Question 24

ergot alkaloid adverse reactions

Answer 24

-upsetting GI symptoms
-occurs in 10% of patients due to activation of dopamine receptors in chemoreceptor trigger zone
-may require adjunct therapy with antiemetic (10mg oral metoclopramide)

Question 25

ergot alkaloid prototype

Answer 25

-dihydroergotamine (DHE 45) -administered parenterally or via nasal spray

Question 26

chemistry and pharmacokinetics of triptans

Answer 26

-subcutaneous injection, oral tablets, nasal spray/powder or transdermal patch -metabolized by MAO-A, contraindicated with use of MAO inhibitor within 2 week time span -can be administered up to 4 hrs after onset of headache and still be effective

Question 27

Triptan drugs

Answer 27

-first line drugs used for migraines -sumatriptan (1st gen, 1b/1d agonist) -zolmitriptan (2nd gen 1b/1d)

Question 28

sumatriptan

Answer 28

-triptan drug -can be subcutaneous injection, oral tablet, nasal spray/powder, transdermal patch -type 1 serotonin receptor agonist (similar to to ergot alkaloid) -relieves nausea/vomiting and photo/phonophobia

Question 29

toxicity and adverse reactions of triptans

Answer 29

-adverse cardiovascular symptoms -several fatalities reported due to subcutaneous injection of triptans resulting in MIs -do NOT give IV -Do not give within 24 hours of ergot alkaloid

Question 30

describe 2nd gen triptans

Answer 30

-act at the peripheral components of the trigeminovascular symptoms (like 1st gen) -greater lipid solubility leads to them acting centrally to inhibit pain transmission in trigeminal nucleus -better oral absorption

Question 31

describe dopamine receptor antagonists

Answer 31

-metoclopramide, prochlorperazine, and chlorpromazine -useful when triptans, DHE, and analgesics don't work -given by IV in emergency departments -relieve headaches and have anti-emetic activity

Question 32

when to consider prophylactic drug therapy

Answer 32

-when patients don't respond to acute therapies and have more than 3 migraines a week -need to be tried for 2-3 months before being considered ineffective -should only use for 3-6 months then stop

Question 33

beta blockers

Answer 33

-propanolol, metoprolol, timolol -prophylactic drugs -mechanism of action not clear (serotonin related?) -b-blockers with intrinsic sympathomimetic activity not effective

Question 34

antidepressants

Answer 34

-amitriptyline -prophylactic drug -mechanism of action unknown, but independent from antidepressant action -sedation and anticholinergic side effects present

Question 35

anticonvulsants

Answer 35

-topiramate -prophylactic drugs -mechanism of action unknown, perhaps GABA transmission? -topiramate has some side effects (paresthesia, fatigue, anorexia/nausea, diarrhea, weight loss, cognitive problems)

Question 36

CGPR ligand inhibitors

Answer 36

-prophylactic drugs -rimegepant is also used for acute treatment -mab suffix denotes human monoclonal antibodies -modest effects shown in clinical trials

Question 37

botulinum toxin A

Answer 37

-prophylactic drug -also used for cosmetics -only medication for rebound headaches -anti migraine effect can last for up to 3 months

Question 38

calcium channel blockers

Answer 38

-prophylactic drugs -less effective than other drugs, last resort

Question 39

migraines in children

Answer 39

-shorter duration of pain (30 min) -1st step is to eliminate possible food triggers