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PR3153 > IC5- Tx of migraine > Flashcards

IC5- Tx of migraine Flashcards

1
Q

What are the acute Tx goals? (6)

A
  • Rapid and consistent freedom from pain and associated symptoms, especially the most bothersome symptom, without recurrence
  • 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, clinician and ambulatory infusion center visits).
  • Minimal or no adverse events
  • Cost-effective treatment
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2
Q

How soon do we give medications for acute Tx of migraine?

Why? (can just read through)

A

As early as possible.

Effective acute treatment is associated with a significant beneficial response within 2 h from the time of administration, confers a sustained pain-free response over 24 h and reIduces disability quickly during attacks

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3
Q

Is stratified approach (guided by pain severity) or step by step approach (starting with mildest medication first) preferred for migraine Tx?

A

Stratified approach → better clinical outcomes & cost effective

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4
Q

If migraine pts also have n/v SSx, what type of migraine medications can you prescribe them?

A

Anti-emetics

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5
Q

How can we choose appropriate formulations and dosage forms for pts?

A
  • E.g. nausea exacerbated with drinking water > orally disintergrating tablet
  • E.g. severe nausea vomiting / fullblown symptoms at outstart > parenteral formulation
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6
Q

What are the different migraine-specific medications?

State the ones with established efficacy (4), and ones that are probably effective (2)

A

Established efficacy:
-triptans
- Ergotamine derivatives
- Gepants
- Lasmiditan

Probably effective:
- Ergotamine
- Other forms of dihydroergotamine

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7
Q

What are the different non-specific medications for migraine?

State the ones with established efficacy (2), and ones that are probably effective (4)

A

Established efficacy:
- NSAIDs: aspirin, celecoxib oral solution, diclofenac, ibuprofen, naproxen
- Combination analgesic: acetaminophen + aspirin + caffeine

Probably effective:
- NSAIDs: flurbiprofen, ketoprofen, IV/ IM ketorolac
- IV magnesium
- Isometheptene-containing compounds
- Antiemetics: chlorpromazine, droperidol, metoclopramide, prochlorperazine, promethazine

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8
Q

What type of migraine attacks are NSAIDs used for?

A

Mild-to-moderate migraine attacks

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9
Q

MOA of NSAIDs in migraine?

A

Inhibit PG synthesis → prevent neurogenically mediated inflammation in trigeminovascular system

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10
Q

ADEs of NSAIDs in migraine?

A
  • Hypersensitivity
  • GI (dyspepsia, n/v/d)
  • CNS: somnolence (drowsiness), dizziness
  • Upper GI effects
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11
Q

NSAIDs- use with caution in which type of patients? (4)

A
  • Hx of PUD
  • Renal disease
  • Severe CVD
  • Hypersensitivity to aspirin
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12
Q

Name some -triptans

A

Eletriptan, Sumatriptan, Zolmitriptan

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13
Q

MOA of triptans?

A

Selective agonist at 5-HT1B and 5-HT1D receptors:
- Vasoconstriction of intracranial extracerebral blood vessels
- Inhibition of vasoactive peptide release by trigeminal neurons
- Inhibition of nociception neurotransmission within trigeminocervical complex

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14
Q

What should we do if a pt does not respond to a triptan? Do we change to another medication class?

A

No. We try another triptan

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15
Q

What is something to note about recurrent migraines when taking triptans?

A

~20-50% of pts experience recurrent migraine within 48h of first dose of triptan → additional dose of triptan will be effective

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16
Q

What are some common SEs of triptans? (3)

A
  • Pressure sensation on chest
  • Nausea
  • Distal paraesthesia and fatigue
17
Q

What are some contraindications of triptans for migraines? (pre-existing conditions- 7; drug: 2)

A

Pre-existing conditions:
- Stroke/ TIA
- Ischemic coronary artery disease
- Coronary artery vasospasm
- Uncontrolled HTN
- Peripheral vascular disease
- GI ischaemia
- Hx of hemiplegic or basilar migraine

Drugs:
- Concomitant use of ergotamine-containing/ ergot-type medication (eg. dihydroergotamine) within 24 hours
- Concomitant administration of MAO-A inhibitors/ use within 2w of discontinuation of MAO-A inhibitor therapy

18
Q

MOA of ergotamine in Cafergot?

A
  • Agonist of 5-HT-1B/1D on intracranial vessels → induce vasoconstriction
  • Inhibit norepinephrine uptake and alpha-adrenoreceptors: leads to prolonged vasoconstriction
19
Q

MOA of caffeine in Cafergot?

A
  • Adenosine A1, A2A, and A2B receptors antagonist: vasoconstrict cerebral vasculature
  • May enhance GI absorption of ergotamine by ↑ solubility of ergotamine & decrease gastric pH
20
Q

Common SEs of Ergotamines & Dihydroergotamines? (4)

A
  • N/V
  • Cramps
  • Insomnia
  • Transient (temporary) lower limb muscle pain
21
Q

When do we use -gepants & -ditans for migraine Tx?

A

Either of the following:
- Contraindications to or inability to tolerate triptans
- Inadequate response to ≥ 2 oral triptans by: (1) validated acute Tx patient-reported outcome questionnaire, (2) clinician attestation

22
Q

What are some contraindications of Ergotamines & Dihydroergotamines for migraines? (pre-existing conditions- 7; drug: 2)

A

Pre-existing conditions:
- Stroke/ TIA
- Ischemic coronary artery disease
- Coronary artery vasospasm
- Uncontrolled HTN
- Peripheral vascular disease
- GI ischaemia
- Hx of hemiplegic or basilar migraine

Drugs:
- Concomitant use of triptans within 24h
- Potent CYP3A4 inhibitors (eg. protease inhibitors and macrolides)

23
Q

Should we use opioids for migraine Tx?

A

No

24
Q

What are the preventative Tx goals for migraine? (8)

A
  • Reduce attack frequency, severity, duration, and disability
  • Improve responsiveness to and avoid escalation in 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 (HRQoL).
  • Reduce headache-related distress and psychological symptoms.
25
Q

According to American Headache Society (AHS), what is the criteria for preventative migraine tx?

A
  • ≥ 3 MHDs + severe disability
  • ≥ 4 MHDs + some disability
  • ≥ 6 MHDs + no disability
26
Q

According to AHS, what is the criteria for preventative migraine tx?

A
  • Migraine impairs QoL + attacks cause disability on ≥ 2 days/ month + optimized acute Tx does not help
    OR
  • Migraine impairs QoL + risk of over-frequent use of acute Tx + pt willing to take daily medication
27
Q

What oral medications have established efficacy in migraine prevention? (8)

A
  • Candesartan
  • Divalproex sodium
  • Frovatriptan
  • Metoprolol
  • Propranolol
  • Timolol
  • Topiramate
  • Valproate Sodium
28
Q

What are some parenteral medications for migraine prevention? (4 of them are CGRPs)

A

CGRPs:
- Eptinezumab
- Erenumab
- Fremanezumab
- Galcanezumab

Others:
- Onabotulinumtoxin A

29
Q

What are the 3 different types of anti-CGRP therapies for migraine?

What are their MOAs?

A
  1. Gepants – CGRP receptor antagonists, which bind to the CGRP receptor and prevent signalling.
  2. Anti-CGRP antibodies, which prevent CGRP interacting with its receptor.
  3. Anti-CGRP receptor antibodies, which bind to the CGRP receptor and prevent signalling.
30
Q

What is the issue with CGRP blockade?

A
  • Not completely sure of the SEs (not well studied)
  • Not sure of risks associated with the long-term use of CGRP blockers
  • Endogenous CGRP has multiple protective roles
31
Q

State the main principles of preventive Tx of migraine

A
  1. Start low and titrate
  2. Reaching a therapeutic dose
  3. Giving an adequate trial
  4. Establish realistic expectations
  5. Optimize drug selection and maximise adherence
32
Q

Elaborate on the principle of preventive treatment ‘Start low and titrate’

A
  • Start at a low dose and titrate slowly until the target response / maximum or target dose reached/ tolerability issues emerge
  • When there is a partial but suboptimal response or dose-limiting AEs, combining preventive drugs from different drug classes may be useful
33
Q

Elaborate on the principle of preventive treatment ‘Reaching a therapeutic dose’

A
  • With oral treatments, an initial target dose should be set (e.g., topiramate 100 mg) and patients advised to stop the titration if the maximal dose is reached, when efficacy is optimal, or when AEs become intolerable
34
Q

Elaborate on the principle of preventive treatment ‘Giving an adequate trial’

What is the minimum duration for trial?

A

– Oral treatments: minimum of 8 weeks at a target therapeutic dose before lack of effectiveness can be determined
– If there is no response to treatment after at least 8 weeks - switching preventive treatments is recommended.
– Partial response: cumulative benefits may occur over 6–12 months of continued use.
– Injectable CGRP mAbs: at least 3 months of treatment for those administered monthly and at least 6 months after the start of quarterly treatments
– Clinicians and patients should reassess the benefits of mAbs and continue treatment only if benefits have been achieved

35
Q

Elaborate on the principle of preventive treatment ‘Establish realistic expectations’ (i.e. name some markers for treatment success) (6)

A
  • 50% reduction in the frequency of days with headache or migraine.
  • Significant decrease in attack duration as defined by patient.
  • Significant decrease in attack severity as defined by patient.
  • Improved response to acute treatment.
  • Reduction in migraine-related disability and improvements in functioning in important areas of life.
  • Improvements in HRQoL and reduction in psychological distress due to migraine
36
Q

Elaborate on the principle of preventive treatment ‘Optimize drug selection & maximize adherence’ (12)

Don’t need to memorise everything, but generally know some of them

A

Factors to consider:
- Tolerability
- Headache subtype (episodic/ chronic)
- Concomitant medications
- Body habitus
- Ease of use
- Contraindications/ allergies
- Patient preference
- Co-morbs
- Physiological factors (HR, BP)
- Pregnancy/ potential for pregnancy (women)
- Response to prev Tx
- Cost

37
Q

How should we assess treatment efficacy?

A
  1. Headache diary
  2. Disability assessment (e.g. MIDAS)
  3. Adverse effect from medications

PR3153 (11 decks)

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