Pharmacology - Migraine Drugs (IC4) Flashcards
Cafergot MOA
Cafergot - contains caffeine + ergotamine
- Stimulates alpha-adrenergic and 5-HT receptors (esp 5HT1B, 5HT1D on vascular smooth muscles), thereby vasoconstricting the vascular smooth muscles in the external carotid network
- This prevents release of neuropeptides, and inflammatory mediators
Cafergot SEs
- Nausea, vomiting
- Hypersensitivity
- Myocardial infarct
- Ergotism (vascular ischemia)
Cafergot DDI
Cafergot - CYP3A4 substrate
- Usage with other CYP3A4 inhibitors such as macrolides can elevate exposure to ergot toxicity (vasospasm, tissue ischemia)
U2D: Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of ergotamine/caffeine with potent CYP 3A4 inhibitors including protease inhibitors and macrolide antibiotics. Because CYP3A4 inhibition elevates the serum levels of ergotamine/caffeine, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased. Hence, concomitant use of these medications is contraindicated.
Cafergot Special Precautions with its use
- DO NOT use within 24h of other vasoconstrictor agents (ergot alkaloids, triptans, other 5HT1 agonists)
Sumatriptan MOA
Selective vascular serotonin (5HT1B, 5HT1D) receptor agonist
- Vasoconstriction of cerebral blood vessels
- Vascular mechanism: selective constricts the carotid arterial circulation (dura and meningeal blood vessels) but does not alter cerebral blood flow
- Inhibition of vasoactive peptide release by trigeminal neurons
- Central mechanism: inhibit release of neuropeptides (e.g., CGRP) by trigeminal nerves innervating the intracranial vessels and dura mater, thereby inhibiting trigeminal nerve activity
- Inhibition of nociception
- Trigeminovasuclar mechanism: inhibits trigeminal nerve activation, thereby inhibiting nociceptive neurotransmission
Sumatriptan SEs
Common side effects:
- Feeling sleepy, dizzy, tired
- Flushing, tingling sensation
- Transient increase in BP, hypertension
- Pressure or tightness in chest/jaw/neck/throat
- Muscle weakness
- Sore throat
- Dysgeusia (unpleasant taste) - intranasal
- N/V/D
- Vertigo
- Dizziness, drowsiness
Serious side effects
- Serotonin syndrome - hyperreflexia, hyperthermia, pricking sensation, fever, sweating, tremors, N/V/D
- Mental status change (SS) - agitation, hallucinations
- Autonomic instability (SS) - tachycardia, labile BP, hyperthermia
- Neuromuscular changes (SS) - rigid or twitching muscles
- GI
- Seizures (lower seizure threshold)
- Arrhythmias
- Prolonged QT, TdP
- AMI
- Cerebrovascular events
- Incr BP - hypertensive crisis
Sumatriptan DDIs
Sumatriptan is metabolized by monoamine oxidase A (MAO)
- DDI with MAO inhibitors - may increase plasma Sumatriptan levels, result in toxicities (ischemia due to vasoconstriction)
- Additionally, Serotonin 5-HT1D Receptor Agonists (Triptans) may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome.
- Contraindication: concurrent or within 2 weeks of discontinuation of MAOi type A
Serotonin syndrome may arise from concurrent use of Sumatriptan w MAOi, SSRI, SNRI, TCAs
E.g., MAOi: isocarboxazid; SSRI: fluoxetine, SNRI (venlafaxine), TCA (amitriptyline)
Sumatriptan CIs
- Hypersensitivity
- Concurrent administration of MAOi
- Myocardial infarct
- Uncontrolled HTN
- Ischemic heart disease
- Prinzmetal’s angina/coronary vasospasm
- Peripheral vascular disease
- History of previous cerebrovascular accident
- TIA
- Severe hepatic impairment
Caution in pt with seizures
Sumatriptan Special Precautions with its use
- DO NOT use within 24h of other vasoconstrictor agents (ergotamine derivatives, other 5HT1 agonists)
Can Sumatriptan be used in pregnancy and lactation?
Pregnancy
- not teratogenic
- may increase rate of preterm birth
- use with caution
Lactation
- SubQ excreted into breastmilk, avoid breastfeeding for 12h after treatment
Sumatriptan use in older population
- initiate at lower end of dosing range
- perform CV evaluation prior to initiation of therapy in older adults with CV risk factors + periodic CV evaluation during intermittent long term use
Does Sumatriptan require renal or hepatic dose adjustment?
Renal: NIL
Hepatic:
- mild-mod: max dose 50mg (oral tablet)
- severe: CI
Sumatriptan safety monitoring
- BP
- S&S of serotonin syndrome (mental status change, autonomic instability, neuromuscular change)
- S&S of angina, CV evaluation
- GI symptoms
- Seizures
Can Sumatriptan tablets be crushed?
No
Erenumab MOA
Erenumab is a CGRP inhibitor (anti-CGRP receptor antibody)
- CGRP is a nociceptive neuropeptide at the trigeminal ganglion that transmits pain sensation
- CGRP is also a potent vasodilator
Therefore, inhibition of CGRP causes: reduced pain transmission, less vasodilation of cerebral blood vessels, less neurogenic inflammation
