Neuropharmacology - Anti-migraine

Question 1

What is the MOA of cafergot?

Answer 1

Tonic action on vascular smooth muscles in the external carotid network. Leads to vasoconstriction by stimulating alpha-adrenergic and 5-HT receptors (esp 5-HT1b and 5-HT1d)

Question 2

What is the indication for cafergot

Answer 2

For acute treatment of migraine (given at first symptom of attack)

Question 3

What are the pharmacokinetic attributes of cafergot?

Answer 3

→ PO (and also PR)
→ Rapidly absorbed – max plasma conc reached in 1.5-2h
→ High plasma protein binding, low absolute bioavailability

Question 4

What DDIs does cafergot have?

Answer 4

• Inhibits liver CYP3A - should not use w other CYP3A inhibitors (eg macrolide antibiotics) due to inc exposure to ergot toxicity
• Should not be used w other vasoconstrictors (incl ergot alkaloids, sumatriptan and other 5HT1 agonists)

Question 5

What are the common side effects of cafergot?

Answer 5

nausea and vomiting

Question 6

What are the rare (and serious) side effects of cafergot?

Answer 6

hypersensitivity, MI, ergotism (vascular ischaemia)

Question 7

What is the MOA of sumatriptan?

Answer 7

• Selective vascular serotonin (5-HT1d) receptor agonist.
• Selectively constricts the carotid arterial circulation, but does not alter cerebral blood flow.
• Inhibits trigeminal nerve activity

Question 8

What is the indication of sumatriptan?

Answer 8

For acute treatment of migraine with or without aura

Question 9

What are the pharmacokinetic attributes of sumatriptan?

Answer 9

→ PO, nasal, IV
→ Rapidly absorbed, low plasma protein binding
→ Eliminated primarily by oxidative metabolism mediated by monoamine oxidase A (MAO)

Question 10

What are the contraindications for sumatriptan?

Answer 10

→ Known hypersensitivity to triptans
→ Concurrent administration w MAOI
→ MI

Question 11

What are the common side effects of sumatriptan?

Answer 11

Dysgeusia, transient BP increase, flushing, sensation of cold, pressure, tightness

Question 12

What are the rare side effects of sumatriptan?

Answer 12

Minor disturbances in liver function tests

Question 13

What is the MOA of erenumab?

Answer 13

Mab that serves as a calcitonin gene-related peptide (CGRP) inhibitor

CGRP: nociceptive neuropeptide at the trigeminal ganglion, vasodilator. Known to increase w migraine and can trigger migraine-like headaches when given IV in clinical studies

Question 14

What is the indication for erenumab?

Answer 14

prophylaxis of migraine in adults who have at least 4 migraine days per month

Question 15

What are the pharmacokinetic attributes of erenumab?

Answer 15

→ Monthly SC injection
→ Clinical benefit usually within 3 months
→ Linear kinetics at therapeutic doses (past therapeutic dose, CGRP receptor binding is saturated)

Question 16

What are the side effects of erenumab?

Answer 16

Hypersensitivity reactions, injection site reactions, constipation, pruritis