Migraine and IBS

• what causes the aura that migraine patients can get?

  wave of decreased neuronal activity spreading across the brain which causes spreading cortical depression leading to aura
• describe the causes of migraine

  increased neuronal activity from the brainstem which activates the trigeminal nerve and innervates the face and forehead.

  terminals of trigeminal nerve in meninges release CGRP which leads to pain

  CGRP involved in vasodilation of cranial arteries which leads to pain - there is not a lot of space between the meninges and cranial arteries and skull so increased pressure and vasodilation leads to pain
• what causes the N+V and photophobia symptoms associated with migraine

  projections to the chemo-receptor trigger zone causes the N+V and some stimulation to the hypothalamus leads to photophobia
• how is serotonin involved in migraines?

  5-HIAA levels increase during a migraine attack - metabolite of serotonin which can be detected in the urine therefore 5-HT must be involved somewhere

  used to inject 5-HT via IV to treat migraines before treatment was available

  suggests that 5-HT receptor agonists would make the best drugs for migraines
• where are the 3 places that serotonin receptor agonists can be found to target?

  1 = receptors on smooth muscle cells of large intracranial arteries - this causes vasoconstriction and reduces nerve activation and CGRP release

  2 = receptors on peripheral trigeminal nerve terminals - switches off CGRP release which reduces vasodilation

  3 = receptors thought to inhibit central trigeminal nerve firing - works in areas of the brainstem which triggers attacks
• what is the order of treatment for acute migraines?

  analgesics, triptans, anti-emetics, 5-HT receptor agonists
• which analgesics are prescribed for acute migraine in order?

  aspirin, ibuprofen, naproxen, diclofenac, mefenamic acid for menstrual migraine
• which triptans are prescribed in order for acute migraine and how do they work?

  sumatriptan, almotriptan, naratriptan, other triptans then sumatriptan and naproxen combined.

  note that triptans cause vasoconstriction and reduce inflammation - actually targets the cause of migraines so tend to be quite helpful
• which anti-emetics are used for acute migraine and whats important to note about it?

  prochlorperazine and metoclopramide used to relieve vomiting but not normally used if patient is nauseous
• how do 5-HT agonists work when used for migraine?

  taken at onset of migraine not aura

  2nd dose taken at least 2 hours after 1st only if inadequate response seen to 1st dose

  can initially cause some discomfort since they are vasoconstrictors - can cause pressure or tightness in chest

  for this reason contraindicated in CV and arterial disease patients

  use with caution in the elderly - not licensed
• what are the main goals of migraine prophylaxis?

  reduce attack severity, frequency and duration

  improve responsiveness to treatment of acute attacks

  improve function and reduce disability

  prevent progression from episode to chronic migraine
• what is the criteria to provide prophylaxis for migraines?

  must suffer from frequent migraines - more than 1 a week

  increased frequency from before

  can't use acute treatments

  prolonged and severe even with acute treatments

  serious adverse events from acute treatment

  risk of medication overuse headaches
• what are the drugs used in migraine prophylaxis in order?

  propranolol - blocks 5-HT receptors

  anti-convulsants - topiramate, sodium valproate and valproic acid - TERATOGENIC - PREGNANCY

  tricyclic antidepressants - amitriptyline - blocks reuptake of 5-HT and noradrenaline

  ARBs - candesartan

  botox

  MAbs

  flunarizine - specialist only

  pizotifen - vasoconstriction but unwanted side effects - weight gain

  menstrual migraine prophylaxis - triptans - risk of medication overuse headaches
• what is the role of serotonin in the GI tract?

  increases motility and contractility, comes from enterochromaffin cells

  direct effects = relaxant effect on smooth muscle cells and contractile effects on the smooth muscle cells

  indirect effect = on enteric nerves leading to the release of ACh, and contraction and relaxation - relaxation happens without ACh release
• how do serotonin receptor stimulants and antagonists help with IBS?

  5-HT receptor stimulation = increase peristalsis and gut transit and increased fluid secretion and bowel movements - too much leads to diarrhoea and loose stools - good for if IBS is constipation predominated

  5-HT receptor antagonists = increase water and sodium reabsorption = constipation, decreased bowel movements and decreased sensitivity - too little 5-HT produces constipation and decreased bowel movements - good if iBS is diarrhoea predominated
• what are the treatment options for IBS?

  1 = diet and lifestyle modification - trigger foods - keeping a diary

  2 = anti-spasmodics = anti-muscarinic agents such as hyoscine, atropine and propantheline

  3 = other anti-spasmodics - mebeverine and peppermint oil

  4 = osmotic laxatives for constipation - soluble fibre, macrogols, oats and bran

  5 = drug for constipation - linaclotide

  6 = 2nd line - antidepressants - amitriptyline
• what drug should you use with chronic constipation resistant to other laxatives?

  prucalopride