PR3153 CA Recap

Question 1

what is saltatory conduction

Answer 1

electrical impulse skips from node to node down the axon (can be done because of myelin sheath!)

Question 2

How can we determine if a seizure might or might not be a recurrent one?

Answer 2

eeg (normal vs epileptiform), brain scan, prev undx seizures vs first seizure

Question 3

how do migraines occur

Answer 3

vasodilation of intracranial extracerebral blood vessels –> activation of perivasc trigeminal nerves –> release vasoactive neuropeptides –> promotion of neurogenic inflammation

SEROTONIN helps reduce vasodilation (it promotes vasoconstriction!) by binding to 5ht1 recep

Question 4

what are the MoA of the AEM (1st gen)

Answer 4

PHT - block na+ channel
CBZ - block na+ channel
VPA - block na+ and ca2+ channel and inhibit GABA transaminase
Benzodiazepines - bind to reg site of GABA recep to potentiate influx of Cl-
Barbiturate - bind to site distingct from benzodiazepines to potentiate influx of Cl-

Question 5

what are the types of seizures each AEM is used for? (1st gen)

Answer 5

PHT - all except absence
CBZ - all except absence
VPA - all
benzodiazepines - diazepam for SE
barbiturate - usually only for paeds and neonates

Question 6

what are things to note for pht?

Answer 6

• tdm needed due to narrow ther range (10-20 mg/L)
• teratogenic so use w caution in women of repro age
• non linear rs btw dose and plasma conc (dont anyhow dbl dose) [0 order kinetic]
• diff ppl have diff response to same dose
• if dose >400mg, split dose to help incr bioF
• space 2h w enteral feeds
• highly bound (watch for drugs that r also highly bound, or for low protein lvl in pt)

Question 7

what are things to note for cbz?

Answer 7

• PGx needed HLA-B15:01
• hypersensi SJS/TEN
• autoinduction as cyp450 (3a4) inducer, will own metabolism, t1/2 might shorten with time, dose incr over time needed (max autoinduction usu 2-3wks aft initiation)
• dont start imm w desired maintainence dose, shld incr grad instead cos of induction
• high binding

Question 8

what are things to note for vpa?

Answer 8

• highly protein bound also
• no good eqn to est free vpa so dont anyhow incr dose

Question 9

what are things to note for benzodiazepines?

Answer 9

• respi depression can happen (too much inhib of neur)
• if OD and go to respi depression, use flumazenil (will not work for barbi tho), it is a benzo antag
• abuse potential, can develope tolerance and dependence
• gradual withdrawal needed

Question 10

what are things to note for PB?

Answer 10

• can dev tolerence and dependence
• gradual withdrawal needed
• flumazenil cnt use if OD
• will not plateau when incr dose –> vv dangerous!

Question 11

what is the MoA of 2nd gen AEM

Answer 11

levetiracetam - dk
lamotrigine - block na+ channel and inhib glutam8 release
topiramate - dk

Question 12

what are the things to note for levetiracetam?

Answer 12

• adjunct tx for partial/gen epi
• monotx for newly dx partial epi
• can cause agranulocytosis

Question 13

what are the things to note for lamotrigine?

Answer 13

• lennox gastaut
• adj/mono for partial/gen epi
• mono for absence
• t1/2 shorter in kids, cbz, pht
• t1/2 longer w vpa
• can cause agranulocytosis and mvment disorder

Question 14

what are some things to note for topiramate?

Answer 14

• adj for lennox gastaut
• mono for partial/gen epi
• prophylaxis for migraine and headache
• can cause neutropenia

Question 15

what is the MoA of headache and migraine meds?

Answer 15

cafergot - ergot bind to 5ht1d/b, incr tonicity of vasc sm of carotid network hence incr vasoconstriction; caffeine is adenosine antag hence allow vasoconstriction also and also incr solubility and hence abs of ergot

suma - selective (5ht1d) recep agonist hence allow vasoconstriction of carotid artery, inhib neuropeptide release, inhib nociception neurotrans

erenumab - cgrp inhibitor by binding to cgrp recep

Question 16

when are these migraine/headache meds used?

Answer 16

cafergot - acute
sumatriptan - acute w / wo aura
erenumab - prophy if at least 4mmd

Question 17

what are some things to note for cafergot?

Answer 17

• cyp3a4 inhib so dont use w other inhibs as will incr ergot exposure
• dont use w other vasoconstrictors (too much vasocons, space 24h)

Question 18

what are some things to note for sumatriptan?

Answer 18

• elim by MAO so dont use w MAOi
• dont use w other vasoconstricters too like ergot (space 24h)

Question 19

what is the pharm mngment of tth?

Answer 19

acute: nsaid, paracetamol
prophy: amtriptyline, venlafaxine, mirtazapine

Question 20

how long does each phase of a migraine last and what is the pathophysio of it?

Answer 20

prodrome - 48h, hypothalamus messes with homeostatis giving rise to sx
aura - 5-60min, cortical spreading depression, slow spreading depolarisation which activate trigeminovasc system
ictal (headache) - 4-72h, neuropeptides lead to sensitisation of trigeminovasc system
postdrome - 48h, hypothalamus, same as prodrome

Question 21

Differentiate the Dx between migraine with aura and migraine without aura.

Answer 21

wo aura
- =>5 fulfilling the next 3 categories
- headache last 4-72h
- 2/4 of unilateral, pulsating, aggravated by phy act, mod-sev pain
- 1 of n/v or photo/phonophob

w aura =
- =>2 fulfilling next 2 categories
- => 1 reversible aura sx (visual, sensory, speech etc.)
- =>3 of sx spread gradually over 5min, 2 or more aura sx btb, lasts 5-60min, unilateral

Question 22

differentiate between chronic and episodic migraine

Answer 22

chronic
- =>15 mhd of which =>8 are mmd; persist for >3mth
episodic
- <15mhd/mmd OR =>5 migraine attacks lasting 4-72h in the lifetime

Question 23

what are the pharm options for migraine?

Answer 23

acute - nsaid, ergotamine, sumatriptan (gepants, ditans)
prophy - cgrp mabs

Question 24

when to start preventative tx for migraine

Answer 24

• =>4 mhd
• qol affected
• tx failure / se intolerable
• ci with acute tx
• pt pref

Question 25

what types of cgrp blockage are there

Answer 25

• gepants: block cgrp recep (antagonist)
• anti cgrp recep ab
• anti crgp ab

Question 26

when can cgrp mabs be used? (ie what is the criteria)

Answer 26

• => 18 yrs old
• 4-7mmd (8 wk trial for 2 classes, at least mod disability - midas 11 & abv)
• 8-14mmd (8 wk trial for 2 classes)
• 15mmd and abv [chronic] (8 wk trial for 2 class, 2 quarterly inj (6mth) of onabotulinumtoxin A, cnt solve)

Question 27

what is the criteria for continuing mabs

Answer 27

• mmd reduce by at least half
• improvement in qol using scale (midas reduce =>5 pts when initial was 11-20; =>30% when initial was >20; hit6/mpfid reduce =>5)

Question 28

what is the limit of acute tx one can use for headaches?

Answer 28

it shld be limited to avg of 2 headache days a week

Question 29

what is considered medication overuse for headache and migraine?

Answer 29

• =>15mhd for non-specific migraine meds (nsaids, paracetamol etc.)
• =>10mhd for specific migraine meds (triptans, ergots, gepants etc.)