Salisbury: Kinins, Serotonine and Drug therapy for Migraine Headaches

Question 1

Propranolol/ Atenolol

Answer 1

Beta blockers
MoA: Reduces hyperfunctioning of sympathetic nervous system?
Oral
Takes 3wks to be effective
Well tolerated and effective
ADR: Teduced energy, Tiredness
Contra: Asthma patients {beta2, normally activated by Epinephrine}

Question 2

Amitriptyline/ Nortriptyline

Answer 2

Tricyclic antidepressants (TCA)
MoA: Inhibit serotonin reuptake, Block muscarinic receptor
Oral
ADR: Amtimuscurinic (dry mouth, constipation etc), Weight gain, Tiredness

Question 3

Valproic acid/ Topiramate/ Gabapentin/ Levetiracetam

Answer 3

Anticonvulsants
MoA: Increase GABAsignaling
Oral

Question 4

Valproic acid

Answer 4

Anticonvulsant
For Migraine + Epilepsy/ Anxiety disorders
ADR: Drowsiness ,Anorexia, Nausea, Ataxia, Alopecia, Tremor, Liver toxicity
Contra: Pregnancy {tetragenicity}**

Question 5

Verapamil

Answer 5

Calcium channel blockers
Antihypertensive drug
Reduces migraine incidence
MoA: unknown
ADR: Negative inotropic cardiac effects and Hypotension

Question 6

Cyproheptadine

Answer 6

Potent antagonist of Histamine, ACh, and Serotonin
For seasonal allergy and Puritus from Histamine release
Prophylaxis of migraine headache
ADR: high incidence of CNS depression and sleepiness

Question 7

Nonspecific rescue/ abortive drugs for migraine

Answer 7

INSAIDS, Ibuprofen, Naproxen, Acetaminophen, Ketorolac

Question 8

Abortive migraine agents: mild to moderate migraine

Answer 8

Acetaminophen, Aspirin, Ibuprofen, Naproxen

Combinations of Acetaminophen, Aspirin, Caffeine

Question 9

Abortive migraine agents: moderate to severe migraine

Answer 9

Ketorolac (IV or oral) for max 5 days

{Gets GI bleeding with chronic use…}

Question 10

Abortive migraine agents: children

Answer 10

Acetaminophen, Ibuprofen

Question 11

Abortive migraine agents: pregnant women

Answer 11

Acetaminophen, Ibuprofen
{All NSAIDs should be avoided in last trimester}
{Increased bleeding and Preamature closure of Ductus arteriosus}

Question 12

Ergotamine/ Dihydroergotamine

Answer 12

Ergot alkaloids
MoA: 5-HT1 receptor agonist
{Partial agonist and antagonist activity at serotonergic, Dopaminergic and Adrenergic receptors}
For moderate to severe migraine attacks
Combined with antiemetics to for nausea
Not for prophylactic therapy, only for rescue
Ergotamine= Sublingual {first pass effect}
Dihydroergotamine= nasal spray/ injection
Cheap
Don’t use in MI, Hypertension, Pregnancy
Replaced by Triptans (more specific but more expensive)
ADR: Nausea and Vomiting, Generalized vasoconstriction {coronary vasospasm, MI, etc}
Contra: Pregnancy, Peripheral vascular disease, Ischemic heart disease, Triptans within 24hrs

Question 13

Triptans: use

Answer 13

Abortive migraine attack agents
Never for daily uses {NOT for prophylaxis}
{If used daily= increases number of attacks…}

Question 14

Triptans: advantages

Answer 14

Less nausea and generalized vasoconstriction than Ergot alkaloids
More selective MoA {Selective 5-HT1B/D receptor agonist}

Question 15

Triptans: MoA

Answer 15

Vascular: Vasoconstriction of cranial blood vessels
Neuorogenic: Reduction of Trigenimal sensory nerve activation and inhibition of vasoactive neuropeptide release
Central: Inhibition of neurotransmitter release from activated Trigeminal nerves in the brain stem and upper cervical spinal column

Question 16

Sumatriptan

Answer 16

Short onset and duration of action
Subcutaneous (fastest), Oral, Nasal spray
Relief within 1 hr
Half life = 2 hr
Low bioavailability
Short plasma half-life

Question 17

Naratriptan/ Zolmitriptan

Answer 17

Oral
Lipohilic= greater distribution to brain stem
Greater bioavailability
Lower instance of recurring headache
Longer duration of action (half life= 6 hr)
P450 metabolism (50% urine excretion, unchanged)
Lower dose in renal dysfunction

Question 18

Frovatriptan

Answer 18

Longest acting Triptan (half life = 24 hours)
Highest affinity for 5HT1B rceptor
Slower onset of action than other Triptans

Question 19

Rizatriptan

Answer 19

Oral tablet
Faster onset than Sumatriptan {Fastest acting}
Less nausea than sumatriptan
Half-life= 2 hrs
Metabolism MAO

Question 20

Triptan: ADR

Answer 20

Heache recurrence

Tingling, Paresthesia, Dizziness, Flushing, Neck pain, Drowsiness

Question 21

Triptan: Contra

Answer 21

Ergot alkaloids within 24 hours
Peripheral vascular disease
Ischemic heart disease
SSRI concurrent use

Question 22

Serotonin syndrome

Answer 22

Caused with SSRI + Triptan etc

Restlessness, Hallucination, Loss of coordination, Diarrhea

Question 23

Cluster headaches

Answer 23

Episodic, Unilateral, Stabbing headaches

Appear at same time each time (Circadian rhythm)

Question 24

Cluster headaches: treatment

Answer 24

Oxygen
Triptans (Rapid onset= Sumi and Roza)

Question 25

Cluster headaches: prophylactic

Answer 25

High doe prednisone (steroid) | Calcium Chanel blockers (Verapamil)

Question 26

Tension headaches

Answer 26

Squeezing sensation or pressure felt around head | Not associated with nausea or vomiting (as opposed to migraine)

Question 27

Tension headache: abortive meds

Answer 27

Acetaminophen and NSAIDs

Question 28

Tension headache: prophylactic

Answer 28

TCA (Amitriptyline) | Antiepileptic (Gabapentin)

Question 29

Idiopathic intracranial hypertension (IIH)

Answer 29

Increased ICP | Obese young women

Question 30

Idiopathic intracranial hypertension (IIH): treatments

Answer 30

Weight loss Removal of drugs (Tetracycline, Oral contraceptives, Vitamins) Carbonic anhydrase inhibitors (Acetazolamide, Topiramate)

Question 31

Carbonic anhydrase inhibitors: function

Answer 31

Reduce CSF production | Useful for IIH

Question 32

Carbonic anhydrase inhibitors: ADR

Answer 32

Nausea, Fatigue, Tingling in hands and feet, Altered taste, Distal paresthesia, Concentration difficulties, Weight loss

Question 33

Agents that induce pain

Answer 33

Bradykinin and Kalidin | {Other enzymes in Kinin pathway}

Question 34

ACE inhibitor increases Kallidin level by inhibiting what

Answer 34

Kininase II (ACE)

Question 35

Pounding headache, Aura , Nausea=

Answer 35

Acute migraine attack

Question 36

Acute migraine attack: abortive med

Answer 36

Rizatriptan (Sumitriptan too}

Question 37

Pregnant women, acute migraine attack, contra=

Answer 37

Ergots (Ergotamine/ Dihydroergotamine) | NSAIDs (Ibuprofen etc, if in last trimester)