P H R M A C O L O G Y - NOTE 15 – Anit-migraine Drugs

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ANTI-MIGRINE DRUGS

Acute Attack

Mild to Moderate

NSAIDs

Aspirin

Paracetamol

Ibuprofen

Indomethacin

Naproxene

Opioids

Moderat to Sever

Anti- emetics

Diphenhydr-amine

Promethazine

prokinetic

Metocloper-amide

Domperidone

Diclofenac

Specific drug

5-HT Agonist

Sumatripan

Almotriptan

Naratriptan

Pizatriptan

Zolmitriptan

P Agonest for α-Adrenceptors & 5-

HT R

Ergotamine

Prophylaxis

β adrenergic blockers

Propranolol

Metoprolol

Nadolol

Atenolol

Timolol

Ca channel blockers

Flunarizine

Nicardipine

Nifedipine

Nimodipine

Verapamil

5-HT2

antagonist

Pizotifen

Cyprohepata-dine

5HT2 antagonist /partial agonist

Methysergide

Other

Amitryptyline

Imipramine

Sertraline

Fluoxetine

Clonidine

Valporate

P H R M A C O L O G Y - NOTE 15 – Anit-migraine Drugs

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Acute attack of Migraine DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT

Mild

to

Mo

der

ate

a

tta

ck

NSA

IDs

Aspirin Given orally.

they must be given early to be absorbed before there is vomiting.

Analgesic. acute migraine attack.

Paracetamol

Ibuprofen

Indomethacin

Naproxene

Opioids Given parentrally (I.V. or I.M.). Refractory cases of acute attack of migraine(rarly)

Mo

der

at

to S

ever

a

tta

ck

An

ti-

emet

ics Diphenhydramine Prevent vomiting.

Promethazine

pro

kin

etic

Metocloperamide Given by I.V. injection. They promote gastric emptying, So, enhances absorption of

analgesics.

With very severe vomiting.

Domperidone Given as rectal suppositories for vomiting can be tried

Diclofenac

Spec

ific

dru

g fo

r a

cute

att

ake

5-H

T A

gon

ist

Sumatripan Given by oral route or S.C. injection.

Fast absorbtion.

Bioavailabilty by s.c. route is 96%

Dose not cross BBB.

Plasma t1/2 is 2 hours.

stimulate 5-HT1 R on pre-synaptic endings of V cn. inhibit releasing of

vasodilators .

selectively stimulates 5HT1B/1D R in cranial BV,

constrict them.

acute severe migraine attack(1st line).

NOT used with IHD. unstable angina. previous MI

Malaise ,fatigue.

Sedation.

Dizziness, vertigo, nausea & vomiting.

feeling of chest pressure, tightness & pain.

CARDIAC ARRHYTHMIA & myocardial infarction. due to coronary artery spasm.

Almotriptan they are congeners of Sumatriptan.

improved pharmacokinetic

better Bioavailability.

better and longer duration. + ef

fect

s

on

CN

S

Less side effects.

Reduce cardiac side effects. Naratriptan

Pizatriptan

Zolmitriptan

P A

go

nest fo

r α

-Ad

ren

cep

tors

& 5

-HT

R

Ergotamine Ergotamine tartrate stimulate 5-HT1 R on pre-synaptic endings of V cn. inhibit releasing of

vasodilators .

Migrine (high specific).

NOT used with disease of: Coronary BV. Peripheral BV.

Paresthesiae in hands & feet.

Peripheral ischaemia.

Peripheral GANGRENE with overdose.

Precipitate angina pectoris.

Fetal damage.

Given by o Entral route (oral, sublingual, rectal). o Parentral route (inhaler).

rectal route is preferred ???. caffeine facilitates absorption of ergot alkaloid. It metabolized in the liver.

t ½ is 2 hrs

DOSE. o Tablet (1mg + Caffeine 100mg). o 1-2 tab. at onset ,then 1 tab/ 30min. o NO > 6 mg/attack & NO >10 mg/wk.

For severe attack, it ginen may be IM/IV injct.

Dihydroergotamine o For intractable migraine. o Given by IV inj.(0.5-1mg)

Efficient use of analgesic &

antiemetic is sufficient for the

majority of ACUTE ATTACKS

P H R M A C O L O G Y - NOTE 15 – Anit-migraine Drugs

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Involvement of

Focal Seizures

Generalized Seizures

TREATMENT

• motor area (convulsion)

• hypothalamus (autonomic discharge)

• reticular formation (unconsciousness)

• Repeated seizure activity leads to neurodegeneration due to excitotoxicity

•remains localized

•primary (involve all cortical neurons)

•secondary (spread afterward)

• inhibitory NT.

• excitatory Nt

•alter the permability of membrane to ions (Na, K or Ca)

Prophylaxis drugs for Migrine. DRUG PHARMACOKINETIC ACTION USES SIDE EFFECT

β a

dre

ner

gic

blo

cker

s

Propranolol • PROPRANOLOL– (effect , also prevent migraine ).

the d-isomer part of structure lacks β blocking action; Alter the permeability of the

membrane.

They are effective and widely used.

Fatigue.

Broncho-constriction.

Metoprolol

Nadolol

Atenolol Timolol

Ca

ch

an

nel

blo

cker

s

Flunarizine Block Ca channel. effective in the preventive treatment of Migraine

Nicardipine

Nifedipine

Nimodipine

Verapamil

5-H

T 2

an

tag

on

ist Pizotifen antagonize5-HT2 receptors.

Atropine like action.

They are RARELY used Weight gain.

Anti-cholinergic side effects.

Cyprohepatadine Antagonize 5-HT2 R & H 1 R.

Block Ca channels

Sedation.

weight gain.

5H

T 2 a

nta

go

nis

t

/pa

rtia

l ag

on

ist Methysergide effective in about 60% patients. It is 5HT2 antagonist /partial agonist Serious Toxicities like;

o RETROPERITONEAL obstruction to the Ureters.

o Subendocardial, Pericardial or Pleural fibrosis.

Nausea, vomiting & diarrhoea.

Oth

er

Amitryptyline effective for the PROPHYLAXIS of migraine in some patients.

Imipramine Sertraline

Fluoxetine

Clonidine

Valporate