Drugs for treatment of Migraine and VertigoDharma Permana, Apt, PhDAnti-migraine DrugsDharma Permana, Apt, PhDMIGRAINEDefinition Common migraine No aura Attacks ast ! " #$ hours %he first indication that &ou are going to ha'e a migraine is the pain Diagnosed as migraine if there is( At east $ of( )niatera pain Pusating pain Moderate*se'ere pain Pain is aggra'ated +& mo'ement And , of( Nausea Photopho+ia and phonopho+ia -e.cessi'e sensiti'it& to e.terna stimui/ Classic migraine Aura present $ attacks per month 0ith at east 1 of( , or more aura s&mptoms , aura s&mptom de'eoping more than ! min or$successi'e aura s&mptoms 2&mptoms asting ess than , hour 3eadaches start ess than , hour after the aura %he first indication that &ou are going to ha'e amigraine is the aura An aura is a change in perception -sometimes peope see ights/Aura s&mptomsVisua distur+ances are the most common feature of migraine aura4 2igns and s&mptoms ma& incude( 2himmering spots or stars 5ig6ag ines that gradua& foat across &our fied of 'ision 7oss of 'ision 8ind spots -scotomas/ 9ashes of ight Aura s&mptoms:ther t&pes of sensations ma& accompan& &our 'isua distur+ances, incuding( 9eeings of num+ness, t&pica& fet as tinging in an e.tremit& or on &our face ;onfusion Difficut& 0ith speech or anguage Aura s&mptoms:ther signs and s&mptoms of migraine 0ith aura incude( 2ensiti'it& to ight Nausea and 'omiting Mechanism of migraine Vascuar cause Neura cause 8otht kno0:ne potentia mediator(" 2erotonin? Pasma e'es of serotonin -housed in pateets/ aredecreased during a migraine attack and e'es of serotonin meta+oites are increased in the urine? 2erotonin is stored in pateets"%here is a massi'e reease of serotonin, causing'asoconstriction " =hen serotonin has +een depeted, there is 'asodiation -headache/ ?Gi'ing serotonin stops the headache%herap&Designed to: ,4 Pre'ent an attack $4 Reduce the s&mptoms of an acute attackPreventing a migraine attack* Adjust the lifestyle to avoid triggering factors, e.g. Avoiding( ;ertain foods -cheese, 0ine, chocoate/ "%he t&pe of food depends on the indi'idua -the foods often contain t&ramine/ ;hanges in temperature, humidit&, atitude Vasodiator drugs 2tress Irreguar seep patterns -%oo itte or too much /*Pharmacological measures: :n& used if the attacks are fre@uent and 'er& se'ere*Pharmacological measuresPizotifen 0, !", mg#hari A3%$ antagonist Ad'erse effects( Dro0siness =eight gain %he drug causes h&pog&cemia, Pro$ranolol %0 ! &'0 mg, ' kali sehari + adrenoreceptor antagonist 3as some A3%$ antagonist acti'it& )sed to pre'ent the 'asodiation 0hich causes the pain*Pharmacological measures :(ethysergide %)* mg#hari Most effecti'e at pre'enting an attack A3%$ antagonist -partia agonist/ Not terri+& seecti'e4 Ma& ha'e effects on A3%, )se is imited +& a range of ad'erse effects( Nausea, dro0siness Vasoconstriction Especia& in the coronar& 'esses, eading to cardiac ischaemia 2houd not +e used in peope 0ith an& pre e.isting coronar& arter& disease or in h&pertensi'e patients3o0e'er, this is necessar& to a'oid these potentia& ife threatening side effectsAmitri$tyline' ! "0 mg#hari Not used aone A tric&cic antidepressant -e4g4 imiprimine, desiprimine/ A3% uptake inhi+itor )sed in com+ination 0ith propranoo, pi6otifen or meth&sergide%reatment of an acute migraine attackAims: ,4 %o reduce the pain $4 %o pre'ent the nausea and 'omiting 0hich accompanies the pain 14 8est to treat as ear& as possi+e -during the aura phase for cassic migraine/Non pharmacoogica techni@ues( Reduce e.terna stimui -sensiti'it& to mo'ement, ight, sound/ Pharmacoogica techni@ues( Pharmacoogica techni@ues(As$irin, +,A-Ds .e.g. +a$ro/en0 %he doses tend to +e higher than for a norma headache ,st ine of defence(etaclo$romide D$ antagonist Anti emetic If there is 'omiting, it is difficut to gi'e an& drug ora& Pharmacoogica techni@ues( 1rgotamine Ergot akaoid4 9irst" pass meta+oism Partia agonist at a receptors and A3% receptors Effects 'ar& at different 'ascuar +eds Main action is to constrict the cere+ra 'esses4;inica uses com+ination 0ith caffein Ad'erse effects( M&ocardia ischaemia 3&pertension4 ;ontraindications( pregnant 0omen, per&pheraandcardio 'ascuardiseases, impaired rena and hepar functionPreparat ( ;afergot ta+- Ergotamin , mg and caffein ,BB mg 2uppositoria - ergotamin $ mg dan caffein ,BB mg / Pharmacoogica techni@ues(,umatri$tan 2pecifica& de'eoped for the treatment of migraine A3%,D agonist ;onstricts cere+ra 'esses Aso inhi+its the reease of ;GRP Not gi'en IV +ecause it can cause coronar& 'asoconstriction Ad'erse effects( ;oronar& 'asoconstriction %he coronar& 'ascuature has A3%,D receptors causing 'asoconstriction4Deri'at 5omitriptan, naratriptan,ri6atriptanDrugs for %reatment of Vertigo2ertigo ,ym$toms%o determine if true 'ertigo e.ists, &ou must descri+e a sensation of disorientation or motion4 In addition, &ou ma& aso ha'e an& or a of these s&mptoms( " Nausea or 'omiting " 20eating " A+norma e&e mo'ements Drugs for %reatment of VertigoPharmacology%here are at east four maCor neurotransmitters of the 'esti+uar s&stem in'o'ed in the Dthree neuron arcD +et0een the 'esti+uar hair ces and ocuomotor nucei that dri'es the 'esti+uocuar refe.4 %here are aso a host of other neurotransmitters 0hich moduate function4 Glutamate is the maCor e.citator& neurotransmitter -2erafin et a, ,EE$/4 Acetylcholine -A;3/ is +oth a periphera and centra agonist affecting muscarinic receptors4 Receptors found in the pons and medua, presuma+& those in'o'ed 0ith di66iness, are amost e.cusi'e& of the M$ su+t&pe -8arton et a, ,EE!/4 Gamma-aminobutyric acid -GA8A/ and glycine are inhi+itor& neurotransmitters found in connections +et0een second order 'esti+uar neurons and onto ocuomotor neurons -2pencer et a, ,EE$/4 2timuation of the t0o t&pes of GA8A receptors, GA8A"A and GA8A"8, ha'e simiar effects on 'esti+uar path0a&s -Neer'en et a, ,EFE/, %he circuitr& +& 0hich se'era other neurotransmitters affect 'esti+uar responses is ess 0e understood4 Histamine is found diffuse& in centra 'esti+uar structures and centra& acting antihistamines moduate s&mptoms of motion sickness -%akeda et a, ,EFE/4 8oth the 3, and 3$ su+t&pes of histamine receptors affect 'esti+uar responses -2erafin et a, ,EE$/4 2esti3ular su$$ressant and antiemetic drugs are the mainsta& of treatment of 'ertigo4 %he term D'esti+uar suppressantD is a 'ague one genera& used to indicate drugs that reduce n&stagmus e'oked +& a 'esti+uar im+aance or 0hich reduce motion sickness Drugs for %reatment of Vertigo2esti3ular su$$ressant". Anticholinergics 0hich affect muscarinic receptors, such as scopoamine, increase motion toerance4 Antichoinergics aso affect compensation, producing a re'ersi+e o'ercompensation if administered after compensation has +een attained to a 'esti+uar im+aance -5ee, ,EFF/4 Agents 0ith centra antichoinergic effects are most important in treating 'ertigo'. Antihistamines4 =hie the precise roe of histamine in centra 'esti+uar processing is uncertain, there are data indicating that centra& acting antihistamines pre'ent motion sickness and reduce the se'erit& of its s&mptoms e'en if taken after the onset of s&mptoms -%akeda et a, ,EFE/4 A the antihistamines in genera use for contro of 'ertigo aso ha'e antichoinergic acti'it& Drugs for %reatment of Vertigo144enzodiaze$ines are GA8A moduators, acting centra& to suppress 'esti+uar responses4 In sma doses, these drugs are e.treme& usefu4 Addiction, impaired memor&, increased risk of faing, and impaired 'esti+uar compensation are their main shortcomings4 Antiemetics ,4 Antichoinergic$4 Antihistamin14 Anti serotoninTable 1: Vestibular Suppressants (order of preference)Drug Dose Adverse Reactions Pharmacologic Class and PrecautionsPregnancyCategoryMeclizine (Antivert, Bonine)25-5 mg ! "-#h sedating antihistamine anticholinergic $recautions i% $rostatic enlargementB&oraze$am (Ativan)'5 mg B(Dmildl) sedating *enzodiaze$ine drug de$endenc) Clonaze$am (+lono$in) '5 mg B(Dmildl) sedating *enzodiaze$ine drug de$endenc) Dimenh)drinate (Dramamine)5 mg ! "-#h same as Meclizine antihistamine anticholinergicBDiaze$am(,alium)2 *id P- 5 mg (, (. dose)sedating*enzodiaze$ine drug de$endenc) Precaution in glaucoma'DAmitri$t)line (/lavil).-5 hssedating, in overdose cardiac arrh)thmiaanticholinergic tric)clic antihistamineTable 2:Antiemetics Drug Usual Dose (Adults)Adverse Reactions Pharmacologic Classgranisetron(Kytril)1 mg PO BID 1 ug!"g I# dailyheadachesedation$%&' antagonistmecli(ine (Antivert) Bonine)1*+$,*$ mg -.,/h POsedating Precautions in glaucoma) 0rostate enlargementantihistamine anticholinergicmetoclo0ramide(Reglan)1 mg PO &ID or 1 mg I1restlessness or dro2siness e3tra0yramidaldo0amine antagonist stimulates u00er gastrointestinal motilityondansetron (4o5ran).,6 mg PO &ID '* mg I# one dose 0recaution in he0atic dys5unction$%&' antagonist0er0hena(ine(&rila5on)* , . mg PO) u0 to 7ID or $mg I1) u0 to &IDsedating e3tra0yramidal0henothia(ine%hank Gou