Arti- Meatarial Bruges a ( | ¥| = — "do these are dugs used for prophylexts, treatment 4 a8 prevention GF TeLapies of malaria - Clei fication p —— il rT »x~Vf oy © . fF Ueamino quindines — Quincline-melherel —Cinchene- Biquanide us . alkalol Chloroquine (cg) *Mefloguine . + proguanil ine on ‘Quinine + Amodiagnine (AQ) Houieaaive (Ghtoreguanitdy . Piperaquine | _ =S= SSS (Ganon Siena . | Diaminopyramidire, B= Aminoainctine Sulfonamides Antibiotics « | . § Sulbones + PYrimethamine + prima quine -Sulfedoxine + Tetratyy lire’ ‘Tapencgrine < Suljornethepypajine + Doxyuy ling \ i V+ * Dopsons. *Clindamycin | : I v 1! Sesquiterpine Aminp-alechols Napthyridine — Napthequinene | i, Me spn stm epulemsthur + dumefantine + Arte ethor Lv prtetane auesyant | ye Objectives aang te of Anti-matascal dogs GT prevent clinical attack of malaria (prophylactic ) (iy To Heat clinical allack ef malaria CClmical crrative) | Wii) To completely eradicatt dhe parastle fro the patients . body (radial otrotive)tiny To dutdmon human te masqutto tonamissien Comite, Pre evythioujhe — Schi Ak Tissue, schigontorides ae igogeny Exo eustrrocytie Sthizeqeny Jd + 3 - Amine quinoline Primaqpiine mat, Parmoquine Pentaquing Teopentaguine + DHRs inhibitors IBIgquanicles Proguanit } chiey egean Brom eg Moja ! " ) Diaminopyramiding Pyyetmethamé; py 2 Se = » Sulfonamity, Trimaltapring y + Sesquiterpine lactoner inet pen wroeqai * Atkeethan Artevoloune + Blood schigonticides Buzihncaytie ' Schigo " oe ~ . ny leak ater’ vidys DHRaye inhibitors... (Chloroquine (emnimethamsne) ‘ Quinine Halofantine Chioveqysine aso) x Gamtowdes — Gamefoujter ay 7 2 otto losintly tnavorq c lp i Miollo Insinila Jaort (Prvivar) = Hn, Heptogine oo a — ¢ Andi mole wv Causrod 7 + Prdrnerqyal — nbs Recor en promir ond + Pregues —"ok liver resis PF =a thplloroing det jal trsenpy egies dn xo Causal pretilass woot profits preeryinrory Be phase Cin liven) Target > = prophytattia 18 Bur to ik tence potatial fe Te nek used cin mast . Prinaquins ——— smatasial 4p Uprog yam me ~ Catal G- 67 PD levels — O-5mg|kg TAttive against both p-f & p-v “fetommenda| tk for Shore duration travel “te Povivax prominent areas » % for Subjede tho cannet take any other prophylactre dung: Proguanil - primanily for p+ emct used tn Sndio , Gecame of weak activity agatnst liver stages’ Of Pev and development of tapid yesistance hin used atone - Pe 3 4 > pre -euythrocy Hie ‘pase 4 Suythroaytre phase Tat > onset Duration - shart Resistance — Rapid Inhibition — Gamels toxicity grading - + . Q- Suppressive Prophiytasis *- : 9 Supe the euythrougtic Phase, and thus altecks af vmofaviat favey j can be used ay prophylactics Though the caoerythrocytic phase oH case of Viva and , Other velapsing — matartas — continuet y CWnveal disease does nok appears ——— _ _J+ Chloroquinn (CG) - 300mg (base™ Jor Smg}kg torekty . | ry travellers staat ene week before ith a loading 4 dese of iomalkg & Continue HI ene month apt, = yelurn fem endemic eA + Bee’ a Used uh CO —Senbibve Pet Plyrime Since, CQ resistant Pf oIs ux coide spread In India, (ase SE is 7 Longer eempled a provhylachc Can dndia’ = 2 uKS before taker + Meflequine - 250mg Slavted 4 ° 7 C m (age) Ispoma) b Recommended by WHO 3-Clinical Cure / The ery thtouy He Schigontoudes a7e Uced ow te terminate 9h eptsede of malarial Fever * athe available dyuge can be dtvided Into! cor High — efficacy ATHGE (by Lows - efficacy drugs | (0) High - The eruthroutte schigontoudin ave radical araltee fe falciparum , bub wok 4d viva & ovale matonual veh!) Howwer , recrudercerces ocutrs In faluipanum in furr PAL bleed “Te nek Metetly cleared ef he posaaifs oy he drug. a Treat = A) Vivou = chic + Avie Suu B) chi *chiore (as awe Treatment Of Ontom plicated MoaLescicn 3 — = A) Vivar (also ovale, mafariae) mataria “Fie oquine Goomg followed by Zoorng after Bhis Cismglkg) CSmglkg) x 3days 4 “f Primaquine 15 mg x14 days (or 5mg1 kg) + Av demistinig based combination Therapy + Primaquine Cov Suioing Georg dhily 2a dois 4 Dory ueline toomg daily rx adayt+ + Clindamytin Goomg i2hiy xFdou + Primaguine (as above - ISmgxiddayr) | B) Chioroqin — sensitive faleipardim’ malaria schieroquina y Bdays + primaquine USmg Single doce (as above) (0+45mg «9 ) al, ‘ ' . OA Jamebedal - c) Chioroquins — resistant foltparwen mortoria!- » Artesunate too my BD (4 rg ] Kgldoay) xB day { + Suljodexine spo i Zodouine 3 + pyrimethamine, AS m4. Sing he Casmalky) Geasmoleg) Fer ke (|+ Arkesunate toorng BD * 3 dors CY mg fxg lay ) + Mesloiine” a50mg OF ah day an stomg 07 1 Sey (15mgika) oeng/ kg) + Avtemethey Fomg + Lumetan tine Ytomg twice daity , Bday Cehild 25-35 kg BW 3)y doses \F-35. ha) giv ‘pa doses 5-15 kg Bu Vy dose ) * Artevolone (as maleate) So mq an x Sdays Piperaquine +50 mq once daily + Quinine 600mg (tomglkg)) & hily ‘4 Doxyajdine 100mg datly K days + Clindomaycin Soom rahily “GQinineg ¥ > Avkecunate 2 fivsk line ACT Undey Nvepep ae SIP of rnefloqpir atone alto ured yuk prefers be combined \sith’’ dvkesitnals. ’ > dn Sndia (including under NvBper) oll Pe f cot Trcespenve of CH- resistance status, are freated with artemisinin — bored combination \ Ahunepyt ACT)= -) Rulapse - P*f -indicates “resistance - wkernodive | drug is pregened- j % Severe and Complicated falciparum malaria © | “ythis jineudes Pr faldparum infection diended) 6g ane or more Of * + Hyperparasitaemia > hyper pyreaia * Pld and elecholyte Imbalance «acidosis « Hypoglycoemt'a. © proshahen * Cardiovasuuar collaps? . Hasmoglobinurio * Taundice + Black woter fever + Swere anaemia. * Renal failure + Spontaneous bleeding © Cerebral matarlen spulmonasy | edema. =) paventicd’ (iam [fev)) dvugs have fo be used yore diugs | may be aubsttuked when the condition improvese HK TREATMENT FOR SEVERE | & COMPLI CATE + Avkesunate 2-H mglKg * [enter follorsed bby artuengl aly xt dos DPOF MPLARIAI after 12 § Quhys, € ahen once a Cire 0-12-24) 4f patient is stable fo tolerate? oral medication Switch over to 3 day ord ACT+ Avkermether 4 342mg [kg Leno] on the Ast day—) +6 cg at | stable 6 mag] Kg % eu d Swit over to 3 day oval ACT* sAvteether 2 3°2 glk ED on the det day b Iegmg|ug eX HU days ( Stable Bday oral ACT x | *Quinine dit Hel - 20™9 | kg (Tosding dose Jdiluted Ste dethose | dexHose - Saline. g infurd¥ | | Over Ubrs -follewed by 10. mglKG ivy | | (raaintainante dese ) | infusion vey Urs every gis Cocuatts)) 7 Maintdnar\ce dose i-v infusion over 215 ty Childvens for ‘every! 8 brs) until the pottient ay Sunallovs dl, Sable Syatch over te ove, quinine wonglkg ghylys 9 axtesunate Note * Avteeher (im) Ys ‘slower “acting? than (uv) ond atbears less Cfyrcactour . dt is used rls ta Andon “Gia Volume of Fuld lI TV infusion Of qusinine sho! be ‘weduiceck in yotients T Volume over leas } pubnonwry edama+ea ud) Jf possible oral quinine shaild be substituted by a i 3 day oral ACT, or doxytytline toomg daly should | be, combined x ik + Civiy Chlevoquine Hel tv to be used only if none of the above is available and only in adults © ¥ Tafenoquine 3. Exo erythrocytic Schigontocide » Single dose anti velapse drug for Vivo meclarta + y Ye Radical cue '- For ‘Complele eradication of pavasile Dregs which allack 0m eto - erythrocyte Steige , + clinical curative dug Pad ica *Primaquine 18mg klY days 4+ Chlovoqtrine [ other Schi zon tecide | Note: Only cto individuale coho test -Ve™ foy G-6- PD ckfitin, 5) Gametocidal: Gameticidal avtien to reduce the transmission to ernsquito * Falciparum malaria duving pre pany’, Jb mut be created -Prinviquine YSmg Gngle ore TACT: | | Promptly § aggresciely » can’ be uted + Quinine 600mg TDS %7 days during all ry himesters, Speaelly the Clindoumay ein 300 m9, TOS[Qip¥ aday ast Cay fxg’)TACT © Better tolerated 3 day regimen « © Ghloroquune | ————$ Seythrouytic Shiggntic de aguhst all spec of plasmas, > Gntrole most Clinteal attacks In 1-2 daye @ disappear, OF parasites fromm feripheval bleccl in 1-3 days - -) IS-30mg}mt = Therapeutic. plasma cont? ae CH is atively concenhated by sensitive, intaterythrory he plasmedia 5 high conc” "6 found Im [nfected RBCs than non -infected ones - Parasitic = lysosomes —4 Haemoglobin L CQ 2 > Haern (toxic) cq. heam \a- Comple of Polmertgcuen mn Hoemagoin (non - oH ) > . : BD by accuumilading’ iq the acitie vacuoles of fhe paraite ¢ beo, op ule weekly bag ature, it y, atses the vacuolar BH and thereby Integers wit 3 t egadation of Hb by farauitie — lysosomer © =P Hoan self or W's Lompler & CQ than damage the plasm otal menlovane s 1} abe aOther attions i- — Reve againsk t Entameoba * histolytica , Giardia (arblix St hag ant -loflammatery , lol writant and local anaetthatic tweak smooth muscle Yelarant + LN anti histamic and antiarrhythmic — properties Kose? Phar mecvekine ses " ay . : ae 7K S NH = CH = CH5-CH= CHa — NO \ Guy ° a Nn | myo’ oral absorption ef CQ is excellent . About Soy. get 4c ee bound in the plasma- 2S High ag finity - melanin & nutlear Chromah'h * Conc™ in — liver Spleen kidney Langs Skin “Melakougahen ~ partly metabolized in liver Eteretom —- Slooly exerted In Urine * Plame, tH ~ 3 te 1@ daye sTeroingd (Y= tte 2 monte Notes Zils selective Gcumulabion In vein Ts ~— Yespon sible for the ocular doxiarty TF prelongec cure S€on7. Gide effecte! Naureo 7 Vomiting Anoveria bi $ Unconhollable itching Epigarstic pain : Uneasinese ; : Headache s Avble theuts * @ toxicity is low ue doses Cas needed fer Rheumatoid .. Prolonged use of high C on du Go: tae visi arthritis DLE ekees may Cause loss _ of Tetinal damage * ; mental digtvbances 5 + Loss OF heaving Yashes » photoallerg 4 ’ tang a myopathy and graying of Whar can cus On tem ues 5 Cardiac depressirg sv in) OF CQ - can couse hypotension 5 Oyrhylhmlar § CNS &eh toxtelty inttiag Sei qures | (more Whely in children) DS tautien Sn presence of liver damage , Strert- Gr, neurological , retinal hearnasotogical disearu* | Attacks of Seigures porphyria. & psortasi’s paste may be precipitated » ACQ Should hot be co-administerd t other ani -arrbythmics Cmefloquine , Aminodéiens) = vin ¥ Chiooqpine Phosphate (aso mg = (so mg bue) this ‘ - thegy is hotrdly ‘any "indication for parentaral (lev) Chioveqyuine + IE Should not be injected bm duc & ity local tissue toalcity «Users > Disappearance ef Parartacmuia > tutraintesHnal Amoebiasis AV Rheumatoid avtaritis ‘ > Discoid lupus Srythemalous ~ Very effective lese valuable in systemic. tg > Lepra veattion > Photogenic Gasket Trfettious morenudleosis’ Affords Symptomalie wléep Nok: COIS no longer usecl A.A Suppressive Prophyloaiy in dndias | = Gis A Amodioguin (AQ) ota NO modioguin (AQ oH aks DAS|AG— Ast Bline treatment of P+ f — African counhies a a Approved in dndin AE Ts ‘not recommended for prophylaxic « Aaverce effet + Agronuilaytare and Hepaetortity — tong He ie. Side effect: Newhopenin ¢ dn HIV paltént revving — » Antivetroviral — Cherapy,+ at Dose? 95 -omglkg AS days oe oS_- Methanol '. inoline x Quingl ne’ Arete! 5 Fask ating erythtocytite — $chigontoude (but Stowerr than CQ or quinine due te prolonged Absorption ayter oral ingestion ) » > Gffetive againse CG= vesictant ¢ censitve plarnredio « ‘emal ing pasaiites - Single dose Usrs| 2) cian cael by PLS ss Hay Sn” Smmune ay well as cian intina t individuals’ ait is alto an efficacious Suppressive prophylathic Yet = multi-tesistant P+ faluparum and other types af malaria | MOA!- Similar te C@ ybut site of athion OB NG fs in the parasite tytosoh tater! In the aud vacuoles, Mg - Reststance ‘ Transalation ef Pfindy 4 gene, thoiigh Pgere. mutation may alto be involved = bovt aResistante fe) MQ Confers ont Holofant ine « “ee, oa Cross yesistance : ty Quinine Cry vat Absorption - Geecl y Bat peaks Slooty » “Highly plane ‘probe! bound: cand — Coneentrated in many Ovgany Lite, Jang, » Auves § lubechwers | concn are reached> Extensive metabolic - liver Primarily Secreted in bile ath » ato 3Wk- ~Mtannyees « Abdominal pain + Vomiting, * Sinus bradycardia © Diarrhea Q-7 prolongation + Disziness © Neuve payihiatic Y%™ (Alaata ,, anictys tavely conv Ubi ena) cvthese ave’ ‘doce -yelatzds andl) sdubside, ) OVO I Bitty on discomi nation « ; amatety , depression psychosi's y & in thote ©) Cardtat Ml viConduttion) clefrcty yyy } 1 a aM is wntraindtcated im patent Prlenackor, ( Halstanhine OTe Leng thning 5 Showld pot! be Quinine L heats to adm)jnitinid if cg Cardiac avvests 1 MQ hay been WZ _ yen ] Current tecommendahon & bo usei it only iw wy, aAssg dud) Lembination with » MQ sh ACT |-nuncdmplicaled |, matarin CQ -vecistant cares CQ tSulke ~pyTamethami ne (S[p)-vesghant carer a) a iOrHizeg & Sogn ir ‘f COrquinine 4 doxycycline resistant Cares y Pov “HG can not be givtn parentarally and is not Used in Complicatel [severe malaria « * Cinchona - Altaloid + Buinine + (weak bare) PErythrerytic — Schigontieide « Mk epes ef plaamedia « aS hat no thee on hypnogoi be, of Tetapeing malaria, but kill vivax gamete “RIS Lece effechve but more toxic than CQ 7) Resurgence of interect Gin quinine ft due lo the fact that most CQ and muuttids wg — rerittant *baing Of Pf SHU respond to its +n Bragit - Quinine + Teharycline — Standord heatment ef Gmplicaled malaria APDOLYCYUine Cory Clindamycin ee tory addecl to i fet Complelé parasite Clearance « Mont: Similay te CQ: Quinine Ruislinu’ Similar te MQ . Other Autens © Cardiodépretsant , anti arthythmte , hypotensive Acton | decreates Contractile power ‘of Skelelal muscle fibre hypoglycaemia (due to Teleae of insulin) 5 PGarhic & Secretion (bes epigattrc discomfert ) 3 St Stimuwteabs mgermatrium § tan Baue abedtion in ‘ everit snot a dependable early pregnancy However is eeePharmacokinetice. * AWQuinine is rapidly cond completely absorbed rally , +407 bound te plasne. . proteins , expecially, “1 cud Glycoprotein + * CSF Cenc? :- bow + Metaboltgahion - CYP3AY () * ticvehion —- Urine sbi T10)te lahrs) ; Aduerse Effecti $+ ‘Toxitity is high & doce related *S-logm taken in single clove. ene be fatal - + Cinchonismt 4 large. Single dose, ov, higher therapeutic doses taken for a few clays produces cx, Sy ndlvone Called... cinchonism « , Effect Ringing im EAN Fmaeteea s vomihing (Gautric ints, + 1L ¢Keal ahs headache 5 verge ty mental confusion 7 difgreutty in hearing. > virtual defects , Otarrhoen, shuukiyg © . ; the cyncheme _ subsder “completely athe dyug fs ie 4 During pregnancy tt Ahold he «rect aly en life * threaming, Ihection ) © Spewat cane. t8 “Proven b Wg PRUE casio of >!Uses, \ + Orally tor untomplicated CQ resistant molarie. - + LY for complicated [cerebral malaria - AVoremplicated — Recistank faluiparum melavia 4 Quinine nay be ured orally ar an alternakive to S[P -RCT uncom plicated CO - vesistant faluiparum malaria «Acti more rapidly then Sip alonee = 2d tine’ Aieedment Of CG-retictant matlaria- Quinine + Doxycycline [elindamysin regimen KA daye sCerlain CQ -reristant Shaing ave also verishank to 5[P , laut veipend to quinine = > Congicoted & Severe malaria including, Corebrak malaaiat- * Quinine Cv) has: been ‘the duug of tholce for cerebrok Fe lyome. Nady malaria. (falcipawm malaria Z impaired consciousness) & |) other forms af complicated “roles « ulatim) oo. 7 | + Parental artemisinin, are faster adlings more efycekive better tolerated |and more conveniently administered + 5 dm fe Avkesunate (iewliem) or attemether (im) or artecthey ppd ; \ RBypoghycacmia. dur to hyperinsulinemia i tha most ee mene { important Sde etek which can be prevented by | tngusting Yinine tn S-/- dextrose + Supportive headmunt needed in Cereloral malarin w Cerelorat me cooling fh fuer sity diayepam for convidsions ; iclosis . | samen ot fluid % electrolyte drolane & acidosis a. ee (ism) ave now preferred over, quinine yfer seureve malar!sNOTE ** Covkcotteroide are useless, mor] be howmul ~ atrold he QUININE — 300,600 mg tale | Geom [aml ing # Proguaril) Cehlorequanicle) “Enutheuytic Stnigontiide Pres erytinouytic 4! Pe a Gamétoujtes expored Uo proquanil ave not killed bub may fal ty develop propedy In the masquite « Mon: Proguanil |: utcsatien Gin body >) Cytlequaril (hlagine derivative ) ' le ONF Rose. —Thymi lidale Systheuie 2 dy Snkiéitron Of PNA. synthesis « Pr il Rest te oquanil Resislince 3 Mutational changes in the Plarmodial | DHERaie = thymidylate» synthase. €ngyme + Note there’ if a. parbiall ‘evoss Yeuiclade, Bleo Propuand and pyrimethamine. . : iT matokinélics = a Mbiorption of Oral proquani( i¢ slow, but almost vomplete ' 5; * Melabolizalion § Exrelien ~ partly Unete Ap 1G to 20 bys 2 4b ts Nery well Teleraled side effects te Cg- Abs 3 ave ese wmmpared Mild abdominal synplains a , + Uomsitings ; + Occanional Stomatitis + Hocmetionia. « Rathes “Fansient lore of haiy : * Proguanil + Atovaquone fet ais pico bout Conversion te Cyleguanil) Schizentitide for Heabmant| by adHE Race untelatid action Of MDR Pet Buk , most Pelentiatt, the schyonfuldal acim | oS i 7 i Usp, Thitland § oer *t Promuon [counter PRaserantit PROGUHAL toomg Tab 26 Pyrémethamine 1 = = Slee asting erythrocytic Suvigonh'cide > Does wot etyminate the the pre evyttvouyh'c phate of PsP ocd) cr0e YY throutic phase of Pevtivas d / | Pyrirmetnomine 2 pypRase, —Thymilidate Synth are Swhi bits DNA synthesisigh affanih SSdlecive aukmetarial achion depende om hid Ht ily fay plasmadial enayme (2000 timer reales than fa, dhe mamimelion engyre ) 7D Schiangony of malarial paraile — tn blood gradually Hops under =the Influence of. tyrimethaming « Ak hiep, doses it Inhibits betoplazma gondi: —) Pyrimethamine ic more potent — than proguanil « Resistance 4 Similar to proguanil - Pharmatckinetics + —— 7 Absorption ot pytimethamine — fem griek ie qoed but stew * AF Conc® + liver Spleen, Kidney lungs 9 Metabolization and etevetlen + urine , > XL'2 3 4 days entre ime in’ blood! go¥ 2 woke: > Prophylack'c Contentcrtions yemes n Advers. ars ese seed 7 Putimethomine TH weletivdy safe = Side e€fecty :- Nawsea Rashes - | — + Megokoblartic anatmio Gronulocy topent a CT high dota meu © Gy y i OCcuT * Folate debicieney Gare ) > Use - For a a Sulf > Sy 7 Su an Whea Use For Heatment te P*F only in combinatron with a Gulgonamide (s|P? or Dapsone - pyremethamin (s [P2 © amide - a Selfners 2 Synergetic combinaken due te sequential blotk + FS sutgonamides | dapsone are not pay Neularly effective have some dre ant-malaial dvuge bn their eon might > ‘hen Inbibitey influence on — the erythrocy He phase espuiallyy y Pek Though 5 both Componente! sare Sloto.aching:) the Combinaln SDibeopoater se that it canbe. ernpleyed.s a4 Clinical Corakive y pathcutarly for Pet By the addition of sulfonamide y deelepment’ of Tesistance To pyrimethamine. ts, vetarded + Ac dlintcal euratve Sulyadoxing 1S0omg. + PYytimethamine +Smg (3 tabs.) ~~ . Si ‘ children 8 @=tUyy Q tab.) NSE dese S-€yr t fa tab es pie revi, edgy te) he Popular Combinations aye + iy ms pac s Domy + Pyrimethamine asmyytab)? , Sulyameths pyragi , pepeyadine 500M +e PYVime Thamine ASmg tok Pagsone \oomg FPYtimethamine asmg tabRe, aa 9 Sulkadoxine and Sulbomethopyteaine are Ultra long Athi | Stuljonamides = clad Low blood tone yuk ave able to synerg ise with pyrimethamine which aio has long +1123 >the use 18 Teshicted te single dose treatment of uncomplicated Cg - resistant Prt beog S| adverse ested. ~ Prophylacte use , needing multiple unsuperviced doses is nok approved « the major importance of this Combination it due ite itty efficauy againt tg - resistance P-£ compliance i¢ qood due to tingle doce therapy and. feuriside ehectt + 1 Adverse. effects. | 1. ’ t , ' + Exfoliative dermatitis’: + Skevens = Toltncon’ Syndrome Contialidtcation: “Tntants ' Mergic to Sulkonamide TH Te not an effective | drug for Vivat malaria + + Sip - \St choice treatment = texoplasms — immuno % Primaquing wig + pvoce Staetinafset patient Terget =. Pre erythroeytion staige’ of Bf then that of Pv send gerin gd prwoat 9619247 —) Poor erythrowyhe — gchizontecde hax weak acho o Pe vivax rbut blood forms op Pf are. —— Vote a dt > 4 a he dt Advers a Dose cHae “MM Tr ats DNor mn que Porte PrimeFFect dent Votally insensitive « 8 Is highty active against gameloyter and hypnoreity DAM The Mon of primaquine is nok known bit fo eluddate it can generat, “sachive oMygen tpLs that cause outdative damage te cellular eomponent- Resistance ; Though | Rests tance among P+ Vivax against primaquine can be induced jit is not @ Clinical problem — Phormacckine hte » Readily absorbed after ova) ingestion = = St is ontdtzed im liver D> tts rote thes PEaveted in urine viothin aUhy « \ Sse Te HEE a. uurmala ve aug AAVE Se. efrecty . 7 ' > Dose velated. + Haemolysis * Methe em egicbinacmie | ~ Ta chy pron, *Gynosig toys Normal G-6-PO levels - Dose ~ Pou roge af lak urine te an wudication 4 haemolysis 5 Primaquine thoud be promptly Hopped i it occurs «_— Usual doses * Abdeminal pain + GT Upset * Gleakness fed uncariness in chert Minimiged by (king drug © meals * Lemtopenia, 2 larger docer SThe visk of faemolysis & leucopenia | \acreased in, + sLé and there Patient of Rheumatsid arthrihs cxcately ill - Contraintication: Primaquine sheuld net be vexed, given daving Preqnancy , becasue fochu it G-6-PO deficient - wo Ose + Radical uve of relapsing Wa molartin | Seng [day KIM, cays, & ether blood, sthigonbiedla edn Ref to Kil the gernelsy and, sunk... doson. transmission nos? et to mosquito Sel —Seng Single dese curative dose) of CQ ef AT Beet g Sng Notes Primaquins WSmgldexy given % clindamycin : oom TDs & an alternalive drug for Pr cumeyh Jivovect preumonla Iw ADS patient - ean? se Tafenogpine : doce “ald Yalepee’! dvug for oratanin Cuiyar) P 8 fighu actve again Vivax h no got? wy 3 wP \ a single A Tafenoqine is dt har able ahoww Soke Maer S Par and Ps f achive lagasinat aerial euylhyouy he icatherefore iE muck be arcom pained by ep oy snothax Linduading cq = tesiskart Sains) but clearance} fever anc povasitacmia, were — Slao+ srepidlay, ackug erythro He SthtaonHdde for viwear malaria vin porte ol kia lS Ge 1d days Ls 3. day treatment Calong @ cg ) = Hoot/+ relapse prevenken dn phase 3) clini \ tefale:) A ADR's are similar te brlmaquine , but overall Aolevabilihy appears te” be geod! + a Settling and Donslne a slowly auhng- and wealx erythrouytic Sivizonbivdlall Quien eqaimat all pluimodiol | per imduding CO, M9, SIP resistant Pep. AMTebranyiline” ae never” Used alode tel het ‘ronan, ao {buk only Ln winbinatin = @uinide ‘for Cop reistant |" Pf and PV - fob ovine) be Dos 250mg G1D Tekauelinge Yd HUH? Ipryra WA te fiane Po oslgvenq avi t ts affetea coud, samilar loo mg od Doxyel cine > Doxytythine /2o0mg [daw T Act - resistant Pez oapok speegire loo i 499 ling pre prylaclic fr Short ~ lem Aravellere ito CP-verizlant Pop Aven + Cophat edison: Tehaujliner ave nok be given te children and pregnant Women « =os Noter No clinical useful achen is exerted on he ‘Preerythrouste stage © Garnete wy Te ond Vivex hy hyproanits ave algo nok Killed - O Clindaray in | % 4 Batteriostehc ankbioke that! har «lous aching rion, Gcizontiidal property agatnck all spit of Plarrneda, lacluding MADR ctraine ef pf - Pelertiater the antimalarial, avivity © quinine tart avtemfssinin ( absaiy’ ‘sed in’ combinahen & ove . * true) 34 thdee: dung te doryiyetine (or MOR Pof ev CO Reis tink Wier | 44t can be wed lq children and Preqnant. women er sack, uted for prophylactic treadment, cue ‘te vist ot adverse epectt Chrice dosing) x ARTEMISININ DERIVATIVES. = Ay temitinia lit. Are atktve rieuie ej the plant Qieme Sia annua * Ad ic o tesqpiierpive lactone encloperoxidare ahve aijotnit Ps faleiperurn resistant | to all other ank aataadd dotig ay, toch ot and other mnadaviel Bpetn dome ed wensihye Synwe > Poknt & qyticker ropicl schizontitide auton ts ercrted altiting defervescence G parasitarmla’ clearance (cushy (dee th bedity emp) than CQ or arup. other drug e frerk ation -Ring forme to early sthizont « a (oroadest time window of ankm aiken ) A Arkemicinin is pooty Soluble in weiter as well arin als lal + Artemether - Soluble in ail orally oy lem l sArkesunak (sod) - Soluble in water - orally ev 7 | fener BY Arden isinint + Arteether ~Soluble. in cil) - jen, | = AriewOlane ~ orally. ~ Synthefic compound che duvation of action ie chore and recvadescence vate Is high) chin Shey ate ured alone sia short courses “| ie in yeermpha sizer atte need — be cue arte misinine onky, c tombinalion t a drug cahich ach by x duitent muchanism + No trate vetislance 9) Ssothen) claw 4 ant malarial diye “aRatslance to Pe foie mob a clinical problem yet s AReoudecence con be telally jreuestid hy wombining , 3 day ontmitiin |Z lows, aking dng: fa carly stage material doug ave (the ay ¥ fa Qlae Thee —T1 td nptiimAtuve ohh, [ey donot totally ante b ; Biscare -Hranmitsten + Arbemisinint do not Wher wept a Uvex hupnogeiler a Inge fore dh {PRezotter i i7? Endoperoride Bridge 4 Haeme Cin parecite) (drug) ‘i Ferrous’ iron - mediated Cleavoge of the bridge | Releases Highly reautve free radical stg L Binds to membrane pron, : a lipid peroaldatian | damiage, “Enideplaimio ehaalire deo bypis ' AThe avkemisinin free vadicale Speet ficadly inhi: ¥ a paimedial \farcoplaim ie -endoplaimiz calor ATP be labelled “PE apg?” Phar maxckinele » : -1PK of artemisinin’ > derivabver es Keni tech & incom pl 3 Beth adetnate | and artemesher, ave prodxeys ae We tesunabe | =_— aghe $edium | sotk Cue waders! and is adminittered by oral 4 ibm (or tev - route : -yRocorprion is incom plefe but, fast, \,veachIng Peck in <60lmin Cov atly )metebolicaton ; “ 1 Arkesunate TS PSEAIM pHa (Dihydre artemisinin) Adive metabolite with of DHA % 4 to rhys _y after Yepeated dosing > avkesunale causes ae induction (sel regulation ) 4 it oon metabolism by CYP, @6 and cyPZpy- / FALCIGO 50 mg tab, 60 mg [viel dy + x Artemether } nT _y4t is lipre - soluble Ron s Oral ov km = Absorption, abter oral cx well ar tem dosing ig Slower faking 2-6 bys * Avtemether 2 DUA (aictve metabolite) yields a variable - | >) Eitengive metabolism by CYPSAY A'fp - 3 & hts: LARITHER » MALITHER Semg ny (Cin aml axaw) vil PALUTHER 4 @ x |p _prtecther= " rioted YIem administt aber ony cclulks | fo Complicate maloriat | kNfe aphies dk is concidered less epencdab le in severe [tomplicated mabe ' Sythe WHO Yecomimendr a day course Dose += 15D mg bm KB Aays iH adults - FALCY Isa mg [2ml omP» Dihydyo artemisinin and Arte volane hese are available 407 oval and are considered with ACTS Adverse effect + -y Mild, t7 Natiea Brug fever Voriting \eAbdominal pais iit Tching 7 Rare = - Headache “9-7 prolongation " Tinnitus * ST Segment changes Dizziness © Fivsk degree »A-Voblet Bleeding + Transient , Vet cutopen io- ~ Dark urine . leuce penta - csThece ADRs subsides tohen the patent ‘im proves or drug is stopped 7 «IV avtesunate ts much safer than eV quinine. Tntriactions | & Attemisinine © avag prolenging 9-1 may, increase the ivisk of cardlac, conduction defectt+ Q- T prolonging drugs $- As temizole (ant h'stunix) Andi —arthythm ics \ Tricyettc depressant; Phenothiar ines), >, | uce only wm Combinak,= = | Use bo ‘ } + Uncomplicated falciparum rralaria — | Oras prtemisining - teatment of all cater ef Un complica | Prt as Aer’ (Cq- resistant Senshi) ain order to preserve their Powerful ankmalarial adivity and to reduce Yecrudeccence Yeutes thay mut be wed in cwmbinaten with w leng - aching Schizentiide which acti! by different mechanism - % For vivax malaria yar temisinins Cac ACT) are indicated only In case Of C@-vesistank infect and when | Quinine + doxyuyetioe [ clindamycin also can not be ced « 3Use of axvtemisinins for prophylaxis of malaria is nok | allowed ) due to their short duration ef action and : i higher potential toxicity + Morever 5 wide spread prephy- -che Use wll faster resistance « * Swere and complicated falciparum) malaria t- parenteral arvtemiginins are highly effective \énd are | the drugs of. cholce , irrespech’ve,. of CO-vesis tance { Stodus« Quinine tntused is osadrag of chaice — Severe and t at Complicated malaria y But now, fe] fm artemisinin, are pre ferred y while quinine és used only aan AUernabve when artemisinin ¢ Cannot be used « Advantage of Artesunafey Civ), s SE comer foster parciite clearance. than BY yxinine +S 1 tobe and better than tolemlal than Y quinine SsTHE doting kchecule it simpler + Recent evidence indicates higher efficacy and lowe, mortaltty + athe Nugpce , har decided te ute erly fev artesunate fos Seve malaria as only artesunate, Sed tan be given EV Cenove Yapid peak cont?) sMatofanhine e TT Phenamthrene methanol bleed. schrzontbeide THACKYITY comparable ty Preflequine uaith «hich vik exhibits cose resistance > Bffechve against cg and S[p vetistanb Pe fand P.v A Oral abserpiion is low) anid evrake! ahd” elde effect are relatively Lommen Cprclengahten 4 Qt intreral) 3 Tt is not afriouel in Sndia NEEM TE Gs poke achive agtidel dametouy tes ov hepatic Stages epidthe\ malarial paraite, + Movaniene’d iCayathelte ‘Mapthoniinone ) . > Rapidly arting crythroah'e § Schizontoade av ebell an. an attve against ee tM oe stage °F Pot and Pey. ** of S> Plarmedial mitochondrial membrane Atovaquone 7 1 O_) ATP productinen «+ Plovacitone + proquanit * sdays. — uncomplicated ab CG - resistant Peg £ Potenteites cancel prevent Pav ; Teristance Cnok in dndia ) a Provaqiene — prephylacte drag a Meaquone - and line of diugi= P jiroveci 4 finiee T. gondit Side egfects t- Diortheea Nomi ting Headache Rashes fever Conha indication t Dertag Pregnanuy ) a Artemisinin — Based Combinak'en Therapy cact) | ~ Bue te emergence of CO-resistant”, followed “by MDR Pet | the WHO has Yetommended that all cases | Of acute uncomplicated falciparum malaria, sheuld | be heated only by terabining one Of. the arbemitinn, Compounds with cinother e@ Ffechve ery throcy Ke Sthizen hud Select PSeegton | of a Sermppanion’ ‘drag’. O Ahination t's Effective comers Tn blend muck be maintained for atleagk 3-4 > asexual Cycles of the parasite ire G-§ days te exhaurt the porcaute \ burden A shork Uf. => x doy cory =) To 8 doy longer (if, 2 Kt To Belgos Buk lenge + \a deuge allow — subinhibs tory tonen, te pevsick. wn the blooel facilitating selection of ' Tesistank mutant. ie, Combining a short © Ie Airing th long tla drug in the conventional 3 day regin, Yuns the vick of de facta monotherapy afler the ta divig is elimincled bf aaenh ® 80 :that Cheesing a sherk t'la dug thak reduc ty Parasite loa! topldly and drastically fey Short Attemisinins — kill >45+/- plasmedia L Reraining can be eliminated by the Leng Ufa drug reducing chances ‘of-nutastitn Adwartaga bp Acr: : aa Rapid clinical and paracitological care : | > High aire wafer (>45 7.) and low recrudescence ele arhbence of poraule veaistance (the Lompenentt prevent clevelepment of retiélance te cach ethey) Good folerability profile . “oral ACTe = Uncerplicated Pe = Appice Ly WHO Alveady bh wd JF te tee dren lena act to tbe ated in Severe ov complicated malarte | he, parental Aru Or needed- bor a ACTs» oO Arkesunate - Sulfadozine + pyrimethamine (AS- sip) eFivst line drug fer uncomplicated RE Candew NADI) ich ore NV e Not effective against MOR shains which are nontesponsye To slp © >46 t/+ Sucese vate “NuBocp continues ‘te Use AS- JP ACT as the firetline theraty 1 induding thet duving andg 37d nimesker of Pregnancy + * Produces fewer side effects than artesundte ( mefloquine . © Artesunate — Mefloquine | (AsiMg) *Gandard and most extensively ured ACT In some~ | counbias 5 but iE use in Sadia. it limited fo.an extent = © Highly effective and welt “tolerated in uncomplicated Ps 4 ceoeniangh with AS, farther spread aq] MG yeistance was | checked some of them ra sunitched ower alternatis, ACTS. Side effects Of MQ are to be watched « ® Artemethey - Lumefantvine eiibey . Lumefantrine - orally active high efficacoul long - acting arythroey he tchizonticide MOAI Similar te Mg + Halofantine Cchemicaly alte) » ‘Raditionally 3 nucleic aud and protein ‘synthesis of the e faraite fy eggected .of Yi Note: Vivas hyprozoites are nok effected - Pharmacekineticr +. =—— > Lumefantine i¢ highly Gpophilic and absorption start after dhs of ingesHon and peaks at 6- hrs > Plaima protein binding i= 19-/+ > Mekaboligation - CYP3AY, a Terminal t'h s Qte 3clays 4 6 days [in malaria pots a Ackon tr slower than cq: + Lumefanki r . forking | is ied enty in Combinatin with artemehery as fixed Dose combination cfoc) tablets + The too components protect each other from plaimeltal membrark Tesis tance * + No dinteally srelevan & aye ststante for: « Clintally epeacyy ~lumefcantit ne hai developed 50 - high achiewing 45-99 t]- Cure role « Avkemether ig active even in Mork tesiskank anc MQ — resistant Pe quickly reduces peneesi be £ Aves biomass, and *Arkemether my resolver Symptons > wee tude SNe + Lunes tine prevent Gameterylt population ix veducech y Checking Hoanamission +Administabin x uotth fay food or mils (te ensure absorp li tnd stake Hee levels — faatere mad teal“ Tecrudes cence ) sThit ACT. is genexatly well toleadtad [bets tobneti| Hoan As (mq) Side Efe ( Headache Dizziness Abdominal pain Sleap dishbancel Avihrald ie Hyalgin prarihs Raah rdera tion — Lumefantine inhibitt the Iscengyme should not be given with drugs metabolized by cyP2 DG ise, Metoprolol Neutolep 8 Tricyetic antidepres Si Mepreaae CYP2OG* So AM=-L athis ACT must nat be given with drugs prolonging Qie | Simte these dvuge Can alto prolong QTc» Genki Indication: During Fivsl trimester oy Prec nancy Breast feeding (YW) Dihydro artemisinin (ona) - Pipcro.quine ). —rPipevoquive ~4- ammoguimoline — High efficacy. long akg engi roche Schconbucle —> Slower anscl of action because of danquc of distubution + wrote,Men | Smiley to CQ + ast ic equally active against CO Sensitive , bud mg ackive against cg - resistant Paf QD Lie + Be Yo. *Pipevaquine har been toformutatad with DHA Ing dose vakio of BSL and ctlentively woluaked jy NDR Pf areas + Some teuntle: Latth high Suce ts Take - + Safety prefile % pA - piperaquine ie ged and jt is well tolerated even ty Children - Side ebtettis Dizzinecs Memiti : other 4 4 dk: 48 Sptoms axher 4 Rare - DHA ~ Pperoquine 0c how. Cornpleted » clinical voter trails im Andio. -broducin +A. wespete robe te ebncom pleated P-F yand ik ic Rieti te be approved hoon = ’ Date 1 ptta oma + Plpcragtine, AED nq daily X38 dau (amg fxg) a) f . CARTERIN) Aa Artesunate —- amediag ine CAs (ag) AQ itsele har a Short tb dus to mpi mutabeliom | its metabolite | an cently ‘ehh antimatarie] has dong tie of to- LY etaytYr Oo “AG may not be cfhective tn aren, 69 vevistank ae Aviaty = In Advice v Sotte{actory retponte LAddition of AS favther tmprowed the atre ¢etF> eo dndio. - Clinical dad — aa yecute of PF Dees Auesunate Joomg + Amodiaquine Goong % 3 deeape (Umgikg) emg 1k) Atletunate Img [S0fioo + Amediacprins 635mg] 135/40 Foe hat been approved in drdia « © Ariexolane “Piperaquine - | JAderolane att rapidly ak all Atages of ascxued \ Schigegony 84 reafentel ponastle netding MPR Pf | but -has no effect om Aepatic Atager de actiumufota in the food vacuole of the porctile, § Aux difhers Gem the arkemisinine which denot attumulate at this site Sk also har moderate gqrinetiocidal activity | Aimilox be hal of Artemethen ~ Lumefantrine Both anterotane & Piperaqung | are uxt absorbed drally , and abschpiten SH) Unebbtcted by food - “Peale plata cone” levelr 2 Bite Shes, har lange Volume ot dis hibuttory - + Atterolane = piperaquins - melabeligahin - CY PaAy Veecri ype~~ + Clinical effttary — 215¢)+ + fever § paraiitarmie Cleavance time - 24 te Uhr Side Epheetis Mild headache Postural dizziness Vemiking Abdominal fain Diavvhoen. ® Avtesunate — Pyxonaridine > = v this ACT shar not yet been approve in dnd. = pyronaxidine -rwaler xolubte erythronytic Schizontourde Thigh efficacy. ~Attive again t beth C@—seruibve & teristant Pa onset of ation ie Slower F duration lo, mon + Similar to cq. A Aecminal tla > Adauys * Clinteal effiecey © artesunake ~ pysonartdine PC (I) 7 7QS*]o ero recrudescence Wm ag oat eMDR PE and Pv alro ~reipond « “Mb ts well bo levated: Abdominal: pain 5 palpitation - Vomitr es \ Tene €CG thanges Dizziness he Aerlouy yar Ocul loss 4 Appetite |