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C.8. C.9. /S.II G Courses Prof Cursuri Romeo T. Cristina T. Romeo Cursuri C.8. C.9. Image soure: ®® http://www.colonlove.com/assets/images/Parasites.jpg /S.II Antiparasitic medication Courses Prof. Romeo T. Cristina® Introduction thethetheantiparasitic therapy isisis based ononon aaa large number ofofof substances, thethethe majority ofofof them areareare syntheticsynthetic.... Most antiparasitic drugs affect thethethe neuromuscular system ofofof thethethe parasite bybyby blocking thethethe neuromuscular junctions, with thethethefinal result ofofof: of ::: paralysis, death and disposaldisposal.... itititisisis known that helminths have also aaa reversible paralysis, sososothat ififif they areareare not eliminated ininin due time, they will recoverrecover. ... Courses Prof. Romeo T. Cristina® The substances ofofof tehthe tehorganophosphorus group eraare era knownforfor fortheir effectiveness onon onboth helminths and ectoparasitesaerare aergrafted ininin their useuse usebybyby relative high toxicity ... Their mechanism isisis based onon on blocking ehtthe eht acetylcholinesterase enzyme, which isisis tehthe tehenzyme necessaryforfor the forthe thehydrolysis ofofof acetylcholineacetylcholine. ... ByBy Byblocking this enzyme, tehthe tehmediator can onno onlongerbebe be releasedreleased,teh,,, the tehstimulus remains open resulting htethe hte exhaustion and death theofofof the theparasiteparasite. ... Courses Prof. Romeo T. Cristina® Other substances interfere with thethethe processes ofofofATP phosphorylationphosphorylation.... dichlorophenol, niclosamide, benzimidazoles block thethethe incorporation ofofofofofofof phosphorus into ATP molecule and interferes succinate and fumarate reductase enzymatic systems ... The inhibitory effect occurs ononon mitochondriamitochondria. ... Other actionaction: ::: ovigere inhibition function (((benzimidazoles,(benzimidazoles, phenothiazines)phenothiazines).... Courses Prof. Romeo T. Cristina® Currently there areareare fewfewfew substances (avermectin(avermectinssss)))) that act selectively ononon thethethe parasites located ininin thethethe CNS, serouses and musclesmuscles. ... External aaantiparasitic also benefit from uptake ofofof vegetable orororsynthetic contact insecticides, Carbamates and organophosphates arearearethethethe most importantimportant. ... The advisable mode ofofof removing helminths isisis tototo treat pregnant animalsanimals, ,,,atatat calving and then 222-2---3333timestimes/ ///yearyear thethethe young animalsanimals. ... Courses Prof. Romeo T. Cristina® AAAcomplete anthelminticanthelmintic: ::: high therapeutic indexindex; ;;; broad spectrum anthelminticanthelmintic, ,,, onononadult forms and especially ononon young onesones; ;;; absence ofofof side effects and lowlowlow toxicity ;;; short residual timetime; ;;; high retention timetime; ;;; Drugs from thethethe last generation (Ivomec, Abamectin, Closantel) have aaa aaa quite long persistencepersistence, ,,,that’s why two orororthree treatments areareare sufficientsufficient. ... Courses Prof. Romeo T. Cristina® http://3.bp.blogspot.com/_bBqysXGhPys/TVLcNzxDlFI/AAAAAAAACT4/NcJYzxRtYjo/s1600 /intestin%252Billd%252Bwith%252Bround%252Bworms.JPG Modality of action of the anthelmintic substances Courses Prof. Romeo T. Cristina® So farfar,,,, there are known four main mechanisms of actionaction:::: 1. Affect neurophysiology -- atatatthethethe interneuronal and neuromuscular synapses levellevel: ::: -- acetylcholinesterase (O(O(O ...PPP...)))::: neguvon and cuma phphph ososos ,,, couples tototo cholinesterase inhibiting thethethedegradation ofofof acetylcholine ininin choline and acetateacetate. ... Acetylcholine acts ononon thethethe postsynaptic receptors causing spastic paralysis ofofofthethethe nematodes that ininin this case stays nonono longer attachedattached, ,,,being expulsedexpulsed. ... Courses Prof. Romeo T. Cristina® Cholinomimetics ---iiimidazothiazole imidazothiazolemidazothiazolessss and tetrahydropyrimidinetetrahydropyrimidinessss arearearefixed also ononon thethethe postsynaptic receptorsreceptors: ::: ---ItItIt produces intense depolarizationdepolarization, ,,, but reversiblereversible, ,,,ofofof thethethe muscular fiber ... AnticholinergicAnticholinergicssss (eg(eg(egpiperazines group) ininin helminths and invertebrates affectaffectssss acetylcholine and gamma amino butyric acid inhibitor (GABA )))neuroneuro- ---transmitterstransmitters causing reversible flaccid paralysisparalysis. ... Courses Prof. Romeo T. Cristina® 222.2... That decouple thethethe oxidative phosphorylation Salicylanilides and substituents ofofof nitrophenols, Act ononon thethethe mitocondrial wall and decouples thethethe oxidative phosphorylation after succinate synthesis which accumulates ininincells, with thethethe production ofofof ATPATP. ... 333.3... AAAffectAffect cell integrity Some anthelmintic components prevent thethethe polymerization ofofof tubulin from which result microtubules (((formations(formations with constitutive role ininin cytoskeleton, present ininincytoplasm and mitochondrial membrane)membrane). ... Courses Prof. Romeo T. Cristina® Benzimidazoles bind tototo tubulin dimers and prevents them from polymerizingpolymerizing.... -- this action onononmicrotubules isisistranslated bybyby: by ::: -- inhibition ofofof glucose uptake bybybythethethe parasite and -- reduction ofofof reserve ofofof glycogen, -- reduced secretion ofofofacetylcholinesterase bybyby parasitesparasites. ... Depolymerization -- takes place bybybybinding tototobetabeta- ---tubulintubulintubulin.... -- this explains thethethe lowlowlow toxicity forforfor thethethe vertebrate cell cytoskeletoncytoskeleton. ... Courses Prof. Romeo T. Cristina® InInInthethethe reactions ofofof phase III thethetheparticipating enzymes areareare:are ::: flavin monooxygenase (catalyses thethethe oxidation ofofof NNN ororor S)S)S);S) ;;; dehdehyyyydrogenadrogenadrogenasesesese;;;; xanthine dehydrogenasedehydrogenase; ;;; glutathione peroxidases from mitochondria ;;; esterases === break thethethe esteric and amidic intermolecular bonds, resulting ininin conjugation (phase II)II)II). II) ... InInIn phase IIIIII isisisnot important only thethethedrug ,,,but also bilirubin, bile acids, steroid hormones occurring from thethethe conjugation reaction inininthethethe endoplasmic reticulum ininin thethethe presence ofofof glucuronyl transferase, acetylacetyl- ---transferase,transferase, sulfo and methyl transferasetransferase. ... Courses Prof. Romeo T. Cristina® The metabolization occurs especially ininin thethethe liver and isisis biphasicbiphasic.... aaa.a...Initial biotransformationbiotransformation: ::: -- oxidation, -- reductions and -- hydrolysis (catalyzed bybyby microsomal enzymesenzymes) ))).... Monooxygenase have mixed functions with catalytic role ofofof oxidation ofofof exogenous lipophilic substancessubstances. ... Cytochrome PPP450 P450 isisis(((usually) (usually) ininin helminths thethetheterminal catalytic element ofofofthethethe oxidant systemsystem. ... Courses Prof. Romeo T. Cristina® The enzymatic induction ofofof anthelmintics Those containing imidazole nucleus areareare inducers ofofof biotransformation enzymes ::: levamisole, benzimidazole, clotrimazole, miconazolemiconazole. ... Antiparasitics areareare subjected ininin particular tototo hepatic oxidative metabolization ::: --- molecules ororor their metabolites become substrates forforfor flavin monooxmonooxy yyygenagenagenasssseeee and cccycyyytoctoctoctochhhhromromromromeeeePPP450 P450 ... The toxicity ofofof antiparasitic products New substances have aaabetter electivity against parasites and arearearegenerally well tolerated inininthethethe body ofofof thethethe host animalanimal. ... Courses Prof. Romeo T. Cristina® TetramisoTetramisolelelele === toxicity especially inininhorses (cholinergic)(cholinergic); ;;; Metyridine === local reactions when administered scscsc; sc ;;; The associationassociation: ::: metyridine +++ trovamil === deadly effectseffects. ... RafoxanidRafoxanideeee ===safety average margin, may produce amaurosis even atatat lowlowlow ororor medium doses ... NiclofolNiclofolanananan,,,,bromobromo- ---salycilinidesalycilinidesalycilinide,,,, ininintototo aaa lesser extent oxyclozanide, Nitroxinil should bebebe administered with cautioncaution.... New cestocidal substances generally have lowlowlowtoxicitytoxicity. ... InInInallallall cases, youyouyou must pay aaaspecial attention tototo thethetheanimals that areareare tiredtired, ,,,weakened, cachectic and debilitated, with chronic diseases, tototo pregnant females ororor young groupsgroups. ... Courses Prof. Romeo T. Cristina® Classification of antiparasitic substances Courses Prof. Romeo T. Cristina® Antiparasitics areareare : internal and external. The internal ones have action ononon nemathelminthes and platyhelminthesplatyhelminthes.... A. Affect nematodes (old): Santonin Alkaloid from the plant Artemisia cinae. Photosensitive turning from white to yellow. Needs to be conserved into darkness: Separanda ... Courses Prof. Romeo T. Cristina® Acts especially ononon those with well developed muscles, causing their paralysisparalysis.... Good results ininin: in ::: ascaridiosis, ininin swine and dogsdogs. ... Has nonono effect ononon immature ororor larval migrans forms ... Phenothiazines --- synthetic substancesubstance. ... Very sensitive tototo moisture and light, this isisis thethethe reason why isisis kept ininin tightly closed vessels ininin thethethe darkdark. ... Has hemolytic actionaction. ... Courses Prof. Romeo T. Cristina®
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