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Pharma
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PRESENTED BY
LAKSHMI MENON
IV PHARM.D.
DRUG INDUCED BLOOD DISORDERS
PROTOCOL
INTRODUCTION
DRUG INDUCED APLASTIC ANAEMIA
DRUG INDUCED AGRANULOCYTOSIS
DRUGS
MOA
SIGNS $ SYMPTOMS
TREATMENT
REFERENCES
DRUG INDUCED BLOOD DISORDERS
Adverse effects
Rare
Morbidity $ mortality
TYPES
1.APLASTIC ANAEMIA2.AGRANULOCYTOSIS(GRANULOCYTOPENIA)3.HAEMOLYTIC ANAEMIA4.MEGALOBLASTIC ANAEMIA5.THROMBOCYTOPENIAMOA
1.DRUG INDUCED APLASTIC ANAEMIA
Most seriousPancytopeniaHypocellular bone marrowNeutrophil count: 0.5 109 /Le
CATEGORY DRUGSANTIBACTERIALSChloramphenicol Co-trimoxazoleANTIRHEUMATIC DRUGSPenicillaminegoldANTI INFLAMMATORY AGENTSPhenylbutazonediclofenacANTI EPILEPTICSPhenytoincarbamazepineANTI THYROID DRUGSCarbimazolepropylthiouracilANTI MALARIALSPyrimethamine ANTIDEPRESSSANTS $ ANTIPSYCHOTICSChlorpromazinedosulpineANTI HYPERTENSIVESlisnoprilANTI NEOPLASTICSmethotrexateANTI DIABETICSChlorpropamidetolbutamideOTHERacetazolamideMOA
DOSE DEPENDANTDOSE INDEPENDENTIMMUNE REACTIONHaematopoietic supressionPharmcokinetics $ hypersensitivityMost commonCause-chemotherapy/radiotherapy leads to apoptosisActivates immune systemChloramphenicol Nitrobenzene ring
Injury of mitochondria nitroso group
Affects erythroid cell lines react with DNA
reticulocytes $ PCV damage to chromosomes
cell death
CHLORAMPHENICOL INDUCED APLASTIC ANAEMIA
DOSE DEPENDANT
DOSE INDEPENDANT
SIGNS AND SYMPTOMS
ACUTE
CHRONIC
WEAKNESSPALLORFATIGUEDYSPNOEALASSITUDEPETECHIAEINFECTIONSSEVERE BLEEDINGARRYTHMIASDEATH MAY OCCURTREATMENT
Remove suspected offending agentSupportive careHSCTImmunosupressive therapyG-CSFGM-CSFI44IMMUNOSUPPRESSIVE THERAPY
1.Antithymocyte globulin(ATG)
immunosupressive effects
DOSE:40mg/kg/day for 4 days.
15-20mg/kg/day for 8-14 days .
ADR:serum sickness.
2.ATG+methylpredisolone
3.ALG
4.Cyclosporine
5.glucocorticoids
2.DRUG INDUCED AGRANULOCYTOSIS(GRANULOCYTOPENIA)
decrease in leukocytesMainly neutropeniaNeutrophil count:0.5 109 /LDRUGS
CATEGORY DRUGSANTIEPILEPTICS1.cabamazepine2.phenytoinANTI INFLAMMATORY1.penicillamine2.NSAIDSANTIPSYCHOTICS $ ANTIDEPRESSANTS1.chlorpromazine2.clozapineANTITHYROID DRUGS1.propylthiouracil2.methimazoleANTIPLATELETS1.ticlopidineANTIMICROBIALS1.penicillins2.dapsoneCARDIAC DRUGS1.ACE inhibitors2.procainamideOTHERS1.methyldopa2.allupurinolMOA
TYPE I TYPE IITYPE IIIImmune mechanismToxic mechanismBotheg:quinidineEg:penicillinDIFF. TYPES OF IMMUNE MEDIATED
1.DRUG ADSORPTION MECHANISM
2.INNOCENT BYESTANDER MECHANISM
3.PROTEIN CARRIER MECHANISM
4.SPOILED MEMBRANE MECHANISM
1.DRUG ADSORPTION MECHANISM
Drug +membrane
complex
antibodies
complex
cell toxicity
2.INNOCENT BYESTANDER MECHANISM
drug antibody
complex
Cell membrane
activate complement
cell destruction
3.PROTEIN CARRIER MECHANISM
drug+protein carrier
complex
antibody
activate complement
Cell destruction
4.SPOILED MEMBRANE MECHANISM
drug
membrane
autoantibodies
destruction of cells
CLOZAPINE INDUCED AGRANULOCYTOSIS
An antipsychotic drug10 fold higher incidence of agranulocytosisIncreases with ageIn femalesNot dose relatedSIGNS $ SYMPTOMS
Sore throat
fever
malaise
weakness
Chills
Perianal pain
skin inflammation
TREATMENT
removal of offending drugDiscontinuation of drugGM-CSFG-CSFClozapine induced agranulocytosisconcomitant clozapine $ G-CSF
Corticosteroid therapyAntibiotics therapyREFERENCES
1.Pharmacotherapy by JOSEPH.T.DIPIRO,6th edition,pg no:1875-1881
2.Pharmacology $ pharmacotherapeutics bySATOSKAR,17th edition,pg no:491-493
3.DAVISONS principles and pratices of medicine,20th edition,pg no:1002-1006
4.Medicine for students,GOLWALLA,20th editio,pg no:340-342
5.www.wrongdiagnosis.com
6.www.mayoclinic.com
THANK YOU