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.THROMBOCYTOPENIA

MOA

DRUG INDUCED BLOOD DISORDERS CAUSES1.APLASTIC ANAEMIA RBC,WBC,PLATELETS2.AGRANULOCYTOSIS WBC3.HAEMOLYTIC ANAEMIA RBC4.MEGALOBLASTIC ANAEMIA RBC 5.THROMBOCYTOPENIA PLATELETS

1.DRUG INDUCED APLASTIC ANAEMIA

Most seriousPancytopeniaHypocellular bone marrowNeutrophil count: 0.5 109 /L

e

CATEGORY DRUGSANTIBACTERIALSChloramphenicol Co-trimoxazoleANTIRHEUMATIC DRUGSPenicillaminegoldANTI INFLAMMATORY AGENTSPhenylbutazonediclofenacANTI EPILEPTICSPhenytoincarbamazepineANTI THYROID DRUGSCarbimazolepropylthiouracilANTI MALARIALSPyrimethamine ANTIDEPRESSSANTS $ ANTIPSYCHOTICSChlorpromazinedosulpineANTI HYPERTENSIVESlisnoprilANTI NEOPLASTICSmethotrexateANTI DIABETICSChlorpropamidetolbutamideOTHERacetazolamide

MOA

DOSE DEPENDANTDOSE INDEPENDENTIMMUNE REACTIONHaematopoietic supressionPharmcokinetics $ hypersensitivityMost commonCause-chemotherapy/radiotherapy leads to apoptosisActivates immune system

Chloramphenicol 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 OCCUR

TREATMENT

Remove suspected offending agentSupportive careHSCTImmunosupressive therapyG-CSFGM-CSFI44

IMMUNOSUPPRESSIVE 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 /L

DRUGS

CATEGORY DRUGSANTIEPILEPTICS1.cabamazepine2.phenytoinANTI INFLAMMATORY1.penicillamine2.NSAIDSANTIPSYCHOTICS $ ANTIDEPRESSANTS1.chlorpromazine2.clozapineANTITHYROID DRUGS1.propylthiouracil2.methimazoleANTIPLATELETS1.ticlopidineANTIMICROBIALS1.penicillins2.dapsoneCARDIAC DRUGS1.ACE inhibitors2.procainamideOTHERS1.methyldopa2.allupurinol

MOA

TYPE I TYPE IITYPE IIIImmune mechanismToxic mechanismBotheg:quinidineEg:penicillin

DIFF. 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 related

SIGNS $ SYMPTOMS

Sore throat

fever

malaise

weakness

Chills

Perianal pain

skin inflammation

TREATMENT

removal of offending drugDiscontinuation of drugGM-CSFG-CSFClozapine induced agranulocytosis

concomitant clozapine $ G-CSF

Corticosteroid therapyAntibiotics therapy

REFERENCES

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