DRUG INDUCED BLOOD

DISORDERS

PRESENTED BY
LAKSHMI
MENON

PROTOCOL
o INTRODUCTION
o DRUG INDUCED APLASTIC ANAEMIA
o DRUG INDUCED AGRANULOCYTOSIS

DRUGS
MOA
SIGNS $ SYMPTOMS
TREATMENT
o REFERENCES

DRUG INDUCED BLOOD

DISORDERS

Adverse effects
Rare
Morbidity $ mortality

TYPES

1.APLASTIC ANAEMIA
2.AGRANULOCYTOSIS(GRANULOCYTOPE

NIA)
3.HAEMOLYTIC ANAEMIA
4.MEGALOBLASTIC ANAEMIA
5.THROMBOCYTOPENIA

MOA

DRUG INDUCED BLOOD

DISORDERS
1.APLASTIC ANAEMIA

2.AGRANULOCYTOSIS

CAUSES

RBC,WBC,PLATELETS

WBC

3.HAEMOLYTIC ANAEMIA

RBC

4.MEGALOBLASTIC ANAEMIA

RBC

5.THROMBOCYTOPENIA

PLATELETS

1.DRUG INDUCED APLASTIC

ANAEMIA

Most serious
Pancytopenia
Hypocellular bone marrow
Neutrophil count: 0.5

109 /L

CATEGORY

ANTIBACTERIALS

DRUGS
Chloramphenicol
Co-trimoxazole

ANTIRHEUMATIC DRUGS

Penicillamine
gold

ANTI INFLAMMATORY AGENTS

Phenylbutazone
diclofenac

ANTI EPILEPTICS

Phenytoin
carbamazepine

ANTI THYROID DRUGS

Carbimazole
propylthiouracil

ANTI MALARIALS

Pyrimethamine

ANTIDEPRESSSANTS $
ANTIPSYCHOTICS

Chlorpromazine
dosulpine

ANTI HYPERTENSIVES

lisnopril

ANTI NEOPLASTICS

methotrexate

ANTI DIABETICS

Chlorpropamide

MOA
DOSE DEPENDANT

DOSE INDEPENDENT

IMMUNE REACTION

Haematopoietic
supression

Pharmcokinetics $
hypersensitivity

Most common

Causechemotherapy/radiothe
rapy

leads to apoptosis

Activates immune
system

CHLORAMPHENICOL INDUCED APLASTIC

ANAEMIA
DOSE DEPENDANT

Chloramphenicol
Nitrobenzene ring
Injury of mitochondria
Affects erythroid cell lines
DNA
reticulocytes $ PCV
chromosomes

DOSE
INDEPENDANT

nitroso group
react with

damage to

cell
death

SIGNS AND SYMPTOMS

ACUTE

CHRONIC

WEAKNESS

INFECTIONS

PALLOR

SEVERE BLEEDING

FATIGUE

ARRYTHMIAS

DYSPNOEA

DEATH MAY OCCUR

LASSITUDE
PETECHIAE

TREATMENT
Remove suspected offending

agent
Supportive care
HSCT
Immunosupressive therapy
G-CSF
GM-CSF
I44

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 leukocytes
Mainly neutropenia
Neutrophil count:0.5

109 /L

DRUGS
CATEGORY

DRUGS

ANTIEPILEPTICS

1.cabamazepine
2.phenytoin

ANTI INFLAMMATORY

1.penicillamine
2.NSAIDS

ANTIPSYCHOTICS $
ANTIDEPRESSANTS

1.chlorpromazine
2.clozapine

ANTITHYROID DRUGS

1.propylthiouracil
2.methimazole

ANTIPLATELETS

1.ticlopidine

ANTIMICROBIALS

1.penicillins
2.dapsone

CARDIAC DRUGS

1.ACE inhibitors
2.procainamide

OTHERS

1.methyldopa
2.allupurinol

MOA
TYPE I

TYPE II

Immune
mechanism

Toxic
mechanism

eg:quinidin
e

Eg:penicilli
n

TYPE III
Both

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 drug
10 fold higher incidence of

agranulocytosis
Increases with age
In females
Not dose related

SIGNS $ SYMPTOMS
Sore throat
fever
malaise
weakness
Chills
Perianal pain
skin inflammation

TREATMENT
removal of offending drug
Discontinuation of drug
GM-CSF
G-CSF
Clozapine induced agranulocytosis
concomitant clozapine $ G-CSF
Corticosteroid therapy
Antibiotics 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