Monocytes are the largest leukocytes in the circulation. These are agranulocytes Largest cells of normal blood Body's second line of defense against infection

1. DRUG INDUCED MONOCYTOSIS
By: AYESHA ASIF ALI
PHARM-D
SULTAN-UL-ULOOM COLLEGE OF PHARMACY,
HYDERABAD
GUIDED BY:
Dr.S.P.SRINIVAS NAYAK, ASSISTANT PROFESSOR ,
DEPT. OF PHARMACY PRACTICE, SUCP, HYD.

2. What are monocytes?
● Monocytes are the largest leukocytes in the circulation.
● These are agranulocytes
● Largest cells of normal blood
● Body's second line of defense against infection.
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4. Differentiation of Monocytes
● Monocytes are white blood cells that differentiate into macrophages and
dendritic cells in the immune system
● Histiocytes, which are large macrophagic phagocytes, are classified as
monocytes in a differential leukocyte count.
● Histiocytes and monocytes are capable of reversible transformation from
one to the other.
● These monocytic/dendritic cells are derived primarily from bone marrow
hematopoietic stem cells
● They are highly versatile with capacity to migrate to sites of inflammation,
differentiate into tissue macrophages and specialized dendritic cell
subtypes
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6. Role of Monocytes
● Circulating peripheral blood monocytes are key players in the innate
immune system.
● Secrete cytokines and chemokines to attract other inflammatory cells.
● Phagocytose tissue debris and microorganisms.
● They participate in the initiation of adaptive immunity by presenting
antigens to antigen‐specific lymphocytes.
● The effector functions and roles played by these cells are in mediating
acute and chronic inflammation, antimicrobial defense, and tissue repair
and wound healing , vital to the maintenance of a healthy steady state.
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7. What is Monocytosis?
● Monocytosis is an increase in the number of monocytes
circulating in the blood.
● with a level above 950/microLiter usually considered
elevated.
● In patients with a normal leukocyte count, differentials
with equal to or greater than 10% monocytes can also be
considered monocytosis.
● In humans, monocytosis occurs when there is a sustained
rise in monocyte counts greater than 800/mm3 to
1000/mm3A high monocyte count is indicative of chronic 7

8. Causes of Monocytosis
Monocytosis often occurs during chronic inflammation. Diseases that produce such a chronic
inflammatory state:
● Infections: tuberculosis, brucellosis, listeriosis, subacute bacterial endocarditis, syphilis, and
other viral infections and many protozoal and rickettsial infections (e.g. kala azar, malaria,
Rocky Mountain spotted fever).
● Blood and immune causes: chronic neutropenia and myeloproliferative disorders.
● Autoimmune diseases and vasculitis: systemic lupus erythematosus, rheumatoid arthritis
and inflammatory bowel disease.
● Malignancies: Hodgkin's disease and certain leukaemias, such as chronic myelomonocytic
leukaemia (CMML) and monocytic leukemia.Recovery phase of neutropenia or an acute
infection.
● Miscellaneous causes: sarcoidosis and lipid storage disease.
During these stages of extreme inflammation, monocytosis can damage tissues because it
increases the activation of the immune response and prevents the inflammation from subsiding
which is seen in cases where sepsis occurs.
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9. Diagnosis
Confirm the presence of monocytosis by blood smear review
Blood test checking for monocytosis (Abnormal ranges: >10%)
● If monocytosis is sustained, unexplained, and/or features concerning for a
hematologic neoplasm are present then further clinicopathologic workup
should be considered including
● bone marrow examination with cytogenetic analysis
● flow cytometry
● Immunohistochemistry
● cytochemical stains
● special stains
● molecular genetic studies.
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10. Drugs can induce almost the entire spectrum of hematologic disorders,
affecting white cells, red cells, platelets, and the coagulation system.
Drugs can induce toxicities spanning many hematologic syndromes, mediated
by a variety of mechanisms.
Physicians need to be alert to the potential for iatrogenic drug-induced
hematologic complications.
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11. Drugs that induce monocytosis
Monocytosis may be seen in patients receiving
1. cytokines (GM-CSF, M-CSF) TNF-alpha or
2. drugs that increase levels of IL- 3, IL-6, or IL-1.
It has also been described in patients taking
1. Olanzapine,
2. allopurinol,
3. corticosteroids,
4. Griseofulvin etc
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12. TNF ALPHA
● Excess TNF-α in the blood activates monocytes with the potential to
directly form lipid-laden ‘foam’ cells, a hallmark of atherosclerosis from
stable to unstable state.
● These data demonstrate that excess TNF-α in the blood is the primary
trigger for the development of atherosclerosis and CHD.
● The chronic inflammation or nonresolving inflammation involving
monocyte increase , contributes to the pathophysiology of
atherosclerosis.
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13. Allopurinol
● Immune cells of the monocyte/macrophage cell lineage play a pivotal role in
gouty inflammation.
● These cells are involved in all stages of disease progression, from triggering
MSU crystal-induced inflammation in an acute attack .
● Based on clinical data , monocytes from gout patients with hyperuricaemia
produce significantly less proinflammatory cytokines compared to monocytes
from healthy volunteers.
● These differences indicated that hyperuricaemia may directly alter monocyte
function.
● Allopurinol resulted in increased production of monocytes thereby increased
production of proinflammatory cytokines (e.g. TNFa and IL-12)
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14. Cortecosteroids
● The corticosteroid may stimulate interleukin-1 and granulocyte-
macrophage colony stimulating factor to induce proliferation of colony
forming unit i.e. granulocytesmacrophages
● These increase monocyte production.
Olanzapine and Ziprasidone
● Infrequent and rarely , monocytosis was observed on higher doses of
olanzapine and ziprasidone.
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15. False-positive values may be caused by:
Alprazolam
Ampicillin
Carbenicillin
Chlorpromazine
Granulocyte-colony stimulating factor (G-CSF)
Griseofulvin
Haloperidol
Lomefloxacin
Methsuximide
Paroxetine
Penicillamine
Piperacillin
Prednisone
Propylthiouracil
Quazepam.
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16. Management of Monocytosis
Management of Clinical Problem Monocytosis.
Monocytosis itself is a sign only and does not require treatment.
Treatment of the underlying etiology will cause resolution of this condition.
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17. THANK YOU
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