Topic: Immunosuppressive Drugs

Sreedam Das, PhD II Associate Professor

Dept. of Clinical Pharmacy and Pharmacology
University of Dhaka sreedamspph@iub.edu.bd
2 IMMUNOSUPPRESSANT DRUGS
➢ These are drugs which inhibit cellular/humoral or both immune response
and have their major use in organ transplantation and autoimmune
diseases.

CLASSIFICATION
Types of Immunity
Antigen-presenting cells (APCs) are a heterogeneous
group of immune cells that mediate the cellular
immune response by processing and presenting
antigens for recognition by certain lymphocytes such
as T cells. Classical APCs include dendritic cells,
macrophages, Langerhans cells and B cells.
5 Humoral and Cell-mediated Immune Response

➢ The antigen (Ag) is processed by

macrophages or other antigen
presenting cells (APC), coupled with
class II major histocompatibility
complex (MHC) and presented to
the CD4 helper cell which are
activated by interleukin-I (IL-1),
proliferate and secrete cytokines.
These in turn promote proliferation
and differentiation of antigen
activated B cells into antibody (Ab)
secreting plasma cells. Antibodies
finally bind and inactivate the
antigen.

Cytotoxic T lymphocytes (CTLs)

6 Humoral and Cell-mediated Immune Response
➢ In cell-mediated immunity—foreign
antigen is processed and presented
to CD4 helper T cell which elaborate
IL-2 and other cytokines that in turn
stimulate proliferation and
maturation of precursor cytotoxic
lymphocytes (CTL) that have been
activated by antigen presented with
class I MHC. The mature CTL (Killer
cells) recognize cells carrying the
antigen and lyse them.
7 Calcineurin Inhibitors - Cyclosporine
➢ Cyclosporine binds to an
intracellular protein ‘Cyclophilin’ and
this complex inhibits Ca2+-
Calmodulin (Ca2+-CAM) activated
enzyme ‘Calcineurin’. Normally,
after activation through T-Cell
receptor calcineurin activates
cytokine genes through a ‘Nuclear
factor of activated T-cells’ (NFAT)
resulting in transcription of cytokine
genes and production of IL-2 and
other cytokines. These pathways
become un-operational in the
presence of cyclosporine.
8 Calcineurin Inhibitors - Cyclosporine
➢ Cyclosporine selectively suppresses cell-mediated immunity, prevents graft
rejection and yet leaves the recipient with enough immune activity to
combat bacterial infection. Humoral immunity remains intact.

➢ It is nephrotoxic—the major limitation, and impairs liver function.

➢ Cyclosporine is the most effective drug for prevention and treatment of

graft rejection reaction. It is routinely used in renal, hepatic, cardiac, bone
marrow and other transplantations.

➢ For induction it is started orally 12 hours before the transplant and

continued for as-long-as needed. When graft rejection has started, it can
be given IV, because oral bioavailability is low, dependent on presence of
bile and is highly variable.
9 Calcineurin Inhibitors - Cyclosporine

➢ Cyclosporine is a second line drug in autoimmune diseases, like severe

rheumatoid arthritis, uveitis, bronchial asthma, inflammatory bowel
disease, dermatomyositis, etc. and in psoriasis, especially to suppress
acute exacerbations.

➢ It is often used along with corticosteroids or Mtx. Good results have been
obtained in some cases of aplastic anaemia.

➢ For these conditions, lower doses (2–5 mg/kg/day) are needed and adverse
effects are mild. However, it is not curative and relapses occur when the
drug is withdrawn.