Immunopharmacology Flashcards
Immunopharmacology definition
It is the study of the use of pharmacological agents as modulators of immune responses
There are two major groups of immuno-pharmacological drugs
Immunosuppressive drugs
Immunostimulant drugs
Immunosuppressive drugs
and Immunostimulant drugs
what are they?
Immunosuppressive drugs:
Those drugs that suppress the immune system
Important for the cases where immune response needs to be controlled
Immunostimulant drugs:
Those drugs that stimulate the immune system
Important for the cases where the immune system needs a boost
Immunomodulators
Tolerogens (Induction of tolerance)
Cytokines
Hematopoetic growth factors
Antibodies targeting key cell receptors/ligands, or
Antibody-mediated drug delivery
Why Suppress Immunity?
- Prevention/reduction of rejection in organ transplantation
Suppression of an “appropriate” immune reaction to a foreign tissue (e.g. heart, kidney, lung) - Treatment of autoimmune diseases
Suppression of an inappropriate immune reaction to a “self “tissue (e.g. lupus nephritis, rheumatoid arthritis) - Treatment of some other resistant inflammatory diseases
Suppression of an inappropriate immune reaction to a foreign antigen (glucocorticoids for allergic asthma)
Major steps in immune responses
Antigen recognition
IL-1 production
IL-2 and other cytokine expression
Lymphocyte proliferation & differentiation
Major immunosuppressants
(4)
Major immunosuppressants
1.Cytotoxic Agents
2.Glucocorticoids
3.Immunophilin ligands
4.Immunosuppressive Ab
Cytotoxic agents (4)
1.Azathioprine
2.Methotrexate
3.Cyclophosphamide
4.Mycophenolate mofetil (MMF)
Azathioprine
write mechanism of action, uses, Therapeutic immunosuppression, adverse effects and long term use
Azathioprine
Mechanism of action:
-Hepatically metabolized to purine analogue 6-mercaptopurine
-Incorporates into DNA
Uses:
Transplantation
Rheumatoid arthritis
Crohn’s disease
Ulcerative colitis
GVHD (graft versus host disease)
Therapeutic immunosuppression: 1.5 mg/kg b.w.
Adverse effects: Mainly due to impaired proliferation of other rapidly dividing cells
Gut
Bone marrow:
-Low white cell count -> Infection
-Low platelet count -> Bleeding
Long term use: high risk of squamous carcinoma of skin, lymphoma, bacterial and opportunistic infections
Methotrexate write
Mechanism of action, uses,adverse effects
Methotrexate
Mechanism of action:
Inhibits dihydrofolate reductase resulting in…
-Accumulation of inactive oxidized folates, and
-Cessation of nucleotide synthesis
Kills cells in S-phase, non-proliferative cells are resistant
Inhibits macrophage activation
Uses:
GVHD
Rheumatoid arthritis
SLE (systemic lupus erythematosus)
Psoriasis
Adverse effects
Long term use -> Hepatic fibrosis leading to cirrhosis
Teratogenic
Not carcinogenic
Cyclophosphamide
write the Mechanism of action, uses, adverse effects
Cyclophosphamide
Mechanism of action:
An alkylating agent that forms covalent bonds with DNA
Leads to DNA fragmentation, mutations and cell death
Suppress cellular immunity and inhibits Ab and autoAb production
Uses:
Hematopoietic cell transplantation
SLE
Vasculitis
Wegener’s granulomatosis (Granulomatosis with polyangiitis)
Adverse Effects:
Leukopenia
Sterility
Hemorrhagic cystitis (acrolein)
Malignancy (leukemia and transitional cell carcinoma)
Mycophenolate mofetil (MMF) write
Mechanism of action, uses and adverse effects
Mycophenolate mofetil (MMF)
Mechanism of action:
-Mycophenolic acid is a fungal derived inhibitor of de novo guanosine monophosphate synthesis
-B and T cells depend on de novo synthesis as they lack salvage pathway for guanine recovery
-Leads to specific inhibition of DNA and RNA synthesis and other GTP and cGMP requiring pathways
-Potent cytostatic effects on T and B lymphocytes
-Inhibits Ab production by B lymphocytes
-Inhibits T cell proliferation after mitogen and allogeneic stimulation
-Prevents glycosylation of adhesion proteins (inhibits recruitment of lymphocytes to inflammatory foci)
Uses:
Prevention of organ rejection
Autoimmune diseases – under study
Adverse Effects:
Diarrhea, leukopenia and CMV infections
Increased incidence of lymphomas and other malignancies
Corticosteroids - mechanism of action, uses, adverse effects - immediate and long term
Mechanisms of Action
Suppress antibody and complement binding
Impairs secretion of IL-1 by macrophages
Reduce synthesis of IL-2 and IFN-
Decreases release of kinins and pro-inflammatory eicosanoids (prostaglandins and leukotrienes)
Inhibit expression of adhesion molecules
Reduce inflammatory cell migration
E.g. prednisone, prednisolone, betamethasone
Uses:
GVHD
Graft rejection in hematopoietic cell transplantation and solid organ transplantation
Allergic conditions
Autoimmune disease
Inflammatory conditions
Adverse effects:
Immediate effects (1–3 months)
Weight gain
Peptic ulcer disease
Hypertension
Hyperlipidemia, Diabetes (5-10%; transient)
Acne, Hirsutism (unwanted male-pattern hair growth in women)
Cataracts (10% w/ high doses)
Mood changes/Psychiatric disturbances
Infection
Long-term:
Osteoporosis
Avascular necrosis (loss of blood supply to bones) (10-15% w/ high doses)
Growth retardation
Skin atrophy (thinning of skin)
