Review of Pharmacology - 9E (2015)

Review of Pharmacology
Everolimus has recently been
approved for treatment of patients
with subependymal giant
cell astrocytoma (SEGA) associated
with tuberous sclerosis.
shorter half life (43 hours as compared to 60 hours with sirolimus) and is useful in cardiac
transplantation. These drugs increase the risk of hemolytic uremic syndrome. Everolimus has
recently been approved for treatment of patients with subependymal giant cell astrocytoma (SEGA)
associated with tuberous sclerosis.
Mycophenolate does not cause
nephrotoxicity
4. Purine synthesis inhibitor
Mycophenolate mofetil inhibits inosine monophosphate dehydrogenase after conversion to
its active metabolite mycophenolic acid. This enzyme is necessary for de novo synthesis
of purines. It is used as immunosuppressant in patients who are refractory to steroids.
GI disturbances and myelosuppression are major adverse effects of this drug.
Immunomodulators
5. Antimetabolites
Azathioprine is the only antimetabolite that is used as immunosuppressant but not as an
anticancer drug. It is a prodrug and is activated in the body to 6-mercaptopurine (anticancer
drug). It lacks anticancer properties because conversion to active metabolite occurs only in
lymphoid cells. Major toxic effect is bone marrow suppression. Its dose should be reduced
if allopurinol is used concurrently because 6-MP is also metabolized by xanthine oxidase.
6. Other cytotoxic agents
Cyclophosphamide, chlorambucil and methotrexate are other anticancer drugs that can
be used as immunosuppressants. Cyclophosphamide and chlorambucil are used in treating
childhood nephrotic syndrome. Cyclophosphamide is also used for treatment of SLE and Wegner’s
granulomatosis.
7. Leflunomide
Active metabolite of this prodrug inhibits dihydro-orotate dehydrogenase resulting in
inhibition of pyrimidine synthesis. It is an orally active drug with long half life of several
weeks. Liver and kidney damage are major toxicities. Cholestyramine increases its excretion. It
is increasingly being used for polyoma virus nephropathy.
8. Thalidomide
• It is a sedative drug that was withdrawn due to teratogenic (phocomelia) effects. It
has come into market again due to its anti-angiogenic, immunomodulatory and antiinflammatory
effects.
• Currently, it is being used for multiple myeloma, erythema nodosum leprosum and
skin manifestations of SLE.
• Important adverse effects of thalidomide include tetratogenicity, peripheral neuropathy,
constipation, hypothyroidism and increased risk of thrombosis particularly DVT.
Immunomodulatory derivatives of thalidomide are termed IMiDs. Lenalidomide is an
IMiD approved for myelodysplastic syndrome and multiple myeloma. Anothert group of
thalodomide analogs, SelCIDs (SELective Cytokine Inhibitory Drugs) are phosphodiesterase-4
(PDE 4) inhibitors with potent anti-TNFα activity.
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