Immunomodulatory Drugs (IMiDs) Flashcards
What are the immunomodulatory drugs (IMiDs)?
- Lenalidomide
- Pomalidomide
- Thalidomide
What is Thalidomide and what is it used for?
-Developmental toxin approved for use in treatment of Hansen’s disease and in multiple myeloma (it has sig. off-label use in AIDS treatment)
What is the bad side effect associated with Thalidomide?
-Significant teratogenic effects (esp. phocomelia) in the children and grandchildren of women who take the drug while pregnant.
How do immunomodulatory drugs work in Hansen’s disease?
- Treats a complication of Hansen’s disease called erythema nodosum leprosum (ENL) that is characterized by painful skin nodules and nerve damage
- It works by suppressing immune and inflammatory reactions, i.e. it doesn’t function as an antibiotic - as soon as treatment is stopped, symptoms reappear
How do immunomodulatory drugs work as antineoplastics?
- Unknown, complex mechanism of action
- No cytotoxic effects on immune system cells, but does alter ratios of immune cells and changes the expression of molecular markers on their surfaces
- -Antiangiogenic (dec. FGF) - also causes decreased cell movement (anti-metastatic?)
- -Th2 response over Th1 (“more interleukins, less interferon and TNF”) - perhaps the most effective anti-TNF agent known (which is why it’s under investigation for use in inflammatory bowel disease)
How do immunomodulatory drugs work in morning sickness/pregnancy?
- Is sedating and improves well being - restores appetite and decreases wasting
- –Originally developed as an antihistamine in the 1950s (sedation), and marketed as a “wonder drug for prevention of morning sickness” because of its ability to relieve the “anxiety and stress of pregnancy”
What are the pharmacokinetics of immunomodulatory drugs?
- Oral
- Renal excretion of metabolites
What are the side effects of immunomodulatory drugs in adult males and non-pregnant females?
- Nausea, rashes, constipation, peripheral neuropathy
- Increased risk of deep vein thrombosis, particularly in multiple myeloma patient s(most are placed on warfarin before thalidomide is started)
What are the teratogenic effects of immunomodulatory drugs?
Severe effects occur 3-4 wks post conception in both children and grandchildren of patients treated with thalidomide
- -Defects include malformed intestines, hearing defects, absent ears, ocular and renal anomalies and phocomelia.
- -40% of THALIDOMIDE victims die within a year of birth - there are ~5,000-20,000 survivors wold-wide, and new cases occur every year
- Prescription requires participation by the doctor and patient in an FDA oversight program
What is phocomelia?
- Congenital malformation in which the hands and feet are attached to abbreviated arms and legs
- The word phocomelia combines photo- (seal) and melia (limb) to designate a limb like a seal’s flipper
