Seminar on thalidomide: a banished drug return.

1. THALIDOMIDE: A
BANISHED DRUG RETURNS
Presented By:
Suman Kumari Shaw
Class: 3rd
year, Sem: 6th
Registration No: 141890210114
Roll No: 18901914114
Guided By: Sancharee Mondal
Dr.B.C. Roy College OF Pharmacy &
A.H.S

2. CONTENT
 History
 Chemistry
 Pharmacokinetics
 The thalidomide disaster
 Symptom pattern
 Thalidomide today
 Adverse effects of thalidomide
 Uses
 Precautions & concerns
 Reference

3. HISTORY
 Developed by German pharmaceutical
company Grünenthal in Stolberg
 Introduced as a Sedative drug in the late 1950s
 Was found to act as an effective tranquilizer and
painkiller and was proclaimed a "wonder drug" for
insomnia, coughs, colds and headaches.
 Found to be an effective antiemetic which had
an inhibitory effect on morning sickness, and so
thousands of pregnant women took the drug to
relieve their symptoms

4. THALIDOMIDE – THE SLEEPING PILL
Hailed as a "wonder drug" that provided a
"safe, sound sleep".
However the drug was also found to cure
morning sickness in pregnant women
Was available as OTC drug

5. CHEMISTRY OF THALIDOMIDE
 Thalidomide, a-(N-phthalimido) glutarimide,
 Consists of ringed structure with an asymmetric carbon
in the glutarimide ring.
 Exists as an equal mixture of S-(-) and R-(+) enantiomers.
 These enantiomers rapidly get interconverted under
physiological conditions
 Thalidomide is sparingly soluble in water and ethanol,
which to date had prevented its availability as an
intravenous formulation

6.  R(+) acts as sedative
 S(-) potently inhibits the
release of TNF-α.
 It is the teratogenic form of
Thalidomide

7. PHARMACOKINETICS
 Absorption and Elimination
 Absorbed in GIT, not affected by food consumption
 Metabolized through a nonenzymatic pathway,
undergoing spontaneous hydrolysis in the blood and
tissues
 Found to be present in semen, not clear if it is in breast
milk
 Eliminated from the body in about 5-7 hours (not through
feces) (only a very small amount is metabolized by
cytochrome P-450)

8. THE THALIDOMIDE DISASTER
 In the late 1950s and early 1960s, more than 10,000
children in 46 countries were born with deformities such
as phocomelia as a consequence of thalidomide use
 The Australian obstetrician William McBride and the
German pediatrician Widukind Lenz suspected a link
between birth defects and the drug
 They were later awarded a number of honors for this
contribution
 In the United Kingdom the drug was licensed in 1958. Of
the approximately 2,000 babies born with defects, 466
survived. The drug was withdrawn in 1961.

9. DAMAGE
 10,000-12,000 thalidomide babies
 46 affected countries
 40% of victims died within a year of birth
 Today, there are approximately 5000
thalidomide survivors.

10. SYMPTOM PATTERN
 Phocomelia i.e. abnormal limbs
 Amelia i.e. missing limbs
Other Teratogenic Effects :
 Abnormal number of digits
 Missing/malformed eye and ear
 Anal atresia
 Brain damage/autism
 spinal cord defects
 Cleft lip or palate
 Heart, Kidney ,GIT and Genital defects

11. THALIDOMIDE TODAY
 Gained FDA approval & Reintroduced in market in
1998 for ENL
 “What was once the most feared drug in
pharmaceutical armory could become one of its most
valuable.”
 Gained FDA approval for MDS associated with 5q
syndrome in 2005 & for Multiple Myeloma in 2006
 Now under consideration for various cancers and
other conditions
 Various off label uses

12. ADVERSE EFFECTS OF THALIDOMIDE
 Teratogenesis : “species – specific” teratogenesis”
 Non-teratogenic in animal models of rats, mice, hamster &
chick embryos.
 Teratogenic in rabbit & Humans are also highly sensitive
(maximum risk at 34-50 days of gestation).
 CNS effects: sedation, tremors, Peripheral (Sensory)
Neuropathy
 Hypersensitivity: skin rashes, urticaria, eosinophilia
 Haematological: neutropenia
 GIT: Constipation
 Venous Thromboembolism: more risk when combined with
dexamethasone for MM (Black Box Warning by FDA)
↓
PROPHYLAXIS SHOULD BE GIVEN

13. USES OF THALIDOMIDE
Cachexia and weight
loss
 HIV associated
 Tuberculosis
 Cancer cachexia
Dermatological
conditions
 Discoid lupus
erythematosus
 Actinic prurigo
 pyoderma
gangrenosum
FDA approved :ENL
Multiple Myeloma :
Myelodysplastic syndrome
Promising uses
Prostate cancer
 Aphthous ulcers (in HIV)
 Anti-neoplastic effects :
 AIDS related Kaposi’s sarcoma
Potential uses
 Autoimmune conditions
 RA & Ankylosing Spondylitis
 Inflammatory bowel disease

14. PRECAUTIONS AND CONCERNS
 Required pregnancy test in most cases
 Education about the drug is required
 Drug may enter semen and men could affect female
partners
 To avoid this thalidomide’s marketing and use is
restricted through the mandatory System for
Thalidomide Education and Prescribing Safety (STEPS)
program.
 This unique system of monitoring oversees the
prescribing, dispensing, and dosing of thalidomide.

15. REFERENCE
 Wikipedia (http://en.m.Wikipedia.org)
 SlideShare app (www.slidrshare.net)
 www.who.int/lep/research/Thalidomide.pdf
 Toxicological Sciences, James H. Kim, Anthony R.
Scialli; (2011) 122 (1)

16. THANK
YOU