Thalidomide

THALIDOMIDE

Q. 1 Thalidomide is used in
 A Lepra 2 reaction            
 B MM
 C Ulcerative Colitis
 D All of the above
Q. 1 Thalidomide is used in
 A Lepra 2 reaction            
 B MM
 C Ulcerative Colitis
 D All of the above
Ans. D

Explanation:

All of the above

Thalidomide is used for lepra II reaction. Recently it is used for Multiple myeloma & also as a immunosuppressive agent so is being used for treatment of ulcerative colitis.


Q. 2 Phocomelia is an adverse effect due to:
 A Thalidomide
 B Warfarin
 C Enalapril
 D Phenytoin
Q. 2 Phocomelia is an adverse effect due to:
 A Thalidomide
 B Warfarin
 C Enalapril
 D Phenytoin
Ans. A

Explanation:

Thalidomide


Q. 3 Thalidomide is not used in:
 A HIV associated neuropathy
 B HIV associated recurrent oral ulcers
 C Erythema nodosum leprosum
 D Behcets diseases
Q. 3 Thalidomide is not used in:
 A HIV associated neuropathy
 B HIV associated recurrent oral ulcers
 C Erythema nodosum leprosum
 D Behcets diseases
Ans. A

Explanation:

HIV associated neuropathy

Quiz In Between


Q. 4

All of the following statements about thalidomide are true, Except:

 A

It has been re introduced for its activity in ENL

 B

Developed as antiemetic in pregnancy but withdrawn because of phacomelia

 C

Used for new and relapsed cases of Multiple myeloma

 D

Most common side effects are diarrhea and euphoria

Q. 4

All of the following statements about thalidomide are true, Except:

 A

It has been re introduced for its activity in ENL

 B

Developed as antiemetic in pregnancy but withdrawn because of phacomelia

 C

Used for new and relapsed cases of Multiple myeloma

 D

Most common side effects are diarrhea and euphoria

Ans. D

Explanation:

Thalidomide is associated with the development of constipation, rashes and peripheral neuropathy.
 
Ref: Essentials of Medical Pharmacology By KD Tripathi, 5th Edition, Page 782; DeVita, Hellman, and Rosenberg’s cancer : Principles And Practice of  Oncology By Vincent T DeVita, Theodore S Lawrence, Steven A Rosenberg,  Volume 1, Page 493; Reproductive and Developmental Toxicology By Ramesh C Gupta, Page 401

Q. 5

Thalidomide can be used in all of the following conditions, EXCEPT:

 A

Behcet’s syndrome

 B

HIV associated peripheral neuropathy

 C

HIV associated mouth ulcers

 D

Erythema nodosum leprosum

Q. 5

Thalidomide can be used in all of the following conditions, EXCEPT:

 A

Behcet’s syndrome

 B

HIV associated peripheral neuropathy

 C

HIV associated mouth ulcers

 D

Erythema nodosum leprosum

Ans. B

Explanation:

Thalidomide has been used for many years in the treatment of some manifestations of leprosy and has been used  for erythema nodosum leprosum; it is also useful in management of the skin manifestations of lupus erythematosus.

The most important toxicity is teratogenesis.
Because of this effect, thalidomide prescription and use are closely regulated by the manufacturer.
Other adverse effects of thalidomide include peripheral neuropathy, constipation, rash, fatigue, hypothyroidism, and increased risk of deep vein thrombosis. 
In more serious cases of Behcet syndrome, thalidomide (100 mg/d) is effective.
Ref: Lake D.F., Briggs A.D., Akporiaye E.T. (2012). Chapter 55. Immunopharmacology. In B.G. Katzung, S.B. Masters, A.J. Trevor (Eds), Basic & Clinical Pharmacology, 12e.

Q. 6

Thalidomide is used in the treatment of:

 A

Multiple myeloma

 B

Melanoma

 C

Lung carcinoma

 D

None of the above

Q. 6

Thalidomide is used in the treatment of:

 A

Multiple myeloma

 B

Melanoma

 C

Lung carcinoma

 D

None of the above

Ans. A

Explanation:

Thalidomide is currently used in the treatment of multiple myeloma at initial diagnosis and for relapsed-refractory disease.
Patients generally show signs of response within 2–3 months of starting the drug, with response rates from 20% to 70%.
 
When combined with dexamethasone, the response rates in myeloma are 90% or more in some studies. Many patients have durable responses—up to 12–18 months in refractory disease and even longer in some patients treated at diagnosis.
 
The success of thalidomide in myeloma has led to numerous clinical trials in other diseases such as myelodysplastic syndrome, acute myelogenous leukemia, and graft-versus-host disease, as well as in solid tumors like colon cancer, renal cell carcinoma, melanoma, and prostate cancer, with variable results to date.
 
Thalidomide has been used for many years in the treatment of some manifestations of leprosy and has been reintroduced in the USA for erythema nodosum leprosum; it is also useful in management of the skin manifestations of lupus erythematosus.
 
Ref: Katzung 11th edition Chapter 61.

Quiz In Between


Q. 7

An example of IMiD (Immunomodulatory derivatives of thalidomide) is:

 A

Pavalizumab

 B

Rbavirin

 C

Lenalidomide

 D

None of the above

Q. 7

An example of IMiD (Immunomodulatory derivatives of thalidomide) is:

 A

Pavalizumab

 B

Rbavirin

 C

Lenalidomide

 D

None of the above

Ans. C

Explanation:

Owing to thalidomide’s serious toxicity profile, considerable effort has been expended in the development of analogs.
Immunomodulatory derivatives of thalidomide are termed IMiDs.
 
Some IMiDs are much more potent than thalidomide in regulating cytokines and affecting T-cell proliferation.
Lenalidomide is an IMiD that in animal and in vitro studies has been shown to be similar to thalidomide in action, but with less toxicity, especially teratogenicity. 
 
Ref: Katzung 11th edition Chapter 61.

Q. 8

Thalidomide is used in treatment of all, EXCEPT:

 A

Multiple myeloma

 B

DLE

 C

AML

 D

Malaria

Q. 8

Thalidomide is used in treatment of all, EXCEPT:

 A

Multiple myeloma

 B

DLE

 C

AML

 D

Malaria

Ans. D

Explanation:

Thalidomide is currently used in the treatment of multiple myeloma at initial diagnosis and for relapsed-refractory disease.
Patients generally show signs of response within 2–3 months of starting the drug, with response rates from 20% to 70%.
When combined with dexamethasone, the response rates in myeloma are 90% or more in some studies.
Many patients have durable responses—up to 12–18 months in refractory disease and even longer in some patients treated at diagnosis.
The success of thalidomide in myeloma has led to numerous clinical trials in other diseases such as myelodysplastic syndrome, acute myelogenous leukemia, and graft-versus-host disease, as well as in solid tumors like colon cancer, renal cell carcinoma, melanoma, and prostate cancer, with variable results to date.
Thalidomide has been used for many years in the treatment of some manifestations of leprosy and has been reintroduced in the USA for erythema nodosum leprosum; it is also useful in management of the skin manifestations of lupus erythematosus.
 
Ref: Katzung 11th edition, Chapter 61.

Q. 9

Thalidomide is used in all, EXCEPT:

 A

Erythema nodosum leprosum

 B

HIV neuropathy

 C

HIV associated ulcer

 D

Multiple myeloma

Q. 9

Thalidomide is used in all, EXCEPT:

 A

Erythema nodosum leprosum

 B

HIV neuropathy

 C

HIV associated ulcer

 D

Multiple myeloma

Ans. B

Explanation:

Thalidomide is indicated for the treatment of patients with erythema nodosum leprosum and multiple myeloma.

In addition, it has orphan drug status for mycobacterial infections, Crohn’s disease, HIV-associated wasting, Kaposi sarcoma, lupus, myelofibrosis, brain malignancies, leprosy, graft-versus-host disease, and aphthous ulcers.

Also Know:
 
Thalidomide should never be taken by women who are pregnant or who could become pregnant while taking the drug.It is best known for the severe, life-threatening birth defects it caused when administered to pregnant women.

 

Quiz In Between


Q. 10

Which of the following condition is NOT an indication for using thalidomide for treatment?

 A

Prurigo nodularis

 B

Erythema nodosum leprosum

 C

Impetigo

 D

Behcet’s disease

Q. 10

Which of the following condition is NOT an indication for using thalidomide for treatment?

 A

Prurigo nodularis

 B

Erythema nodosum leprosum

 C

Impetigo

 D

Behcet’s disease

Ans. C

Explanation:

Indications for using thalidomide:
  • Erythema nodosum leprosum
  • Multiple myeloma
  • Actinic prurigo
  • Aphthous stomatitis
  • Behçet’s disease
  • Kaposi sarcoma
  • Cutaneous manifestations of lupus erythematosus
  • Prurigo nodularis
  • Uremic prurigo
Ref: Burkhart C., Morrell D., Goldsmith L. (2011). Chapter 65. Dermatological Pharmacology. In L.L. Brunton, B.A. Chabner, B.C. Knollmann (Eds), Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12e.  

 


Q. 11

Which of the following is wrong match about the teratogenic effects of the drugs –

 A

Zidovudine : skull defects

 B

Thalidomide : Limb defects

 C

Phenytoin : facial defects

 D

Tetracycline : Teeth abnormalities

Q. 11

Which of the following is wrong match about the teratogenic effects of the drugs –

 A

Zidovudine : skull defects

 B

Thalidomide : Limb defects

 C

Phenytoin : facial defects

 D

Tetracycline : Teeth abnormalities

Ans. A

Explanation:

Ans. is ‘a’ i.e., Zidovudine skull defects

Zidovudine is not a teratogenic drug.


Q. 12

Thalidomide acts through –

 A

Inhibiting angiogenesis

 B

Inhibiting thymidylate synthase

 C

Inhibition of Topo-isomerase I

 D

All

Q. 12

Thalidomide acts through –

 A

Inhibiting angiogenesis

 B

Inhibiting thymidylate synthase

 C

Inhibition of Topo-isomerase I

 D

All

Ans. A

Explanation:

Ans. is ‘a’ i.e., Inhibiting angiogenesis

o The major antitumor activity of thalidomide is due to inhibition of angiogenesis.

Quiz In Between


Q. 13

Thalidomide, used for multiple myeloma, is

 A

Associated with peripheral neuropathy

 B

Characterized by enantiomeric interconversion

 C

Metabolized extensively by hepatic CyP system

 D

a and b

Q. 13

Thalidomide, used for multiple myeloma, is

 A

Associated with peripheral neuropathy

 B

Characterized by enantiomeric interconversion

 C

Metabolized extensively by hepatic CyP system

 D

a and b

Ans. D

Explanation:

Ans. is ‘a’ i.e., Associated with peripheral neuropathy; ‘b’ i.e., Characterized by enantiomeric interconversion

There are two isomers of thalidomide:

i)          S isomer –> responsible for teratogenic effect

ii)        R isomer       responsible for sedative effect

o Giving R isomer does not protect against teratogenic potential as the safe isomer (R isomer) can be converted to teratogenic isomer (S isomer) once in the human body —> Enantiomeric interconversions.

o Apart from teratonecity, the main side effects of thalidomide are:

i)

Peripheral neoropathy

iv)

DVT

ii)

Fatigue

v)

Pulmonary edema, atelectasis, aspiration pneumonia

iii)

Constipation

vi)

Refractory hypotension


Q. 14

Which of the following is not true about thalidomide‑

 A

Its use have been avoided due to phacomelia caused by it in pregnant female

 B

It was reintroduced because of its broad anti­leprosum action

 C

It can cause euphoria and diarrhea

 D

It is useful in treatment of rearrent relapsing multiple myeloma

Q. 14

Which of the following is not true about thalidomide‑

 A

Its use have been avoided due to phacomelia caused by it in pregnant female

 B

It was reintroduced because of its broad anti­leprosum action

 C

It can cause euphoria and diarrhea

 D

It is useful in treatment of rearrent relapsing multiple myeloma

Ans. C

Explanation:

Ans. is ‘c’ i.e., It can cause euphoria and diarrhea

o Thalidomide causes constipation (not diarrhea) and euphoria is not a side effect (side effects have been explained)

o Thalidomide was withdrawn from market after being found to be a cause of severe birth defects (phacomelia), in pregnant females.

o It was reintroduced as a drug for erythema nodosum leprosum.

o It is useful in treatment of recurrent relapsing multiple myeloma.


Q. 15

All of the following are known adverse effects of thalidomide, except:

 A

Diarrhoea

 B

Teratogenicity

 C

DVT

 D

Neuropathy

Q. 15

All of the following are known adverse effects of thalidomide, except:

 A

Diarrhoea

 B

Teratogenicity

 C

DVT

 D

Neuropathy

Ans. A

Explanation:

Ans is ‘a’ i.e. Diarrhoea

o Thalidomide causes constipation and not diarrhoea.

Quiz In Between


Q. 16

Thalidomide can be used in –

 A

Myocardial infraction

 B

Erythema nodosum leprosum

 C

Wernicke’s encephalopathy

 D

Epilepsy

Q. 16

Thalidomide can be used in –

 A

Myocardial infraction

 B

Erythema nodosum leprosum

 C

Wernicke’s encephalopathy

 D

Epilepsy

Ans. B

Explanation:

Ans. is ‘b’ i.e., Erythema nodosum laprosum


Q. 17

Phocomelia is-

 A

Absence of long bones

 B

Absence of brain

 C

Reduplication of bones

 D

Absence of heart

Q. 17

Phocomelia is-

 A

Absence of long bones

 B

Absence of brain

 C

Reduplication of bones

 D

Absence of heart

Ans. A

Explanation:

Ans. is ‘a’ i.e., Absent long bones

‘Phacomelia’

o Is a term applied to a marked reduction in the size of limbs

The distal part of the limbs are placed very near the trunk (absent long bones).

o Seen in foetuses of mothers who recieved thalidomide during pregnancy.


Q. 18

Thalidomide is drug of choice for:

 A

Lepra I reaction

 B

Lepra II reaction

 C

Both

 D

Nerve Abscess

Q. 18

Thalidomide is drug of choice for:

 A

Lepra I reaction

 B

Lepra II reaction

 C

Both

 D

Nerve Abscess

Ans. B

Explanation:

B i.e. Lepra II reaction

Quiz In Between


Q. 19

The daily dose of thalidomide for controlling E.N.L. is :

 A

100 mg

 B

200 – 300 mg

 C

500 mg

 D

1000 mg only

Q. 19

The daily dose of thalidomide for controlling E.N.L. is :

 A

100 mg

 B

200 – 300 mg

 C

500 mg

 D

1000 mg only

Ans. B

Explanation:

B i.e. 200 – 300 mg


Q. 20

Thalidomide is not used in

 A

ENL

 B

Bechet’s syndrome

 C

HIV associated Oral ulcers

 D

HIV associated neuropathy

Q. 20

Thalidomide is not used in

 A

ENL

 B

Bechet’s syndrome

 C

HIV associated Oral ulcers

 D

HIV associated neuropathy

Ans. D

Explanation:

D i.e. HIV associated neuropathy

Peripheral neuropathy is a dose limiting toxicity of thalidomide & not a therapeutic indicationQ. It causes painful sensory ganglionopathy & axonal neuropathy.

Indications of Thalidomide

Erythema nodosum leprosum (ENL)Q: Only FDA approved use for treatment of cutaneous manifestations . of moderate to severe ENL and for maintenance therapy for prevention and suppression of cutaneous manifestations of ENL recurrence.

Severe, recurrent apthous stomatitisQ, especially in AIDS patients is common off label use. – Behects syndromeQ

Chronic graft versus host disease.

* HIV associated colitis and wasting, multiple myeloma, myelodysplasia, chronic idiopathic myelofibrosis, glucocorticosteroid refractory fistulosis-Chron’s disease, sarcoidosis, prurigo, stomatitis are other rare uses.


Q. 21

Thalidomide is useful in:           

March 2007

 A

Treatment of leprosy

 B

Treatment of type II lepra reaction

 C

Treatment of type I lepra reaction

 D

Treatment of neuritic leprosy

Q. 21

Thalidomide is useful in:           

March 2007

 A

Treatment of leprosy

 B

Treatment of type II lepra reaction

 C

Treatment of type I lepra reaction

 D

Treatment of neuritic leprosy

Ans. B

Explanation:

Ans. B: Treatment of type II lepra reaction

Thalidomide is a sedative-hypnotic, and multiple myeloma medication. The drug is a potent teratogen. Thalidomide was chiefly sold during the late 1950s and early 1960s to pregnant women, as an antiemetic to combat morning sickness.

Children were born with severe malformities, including phocomelia, because their mothers had taken thalidomide during pregnancy.

Apart from its infamous tendency to induce birth defects and peripheral neuropathy, the main side effects of thalidomide include fatigue and constipation.

It also is associated with an increased risk of deep vein thrombosis especially when combined with dexamethasone,for treatment of multiple myeloma. In multiple myeloma patients, concomitant use with zoledronic acid may lead to increased incidence of renal dysfunction.

High doses can lead to pulmonary oedema, atelectasis, aspiration pneumonia and refractory hypotension.

Quiz In Between


Q. 22

Thalidomide is useful in: 

March 2007

 A

Treatment of leprosy

 B

Treatment of type II lepra reaction

 C

Treatment of type I lepra reaction

 D

Treatment of neuritic leprosy

Q. 22

Thalidomide is useful in: 

March 2007

 A

Treatment of leprosy

 B

Treatment of type II lepra reaction

 C

Treatment of type I lepra reaction

 D

Treatment of neuritic leprosy

Ans. B

Explanation:

Ans. B: Treatment of type II lepra reaction

Thalidomide is a sedative-hypnotic, and multiple myeloma medication.

The drug is a potent teratogen.

Thalidomide was chiefly sold during the late 1950s and early 1960s to pregnant women, as an antiemetic to combat morning sickness.

Children were born with severe malformities, including phocomelia, because their mothers had taken thalidomide during pregnancy.

Apart from its infamous tendency to induce birth defects and peripheral neuropathy, the main side effects of thalidomide include fatigue and constipation.

It also is associated with an increased risk of deep vein thrombosis especially when combined with dexamethasone,for treatment of multiple myeloma.

In multiple myeloma patients, concomitant use with zoledronic acid may lead to increased incidence of renal dysfunction. High doses can lead to pulmonary oedema, atelectasis, aspiration pneumonia and refractory hypotension. It is very effective in dermatolgical conditions like: ENL, aphthous stomatitis, Behcet’s disease, LE, and prurigo nodularis


Q. 23

Mechanism of action of thalidomide is:

March 2013

 A

Antimicrobial

 B

Antiemetic

 C

Anti-allergic

 D

Immunomodulation

Q. 23

Mechanism of action of thalidomide is:

March 2013

 A

Antimicrobial

 B

Antiemetic

 C

Anti-allergic

 D

Immunomodulation

Ans. D

Explanation:

Ans. D i.e. Immunomodulation

Thalidomide

  • It is a synthetic derivative of glutamic acid (alpha-phthalimido-glutarimide) with teratogenic, immunomodulatory, anti-inflammatory and anti-angiogenic properties.
  • Thalidomide acts primarily by inhibiting both the production of tumor necrosis factor alpha (TNF-alpha) in stimulated peripheral monocytes and the activities of interleukins and interferons.
  • This agent also inhibits polymorphonuclear chemotaxis and monocyte phagocytosis.
  • In addition, thalidomide inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), thereby inhibiting angiogenesis.

Q. 24

Thalidomide is used in ‑

 A

Mutilple myeloma

 B

Squamous cell carcinoma

 C

Basal cell carcinoma

 D

Masopharyngeal carcinoma

Q. 24

Thalidomide is used in ‑

 A

Mutilple myeloma

 B

Squamous cell carcinoma

 C

Basal cell carcinoma

 D

Masopharyngeal carcinoma

Ans. A

Explanation:

Ans. is ‘a’ i.e., Multiple myeloma

Clinical uses of thalidomide

  • AIDS related aphthous ulcers
  • AIDS related wasting syndrome
  • Multiple myeloma and other solid tumours
  • Prevention of graft versus host disease after transplantation
  • Rheumatoid arthritis
  • Ankylosing spondylitis
  • Crohn’s disease and Bechet’s syndrome
  • Erythema Nodusum Leprosum

Quiz In Between



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