Review of Pharmacology - 9E (2015)

Immunomodulators
Explanations
1. Ans. (a) Myocarditis (Ref: Goodman Gilman 12/e p1742)
• Thalidomide was banned because of teratogenic effects (phocomelia). Now it has come again in the market for use as
an anticancer drug in multiple myeloma and melanoma.
• Lenalidomide is its more potent and non-teratogenic derivative.
• Thalidomide most commonly causes sedation and constipation in cancer patients. It can also cause peripheral sensory
neuropathy.
• Two enantiomers of thalidomide (R and S) are present but these are interconvertible in body, therefore racemic
mixture is used.
2. Ans. (b) Tacrolimus toxicity (Ref: Harrison 18/e p2272, 361, 347, 2308)
To get to the answer, we will look at the options one by one.
Hypocalcemia: Serum calcium in this boy is 7.5 mg/dL. Hypocalcemia can result in seizures but the level should be
very low. Further, if we correct calcium with serum albumin, it will come in normal range. Corrected calcium level in
the serum can be calculated by adding 0.8 mg/dL With every 1.0 g/dL decrease in serum albumin below the normal
value of 4.0 g/dL. Hence, in this patient, corrected serum calcium level will be
7.5 + 0.8 × (4.0 – 1.5) = 9.5 mg/dL
It is in normal range (8.5-10.5 mg/dL) and thus cannot be the cause of seizures in this person.
Uremia: Although blood urea is elevated (78 mg/dL as compared to normal value of 15-40 mg/dL) but serum
creatinine is normal (0.5 mg/dL). For diagnosis of uremia, serum creatinine must be 3 times the normal value. Thus,
uremia cannot be the answer.
Hyponatremia: Serum sodium is at lower normal value (136-152 mEq/L). For causing seizures, serum sodium should
be less than 125 mEq/L. Therefore, this option can also be ruled out.
Tacrolimus toxicity: This child is on tacrolimus therapy. It is a known neurotoxin and can cause seizures. It also can
cause renal failure. Further by ruling out other options, the most likely cause seem to be tacrolimus toxicity.
3. Ans. (b) I.V. immunoglobulins (Ref: CMDT 2012/1378-1379)
• Every patient with a clinical diagnosis Kawasaki disease should be treated.
• IVIG is given within the first 10 days of illness.
• Concomitant aspirin should be started until the patient is afebrile
• If fever persist beyond 36 hours after the initial IVIG infusion, a new dose of IVIG should be given if no other source
of fever is found.
• Methylprednisolone should follow if the disease persists after the second IVIG administration.
• Further options for refractory cases include TNF blockers (eg, infliximab), cyclophosphamide, methotrexate, and
plasmapheresis.
4. Ans. (b) Sulfasalazine (Ref: Harrison 17/e p2083)
Sulfasalazine is one of the drugs implicated in causing SLE, therefore obviously it will not be used in its treatment.
Do not get confused by seeing pregnancy in the question. Other drugs given in the question are used for treatment of SLE
but sulfasalazine is not used at all.
5. Ans. (c) Methotrexate (antifolate) (Ref: Goodman and Gilman 12/e p1691)
De novo synthesis refers to the synthesis of complex molecules from simple molecules such as sugars or amino acids, as
opposed to their being recycled after partial degradation.
Methotrexate and pemetrexed are the inhibitors of dihydrofolate reductase (DHFRase). These drugs also inhibit.
Thymidylate synthase (TS) and the enzymes involved in early purine synthesis like glycinamide ribonucleotide
formyltransferase (GART). These drugs are thus involved in inhibiting the denovo purine synthesis.
6. Ans. (d) It is highly nephrotoxic (Ref: Katzung 11/e p973)
• Mycophenolate mofetil is a prodrug, its active metabolite is mycophenolic acid.
• It is used as an immunosuppressant drug in solid organ transplant patients for refractory rejection and as an alternative
to cyclosporine /tacrolimus in patients who do not tolerate these drugs.
General Immunomodulators
Pharmacology
685
https://kat.cr/user/Blink99/