PAPER : ALL INDIA 2005 (AIPGE 2005 January, Answers, Explanation and Notes)

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Q.276. In-situ DNA nick end labeling can quantitate:
1. Fraction of cells in apoptotic pathways.
2. Fraction of cells in S phase.
3. p53 gene product.
4. bcr/abl gene.

Q.277. Which one of the following serum levels would help in distinguishing an acute liver disease from chronic liver disease?
1. Aminotransaminase.
2. Alkaline phosphatase.
3. Bilirubin.
4. Albumin.

Serum albumin is synthesized exclusively by hepatocytes. Serum albumin has a long half-life: 15 to 20 days, with approximately 4% degraded per day. Because of this slow turnover, the serum albumin is not a good indicator of acute or mild hepatic dysfunction; only minimal changes in the serum albumin are seen in acute liver conditions such as viral hepatitis, drug-related
hepatoxicity, and obstructive jaundice. In hepatitis, albumin levels below 3 g/dL should raise the possibility of chronic liver disease.
Hypoalbuminemia is more common in chronic liver disorders such as cirrhosis and usually reflects severe liver damage and decreased albumin synthesis.
One exception is the patient with ascites in whom synthesis may be normal or even increased, but levels are low because of the increased volume of distribution

Q.278. Which one of the following stains is specific for Amyloid?
1. Periodic Acid schif (PAS).
2. Alzerian red.
3. Congo red.
4. Von-Kossa.
Anderson’s             Pathology  /p.455
Staining characteristics of amyloid

*Hematoxylin and eosin/hematoxylin, phloxine, and saffron

Q.279. Which one of the following diseases characteristically causes fatty change in liver?
1. Hepatitis B virus infection.
2. Wilson’s disease.
3. Hepatitis C virus infection.
4. Chronic alcoholism.

Q.280. A 48-year-old woman was admitted with a history of weakness for two months. On examination, cervical lymph nodes were found enlarged and spleen was palpable 2 cm below ithe costal margin. Her hemoglobin was 10.5 g/dl, platelet count 237 x 10/L and total leukocyte count 40 x 10/L, which included 80% mature lymphoid cells with coarse clumped chromatin. Bone marrow revealed a nodular lymphoid infiltrate. The peripheral blood lymphoid cells were positive for CD19, CD5, CD20 and CD23 and were negative for CD79B and FMC-7.

The histopathological examination of ithe lymph node in this patient will most likely exhibit effacement of lymph node architecture by:
1. A pseudofollicular pattern with proliferation centers.
2. A monomorphic lymphoid proliferation with a nodular pattern.
3. A predominantly follicular pattern.
4. A diffuse proliferation of medium to large lymphoid cells with high mitotic rate.

This is the case of chronic lymphocytic leukemia (CLL) CLL and small lymphocytic lymphoma (SLL) - both are morphologically, phenotypically and genotypically indistinguishable, differing only in the degree of peripheral blood lymphocytosis.
For CLL - peripheral blood lymphocyte should be > 4000/mm3 or > 40x109/L.
 

In addition to Pan B cell marker they have T cell marker (CD23 and CD5) on a small subset of normal B cell.
Prolymphocyte gather together focally to form loose aggregates (not typical follicle like follicular lymphoma) (and cell are not diffuse also)
(So a Pseudofollicular pattern is seen)

Q.281. The following drugs have significant drug interaction with digoxin, except.
1. Cholestyramine.
2. Thiazide diuretics.
3. Quinidine.
4. Amlodipine.

Q.282. One of the following is not true about nesiritide:
1. It is a brain natriuretic peptide analogue.
2. It is used in acutely decompensated heart failure.
3. It has significant oral absorption.
4. It has a short half-life.
Katzung /209,214,Brain natriuretic peptide (BNP

1. Endogenous peptide brain natriuretic peptide (BNP) has recently been approved for use in acute cardiac failure as nesiritide.
2. It increase cGMP in smooth muscle cells
3. Short half-life of T 1/2 - 18 min.
4. It is administered as a bolus i.v. Dose followed by continuous infusion.
5. Trade name (Natrecor)
6. Only parenteral preparation is available.

Q.283. All of the following conditions are known to cause diabetes insipidus except:
1. Multiple sclerosis.
2. Head injury.
3. Histiocytosis.
4. Viral encephalitis.

Q.284. Antipsychotic drug induced Parkinsonism is treated by:
1. Anticholinergics.
2. Levodopa.
3. Selegiline.
4. Amantadine.
Katzung /472,473

Drug induced parkinsonism is treated, when necessary, with conventional antiparkinsonism drugs of the antimuscarinic type or, in rare case with amantadine.
Akathesia and dystonia - diphenhydramine more used than antimuscarinic

Tardive dyskinesia
1. Occur in 20-40% of treated patient
2. Late adverse effect
3. Difficult to reverse, sometime self-limited.
4. First step is tried to discontinue or reduce the current antipsychotic or switch to one of the
newer atypical agent.
5. 2nd step is eliminating all drugs with central anticholinergic action (note it).
6. If both measures fail, then addition of diazepam in doses as high as 30-40 mg/day may add to
the improvement by enhancing GABAergic activity.

Q.285. Which one of the following is used in therapy of Toxoplasmosis?
1. Artensenuate.
2. Thiacetazone.
3. Ciprofloxacin.
4. Pyrimethamine.

Drugs against both T. gondii

Atovaquone, which blocks pyrimidine salvage, has demonstrated activity against both T. gondii and P. carinii.
 

Therapy with spiramycin (100 mg/kg per day) plus prednisone (1 mg/kg per day) has been shown to be efficacious for congenital infection.
Both pyrimethamine and sulfadiazine cross the blood-brain barrier

Q.286. The following statements regarding finasteride are true except:
1. It is used in the medical treatment of benign prostatic hypertrophy (BPH).
2. Impotence is well documented after its use.
3. It blocks the conversion of dihydrotestosterone to testosterone.
4. It is a 5-? reductase inhibitor.

Finasteride is a competitive inhibitor of 5a-reductase type 2. Finasteride blocks the conversion of testosterone to dihydrotestosterone, the principal androgen in the prostate. A dose of 5 mg/d causes an average decrease in prostate size of ~24%, an increase in urine flow rates, and, in some, improvement in symptoms.
The 5a-reductase inhibitor finasteride ameliorate symptoms in a third or more of patients, but its impact is modest and not apparent for many months. Combined treatment with terazosin has proved no better than treatment with an alpha blocker alone in most men.

Q.287. Eternacept acts by one of ithe following mechanisms:
1. By blocking tumor necrosis factor.
2. By blocking bradykinin synthesis.
3. By inhibiting cyclo-oxygenase-2.
4. By blocking lipoxygenase.
Katzung /591            TNF a blocking agents
 

ANOTHER NEW DRUG
LEFLUNOMIDE - Active metabolite A77-1726
Inhibit dihydroorotate dehydrogenase
                ¯
So decreases RNA synthesis.
                 ¯
Arrest of stimulated cells in GI phase

- So it inhibits T cell prolif ration and production of antibodies.
- It is as effective as methotrexate and leflunomide resulted in a 46.2% response compared with 19.5% in-patient receiving methotrexate alone.

Q.288. All of the following are the disadvantages of anesthetic either, except.
1. Induction is slow.
2. Irritant nature of either increases salivary and bronchial secretions.
3. Cautery cannot be used.
4. Affects blood pressure and is liable to produce arrhythmias.

Q.289. In unconjugated hyperbilirubinemia, the risk of kernicterus increases with the use of:
1. Ceftriaxone.
2. Phenobaritone.
3. Ampicillin.
4. Sulphonamide
 

It is recommended that sulfonamides not be administered to the newborn because of concerns that bilirubin may be displaced from protein-binding sites, with subsequent jaundice and kernicterus.
The severe hypersensitivity reactions occurred most commonly after treatment with the long-acting sulfonamides, such as sulfamethoxypyridazine
Photosensitivity reactions are also relatively common with sulfonamides.
In high doses, trimethoprim interferes with the renal secretion of potassium. Hyperkalemia is relatively common among HIV-positive patients and is most often found after 7 days of trimethoprim-sulfamethoxazole therapy for pneumonia caused by Pneumocystis carinii.
Hemolytic anemia is most common in patients with glucose-6-phosphate dehydrogenase deficiency who take long-acting compounds; trimethoprim-sulfamethoxazole rarely causes hemolysis in such subjects.
Renal insufficiency, caused by crystals of the relatively insoluble acetyl metabolite, is observed primarily with the long-acting sulfonamides.

Q.290. Paralysis of 3rd, 4th, 6th nerves with involvement of ophthalmic division of 5th nerve, localizes the lesion to:
1. Cavernous sinus.
2. Apex of orbit.
3. Brainstem.
4. Base of skull.

The cavernous sinus syndrome is a distinctive and life-threatening disorder.

Most frequent causes are
Cavernous sinus thrombosis, often secondary to infection from orbital cellulitis (frequently Staphylococcus aureus),
In Sinusitis especially with mucormycosis in diabetic patients
Due to the anatomy of the cavernous sinus the syndrome may extend to become bilateral.

Q.291. All of the following are topically used sulphonamides except:
1. Sulphacetamide.
2. Sulphadiazine.
3. Silver sulphadiazine.
4. Mafenide.

Q.292. Oculogyric crisis is known to be produced by all of the following drugs except:
1. Trifluoperazine.
2. Atropine.
3. Perchlorperazine.
4. Perphenazine.
Answer is 2             Clinical Pharmacology P.N. Bennett, M.J. Bnrown 9th ed/384-85

Acute extrapyramidal side effects of antipsychotic are
Dystonia - abnormal movements of the tangue and facial muscles with
Fixed postures and spasm,
Include torticolis called Oculogyric crisis
And bizarre eye movement

Hence Answer is (2) atropine
Remaining three are the typical antipsychotic that causes the acute dystonia.
Few important points about atypical anti psychotics –

Q.293. Which of the following drugs is useful in prophylaxis of migrain?
1. Propranolol.
2. Sumatriptan.
3. Domperidone.
4. Ergotamine.

Prophylactic Treatment of Migraine drugs are now available that have the capacity to stabilize migraine

Phenelzine is MAOI; therefore, tyramine-containing foods, decongestants, and meperidine are contraindicated.
Methysergide may cause retroperitoneal or cardiac valvular fibrosis when it is used for more than 8 months, thus monitoring is required for patients using this drug; the risk of the fibrotic complication is about 1:1500 and is likely to reverse after the drug is stopped.
Stimulation of 5-HT1 receptors can stop an acute migraine attack. Ergotamine and dihydroergotamine are nonselective receptor agonists, while the series of drugs known as triptans are selective 5-HT1 receptor agonists. A variety of triptans (e.g., naratriptan, rizatriptan, sumatriptan, zolmitriptan) are now available for the treatment of migraine.
Rizatriptan appears to be the fastest acting and most efficacious of the triptans currently available. Sumatriptan and zolmitriptan have similar rates of efficacy as well as time to onset, whereas naratriptan is the slowest acting and the least efficacious.
Unfortunately, monotherapy with a selective oral 5-HT1 agonist does not result in rapid, consistent, and complete relief of migraine in all patients. Triptans are not effective in migraine with aura unless given after the aura is completed and the headache initiated. They are useless in prophylaxis of migrain. Recurrence of headache is a major limitation of triptan use.

Q.294. Inverse agonist of benzodiazepine receptor is:
1. Phenobarbitone.
2. Flumazenil.
3. Beta-carboline.
4. Gabapentin.

Katzung 357

Q.295. The group of antibiotics which possess additional antiinflammatory and immunomodulatory activities is:
1. Tetracyclines.
2. Polypeptide antibiotics.
3. Fluoroquinolones.
4. Macrolides.

Tacrolimus (originally labeled FK 506) is a macrolide lactone antibiotic isolated from a Japanese soil fungus, Streptomyces tsukubaensis. It has the same mechanism of action as cyclosporine but is 10 to 100 times more potent. The advantage of tacrolimus are minimizing episodes of rejection,
reducing the need for additional glucocorticoid doses, and reducing the likelihood of bacterial and cytomegalovirus infection.
In most transplantation centers, tacrolimus has now supplanted cyclosporine for primary immunosuppression, and many centers rely on oral, rather than intravenous, administration from the outset.
The toxicity of tacrolimus is similar to that of cyclosporine; nephrotoxicity and neurotoxicity are the most commonly encountered adverse effects, and neurotoxicity (tremor, seizures, hallucinations, psychoses, coma) is more likely and more severe in tacrolimus-treated patients.
Both drugs can cause diabetes mellitus, but tacrolimus does not cause hirsutism or gingival
hyperplasia. Because of overlapping toxicity between cyclosporine and tacrolimus, especially nephrotoxicity, and because tacrolimus reduces cyclosporine clearance, these two drugs should not be used together.

Q.296. With which of the following theophylline has an antagonistic interaction?
1. Histamine receptors.
2. Bradykinin receptors.
3. Adenosine receptors.
4. Imidazoline receptors.

Methylxanthines Theophylline and its various salts are medium-potency bronchodilators that work by increasing cyclic AMP by the inhibition of phosphodiesterase. They also shows Adenosine receptors antagonistic interaction.

Q.297. One of the following is not penicillinase susceptible.
1. Amoxicillin.
2. Penicillin G.
3. Piperacillin.
4. Cloxacillin.

Bacteria develop resistance to b-lactam antibiotics by a variety of mechanisms. Most common is the destruction of the drug by b-lactamases.
-lactamases production is plsmid controlled. These enzymes have a higher affinity for the b-lactam antibiotic. Binding results in hydrolysis of the b-lactam ring. Penicillins those are not penicillinase susceptible are methicillin, Cloxacillin, naficillin etc.
A second mechanism of bacterial resistance to b-lactam antibiotics is an alteration in PBP
(penicillin binding proteins) targets so that the PBPs have a markedly reduced affinity for the drug. While this alteration may occur by mutation of existing genes, the acquisition of new PBP genes (as in staphylococcal resistance to methicillin

Q.298. Which one of the following is best associated with Lumefantrine?
1. Antimycobacterial.
2. Antifungal.
3. Antimalarial.
4. Antiamoebic.
Answer is 3

Artemether-lumefantrine and atovaquone-proguanil are recently introduced, well-tolerated antimalarial drugs used in 3-day regimens. They are both effective against multidrug-resistant falciparum malaria.

Q.299. Which one of the following drugs increases gastrointestinal motility?
1. Glycopyrrolate.
2. Atropine.
3. Neostigmine.
4. Fentanyl.
Answer is 3

                Synthetic opioids, sharing properties of opium and morphine, include meperidine, propoxyphene, diphenoxylate, fentanyl, buprenorphine, methadone, and pentazocine. Various opiate effects are analgesia, respiratory depression, constipation, and euphoria. Fentanyl (80 to 100 times more powerful than morphine) is especially dangerous.
                Atropine blocks the muscarinic receptors. Atropine decreases gastrointestinal tract motility and secretion and causes constipation. Although various derivatives and congeners of atropine (such as propantheline, isopropamide, and glycopyrrolate) have been advocated in patients with peptic ulcer or with diarrheal syndromes
                Neostigmine is Cholinesterase inhibitors that enhance the effects of parasympathetic stimulation and leads to reversal of intoxication by agents with a anticholinergic action

Q.300. Which one of the following is the fastest acting inhalational agent?
1. Halothane.
2. Isoflurane.
3. Ether.
4. Sevoflurane.
Answer is 4

Sevoflurane -
• Similar to isoflurane and desflurane, sevoflurane causes slight increase in cerebral blood flow and intracranial pressure at normo carbia.
• High concentration of Sevoflurane (> 1.5 MAC) may impair autoregulation of C.B.F. and thus allowing a drop in C.B.F. during ihemorrhagic hypotension. This effect on CBF is less pronounced than isoflurane.
• Property of sevoflurane -. non purgent and rapid increase in alveolar anesthetic concentration make seroflurane an excellent choice for smooth and rapid inhalation induction in pediatric or adult patient
• Contraindication of seroflurane are
2)Severe hypovolemia 2) Susceptibility to malignant hyperthermia 3) intracranial hypertension.
Desflurane is the fastest acting agent. While 2nd is the Sevoflurane.

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