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Old 03-24-2012
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Drug Drug increases Intralysosomal PH!

Experimental study for the Treatment of autoimmune disorders is done. The medication is used to increase intralysosomal PH and thus inactivating its enzymes.
Which of the following agents were most likely used?

a) Teteracyline
b) Chloramphenicol
c) Probenecid
d) Chloroquine
e) TMP-SMX
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Old 03-25-2012
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wow, tough question

im thinkin either D or E

i'll guess D.
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Old 03-25-2012
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Default D) Chloroquine

Its not Probenecid - thats a chronic gout drug. And tetracyclines and chloramphenicol are used as antibiotics since they work on the 30s and 50s ribosomal subunits, respectively. TMP-SMX inhibit the folate synthesis pathway.

None of the above drugs have any "intralysosomal" functions except for CHLOROQUINE. Its an antimalarial drug that works by entering the parasitic cells and making it a digestive vacuole by getting protonated and the ph becomes acidic. Then the parasitic drug undergoes apoptosis and auto-digestion.

I hope thats right.
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Old 03-25-2012
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Tetracyclines have the ability to accumulate intracelularly that's why they can kill intracelular bacteria like rickettsia and chlamydia, i would go with that one, though question
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Old 03-25-2012
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@hopetopass ur explanation says acidic ph, but the qs asking for basic ph( increase in ph)
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Old 03-25-2012
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Clindamycin is concentrated within human neutrophils and their lysosomes because the intralysosomal pH is highly acidic and this antibiotic behaves as a weak base.
a physiologically-based pharmacokinetic model on the basis of drug lipophilicity and found that drug distribution decreased when NH4Cl was administered concomitantly. In regards to subcellular distribution, the relative specific contents of chlorpromazine, imipramine and biperiden with respect to the protein in lysosomes were 7.3, 9.6 and 4.2, respectively, while those in other subcellular organella, including mitochondria, were only 0.4-1.7, indicating preferential accumulation of these drugs in lysosomes. The uptake of basic drugs into lysosomes depended on both intralysosomal pH and drug lipophilicity. As the lipophilicity of the basic drugs increased, they accumulated more than would have been predicted from the pH-partition theory and raised the intralysosomal pH more potently, probably owing to their binding with lysosomal membranes, with or without intralysosomal aggregation. We conclude that the distribution kinetics of basic drugs is driven by drug lipophilicity and uptake into lysosomes, and these phenomena provide a possible basis for drug interaction in clinical treatments.

The answer is Chloroquine.The effect of chloroquine, an inhibitor of intralysosomal catabolism, on the synthesis, transport, and degradation of cell-coat glycoproteins in absorptive cells of cultured human small-intestinal tissue was investigated by morphometrical, autoradiographical, and biochemical methods. Neither synthesis nor transport of cell-coat material was affected by the drug, but culturing of the absorptive cells in the presence of chloroquine led to a dose- and time-dependent enlargement of the dense bodies; other cell structures showed no alterations. 3H-fucose-labelled material accumulated in the dense bodies of the absorptive cells of these cultures. Since no increase of -glucuronidase and acid phosphatase activity (both lysosomal enzymes of glycoprotein nature) was found, this accumulation of radiolabelled material can be explained as a chloroquine-mediated inhibition of the degradation of cell-coat glycoproteins. These macromolecules probably enter the lysosome-like bodies by a crinophagic mechanism, i.e., fusion of these organelles with the apical vesicles and tubules involved in intracellular transport. These findings suggest that the lysosome-like bodies have a function in the regulation of cell-coat glycoprotein transport in human intestinal absorptive cells, i.e., the degradation of excess cell-coat material.

Source: http://www.springerlink.com/content/h2181h726018588v/
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Last edited by alfjof; 03-25-2012 at 10:33 AM.
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Old 03-25-2012
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Default Answer is Chloroquine

I had an idea to put this like a question while reading granpa robbins chapter I.

they say:
" certain drugs can disturb lysosomal function and cause aquired or drug induced lysosomal diseases. drugs like chloroquine, raises the internal pH of lysosome, thus inactivating its enzymes, chloroqine reduces tissue damage in inflamatory reactions, which are mediated in part by enzymes released from leukocytes; this action is the basis of the use of drug in autoimmune diseases"

i think it's good to share questions like this, because i'm sure many of us have done at least I chapter of robbins but never paid attention to this information.

Well done !
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