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Old 04-07-2011
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Arrow Practice Question: Pharmacology #3

A 45 year old female presents to your office with complaints of a 3 month history of aches and pains in her hands. She says that both of her hands are equally affected, but the pain is limited to only some of her joints. Upon further questioning, you find that the joints that are affected are the MCP's and PIP's. The patient also says that she has morning stiffness for about 45 minutes but gets better when she starts doing her morning chores. A potential treatment for this patient's condition can also be used in the treatment of an infectious disease that causes hemolytic anemia. Which of the following is the correct mechanism of action of this drug?

A. Binds to an inflammatory cytokine
B. Inhibits chemotaxis of inflammatory cells
C. Inhibits an enzyme involved in DNA synthesis
D. Inhibits an enzyme involved in prostaglandin synthesis
E. Is structurally similar to a cell surface receptor

Last edited by apx85; 04-07-2011 at 07:41 PM. Reason: Originally had two potentially correct answers
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The answer is hydroxycloroquine --> B. Inhibits chemotaxis of inflammatory cells

Other Disease-Modifying Antirheumatics Drugs (DMARDS) listed in the options :
A. Binds to an inflammatory cytokine --> etanercept / infliximab
C. Inhibits an enzyme involved in DNA synthesis --> methotrexate
D. Inhibits an enzyme involved in prostaglandin synthesis --> aspirin / NSAID
E. Inhibits action of cell surface receptor involved in inflammation --> anankinra
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Quote:
Originally Posted by harlesmd View Post
The answer is hydroxycloroquine --> B. Inhibits chemotaxis of inflammatory cells

Other Disease-Modifying Antirheumatics Drugs (DMARDS) listed in the options :
A. Binds to an inflammatory cytokine --> etanercept
C. Inhibits an enzyme involved in DNA synthesis --> methotrexate
D. Inhibits an enzyme involved in prostaglandin synthesis --> aspirin / NSAID
E. Inhibits action of cell surface receptor involved in inflammation --> infliximab
There is another drug that has a very similar mechanism that is used in the treatment of a different type of joint pain. Can you name it? ("what am i thinking" type of question )
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Quote:
Originally Posted by apx85 View Post
There is another drug that has a very similar mechanism that is used in the treatment of a different type of joint pain. Can you name it? ("what am i thinking" type of question )
It's colchicine for acute treatment of gout.
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Default answer

choice E is correct.


Hydroxychloroquine, by decreasing TLR signaling, reduces the activation of dendritic cells thus mitigating the inflammatory process.
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I edited my explanation, both etanercept (TNF receptor analog) and infliximab (monoclonal antibody of TNF) bind to inflammatory cytokines. Anakinra is IL-1 receptor antagonist.

The correct answer is still B.
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Quote:
Originally Posted by daniyel View Post
choice E is correct.


Hydroxychloroquine, by decreasing TLR signaling, reduces the activation of dendritic cells thus mitigating the inflammatory process.
Haha daniyel, you just pointed out an error! There are two correct answers here. Both B and E are mechanisms of Hydroxychloroquine. I meant for the answer to be B but you are absolutely right, Hydroxychloroquine also blocks TLR signalling. I'll have to edit the post!
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For those of you reading this after I edited it, the original answer choice E was "Inhibits action of cell surface receptor involved in inflammation" which is also an action of Hydroxychloroquine as daniyel correctly pointed out
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From Wikipedia:

Hydroxychloroquine's mechanism of action in inflammatory conditions has been recently elucidated and involves blocking the activation of toll-like receptors on plasmacytoid dendritic cells (PDCs). Toll-like receptor 9 (TLR 9), which recognizes DNA-containing immune complexes, leads to the production of interferon and causes the dendritic cells to mature and present antigen to T cells. Hydroxychloroquine, by decreasing TLR signaling, reduces the activation of dendritic cells thus mitigating the inflammatory process

From Uptodate:

"inhibits locomotion of neutrophils and chemotaxis of eosinophils"
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Quote:
Originally Posted by apx85 View Post
From Wikipedia:

Hydroxychloroquine's mechanism of action in inflammatory conditions has been recently elucidated and involves blocking the activation of toll-like receptors on plasmacytoid dendritic cells (PDCs). Toll-like receptor 9 (TLR 9), which recognizes DNA-containing immune complexes, leads to the production of interferon and causes the dendritic cells to mature and present antigen to T cells. Hydroxychloroquine, by decreasing TLR signaling, reduces the activation of dendritic cells thus mitigating the inflammatory process

From Uptodate:

"inhibits locomotion of neutrophils and chemotaxis of eosinophils"
Doesn't this question sound a bit squed? I mean drug can be CHQ also.. which inhibits lymphocyte proliferation, phospholipase A, antigen presentation in dendritic cells, release of Enzymes from lysosomes, release of reactive o2 species from macrophages, and production of IL 1?
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Quote:
Originally Posted by patelMD View Post
Doesn't this question sound a bit squed? I mean drug can be CHQ also.. which inhibits lymphocyte proliferation, phospholipase A, antigen presentation in dendritic cells, release of Enzymes from lysosomes, release of reactive o2 species from macrophages, and production of IL 1?
Good thing I don't write questions for USMLE

Was trying to come up with a question that tested the mechanism(s) of Hydroxychloroquine.

If you meant Chloroquine by CHQ, this drug is not used in RA.
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Quote:
Originally Posted by apx85 View Post
Good thing I don't write questions for USMLE

Was trying to come up with a question that tested the mechanism(s) of Hydroxychloroquine.

If you meant Chloroquine by CHQ, this drug is not used in RA.
Haha Im glad you dont write questiosn either, that was sorta difficult

I was also taught in med school that CHQ can be used in the treatment of RA (its an DMARD aswell)

I further looked it up..

http://en.wikipedia.org/wiki/DMARDS

Chloroquine is infact listed!
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Quote:
Originally Posted by patelMD View Post
Haha Im glad you dont write questiosn either, that was sorta difficult

I was also taught in med school that CHQ can be used in the treatment of RA (its an DMARD aswell)

I further looked it up..

http://en.wikipedia.org/wiki/DMARDS

Chloroquine is infact listed!
We just had a lecture on RA and CHQ was not listed as a potential treatment so I was not aware that it can be used. I think HCHQ has a longer half life so it is preferred over CHQ for practical use.

I actually know someone who is taking Hydroxychloroquine. Remember that it rarely causes blindness due to retionpathy! Gotta get those eyes checked regularly
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Quote:
Originally Posted by apx85 View Post
We just had a lecture on RA and CHQ was not listed as a potential treatment so I was not aware that it can be used. I think HCHQ has a longer half life so it is preferred over CHQ for practical use.

I actually know someone who is taking Hydroxychloroquine. Remember that it rarely causes blindness due to retionpathy! Gotta get those eyes checked regularly
Well for practical treatment of RA, HCHQ isn't really a first line drug anyways, but oh well. I'll keep HCHQ in mind. Thanks!

As for other uses, the use of HCHQ/CHQ has pretty much ceased, atleast for malaria.
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Quote:
Originally Posted by patelMD View Post
Well for practical treatment of RA, HCHQ isn't really a first line drug anyways, but oh well. I'll keep HCHQ in mind. Thanks!

As for other uses, the use of HCHQ/CHQ has pretty much ceased, atleast for malaria.
Although I haven't really treated any patients yet , from our lecture it seemed like HCHQ is used pretty often to treat RA. Because Methotrexate needs to be monitored so closely, patients often start out with HCHQ for mild symptoms when they first present. When the pain starts to get worse, then they are switched to Methotrexate. At least this is what our lecturer taught us.
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Although I haven't really treated any patients yet , from our lecture it seemed like HCHQ is used pretty often to treat RA. Because Methotrexate needs to be monitored so closely, patients often start out with HCHQ for mild symptoms when they first present. When the pain starts to get worse, then they are switched to Methotrexate. At least this is what our lecturer taught us.
Hmm that's odd, the clinicians where I did rotations didn't really mention HCQH. But thats alright, I guess I'll use HCHQ if I encounter a patient on the USMLE lol.
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