Antimalarial: Difference between revisions
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'''Antimalarial''' drugs have the obvious connotation of therapeutic utility against [[malaria]], but certain drugs with activity against malaria also are [[immunomodulator]]s used in [[rheumatology]]. | '''Antimalarial''' drugs have the obvious connotation of therapeutic utility against [[malaria]], but certain drugs with activity against malaria also are [[immunomodulator]]s used in [[rheumatology]]. Somewhat confusingly, some antibiotics, which are highly active against malaria are not explicitly called antimalarials. | ||
In general usage, the term applies specifically to synthetic analogs of [[quinine]], rather than [[antibiotic]]s or other drugs with activity against malarial parasites and other protozoa. The major drugs of this type are: | In general usage, the term applies specifically to synthetic analogs of [[quinine]], rather than [[antibiotic]]s or other drugs with activity against malarial parasites and other protozoa. The major drugs of this type are: | ||
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==Treatment of malaria== | ==Treatment of malaria== | ||
For malaria, chloroquine is the most important drug; quinacrine is no longer in commercial tablet production but, as a third-line agent, is available from compounding pharmacies. Chloroquine remains the drug of choice for chemoprophylaxis when resistance has not been reported. | For malaria, chloroquine is the most important drug; quinacrine is no longer in commercial tablet production but, as a third-line agent, is available from compounding pharmacies. Chloroquine remains the drug of choice for chemoprophylaxis when resistance has not been reported. | ||
Note that some antibiotics, such as [[tetracycline]], [[doxycycline]] and [[clindamycin]] are important treatments for malaria, but are not quinine analogs.<ref>{{citation | |||
| url = http://hopkins-abxguide.org/diagnosis/travel_tropical/malaria.html?contentInstanceId=255560 | |||
| title = Plasmodium | |||
| author = Lisa A. Spacek | |||
| date = 6 August 2010 | |||
| publisher = POC-IT Center, [[Johns Hopkins University]]}}</ref> | |||
==Rheumatology== | ==Rheumatology== | ||
These are examples of [[disease-modifying | These are examples of [[Disease-modifying treatment|disease-modifying anti-rheumatic drugs]] ([[DMARD]]), which directly affect the disease process rather than simply providing pain control. | ||
===Indications=== | |||
Their most important use was in [[systemic lupus erythematosus]], <ref name=Pract>{{citation | |||
| title = Practical Rheumatology | | title = Practical Rheumatology | ||
| edition = Third | | edition = Third | ||
| editor = Hochberg MC ''et al.'' | | editor = Hochberg MC ''et al.'' | ||
| publisher = Mosby | year = 2004 | | publisher = Mosby | year = 2004 | ||
| isbn = 0323029396 | | isbn = 0323029396 | ||
}}, pp. 440-442 | }}, pp. 440-442</ref> although monoclonal antibodies are now the first-line drugs. <ref>{{citation | ||
| url = http://www.medscape.com/druginfo/monograph?cid=med&drugid=8633&drugname=Chloroquine+Phosphate+Oral&monotype=monograph | | url = http://www.medscape.com/druginfo/monograph?cid=med&drugid=8633&drugname=Chloroquine+Phosphate+Oral&monotype=monograph | ||
| publisher = | | publisher = American Society of Health System Pharmacists | ||
| title = Monograph: Chloroquine phosphate}}</ref> They also have applicability to [[rheumatoid arthritis]], [[palindromic arthritis]] and psoriatic arthritis. When DMARDs are indicated, other DMARDs are often preferred, such as [[methotrexate]] in rheumatoid arthritis. | | title = Monograph: Chloroquine phosphate}}</ref> They also have applicability to [[rheumatoid arthritis]], [[palindromic arthritis]] and psoriatic arthritis. When DMARDs are indicated, other DMARDs are often preferred, such as [[methotrexate]] in rheumatoid arthritis. | ||
| Line 34: | Line 43: | ||
Their immunologic mode of action was not understood before their therapeutic use, but current thinking is that they decrease antigen production by [[macrophage]]s and [[lymphoid dendritic cell]]s. They do this by increasing their intracytoplasmic pH, leading to changes in the molecular assembly of class II [[major histocompatibility complex]] molecules. | Their immunologic mode of action was not understood before their therapeutic use, but current thinking is that they decrease antigen production by [[macrophage]]s and [[lymphoid dendritic cell]]s. They do this by increasing their intracytoplasmic pH, leading to changes in the molecular assembly of class II [[major histocompatibility complex]] molecules. | ||
With the decreased antigen production, [[T4-lymphocyte]]s produce less cytokines, specifically including IL-1, IL-2, IL-3, IL-4, IL-5, IL-6 and [[tumor necrosis factor]].<ref>''Practical Rheumatology'', p. 441</ref> | With the decreased antigen production, [[T4-lymphocyte]]s produce less cytokines, specifically including IL-1, IL-2, IL-3, IL-4, IL-5, IL-6 and [[tumor necrosis factor-alpha]].<ref>''Practical Rheumatology'', p. 441</ref> | ||
==Side effects== | |||
===Side effects=== | |||
Damage to the eyes are the greatest concerns. These drugs may deposit in the melanin of the pigmented epithelial layer of the [[retina]]. Since early damage is often reversible, thorough opthalmologic examination is advised every 6 to 12 months. | Damage to the eyes are the greatest concerns. These drugs may deposit in the melanin of the pigmented epithelial layer of the [[retina]]. Since early damage is often reversible, thorough opthalmologic examination is advised every 6 to 12 months. | ||
Latest revision as of 13:20, 9 October 2010
Antimalarial drugs have the obvious connotation of therapeutic utility against malaria, but certain drugs with activity against malaria also are immunomodulators used in rheumatology. Somewhat confusingly, some antibiotics, which are highly active against malaria are not explicitly called antimalarials.
In general usage, the term applies specifically to synthetic analogs of quinine, rather than antibiotics or other drugs with activity against malarial parasites and other protozoa. The major drugs of this type are:
- 4-aminoquinolone derivatives
- 9-aminoacridine derivatives
Treatment of malaria
For malaria, chloroquine is the most important drug; quinacrine is no longer in commercial tablet production but, as a third-line agent, is available from compounding pharmacies. Chloroquine remains the drug of choice for chemoprophylaxis when resistance has not been reported.
Note that some antibiotics, such as tetracycline, doxycycline and clindamycin are important treatments for malaria, but are not quinine analogs.[1]
Rheumatology
These are examples of disease-modifying anti-rheumatic drugs (DMARD), which directly affect the disease process rather than simply providing pain control.
Indications
Their most important use was in systemic lupus erythematosus, [2] although monoclonal antibodies are now the first-line drugs. [3] They also have applicability to rheumatoid arthritis, palindromic arthritis and psoriatic arthritis. When DMARDs are indicated, other DMARDs are often preferred, such as methotrexate in rheumatoid arthritis.
In a 1998 study comparing chloroquine and hydrochloroquine, [4] hydroxychloroquine was less toxic but less effective than chloroquine, but there were no firm recommendations of one over the other. Hydroxychloroquine is considerably more expensive.
Their immunologic mode of action was not understood before their therapeutic use, but current thinking is that they decrease antigen production by macrophages and lymphoid dendritic cells. They do this by increasing their intracytoplasmic pH, leading to changes in the molecular assembly of class II major histocompatibility complex molecules.
With the decreased antigen production, T4-lymphocytes produce less cytokines, specifically including IL-1, IL-2, IL-3, IL-4, IL-5, IL-6 and tumor necrosis factor-alpha.[5]
Side effects
Damage to the eyes are the greatest concerns. These drugs may deposit in the melanin of the pigmented epithelial layer of the retina. Since early damage is often reversible, thorough opthalmologic examination is advised every 6 to 12 months.
These drugs can cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency.
References
- ↑ Lisa A. Spacek (6 August 2010), Plasmodium, POC-IT Center, Johns Hopkins University
- ↑ Hochberg MC et al., ed. (2004), Practical Rheumatology (Third ed.), Mosby, ISBN 0323029396, pp. 440-442
- ↑ Monograph: Chloroquine phosphate, American Society of Health System Pharmacists
- ↑ J Antonio Aviña-Zubieta et al. (1998), "Long term effectiveness of antimalarial drugs in rheumatic diseases", Ann Rheum Dis 57: 582-587, DOI:10.1136/ard.57.10.582
- ↑ Practical Rheumatology, p. 441