Metronidazole From Wikipedia, the free encyclopedia Jump to: navigation, search This article may require cleanup

to meet Wikipedia's quality standards. No cleanup reason has been specified. Please help improve this article if you can; the talk page may contain suggestions. (April 2010) This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (December 2009) Metronidazole

Systematic (IUPAC) name 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethanol Clinical data Trade names Flagyl

AHFS/Drugs.com monograph Pregnancy cat. Legal status B (US) B2 (Au) Prescription Only (S4) (AU) POM

(UK) -only (US) Routes oral, topical, rectal, IV, vaginal Pharmacokinetic data Bioavailability 100% (oral) 5994% (rectal) Metabolism Half-life Excretion Hepatic 67 hours Renal (60-80%), biliary (615%) Identifiers CAS number ATC code 443-48-1 A01AB17 , D06BX01, G01AF01, J01XD01, P01AB01, QP51AA01 PubChem DrugBank ChemSpider UNII KEGG ChEBI ChEMBL CID 4173 DB00916 4029 140QMO216E D00409 CHEBI:6909 CHEMBL137

NIAID ChemDB 007953 Chemical data

Formula Mol. mass InChI[show]

C6H9N3O3 171.15 g/mol

Physical data Melt. point 159163 C (318325 F) (what is this?) (verify) Metronidazole (INN) ( /mtrnadzol/) is a nitroimidazole antibiotic medication used particularly for anaerobic bacteria and protozoa. Metronidazole is an antibiotic, amebicide, and antiprotozoal.[1] It is the drug of choice for first episodes of mild-to-moderate Clostridium difficile infection.[2] It is marketed in the U.S.A. by Pfizer and globally by Sanofi under the trade name Flagyl, in Pakistan and Bangladesh also as Nidagyl by Star Laboratories, and in Thailand, as Mepagyl by Thai Nakhorn Patana. It is also marketed in UK by Milpharm Limited and Almus Pharmaceuticals. Metronidazole was developed in 1960. Metronidazole is used also as a gel preparation in the treatment of the dermatological conditions such as rosacea (Rozex and MetroGel by Galderma) and fungating tumours (Anabact, Cambridge Healthcare Supplies). Contents [hide]

1 Medical uses o 1.1 Bacterial o 1.2 Protozoal o 1.3 Nonspecific o 1.4 Preterm births o 1.5 Veterinary use 2 Adverse effects o 2.1 Metronidazole toxicity of the brain o 2.2 Interaction with alcohol o 2.3 StevensJohnson syndrome with mebendazole o 2.4 Potentially fatal serotonin syndrome 3 Shape and color 4 Mechanism of action 5 Synthesis 6 References 7 External links

[edit] Medical uses Metronidazole is indicated for the treatment of: [edit] Bacterial

Bacterial vaginosis, commonly associated with overgrowth of Gardnerella species and coinfective anaerobes (Mobiluncus, Bacteroides), in symptomatic patients Pelvic inflammatory disease in conjunction with other antibiotics such as ofloxacin, levofloxacin, or ceftriaxone Anaerobic infections such as Bacteroides fragilis, spp, Fusobacterium spp, Clostridium spp, Peptostreptococcus spp, Prevotella spp, or any other anaerobes in intra-abdominal abscess, peritonitis, diverticulitis, empyema, pneumonia, aspiration pneumonia, lung abscess, diabetic foot ulcer, meningitis and brain abscesses, bone and joint infections, septicemia, endometritis, or endocarditis Pseudomembranous colitis due to Clostridium difficile Helicobacter pylori eradication therapy, as part of a multi-drug regimen in peptic ulcer disease Dental infection of bacterial origin, such as periapical abscess, periodontal abscess, acute pericoronitis of impacted or partially erupted teeth; often used in conjunction with Amoxicillin

[edit] Protozoal

Amoebiasis: Infections caused by Entamoeba histolytica.[1] Giardiasis: infection of the small intestine caused by the ingestion of infective cysts of protozoan Giardia lamblia.[1] Trichomoniasis: infection caused by Trichomonas vaginalis, which is a common cause of vaginitis and is the most frequently presenting new infection of the common sexually transmitted diseases.[1]

[edit] Nonspecific

Prophylaxis for those undergoing potentially contaminated colorectal surgery or appendectomies and may be combined with neomycin[citation needed] Crohn's disease with colonic or perianal involvement (non-FDA approved) believed to be more effective in combination with ciprofloxacin[citation needed] Topical metronidazole is indicated for the treatment of rosacea, and in the treatment of malodorous fungating wounds.[3]

[edit] Preterm births Metronidazole has also been used in women to prevent preterm birth associated with bacterial vaginosis, amongst other risk factors including the presence of cervicovaginal fetal fibronectin (fFN). A randomised controlled trial demonstrated that metronidazole was ineffective in preventing preterm delivery in high-risk pregnant women and, conversely, the incidence of preterm delivery was actually higher in women treated with metronidazole.[4] In a study it has been found that metronidazole is not the right antibiotic to administer in these circumstances and that it was often administered too late to be of use. Clindamycin administered early

in the second trimester to women who test positive for bacterial vaginosis seemed to be more effective.[5] [edit] Veterinary use Metronidazole is not labeled for animal use but is widely used to treat infections of Giardia in dogs, cats, and other companion animals, although it does not reliably clear infection with this organism and is being supplanted by Fenbendazole for this purpose in dogs and cats.[6] Another common usage is the treatment of systemic and/or GI Clostridial infections in horses. Metronidazole or simply "Metro" is used in the aquarium hobby to treat ornamental fish and as a wide spectrum treatment for bacterial and protozoan infections in reptiles and amphibians. It is also used to treat human enteric (gi) and systemic infections. In general, the veterinary community may use metronidazole for any potentially susceptible anaerobic infection. The U.S. Food and Drug Administration (FDA) prohibits the use of metronidazole in food animals.[7] [edit] Adverse effects Common adverse drug reactions (1% of patients) associated with systemic metronidazole therapy include: nausea, diarrhea, and/or metallic taste in the mouth. Intravenous administration is commonly associated with thrombophlebitis. Infrequent adverse effects include: hypersensitivity reactions (rash, itch, flushing, fever), headache, dizziness, vomiting, glossitis, stomatitis, dark urine, and/or paraesthesia.[3] High doses and/or long-term systemic treatment with metronidazole is associated with the development of leukopenia, neutropenia, increased risk of peripheral neuropathy and/or CNS toxicity.
[3]

Metronidazole is listed by the US National Toxicology Program (NTP) as reasonably anticipated to be a human carcinogen. Although some of the testing methods have been questioned[citation needed], oral exposure has been shown to cause cancer in experimental animals.[8] The relationship between exposure to metronidazole and human cancer is unclear.[8] One study (Beard et al. 1988) found an excess in lung cancer among women (even after adjusting for smoking), while other studies (IARC 1987; Thapa et al. 1998) found either no increased risk, or a statistically insignificant risk.[8] [9] Metronidazole is listed as a possible carcinogen according to the WHO International Agency for Research on Cancer (IARC).[10] Due to its potential carcinogenic properties, metronidazole is banned in the EU and the USA for veterinary use in the feed of animals and is banned for use in any food animals in the USA.[11][12] In the USA, this type of restriction is covered under the Delaney clause. Earlier studies suggested a relation between metronidazole and various birth defects. Those studies are now considered flawed and more recent studies "do not support a significant increased risk for birth defects or other adverse effects on the fetus."[13] Common adverse drug reactions associated with topical metronidazole therapy include local redness, dryness, and/or skin irritation; and eye watering (if applied near eyes).[3] [edit] Metronidazole toxicity of the brain Toxic levels of metronidazole can cause symmetrical lesions in the brain in the corpus callosum and dentate nuclei. Metronidazole toxicity is rare (though the actual incidence is not known with certainty). Patients present with nausea, vomiting, dysarthria, vertigo, and confusion. Other side effects of the metronidazole can include dry mouth, diarrhea, headache, dizziness, or peripheral

neuropathy. An examination of a patient reveals that the patient is confused and has dysarthria (difficult or unclear articulation of speech that is otherwise linguistically normal), ataxia (loss of full control of bodily movements), abnormal eye movements including nystagmus and ophthalmoparesis. Magnetic resonance imaging (MRI) most often shows bilateral symmetric fluid-attenuated inversion recovery (FLAIR) hyperintense lesions of the dentate nuclei (which is one of the deep cerebellar nuclei), as well as symmetric lesions of the corpus callosum and basal ganglia. The brain lesions seen on the MRI rarely enhance and may be Diffusion-Weighted Imaging (DWI) hyperintense. It has a subacute to acute course. Most reports have been seen in patients who receive approximately one gram a day of metronidazole for over 30 days.[14][citation needed] Metronidazole can rarely cause central nervous system toxicity; it does not seem to be a dose- or duration-related phenomenon. Most patients will have MRI abnormalities. Prognosis is excellent with metronidazole cessation.[15][16] [edit] Interaction with alcohol Consuming ethanol (alcohol) while taking metronidazole has long been thought to have a disulfiramlike reaction with effects that can include nausea, vomiting, flushing of the skin, tachycardia (accelerated heart rate), and shortness of breath.[17] Typically a 2006 Medicines Handbook warns that consumption of alcohol should be avoided by patients during systemic metronidazole therapy and for at least 48 hours after completion of treatment.[3] However there are studies calling into question the interaction of alcohol and metronidazole,[18] and the mechanism of this reaction in the clinical setting has been questioned by some authors,[19][20] and a possible central toxic serotonin reaction for the alcohol intolerance suggested.[21] [edit] StevensJohnson syndrome with mebendazole Metronidazole alone rarely causes StevensJohnson syndrome but is reported to occur at high rates when combined with mebendazole.[22] [edit] Potentially fatal serotonin syndrome It is important to note that serotonin syndrome is not fully understood. The complex drug interaction can happen after a couple days or take up to months. The exact mechanism is not known, a theory of serotonin dysfunction helps explain how the syndrome presents and how it is to be treated. Signs and symptoms are muscle rigidity, headache, elevated blood pressure, and changes in blood chemistry. The only direct treatment is to discontinue the offending drugs. Recently, there have been reported cases of SSRI/SNRI antidepressant drugs (e.g. paroxetine, citalopram, fluoxetine, sertraline, venlaxafine, duloxetine) and metronidazole induced serotonin syndrome,[21][23] but this information is not included on the metronidazole patient information leaflet. [edit] Shape and color Metronidazole is available with a prescription under the brand names Flagyl and Protostat. Other brand or generic formulations may also be available.[24] [edit] Mechanism of action Metronidazole, taken up by diffusion, is selectively absorbed by anaerobic bacteria and sensitive protozoa. Once taken up by anaerobes, it is non-enzymatically reduced by reacting with reduced ferredoxin, which is generated by pyruvate oxido-reductase. Many of the reduced nitroso intermediates will form sulfinamides and thioether linkages with cysteine-bearing enzymes, thereby deactivating these critical enzymes. As many as 150 separate enzymes are affected.

In addition or alternatively, the metronidazole metabolites are taken up into bacterial DNA, and form unstable molecules. This function only occurs when metronidazole is partially reduced, and because this reduction usually happens only in anaerobic cells, it has relatively little effect upon human cells or aerobic bacteria.[25] [edit] Synthesis 2-Methylimidazole (1) may be prepared via the Debus-Radziszewski imidazole synthesis, or from ethylenediamine and acetic acid, followed by treatment with lime, then Raney nickel. 2Methylimidazole nitrated to give 2-methyl-4(5)-nitroimidazole (2), which is in turn alkylated with ethylene oxide or 2-chloroethanol to give metronidazole (3):[26][27][28]

Amoxicillin From Wikipedia, the free encyclopedia Jump to: navigation, search

Amoxicillin

Systematic (IUPAC) name (2S,5R,6R)- 6-{[(2R)-2-amino- 2-(4-hydroxyphenyl)acetyl]amino}- 3,3-dimethyl- 7-oxo- 4-thia- 1azabicyclo[3.2.0]heptane- 2-carboxylic acid Clinical data Trade names Actimoxi, Alphamox, Amocla, Amoxil, Trimox, among others AHFS/Drugs.com monograph MedlinePlus Pregnancy cat. Legal status Routes a685001 A (AU) B (US) POM (UK) -only (US) Oral, intravenous Pharmacokinetic data Bioavailability 95% oral

Metabolism

less than 30% biotransformed in liver

Half-life Excretion

61.3 minutes renal Identifiers

CAS number ATC code PubChem DrugBank ChemSpider UNII KEGG ChEBI ChEMBL

26787-78-0 J01CA04 QG51AA03 CID 33613 DB01060 31006 9EM05410Q9 D07452 CHEBI:2676 CHEMBL1082 Chemical data

Formula Mol. mass SMILES InChI[show]

C16H19N3O5S 365.4 g/mol eMolecules & PubChem

(what is this?) (verify)

Amoxicillin BP Amoxicillin (INN), formerly amoxycillin (BAN), and abbreviated amox, is a moderate-spectrum, bacteriolytic, -lactam antibiotic used to treat bacterial infections caused by susceptible microorganisms. It is usually the drug of choice within the class because it is better absorbed, following oral administration, than other -lactam antibiotics. Amoxicillin is one of the most common antibiotics prescribed for children. Amoxicillin is susceptible to degradation by -lactamase-producing bacteria, which are resistant to a broad spectrum of -lactam antibiotics, such as penicillin. For this reason, it is often combined with clavulanic acid, a -lactamase inhibitor. This increases effectiveness by reducing its susceptibility to -lactamase resistance. Contents [hide]

1 Medical uses 2 Adverse effects o 2.1 Nonallergic amoxicillin rash o 2.2 Interaction 3 Mechanism of action 4 Spectrum of Bacterial Susceptibility and Resistance 5 Formulations o 5.1 Modes of delivery o 5.2 Proprietary preparations 6 References 7 Further reading 8 External links

[edit] Medical uses Amoxicillin is used in the treatment of a number of infections including: acute otitis media, streptococcal pharyngitis, pneumonia, skin infections, urinary tract infections, salmonella, lyme disease, and chlamydia infections.[1] It is used to prevent bacterial endocarditis in high risk people who are having dental work done, to prevent strep pneumococus infections in those without a spleen, and for both the prevention and the treatment of anthrax.[1] It is also a treatment for cystic acne.[2] The UK however does not recommend its use for infectious endocarditis prophylaxis.[3] These recommendations have not appeared to have changed the rates of infection.[4] [edit] Adverse effects

Side-effects are as those for other beta-lactam antibiotics. Side-effects include nausea, vomiting, rashes, and antibiotic-associated colitis. Loose bowel movements (diarrhoea) may also occur. Rarer side-effects include mental changes, lightheadedness, insomnia, confusion, anxiety, sensitivity to lights and sounds, and unclear thinking. Immediate medical care is required upon the first signs of these side-effects. The onset of an allergic reaction to amoxicillin can be very sudden and intense - emergency medical attention must be sought as quickly as possible. The initial onset of such a reaction often starts with a change in mental state, skin rash with intense itching (often beginning in fingertips and around groin area and rapidly spreading), and sensations of fever, nausea, and vomiting. Any other symptoms that seem even remotely suspicious must be taken very seriously. However, more mild allergy symptoms, such as a rash, can occur at any time during treatment, even up to a week after treatment has ceased. For some people who are allergic to amoxicillin the side-effects can be deadly. Use of the amoxicillin/clavulanic acid combination for more than one week has caused mild hepatitis in some patients. Young children having ingested acute overdoses of amoxicillin manifested lethargy, vomiting and renal dysfunction.[5][6] [edit] Nonallergic amoxicillin rash Somewhere between 3% and 10% of children taking amoxicillin (or ampicillin) show a latedeveloping (>72 hours after beginning medication and having never taken penicillin-like medication previously), often itchy rash, which is sometimes referred to as the "amoxicillin rash." The rash can also occur in adults. The rash is described as maculopapular or morbilliform (measles-like; therefore, in medical literature, it is called "amoxicillin-induced morbilliform rash"[7]). It starts on the trunk and can spread from there. This rash is unlikely to be a true allergic reaction, and is not a contraindication for future amoxicillin usage, nor should the current regimen necessarily be stopped. However, this common amoxicillin rash and a dangerous allergic reaction cannot easily be distinguished by inexperienced persons, and therefore a healthcare professional is often required to distinguish between the two.[8] A nonallergic amoxicillin rash may also be an indicator of infectious mononucleosis: Some studies indicate approximately 80-90% of patients with acute Epstein Barr virus infection treated with amoxicillin or ampicillin develop such a rash.[9]

Nonallergic amoxicillin rash 8 days after first dose, 24 hours after rash began. Diagnosed by a pediatric resident at local university hospital.

Eight hours after first photo, individual spots have grown and begun to merge.

Twenty-three hours after first photo, the color appears to be fading, and much of rash has spread to confluence. [edit] Interaction Amoxicillin may interact with the following groups of drugs:

Anticoagulants (e.g. warfarin, pradaxa)[10] Allopurinol (gout treatment) Birth control pills[citation needed] Certain antibiotics Cancer treatment (methotrexate) Uricosuric drugs Typhoid vaccine

[edit] Mechanism of action Main article: Beta-lactam antibiotic This drug acts by inhibiting the synthesis of bacterial cell walls. It inhibits cross-linkage between the linear peptidoglycan polymer chains that make up a major component of the cell walls of both Grampositive and Gram-negative bacteria. It has two ionizable groups in the physiological range (the amino group in alpha-position to the amide carbonyl group and the carboxyl group). [edit] Spectrum of Bacterial Susceptibility and Resistance Bacillus subtilis, Enterococcus, Haemophilus, Helicobacter and Moraxella species are generally susceptible to amoxicillin, while Citrobacter, Klebsiella and Pseudomonas aeruginosa are resistant to amoxicillin.[11] Some E. Coli and Staphylococcus aureus have developed resistance to amoxicillin to varying degrees. [edit] Formulations

[edit] Modes of delivery Pharmaceutical manufacturers make amoxicillin in trihydrate form available as capsules, chewable and dispersible tablets plus syrup and pediatric suspension for oral use, and as the sodium salt for intravenous administration (although the IV formulation is not available in the United States[12]). Amoxicillin is most commonly taken orally. The liquid forms are helpful where the patient might find it difficult to take tablets or capsules. Research with mice (published in 2010) indicates successful delivery using intraperitoneally injected amoxicillin-bearing microparticles.[13]

Cephalosporin

From Wikipedia, the free encyclopedia Jump to: navigation, search Cephalosporin Drug class

Core structure of the cephalosporins Use Biological target ATC code Bacterial infection Penicillin binding proteins J01D External links MeSH AHFS/Drugs.com D002511 Drug Classes

Structure of the classical cephalosporins The cephalosporins (sg. /sflsprn/) are a class of -lactam antibiotics originally derived from the fungus Acremonium, which was previously known as "Cephalosporium".[1] Together with cephamycins they constitute a subgroup of -lactam antibiotics called cephems. Contents [hide]

1 Medical use 2 Adverse effects 3 Mechanism of action 4 Classification o 4.1 Other 5 History

6 References

[edit] Medical use Cephalosporins are indicated for the prophylaxis and treatment of infections caused by bacteria susceptible to this particular form of antibiotic. First-generation cephalosporins are active predominantly against Gram-positive bacteria, and successive generations have increased activity against Gram-negative bacteria (albeit often with reduced activity against Gram-positive organisms). [edit] Adverse effects Common adverse drug reactions (ADRs) (1% of patients) associated with the cephalosporin therapy include: diarrhea, nausea, rash, electrolyte disturbances, and/or pain and inflammation at injection site. Infrequent ADRs (0.11% of patients) include: vomiting, headache, dizziness, oral and vaginal candidiasis, pseudomembranous colitis, superinfection, eosinophilia, and/or fever. The commonly quoted figure of 10% of patients with allergic hypersensitivity to penicillins and/or carbapenems also having cross-reactivity with cephalosporins originated from a 1975 study looking at the original cephalosporins,[2] and subsequent "safety first" policy meant this was widely quoted and assumed to apply to all members of the group.[3] Hence it was commonly stated that they are contraindicated in patients with a history of severe, immediate allergic reactions (urticaria, anaphylaxis, interstitial nephritis, etc.) to penicillins, carbapenems or cephalosporins.[4] This, however, should be viewed in the light of recent epidemiological work suggesting that, for many secondgeneration (or later) cephalosporins, the cross-reactivity rate with penicillin is much lower, having no significantly increased risk of reactivity in the studies examined.[3][5] The British National Formulary previously issued blanket warnings of 10% cross reactivity, but, since the September 2008 edition, suggests in the absence of suitable alternatives that oral cefixime or cefuroxime and injectable cefotaxime, ceftazidine, and ceftriaxone can be used with caution, but to avoid cefaclor, cefadrocil, cefalexin, and cefradine.[6] Several cephalosporins are associated with hypoprothrombinemia and a disulfiram-like reaction with ethanol.[7][8] These include latamoxef, cefmenoxime, moxalactam, cefoperazone, cefamandole, cefmetazole, and cefotetan. This is thought to be due to the N-methylthiotetrazole (NMTT) side-chain of these cephalosporins, which blocks the enzyme vitamin K epoxide reductase (likely causing hypothrombinemia) and aldehyde dehydrogenase (causing alcohol intolerance).[9] [edit] Mechanism of action Cephalosporins are bactericidal and have the same mode of action as other beta-lactam antibiotics (such as penicillins) but are less susceptible to penicillinases. Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin-binding proteins (PBPs). PBPs bind to the D-Ala-D-Ala at the end of muropeptides (peptidoglycan precursors) to crosslink the peptidoglycan. Beta-lactam antibiotics mimic the D-Ala-D-Ala site, thereby competitively inhibiting PBP crosslinking of peptidoglycan. [edit] Classification The cephalosporin nucleus can be modified to gain different properties. Cephalosporins are sometimes grouped into "generations" by their antimicrobial properties. The first cephalosporins were designated first-generation cephalosporins, whereas, later, more extended-spectrum cephalosporins

were classified as second-generation cephalosporins. Each newer generation of cephalosporins has significantly greater Gram-negative antimicrobial properties than the preceding generation, in most cases with decreased activity against Gram-positive organisms. Fourth-generation cephalosporins, however, have true broad-spectrum activity. The classification of cephalosporins into "generations" is commonly practised, although the exact categorization of cephalosporins is often imprecise. For example, the fourth generation of cephalosporins is not recognized as such, in Japan.[citation needed] In Japan, cefaclor is classed as a firstgeneration cephalosporin, even though in the United States it is a second-generation one; and cefbuperazone, cefminox, and cefotetan are classed as second-generation cephalosporins. Cefmetazole and cefoxitin are classed as third-generation cephems. Flomoxef, latamoxef are in a new class called oxacephems. Most first-generation cephalosporins were originally spelled "ceph-" in English-speaking countries. This continues to be the preferred spelling in the United States and Australia, while European countries (including the United Kingdom) have adopted the International Nonproprietary Names, which are always spelled "cef-". Newer first-generation cephalosporins and all cephalosporins of later generations are spelled "cef-", even in the United States. Some state that, although cephalosporins can be divided into five or even six generations, the usefulness of this organization system is of limited clinical relevance.[10] Fourth-generation Cephalosporins as of March, 2007 were considered to be "a class of highly potent antibiotics that are among medicine's last defenses against several serious human infections" according to the Washington Post.[11] Description Gram-positive: Activity against penicillinaseCefacetrile (cephacetrile), Cefadroxil producing, methicillin-susceptible staphylococci (cefadroxyl; Duricef), Cephalexin (cephalexin; and streptococci (though they are not the drugs of Keflex), Cefaloglycin (cephaloglycin), choice for such infections). No activity against Cefalonium (cephalonium), Cefaloridine methicillin-resistant staphylococci or enterococci. 1 (cephaloradine), Cefalotin (cephalothin; Keflin), Gram-negative: Activity against Proteus Cefapirin (cephapirin; Cefadryl), Cefatrizine, mirabilis, some Escherichia coli, and Klebsiella Cefazaflur, Cefazedone, Cefazolin (cephazolin; pneumoniae ("PEcK"), but have no activity against Ancef, Kefzol), Cefradine (cephradine; Bacteroides fragilis, Pseudomonas, Acinetobacter, Velosef), Cefroxadine, Ceftezole. Enterobacter, indole-positive Proteus, or Serratia. Cefaclor (Ceclor, Distaclor, Keflor, Raniclor), Cefonicid (Monocid), Cefprozil (cefproxil; Cefzil), Cefuroxime (Zefu, Zinnat, Zinacef, Ceftin, Biofuroksym,[12] Xorimax), Cefuzonam. Gram-positive: Less than first-generation. Second generation cephalosporins with Gram-negative: Greater than first-generation: antianaerobe activity: Cefmetazole, Cefotetan, 2 HEN (Haemophilus influenzae, Enterobacter Cefoxitin. The following cephems are also aerogenes and some Neisseria + the PEcK sometimes grouped with second-generation described above. cephalosporins: Carbacephems: loracarbef (Lorabid); Cephamycins: cefbuperazone, cefmetazole (Zefazone), cefminox, cefotetan (Cefotan), cefoxitin (Mefoxin). 3 Cefcapene, Cefdaloxime, Cefdinir (Zinir, Gram-positive: Some members of this group (in Omnicef, Kefnir), Cefditoren, Cefetamet, particular, those available in an oral formulation, Cefixime (Zifi, Suprax), Cefmenoxime, and those with anti-pseudomonal activity) have Cefodizime, Cefotaxime (Claforan), Cefovecin decreased activity against Gram-positive (Convenia), Cefpimizole, Cefpodoxime (Vantin, organisms. # Members

Gram-negative: Third-generation cephalosporins have a broad spectrum of activity and further increased activity against Gram-negative PECEF), Cefteram, Ceftibuten (Cedax), organisms. They may be particularly useful in Ceftiofur, Ceftiolene, Ceftizoxime (Cefizox), treating hospital-acquired infections, although Ceftriaxone (Rocephin). Third-generation increasing levels of extended-spectrum betacephalosporins with antipseudomonal activity: lactamases are reducing the clinical utility of this Cefoperazone (Cefobid), Ceftazidime (Fortum, class of antibiotics. They are also able to penetrate Fortaz). The following cephems are also the CNS, making them useful against meningitis sometimes grouped with third-generation caused by pneumococci, meningococci, H. cephalosporins: Oxacephems: latamoxef influenzae, and susceptible E. coli, Klebsiella, and (moxalactam). penicillin-resistant N. gonorrhoeae. Since 2007, third-generation cephalosporins (ceftriaxone or cefixime) have been the only recommended treatment for gonorrhea in the United States.[13] Gram-positive: They are extended-spectrum agents with similar activity against Gram-positive organisms as first-generation cephalosporins. Cefclidine, Cefepime (Maxipime), Cefluprenam, Gram-negative: Fourth-generation cephalosporins Cefoselis, Cefozopran, Cefpirome (Cefrom), are zwitterions that can penetrate the outer 4 Cefquinome. The following cephems are also membrane of Gram-negative bacteria.[14] They also sometimes grouped with fourth-generation have a greater resistance to beta-lactamases than cephalosporins: Oxacephems: flomoxef the third-generation cephalosporins. Many can cross the bloodbrain barrier and are effective in meningitis. They are also used against Pseudomonas aeruginosa. Ceftobiprole has been described as "fifthgeneration" cephalosporin,[15][16] though acceptance for this terminology is not universal. Ceftobiprole (and the soluble prodrug medocaril) are on the FDA fast-track. Ceftobiprole has powerful 5 Ceftobiprole, Ceftaroline antipseudomonal characteristics and appears to be less susceptible to development of resistance. Ceftaroline has also been described as "fifthgeneration" cephalosporin, but does not have the anti-pseudomonal or VRE coverage of ceftobiprole[17] [edit] Other These cephems have progressed far enough to be named, but have not been assigned to a particular generation: Cefaloram, Cefaparole, Cefcanel, Cefedrolor, Cefempidone, Cefetrizole, Cefivitril, Cefmatilen, Cefmepidium, Cefoxazole, Cefrotil, Cefsumide, Ceftioxide, Cefuracetime.[citation needed] [edit] History See also: Discovery and development of cephalosporins Cephalosporin compounds were first isolated from cultures of Cephalosporium acremonium from a sewer in Sardinia in 1948 by Italian scientist Giuseppe Brotzu.[18] He noticed that these cultures produced substances that were effective against Salmonella typhi, the cause of typhoid fever, which had beta-lactamase. Guy Newton and Edward Abraham at the Sir William Dunn School of Pathology at the University of Oxford isolated cephalosporin C. The cephalosporin nucleus, 7aminocephalosporanic acid (7-ACA), was derived from cephalosporin C and proved to be analogous

to the penicillin nucleus 6-aminopenicillanic acid (6-APA), but it was not sufficiently potent for clinical use. Modification of the 7-ACA side-chains resulted in the development of useful antibiotic agents, and the first agent cefalotin (cephalothin) was launched by Eli Lilly and Company in 1964.

Spiramycin

From Wikipedia, the free encyclopedia Jump to: navigation, search Spiramycin

Systematic (IUPAC) name (4R,5S,6R,7R,9R,10R,11E,13E,16R)-10-{[(2R,5S,6R)-5(dimethylamino)-6-methyltetrahydro-2H-pyran-2-yl]oxy}9,16-dimethyl-5-methoxy-2-oxo-7-(2oxoethyl)oxacyclohexadeca-11,13-dien-6-yl 3,6-dideoxy4-O-(2,6-dideoxy-3-C-methyl--L-ribo-hexopyranosyl)-3(dimethylamino)--D-glucopyranoside Clinical data Pregnancy cat. Legal status ? Identifiers CAS number 8025-81-8 ATC code PubChem J01FA02 QJ51FA02 CID 5356392 ?

ChemSpider 4512090 UNII 71ODY0V87H

KEGG ChEMBL NIAID ChemDB Synonyms

D05908 CHEMBL1256397 007350

2-[(4R,5S,6S,7R,9R,10R,11E,13E,16R)-6{[(2S,3R,4R,5S,6R)-5-{[(2S,5S,6S)-4,5dihydroxy-4,6-dimethyloxan-2-yl]oxy}-4(dimethylamino)-3-hydroxy-6-methyloxan2-yl]oxy}-10-{[(2R,5S,6R)-5(dimethylamino)-6-methyloxan-2-yl]oxy}4-hydroxy-5-methoxy-9,16-dimethyl-2oxo-1-oxacyclohexadeca-11,13-dien-7yl]acetaldehyde Chemical data

Formula Mol. mass SMILES InChI[show]

C43H74N2O14 843.053 g/mol eMolecules & PubChem

Physical data Solubility in Insoluble in water; Very soluble in water acetonitrile and methanol; Almost completely(>99.5) in ethanol. mg/mL (20 C) (what is this?) (verify) Spiramycin is a macrolide antibiotic. It is used to treat toxoplasmosis and various other infections of soft tissues. Although used in Europe, Canada and Mexico[1], spiramycin is still considered an experimental drug in the United States, but can sometimes be obtained by special permission from the FDA for toxoplasmosis in the first trimester of pregnancy.[2] Spiramycin has been used in Europe since the year 2000 under the trade name "Rovamycine", produced by Rhone-Poulenc Rorer and Famar Lyon, France and Eczacibasi Ilae, Turkey. It also goes

under the name Rovamycine in Canada (distributed by OdanLaboratories), where it is mostly marketed to dentists for mouth infections. Spiramycin is a 16-membered ring macrolide (antibiotic). It was discovered in 1952 as a product of Streptomyces ambofaciens. As a preparation for oral administration it has been used since 1955, in 1987 also the parenteral form was introduced into practice. The antibacterial action involves inhibition of protein synthesis in the bacterial cell during translocation. Resistance to spiramycin can develop by several mechanisms and its prevalence is to a considerable extent proportional to the frequency of prescription in a given area. The antibacterial spectrum comprises Gram-positive cocci and rods, Gram-negative cocci and also Legionellae, mycoplasmas, chlamydiae, some types of spirochetes, Toxoplasma gondii and Cryptosporidium sp., Enterobacteria, pseudomonads and pathogenic moulds are resistant. Its action is mainly bacteriostatic, on highly sensitive strains it exerts a bactericide action. As compared with erythromycin, it is in vitro weight for weight 5 to 20 less effective, an equipotential therapeutic dose is, however, only double. This difference between the effectiveness in vitro and in vivo is explained above all by the great affinity of spiramycin to tissues where it achieves concentrations many times higher than serum levels. An important part is played also by the slow release of the antibiotic from the tissue compartment, the marked action on microbes in sub-inhibition concentrations and the relatively long persisting post-antibiotic effect. Its great advantage is the exceptionally favourable tolerance-gastrointestinal and general. It is available for parenteral and oral administration [edit] References 1. 2. ^ Spiramycin advanced consumer information | Drugs.com ^ Toxoplasmosis at MayoClinic.com [hide]

v t e

Antibacterials: protein synthesis inhibitors (J01A, J01B, J01F, J01G, QJ01XQ) 30S Aminoglycosides (initiation inhibitors) -mycin (Streptomyces)

Streptomycin# Dihydrostreptomycin Neomycin# (

o o o

Framycetin Paromomycin Ribostamycin )

Kanamycin# (
o

Amikacin

o o o o

Arbekacin Bekanamycin Dibekacin Tobramycin )

Spectinomycin# Hygromycin B Paromomycin Gentamicin# (

o o o

-micin (Micromonospora)

Netilmicin Sisomicin Isepamicin )

Verdamicin Astromicin

Tetracycline antibiotics (tRNA binding)

Tetracyclines

Doxycycline# Chlortetracycline Clomocycline Demeclocycline Lymecycline Meclocycline Metacycline Minocycline Oxytetracycline Penimepicycline Rolitetracycline Tetracycline Tigecycline

Glycylcyclines 50S Oxazolidinone (initiation inhibitors)

Linezolid Torezolid Eperezolid Posizolid Radezolid

Peptidyl transferase

Amphenicols

Chloramphenicol# Azidamfenicol

Thiamphenicol Florfenicol Retapamulin Tiamulin Valnemulin Azithromycin# Clarithromycin Dirithromycin Erythromycin# Flurithromycin Josamycin Midecamycin Miocamycin Oleandomycin Rokitamycin Roxithromycin Spiramycin Troleandomycin Tylosin Ketolides (
o o o

Pleuromutilins

Macrolides

MLS (transpeptidation/translocatio n)

Telithromycin Cethromycin Solithromycin )

Lincosamid es

Clindamycin# Lincomycin Pirlimycin Pristinamycin Quinupristin/dalfopristin Virginiamycin

Streptogra mins

EFG

Steroid antibacterials

Fusidic acid

WHO-EM Withdrawn from market Clinical trials: ( o Phase III

M: BAC

bact (clas)

Never to phase III ) gr+f/gr+a(t)/gr-p(c)/gr-o drug(J1p, w, n, m, vacc)

Dexamethasone From Wikipedia, the free encyclopedia Jump to: navigation, search Dexamethasone

Systematic (IUPAC) name (8S,9R,10S,11S,13S,14S,16R,17R)-9- Fluoro-11,17dihydroxy-17-(2-hydroxyacetyl)-10,13,16- trimethyl6,7,8,9,10,11,12,13,14,15,16,17- dodecahydro-3Hcyclopenta[a]phenanthren-3-one Clinical data AHFS/Drugs.com monograph MedlinePlus Pregnancy cat. Legal status Routes a682792 C (US) Prescription only Oral, IV, IM, SC and IO

Pharmacokinetic data Bioavailability Protein binding Metabolism Half-life Excretion 80-90% 70% hepatic 36-54 hours renal Identifiers CAS number ATC code 50-02-2 A01AC02 C05AA09, D07AB19, D10AA03, H02AB02, R01AD03, S01BA01, S02BA06, S03BA01 PubChem DrugBank ChemSpider UNII KEGG ChEBI ChEMBL CID 5743 DB01234 5541 7S5I7G3JQL D00292 CHEBI:41879 CHEMBL384467 Chemical data Formula Mol. mass C22H29FO5 392.461 g/mol

SMILES InChI[show]

eMolecules & PubChem

(what is this?) (verify) Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant. When taken orally, it is 26.6 times more potent than the naturally occurring hormone cortisol and 6.6 times more potent than prednisone. Contents [hide]

1 Therapeutic use o 1.1 Anti-inflammatory o 1.2 Oncologic uses o 1.3 Endocrine o 1.4 Obstetrics o 1.5 High altitude illnesses 2 Off-label use o 2.1 Congenital adrenal hyperplasia o 2.2 Abuses 3 Diagnostic use 4 Veterinary use 5 Contraindications 6 Side effects 7 Interactions 8 Dosage 9 Synthesis 10 References 11 External links

[edit] Therapeutic use [edit] Anti-inflammatory Dexamethasone is used to treat many inflammatory and autoimmune conditions, such as rheumatoid arthritis and bronchospasm.[1] Idiopathic thrombocytopenic purpura, decreased numbers of platelets due to an immune problem, responds to 40 mg daily for four days; it may be administered in 14-day cycles. It is unclear whether dexamethasone in this condition is significantly better than other glucocorticoids.[2] It is also given in small amounts[3] (usually five or six tablets) before and/or after some forms of dental surgery, such as the extraction of the wisdom teeth, an operation which often leaves the patient with puffy, swollen cheeks. It is injected into the heel when treating plantar fasciitis, sometimes in conjunction with triamcinolone acetonide.

It is useful to counteract allergic anaphylactic shock, if given in high doses. It is present in certain eye drops particularly after eye surgery and as a nasal spray (trade name Dexacort), and certain ear drops (Sofradex, when combined with an antibiotic and an antifungal). Dexamethasone is used in transvenous screw-in cardiac pacing leads to minimize the inflammatory response of the myocardium. The steroid is released into the myocardium as soon as the screw is extended and can play a significant role in minimizing the acute pacing threshold due to the reduction of inflammatory response. The typical quantity present in a lead tip is less than 1.0 mg. Dexamethasone is often administered before antibiotics in cases of bacterial meningitis. It then acts to reduce the inflammatory response of the body to the bacteria killed by the antibiotics (bacterial death releases proinflammatory mediators that can cause a response which is harmful to the patient), thus improving prognosis and outcome.[4]

Dexamethasone phosphate for injection [edit] Oncologic uses Cancer patients undergoing chemotherapy are given dexamethasone to counteract certain side effects of their antitumor treatment. Dexamethasone can augment the antiemetic effect of 5-HT3 receptor antagonists, such as ondansetron. In brain tumors (primary or metastatic), dexamethasone is used to counteract the development of edema, which could eventually compress other brain structures. It is also given in cord compression, where a tumor is compressing the spinal cord. Dexamethasone is also used as a direct chemotherapeutic agent in certain hematological malignancies, especially in the treatment of multiple myeloma, in which dexamethasone is given alone or in combination with other chemotherapeutic drugs, including most commonly with thalidomide (thaldex), lenalidomide, bortezomib (Velcade; Vel-dex),[5] or a combination of Adriamycin (doxorubicin) and vincristine (VAD). [edit] Endocrine

Dexamethasone is the treatment for the very rare disorder of glucocorticoid resistance.[6][7] In adrenal insufficiency and Addison's disease, dexamethasone is prescribed when the patient does not respond well to prednisone or methylprednisolone. [edit] Obstetrics Dexamethasone may be given to women at risk of delivering prematurely to promote maturation of the fetus' lungs. This has been associated with low birth weight, although not with increased rates of neonatal death.[8] [edit] High altitude illnesses Dexamethasone is used in the treatment of high altitude cerebral edema, as well as pulmonary edema. It is commonly carried on mountain climbing expeditions to help climbers deal with altitude sickness.
[9][10]

[edit] Off-label use [edit] Congenital adrenal hyperplasia Dexamethasone has been used as an off-label prenatal treatment for the symptoms of congenital adrenal hyperplasia (CAH) in female fetuses. CAH causes a variety of physical abnormalities, notably ambiguous genitalia in girls. Early prenatal CAH treatment has been shown to reduce some CAH symptoms, but it does not treat the underlying congenital disorder. A 2007 Swedish clinical trial found the treatment may cause cognitive and behavioural defects, but the small number of test subjects means the study cannot be considered definitive. Administration of prenatal dexamethasone has been the subject of controversy over issues of informed consent and because treatment must predate a clinical diagnosis of CAH in the female fetus. The treatment has also raised concerns in the LGBT community following an essay[11] posted to the forum of the Hastings Center, a think tank devoted to bioethics, which quoted published research that suggested prenatal treatment of female fetuses could prevent those fetuses from becoming lesbians after birth, may make them more likely to engage in "traditionally" female-identified behaviour and careers, and more interested in bearing and raising children. Referring to a prospective father who attempted to mitigate the effects of the fraternal birth order effect on increasing the chances of homosexuality in male children by using a surrogate mother, the essay suggests prenatal "dex" treatments constitute the first known attempt to use an in utero method to attempt to reduce the incidence of homosexuality in humans.[12] A medical consensus in 2010 by the Endocrine Society and affiliated organizations indicated prenatal dexamethasone for CAH should be regarded as experimental and should only be used in Institutional Review Board-approved controlled clinical trials at centers large enough to collect meaningful data.[13] [edit] Abuses Dexamethasone has also been used in the hope of enhancing sports performance. [14] Long term use of dexamethasone under the brand name Oradexon is widespread among prostitutes in Bangladesh in spite of the dangers, because it helps them develop fat easily.[15][16] [edit] Diagnostic use

Dexamethasone is also used in a diagnostic context, namely in its property to suppress the natural pituitary-adrenal axis. Patients presenting with clinical signs of glucocorticoid excess (Cushing's syndrome) are generally diagnosed by a 24-hour urine collection for cortisol or by a dexamethasone suppression test. During the latter, the response of the body to a high dose of glucocorticoids is monitored. Various forms are performed. In the most common form, a patient takes a nighttime dose of either 1 or 4 mg of dexamethasone, and the serum cortisol levels are measured in the morning. If the levels are relatively high (over 5 g/dL or 150 nmol/L), then the test is positive and the patient has an autonomous source of either cortisol or ACTH, indicating Cushing's syndrome where the tumor does not have a feedback mechanism. If ACTH levels are lowered by at least 50%, this would indicate Cushing's disease, since the pituitary adenoma has a feedback mechanism that has been reset to a higher level of cortisol. Longer versions rely on urine collections on oral dexamethasone over various days. [edit] Veterinary use Combined with marbofloxacin and clotrimazole, dexamethasone is available under the name Aurizon, CAS number 115550-35-1, and used to treat difficult ear infections, especially in dogs. It can also be combined with trichlormethiazide to treat horses with swelling of distal limbs and general bruising.[17] [edit] Contraindications Some of these contraindications are relative:

Existing gastrointestinal ulceration Cushing's syndrome Severe forms of heart insufficiency Severe hypertension Uncontrolled diabetes mellitus Systemic tuberculosis Severe systemic viral, bacterial, and fungal infections Pre-existing wide angle glaucoma Osteoporosis

[edit] Side effects If dexamethasone is given orally or by injection (parenteral) over a period of more than a few days, side effects common to systemic glucocorticoids may occur. These may include:

Stomach upset, increased sensitivity to stomach acid to the point of ulceration of esophagus, stomach, and duodenum Increased appetite leading to significant weight gain A latent diabetes mellitus often becomes manifest, glucose intolerance is worsened in patients with pre-existing diabetes Immunsuppressant action, particularly if given with other immunosuppressants, such as cyclosporine, may allow bacterial, viral, and fungal disease to progress more easily and can become life-threatening; fever as a warning symptom is often suppressed. Psychiatric disturbances, including personality changes, irritability, euphoria, or mania Osteoporosis under long term treatment, pathologic fractures (e.g., hip) Muscle atrophy, negative protein balance (catabolism) Elevated liver enzymes, fatty liver degeneration (usually reversible) Cushingoid (syndrome resembling hyperactive adrenal cortex with increase in adiposity, hypertension, bone demineralization, etc.)

Depression of the adrenal gland is usually seen, if more than 1.5 mg daily are given for more than three weeks to a month. Hypertension, fluid and sodium retention, edema, worsening of heart insufficiency (due to mineral corticoid activity) Dependence with withdrawal syndrome is frequently seen. Increased intraocular pressure, certain types of glaucoma, cataract (serious clouding of eye lenses) Dermatologic: Acne, allergic dermatitis, dry scaly skin, ecchymoses and petechiae, erythema, impaired wound-healing, increased sweating, rash, striae, suppression of reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria. Allergic reactions (though infrequently): Anaphylactoid reaction, anaphylaxis, angioedema.

Other side effects have been noted, and should cause concern if they are more than mild. The short-time treatment for allergic reaction, shock, and diagnostic purposes usually does not cause serious side effects. Novelist Michael Cox believed his first book, The Meaning of Night was a side effect of prescription dexamethasone, giving him both "formidable energy" while quelling his creative doubts.[18] [edit] Interactions

NSAIDs and alcohol: increased risk of gastrointestinal ulceration Mineralocorticoids: increased risk of hypertension, edema and heart problems Oral antidiabetic drugs and insulin: antidiabetic therapy may have to be adjusted

Other interactions (with certain antibiotics, estrogens, ephedrine, digoxin) are known. [edit] Dosage

Shock: 4 to 8 mg intravenously initially, repeat if necessary to a total dose of 24 mg. Autoimmune diseases and inflammations: longterm therapy with 0.5 to 1.5 mg oral per day. Avoid more than 1.5 mg daily, because serious side effects are more frequently encountered with higher doses. Adjuvant to or part of chemotherapy: individual schedule Diagnostic purposes: special schedule

[edit] Synthesis To synthesise dexamethasone, 16-methylprednisolone acetate is dehydrated to the 9,11 dehydro derivative. This is then reacted with a source of hypobromite, such as basic N-bromosuccinimide, to form the 9-bromo-11-hydrin derivative, which is then ring-closed to an epoxide. A ring-opening reaction with hydrogen fluoride in tetrahydrofuran gives dexamethasone.[19] [20]

KALIUM DIKLOFENAK 50 MG

FARMAKOLOGI :

Kalium diklofenak mempunyai sifat analgesik dan anti-inflamasi kuat. Mekanisme kerja yang utama adalah melalui penghambatan pada biosintesis prostaglandin. Pada keadaan inflamasi seperti trauma

setelah operasi, kalium diklofenak meringankan nyeri spontan dan nyeri pada pergerakan, serta menghilangkan pembengkakan dan luka dengan edema. Kalium diklofenak diserap secara lengkap dan kadarnya dalam plasma menunjukkan hubungan yang linear dengan besarnya dosis. Kira-kira setengah dari senyawa aktifnya dimetabolisme pada lintasan pertama melalui hati. Sebanyak 99% diklofenak terikat pada protein serum. Waktu paruh akhir dalam plasma adalah 1-2 jam. Obat ini dimetabolisme hampir lengkap di hati dan kurang dari 1% diekskresi melalui urin sebagai senyawa asal.

INDIKASI :

Pengobatan jangka pendek pada keadaan : * Rasa sakit pada peradangan pasca traumatik, misalnya akibat keseleo. * Peradangan dan nyeri setelah operasi, misalnya setelah bedah mulut atau ortopedik. * Sebagai obat tambahan pada nyeri akibat peradangan telinga, hidung, tenggorokan, misalnya pada faringotonsilitis, otitis. * Sesuai dengan prinsip pengobatan umum, penyakitnya sendiri harus diobati dengan terapi dasar. Demam sendiri bukan suatu indikasi. KONTRA INDIKASI :

Penderita tukak lambung, penderita yang mempunyai hipersensitivitas terhadap bahan aktif dari obat. Penderita yang terkena serangan asma, urtikaria atau rhinitis akut yang disebabkan oleh asam asetilsalisilat atau oleh obat lain yang mempunyai aktivitas penghambatan terhadap pembentukan prostaglandin.

DOSIS : Pada kasus ringan, dosis dewasa dan anak-anak diatas 14 tahun adalah 75-100 mg/hari, dibagi dalam 2-3 dosis. Untuk kasus yang lebih berat, dosis harus dinaikkan sampai 100-150 mg/hari. Kalium diklofenak tablet tidak direkomendasikan penggunaannya pada anak-anak. Sebaiknya digunakan bersama dengan minuman, terutama sebelum makan.

EFEK SAMPING :

* Saluran cerna - Kadang-kadang : nyeri epigastrik, gangguan saluran cerna lain seperti mual, muntah, diare, kram perut, dispepsia, flatulen, anoreksia. - Jarang: perdarahan saluran cerna, hematemesis, melena, tukak peptik dengan atau tanpa perdarahan atau perforasi, diare berdarah. - Kasus khusus: gangguan saluran cerna bagian bawah seperti kolitis hemoragik non-spesifik dan eksaserbasi kolitis ulseratif atau proktokolitis Crohns, stomatitis aftosa, glositis, lesi esofagus, konstipasi.

* Sistem saraf pusat dan perifer - Kadang-kadang : sakit kepala, pusing atau vertigo. - Jarang : mengantuk - Kasus khusus : gangguan perasaan (sensation), termasuk parestesia, disorientasi, gangguan memori, gangguan penglihatan (penglihatan kabur, diplopia), kurang pendengaran, tinitus, insomnia, iritabilitas, konvulsi, depresi, cemas, mimpi buruk, tremor, reaksi psikotik, gangguan pengecapan. * Kulit - Kadang-kadang : ruam atau erupsi kulit. - Jarang: urtikaria. - Kasus khusus : erupsi bulosa, eksim, eritema multiforme, sindroma Stevens - Johnson, sindroma Lyell (epidermalisis toksik akut), eritoderma (eksfoliatif dermalitis), rambut rontok, reaksi fotosensitivitas, purpura, termasuk purpura alergik. *Sistem urogenital - Kasus khusus : gagal ginjal akut, abnormalitas urin seperti hematuria, proteinuria, nefritis interstisial, sindroma nefrotik, nekrosis papiler. * Hati - Kadang-kadang : peningkatan enzim serum aminotransferase (SGOT, SGPT). - Jarang : hepatitis dengan atau tanpa ikterus. - Kasus khusus : hepatitis fulminan. * Darah - Kasus khusus : trombositopenia, leukopenia, anemia (anemia hemolitik, anemia aplastik), agranulositosis. * Hipersensitivitas - Jarang : reaksi hipersensitivitas seperti asma, reaksi anafilaktif/reaksi anafilaktoid sistemik termasuk hipotensi. * Lain-lain - Jarang : edema. - Kasus khusus : palpitasi, nyeri dada, hipertensi. OVER DOSIS :

Penanganan keracunan akut karena obat anti-inflamasi nonsteroid terdiri terutama dari tindakan suportif dan simptomatik. Tindakan yang harus diambil bila terjadi overdosis adalah sebagai berikut : cegah penyerapan sesegera mungkin dengan bilas lambung dan pemberian zat arang aktif. Pengobatan supportif dan simptomatik harus dilakukan untuk komplikasi seperti hipotensi, gagal ginjal, konvulsi, iritasi saluran pencernaan dan depresi pernafasan. Pengobatan spesifik seperti diuresis paksa, dialisis atau hemoperfusi kemungkinan dapat menolong dalam menghilangkan obat anti-inflamasi nonsteroid, karena tingkat pengikatannya dengan protein yang tinggi dan metabolismenya yang ekstensif. PERINGATAN & PERHATIAN :

- Diagnosa pasti dan pengawasan medis ketat merupakan suatu keharusan pada penderita dengan gejala yang menunjukan gangguan saluran cerna dengan riwayat ulserasi saluran cerna, kolitis ulseratif atau penyakit Crohns, juga pada penderita gangguan fungsi hati yang berat.

- Penggunaan pada wanita hamil dan menyusui - Pada kehamilan, kalium diklofenak diberikan hanya dengan alasan yang jelas dan hanya dengan dosis efektif terendah, khususnya pada 3 bulan terakhir kehamilan, seperti halnya inhibitor sintetsisprostaglandin lain (karena kemungkinan terjadi inersia uteri dan/atau penutupan premature duktus arteriosus). - Pada pemberian dosis oral 50 mg setiap 8 jam, bahan aktif diklofenak masuk ke dalam air susu. Seperti halnya obat lain yang diekskresi melalui air susu, penggunaan kalium diklofenak tidak direkomendasikan pada wanita menyusui. - Efek terhadap kemampuan menjalankan atau menggunakan mesin. Penderita yang pusing atau mengalami gangguan saraf pusat lain tidak boleh menjalankan kendaraan atau mengoperasikan mesin.

INTERAKSI OBAT :

Bila diberikan bersama dengan sediaan yang mengandung litium atau digoksin, diklofenak dapat meningkatkan konsentrasi obat-obat tersebut dalam plasma tetapi belum pernah dilaporkan terjadi tanda-tanda klinis overdosis. Berbagai obat anti-inflamasi nonsteroid dapat menghambat aktivitas diuretik. Pemberian bersama diuretik hemat kalium kemungkinan berhubungan dengan peningkatan kadar kalium serum, sehingga perlu dimonitor. Pemberian bersama dengan senyawa anti-inflamasi nonsteroid sistemik dapat meningkatkan terjadinya efek samping. Walaupun penelitian klinis tidak menunjukkan diklofenak mempunyai pengaruh terhadap efek antikoagulan, terdapat laporan khusus mengenai peningkatan resiko perdarahan dengan terapi kombinasi penggunaan diklofenak dan anti-koagulan. Karena itu pada penderita yang demikian, disarankan dilakukan monitoring ketat. Seperti anti-inflamasi nonsteroid lainnya, diklofenak dosis tinggi (200 mg) dapat menghambat agregasi trombosit untuk sementara. Penelitian klinis menunjukkan bahwa diklofenak dapat diberikan bersama dengan obat anti-diabetik oral tanpa mempengaruhi efek klinisnya. Namun terdapat laporan bahwa efek hipoglikemik dan hiperglikemik diklofenak mengharuskan penyesuaian dosis obat-obat hipoglikemik. Perlu diperhatikan bila obat anti-inflamasi nonsteroid diberikan kurang dari 24 jam sebelum atau sesudah pengobatan dengan metotreksat, karena kadar dan toksisitas metotreksat dapat meningkat. Peningkatan nefrotoksisitas siklosporin terhadap prostaglandin ginjal mungkin terjadi melalui efek obat anti-inflamasi nonsteroid.

Cataflam merupakan nama paten dari obat kalium diklofenak, sehingga cataflam juga merupakan derivat dari benzeneacetic acid. Nama kimia dari obat ini adalah 2-[(2,6-dichlorophenyl)amino] benzeneacetic acid, yang termasuk garam monopotassium. Rumus molekul obat ini adalah C14H10Cl2NKO2 dengan berat molekul 334,25. Cataflam sama halnya dengan kalium diklofenak termasuk dalam golongan obat non-steroidal antiinflammatory drug (NSAID) yang mempunyai efek aktivitas anti-inflamasi, analgesik, dan antipiretik. Mekanisme aksi tablet kalium diklofenak seperti golongan obat NSAID lainnya, mungkin terkait

dengan penghambatan sintesis prostaglandin. Obat ini sering digunakan untuk meringankan nyeri inflamasi (pembengkakan) pasca operasi, seperti operasi tulang dan gigi. Komposisi Tiap tablet mengandung Kalium Diklofenak 50 mg Bahan aktif yang terkandung dalam Cataflam meliputi: 1. Kalsium fosfat 2. Colloidal silicon dioxide 3. Iron oxides 4. Magnesium stearat 5. Microcrystalline cellulose 6. Polyethylene glycol 7. Povidone 8. Sodium starch glycolate 9. Maize starch 10. Sucrose 11. Talc 12. Titanium dioxide Indikasi 1. Untuk meringankan nyeri inflamasi (pembengkakan) pasca operasi 2. Untuk pengobatan dysmenorrhea primer 3. Untuk meringankan nyeri ringan sampai sedang 4. Untuk mengatasi gejala osteoarthritis 5. Untuk mengatasi gejala rheumatoid arthritis Kontraindikasi Pasien yang hipersensitif terhadap golongan obat ini Efek samping 1. Reaksi alergi, yang meliputi: gatal-gatal, kesulitan bernafas, pembengkakan wajah, bibir, lidah, atau tenggorokan. 2. Nyeri dada 3. Gangguan penglihatan atau keseimbangan 4. Kotoran (feses) berwarna hitam dan berdarah 5. Batuk atau muntah darah Dosis 1. Dewasa 100-150 mg 2-3 kali sehari 2. Anak Keamanan dan efektivitas pada pasien anak belum ditetapkan

Kemasan Cataflam tersedia dalam bentuk tablet 50 mg (berwarna coklat muda) untuk pemberian melalui mulut (per oral).

Mefenamic acid From Wikipedia, the free encyclopedia Jump to: navigation, search Mefenamic acid

Systematic (IUPAC) name 2-(2,3-dimethylphenyl)aminobenzoic acid Clinical data Trade names AHFS/Drugs.com MedlinePlus Pregnancy cat. Ponstel, Ponstan monograph a681028 C (Australia, United States)

Legal status Routes

-only (U.S.), POM in UK Oral

Pharmacokinetic data Bioavailability Protein binding Metabolism Half-life Excretion 90% 90% Hepatic (CYP2C9) 2 hours Renal and fecal Identifiers CAS number ATC code PubChem IUPHAR ligand DrugBank ChemSpider UNII KEGG ChEMBL 61-68-7 M01AG01 CID 4044 2593 DB00784 3904 367589PJ2C D00151 CHEMBL686 Chemical data

Formula Mol. mass SMILES InChI[show Diclofenac

C15H15NO2 241.285 g/mol eMolecules & PubChem

From Wikipedia, the free encyclopedia Jump to: navigation, search Diclofenac

Systematic (IUPAC) name 2-(2-(2,6-dichlorophenylamino)phenyl)acetic acid Clinical data

Trade names

Cataflam, Voltaren

AHFS/Drugs.com monograph MedlinePlus Pregnancy cat. a689002 C (AU) C (1st. and 2nd. trimenon), D (third trimenon) Legal status P (UK) Rx-only most preparations/countries. Limited OTC some countries. Manufacture and veterinary use is banned in India, Nepal and Pakistan due to imminent extinction of local vultures. Routes oral, rectal, im, iv (renal- and gallstones), topical Pharmacokinetic data Protein binding more than 99% Metabolism Half-life hepatic, no active metabolites exist 1.2-2 hr (35% of the drug enters enterohepatic recirculation) Excretion biliary, only 1% in urine Identifiers CAS number ATC code 15307-86-5 D11AX18 M01AB05, M02AA15, S01BC03 PubChem CID 3033

IUPHAR ligand 2714 DrugBank ChemSpider UNII KEGG ChEBI ChEMBL DB00586 2925 144O8QL0L1 D07816 CHEBI:47381 CHEMBL139 Chemical data Formula Mol. mass SMILES InChI[show] (what is this?) (verify) Diclofenac (marketed under many brand names, see below: Trade names) is a non-steroidal antiinflammatory drug (NSAID) taken to reduce inflammation and as an analgesic reducing pain in certain conditions. The name is derived from its chemical name: 2-(2,6-dichloranilino) phenylacetic acid. In the United Kingdom, India, Brazil and the United States, it may be supplied as either the sodium or potassium salt, in China most often as the sodium salt, while in some other countries only as the potassium salt. Diclofenac is available as a generic drug in a number of formulations. Over-thecounter (OTC) use is approved in some countries for minor aches and pains and fever associated with common infections. Contents [hide]

C14H11Cl2NO2 296.148 g/mol eMolecules & PubChem

1 Medical uses o 1.1 Investigational uses

2 Contraindications 3 Side-effects o 3.1 Cardiac o 3.2 Gastrointestinal o 3.3 Hepatic o 3.4 Renal o 3.5 Mental Health o 3.6 Other 4 Mechanism of action 5 History 6 Ecological effects 7 Formulations 8 Trade names 9 References 10 External links

[edit] Medical uses

Voltaren (diclofenac) 50 mg enteric coated tablets

Arthrotec (diclofenac and misoprostol) 50 mg tablets

Dyloject (diclofenac) 2 mL for IV and IM administration

Sintofarm (diclofenac) for suppository administration Diclofenac is used to treat pain, inflammatory disorders, and dysmenorrhea.[1] Inflammatory disorder may include musculoskeletal complaints, especially arthritis, rheumatoid arthritis, polymyositis, dermatomyositis, osteoarthritis, dental pain, TMJ, spondylarthritis, ankylosing spondylitis, gout attacks,[2] and pain management in cases of kidney stones and gallstones. An additional indication is the treatment of acute migraines.[3] Diclofenac is used commonly to treat mild to moderate post-operative or post-traumatic pain, in particular when inflammation is also present,[2] and is effective against menstrual pain and endometriosis. As long-term use of diclofenac and similar NSAIDs predisposes for peptic ulcer, many patients at risk for this complication are prescribed a combination (Arthrotec) of diclofenac and misoprostol, a synthetic prostaglandin(PGE1) analogue, to protect the gastric mucosa.[citation needed] An external, gel-based formulation containing 3% of diclofenac (Solaraze) is available for the treatment of facial actinic keratosis caused by over-exposure to sunlight. Some countries have also approved the external use of diclofenac 1% gel to treat musculoskeletal conditions. In many countries[where?], eye-drops are sold to treat acute and chronic non-bacterial inflammations of the anterior part of the eyes (e.g., postoperative states).[citation needed] A common brand name is Voltarenoptha. [edit] Investigational uses Diclofenac is often used to treat chronic pain associated with cancer, in particular if inflammation is also present (Step I of the World Health Organization (WHO) Scheme for treatment of chronic pain). Good results (sometimes better than those with opioids) have been seen in female breast cancer and in the pain associated with bony metastases.[citation needed] Diclofenac can be combined with opioids if needed. Combaren, a fixed combination of diclofenac and codeine (50 mg each), is available for cancer treatment in Europe.[citation needed] Combinations with psychoactive drugs such as chlorprothixene

and/or amitriptyline have also been investigated and found useful in a number of cancer patients.[citation
needed]

Fever due to malignant lymphogranulomatosis (Hodgkin's lymphoma) often responds to diclofenac. [citation needed] Treatment can be terminated as soon as the usual treatment with radiation and/or chemotherapy causes remission of fever. Diclofenac has been found to increase the blood pressure in patients with Shy-Drager syndrome and diabetes mellitus. Currently, this use is highly investigative and cannot be recommended as routine treatment. Diclofenac has been found to be effective against all strains of multi drug resistant E. coli, with a MIC of 25 micrograms/mL. Therefore, it may be suggested that diclofenac has the capacity to treat uncomplicated urinary tract infections (UTI) caused by E. coli.[4] It has also been shown to be effective in treating Salmonella infections in mice[5] and is under investigation for the treatment of tuberculosis.[6] Diclofenac is an antiuricosuric.[7] [edit] Contraindications

Hypersensitivity against diclofenac History of allergic reactions (bronchospasm, shock, rhinitis, urticaria) following the use of aspirin or another NSAID Third-trimester pregnancy Active stomach and/or duodenal ulceration or gastrointestinal bleeding Inflammatory intestinal disorders such as Crohn's disease or ulcerative colitis Severe insufficiency of the heart (NYHA III/IV) Recently,[when?] a warning has been issued by the FDA not to use for the treatment of patients recovering from heart surgery Severe liver insufficiency (Child-Pugh Class C) Severe renal insufficiency (creatinine clearance <30 ml/min) Caution in patients with preexisting hepatic porphyria, as diclofenac may trigger attacks Caution in patients with severe, active bleeding such as cerebral hemorrhage NSAIDs in general should be avoided during dengue fever, as it induces (often severe) capillary leakage and subsequent heart failure.

[edit] Side-effects

Diclofenac is among the better tolerated NSAIDs. Though 20% of patients on long-term treatment experience side-effects, only 2% have to discontinue the drug, mostly due to gastrointestinal complaints. And see #Ecological effects below.

[edit] Cardiac

Following the identification of increased risks of heart attacks with the selective COX-2 inhibitor rofecoxib in 2004, attention has focused on all the other members of the NSAIDs group, including diclofenac. Research results are mixed with a meta-analysis of papers and reports up to April 2006 suggesting a relative increased rate of heart disease of 1.63 compared to non-users.[8] Professor Peter Weissberg, Medical Director of the British Heart Foundation said, "However, the increased risk is small, and many patients with chronic debilitating pain may well feel that this small risk is worth taking to relieve their symptoms". Only aspirin was

found not to increase the risk of heart disease; however, this is known to have a higher rate of gastric ulceration than diclofenac. A subsequent large study of 74,838 users of NSAIDs or coxibs, published in May 2006, found no additional cardiovascular risk from diclofenac use.[9] A very large study of 1,028,437 Danish users of various NSAIDs or coxibs, published online on June 8, 2010, found that "Use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with an increased risk of cardiovascular death (odds ratio, 1.91; 95% confidence interval, 1.62 to 2.42; and odds ratio, 1.66; 95% confidence interval, 1.06 to 2.59, respectively), with a dose-dependent increase in risk." .[10]

Diclofenac has similar COX-2 selectivity to celecoxib.[11] A review by FDA Medical Officer David Graham concluded in September, 2006 that diclofenac does increase the risk of myocardial infarction.[12]

[edit] Gastrointestinal

Gastrointestinal complaints are most often noted (see above). The development of ulceration and/or bleeding requires immediate termination of treatment with diclofenac. Most patients receive an ulcer-protective drug as prophylaxis during long-term treatment (misoprostol, ranitidine 150 mg at bedtime or omeprazole 20 mg at bedtime).

[edit] Hepatic

Liver damage occurs infrequently, and is usually reversible. Hepatitis may occur rarely without any warning symptoms and may be fatal. Patients with osteoarthritis more often develop symptomatic liver disease than patients with rheumatoid arthritis. Liver function should be monitored regularly during long-term treatment. If used for the short-term treatment of pain or fever, diclofenac has not been found to be more hepatotoxic than other NSAIDs. As of 12/2009 Endo, Novartis and FDA notified healthcare professionals to add new warnings and precautions about the potential for elevation in liver function tests during treatment with all products containing diclofenac sodium.[13] Cases of drug-induced hepatotoxicity have been reported in the first month, but can occur at any time during treatment with diclofenac. Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases resulted in fatalities or liver transplantation. Physicians should measure transaminases periodically in patients receiving long-term therapy with diclofenac. Based on clinical trial data and postmarketing experiences, transaminases should be monitored within 4 to 8 weeks after initiating treatment with diclofenac.

[edit] Renal

Studies in Pakistan showed that diclofenac caused acute kidney failure in vultures when they ate the carcasses of animals that had recently been treated with it (see below at ecological problems). Species and individual humans that are drug sensitive are initially assumed to lack genes expressing specific drug detoxification enzymes. NSAIDs "are associated with adverse renal [kidney] effects caused by the reduction in synthesis of renal prostaglandins"[14] in sensitive persons or animal species, and potentially during long-term use in non-sensitive persons if resistance to side-effects decreases with age. However, this side-effect cannot be avoided merely by using a COX-2 selective inhibitor because, "Both isoforms of COX, COX-1 and COX-2, are expressed in the kidney... Consequently, the same precautions regarding renal risk that are followed for nonselective

NSAIDs should be used when selective COX-2 inhibitors are administered."[14] However, diclofenac appears to have a different mechanism of renal toxicity.[7] [edit] Mental Health

Mental Health side effects have been reported, these symptoms are rare but exist in significant enough numbers to be included as potential side effects.

These effects include: depression, anxiety, irritability, nightmares, and psychotic reactions. http://www.drugs.com/sfx/diclofenac-side-effects.html [edit] Other

Bone marrow depression is noted infrequently (leukopenia, agranulocytosis, thrombopenia with/without purpura, aplastic anemia). These conditions may be life-threatening and/or irreversible, if detected too late. All patients should be monitored closely. Diclofenac is a weak and reversible inhibitor of thrombocytic aggregation needed for normal coagulation. Induces warm antibody hemolytic anemia by inducing antibodies to Rh antigens, ibuprofen also does this.[15] Diclofenac may disrupt the normal menstrual cycle.

[edit] Mechanism of action The exact mechanism of action is not entirely known, but it is thought that the primary mechanism responsible for its anti-inflammatory, antipyretic, and analgesic action is inhibition of prostaglandin synthesis by inhibition of cyclooxygenase (COX). It also appears to exhibit bacteriostatic activity by inhibiting bacterial DNA synthesis.[16] Inhibition of COX also decreases prostaglandins in the epithelium of the stomach, making it more sensitive to corrosion by gastric acid.[citation needed] This is also the main side-effect of diclofenac. Diclofenac has a low to moderate preference to block the COX2-isoenzyme (approximately 10-fold) and is said to have, therefore, a somewhat lower incidence of gastrointestinal complaints than noted with indomethacin and aspirin.[citation needed] The action of one single dose is much longer (6 to 8 hours) than the very short half-life that the drug indicates.[citation needed] This could be partly because it persists for over 11 hours in synovial fluids.[17] Diclofenac may also be a unique member of the NSAIDs. There is some evidence that diclofenac inhibits the lipoxygenase pathways,[citation needed] thus reducing formation of the leukotrienes (also proinflammatory autacoids). There is also speculation[by whom?] that diclofenac may inhibit phospholipase A2 as part of its mechanism of action. These additional actions may explain the high potency of diclofenac it is the most potent NSAID on a broad basis.{Scholer. Pharmacology of Diclofenac Sodium. Am J of Medicine Volume 80 April 28, 1986} There are marked differences among NSAIDs in their selective inhibition of the two subtypes of cyclo-oxygenase, COX-1 and COX-2.[citation needed] Much pharmaceutical drug design has attempted to focus on selective COX-2 inhibition as a way to minimize the gastrointestinal side-effects of NSAIDs like aspirin. In practice, use of some COX-2 inhibitors with their adverse effects has led to massive numbers of patient family lawsuits alleging wrongful death by heart attack, yet other significantly COX-selective NSAIDs such as diclofenac have been well-tolerated by most of the population.[citation
needed]

Besides the well-known and often-cited COX-inhibition, a number of other molecular targets of diclofenac that could contribute to its pain-relieving actions have recently been identified. These include:

Blockage of voltage-dependent sodium channels (after activation of the channel, diclofenac inhibits its reactivation also known as phase inhibition)[citation needed] Blockage of acid-sensing ion channels (ASICs)[citation needed] Positive allosteric modulation of KCNQ- and BK-potassium channels (diclofenac opens these channels, leading to hyperpolarization of the cell membrane)[citation needed]

[edit] History Diclofenac originated from Ciba-Geigy (now Novartis) in 1973.[18] Diclofenac was first introduced in the UK in 1979.[19][20] Recent research (2010) has linked use of Diclofenac to an increased chance of strokes.[21] [edit] Ecological effects Use of diclofenac in animals has been reported to have led to a sharp decline in the vulture population in the Indian subcontinent, 95% decline in 2003,[22] 99.9% decline as of 2008. The mechanism is, it is presumed, renal failure, a known side-effect of diclofenac. Vultures eat the carcasses of livestock that have been administered veterinary diclofenac, and are poisoned by the accumulated chemical.[23] At a meeting of the National Wildlife Board in March 2005, the Government of India announced that it intended to phase out the veterinary use of diclofenac.[24] Meloxicam is a safer candidate to replace use of diclofenac.[25] It is more expensive than diclofenac, but the price is coming down as more drug companies begin to manufacture it.[26] "The loss of tens of millions of vultures over the last decade has had major ecological consequences across the Indian subcontinent that pose a potential threat to human health. In many places, populations of feral dogs (Canis familiaris) have increased sharply from the disappearance of Gyps vultures as the main scavenger of wild and domestic ungulate carcasses. Associated with the rise in dog numbers is an increased risk of rabies"[25] and casualties of almost 50,000 people.[27] The Government of India cites one of those major consequences as a vulture species extinction.[24] A major shift in transfer of corpse pathogens from vultures to feral dogs and rats can lead to a disease pandemic causing millions of deaths in a crowded country like India; whereas vultures' digestive systems safely destroy many species of such pathogens. The resulting multiplication of feral dogs in India and Pakistan has caused a multiplication of leopards feeding on those dogs and invading urban areas looking for dogs to prey on, resulting in occasional attacks on human children.[28] The loss of vultures has had a social impact on the Indian Zoroastrian Parsi community, who traditionally use vultures to dispose of human corpses in Towers of Silence, but are now compelled to seek alternative methods of disposal.[25] Diclofenac has been shown also to harm freshwater fish species such as rainbow trout.[29][30][31][32] [edit] Formulations

Pennsaid is a minimally systemic prescription topical lotion formulation of 1.5% w/w diclofenac sodium, which is approved in the US, Canada and other countries for osteoarthritis of the knee. Flector Patch is a minimally systemic topical patch formulation of diclofenac. It is indicated for acute pain due to minor sprains, strains, and contusions. The patch has been approved in many other countries outside the U.S.A under different brand names. Voltaren and Voltarol contain the sodium salt of diclofenac. In the United Kingdom Voltarol can be supplied with either the sodium salt or the potassium salt, while Cataflam in some other countries is the potassium salt only. Diclofenac is available in stomach acid resistant formulations (25 and 50 mg), fast-disintegrating oral formulations (25 and 50 mg), powder for oral solution (50 mg), slow- and controlled-release forms (75, 100 or 150 mg), suppositories (50 and 100 mg), and injectable forms (50 and 75 mg). Diclofenac is also available over-the-counter (OTC) in some countries: 12.5 mg diclofenac as potassium salt in Switzerland ("Voltaren dolo"), The Netherlands ("Voltaren K"), United Kingdom (since October 2008 as "Voltarol Pain-eze"), and preparations containing 25 mg diclofenac as the potassium salt in Germany (various trade names), New Zealand, Australia, Japan, ("Voltaren Rapid"), and Sweden ("Voltaren T" and "Diclofenac T"). Diclofenac as potassium salt can be found throughout the Middle East in 25 mg and 50 mg doses ("Cataflam"). Solaraze (3% diclofenac sodium gel) is topically applied, twice a day for three months, to manage the skin condition known as actinic or solar keratosis. Parazone-DP is combination of Diclofenac potassium and Paracetamol, Mfg. and supplied by Ozone pharmaceuticals and chemicals, Gujarat,India