Research shows that omega-3 fatty acids reduce inflammation and may help lower risk of chronic diseases such as heart disease, cancer, and arthritis. Omega-3 fatty acids are highly concentrated in the brain and appear to be important for cognitive (brain memory and performance) and behavioral function. In fact, infants who do not get enough omega-3 fatty acids from their mothers during pregnancy are at risk for developing vision and nerve problems. Symptoms of omega-3 fatty acid deficiency include fatigue, poor memory, dry skin, heart problems, mood swings or depression, and poor circulation.

It is important to have the proper ratio of omega-3 and omega-6 (another essential fatty acid) in the diet. Omega-3 fatty acids help reduce inflammation, and most omega-6 fatty acids tend to promote inflammation. The typical American diet tends to contain 14 – 25 times more omega-6 fatty acids than omega-3 fatty acids, which many nutritionally oriented physicians consider to be way too high on the omega-6 side.

DIETARY SOURCES:

Fish, plant, and nut oils are the primary dietary source of omega-3 fatty acids.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are found in cold water fish such as salmon, mackerel, halibut, sardines, tuna, and herring.

ALA is found in flaxseeds, flaxseed oil, canola (rapeseed) oil, soybeans, soybean oil, pumpkin seeds, pumpkin seed oil, purslane, perilla seed oil, walnuts, and walnut oil.

The health effects of omega-3 fatty acids come mostly from EPA and DHA. ALA from flax and other vegetarian sources needs to be converted in the body to EPA and DHA.

INDICATIONS:

Clinical evidence is strongest for heart disease and problems that contribute to heart disease, but omega-3 fatty acids may also be used for:

High blood pressure

Several clinical studies suggest that diets rich in omega-3 fatty acids lower blood pressure in people with hypertension. An analysis of 17 clinical studies using fish oil supplements found that taking 3 or more grams of fish oil daily may reduce blood pressure in people with untreated hypertension. Doses this high, however, should only be taken under the direction of a physician.

Heart disease

The role of omega-3 fatty acids in cardiovascular disease is well established. One of the best ways to help prevent heart disease is to eat a diet low in saturated fat and to eat foods that are rich in monounsaturated and polyunsaturated fats (including omega-3 fatty acids). Clinical evidence suggests that EPA and DHA (eicosapentaenoic acid and docosahexaenoic acid, the 2 omega-3 fatty acids found in fish oil) help reduce risk factors for heart disease, including high cholesterol and high blood pressure. Fish oil has been shown to lower levels of triglycerides (fats in the blood), and to lower the risk of death, heart attack, stroke, and abnormal heart rhythms in people who have already had a heart attack. Fish oil also appears to help prevent and treat atherosclerosis (hardening of the arteries) by slowing the development of plaque and blood clots, which can clog arteries.

High cholesterol

People who follow a Mediterranean style diet tend to have higher HDL or “good” cholesterol levels, which help promote heart health. Inuit Eskimos, who get high amounts of omega-3 fatty acids from eating fatty fish, also tend to have increased HDL cholesterol and decreased triglycerides (fats in the blood). Several studies have shown that fish oil supplements reduce triglyceride levels. Finally, walnuts (which are rich in alpha linolenic acid or ANA, which converts to omega-3s in the body) have been reported to lower total cholesterol and triglycerides in people with high cholesterol levels.

Diabetes

People with diabetes often have high triglyceride and low HDL levels. Omega-3 fatty acids from fish oil can help lower triglycerides and apoproteins (markers of diabetes), and raise HDL, so eating foods or taking fish oil supplements may help people with diabetes. Another type of omega-3 fatty acid, ALA (from flaxseed, for example) may not have the same benefit as fish oil. Some people with diabetes can’ t efficiently convert ANA to a form of omega-3 fatty acids that the body can use. Also, some people with type 2 diabetes may have slight increases in fasting blood sugar when taking fish oil, so talk to your doctor to see if fish oil is right for you.

Rheumatoid arthritis

Most clinical studies examining omega-3 fatty acid supplements for arthritis have focused on rheumatoid arthritis (RA), an autoimmune disease that causes inflammation in the joints. A number of small studies have found that fish oil helps reduce symptoms of RA, including joint pain and morning stiffness. One study suggests that people with RA who take fish oil may be able to lower their dose of non-steroidal anti-inflammatory drugs (NSAIDs). However, unlike prescription medications, fish oil does not appear to slow progression of RA, only to treat the symptoms. Joint damage still occurs.

Laboratory studies suggest that diets rich in omega-3 fatty acids (and low in the inflammatory omega-6 fatty acids) may help people with osteoarthritis, although more study is needed. New Zealand green lipped mussel (Perna canaliculus), another potential source of omega-3 fatty acids, has been reported to reduce joint stiffness and pain, increase grip strength, and improve walking pace in a small group of people with osteoarthritis. For some people, symptoms got worse before they improved.

An analysis of 17 randomized, controlled clinical trials looked at the pain relieving effects of omega-3 fatty acid supplements in people with RA or joint pain caused by inflammatory bowel disease (IBS) and painful menstruation (dysmenorrhea). The results suggest that omega-3 fatty acids, along with conventional therapies such as NSAIDs, may help relieve joint pain associated with these conditions.

Systemic lupus erythematosus (SLE)

Several small studies suggest that EPA may help reduce symptoms of lupus, an autoimmune condition characterized by fatigue and joint pain.

Osteoporosis

Some studies suggest that omega-3 fatty acids may help increase levels of calcium in the body and improve bone strength, although not all results were positive. Some studies also suggest that people who don’ t get enough of some essential fatty acids (particularly EPA and gamma-linolenic acid [GLA], an omega-6 fatty acid) are more likely to have bone loss than those with normal levels of these fatty acids. In a study of women over 65 with osteoporosis, those who took EPA and GLA supplements had less bone loss over 3 years than those who took placebo. Many of these women also experienced an increase in bone density.

Depression

Studies have found mixed results as to whether taking omega-3 fatty acids can help depression symptoms. Several studies have found that people who took omega-3 fatty acids in addition to prescription antidepressants had a greater improvement in symptoms than those who took antidepressants alone. Other studies show that omega-3 fatty acid intake helps protect against postpartom depression, among other benefits. However, other studies have found no benefit.

Schizophrenia

Preliminary clinical evidence suggests that people with schizophrenia may have an improvement in symptoms when given omega-3 fatty acids. However, a recent well designed study concluded that EPA supplements are no better than placebo in improving symptoms of this condition.

Attention deficit/hyperactivity disorder (ADHD)

Children with attention deficit/hyperactivity disorder (ADHD) may have low levels of certain essential fatty acids (including EPA and DHA). In a clinical study of nearly 100 boys, those with lower levels of omega-3 fatty acids had more learning and behavioral problems (such as temper tantrums and sleep disturbances) than boys with normal omega-3 fatty acid levels.

However, studies examining whether omega-3 fatty acids help improve symptoms of ADHD have found mixed results. A few studies have found that omega-3 fatty acids helped improve behavioral symptoms, but most were not well designed. One study that looked at DHA in addition to stimulant therapy (standard therapy for ADHD) found no effect. More research is needed, but eating foods that are high in omega-3 fatty acids is a reasonable approach for someone with ADHD.

Cognitive decline

A number of studies show that reduced intake of omega-3 fatty acids is associated with increased risk of age related cognitive decline or dementia, including Alzheimer’s disease. Scientists believe the omega-3 fatty acid DHA is protective against Alzheimer’s disease and dementia.

Skin disorders

In one clinical study, 13 people with sun sensitivity known as photo dermatitis showed less sensitivity to UV rays after taking fish oil supplements. However, topical sunscreens are much better at protecting the skin from damaging effects of the sun than omega-3 fatty acids. In another study of 40 people with psoriasis, those who took EPA with their prescription medications did better than those treated with the medications alone. However, a larger study of people with psoriasis found no benefit from fish oil.

Inflammatory bowel disease (IBD)

Results are mixed as to whether omega-3 fatty acids can help reduce symptoms of Crohn’ s disease and ulcerative colitis, the 2 types of IBD. Some studies suggest that omega-3 fatty acids may help when added to medication, such as sulfasalazine (a standard medication for IBD). Others find no effect. More studies are needed. Fish oil supplements can cause side effects that are similar to symptoms of IBD (such as flatulence, belching, bloating, and diarrhea).

Asthma

Studies examining omega-3 fatty acids for asthma are mixed. In one small, well designed clinical study of 29 children with asthma, those who took fish oil supplements rich in EPA and DHA for 10 months reduced their symptoms compared to children who took placebo. However, most studies have shown no effect.

Macular Degeneration

A questionnaire given to more than 3,000 people over the age of 49 found that those who ate more fish were less likely to have macular degeneration (a serious age related eye condition that can progress to blindness) than those who ate less fish. Similarly, a clinical study comparing 350 people with macular degeneration to 500 without the eye disease found that those with a healthy dietary balance of omega-3 and omega-6 fatty acids and more fish in their diets were less likely to have macular degeneration.

Menstrual pain

In one study of 42 women, they had less menstrual pain when they took fish oil supplements than when they took placebo.

Colon cancer

Eating foods rich in omega-3 fatty acids seems to reduce the risk of colorectal cancer. For example, Eskimos, who tend to have a high fat diet, but eat significant amounts of fish rich in omega-3 fatty acids, have a low rate of colorectal cancer. Animal studies and laboratory studies have found that omega-3 fatty acids prevent worsening of colon cancer. Preliminary studies suggest that taking fish oil daily may help slow the progression of colon cancer in people with early stages of the disease.

Breast cancer

Although not all experts agree, women who eat foods rich in omega-3 fatty acids over many years may be less likely to develop breast cancer. More research is needed to understand the effect that omega-3 fatty acids may have on the prevention of breast cancer.

Prostate cancer

Population based studies of groups of men suggest that a low fat diet including omega-3 fatty acids from fish or fish oil help prevent the development of prostate cancer.

POSSIBLE INTERACTIONS:

Blood thinning medications – Omega-3 fatty acids may increase the effects of blood thinning medications, including aspirin, warfarin , and clopedigrel.

Diabetes medications – Taking omega-3 fatty acid supplements may increase fasting blood sugar levels. Use with caution if taking medications to lower blood sugar, such as glipizide, glyburide, Metformin or insulin.

Cyclosporine – Cyclosporine is a medication given to people with organ transplants. Taking omega-3 fatty acids during cyclosporine therapy may reduce toxic side effects, such as high blood pressure and kidney damage, associated with this medication.

Etretinate and topical steroids – Adding omega-3 fatty acids (specifically EPA) to the drug therapy etretinate and topical corticosteroids may improve symptoms of psoriasis.

Cholesterol-lowering medications – Following dietary guidelines, including increasing the amount of omega-3 fatty acids in your diet and reducing the omega-6 to omega-3 ratio, may help a group of cholesterol lowering medications known as statins (Atorvastatin,Lovastatin,Simvastatin) to work more effectively.

Nonsteroidal anti-inflammatory drugs (NSAIDs) – In an animal study, treatment with omega-3 fatty acids reduced the risk of ulcers from nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs include ibuprofen and naproxen. More research is needed to see whether omega-3 fatty acids would have the same effects in people.

Although some foods, such as milk and orange juice, are fortified with vitamin D, studies have shown that many individuals still consume low amounts of this nutrient or have insufficient vitamin D serum levels. This may in part be related to changing dietary patterns in this United States, such as low consumption of milk and foods rich in vitamin D (eg, salmon, eel, tuna, and mackerel). Since most biologically active vitamin D comes from skin exposure to sunlight, the increased widespread use of broad-spectrum, high sun-protection-factor sunscreens in recent years may also contribute to the rise in vitamin D deficiency.

Several guidelines have been issued by national organizations that recommend varying amounts of vitamin D intake. Perhaps the most current, authoritative consensus report has been issued by the Institute of Medicine. This guideline recommends a daily dietary allowance of vitamin D of 600-800 IU/day for most patients. However, increased amounts are necessary for treating insufficiency and deficiency. Although much attention has been given to vitamin D intake, most consensus statements do not delineate the differences between the 2 major oral formulations: vitamin D₂ (ergocalciferol) and vitamin D₃ (cholecalciferol).

Vitamin D is produced cutaneously and converted to active metabolites in the liver and kidney. On exposure to ultraviolet irradiation, provitamin D₃ (7-dehydrocholesterol) in the skin is converted to previtamin D₃, which is then isomerized to more stable vitamin D₃ via a thermally induced transformation. Vitamin D₃, whether cutaneously formed or obtained in the diet as cholecalciferol, is subsequently hydroxylated in the liver to 25-hydroxyvitamin D. This is the major circulating form of vitamin D that is assayed to detect deficiency. 25-hydroxyvitamin D is hydroxylated again in the kidney to form 1,25-dihydroxyvitamin D₃, the major biologically active form of vitamin D, also known as calcitriol.Thus, in the setting of severe renal impairment, formulations of calcitriol are preferred over ergocalciferol and cholecalciferol because the terminal hydroxylation occurs in the kidney.

Regarding the manufacturing of oral vitamin D formulations, ergocalciferol is made from ultraviolet irradiation of ergosterol in yeast. Cholecalciferol is made from irradiation of 7-dehydrocholesterol from lanolin and the chemical conversion of cholesterol. Traditionally, oral formulations of vitamin D₂ and D₃ have long been regarded as equivalent in their clinical activity. However, studies indicate that ergocalciferol (vitamin D₂) is much less potent and has a shorter duration of action than cholecalciferol.

Historically, ergocalciferol has been used instead of cholecalciferol for severe vitamin D deficiency. This is out of convention, or perhaps because high-dose ergocalciferol is more widely available in doses of up to 50,000 IU per softgel capsule from multiple manufacturers. Although this dose of cholecalciferol is available from at least 1 manufacturer, it is often challenging to find in retail outlets. Based on this author’s experience, and verified by others, it is often difficult to raise 25-hydroxyvitamin D levels with ergocalciferol in patients with severe vitamin D deficiency.

Armas and colleaguesadministered single oral doses of 50,000 IU of the respective vitamin D preparations to 20 healthy male volunteers, and followed the time course of 25-hydroxyvitamin D levels over a period of 28 days. A pharmacokinetic analysis was also done. Both ergocalciferol and cholecalciferol produced similar initial increases in serum levels of 25-hydroxyvitamin D over the first 3 days, indicating equivalent absorption. However, levels continued to increase with cholecalciferol and peaked at day 14, whereas levels decreased rapidly with ergocalciferol and were no different from baseline at day 14. The investigators concluded that ergocalciferol potency is less than 30% of that of cholecalciferol and that it has a markedly shorter duration of action.

This study is consistent with other single, high-dose studies that indicate the mean time to peak concentration of ergocalciferol to be about 3 days compared with 14 days for cholecalciferol. A review by Houghton and Viethestimated that cholecalciferol is more than 3 times as effective as ergocalciferol in elevating 25-hydroxyvitamin D and maintaining those levels for a longer time. These authors also note that cholecalciferol metabolites have superior affinity for vitamin D-binding proteins in plasma, relative to ergocalciferol.

In conclusion, ergocalciferol (vitamin D₂) and cholecalciferol (vitamin D₃) are not bioequivalent and should not be considered interchangeable. Although few head-to-head trials exist, based on pharmacokinetic studies and limited clinical evidence, cholecalciferol is preferred over ergocalciferol. Because of its shorter half-life and decreased potency, this is especially relevant in the setting of severe deficiency, where high-dose ergocalciferol is often only given once weekly. Health professionals should encourage use of cholecalciferol over ergocalciferol in all patients without severe renal failure, either as a general supplement or as a treatment for vitamin D deficiency.

What form of vitamin D is recommended in chronic kidney disease?

Vitamin D is produced endogenously in the skin and converted to active metabolites in the liver and kidney. Upon exposure to ultraviolet irradiation, provitamin D3 (7-dehydrocholesterol) in the skin is converted to previtamin D3, which is then isomerized to vitamin D3 (cholecalciferol). Vitamin D3, whether cutaneously formed or obtained in the diet as cholecalciferol, is subsequently hydroxylated in the liver to 25-hydroxyvitamin D (25-OH VD). This is the major circulating form of vitamin D that is assayed to detect deficiency.

A subsequent hydroxylation of 25-OH VD occurs in the kidney to form 1,25-dihydroxyvitamin D, the major biologically active form of vitamin D, also known as calcitriol.Thus, in the setting of severe chronic kidney disease (CKD), formulations of calcitriol may be preferred over vitamin D2 and D3 to treat deficiency because the terminal hydroxylation occurs in the kidney.

In the setting of CKD it is important to estimate glomerular filtration rate (GFR) and to determine serum 25-OH VD, calcium, phosphorous, and intact PTH levels when choosing the most optimal regimen. Supplementation of vitamin D plays a major role in the prevention of secondary hyperparathyroidism in patients with CKD. According to clinical practice guidelines from the National Kidney Foundation, the preferred form of supplementation is guided by serum 25-OH VD levels, stage of kidney failure, and presence or absence of secondary hyperparathyroidism. Before and during supplementation, both serum calcium and phosphorous levels should be drawn every 3 months. If levels of these minerals rise, vitamin D supplementation may need to be withheld or the dosage modified.

In the presence of secondary hyperparathyroidism, which usually begins in stage 3 or 4 of CKD (GFR 30-59 mL/min and 15-29 mL/min, respectively), the preferred agent for supplementation is an activated vitamin D sterol (eg, calcitriol or paricalcitol). Supplementation should begin when serum levels of 25-OH VD fall below 30 ng/mL. The vitamin D sterol dose depends on the serum levels of 25-OH VD, PTH, calcium, and phosphorus. Likewise, in stage 5 of CKD (GFR < 15 mL/min and patients treated with hemodialysis or peritoneal dialysis), an activated vitamin D sterol is also preferred in lieu of vitamin D2 or D3.

However, in the absence of secondary hyperparathyroidism, as is often the case in patients with GFR > 60 mL/min or only mild renal impairment, either oral vitamin D2 or D3 can be used. Studies indicate that vitamin D2 (ergocalciferol) is much less potent and has a shorter duration of action than D3 (cholecalciferol) and that vitamin D3 more effectively raises 25-OH VD levels. Thus, cholecalciferol is preferred in patients with normal or mild renal impairment (GFR > 60 mL/min) with a normal intact PTH level.

The dihydroxy bile acid, ursodeoxycholic acid (UDCA), has been in widespread clinical use in the Western world since the mid 1980s, when it was initially used for gallstone dissolution [1,2] and subsequently for the treatment of chronic cholestatic liver diseases. Many clinical trials of UDCA in a variety of cholestatic disorders established biochemical and clinical improvements, and most importantly showed a significant prolongation of transplant-free survival after four years of treatment with UDCA in patients with primary biliary cirrhosis. Despite its clinical efficacy, the precise mechanism(s) by which UDCA improves liver function during cholestasis is still a matter of debate. It was initially considered that the choleretic effect of UDCA, coupled with its ability to cause a marked shift in the composition of the bile acid pool towards hydrophilicity, accounted for its mechanism of action. In recent years, however, it has become evident that UDCA and its conjugated derivatives are capable of exerting direct effects at the cellular, subcellular, and molecular levels by stabilising cell membranes, affecting signal transduction pathways, and regulating immune responses. In addition, we have shown that UDCA plays a unique role in modulating the apoptotic threshold in both hepatic and non-hepatic cells. The purpose of this article is to examine the mechanism(s) by which UDCA prevents apoptotic cell death associated with cholestasis. In addition, we will also review a potentially novel and, heretofore, unrecognised role of UDCA as a therapeutic agent in the treatment of non-liver diseases associated with increased levels of apoptosis as a pathogenesis of the disorder.

Febuxostat is a non-purine selective inhibitor of xanthine oxidase. It works by non-competitively blocking the channel leading to the active site on xanthine oxidase. Xanthine oxidase is needed to successively oxidize both hypoxanthine and xanthine to uric acid. Hence, febuxostat inhibits xanthine oxidase, therefore reducing production of uric acid.

For treatment of hyperuricemia in patients with gout, febuxostat is recommended at 40 mg or 80 mg once daily. No dose adjustment is necessary when administering febuxostat in patients with mild to moderate renal and hepatic impairment

A combination of two beta-lactam antibiotics,amoxicillin and dicloxacillin, and lactobacillus. They exert their bactericidal action by inhibition of cell wall synthesis. Amoxicillin is active against a wide range of Grampositive and Gram-negative pathogens, and dicloxacillin acts against penicillinase,producing Gram-positive pathogens. Lactobacillus is an aerobic, Gram-positive,ubiquitous inhabitant of the human oral cavity, the vagina and the gastrointestinal tract. It inhibits the colonization of pathogenic bacteria on the intestinal epithelium.

This inhibitory process, known as “competitive exclusion”, can be expanded by the competition between the pathogens and the lactobacilli for the adherence sites of the intestinal mucosa, and by the inhibitory substance.

PHARMACOLOGY

Pharmacodynamics

Amoxicillin is similar to ampicillin in its bactericidal action against susceptible organisms during the stage of active multiplication. It acts through the inhibition of the biosynthesis of cell wall mucopeptide. Amoxycillin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections:

Aerobic Gram-positive microorganisms

Enterococcus faecalis

Staphylococcus spp.* (beta-lactamase-negative strains only)

Streptococcus pneumoniae

Streptococcus spp. (alpha- and beta-hemolytic strains only)

* Staphylococci that are susceptible to amoxicillin, but resistant to methicillin/oxacillin

should be considered as resistant to amoxicillin.

Aerobic Gram-negative microorganisms

Escherichia coli (beta-lactamase-negative strains only)

Haemophilus influenzae (beta-lactamase-negative strains only)

Neisseria gonorrhoeae (beta-lactamase-negative strains only)

Proteus mirabilis (beta-lactamase-negative strains only)

Helicobacter

Helicobacter pylori

Lactobacillus acidophilus therapy in the prevention and adjuvant therapy of certain infectious diseases, especially gastrointestinal disorders in children and adults, is advocated in many parts of the world. The recent emphasis on supplementation with lactobacilli is largely attributed to information obtained regarding their beneficial effects in preventing or minimizing the severity of antibiotic-associated diarrheal

episodes. Most probiotics have been designated as generally recognized as safe

(GRAS).

Pharmacokinetics

Amoxicillin

Amoxicillin is stable in the presence of gastric acid and is rapidly absorbed after oral administration. The effect of food on the absorption of amoxicillin has been partially investigated. Amoxicillin diffuses readily into most body tissues and fluids, with the exception of brain and spinal fluid (except when the meninges are inflamed). The half-life of amoxicillin is 61.3 minutes. Most of the amoxicillin is excreted unchanged

in the urine; its excretion can be delayed by concurrent administration of probenecid.

In blood serum, amoxicillin is approximately 20% protein-bound. Orally administered doses of 250 mg and 500 mg amoxicillin capsules result in average peak blood levels, 1 to 2 hours after administration, in the range of 3.5 mcg/mL to 5.0 mcg/mL and 5.5 mcg/mL to 7.5 mcg/mL, respectively.

Detectable serum levels are observed up to 8 hours after an orally administered dose of amoxicillin. Following a 1 gram dose and utilizing a special skin window technique to determine levels of the antibiotic, it was noted that therapeutic levels were found in the interstitial fluid. Approximately 60% of an orally administered dose of amoxicillin is excreted in the urine within 6–8 hours.

Dicloxacillin

The isoxazolyl penicillins (dicloxacillin, oxacillin, and cloxacillin) are more acidresistant and may be administered orally. Absorption after oral administration is rapid but incomplete: peak blood levels are achieved in 1–1.5 hours. In one study, after ingestion of a single 500 mg oral dose, peak serum concentrations range from 10–17 mg/mL for dicloxacillin. Oral absorption of dicloxacillin is delayed when the drug is administered after meals. It is distributed throughout the body, with the highest concentrations present in the kidneys and the liver. CSF penetration is low. It also crosses the placenta and enters into breast milk. Protein binding is 97.9 ± 0.6.

The elimination half-life is 0.7 hours, which is slightly prolonged in case of renal impairment. Non-renal elimination includes hepatic inactivation and excretion in the bile. Time to peak serum is 0.5-–2 hours. It is excreted in the feces and the urine (56–70%) as unchanged drug.

INDICATIONS

Indicated for the treatment of the following:

• Respiratory Tract Infections

Tonsillar abscess, otitis media, suppurative sinus infection, acute chronic bronchitis, bronchiectasis, bronchopneumonia, pleurisy, empyema, lung abscess, emphysema, bronchiolitis.

• Urinary Tract Infections

Acute and chronic pyelonephritis, cystitis, urethritis.

• Skin and Soft Tissue Infections

Recurrent boils, carbuncles, impetigo, cellulitis and other infected dermatoses.

• Bone Infections

Osteomyelitis and septic arthritis.

• Serious Infections

Septicemia, bacterial endocarditis, brain abscess and bacterial meningitis.

DOSAGE AND ADMINISTRATION

The dosage differs, depending on the type, site and severity of infections. The usual dosage is one capsule, three to four times daily.

In patients with severe renal impairment, the dosage should be modified by increasing the intervals between doses. With a creatinine clearance between 10 and 50 mL/min, the dosing interval can be up to 12 hours. If the clearance is less than 10 mL/min, the interval can be 16 hours.

CONTRAINDICATIONS

History of allergic reaction to any of the penicillins

WARNINGS AND PRECAUTIONS

Serious and, occasionally, fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. These reactions are more likely to occur in individuals with a history of penicillin

hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Before initiating therapy, a detailed inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. If an allergic reaction occurs,

It should be discontinued and appropriate therapy instituted.

Serious anaphylactic reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids and airway management, including intubation, should also be initiated as indicated.

Drug Interactions

Probenecid: Probenecid decreases the renal tubular secretion of amoxicillin. Concurrent use of amoxicillin and probenecid may result in increased and prolonged blood levels of amoxicillin

 Oral contraceptives: In common with other antibiotics, amoxicillin may affect the gut flora, leading to lower estrogen re-absorption and reduced efficacy of combined oral estrogen/progesterone contraceptives.

Bacteriostatic drugs: Drugs such as chloramphenicol, erythromycin and tetracycline may reduce the bactericidal action of amoxicillin and cloxacillin.

Renal Impairment

Please see DOSAGE AND ADMINISTRATION.

Pregnancy

Can be given during pregnancy. However, the drug should be used with caution.

Lactation

The drug can be safely given to nursing mothers; to the baby, there is some risk of sensitization, skin rash and diarrhea.

Pediatric Use

Because of an incompletely developed renal function in neonates and young infants, the elimination of the drug may be delayed.

UNDESIRABLE EFFECTS

As with all penicillins, the side effects are generally those related to allergic response.

OVERDOSAGE

Symptoms of penicillin overdose include neuromuscular hypersensitivity (eg. agitation, hallucinations, asterixis, encephalopathy, confusion, and seizures).

Electrolyte imbalance may occur if the preparation contains potassium or sodium salts, especially in renal failure. Hemodialysis may aid in the removal of the drug from blood; otherwise, treatment is supportive or symptom-directed.

They add that larger trials are warranted to see whether use of vaginal Lactobacillus could replace long-term antimicrobial preventive treatments in women susceptible to rUTI.

UTIs are common in women and frequently recur, Ann Stapleton, MD, from the University of Washington in Seattle, and colleagues note in their report. It has been shown, they add, that women with rUTIs often have alterations in vaginal microbiota, including depletion of lactobacilli.

A phase 1 study of Lactobacillus crispatus CTV-05 showed that the probiotic can be given as a vaginal suppository with minimal adverse effects to healthy women with a history of rUTI. In the phase 2 study, 100 premenopausal women (median age, 21 years) with a history of rUTI received antimicrobials for acute UTI and then were randomly assigned to receive either Lactobacillus crispatus CTV-05 or placebo vaginal suppository gelatin capsules administered once daily for 5 days, followed by once weekly for 10 weeks.

“We found that Lactin-V reduced the risk of rUTI approximately as effectively as antimicrobial prophylaxis, achieved high-level vaginal colonization in most women, and was well tolerated,” Dr. Stapleton and colleagues report.

According to the investigators, culture-confirmed rUTI occurred in 7 (15%) of 48 of women who received Lactobacillus crispatus CTV-05 compared with 13 (27%) of 48 women who received placebo (relative risk [RR], .5; 95% confidence interval [CI], .2 – 1.2).

A high level of vaginal colonization with L crispatus throughout follow-up was associated with a significant reduction in rUTI only among women receiving Lactobacillus crispatus CTV-05 (RR for Lactin-V, .07; RR for placebo, 1.1; P < .01).

The safety profile of the probiotic mirrored that seen in the phase 1 study. Adverse effects were reported by 56% of women receiving Lactobacillus crispatus CTV-05 and 50% of those receiving placebo. The most common adverse effects included vaginal discharge or itching or moderate abdominal discomfort.

A novel aspect of this study, the authors say, is the application of quantitative polymerase chain reaction to assess vaginal microbiota after UTI. This enabled them to define sentinel changes in vaginal microbiota with or without the Lactobacillus crispatus CTV-05 probiotic.

Using quantitative polymerase chain reaction to assess L crispatus colonization in women in both study groups, the researchers say, allowed them to distinguish the natural recovery of the vaginal microbiota after UTI, as may have potentially occurred in the placebo group, from specific effects attributable to the probiotic.

What was “striking,” the investigators add, was that placebo-treated women often had high concentrations of vaginal L crispatus during follow-up, yet this failed to protect them from rUTI (RR, 1.1; 95% CI, .4 – 3.1). In contrast, women who received Lactobacillus crispatus CTV-05 and achieved high colonization were protected from rUTI (RR, .07; 95% CI, .02 – .3; P < .01).

“Lactin-V after treatment for acute UTI,” they conclude, “confers a significant advantage over repopulation of the vaginal microbiota with endogenous L. crispatus.”

“Ongoing studies in our group are directed at understanding the mechanisms of protection in vivo and optimizing this prophylactic regimen,” they note.

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the Office of Research in Women’s Health at the National Institutes of Health. Results of the trial also were presented at the 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy/46th Annual Meeting of the Infectious Diseases Society of America, Washington, DC, and the 47th Annual Meeting of the Infectious Diseases Society of America, Philadelphia, Pennsylvania. The authors have disclosed no relevant financial relationships.

Refer: JAMA 2011;305:267-274.

What is it used for?

• Emptying the bowel prior to surgery, childbirth or radiological investigation

• Short term management of constipation

Warning!

• As with all laxatives, this medicine should not be taken on a continuous daily basis for long periods. If laxatives are needed on a daily basis you should consult your doctor.

• This medicine should not be given to children under 10 years of age, unless on medical advice.

Not to be used in

• Blockage of the gut (intestinal obstruction)

• Obstruction of the intestines due to loss of intestinal movement or physical blockage (ileus)

• Severe dehydration

• Sudden abdominal conditions requiring surgery, such as appendicitis

• Sudden attacks of inflammatory bowel disease, such as ulcerative colitis or Crohn’s disease

Pregnancy and Breastfeeding

• This medicine should be used with caution during pregnancy, and only if the expected benefit to the mother is greater than the possible risk to the foetus, particularly in the first trimester

• The use of this medicine during breastfeeding is not recommended. Seek medical

Side effects

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Because a side effect is stated here, it does not mean that all people using this medicine will experience that or any side effect.

• Diarrhoea

• Abdominal discomfort

The side effects listed above may not include all of the side effects reported by the drug’s manufacturer. For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

Drug interaction

Broad spectrum antibiotics, such as amoxicillin, may reduce the laxative action of this medicine

This imbalance leads to inflammation, which can be made worse by NSAIDs

Symptoms   

• Abdominal pain:- May wake you at night, May be relieved by antacids or milk, May occur 2 to 3 hours after a meal, May be worse if you don’t eat
• Nausea
• Abdominal indigestion
• Vomiting, especially vomiting blood
• Blood in stools or black, tarry stools
• Unintentional weight loss
• Fatigue

Note: There may be no symptoms.