Drug Toxicity Drug Toxicity / Drug Monitoring/ Drug Therapeutic Levels

Therapeutic benefits of a drug on the market far outweighs it risks. All drugs are likely to have some side effects. Therapeutic monitoring of drugs is now readily available to make some of the drugs even safer. The current medindia utility has a list of 88 drugs with complete information in the following areas: Normal levels and critical levels where the drug is likely to be toxic. Physiological action and toxicity of the drug. Interpretation of drug levels. Laboratory test methods for monitoring drug levels. Therapeutic monitoring and management of drug levels. Related drugs and lab test information

http://www.medindia.net/drugs/drug_toxicity/home.asp
Drug toxicity, also called adverse drug reaction(ADR) or adverse drug event (ADE), is defined as the "manifestations of the adverse effects of drugsadministered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning..." The meaning of this expression differs from the meaning of "side effect", as this last expression might also imply that the effects can be beneficial. The World Health Organization defines it as: An adverse drug reaction (ADR) is a response to a medicine which is noxious and unintended, and which occurs at doses normally used in man. In this description it is of importance that it concerns the response of a patient, in which individual factors may play an important role, and that the phenomenon is noxious (an unexpected therapeutic response, for example, may be a side effect but not an adverse reaction). 6% of hospital admissions and 2.5% of emergency department visits for injuries or poisoningsmay be due to adverse drug reactions. Adverse drug reactions also occur among ambulatory outpatients and among inpatients. A minority of drug toxicity is recognized by health care providers. Classification Cause The World Health Organization (WHO) classifies ADRs by cause: y Type A: Dose-related; pharmacologically predictable. In a study of older adults, this type was the most common with the most common offending drugs being warfarin, insulin, and digoxin. Type B: Non-dose related; bizarre and unpredictable.

o o

Immune related such as hypersensitivity reactions. Non-immune reactions such as porphyria, malignant hyperthermia, neuroleptic malignant syndrome, or malignant hyperthermia. As the mechanisms of these specific reactions are better understood, these reactions may be re-classified as Type A.

Type C: Dose-related and time-related. This is related to duration and dosage of exposure. An example is hypothalamic-pituitary-adrenal suppression from glucocorticoid therapy. Type D: Time-related; delayed reaction. An example is tardive dyskinesia. Type E: Withdrawal; end of dose reaction. An example is narcotic or beta-blocker withdrawal. Type F: Unexpected failure of therapy. This may be caused by drug interactions. An example is failure of oral contraceptives due to induction of enzymes by a second drug.

y y y

Types A and B were proposed in the 1970s, and the other types were proposed subsequently when the first two proved insufficient to classify ADRs. Manifestation Drug-induced liver injury Drug reaction with eosinophilia and systemic symptoms Drug reaction with eosinophilia and systemic symptoms (DRESS) may be caused by medications including allopurinol, phenytoin, dapsone, carbamazepine, trimethoprim-sulfamethoxazole, penicillin, and non-steroidal anti-inflammatory agents.About half of cases have eosinophilia. Drug-drug interactions Some interactions are due to the system of cytochrome P-450 enzymes used to clear drugs from the body. These interactions can be complex, involving either increasing or decreasing the activity of a given cytochrome pathway, or preferentially (i.e., competitive inhibition) using the pathway rather than other drugs. As one example, theophylline and ciprofloxacin up-regulate the cytochrome pathway that also clears estrogen and phenytoin. As a result, oral contraceptives and anticonvulsants may fail because the pathway clears them too quickly and an adequate blood level cannot be maintained. Drug-disease interactions Drug-food interactions Monoamine oxidase inhibitors can cause fatal hypertension in patients who have also consumed food containing high concentrations of tyramine. The suspect foods form an odd assortment, such as Chianti wine, some smoked fish and aged cheese. QT interval prolongation Thombocytopenia Describing ADRs ADRs may be described by their frequency and severity

Frequency The World Health Organization recommends standardization of descriptions of frequency.Although the WHO document is not currenlty available online, their recommendations have been summarized by others. y y y y y very common (>1/10 patients) common (>1/100) uncommon (>1/1000) rare (>1/10,000) very rare (<1/100,000)

Severity The American Food and Drug Administration defines severe effects as: y y y y Death Life-Threatening Hospitalization (initial or prolonged) Disability - significant, persistent, or permanent change, impairment, damage or disruption in the patient's body function/structure, physical activities or quality of life. Congenital Anomaly - or Requires Intervention to Prevent Permanent Impairment or Damage

y y y

Etiology / cause As research better explains the biochemistry of drug use, less ADRs are Type B ('idiosyncratic') and more are Type A (pharmacologically predictable). Common mechanisms are: y Abnormal pharmacokinetics due to o o y genetic factors comorbid disease states

Synergistic effects between either o o a drug and a disease two drugs

Risk factors are:

y y y y y y

The number of drugs History of prior drug toxicity Presence of heart failure Presence of liver disease Presence of renal failure Presence of 4 or more medical conditions

Abnormal pharmacokinetics Comorbid disease states Various diseases, especially those that cause renal or hepatic insufficiency, may alter drug metabolism. Resources are available that report changes in a drug's metabolism due to disease states. However, heavy physician workload may reduce the ability of the physician to use these resources. Genetic factors Abnormal drug metabolism may be due to inherited factors of either Phase I oxidation or Phase II conjugation.Pharmacogenomics is the study on the inherited basis of drug reactions. Among drugs frequently cited in adverse drug reactions, 60% are metabolized by enzymes with genetic variations in metabolism. 7% to 22% of randomly selected have such variation. Phase I reactions Inheriting abnormal alleles of cytochrome P-450 can alter drug metabolism. Tables are available to check for drug interactions due to cytochrome P-450 interactions. Inheriting abnormal butyrylcholinesterase (pseudocholinesterase) may affect metabolism of drugs such as succinylcholine Phase II reactions Inheriting abnormal N-acetyltransferase which conjugated some drugs to facilitate excretion may affect the metabolism of drugs such as isoniazid, hydralazine, and procainamide. Inheriting abnormal thiopurine S-methyltransferase may affect the metabolism of the thiopurine drugs mercaptopurine andazathioprine. Impaired hepatic function Food and Drug Administration provides guidance on the labeling of prescription medications to guide dosing for patients with impaired hepatic function. Impaired renal function The National Kidney Disease Education Program provides guidance on dosing drugs in patients with reduced glomerular filtration rate.Food and Drug Administration provides guidance on the labeling of prescription medications to guide dosing for patients with impaired renal function. Although this

categorization uses estimated creatinine clearance, using estimated glomerular filtration yields similar recommendations for dosing adjustments. Interactions with other drugs Synergistic effects An example of synergism is two drugs that both prolong the cardiac QT interval. Other factors that my increase ADRs Polypharmacy The risk of drug interactions may be increased with polypharmacy. Using 11 or more chronic medications is a risk factor for drug toxicity. Fragmented health care When controlled for other factors such as the number of prescribing physicians, the number of medicatations may not be a risk factor for adverse drug reactions. Assessing causality A scale proposed by the World Health Organization (WHO) is below: Certain y "A clinical event, including a laboratory test abnormality, that occurs in a plausible time relation to drug administration, and which cannot be explained by concurrent disease or other drugs or chemicals" "The response to withdrawal of the drug (dechallenge) should be clinically plausible" "The event must be definitive pharmacologically or phenomenologically, using a satisfactory rechallenge procedure if necessary"

y y

Probable/likely y "A clinical event, including a laboratory test abnormality, with a reasonable time relation to administration of the drug, unlikely to be attributed to concurrent disease or other drugs or chemicals, and which follows a clinically reasonable response on withdrawal (dechallenge)" "Rechallenge information is not required to fulfil this definition"

Possible y "A clinical event, including a laboratory test abnormality, with a reasonable time relation to administration of the drug, but which could also be explained by concurrent disease or other drugs or chemicals" "Information on drug withdrawal may be lacking or unclear"

Unlikely

"A clinical event, including a laboratory test abnormality, with a temporal relation to administration of the drug, which makes a causal relation improbable, and in which other drugs, chemicals, or underlying disease provide plausible explanations"

Conditional/unclassified y "A clinical event, including a laboratory test abnormality, reported as an adverse reaction, about which more data are essential for a proper assessment or the additional data are being examined"

Unassessable/unclassifiable y "A report suggesting an adverse reaction that cannot be judged, because information is insufficient or contradictory and cannot be supplemented or verified"

An alternative scale is the Naranjo algorithm. Intolerance to multiple drugs Amplification may contribute to multiple-drug intolerance (if the adverse effects that are reported are nonspecific). This is distinct from multiple drug hypersensitivity. Detection of toxicity in individual patients The question "In the past XX months, have you noticed any side effects, unwanted reactions, or other problems with medications you have taken?" may help detect toxic reactions. Detection of previously unrecognized toxicity in populations Unfortunately, more drug toxicity is not reported. Reports of more than three cases of a rare disease associated with a drug suggests the drug may be causing the disease. More complicated rules for signals are available. Monitoring bodies Many countries have official bodies that monitor drug safety and reactions. On an international level, the World Health Organization (WHO) runs the Uppsala Monitoring Centre, and the European Union runs the European Medicines Agency(EMEA). In the United States, the Food and Drug Administration (FDA) is responsible for monitoring post-marketing studies. However, the book, Physicians' Desk Reference, which is a collection of FDA approved drug labels, may contribute to adverse drug effects by systematically underreporting the lowest effect dose of drugs. Prevention Criteria have been developed for predictable adverse drug reactions and thus provide a list of medications to avoid. The role of computerized provider order entry (CPOE) has been inconsistent with both positive and negativeeffects on process measures. CPOE has difficulty in precision of alerting.

http://en.citizendium.org/wiki/Drug_toxicity

LAGUNDI Vitex negundo, commonly known as the five-leaved chaste tree, is a large aromatic shrub with quadrangular, densely whitish, tomentose branchlets. It is widely used in folk medicine, particularly in South and Southeast Asia. Vitex negundo is an erect shrub or small tree growing from 2 to 8 m (6.6 to 26 ft) in height. The bark is reddish-brown. It leaves are digitate, with five lanceolate leaflets, sometimes three. Each leaflet is around 4 to 10 cm (1.6 to 3.9 in) in length, with the central leaflet being the largest and possessing a stalk. The leaf edges are toothed or serrated and the bottom surface is covered in hair. The numerous flowers are borne in panicles 10 to 20 cm (3.9 to 7.9 in) in length. Each is around 6 to 7 cm (2.4 to 2.8 in) long and are white to blue in color. The petals are of different lengths, with the middle lower lobe being the longest. Both the corolla and calyx are covered in dense hairs. The fruit is a succulent drupe, 4 mm (0.16 in) in diameter, rounded to egg-shaped. It is black or purple when ripe. Vitex negundo is native to tropical Eastern and Southern Africa and Asia. It is widely cultivated and naturalized elsewhere. Countries it is indigenous to include Afghanistan, Bangladesh, Bhutan, Cambodia, China, India, Indonesia, Japan, Kenya, Madagascar, Malaysia, Mozambique, Myanmar, Nepal, Pakistan, the Philippines, Sri Lanka, Taiwan, Tanzania, Thailand, and Vietnam. Vitex negundo are commonly found near bodies of water, recently disturbed land, grasslands, and mixed open forests. Folk medicine The principal constituents the leaf juice are casticin, isoorientin, chrysophenol D, luteolin, p hydroxybenzoic acid and D-fructose. The main constituents of the oil are sabinene, linalool, terpinen-4-ol, -caryophyllene, -guaiene and globulol constituting 61.8% of the oil.[citation needed] In vitro and animal studies have shown that the plant has potential anti-inflammatory,[8] antibacterial, antifungal and analgesic activities. Vitex negunda is used for treating stored garlic against pests in the Philippines. http://en.wikipedia.org/wiki/Vitex_negundo Botany Lagundi is an erect, branched tree or shrub, 2 to 5 meters high. Leaves are usually 5-foliate, rarely with 3 leaflets only, and palmately arranged. Leaflets are lanceolate, entire, 4 to 10 centimeters long, slightly hairy beneath, and pointed at both ends, the middle leaflets being larger than the others, and distinctly stalked. Flowers are numerous, blue to lavender, 6 to 7 millimeters long, borne in terminal inflorescences (panicles) 10 to 20 centimeters long. Calyx is hairy, and 5-toothed. Corolla is densely hairy in the throat, and the middle lobe of the lower lip is longest. Fruit is a succulent drupe, globose, black when ripe, about 4 millimeters in diameter. Distribution

- Widely distributed in the Philippines. - At low and medium altitudes, in thickets and waste places. - Flowering year round. Best propagated by use of mature, leafless stem cuttings. - Also occurs in tropical East Africa, Madagascar, India to Japan, and southward through Malaya to western Polynesia. Parts utilized - Leaves, bark, roots and seeds. - Leaves may be harvested three months after establishment. Properties Plant is considered antiinflammatory, astringent, antibacterial, antifungal, analgesic, alterant, depurative, rejuvinating, stomachic. Roots considered tonic, febrifuge, antirheumatic, diuretic and expectorant. Leaves and seeds considered vulnerary. Leaves are considered aromatic, bitter, anti-inflammatory, bronchial smooth muscle relaxant, lactagogue, emmenagogue, insecticide, and vermifuge. Flowers are astringent, carminative, hepatoprotective, digestive, vermifuge and febrifuge. Fruit is considered nervine, cephalic, aphrodisiac, emmenagogue and vermifuge. Constituents Volatile oil; resin; alkaloid; lichen acids; glucoside. Constituents of oil: sabinene, linalool, terpinen-4-ol, b-caryophyllene, a-guaine and globulol. Study on essential oils showed B-caryophyllene common to leaves, flowers and dried fruits. Leaves yield a colorless essential oil and a resin; the fruit yields an acid resin, an astringent organic acid, mallic acid, and coloring matter. Leaves contain an alkaloid nishindine, flavones, luteolin-7-glucoside, casticin, iridoid glycosides. Phytochemical screening of ethanol leaf extract yielded alkaloids, iridoids, phenolic acids, flavonols and flavonoids. Seeds contain hydrocarbons, B-sitosterol, benzoic acid and phthalic acid, antiinflammatory diterpene, flavonoids and triterpenoids. Uses Folkloric

- Decoction of leaves used externally for cleaning ulcers and internally for flatulence. Also used as a lactagogue and emmenagogue. - Decoction of bark, tops and leaves used as antigastralgic. - Leaves used in aromatic baths; also as insectifuge. - Vapor bath prepared with the plant used for treatment of febrile, catarrhal, and rheumatic affections. - Decoction of leaves used as warm bath by women suffering with after-pains in the puerperal period - Seeds are boiled in water and eaten or the water drunk to prevent the spread of toxin from bites of poisonous animals. - Infusion of seeds used for disinfecting wounds and ulcers. - Infusion of seeds in wine used for dropsy. - Pounded leaves applies on the forehead and temples for headaches. - Leaf decoction for fever, headache, toothache, cough, asthma. - Root used as tonic, febrifuge and expectorant. - Fruit used as nervine, cephalic, and emmenagogue. - Tincture of root bark used for irritable bladder and for rheumatism. - Powdered root used for piles as demulcent; also for dysentery. - Root used for dyspepsia, colic, rheumatism, worms, boils, and leprosy. - Flowers are used for diarrhea, cholera, fever, and diseases of the liver; and also as cardiac tonic. - Powdered flowers and stalks are used for bleeding from the stomach and bowels. - Fruit used for headaches, catarrh, and watery eyes. Dried fruits are used as vermifuge. - Seeds are prepared as cooling mediing for skin diseases, leprosy, and inflammation of the mouth. - Oil prepared with the juice used for sinuses and scrofulous sores. Oil also used as a rubbing application to glandular or tubercular swelliings of the neck. Oil also used for treatment of sloughing wounds and ulcers. - Leaves used for reducing inflammatory and rheumatic swellings of the joints and testicular swelling associated with gonorrheal epididymitis and orchitis. Poultice of leaves also applied to sprained limbs, contusions, leech bites, etc. For these, fresh leaves in an earthen pot are heated over fire, and applied and applied as tolerated over the bruised parts. Leaves heated over fire are also applied with oil externally on wounds. - Pillow stuffed with leaves is placed under the head for relief of catarrh and headache. Dried leaves when smoked also used to relieve catarrh and headaches.

- Decoction of leaves and long pepper used for catarrhal fever associated with head congestion and dullness of hearing. - Juice of leaves used to remove fetid discharges and worms from ulcers. - Plaster of leaves applied to enlarged spleens. - Folkloric preparations: (1) For fever and toothaches, boil 6 tbsp of the chopped leaves in 2 glasses of water for 15 minutes; strain and cool. Divide the decoction in 3 parts and take one part every 3-4 hours. Also, bruised leaves may be applied to forehead. (2) For asthma and cough: Take 1/4 of the decoction three times a day. (3) Aromatic bath or sponge bathing: Boil 4 handfuls of leaves in a pot of water for 5 minutes; use the lukewarm decoction for sponge bathing. - In Ayurveda and Unani, leaves and seeds used for rheumatism and joint inflammation. Decoction of leaves taken as a diuretic. - In Indo-China, root decoction used for intermittent fevers. Others - Insecticide: Leaves considered insecticide and placed between pages of books and folds of silk and woolen clothing to preserve them from insects. Recent Use Lagundi has been proven to be an effective analgesic and antitussive (prepared as a pleasant tasting cough syrup) and has been considered as a replacement for dextromethorphan in the public health system. New Application Studies have shown benefit through reduction of coughing and relaxation of the bronchial smooth muscles. Being promoted by the Department of Health (DOH) for cough and asthma. One of a few herbs recently registered with the Bureau of Foods and Drugs (BFAD) as medicines. Preparation How to make lagundi syrup Clean fresh lagundfi leaves and chop. In 4 glasses of water, boil 4 tablespoons of minced lagundi leaves for 15 minutes. Strain the liquid extract and add 1 part honey to 4 parts extracts. Boil in an earthen pot or enamel-lined saucepan for 15 minutes until the desired viscosity is attained; cool. Pour the syrup in clear amber-colored bottles. Studies Anti-Venom: Tested against Vipera russellii and Naja kaouthia venom, a methanolic extract study of VN showed it possesses potent snake venom neutralizing capacity and suggests further investigation.

 Anti-Inflammatory: (1) VN significantly potentiated antiinflammatory activity of phenylbutazone and ibuprofen in albino rats.(2) Study suggests VN possess anti-imflammatory activity against acute and subacute inflammation probably due to prostaglandin inhibition and reduction of oxidative stress. Anti-Inflammatory / Analgesic: Study showed the fresh leaves of VN have anti-inflammatory and pain suppressing activities possibly mediated through PG synthesis inhibition, antihistmine, membrane stabilizing and antioxidant activities. Antibacterial / Essential Oil: Study showed the essential oils and extracts to have antibacterial activity. Essential oil and extracts showed promising results against B subtilis and E coli. Ethyl acetate and ethanol extracts showed prominent antibacterial activity against all tested strains. Antibacterial / Leaf, Flower and Fruits: Study of extracts of leaf, flower and fruit of VN was done to evaluate in vitro antibacterial activity against phytopathogens Pseudomonas solanacearum and Xanthomonas axonopodis. The ethyl acetate extract showed significant inhibition. Phytochemical screening yielded alkaloids, flavonoids, tannins, cardiac glycosides and terpenoids. Antifungal: (1) New antifungal flavonoid glycoside from Vitex negundo: Study found a new isolated flavone glycoside and a known compound to have significant antifungal activity against Tricophyton mentagrophytes and Cryptococcus neoformans. (2) Ethanol extract of fruit seeds showed significant activity against Fusarium solani and moderate response against Microsporum canis with no effect against C albicans. Larvicidal: Differential larvicidal efficacy of four species of Vitex against Culex quinquefasciatus larvae: The methanolic extracts of all Vitex species showed varying levels of larvicidal activity. Anthelmintic: Study of ethanolic extracts of Moringa oleifera and Vitex negundo on anthelmintic activity against Indian earthworm Pheritima posthuma showed both to have dose dependent activity, with Moringa oleifera showing more activity. Antioxidant: (1) Study of 17 Indian medicinal plants, including the alcoholic extract of VN, all showed dose-dependent nitric oxide (NO) scavenging activity. (2) Report indicated VN can produce reduction of oxidative stress mainly by reduciing lipid peroxidation. (3) Study of ethanolic leaf extract showed antioxidant activity attributed to the presence of phenolic compounds like flavonoids and flavonols. (4) Study showed the leaves showed 23.21 mg/100 of Ascorbic acid Equivalent Antioxidant Capacity (AEAC). Anticonvulsant / Adjuvant Therapy: Study evaluated the anticonvulsant activity of VN leaf extracts in albino mice. Results suggest that VN possesses anticonvulsant activity particularly against PTZ (pentylenetetarazole) induced seizures, with a significant reduction of number and duration of convulsions.The potentiation of diphenylhydantoin and valproic acid suggests it may be useful as adjuvant therapy to lower the requirements of the drug therapies. Insecticidal / Pesticidal: Studies have shown the plant products to possess insecticidal activity against mosquite larvae, houseflies and stored product pests. Pharmacokinetic Interaction / Paracetamol: Study showed a significant decline in plasma concentration of paracetamol. Results conclude that if the VN extract or an ayurvedic formulation is co-admiinstered with an allopathic drug like paracetamol, the allopathic drug has to be adjusted for achieve its desired therapeutic response.

 Antibacterial / Cytotoxic: (1) Sudy showed all fractions with prominent zones of inhibition against B subtilis, B megaterium, S typhi, Vibrio mimicus and a fungal strains, A niger. Results also showed significant cytotoxic activity against brine shrimp nayplii. (2) Extracts were tested against five bacterial species (S aureus, P vulgaris, B subtilis, E coli, P aeruginosa) and three fungal species ( A niger, A flavon, C albicans). Among all extracts the water/ethanol extract showed maximum antimicrobial activity and the water extract, maximum antifungal activity agaiinst all species tested. Gastroprotective / Flavonoids: Study in albino rats investigating the gastroprotective activity of the aqueous extract of VN against aspirin-induced mucosal damage revealed VN to have a pivotal role in treating ulcer. Phytochemical studies yielded the presence of flavonoids probably responsible for its gastroprotection. Hepatoprotective / Negundoside: Negundoside, an iridoid glycoside from the leaves of VN was studied for its hepatoprotective effect on CCl4-induced liver toxicity. Results showed NG exerts a protective effect of CYP2E1-dependent CCl4 toxicity via inhibition of lipid peroxidation, followed by improved intracellular calcium homeostass and inhibition of Ca-dependent proteases. Anxiolytic: Study showed VN is an effective anxiolytic agent. The action of the extract upon anxiety models tested were consistent with the traditional use of VN and presents a potential for use in primary medical care. Essential Oil / Flowers: Study on the essential oil of flowers of VN yielded 45 components. The major compounds were sabinene (20.3%), B-caryophyllene (14.1%) and globulol (19.2%). Antinociceptive / Anti-Inflammatory / Seeds: Study showed ethanol extract of VN seeds interacted with the opioid system and may be more effective3 on inflammatory pain. Further results suggest that the analgesic effectsw may be partially mediated by it anti-inflammatory activuty. The analgesic activity could be due to the abundance of fatty acids with synergistic effects. Anti--microfilarial: Study investigating the antifilarial effect against Brugia malayi microfilariae, the roots extract of VN caused complete loss of motility of microfilariae after 48 hrs of incubation. Study yielded the presence of alkaloids, saponins and flavanoids from the roots of VN. Antinociceptive: Study in mice investigating the antinociceptive activity of an ethanolic leaf extract showed significant dose-dependent analgesic activity. Ten times the extract dose produced the effects comparable to the standard drug meperidine. Naloxone did not reverse the analgesic effect of the VN extract. Results suggest both central and peripheral analgesic activity and also suggests a potential as adjuvant therapy with analgesic drugs. Antiamnesic: Study investigated the anti-amnesic activity of VN in scopolamine-induced amnesia in rats. Results showed that VN treated groups had decreased phenomenon of amnesia by increasing learning of memory through antioxidant effect and decreasing AChE activity. Antitumor: Study of ethanol and aqueous extract of leaves of Vitex negundo against Dalton's Ascitic Lymphoma showed antitumor effect. Availability Wild-crafted. Commercial formulations: Tablets, capsules, teas, and syrup.

http://www.stuartxchange.org/Lagundi.html Lagundi (scientific name: Vitex negundo) is a shrub that grows in the Philippines. It is one of the ten herbal medicines endorsed by the Philippine Department of Health as an effective herbal medicine with proven therapeutic value. Commonly known in the Ilocos region as dangla, lagundi has been clinically tested to be effective in the treatment of colds, flu, bronchial asthma, chronic bronchitis, and pharyngitis. Studies have shown that Lagundi can prevent the body's production of leukotrienes, which are released during an asthma attack. Lagundi contains Chrysoplenol D, a substance with anti-histamine and muscle relaxant properties. Even in Japan, lagundi is becoming recognized as an effective herbal medicine, especially since researches have shown that it contains properties that make it an expectorant and it has been reported to function as a tonic as well. More than that, most of the parts of the lagundi plant are associated with medicinal value.

The roots of this shrub are also used as treatment for rheumatism, dyspepsia, boils, and leprosy. The leaves, flowers, seeds, and root of Lagundi can all be used as herbal medicine. A decoction is made by boiling the parts of the plant and taken orally. Today, Lagundi is available in capsule form and syrup for cough. For its part, the flowers are recommended as a cardiac tonic, as cure for liver diseases, and other internal disorders such as diarrhea and cholera. The lagundi plant also has anti-inflammatory functions, and its cooling effects are ideal as treatment for skin diseases such as leprosy. Herbal Benefits of Lagundi: Relief of asthma & pharyngitis Recommended relief of rheumatism, dyspepsia, boils, diarrhea Treatment of cough, colds, fever and flu and other bronchopulmonary disorders Alleviate symptoms of Chicken Pox Removal of worms, and boils Preparation & Use: Boil half cup of chopped fresh or dried leaves in 2 cups of water for 10 to 15 minutes. Drink half cup three times a day. For skin diseases or disorders, apply the decoction of leaves and roots directly on skin. The root is specially good for treating dyspepsia, worms, boils, colic and rhumatism A decoction (boiling in water) of the roots and leaves of Lagundi are applied to wounds, and used as aromatic baths for skin diseases. Boiled seeds are eaten in order to prevent the spreading of toxins and venom from bites of poisonous animals. Juice extracted from the flowers of lagundi is taken in as an aid for disorders like fever, diarrhea, liver disorders, and even cholera. While a decoction of the plant leaves is suggested to be taken by individuals to help increase the flow and production of milk, as well as to induce menstruation. http://www.philippineherbalmedicine.org/lagundi.htm http://ejarr.com/Volumes/Vol3/EJBS_3_05.pdf

METATHIONE ALA - alpha lipoic acid is an anti-oxidant and is used widely in prevention of various diseases. Its main function is to increase the production of glutathione, processing from meat & veggies we ate. It helps dissolve toxic substances in the liver, thus neutralizes free radicals (smoking, pollution & fried oils) & protect cells from damages. since it is absorbed quickly by the blood, whitening process makes it easier & quicker. MET-TATHIONE - is used to help treat blood disorders, and detoxify the liver of heavy metals, toxins, and alcohol. It has a long history of being used by those exposed to radiation and chemotherapy during cancer therapies. IT helps to protect cells and tissues against oxidants. It is thought that MET-TATHIONE has anti-aging effects, and as we grow older, supplementing MET-TATHIONE can help prevent the levels from dropping. Dermatologists prescribe MET-TATHIONE for its only side effect: whitening of dark skin. People with darker skin tone report that taking MET-TATHIONE capsules along with vitamin C for three to six months or more actually lightens the color of their skin. This side effect varies from person to person and it assures to really whiten your skin in the shortest period of time for it has combined the main components for an active whitening result. MET-TATHIONE - is a kind of GLUTATHIONE which is a small protein composed of 3 amino acids called cysteine, glutamic acid, and glycine, produced normally by the body in response to todays environment such as pollution in the air we breathe, water we drink, chemicals & pesticides in the food we eat that cause damages in our cells & system. MET-TATHIONE - is often referred to as Master Anti-oxidant in the body. a small molecule made up of linked amino acids and anti-oxidant naturally produced in the body. It has been widely heralded for its importance for good health and long life, the greater the exposure to toxins, the faster the body uses up its supply of glutathione. Without the protection of Glutathione, cells die at a faster rate, making people age quicker & putting them at risk for toxin induced diseases including cancer. It is the most powerful anti-oxidant occurring naturally in all of 70-100 trillion cells that make up the human body. That is why it is called the master antioxidant (MA) the effectiveness of all other anti-oxidants Vitamin A, Vitamin C, Vitamin E and Selenium. MET-TATHIONE should be taken together with Vitamin C to work properly. What is GLUTATHIONE? Glutathione is a master anti-oxidant, and a very effective whitening agent if taken in greater dosage 1. One of the more popular benefits of taking glutathione is that it cleanses the liver; and being an antioxidant, it rids the body of free radicals that contribute to aging and sicknesses. 2. The advisable dosage of glutathione as anti-oxidant is 10-20mg per kilogram of body weight. In order to use as a skin whitening agent, it has to be taken at a dosage of 20-40mg per kilogram of body weight. For instance, 50kg x 20mg = 1000mg. It has to be taken with an appropriate amount of vitamin c to be able to maximize its whitening effect, which as advised, is double the amount of your glutathione intake. As a precaution, please consult your doctor first before taking any kind of supplement. 3. On average, the first 3 months use of glutathione builds its foundation in your body and you will experience lightening gradually, speed normally depends on your metabolism and body chemical functioning. For some the results take longer. As you lighten you will notice that your skin is shinier and healthier than before. 4. It is advisable to take glutathione with meals and one taking it should try to avoid liquor or any alcoholic

drink. It is also advisable to put on sunblock cream and lotion for the face and body. How Does MET-TATHIONE WORK? You will notice that youre starting to look fairer and skin is glowing. Makes your skin smooth and rosy as a long-term result Heals dark spots cause by acne and prevents it from coming back Lips will become pinkish because the melanin pigments your lip will also decrease Underarms will lighten Bikini line will lighten

Helps us to maintain clear vision and if you have blurred vision or cataract this will help your eyesight since the sclera of the eyes are also rich in Glutathione

BENEFITS OF MET-TATHIONE: Master Anti-Oxidant Aging Dark Skin Cataracts Memory Loss ( Alzheimer's Disease ) Osteoarthritis Parkinson's Disease Peptic Ulcer Alcohol Drinkers Low Sperm Count Liver Problem i.e. Hepatitis Chemotheraphy Recovery Atherosclerosis ( Heart Disease ) Body Builders Anti-Cancer Anti-Ashma/ Allergies

Boost Immune System Regulates Blood And Sugar Level

http://ernesto4.webs.com/metathione.htm http://metathione.blogspot.com/ MET-TATHIONE is used to help treat blood disorders, and detoxify the liver of heavy metals, toxins, and alcohol. It has a long history of being used by those exposed to radiation and chemotherapy during cancer therapies. MET-tathione helps to protect cells and tissues against oxidants. It is thought that METtathione has anti-aging effects, and as we grow older, supplementing MET-tathione can help prevent the levels from dropping. Dermatologists prescribe MET-TATHIONE for its only side effect: whitening of dark skin. People with darker skin tone report that taking MET-tathione capsules along with vitamin C for three to six months or more actually lightens the color of their skin. This side effect varies from person to person and our METtathione assures to really whiten your skin in the shortest period of time for it has combined the main components for an active whitening result. MET-TATHIONE CAPSULE CONTAINS THE IMPORTANT REGENERATING ANTI-OXIDANT. MET TATHIONE is the most powerful anti-oxidant occurring naturally in all of 70-100 trillion cells that make up the human body. That is why MET-tathione is called the master antioxidant(MA) the effectiveness of all other anti-oxidants Vitamin A, Vitamin C, Vitamin E and Selenium all depends upon the availability of MET-tathione. VIT C and MET-tathione in the skin act as photo protectants and neutralize the oxygen radicals so that they no longer damage the skin. MET-tathione needs VIT C to work properly. http://www.glutathioneskinwhitening.com/2009/04/tell-me-about-metathione-made-in-japan/ GLUTATHIONE Glutathione (GSH) is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine (which is attached by normal peptide linkage to a glycine) and the carboxyl group of the glutamate side-chain. It is an antioxidant, preventing damage to important cellular components caused by reactive oxygen species such as free radicals and peroxides. Thiol groups are reducing agents, existing at a concentration of approximately 5 mM in animal cells. Glutathione reduces disulfide bonds formed within cytoplasmic proteins to cysteines by serving as an electron donor. In the process, glutathione is converted to its oxidized form glutathione disulfide (GSSG), also called L(-)-Glutathione. Once oxidized, glutathione can be reduced back by glutathione reductase, using NADPH as an electron donor. The ratio of reduced glutathione to oxidized glutathione within cells is often used as a measure of cellular toxicity. Biosynthesis Glutathione is not an essential nutrient (meaning it does not have to be obtained via food), since it can be synthesized in the body from the amino acids L-cysteine, L-glutamic acid, and glycine. The sulfhydryl (thiol) group (SH) of cysteine serves as a proton donor and is responsible for the biological activity of

glutathione. Provision of this amino acid is the rate-limiting factor in glutathione synthesis by the cells, since cysteine is relatively rare in foodstuffs. Furthermore, if released as the free amino acid, cysteine is toxic and spontaneously catabolized in the gastrointestinal tract and blood plasma. Glutathione is synthesized in two adenosine triphosphate-dependent steps: First, gamma-glutamylcysteine is synthesized from L-glutamate and cysteine via the enzyme gammaglutamylcysteine synthetase (a.k.a. glutamate cysteine ligase, GCL). This reaction is the rate-limiting step in glutathione synthesis. Second, glycine is added to the C-terminal of gamma-glutamylcysteine via the enzyme glutathione synthetase. Animal glutamate cysteine ligase (GCL) is a heterodimeric enzyme composed of a catalytic (GCLC) and modulatory (GCLM) subunit. GCLC constitutes all the enzymatic activity, whereas GCLM increases the catalytic efficiency of GCLC. Mice lacking GCLC (i.e., all de novo GSH synthesis) die before birth. Mice lacking GCLM demonstrate no outward phenotype, but exhibit marked decrease in GSH and increased sensitivity to toxic insults. While all cells in the human body are capable of synthesizing glutathione, liver glutathione synthesis has been shown to be essential. Mice with genetically-induced loss of GCLC (i.e., GSH synthesis) only in the liver die within 1 month of birth. The plant glutamate cysteine ligase (GCL) is a redox-sensitive homodimeric enzyme, conserved in the plant kingdom. In an oxidizing environment, intermolecular disulfide bridges are formed and the enzyme switches to the dimeric active state. The mid-point potential of the critical cysteine pair is -318 mV. In addition to the redox-dependent control is the plant GCL enzyme feedback inhibited by GSH. GCL is exclusively located in plastids, and glutathione synthetase is dual-targeted to plastids and cytosol, thus are GSH and gamma-glutamylcysteine exported from the plastids. Both glutathione biosynthesis enzymes are essential in plants; knock-outs of GCL and GS are lethal to embryo and seedling. The biosynthesis pathway for glutathione is found in some bacteria, like cyanobacteria and proteobacteria, but is missing in many other bacteria. Most eukaryotes synthesize glutathione, including humans, but some do not, such as Leguminosae, Entamoeba, and Giardia. The only archaea that make glutathione are halobacteria. Function Glutathione exists in reduced (GSH) and oxidized (GSSG) states. In the reduced state, the thiol group of cysteine is able to donate a reducing equivalent (H++ e-) to other unstable molecules, such as reactive oxygen species. In donating an electron, glutathione itself becomes reactive, but readily reacts with another reactive glutathione to form glutathione disulfide (GSSG). Such a reaction is possible due to the relatively high concentration of glutathione in cells (up to 5 mM in the liver). GSH can be regenerated from GSSG by the enzyme glutathione reductase. In healthy cells and tissue, more than 90% of the total glutathione pool is in the reduced form (GSH) and less than 10% exists in the disulfide form (GSSG). An increased GSSG-to-GSH ratio is considered indicative of oxidative stress. Glutathione has multiple functions:

It is the major endogenous antioxidant produced by the cells, participating directly in the neutralization of free radicals and reactive oxygen compounds, as well as maintaining exogenous antioxidants such as vitamins C and E in their reduced (active) forms. Regulation of the nitric oxide cycle, which is critical for life but can be problematic if unregulated It is used in metabolic and biochemical reactions such as DNA synthesis and repair, protein synthesis, prostaglandin synthesis, amino acid transport, and enzyme activation. Thus, every system in the body can be affected by the state of the glutathione system, especially the immune system, the nervous system, the gastrointestinal system and the lungs. It has a vital function in iron metabolism. Yeast cells depleted of or containing toxic levels of GSH show an intense iron starvation-like response and impairment of the activity of extra-mitochondrial ISC enzymes, followed by death. Reaction mechanism of human glutathione reductase NADPH reduces FAD present in GSR to produce a transient FADH- anion. This anion then quickly breaks a disulfide bond (Cys58 - Cys63) and leads to Cys63's nucleophilically attacking the nearest sulfide unit in the GSSG molecule (promoted by His467), which creates a mixed disulfide bond (GS-Cys58) and a GSanion. His467 of GSR then protonates the GS- anion to form the first GSH. Next, Cys63 nucleophilically attacks the sulfide of Cys58, releasing a GS- anion, which, in turn, picks up a solvent proton and is released from the enzyme, thereby creating the second GSH. So, for every GSSG and NADPH, two reduced GSH molecules are gained, which can again act as antioxidants scavenging reactive oxygen species in the cell.

Function in animals GSH is known as a substrate in both conjugation reactions and reduction reactions, catalyzed by glutathione S-transferase enzymes in cytosol, microsomes, and mitochondria. However, it is also capable of participating in non-enzymatic conjugation with some chemicals. In the case of N-acetyl-p-benzoquinone imine (NAPQI), the reactive cytochrome P450-reactive metabolite formed by paracetamol (or acetaminophen as it is known in the US), which becomes toxic when GSH is depleted by an overdose of acetaminophen, glutathione is an essential antidote to overdose. Glutathione conjugates to NAPQI and helps to detoxify it. In this capacity, it protects cellular protein thiol groups, which would otherwise become covalently modified; when all GSH has been spent, NAPQI begins to react with the cellular proteins, killing the cells in the process. The preferred treatment for an overdose of this painkiller is the administration (usually in atomized form) of N-acetyl-L-cysteine (often as a trademarked preparation called Mucomyst ), which is processed by cells to L-cysteine and used in the de novo synthesis of GSH. Glutathione (GSH) participates in leukotriene synthesis and is a cofactor for the enzyme glutathione peroxidase. It is also important as a hydrophilic molecule that is added to lipophilic toxins and waste in the liver during biotransformation before they can become part of the bile. Glutathione is also needed for the detoxification of methylglyoxal, a toxin produced as a by-product of metabolism.

This detoxification reaction is carried out by the glyoxalase system. Glyoxalase I (EC 4.4.1.5) catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-lactoyl-glutathione. Glyoxalase II (EC 3.1.2.6) catalyzes the hydrolysis of S-D-lactoyl-glutathione to glutathione and D-lactic acid. Glutathione has recently been used as an inhibitor of melanin in the cosmetics industry. In countries like Japan and the Philippines, this product is sold as a whitening soap. Glutathione competitively inhibits melanin synthesis in the reaction of tyrosinase and L-DOPA by interrupting L-DOPA's ability to bind to tyrosinase during melanin synthesis. The inhibition of melanin synthesis was reversed by increasing the concentration of L-DOPA, but not by increasing tyrosinase. Although the synthesized melanin was aggregated within 1 h, the aggregation was inhibited by the addition of glutathione. These results indicate that glutathione inhibits the synthesis and agglutination of melanin by interrupting the function of LDOPA." Function in plants In plants, glutathione is crucial for biotic and abiotic stress management. It is a pivotal component of the glutathione-ascorbate cycle, a system that reduces poisonous hydrogen peroxide. It is the precursor of phytochelatins, glutathione oligomeres that chelate heavy metals such as cadmium. Glutathione is required for efficient defence against plant pathogens such as Pseudomonas syringae and Phytophthora brassicae. APS reductase, an enzyme of the sulfur assimilation pathway uses glutathione as electron donor. Other enzymes using glutathione as substrate are glutaredoxin, these small oxidoreductases are involved in flower development, salicylic acid and plant defence signalling. Supplementation Raising GSH levels through direct supplementation of glutathione is difficult. Research suggests that glutathione taken orally is not well absorbed across the gastrointestinal tract. In a study of acute oral administration of a very large dose (3 grams) of oral glutathione, Witschi and coworkers found "it is not possible to increase circulating glutathione to a clinically beneficial extent by the oral administration of a single dose of 3 g of glutathione." Calcitriol, the active metabolite of vitamin D synthesized in the kidney, increases glutathione levels in the brain and appears to be a catalyst for glutathione production. In addition, plasma and liver GSH concentrations can be raised by administration of certain supplements that serve as GSH precursors. N-acetylcysteine, commonly referred to as NAC, is the most bioavailable precursor of glutathione.Other supplements, including S-adenosylmethionine (SAMe) and whey protein have also been shown to increase glutathione content within the cell. NAC is available both as a drug and as a generic supplement. Alpha lipoic acid has also been shown to restore intracellular glutathione. Melatonin has been shown to stimulate a related enzyme, glutathione peroxidase, and silymarin, an extract of the seeds of the milk thistle plant (Silybum marianum), has also demonstrated an ability to replenish glutathione levels in lab rats. Glutathione is a tightly regulated intracellular constituent, and is limited in its production by negative feedback inhibition of its own synthesis through the enzyme gamma-glutamylcysteine synthetase, thus greatly minimizing any possibility of overdosage. Glutathione augmentation using precursors of glutathione synthesis or intravenous glutathione is a strategy developed to address states of glutathione deficiency, high oxidative stress, immune deficiency, and xenobiotic overload in which glutathione plays a part in the detoxification of the xenobiotic in question (especially through the hepatic route). Glutathione deficiency states include, but are not limited to, HIV/AIDS, chemical and infectious hepatitis, myalgic

encephalomyelitis chronic fatigue syndrome ME / CFS, prostate and other cancers, cataracts, Alzheimer's disease, Parkinson's disease, chronic obstructive pulmonary disease, asthma, radiation poisoning, malnutritive states, arduous physical stress, and aging, and has been associated with suboptimal immune response. Many clinical pathologies are associated with oxidative stress and are elaborated upon in numerous medical references. Low glutathione is also strongly implicated in wasting and negative nitrogen balance, as seen in cancer, AIDS, sepsis, trauma, burns and even athletic overtraining. Glutathione supplementation can oppose this process, and in AIDS, for example, result in improved survival rates. However, studies in many of these conditions have not been able to differentiate between low glutathione as a result of acutely (as in septic patients) or chronically (as in HIV) increased oxidative stress, and increased pathology as a result of preexisting deficiencies. Schizophrenia and bipolar disorder are associated with lowered glutathione. Accruing data suggest that oxidative stress may be a factor underlying the pathophysiology of bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ). Glutathione (GSH) is the major free radical scavenger in the brain. Diminished GSH levels elevate cellular vulnerability towards oxidative stress; characterized by accumulating reactive oxygen species. Replenishment of glutathione using N-acetyl cysteine has been shown to reduce symptoms of both disorders. Cancer Preliminary results indicate glutathione changes the level of reactive oxygen species in isolated cells grown in a laboratory, which may reduce cancer development. None of these tests were performed in humans. However, once a cancer has already developed, by conferring resistance to a number of chemotherapeutic drugs, elevated levels of glutathione in tumour cells are able to protect cancerous cells in bone marrow, breast, colon, larynx, and lung cancers. Pathology Excess glutamate at synapses, which may be released in conditions such as traumatic brain injury, can prevent the uptake of cysteine, a necessary building-block of glutathione. Without the protection from oxidative injury afforded by glutathione, cells may be damaged or killed. Methods to determine glutathione Reduced glutathione may be visualized using Ellman's reagent or bimane derivates such as monobromobimane. The monobromobimane method is more sensitive. In this procedure, cells are lysed and thiols extracted using a HCl buffer. The thiols are then reduced with dithiothreitol (DTT) and labelled by monobromobimane. Monobromobimane becomes fluorescent after binding to GSH. The thiols are then separated by HPLC and the fluorescence quantified with a fluorescence detector. Bimane may also be used to quantify glutathione in vivo. The quantification is done by confocal laser scanning microscopy after application of the dye to living cells. Another approach, which allows to measure the glutathione redox potential at a high spatial and temporal resolution in living cells is based on redox imaging using the redox-sensitive green fluorescent protein (roGFP) or redox sensitive yellow fluorescent protein (rxYFP) http://en.wikipedia.org/wiki/Glutathione VITAMIN E

Vitamin E refers to a group of eight fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which -tocopherol is the most common in the North American diet. -Tocopherol can be found in corn oil, soybean oil, margarine and dressings. Tocopherol, the most biologically active form of vitamin E, is the second most common form of vitamin E in the North American diet. This variant of vitamin E can be found most abundantly in wheat germ oil, sunflower, and safflower oils. It is a fat-soluble antioxidant that stops the production of reactive oxygen species formed when fat undergoes oxidation. Health effects While it was initially hoped that vitamin E supplementation would have a positive effect on health, research has not supported these conclusions. Vitamin E does not decrease mortality in adults, even at large doses, and may slightly increase it. It does not improve blood sugar control in an unselected group of people with diabetes mellitus or decrease the risk of stroke. Daily supplementation of vitamin E does not decrease the risk of prostate cancer and may increase it. Studies on its role in age related macular degeneration are ongoing as even though it is of a combination of dietary antioxidants used to treat the condition it may increase the risk. Deficiency Vitamin E deficiency can cause: spinocerebellar ataxia myopathies peripheral neuropathy ataxia skeletal myopathy retinopathy impairment of the immune response Functions Vitamin E has many biological functions; the antioxidant function being the most important and/or best known.Other functions include enzymatic activities, gene expression and neurological function(s). It's also been suggested that the most important function of vitamin E is in cell signaling (and, that it may not have a significant role in antioxidant metabolism). As an antioxidant, vitamin E acts as a peroxyl radical scavenger, preventing the propagation of free radicals in tissues, by reacting with them to form a tocopheryl radical which will then be oxidized by a hydrogen donor (such as Vitamin C) and thus return to its reduced state. As it is fat-soluble, it is incorporated into cell membranes, which protects them from oxidative damage. As an enzymatic activity regulator, for instance, protein kinase C (PKC), which plays a role in smooth muscle growth, can be inhibited by -tocopherol. -Tocopherol has a stimulatory effect on the dephosphorylation enzyme, protein phosphatase 2A, which in turn, cleaves phosphate groups from PKC leading to its deactivation, bringing the smooth muscle growth to a halt.

Vitamin E also has an effect on gene expression. Macrophages rich in cholesterol are found in the atherogenetic tissue. Scavenger receptor CD36 is a class B scavenger receptor found to be up-regulated by oxidized low density lipoprotein (LDL) and binds it. Treatment with alpha tocopherol was found to down regulate the expression of the CD36 scavenger receptor gene and the scavenger receptor class A (SR-A) and modulates expression of the connective tissue growth factor (CTGF). CTGF gene, when expressed, is responsible for the repair of wounds and regeneration of the extracellular tissue that is lost or damaged during atherosclerosis. Vitamin E also plays a role in neurological functions, and inhibition of platelet aggregation. So far, most human supplementation studies about vitamin E have used only alpha-tocopherol. This can affect levels of other forms of vitamin E, e.g. reducing serum gamma- and delta-tocopherol concentrations. Moreover, a 2007 clinical study involving alpha-tocopherol concluded that supplementation did not reduce the risk of major cardiovascular events in middle aged and older men. http://en.wikipedia.org/wiki/Vitamin_E Vitamin E is a vitamin that dissolves in fat. It is found in many foods including vegetable oils, cereals, meat, poultry, eggs, fruits, vegetables, and wheat germ oil. It is also available as a supplement.

Vitamin E is used for treating vitamin E deficiency, which is rare, but can occur in people with certain genetic disorders and in very low-weight premature infants.

Some people use vitamin E for treating and preventing diseases of the heart and blood vessels including hardening of the arteries, heart attack, chest pain, leg pain due to blocked arteries, and high blood pressure.

Vitamin E is also used for treating diabetes and its complications. It is used for preventing cancer, particularly lung and oral cancer in smokers; colorectal cancer and polyps; and gastric, prostate, and pancreatic cancer.

Some people use vitamin E for diseases of the brain and nervous system including Alzheimers disease and other dementias, Parkinsons disease, night cramps, restless leg syndrome, and for epilepsy, along with other medications. Vitamin E is also used for Huntingtons chorea, and other disorders involving nerves and muscles.

Women use vitamin E for preventing complications in late pregnancy due to high blood pressure (preeclampsia), premenstrual syndrome (PMS), painful periods, menopausal syndrome, hot flashes associated with breast cancer, and breast cysts.

Sometimes vitamin E is used to lessen the harmful effects of medical treatments such as dialysis and radiation. It is also used to reduce unwanted side effects of drugs such as hair loss in people taking doxorubicin and lung damage in people taking amiodarone.

Vitamin E is sometimes used for improving physical endurance, increasing energy, reducing muscle damage after exercise, and improving muscle strength.

Vitamin E is also used for cataracts, asthma, respiratory infections, skin disorders, aging skin, sunburns, cystic fibrosis, infertility, impotence, chronic fatigue syndrome (CFS), peptic ulcers, for certain inherited diseases and to prevent allergies.

Some people apply vitamin E to their skin to keep it from aging and to protect against the skin effects of chemicals used for cancer therapy (chemotherapy).

The American Heart Association recommends obtaining antioxidants, including vitamin E, by eating a well-balanced diet high in fruits, vegetables, and whole grains rather than from supplements until more is known about the risks and benefits of taking supplements.

How does it work? Vitamin E is an important vitamin required for the proper function of many organs in the body. It is also an antioxidant. This means it helps to slow down processes that damage cells. Possibly Effective for: y Bladder cancer. Taking 200 IU of vitamin E by mouth for more than 10 years seems to help prevent death from bladder cancer. Alzheimers disease. Vitamin E might slow down the worsening of memory loss in people with moderately severe Alzheimers disease. But vitamin E does not seem to prevent moving from mild memory problems to full-blown Alzheimers disease. Painful menstruation (dysmenorrhea). Taking vitamin E for 2 days before and for 3 days after bleeding begins seems to decrease pain severity and duration, and reduce menstrual blood loss. Premenstrual syndrome (PMS). Taking vitamin E by mouth seems to reduce anxiety, craving, and depression in some women with PMS. Chemotherapy-related nerve damage. Taking vitamin E before and after treatment with cisplatin chemotherapy might reduce the chance of getting nerve damage. Ischemic stroke. Some research shows that taking vitamin E might slightly decrease the chance of having a stroke caused by a blood clot (ischemic stroke). But taking vitamin E might also

increase the chance of having a more severe type of stroke, called hemorrhagic stroke. This kind of stroke occurs when there is bleeding into the brain. y Liver disease called nonalcoholic steatohepatitis. Taking vitamin E 400-1200 IU daily seems to significantly improve symptoms in adults and children after 4-24 months of treatment. Huntingtons chorea. Natural vitamin E (RRR-alpha-tocopherol) can significantly improve symptoms in people with early Huntingtons disease, but it doesnt seem to help people with more advanced disease. Macular degeneration. Taking vitamin E by mouth in combination with vitamin C, beta-carotene and zinc might slow the worsening of advanced age-related macular degeneration (AMD). There isnt enough information to know if this combination helps people with less advanced macular disease or prevents AMD. Zinc needs to be present in the combination for there to be any effect on AMD. Rheumatoid arthritis (RA). Vitamin E taken along with standard treatment is better than standard treatment alone for reducing pain in people with RA. But this combination doesnt reduce swelling (inflammation). Male infertility. High blood pressure during pregnancy (pre-eclampsia). Movement disorders called tardive dyskinesia and dyspraxia. Parkinsons disease. Kidney problems in children (glomerulosclerosis). Helping to treat an inherited disorder called G6PD deficiency. Beta-thalassemia. Dementia. Healing a type of skin sore called granuloma annulare when put on the skin. Uveitis. Sunburn. Helping the eyes heal after surgery. Treating a type of eye disease in newborns called retrolental fibroplasia. Decreasing brain and heart bleeding in premature babies. Helping some heart medications called nitrates work better. Improving physical performance and strength in the elderly. Fibrosis caused by radiation.

y y y y y y y y y y y y y y y y y

Possibly Ineffective for: y y y y y y y y y y y Anemia in people having hemodialysis. Chest pain (angina). Hot flashes in people who have had breast cancer. Hardening of the arteries (atherosclerosis). Breathing problems in newborns. Lung infections in elderly persons. Heart failure. Treating muscle diseases called Duchenne muscular dystrophy and myotonic dystrophy. High blood pressure. Helping people walk without pain when they have a disease called intermittent claudication. A type of arthritis called osteoarthritis. Vitamin E does not seem to decrease pain or stiffness and does not seem to prevent osteoarthritis from getting worse. Head and neck cancer. Sores in the mouths of people who smoke. Cancer of the pancreas. Pharyngeal cancer. Reducing scarring after surgery. Colorectal cancer. An eye condition called retinitis pigmentosa.

y y y y y y y

Likely Ineffective for: y Preventing heart disease. Taking vitamin E supplements does not prevent heart disease. But increasing vitamin E in the diet might be beneficial. Benign breast disease. Breast cancer. Lung cancer. Prostate cancer. Research on the effects of vitamin E on prostate cancer risk has produced results that dont agree. Some studies suggest that taking more vitamin E seems to prevent prostate cancer. But other large studies find no benefit. Some research has also shown that

y y y y

taking vitamin E might increase the chance of developing prostate cancer. Overall, the best research indicates that vitamin E does not help prevent prostate cancer and might increase the chance of developing prostate cancer. Insufficient Evidence for: y Asthma. There is inconsistent evidence about the role of vitamin E in asthma. Some research suggests that getting more vitamin E from the diet seems to prevent asthma. But getting vitamin E from supplements doesnt have the same benefit. Cancer. Some research suggests a combination of vitamin E with vitamin C, beta-carotene, selenium, and zinc lowers the risk of cancer in men, but not women. Researchers suspect that men get a lower amount of these vitamins from food, so they might benefit more from supplements. Stomach cancer. Taking vitamin E plus beta-carotene or vitamin C and beta-carotene does not seem to prevent stomach cancer. But there is limited evidence that getting more vitamin E from the diet might slow the progress of stomach cancer. Sickle cell disease. Taking vitamin E with aged garlic extract and vitamin C might be useful for sickle cell anemia. Stroke caused by a clot (ischemic stroke). There is some evidence that synthetic vitamin E (allrac-alpha-tocopherol) might help prevent stroke in male smokers who have high blood pressure and diabetes. Skin disorders. Cloudy vision in older people (cataracts). Diabetes. Esophageal cancer. Allergies. Chronic fatigue syndrome (CFS). Oral cancer. Skin cancer. Epilepsy. Menstrual disorders. High blood fat levels. Leg cramps. Common cold. Other conditions.

y y y y y y y y y y y y y y

Vitamin E is LIKELY SAFE for most healthy people when taken by mouth or applied to the skin. Most people do not experience any side effects when taking the recommended daily dose, which is 15 mg. Vitamin E is POSSIBLY UNSAFE if taken in high doses. If you have a condition such as heart disease or diabetes, dont take doses of 400 IU/day or more. Some research suggests that high doses might increase the chance of death and possibly cause other serious side effects. The higher the dose, the greater the risk of serious side effects. There is some concern that vitamin E might increase the chance of having a serious stroke called hemorrhagic stroke, which is bleeding into the brain. Some research shows that taking vitamin E in doses of 300-800 IU each day might increase the chance of this kind of stroke by 22%. However, in contrast, vitamin E might decrease the chance of having a less severe stroke called an ischemic stroke. There is contradictory information about the effect of vitamin E on the chance of developing prostate cancer. Some research suggests that taking large amounts of a multivitamin plus a separate vitamin E supplement might actually increase the chance of developing prostate cancer in some men. High doses can also cause nausea, diarrhea, stomach cramps, fatigue, weakness, headache, blurred vision, rash, and bruising and bleeding. Special Precautions & Warnings: Pregnancy and breast-feeding: When used in the recommended daily amount, vitamin E is POSSIBLY SAFE for pregnant and breast-feeding women. There has been some concern that taking vitamin E supplements might be harmful to the fetus when taken in early pregnancy. But it is too soon to know if this is an important concern. Until more is known, do no take vitamin E supplements during early pregnancy without talking with your healthcare provider. Angioplasty, a heart procedure: Avoid taking supplements containing vitamin E or other antioxidant vitamins (beta-carotene, vitamin C) immediately before and following angioplasty without the supervision of a health care professional. These vitamins seem to interfere with proper healing. Low levels of vitamin K (vitamin K deficiency): Vitamin E might worsen clotting problems in people whose levels of vitamin K are too low. An eye condition called retinitis pigmentosa: All-rac-alpha-tocopherol (synthetic vitamin E) 400 IU seems to speed vision loss in people with retinitis pigmentosa. However, much lower amounts (3 IU) dont seem to produce this effect. If you have this condition, its best to avoid vitamin E. Bleeding disorders: Vitamin E might make bleeding disorders worse. If you have a bleeding disorder, avoid taking vitamin E supplements. Head and neck cancer: Dont take vitamin E supplements in doses of 400 IU/day or more. Vitamin E might increase the chance that cancer will return. Prostate cancer: There is concern that taking vitamin E might increase the chance of developing prostate cancer. The effect of vitamin E in men who currently have prostate cancer is not clear. But, in theory, taking vitamin E supplements might worsen prostate cancer in men who already

y y

have it. Surgery: Vitamin E might increase the risk of bleeding during and after surgery. Stop using vitamin E at least 2 weeks before a scheduled surgery. http://www.webmd.com/vitamins-supplements/ingredientmono-954VITAMIN%20E.aspx?activeIngredientId=954&activeIngredientName=VITAMIN%20E PARACETAMOL Paracetamol is a widely used over-the-counter analgesic (pain reliever) and antipyretic (fever reducer). It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies. In combination with opioid analgesics, paracetamol can also be used in the management of more severe pain such as post-surgical pain and providing palliative care in advanced cancer patients. The onset of analgesia is approximately 11 minutes after oral administration of paracetamol, and its half-life is 14 hours. Though acetaminophen is used to treat inflammatory pain, it is not generally classified as an NSAID because it exhibits only weak anti-inflammatory activity. While generally safe for use at recommended doses (1,000 mg per single dose and up to 4,000 mg per day for adults), acute overdoses of paracetamol can cause potentially fatal liver damage and, in rare individuals, a normal dose can do the same; the risk is heightened by alcohol consumption. Paracetamol toxicity is the foremost cause of acute liver failure in the Western world, and accounts for most drug overdoses in the United States, the United Kingdom, Australia and New Zealand. It is the active metabolite of phenacetin, once popular as an analgesic and antipyretic in its own right, but unlike phenacetin and its combinations, paracetamol is not considered carcinogenic at therapeutic doses. The words acetaminophen (used in the United States, Canada, Japan, South Korea, Hong Kong, and Iran) and paracetamol (used elsewhere) both come from a chemical name for the compound: paraacetylaminophenol and para-acetylaminophenol. In some contexts, it is simply abbreviated as APAP, for acetyl-para-aminophenol. Medical uses Fever Paracetamol is approved for reducing fever in people of all ages. The World Health Organization (WHO) recommends that paracetamol only be used to treat fever in children if their temperature is greater than 38.5 C (101.3 F). The efficacy of paracetamol by itself in children with fevers has been questioned and a meta-analysis showed that it is less effective than ibuprofen. Paracetamol has a well-established role in pediatric medicine as an effective analgesic and antipyretic. Pain Paracetamol is used for the relief of pains associated with many parts of the body. It has analgesic properties comparable to those of aspirin, while its anti-inflammatory effects are weaker. It is better tolerated than aspirin in patients in whom excessive gastric acid secretion or prolongation of bleeding time may be a concern. Available without a prescription, it has in recent years increasingly become a common household drug.

Paracetamol can relieve pain in mild arthritis but has no effect on the underlying inflammation, redness, and swelling of the joint. It is as effective as the non-steroidal anti-inflammatory drug ibuprofen in relieving the pain of osteoarthritis of the knee. Paracetamol has relatively little anti-inflammatory activity, unlike other common analgesics such as the NSAIDs aspirin and ibuprofen. Regarding comparative efficacy, studies show conflicting results when compared to NSAIDs. A randomized controlled trial of chronic pain from osteoarthritis in adults found similar benefit from paracetamol and ibuprofen. The efficacy of paracetamol when used in a combination form with weak opioids (such as codeine) has been questioned by recent data studies; the small amount of data available have made reaching a conclusion difficult. Combination drugs of paracetamol and strong opioids like morphine have been shown to reduce the amount of opioid used and improve analgesic effect as well as discouraging overuse of addictive opioids due to APAP's potentially toxic effects. A randomized controlled trial of acute musculoskeletal pain in children found that the standard over-thecounter dose of ibuprofen gives greater pain relief than the standard dose of paracetamol. Adverse effects In recommended doses, the side effects of paracetamol are mild to non-existent. In contrast to aspirin, it is not a blood thinner (and thus may be used in patients where coagulation is a concern), and it does not cause gastric irritation. Compared to Ibuprofenwhich can have adverse effects that include diarrhea, vomiting, and abdominal painparacetamol is well tolerated with fewer side effects. Prolonged daily use increases the risk of upper gastrointestinal complications such as stomach bleeding, and may cause kidney or liver damage. Paracetamol is metabolized by the liver and is hepatotoxic; side effects may be more likely in chronic alcoholics or patients with liver damage. Until 2010 paracetamol was believed safe in pregnancy (as it does not affect the closure of the fetal ductus arteriosus as NSAIDs can). However, in a study published in October 2010 it has been linked to infertility in the adult life of the unborn. Like NSAIDs and unlike opioid analgesics, paracetamol has not been found to cause euphoria or alter mood although recent research shows some evidence that paracetamol can ease psychological pain. Unlike aspirin, it is safe for children, as paracetamol is not associated with a risk of Reye's syndrome in children with viral illnesses. Paracetamol use for fever in the first year of life was associated with an increase in the incidence of asthmatic symptoms at 67 years, and that paracetamol use, both in the first year of life and in children aged 67 years, was associated with an increased incidence of rhinoconjunctivitis and eczema. The authors acknowledged that their "findings might have been due to confounding by indication", i.e., that the association may not be causal but rather due to the disease being treated with paracetamol, and emphasized that further research is needed. Furthermore a number of editorials, comments, correspondence, and their replies have been published in The Lancet concerning the methodology and conclusions of this study. The UK regulatory body the Medicines and Healthcare products Regulatory Agency, also reviewed this research and published a number of concerns over data interpretation, and offer the following advice for healthcare professionals, parents, and care-givers: "The results of this new study do not necessitate any change to the current guidance for use in children. Paracetamol remains a safe and appropriate choice of analgesic in children. There is insufficient evidence from this research to change guidance regarding the use of antipyretics in children. " Chronic users of paracetamol may have a higher risk of developing blood cancer.

Overdose Paracetamol hepatotoxicity is, by far, the most common cause of acute liver failure in both the United States and the United Kingdom. Paracetamol overdose results in more calls to poison control centers in the US than overdose of any other pharmacological substance. Signs and symptoms of paracetamol toxicity may initially be absent or vague. Untreated overdose can lead to liver failure and death within days. Treatment is aimed at removing the paracetamol from the body and replacing glutathione. Activated charcoal can be used to decrease absorption of paracetamol if the patient presents for treatment soon after the overdose. While the antidote, acetylcysteine, (also called N-acetylcysteine or NAC) acts as a precursor for glutathione, helping the body regenerate enough to prevent damage to the liver, a liver transplant is often required if damage to the liver becomes severe. There are tablets available (brand-name in the UK Paradote) that combine paracetamol with an antidote (methionine), to protect the liver in case of an overdose. In June 2009, a U. S. Food and Drug Administration (FDA) advisory committee recommended that new restrictions should be placed on paracetamol usage in the United States to help protect people from the potential toxic effects. The maximum dosage at any given time would be decreased from 1000 mg to 650 mg, while combinations of paracetamol and narcotic analgesics would be prohibited. Committee members were particularly concerned by the fact that the present maximum dosages of paracetamol had been shown to produce alterations in hepatic function. On January 13, 2011, the FDA asked manufacturers of prescription combination products containing paracetamol to limit the amount of paracetamol to no more than 325 mg per tablet or capsule and began requiring manufacturers to update the labels of these products to warn of the potential risk for severe liver damage. Manufacturers will have three years to limit the amount of paracetamol in their prescription drug products to 325 mg per dosage unit. The FDA also is requiring manufacturers to update labels of all prescription combination paracetamol products to warn of the potential risk for severe liver injury. In November 2011, the Medicines and Healthcare products Regulatory Agency revised UK dosing of liquid paracetamol for children. Classification Paracetamol is part of the class of drugs known as "aniline analgesics"; it is the only such drug still in use today. It is not considered an NSAID because it does not exhibit significant anti-inflammatory activity (it is a weak COX inhibitor). This is despite the evidence that paracetamol and NSAIDs have some similar pharmacological activity.

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