Tacrolimus Health Dictionary

Tacrolimus: From 2 Different Sources


An IMMUNOSUPPRESSANT drug used for primary immunosuppression in recipients of kidney or liver transplants (see TRANSPLANTATION) where the natural rejection process has been resistant to conventional immunosuppression regimens such as CORTICOSTEROIDS, AZATHIOPRINE and CICLOSPORIN A. It is also used, with caution, in some severe cases of eczema (see DERMATITIS).
Health Source: Medical Dictionary
Author: Health Dictionary
n. a powerful *immunosuppressant administered to prevent rejection of transplanted organs. Side-effects include gastrointestinal disturbances, tremor, headache, and liver and kidney impairment; it may have adverse effects on the heart. It is also used for the treatment for atopic *eczema.
Health Source: Oxford | Concise Colour Medical Dictionary
Author: Jonathan Law, Elizabeth Martin

Grapefruit

(Ugli fruit)

Nutritional Profile Energy value (calories per serving): Low Protein: Low Fat: Low Saturated fat: Low Cholesterol: None Carbohydrates: High Fiber: Moderate Sodium: Low Major vitamin contribution: Vitamin A, vitamin C Major mineral contribution: Potassium

About the Nutrients in This Food Grapefruit and ugli fruit (a cross between the grapefruit and the tangerine) have moderate amounts of dietary fiber and, like all citrus fruits, are most prized for their vitamin C. Pink or red grapefruits have moderate amounts of vitamin A. One-half medium (four-inch diameter) pink grapefruit has 1.4 g dietary fiber, 1,187 IU vitamin A (51 percent of the R DA for a woman, 40 percent of the R DA for a man), and 44 mg vitamin C (59 percent of the R DA for a woman, 49 percent of the R DA for a man). One half medium (3.75-inch diameter) white grapefruit has 1.3 g dietary fiber, 39 IU vitamin A (2 percent of the R DA for a woman, 1 percent of the R DA for a man), and 39 mg vitamin C (52 percent of the R DA for a woman, 43 percent of the R DA for a man). Pink and red grapefruits also contain lycopene, a red carotenoid (plant pigment), a strong antioxidant that appears to lower the risk of cancer of the prostate. The richest source of lycopene is cooked tom atoes.

The Most Nutritious Way to Serve This Food Fresh fruit or fresh-squeezed juice.

Buying This Food Look for: Firm fruit that is heavy for its size, which means that it will be juicy. The skin should be thin, smooth, and fine-grained. Most grapefruit have yellow skin that, depending on the variety, may be tinged with red or green. In fact, a slight greenish tint may mean that the grapefruit is high in sugar. Ugli fruit, which looks like misshapen, splotched grapefruit, is yellow with green patches and bumpy skin. Avoid: Grapefruit or ugli fruit with puff y skin or those that feel light for their size; the flesh inside is probably dry and juiceless.

Storing This Food Store grapefruit either at room temperature (for a few days) or in the refrigerator. Refrigerate grapefruit juice in a tightly closed glass bottle with very little air space at the top. As you use up the juice, transfer it to a smaller bottle, again with very little air space at the top. The aim is to prevent the juice from coming into contact with oxygen, which destroys vitamin C. (Most plastic juice bottles are oxygen-permeable.) Properly stored and protected from oxygen, fresh grapefruit juice can hold its vitamin C for several weeks.

Preparing This Food Grapefruit are most flavorful at room temperature, which liberates the aromatic molecules that give them their characteristic scent and taste. Before cutting into the grapefruit, rinse it under cool running water to flush debris off the peel. To section grapefruit, cut a slice from the top, then cut off the peel in strips—starting at the top and going down—or peel it in a spiral fashion. You can remove the bitter white membrane, but some of the vitamin C will go with it. Finally, slice the sections apart. Or you can simply cut the grapefruit in half and scoop out the sections with a curved, serrated grapefruit knife.

What Happens When You Cook This Food Broiling a half grapefruit or poaching grapefruit sections reduces the fruit’s supply of vitamin C, which is heat-sensitive.

How Other Kinds of Processing Affect This Food Commercially prepared juices. How well a commercially prepared juice retains its vitamin C depends on how it is prepared, stored, and packaged. Commercial flash-freezing preserves as much as 95 percent of the vitamin C in fresh grapefruit juices. Canned juice stored in the refrigerator may lose only 2 percent of its vitamin C in three months. Prepared, pasteurized “fresh” juices lose vitamin C because they are sold in plastic bottles or waxed-paper cartons that let oxygen in. Commercially prepared juices are pasteurized to stop the natural enzyme action that would otherwise turn sugars to alcohols. Pasteurization also protects juices from potentially harmful bacterial and mold contamination. Following several deaths attributed to unpas- teurized apple juices containing E. coli O157:H7, the FDA ruled that all fruit and vegetable juices must carry a warning label telling you whether the juice has been pasteurized. Around the year 2000, all juices must be processed to remove or inactivate harmful bacteria.

Medical Uses and/or Benefits Antiscorbutic. All citrus fruits are superb sources of vitamin C, the vitamin that prevents or cures scurvy, the vitamin C-deficiency disease. Increased absorption of supplemental or dietary iron. If you eat foods rich in vitamin C along with iron supplements or foods rich in iron, the vitamin C will enhance your body’s ability to absorb the iron. Wound healing. Your body needs vitamin C in order to convert the amino acid proline into hydroxyproline, an essential ingredient in collagen, the protein needed to form skin, ten- dons, and bones. As a result people with scurvy do not heal quickly, a condition that can be remedied with vitamin C, which cures the scurvy and speeds healing. Whether taking extra vitamin C speeds healing in healthy people remains to be proved. Possible inhibition of virus that causes chronic hepatitis C infection. In Januar y 2008, research- ers at Massachusetts General Hospital Center for Engineering in Medicine (Boston) published a report in the medical journal Hepatology detailing the effect of naringenin, a compound in grapefruit, on the behavior of hepatitis viruses in liver cells. In laborator y studies, naringenin appeared to inhibit the ability of the virus to multiply and/or pass out from the liver cells. To date, there are no studies detailing the effect of naringenin in human beings with hepatitis C.

Adverse Effects Associated with This Food Contact dermatitis. The essential oils in the peel of citrus fruits may cause skin irritation in sensitive people.

Food/Drug Interactions Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen and others. Taking aspirin or NSAIDs with acidic foods such as grapefruit may intensif y the drug’s ability to irritate your stomach and cause gastric bleeding. Antihistamines, anticoagulants, benzodiazepines (tranquilizers or sleep medications), calcium channel blockers (blood pressure medication), cyclosporine (immunosuppressant drug used in organ transplants), theophylline (asthma drug). Drinking grapefruit juice with a wide variety of drugs ranging from antihistamines to blood pressure medication appears to reduce the amount of the drug your body metabolizes and eliminates. The “grapefruit effect” was first identified among people taking the antihypertensive drugs felodipine (Plendil) and nifedip- ine (Adalat, Procardia). It is not yet known for certain exactly what the active substance in the juice is. One possibility, however, is bergamottin, a naturally occurring chemical in grapefruit juice known to inactivate cytochrome P450 3A4, a digestive enzyme needed to convert many drugs to water-soluble substances you can flush out of your body. Without an effective supply of cytochrome P450 3A4, the amount of a drug circulating in your body may rise to dangerous levels. Reported side effects include lower blood pressure, increased heart rate, headache, flushing, and lightheadedness. Some Drugs Known to Interact with Grapefruit Juice* Drug Class  Generic (Brand name) Antianxiety drug  Diazepam ( Valium) Antiarrhythmics  Amiodarone (Cordarone) Blood-pressure drugs  Felodipine (Plendil), nicardipine (Cardene), nimodipine (Nimotop), nisoldipine (Sular), verapamil ( Verelan) Cholesterol-lowering drugs  Atorvastatin (Lipitor), lovastatin (Mevacor), simvastatin (Zocor), simvastatin/ezetimibe ( Vytorin) Immune Suppressants  Cyclosporine (Neoral), tacrolimus (Prograf ) Impotence Drug  Sildenafil ( Viagra) Pain Medication Methadone (Dolophine, Methadose) * This list may grow as new research appears.... grapefruit

Immunosuppression

The term given to suppression of harmful immune responses (see IMMUNITY), the most obvious application being the prevention of organ rejection by people who receive kidney, heart or bone-marrow transplants (see TRANSPLANTATION). Immunosuppression is also used in certain diseases in a way that is non-speci?c – that is, it inhibits the entire immune system, not just harmful reactions. CORTICOSTEROIDS are the commonest dugs used in this way, as are METHOTREXATE and AZATHIOPRINE. Tacrolimus, a macrolide (see MACROLIDES) IMMUNOSUPPRESSANT, is used not only for engrafted patients but also in treating eczema (see DERMATITIS).

There has been a rapid introduction in recent years of monoclonal antibodies which prevent T-cells from proliferating. They can be recognised by the su?x ‘mab’ (standing for monoclonal antibody) and include rituximab and alemtuzumab. In?iximab, used in CROHN’S DISEASE and RHEUMATOID ARTHRITIS, inhibits tumour necrosis factor alpha.... immunosuppression

Transplantation

Transplantation of tissues or organs of the body are de?ned as an allotransplant, if from another person; an autotransplant, if from the patient him or herself – for example, a skin graft (see GRAFT; SKIN-GRAFTING); and a xenotransplant, if from an animal.

The pioneering success was achieved with transplantation of the kidney in the 1970s; this has been most successful when the transplanted kidney has come from an identical twin. Less successful have been live transplants from other blood relatives, while least successful have been transplants from other live donors and cadaver donors. The results, however, are steadily improving. Thus the one-year functional survival of kidneys transplanted from unrelated dead donors has risen from around 50 per cent to over 80 per cent, and survival rates of 80 per cent after three years are not uncommon. For a well-matched transplant from a live related donor, the survival rate after ?ve years is around 90 per cent. And, of course, if a transplanted kidney fails to function, the patient can always be switched on to some form of DIALYSIS. In the United Kingdom the supply of cadaveric (dead) kidneys for transplantation is only about half that necessary to meet the demand.

Other organs that have been transplanted with increasing success are the heart, the lungs, the liver, bone marrow, and the cornea of the eye. Heart, lung, liver and pancreas transplantations are now carried out in specialist centres. It is estimated that in the United Kingdom, approximately 200 patients a year between the ages of 15 and 55 would bene?t from a liver transplant if an adequate number of donors were available. More than 100 liver transplants are carried out annually in the United Kingdom and one-year-survival rates of up to 80 per cent have been achieved.

The major outstanding problem is how to prevent the recipient’s body from rejecting and destroying the transplanted organ. Such rejection is part of the normal protective mechanism of the body (see IMMUNITY). Good progress has been made in techniques of tissue-typing and immunosuppression to overcome the problem. Drugs are now available that can suppress the immune reactions of the recipient, which are responsible for the rejection of the transplanted organ. Notable among these are CICLOSPORIN A, which revolutionised the success rate, and TACROLIMUS, a macrolide immunosuppressant.

Another promising development is antilymphocytic serum (ALS), which reduces the activity of the lymphocytes (see LYMPHOCYTE) cells which play an important part in maintaining the integrity of the body against foreign bodies.

Donor cards are now available in all general practitioners’ surgeries and pharmacies but, of the millions of cards distributed since 1972, too few have been used. The reasons are complex but include the reluctance of the public and doctors to consider organ donation; poor organisation for recovery of donor kidneys; and worries about the diagnosis of death. A code of practice for procedures relating to the removal of organs for transplantation was produced in 1978, and this code has been revised in the light of further views expressed by the Conference of Medical Royal Colleges and Faculties of the United Kingdom on the Diagnosis of Brain Death. Under the Human Tissue Act 1961, only the person lawfully in possession of the body or his or her designate can authorise the removal of organs from a body. This authorisation may be given orally.

Patients who may become suitable donors after death are those who have suffered severe and irreversible brain damage – since such patients will be dependent upon arti?cial ventilation. Patients with malignant disease or systemic infection, and patients with renal disease, including chronic hypertension, are unsuitable.

If a patient carries a signed donor card or has otherwise recorded his or her wishes, there is no legal requirement to establish lack of objection on the part of relatives – although it is good practice to take account of the views of close relatives. If a relative objects, despite the known request by the patient, sta? will need to judge, according to the circumstances of the case, whether it is wise to proceed with organ removal. If a patient who has died is not known to have requested that his or her organs be removed for transplantation after death, the designated person may only authorise the removal if, having made such reasonable enquiry as may be practical, he or she has no reason to believe (a) that the deceased had expressed an objection to his or her body being so dealt with after death, or (b) that the surviving spouse or any surviving relative of the deceased objects to the body being so dealt with. Sta? will need to decide who is best quali?ed to approach the relatives. This should be someone with appropriate experience who is aware how much the relative already knows about the patient’s condition. Relatives should not normally be approached before death has occurred, but sometimes a relative approaches the hospital sta? and suggests some time in advance that the patient’s organs might be used for transplantation after death. The sta? of hospitals and organ exchange organisations must respect the wishes of the donor, the recipient and their families with respect to anonymity.

Relatives who enquire should be told that some post-mortem treatment of the donor’s body will be necessary if the organs are to be removed in good condition. It is ethical (see ETHICS) to maintain arti?cial ventilation and heartbeat until removal of organs has been completed. This is essential in the case of heart and liver transplants, and many doctors think it is desirable when removing kidneys. O?cial criteria have been issued in Britain to recognise when BRAIN-STEM DEATH has occurred. This is an important protection for patients and relatives when someone with a terminal condition

– usually as a result of an accident – is considered as a possible organ donor.... transplantation

Calcineurin Inhibitors

drugs that act by inhibiting the calcium-dependent protein *phosphatase calcineurin, an enzyme that initiates a sequence of events that bring about activation of T *lymphocytes. The group includes *ciclosporin and *tacrolimus, which are major maintenance immunosuppressants used in transplantation. Topical calcineurin inhibitors (e.g. tacrolimus, pimecrolimus [Elidel]) are used in the treatment of eczema when topical steroids have failed or are contraindicated. Stinging is a common transient side-effect, and reactivation of infections may occur.... calcineurin inhibitors



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