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Cefotan

Cefotetan is an injectable antibiotic of the cephamycin type for prophylaxis and treatment of bacterial infections. It is a second generation cephalosporin that has some anaerobe converage.

Cefotetan was developed by Yamanouchi. It is marketed outside Japan by AstraZeneca with the brand names Apatef and Cefotan.

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Heparin
From Gale Encyclopedia of Cancer, by MSc. Crystal Heather Kaczkowski

Definition

Heparin is a drug that helps prevent blood clots from forming and belongs to the family of drugs called anticoagulants (blood thinners), although it does not actually thin the blood. It is sold in the U.S. under the brand names of Calciparine, Liquaemin, Calciparine, Hepalean, and Heparin Leo, and Calcilean in Canada.

Purpose

Heparin is used to decrease the clotting ability of the blood and to help prevent harmful clots from forming in the blood vessels. Heparin will not dissolve blood clots that have already formed, but it may prevent the clots from becoming larger and causing more serious problems. Heparin possesses several antithrombotic mechanisms. It is often used as a treatment for certain blood vessel, heart, and lung conditions and is also used to prevent blood clotting during open-heart surgery, bypass surgery, and dialysis. Heparin is used in low doses to prevent the formation of blood clots in certain patients, especially those who must have certain types of surgery or who must remain in bed for a long time. It is also used for the long-term treatment of thromboembolic disease, a common side effect of cancer.

One of the most common hematological complications is disordered coagulation. Approximately 15% of all cancer patients are affected by thromboembolic disease, which is the second leading cause of death for cancer patients. However, thromboembolic disease may represent only one of many complications in end-stage patients. Thromboembolic disease includes superficial and deep venous thrombosis, pulmonary emboli, thrombosis of venous access devices, arterial thrombosis, and embolism. The cancer itself or cancer treatments may induce coagulation. For example, chemotherapy can increase the risk of thromboembolic disease. An increased risk for arterial thrombosis has been observed with chemotherapy treatment.

Cancer and its treatment can affect all three causes of thromboembolic disease, including the alteration of blood flow, damage to endothelial cells (the cells in blood vessels), and enhancing procoagulants (causing the blood to clot). Cancer can affect blood flow by mechanically affecting blood vessels close to a tumor. In addition, tumors cause angiogenesis, which may create complexes of blood vessels that have a disordered appearance and flow (varying in magnitude and direction). Chemotherapy or tumors may directly damage endothelial cells. Procoagulants may be secreted into the blood stream by cancer cells or can be increased on the surface of cancer cells.

Description

Heparin is the most common anticoagulant used and the generic name product may be available in the U.S. and Canada.

Mechanisms of action:

Heparin increases the release of specific proteins, like tissue plasminogen activator and tissue factor pathway inhibitor (TFPI), into the blood in order to inhibit blood coagulation. It can also increase the activity of these proteins. Heparin augments the activity of anti-thrombin III, a natural compound that inhibits activated clotting factors from contributing to more coagulation. Furthermore, heparin has been found to inhibit substances that may contribute to angiogenesis, including vascular endothelial growth factor, tissue factor, and platelet-activating factor.

Whether anticoagulants like heparin may also improve cancer survival rates independent of their effect on thromboembolism has been investigated. In fact, experimental and clinical data have demonstrated that heparin is an effective compound in preventing metastases. Many investigators have shown that heparin inhibits tumor metastasis in experimental animals; a few clinical trials also suggest a positive effect in humans with cancer.

Recommended dosage

Heparin is available only with a doctor's prescription, in parenteral and injection (U.S. and Canada) dosage forms. A doctor will need to prescribe a specific dose for an individual's based on the type of heparin, as well as the patient's medical condition and body weight.

Dosing schedule

Heparin should be taken under the doctor's direction and at the same time every day. If a dose is missed, take it as soon as possible. However, if a dose is missed until the following day, patients should not double-dose, but just take the usual daily dose. Double-dosing may cause bleeding.

Precautions

Some medications should not be combined. Over-the-counter medicines, vitamins, and herbal products may cause interactions when combined with heparin, so the patient should check with the doctor monitoring the heparin medication before taking any new medication, even when prescribed by another doctor.

Patients who are pregnant, breastfeeding, have given birth recently, or using an IUD for birth control should consult their doctor. The doctor should also be notified if radiation treatments, surgery, or a fall or other injury has recently occurred.

The presence of other medical problems may affect the use of heparin. Patients should be sure to tell their doctor about any other medical problems, in particular:

  • allergies or asthma (or history of)

  • blood disease or bleeding problems

  • colitis or stomach ulcer (or history of)

  • diabetes mellitus

  • high blood pressure (hypertension)

  • kidney disease

  • liver disease

  • tuberculosis (active)

Side effects

The doctor should be contacted immediately if any of these side effects are present:

  • wheezing or trouble breathing

  • skin rash, itching, or hives

  • red or "coffee ground" vomit

  • unexplained nosebleeds

  • swelling in the face, lips, or tongue

  • blood in urine or stools

  • black tarry stools

Interactions

Using any of the following medicines together with heparin may increase the risk of bleeding. Again, candidates for heparin should alert their physicians if they are taking any of these medications:

  • aspirin

  • persantine

  • carbenicillin by injection (e.g., Geopen)

  • cefamandole (e.g., Mandol)

  • cefoperazone (e.g., Cefobid)

  • cefotetan (e.g., Cefotan)

  • dipyridamole (e.g., Persantine)

  • divalproex (e.g., Depakote)

  • medicine for inflammation or pain (Motrin, Aleve), except narcotics

  • medicine for overactive thyroid

  • pentoxifylline (e.g., Trental)

  • plicamycin (e.g., Mithracin)

  • probenecid (e.g., Benemid)

  • sulfinpyrazone (e.g., Anturane)

  • ticarcillin (e.g., Ticar)

  • valproic acid (e.g., Depakene)

  • medicines via intramuscular injection

KEY TERMS

Angiogenesis
The formation of new blood vessels that occurs naturally under certain circumstances, for example, in the healing of a cut.

Anticoagulant
Anticoagulants are nonhabit-forming medications that prevent the formation of new blood clots and keep existing blood clots from growing larger.

Blood clot
A clump of blood that forms in or around a vessel as a result of coagulation. The formation of blood clots when the body has been cut is essential because without blood clots to cease the bleeding, a person would bleed to death from a relatively small wound.

Coagulation
The blood's natural tendency to clump and stick.

Embolism
An embolism occurs when a clump of material such as a broken-off piece of plaque, a blood clot, or air travels through the bloodstream and becomes lodged in a blood vessel.

Endothelial cells
The cells lining the inside of blood vessels.

Parenteral
Medications administered through intravenous, subcutaneous, or intramuscular injection.

Procoagulants
Inducing the blood to clot.

Thromboembolism
Another word for embolism (see embolism).

Thrombosis
The formation of a blood clot in an artery or vein that may be accompanied by inflammation. If untreated in arteries, thrombosis can lead to death of the nearby tissue.

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