Pharmacy

AIDS

2007-09-30T14:00:00.000-07:00

Acquired immune deficiency syndrome or acquired immunodeficiency syndrome (AIDS or Aids) is a collection of symptoms and infections resulting from the specific damage to the immune system caused by the human immunodeficiency virus (HIV) in humans,^[1] and similar viruses in other species (SIV, FIV, etc.). The late stage of the condition leaves individuals susceptible to opportunistic infections and tumors. Although treatments for AIDS and HIV exist to slow the virus' progression, there is no known cure. HIV, et al., are transmitted through direct contact of a mucous membrane or the bloodstream with a bodily fluid containing HIV, such as blood, semen, vaginal fluid, preseminal fluid, and breast milk.^[2]^[3] This transmission can come in the form of anal, vaginal or oral sex, blood transfusion, contaminated hypodermic needles, exchange between mother and baby during pregnancy, childbirth, or breastfeeding, or other exposure to one of the above bodily fluids.

HIV test

Many people are unaware that they are infected with HIV.^[24] Less than 1% of the sexually active urban population in Africa has been tested, and this proportion is even lower in rural populations. Furthermore, only 0.5% of pregnant women attending urban health facilities are counseled, tested or receive their test results. Again, this proportion is even lower in rural health facilities.^[24] Therefore, donor blood and blood products used in medicine and medical research are screened for HIV. Typical HIV tests, including the HIV enzyme immunoassay and the Western blot assay, detect HIV antibodies in serum, plasma, oral fluid, dried blood spot or urine of patients. However, the window period (the time between initial infection and the development of detectable antibodies against the infection) can vary. This is why it can take 3–6 months to seroconvert and test positive. Commercially available tests to detect other HIV antigens, HIV-RNA, and HIV-DNA in order to detect HIV infection prior to the development of detectable antibodies are available. For the diagnosis of HIV infection these assays are not specifically approved, but are nonetheless routinely used in developed countries.

Treatment

See also HIV Treatment and Antiretroviral drug.

There is currently no vaccine or cure for HIV or AIDS. The only known methods of prevention are based on avoiding exposure to the virus or, failing that, an antiretroviral treatment directly after a highly significant exposure, called post-exposure prophylaxis (PEP).^[75] PEP has a very demanding four week schedule of dosage. It also has very unpleasant side effects including diarrhea, malaise, nausea and fatigue.^[82]

The chemical structure of Abacavir

Current treatment for HIV infection consists of highly active antiretroviral therapy, or HAART.^[83] This has been highly beneficial to many HIV-infected individuals since its introduction in 1996 when the protease inhibitor-based HAART initially became available.^[6] Current optimal HAART options consist of combinations (or "cocktails") consisting of at least three drugs belonging to at least two types, or "classes," of anti-retroviral agents. Typical regimens consist of two nucleoside analogue reverse transcriptase inhibitors (NARTIs or NRTIs) plus either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRTI). Because HIV disease progression in children is more rapid than in adults, and laboratory parameters are less predictive of risk for disease progression, particularly for young infants, treatment recommendations are more aggressive for children than for adults.^[84] In developed countries where HAART is available, doctors assess the viral load, rapidity in CD4 decline, and patient readiness while deciding when to recommend initiating treatment.^[85]

HAART allows the stabilization of the patient’s symptoms and viremia, but it neither cures the patient of HIV, nor alleviates the symptoms, and high levels of HIV-1, often HAART resistant, return once treatment is stopped.^[86]^[87] Moreover, it would take more than the lifetime of an individual to be cleared of HIV infection using HAART.^[88] Despite this, many HIV-infected individuals have experienced remarkable improvements in their general health and quality of life, which has led to the plummeting of HIV-associated morbidity and mortality.^[89]^[90]^[91] In the absence of HAART, progression from HIV infection to AIDS occurs at a median of between nine to ten years and the median survival time after developing AIDS is only 9.2 months.^[7] HAART is thought to increase survival time by between 4 and 12 years.^[92]^[93] This average reflects the fact that for some patients — and in many clinical cohorts this may be more than fifty percent of patients — HAART achieves far less than optimal results. This is due to a variety of reasons such as medication intolerance/side effects, prior ineffective antiretroviral therapy and infection with a drug-resistant strain of HIV. However, non-adherence and non-persistence with antiretroviral therapy is the major reason most individuals fail to get any benefit from and develop resistance to HAART.^[94] The reasons for non-adherence and non-persistence with HAART are varied and overlapping. Major psychosocial issues, such as poor access to medical care, inadequate social supports, psychiatric disease and drug abuse contribute to non-adherence. The complexity of these HAART regimens, whether due to pill number, dosing frequency, meal restrictions or other issues along with side effects that create intentional non-adherence also has a weighty impact.^[95]^[96]^[97] The side effects include lipodystrophy, dyslipidaemia, insulin resistance, an increase in cardiovascular risks and birth defects.^[98]^[99]

Daily multivitamin and mineral supplements have been found to reduce HIV disease progression among men and women. This could become an important low-cost intervention provided during early HIV disease to prolong the time before antiretroviral therapy is required.^[100] Some individual nutrients have also been tried.^[101]^[102] Anti-retroviral drugs are expensive, and the majority of the world's infected individuals do not have access to medications and treatments for HIV and AIDS.^[103] It has been postulated that only a vaccine can halt the pandemic because a vaccine would possibly cost less, thus being affordable for developing countries, and would not require daily treatments.^[103] However, after over 20 years of research, HIV-1 remains a difficult target for a vaccine.^[103]

Research to improve current treatments includes decreasing side effects of current drugs, further simplifying drug regimens to improve adherence, and determining the best sequence of regimens to manage drug resistance. A number of studies have shown that measures to prevent opportunistic infections can be beneficial when treating patients with HIV infection or AIDS. Vaccination against hepatitis A and B is advised for patients who are not infected with these viruses and are at risk of becoming infected.^[104] Patients with substantial immunosuppression are also advised to receive prophylactic therapy for Pneumocystis jiroveci pneumonia (PCP), and many patients may benefit from prophylactic therapy for toxoplasmosis and Cryptococcus meningitis as well.^[82]

Various forms of alternative medicine have been used to treat symptoms or alter the course of the disease.^[105] In the first decade of the epidemic when no useful conventional treatment was available, a large number of people with AIDS experimented with alternative therapies. The definition of "alternative therapies" in AIDS has changed since that time. Then, the phrase often referred to community-driven treatments, untested by government or pharmaceutical company research, that some hoped would directly suppress the virus or stimulate immunity against it. Examples of alternative medicine that people hoped would improve their symptoms or their quality of life include massage, stress management, herbal and flower remedies such as boxwood,^[106]^[107] and acupuncture;^[105] when used with conventional treatment, many now refer to these as "complementary" approaches. Despite the widespread use of complementary and alternative medicine by people living with HIV/AIDS, the effectiveness of these therapies has not been established.

Peritonial mesothelioma cancer

2007-09-28T14:47:00.000-07:00

Asbestosis cancer has impact on the tummy, the chest cavity, including the locality ringing the heart. Malignant mesothelioma is of a pretty uncommon nature, as well as hence super hard to correctly diagnose including handle. The definitely most common cause of its occurrence is conveniently exposure to asbestos, a material formerly available in many environments.

Mesothelioma will be deadly whether it is of the peritoneal, pleural or of pericardial types. There are three chief types of mesothelioma cancer - the epithelioid, sarcomatoid including mixed/biphasic. The commonest kind is Epithelioid and it can affect around more than half of all mesothelioma patients. Epithelioid patients have better chances of pulling through as compared to other malignant sorts. It will affect the epithelial layer of the organs. Sarcomatoid will lead to a tremendously more serious affliction as it affects the secondary tissues in the body such as cartilage, muscles, bone including fat. Mixed/biphasic is having each of the kinds of the carcinoma at once and is definitely common in occurence. Note that Peritonial mesothelioma cancer is the subject matter at hand.

All the people who have been around asbestos a long time are at a quite high risk for getting malignant mesothelioma. Small exposures to this carcinoma-causing building material can also result in malignant mesothelioma. But mesothelioma cancer is able to also remain latent for just about thirty - forty years as has been indicated by several people who have been previously exposed to asbestos now show symptoms. Please don't forget that men are typically affected more, because of the common presence of asbestos in industries where men usually worked.

Each form of mesothelioma shows some symptoms including respiratory distress, a lasting cough, including pneumonia. Yet these symptoms may easily be mistaken for less serious ailments including what is even more alarming is that many patients do not show any signs at all. Moreover the first symptoms of mesothelioma cancer may take about a decade to forty years following the initial exposure and this is what makes it super hard to correctly diagnose. The peak in mesothelioma cases is expected to be reached as much as five years from now as predicted from the rapid growth of industrialization.

further Peritonial mesothelioma cancer

Provides lung cancer information mesothelioma facts about and cancer Talks about what lung cancer is, cancer cells, carcinogens that can cause cancers like smoking and MESOTHELIOMA. Mesothelioma Pleural / Peritonial. Pleural also cancer is mesothelioma known as cancer of the lung. The common most place for mesothelioma cancer to develop is in the pleural Most mesothelioma cases develop in the pleural mesothelium or lung lining.

From Update. Notes Mesothelioma/Asbestos New Zealand Peritonial Mesothelioma, a Search surgery Help Auckland, New Zealand Before this diagnosis she underwent for to remove the cancer from her omentum as. MESOTHELIOMA ASBESTOS CANCER, ASBESTOSIS MESOTHELEOMA, MALIGNANT. Malignant peritoneal pleural mesothelioma asbestos cancer and treatment like malignant mesothelioma, pleural mesothelioma, peritonial mesothelioma.

Source : http://www.mesothelioma-asbestosis-cancer.info/Peritonial-mesothelioma-cancer.php

2007-09-26T06:21:00.000-07:00

LASIK is the acronym for Laser-Assisted in Situ Keratomileusis, a type of refractive laser eye surgery performed by ophthalmologists for correcting myopia, hyperopia, and astigmatism.^[1] The procedure is generally preferred to photorefractive keratectomy, PRK, (also called ASA, Advanced Surface Ablation) because it requires less time for the patient's recovery, and the patient feels less pain, overall; however, there are instances where PRK/ASA is medically indicated as a better alternative to LASIK. Many patients choose LASIK as an alternative to wearing corrective eyeglasses or contact lenses.

Procedure

There are several necessary preparations in the preoperative period. The operation itself is made by creating a thin flap on the eye, folding it to enable remodeling of the tissue underneath with laser. The flap is repositioned and the eye is left to heal in the postoperative period.

Preoperative

Patients wearing soft contact lenses typically are instructed to stop wearing them approximately 10 to 15 days before surgery. One industry body recommends that patients wearing hard contact lenses should stop wearing them for a minimum of six weeks plus another six weeks for every three years the hard contacts had been worn. [3] Before the surgery, the patient's corneas are examined with a pachymeter to determine their thickness, and with a topographer to measure their surface contour. Using low-power lasers, a topographer creates a topographic map of the cornea. This process also detects astigmatism and other irregularities in the shape of the cornea. Using this information, the surgeon calculates the amount and locations of corneal tissue to be removed during the operation. The patient typically is prescribed an antibiotic to start taking beforehand, to minimize the risk of infection after the procedure.

Operation

The operation is performed with the patient awake and mobile; however, the patient typically is given a mild sedative (such as Valium) and anesthetic eye drops.

LASIK is performed in two steps. The first step is to create a flap of corneal tissue. The second step is remodeling of the cornea underneath the flap with laser. Finally, the flap is repositioned.

Flap creation

A corneal suction ring is applied to the eye, holding the eye in place. This step in the procedure can sometimes cause small blood vessels to burst, resulting in bleeding or subconjunctival hemorrhage into the white (sclera) of the eye, a harmless side effect that resolves within several weeks. Increased suction typically causes a transient dimming of vision in the treated eye. Once the eye is immobilized, the flap is created. This process is achieved with a mechanical microkeratome using a metal blade, or a femtosecond laser microkeratome (procedure known as IntraLASIK) that creates a series of tiny closely arranged bubbles within the cornea.[4] A hinge is left at one end of this flap. The flap is folded back, revealing the stroma, the middle section of the cornea. The process of lifting and folding back the flap can be uncomfortable.

Laser remodeling

The second step of the procedure is to use an excimer laser (193 nm) to remodel the corneal stroma. The laser vaporizes tissue in a finely controlled manner without damaging adjacent stroma. No burning with heat or actual cutting is required to ablate the tissue. The layers of tissue removed are tens of micrometers thick. Performing the laser ablation in the deeper corneal stroma typically provides for more rapid visual recovery and less pain, than the earlier technique photorefractive keratectomy (PRK).

During the second step, the patient's vision will become very blurry once the flap is lifted. He/she will be able to see only white light surrounding the orange light of the laser. This can be disorienting.

Currently manufactured excimer lasers use an eye tracking system that follows the patient's eye position up to 4,000 times per second, redirecting laser pulses for precise placement within the treatment zone. The energy of each pulse is usually in the milliwatt range [5] Typically, each pulse is on the order of 10–20 nanoseconds.

Reposition of flap

After the laser has reshaped the stromal layer, the LASIK flap is carefully repositioned over the treatment area by the surgeon, and checked for the presence of air bubbles, debris, and proper fit on the eye. The flap remains in position by natural adhesion until healing is completed.

Postoperative

Patients are usually given a course of antibiotic and anti-inflammatory eye drops. These are discontinued in the weeks following surgery. Patients are also given a darkened pair of goggles to protect their eyes from bright lights and protective shields to prevent rubbing of the eyes when asleep.

Complications

A subconjunctival hemorrhage is a common and minor post-LASIK complicationThe incidence of refractive surgery patients having unresolved complications six months after surgery has been estimated from 3%^[4] to 6%.^[5] The following are some of the more frequently reported complications of LASIK^[6][6]:

Surgery induced dry eyes
Overcorrection^[7] or undercorrection
Visual acuity fluctuation
Halos^[8] or starbursts^[9] around light sources at night
Light sensitivity
Ghost images^[10] or double vision
Wrinkles in flap (striae)^[11]
Decentered ablation
Debris or growth under flap
Thin or buttonhole flap ^[12]
Induced astigmatism
Corneal Ectasia
Epithelium erosion
Posterior vitreous detachment^[13]
Macular hole^[14]

Complications due to LASIK have been classified as those that occur due to preoperative, intraoperative, early postoperative, or late postoperative sources:^[15]

Source :
www.lasikindia.com/
www.allaboutvision.com/visionsurgery
en.wikipedia.org/wiki/LASIK
www.fda.gov/cdrh/lasik/

Botox

2007-09-26T06:17:00.000-07:00

Botulinum toxin is a neurotoxin protein produced by the bacterium Clostridium botulinum. It is one of the most poisonous naturally occurring substances in the world, and it is the most toxic protein.^[1] Though it is highly toxic, it is used in minute doses both to treat painful muscle spasms, and as a cosmetic treatment in some parts of the world. It is sold commercially under the brand names Botox and Dysport for this purpose. The terms Botox and Dysport are trade names and are not used generically to describe the neurotoxins produced by the clostridia species.

Medical uses

Cosmetically desirable effects of Botox were quickly discovered thereafter when the frown lines between the eyebrows were observed to soften following treatment for eye muscle disorders, leading to clinical trials and subsequent FDA approval for cosmetic use in April 2002. As of 2006, Botox injection is the most common cosmetic operation in the United States.

Besides its cosmetic application, Botox is used in the treatment of

migraine headaches

cervical dystonia (a neuromuscular disorder involving the head and neck)^[2]

blepharospasm (involuntary contraction of the eye muscles)^[3]

severe primary axillary hyperhidrosis (excessive sweating)^[4]

achalasia (failure of the lower esophageal sphincter to relax)

Other uses of botulinum toxin type A that are widely known but not specifically approved by FDA include treatment of:

involuntary microexpression facial triggers (concealing a lie)^{[citation needed]}

pediatric incontinence^[5], incontinence due to overactive bladder,^[6] and incontinence due to neurogenic bladder.^[7]

anal fissure^[8]

spastic disorders associated with injury or disease of the central nervous system including trauma, stroke, multiple sclerosis, Parkinson's disease, or cerebral palsy

focal dystonias affecting the limbs, face, jaw, or vocal cords

TMJ pain disorders

diabetic neuropathy

wound healing

excessive salivation

In the Journal of Dermatologic Surgery, Eric Finzi claims to have treated clinically depressed patients with botox. On Good Morning America, he claimed that by taking away the ability to frown, he was somehow taking away the ability to feel depressed.^[9]

Treatment and prevention of chronic headache^[10] and chronic musculoskeletal pain^[11] are emerging uses for botulinum toxin type A. In addition, there is evidence that Botox may aid in weight loss by increasing the gastric emptying time.^[12]

Biochemical mechanism of toxicity

Target molecules of botulinum (BoNT) and tetanus (TeNT) toxins inside the axon terminal.[1]

The heavy chain of the toxin is particularly important for targeting the toxin to specific types of axon terminals. The toxin must get inside the axon terminals in order to cause paralysis. Following the attachment of the toxin heavy chain to proteins on the surface of axon terminals, the toxin can be taken into neurons by endocytosis. The light chain is able to leave endocytotic vesicles and reach the cytoplasm. The light chain of the toxin has protease activity. The type A toxin proteolytically degrades the SNAP-25 protein, a type of SNARE protein. The SNAP-25 protein is required for the release of neurotransmitters from the axon endings.^[18] Botulinum toxin specifically cleaves these SNAREs, and so prevents neuro-secretory vesicles from docking/fusing with the nerve synapse plasma membrane and releasing their neurotransmitters.

Though it affects the nervous system, common nerve agent treatments (namely the injection of atropine and 2-pam-chloride) will increase mortality by enhancing botulin toxin's mechanism of toxicity. Attacks involving botulinum toxin are distinguishable from those involving nerve agent in that NBC detection equipment (such as M-8 paper or the ICAM) will not indicate a "positive" when a sample of the agent is tested. Furthermore, botulism symptoms develop relatively slowly, over several days compared to nerve agent effects, which can be instantaneous.

Source :
en.wikipedia.org
www.botox.co.in/myths.htm

Mesothelioma(Cancer)

2007-09-20T09:26:00.000-07:00

Mesothelioma is a form of cancer that is almost always caused by previous exposure to asbestos.Asbestos is a naturally occurring mineral, distinguished from other minerals by the fact that its crystals form long, thin fibers. In this disease, malignant cells develop in the mesothelium, a protective lining that covers most of the body's internal organs. Its most common site is the pleura (outer lining of the lungs and chest cavity), but it may also occur in the peritoneum (the lining of the abdominal cavity) or the pericardium (a sac that surrounds the heart).

Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles, or have been exposed to asbestos dust and fibre in other ways, such as by washing the clothes of a family member who worked with asbestos, or by home renovation using asbestos cement products. Unlike lung cancer, there is no association between mesothelioma and smoking

Risk factors

Working with asbestos is the major risk factor for mesothelioma. A history of asbestos exposure exists in almost all cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos. In rare cases, mesothelioma has also been associated with irradiation, intrapleural thorium dioxide (Thorotrast), and inhalation of other fibrous silicates, such as erionite.

Asbestos is the name of a group of minerals that occur naturally as masses of strong, flexible fibers that can be separated into thin threads and woven. Asbestos has been widely used in many industrial products, including cement, brake linings, roof shingles, flooring products, textiles, and insulation. If tiny asbestos particles float in the air, especially during the manufacturing process, they may be inhaled or swallowed, and can cause serious health problems. In addition to mesothelioma, exposure to asbestos increases the risk of lung cancer, asbestosis (a noncancerous, chronic lung ailment), and other cancers, such as those of the larynx and kidney.

The combination of smoking and asbestos exposure significantly increases a person's risk of developing cancer of the airways (lung cancer, bronchial carcinoma). The Kent brand of cigarettes used asbestos in its filters for the first few years of production in the 1950s and some cases of mesothelioma have resulted. Smoking modern cigarettes does not appear to increase the risk of mesothelioma.

Some studies suggest that simian virus 40 (SV40) may act as a cofactor in the development of mesothelioma

Signs and symptoms

Symptoms of mesothelioma may not appear until 20 to 50 years after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space are often symptoms of pleural mesothelioma.

Symptoms of peritoneal mesothelioma include weight loss and cachexia, abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other symptoms of peritoneal mesothelioma may include bowel obstruction, blood clotting abnormalities, anemia, and fever. If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.

These symptoms may be caused by mesothelioma or by other, less serious conditions.

Mesothelioma that affects the pleura can cause these signs and symptoms:

chest wall pain
pleural effusion, or fluid surrounding the lung
shortness of breath
fatigue or anemia
wheezing, hoarseness, or cough
blood in the sputum (fluid) coughed up

Treatment
Chemotherapy
In February 2004, the United States Food and Drug Administration approved pemetrexed (brand name Alimta) for treatment of malignant pleural mesothelioma. Pemetrexed is given in combination with cisplatin. Folic acid is also used to reduce the side-effects of pemetrexed

Currently, cisplatin as a single drug has been used as the standard drug for phase III clinical trials. None of the standard treatment options has improved survival. The most active agents are anthracycline, platinum, and alkylating agents; each produces a response rate of 10-20%.

Vogelzang et al presented the results of a phase III study of pemetrexed in combination with cisplatin versus cisplatin alone. Pemetrexed (500 mg/m²/d) and cisplatin (75 mg/m²/d) or cisplatin (75 mg/m²/d) was given on day 1. Both arms were given every 21 days. The median time to survival in the cisplatin/pemetrexed arm was 12.1 months versus 9.3 months for cisplatin alone. The response rate was 41.3% for the cisplatin/pemetrexed arm and 16.7% for the cisplatin arm. Folic acid and vitamin B-12 were given routinely to prevent the adverse effects of pemetrexed. This trial established the regimen as the standard choice for this disease.

A 1999 phase II study by Byrne et al using cisplatin (100 mg/m²) on day 1 and gemcitabine (1000 mg/m²) administered intravenously on days 1, 8, and 15 of a 28-day cycle for 6 cycles showed response rates of 47.6% (complete and partial response), 42.8% (stable disease), and 9.5% (progressive disease). The median response duration was 25 weeks, progression-free survival was 25 weeks, and the overall survival was 41 weeks. Toxicity was mainly gastroenterologic and hematologic in nature.

Several other combinations have been found to be active, including cisplatin/doxorubicin (Adriamycin)/mitomycin C, bleomycin/intrapleural hyaluronidase, cisplatin/doxorubicin (Adriamycin), carboplatin/gemcitabine, and cisplatin/vinblastine/mitomycin C. The cisplatin/gemcitabine combination has yielded the best results.

Ranpirnase (Onconase) is a novel cytotoxic ribonuclease. It is a nonmyelossuppresive agent with minimal apparent toxicity to vital organs. It binds to the cell surface and penetrates the cell's interior through the energy-dependent endocytotic process. In the cytosol, it degrades tRNA and this damage constitute a signal for apoptosis and contributes to inhibition of cell growth and proliferatio

Source :

en.wikipedia.org

Disease - Cancer

2007-09-20T09:23:00.000-07:00

Cancer is a group of diseases in which cells are aggressive (grow and divide without respect to normal limits), invasive (invade and destroy adjacent tissues), and/or metastatic (spread to other locations in the body). These three malignant properties of cancers differentiate them from benign tumors, which are self-limited in their growth and do not invade or metastasize (although some benign tumor types are capable of becoming malignant). Cancer may affect people at all ages, even fetuses, but risk for the more common varieties tends to increase with age.^[1] Cancer causes about 13% of all deaths.^[2] Apart from people, forms of cancer may affect animals and plants.

Nearly all cancers are caused by abnormalities in the genetic material of the transformed cells. These abnormalities may be due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals, or infectious agents. Other cancer-promoting genetic abnormalities may be randomly acquired through errors in DNA replication, or are inherited, and thus present in all cells from birth. Complex interactions between carcinogens and the host genome may explain why only some develop cancer after exposure to a known carcinogen. New aspects of the genetics of cancer pathogenesis, such as DNA methylation, and microRNAs are increasingly being recognized as important.

Genetic abnormalities found in cancer typically affect two general classes of genes. Cancer-promoting oncogenes are often activated in cancer cells, giving those cells new properties, such as hyperactive growth and division, protection against programmed cell death, loss of respect for normal tissue boundaries, and the ability to become established in diverse tissue environments. Tumor suppressor genes are often inactivated in cancer cells, resulting in the loss of normal functions in those cells, such as accurate DNA replication, control over the cell cycle, orientation and adhesion within tissues, and interaction with protective cells of the immune system.

Cancer is usually classified according to the tissue from which the cancerous cells originate, as well as the normal cell type they most resemble. These are location and histology, respectively. A definitive diagnosis usually requires the histologic examination of a tissue biopsy specimen by a pathologist, although the initial indication of malignancy can be symptoms or radiographic imaging abnormalities. Most cancers can be treated and some cured, depending on the specific type, location, and stage. Once diagnosed, cancer is usually treated with a combination of surgery, chemotherapy and radiotherapy. As research develops, treatments are becoming more specific for different varieties of cancer. There has been significant progress in the development of targeted therapy drugs that act specifically on detectable molecular abnormalities in certain tumors, and which minimize damage to normal cells. The prognosis of cancer patients is most influenced by the type of cancer, as well as the stage, or extent of the disease. In addition, histologic grading and the presence of specific molecular markers can also be useful in establishing prognosis, as well as in determining individual treatments.

Nomenclature

The following closely related terms may be used to designate abnormal growths:

Neoplasm: a scientific term which refers to an abnormal proliferation of genetically altered cells.
Malignant neoplasm: synonymous with cancer.
Tumor: broadly defined, can be any swelling or mass. However, the vast majority of entities referred to as 'tumors' in common usage are in fact neoplasms. Specifically, a tumor is a solid neoplasm; some neoplasms, such as cancers of the blood, are not solid.
Benign tumor: a tumor (solid neoplasm) that has self-limiting growth and does not invade other tissues nor metastasize. Usually not cancerous.
Pre-malignancy: A non-invasive neoplasm that may not form an obvious mass, but has the potential to progress to cancer if left untreated. Pre-malignant neoplasms may show distinctive microscopic changes such as dysplasia or atypia.

Cancers are classified by the type of cell that resembles the tumor and, therefore, the tissue presumed to be the origin of the tumor. Examples of general categories include:

Carcinoma: Malignant tumors derived from epithelial cells. This group represents the most common cancers, including the common forms of breast, prostate, lung and colon cancer.
Sarcoma: Malignant tumors derived from connective tissue, or mesenchymal cells.
Lymphoma and leukemia: Malignancies derived from hematopoetic (blood-forming) cells
Germ cell tumor: Tumors derived from totipotent cells. In adults most often found in the testicle and ovary; in fetuses, babies, and young children most often found on the body midline, particularly at the tip of the tailbone; in horses most often found at the poll (base of the skull).
Blastic tumor: A tumor (usually malignant) which resembles an immature or embryonic tissue. Many of these tumors are most common in children.

Malignant tumors are usually named using the Latin or Greek root of the organ of origin as a prefix and the above category name as the suffix. For instance, a malignant tumor of the liver is called hepatocarcinoma; a malignant tumor of the fat cells is called liposarcoma. For common cancers, the English organ name is used. For instance, the most common type of breast cancer is called ductal carcinoma of the breast or mammary ductal carcinoma. Here, the adjective ductal refers to the appearance of the cancer under the microscope, resembling normal breast ducts.

Signs and symptoms

Roughly, cancer symptoms can be divided into three groups:

Local symptoms: unusual lumps or swelling (tumor), hemorrhage (bleeding), pain and/or ulceration. Compression of surrounding tissues may cause symptoms such as jaundice.
Symptoms of metastasis (spreading): enlarged lymph nodes, cough and hemoptysis, hepatomegaly (enlarged liver), bone pain, fracture of affected bones and neurological symptoms. Although advanced cancer may cause pain, it is often not the first symptom.
Systemic symptoms: weight loss, poor appetite and cachexia (wasting), excessive sweating (night sweats), anemia and specific paraneoplastic phenomena, i.e. specific conditions that are due to an active cancer, such as thrombosis or hormonal changes.

Every symptom in the above list can be caused by a variety of conditions (a list of which is referred to as the differential diagnosis). Cancer may be a common or uncommon cause of each item.

Diagnosis

Most cancers are initially recognized either because signs or symptoms appear or through screening. Neither of these lead to a definitive diagnosis, which usually requires the opinion of a pathologist.

Investigation

Chest x-ray showing lung cancer in the left lung.

People with suspected cancer are investigated with medical tests. These commonly include blood tests, X-rays, CT scans and endoscopy.

Biopsy

A cancer may be suspected for a variety of reasons, but the definitive diagnosis of most malignancies must be confirmed by histological examination of the cancerous cells by a pathologist. Tissue can be obtained from a biopsy or surgery. Many biopsies (such as those of the skin, breast or liver) can be done in a doctor's office. Biopsies of other organs are performed under anesthesia and require surgery in an operating room.

The tissue diagnosis indicates the type of cell that is proliferating, its histological grade and other features of the tumor. Together, this information is useful to evaluate the prognosis of this patient and choose the best treatment. Cytogenetics and immunohistochemistry may provide information about future behavior of the cancer (prognosis) and best treatment.

Chemotherapy

Main article: Chemotherapy

Chemotherapy is the treatment of cancer with drugs ("anticancer drugs") that can destroy cancer cells. In current usage, the term "chemotherapy" usually refers to cytotoxic drugs which affect rapidly dividing cells in general, in contrast with targeted therapy (see below). Chemotherapy drugs interfere with cell division in various possible ways, e.g. with the duplication of DNA or the separation of newly formed chromosomes. Most forms of chemotherapy target all rapidly dividing cells and are not specific for cancer cells, although some degree of specificity may come from the inability of many cancer cells to repair DNA damage, while normal cells generally can. Hence, chemotherapy has the potential to harm healthy tissue, especially those tissues that have a high replacement rate (e.g. intestinal lining). These cells usually repair themselves after chemotherapy.

Because some drugs work better together than alone, two or more drugs are often given at the same time. This is called "combination chemotherapy"; most chemotherapy regimens are given in a combination.

The treatment of some leukaemias and lymphomas requires the use of high-dose chemotherapy, and total body irradiation (TBI). This treatment ablates the bone marrow, and hence the body's ability to recover and repopulate the blood. For this reason, bone marrow, or peripheral blood stem cell harvesting is carried out before the ablative part of the therapy, to enable "rescue" after the treatment has been given. This is known as autologous stem cell transplantation. Alternatively, hematopoietic stem cells may be transplanted from a matched unrelated donor (MUD).

Source :

en.wikipedia.org

Pharmacodynamics ( What Drug Does to Body)

2007-09-19T14:26:00.000-07:00

Pharmacodynamics

From Wikipedia, the free encyclopedia

Pharmacodynamics is the study of the biochemical and physiological effects of drugs and the mechanisms of drug action and the relationship between drug concentration and effect. One dominant example being drug-receptor interactions as modeled by:

where L=ligand (drug), R=receptor (attachment site), reaction dynamics that can be studied mathematically through tools such as free energy maps. Pharmacodynamics is often summarized as the study of what a drug does to the body, whereas pharmacokinetics is the study of what the body does to a drug. Pharmacodynamics is sometimes abbreviated as "PD", and when referred to in conjunction with pharmacokinetics can be referred to as "PKPD".

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Effects on the body

There are 4 main drug actions:

Desired activity

The desired activity of a drug is mainly due to one of the following:

Cellular membrane disruption
Chemical reaction
Interaction with enzyme proteins
Interaction with structural proteins
Interaction with carrier proteins
Interaction with ion channels
Ligand binding to receptors:
- Hormone receptors
- Neuromodulator receptors
- Neurotransmitter receptors

General anesthetics were once thought to work by disordering the neural membranes, thereby altering the Na⁺ influx. Antacids and chelating agents combine chemically in the body. Enzyme-substrate binding is a way to alter the production or metabolism of key endogenous chemicals, for example aspirin irreversibly inhibits the enzyme prostaglandin synthetase (cyclooxygenase) thereby preventing inflammatory response. Colchicine, a drug for gout, interferes with the function of the structural protein tubulin, while Digitalis, a drug still used in heart failure, inhibits the activity of the carrier molecule, Na-K-ATPase pump. The widest class of drugs act as ligands which bind to receptors which determine cellular effects. Upon drug binding, receptors can elicit their normal action (agonist), blocked action (antagonist), or even action opposite to normal (inverse agonist).

In principle, a pharmacologist would aim for a target plasma concentration of the drug for a desired level of response. In reality, there are many factors affecting this goal. Pharmacokinetic factors determine peak concentrations, and concentrations cannot be maintained with absolute consistency because of metabolic breakdown and excretory clearance. Genetic factors may exist which would alter metabolism or drug action itself, and a patient's immediate status may also affect indicated dosage.

Undesirable effects

Undesirable effects of a drug include:

Increased probability of cell mutation (carcinogenic activity)
A multitude of simultaneous assorted actions which may be deleterious
Interaction (additive, multiplicative, or metabolic)
Induced physiological damage, or abnormal chronic conditions

Receptor binding

The binding of ligands (drug) to receptors is governed by the law of mass action which relates the large-scale status to the rate of numerous molecular processes. The rates of formation and un-formation can be used to determine the equilibrium concentration of bound receptors. The equilibrium dissociation constant is defined by:

where L=ligand, R=receptor, square brackets [] denote concentration. The fraction of bound receptors is found as (1+[R]/[L·R])^-1 , which can then be expressed using K_d as,

Semi-log plots of two agonists with different K_d.

This expression is one way to consider the effect of a drug, in which the response is related to the fraction of bound receptors. The fraction of bound receptors is known as occupancy. The relationship between occupancy and pharmacological response is usually non-linear. This explains the so called receptor reserve phenomenon i.e. the concentration producing 50% occupancy is typically higher than the concentration producing 50% of maximum response.

Often the response is determined as a function of log[L] to consider many orders of magnitude of concentration. However, there is no biological or physical theory which relates effects to the log of concentration. It is just convenient for graphing purposes. It is useful to note that 50% of the receptors are bound when [L]=K_d .

The graph shown represents the conc-response for two hypothetical receptor agonists, plotted in a semi-log fashion. The curve toward the left represents a higher potency (potency arrow does not indicate direction of increase) since lower concentrations are needed for a given response. The effect increases as a function of concentration.

Multicellular pharmacodynamics

The concept of pharmacodynamics has been expanded to include Multicellular Pharmacodynamics (MCPD). MCPD is the study of the static and dynamic properties and relationships between a set of drugs and a dynamic and diverse multicellular 4 dimensional organization. It is the study of the workings of a drug on a minimal multicellular system (mMCS), both in vivo and in silico. Networked Multicellular Pharmacodynamics (Net-MCPD) further extends the concept of MCPD to model regulatory genomic networks together with signal transduction pathways, as part of a complex of interacting components in the cell.

Source :

en.wikipedia.org

Pharmacokinetics ( What body Does to the Drug)

2007-09-19T14:22:00.000-07:00

Pharmacokinetics

From Wikipedia, the free encyclopedia

Pharmacokinetics (in Greek: "pharmacon" meaning drug and "kinetikos" meaning putting in motion, the study of time dependency) is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism. In practice, this discipline is applied mainly to drug substances, though in principle it concerns itself with all manner of compounds ingested or otherwise delivered externally to an organism, such as nutrients, metabolites, hormones, toxins, etc. Pharmacokinetics is often divided into several areas including, but not limited to, the extent and rate of Absorption, Distribution, Metabolism and Excretion. This sometimes is referred to as the ADME scheme.

Absorption is the process of a substance entering the body. Distribution is the dispersion or dissemination of substances throughout the fluids and tissues of the body. Metabolism is the irreversible transformation of substances and its daughter metabolites. Excretion is the elimination of the substances from the body. In rare cases, some drugs irreversibly accumulate in a tissue in the body.

Pharmacokinetics is often studied in conjunction with pharmacodynamics. So while pharmacodynamics explores what a drug does to the body, pharmacokinetics explores what the body does to the drug.

Pharmacokinetics is sometimes abbreviated as "PK".

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1 Pharmacokinetic Analysis

Pharmacokinetic Analysis

Pharmacokinetic analysis is performed by noncompartmental (model independent) or compartmental methods. Noncompartmental methods estimate the exposure to a drug by estimating the area under the curve of a concentration-time graph. Compartmental methods estimate the concentration-time graph using kinetic models.

Noncompartmental PK Analysis

Noncompartmental PK analysis is highly dependent on estimation of total drug exposure. Total drug exposure is most often estimated by Area Under the Curve methods, with the Trapezoidal Rule the most common area estimation method. Due to the dependence of the length of 'x' in the trapezoidal rule, the area estimation is highly dependent on the blood/plasma sampling schedule. That is, the closer your time points are, the closer the trapezoids are to the actual shape of the concentration-time curve.

Compartmental PK Analysis

Compartmental PK analysis uses kinetic models to describe and predict the concentration-time curve. PK compartmental models are often similar to kinetic models used in other scientific disciplines such as chemical kinetics and thermodynamics. The advantage of compartmental to noncompartmental analysis is the ability to predict the concentration at any time. The disadvantage is the difficulty in developing and validating the proper model. The simplest PK compartmental model is the one-compartmental PK model with IV bolus administration and first-order elimination.

Bioanalytical Methods

Bioanalytical methods are necessary to construct a concentration-time profile. Chemical techniques are employed to measure the concentration of drugs in biological matrix, most often plasma. Proper bioanalytical methods should be selective and sensitive.

Mass Spectrometry

Pharmacokinetics is often studied using mass spectrometry because of the complex nature of the matrix (often blood or urine) and the need for high sensitivity to observe low dose and long time point data. The most common instrumentation used in this application is LC-MS with a triple quadrupole mass spectrometer. Tandem mass spectrometry is usually employed for added specificity. Standard curves and internal standards are used for quantitation of usually a single pharmaceutical in the samples. The samples represent different time points as a pharmaceutical is administered and then metabolized or cleared from the body. Blank or t=0 samples taken before administration are important in determining background and insuring data integrity with such complex sample matrices. Much attention is paid to the linearity of the standard curve; however it is not uncommon to use curve fitting with more complex functions such as quadratics since the response of most mass spectrometers is less than linear across large concentration ranges.

There is currently considerable interest in the use of very high sensitivity mass spectrometry for microdosing studies, which are seen as a promising alternative to animal experimentation.

Source:

en.wikipedia.org

History of Pharmacy

2007-09-19T14:13:00.000-07:00

BEFORE THE DAWN OF HISTORY

From beginnings as remote and simple as these came the proud profession of Pharmacy. Its development parallels that of man. Ancient man learned from instinct, from observation of birds and beasts. Cool water, a leaf, dirt, or mud was his first soothing application. By trial, he learned which served him best. Eventually, he applied his knowledge for the benefit of others. Though the cavemen's methods were crude, many of today's medicines spring from sources as simple and elementary as those which were within reach of early man.

PHARMACY IN ANCIENT BABYLONIA

Babylon, jewel of ancient Mesopotamia, often called the cradle of civilization, provides the earliest known record of practice of the art of the apothecary. Practitioners of healing of this era (about 2600 B.C.) were priest, pharmacist and physician, all in one. Medical texts on clay tablets record first the symptoms of illness, the prescription and directions for compounding, then an invocation to the gods. Ancient Babylonian methods find counterpart in today's modern pharmaceutical, medical, and spiritual care of the sick.

PHARMACY IN ANCIENT CHINA

Chinese Pharmacy, according to legend, stems from Shen Nung (about 2000 B.C.), emperor who sought out and investigated the medicinal value of several hundred herbs. He reputed to have tested many of them on himself, and to have written the first Pen T-Sao, or native herbal, recording 365 drugs. Still worshiped by native Chinese drug guilds as their patron god, Shen Nung conceivably examined many herbs, barks, and roots brought in from the fields, swamps, and woods that are still recognized in Pharmacy today. In the background is the "Pa Kua," a mathematical design symbolizing creation and life. Medicinal plants include podophyllum, rhubarb, ginseng, stramonium, cinnamon bark, and, in the boy's hand, ma huang, or Ephedra.

DIOSCORIDES - A SCIENTIST LOOKS AT DRUGS

In the evolution of all successful and enduring systems of knowledge there comes a time when the observations of many men, or the intensive studies of one, transcend from the level of trade or vocation to that of a science. Pedanios Dioscorides (first century A.D.), contributed mightily to such a transition in Pharmacy. In order to study materia medica, Dioscorides accompanied the Roman armies throughout the known world. He recorded what he observed, promulgated excellent rules for collection of drugs, their storage and use. His texts were considered basic science as late as the sixteenth century.

Today the whole scenario has changed.. there is significant and unbelievable change in pharmaceutical sciences and with the help of Genetics and Bio technology Pharmaceutical sciences Doing wonders !! hats off to this noble sercice

In modern time The most importantpharmaceutical aspect of a drug or medicine is evaluated or expressed interms of

1. Pharmacokinetics
Its nothing but what the body does to the drug after entering into the body.
The four major steps are Absorption , Distribution,Metabolism,Excretion ( ADME)

2.Pharmacodynamics

It is the action of drug on the body. what the drug does to our body.
It may bind to receptors activate or deactivate them .
Initiate or stop some bio chemical process in body.
Alter physiological activity. etc

Pharmacy

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Pharmacodynamics ( What Drug Does to Body)

Pharmacodynamics

From Wikipedia, the free encyclopedia

Contents

Effects on the body

Desired activity

Undesirable effects

Receptor binding

Pharmacokinetics ( What body Does to the Drug)

Pharmacokinetics

From Wikipedia, the free encyclopedia

Contents

Pharmacokinetic Analysis

Noncompartmental PK Analysis

Compartmental PK Analysis

Bioanalytical Methods

Mass Spectrometry

History of Pharmacy