HIV

HIV, the human immunodeficiency virus, is the virus that causes AIDS, a debilitating and deadly disease of the human immune system. HIV is one of the world's most serious health problems: at the end of 2001, more than 40 million people worldwide were infected with HIV and living with the virus or AIDS. The World Health Organization estimates that about 20 million people have died from AIDS since the infection was first described in 1981. Nearly 500,000 of those deaths have occurred in the United States. Although there is no cure for the disease, therapies exist that reduce the symptoms of AIDS and can extend the life spans of HIV-infected individuals. Researchers are also pursuing protective vaccines, but a reliable vaccine might still require years to develop.

Hiv and Aids

HIV infects certain cells and tissues of the human immune system and takes them out of commission, rendering a person susceptible to a variety of infections and cancers. These infections are caused by so-called opportunistic agents, pathogens that take advantage of the compromised immune system but that would be unable to cause infection in people with a healthy immune system. Rare cancers such as Kaposi's sarcoma also take hold in HIV-infected individuals. The collection of diseases that arise because of HIV infection is called acquired immune deficiency syndrome, or AIDS. HIV is classified as a lentivirus ("lenti" means "slow") because the virus takes a long time to produce symptoms in an infected individual.

Hiv Life Cycle: Entering Cells

Like a typical virus, HIV infects a cell and appropriates the host's cellular components and machinery to make many copies of itself. The new viruses then break out of the cell and infect other cells. HIV stores its genetic information on an RNA molecule rather than a DNA chromosome. This is a distinguishing characteristic of retroviruses, which are viruses that must first convert their RNA genomes into DNA before they can reproduce.

Each HIV virion (viral particle) is a small sphere composed of several layers. The external layer is a membrane coat, or envelope, obtained from the host cell in which the particle was made. Underneath this membrane lies a shell made from proteins, called a nucleocapsid. Inside the protein shell are two copies of the virion's RNA genome and three kinds of proteins, which are used by the virion to establish itself once inside the cell that it infects.

Two proteins, called gp120 and gp41, enable the virion to recognize the type of cell to enter. These proteins project from the HIV membrane coat. Gp120 binds to two specific proteins found on the target cell's surface (these target-cell proteins are called receptors). The first receptor, CD4, is found on immune system cells known as CD4 T cells, and also sometimes on two cell types known as macrophages and dendritic cells. The immune system uses CD4 T cells in the initial step in making antibodies against infectious agents. After binding to CD4, the HIV protein called gp120 binds with a second cell membrane protein, commonly referred to as the co-receptor. The co-receptor can be one of many different proteins, depending on the cell type. The two most common are CXCR4, which is normally found on CD4 T cells, and CCR5, a receptor found on CD4 T cells as well as on certain macrophages and dendritic cells. In the absence of HIV, CXCR4 and CCR5 allow these immune system cells to respond to chemical signals, but when HIV infects the cells, the HIV commandeers their usage. In some cases, individuals have a mutation in their co-receptor that prevents HIV from entering their cells.

Once gp120 has bound to both the CD4 receptor and co-receptor, the gp41 protein fuses HIV's membrane envelope with the cellular membrane, injecting the virus into the target cell. Once in the cytoplasm, the viral protein shell opens up and releases the viral proteins—a reverse transcriptase, a viral integrase, and a protease—along with the viral RNA strands. The reverse transcriptase copies the RNA strands into DNA. The viral integrase then helps insert the DNA copies into the cell's chromosome. At this point, the virus is called a provirus, and the life cycle halts. The provirus may remain dormant in the cell's chromosome for months or years, waiting for the T cell to become activated by the immune system.

Hiv Life Cycle: Reproduction

When the immune system recruits T cells to fight an infection, the T cells start producing many proteins. Along with the normal cellular protein products, a T cell carrying an HIV provirus also produces HIV proteins. The first HIV proteins made are called Tat and Rev. Tat encourages the cellular machinery to copy HIV's proviral DNA into RNA molecules. These RNA molecules are then processed in the nucleus to become templates for several of the HIV proteins, some of whose functions are not well understood.

Rev, on the other hand, ushers the HIV's RNA molecules from the nucleus, where they are being reproduced, into the host cell's cytoplasm. Early in HIV reproduction, with only a few RNA molecules from which to make protein, a small quantity of Rev is made. Therefore, most of the RNA molecules remain in the nucleus long enough to get processed. As time passes, however, and Tat continues to instigate RNA production, more Rev is made. A higher amount of Rev protein increases the speed with which RNA molecules are ejected from the nucleus. These RNA molecules, which have undergone little or no processing, become templates to make different HIV proteins. The newer proteins are made in long chains that require trimming before they become functional. One of the proteins in the chain is the protease, the protein that trims. Other proteins include those that make up the protein shell, the reverse transcriptase, and integrase.

After the newly created proteins are processed to the right size, they form new virions by first assembling into a shell, then drawing in two unprocessed RNA molecules and filling up the remaining space with integrase, protease, and replicase. The new virions bud from the host-cell membrane, appropriating some of that membrane to form an outer coat in the process. The mature virus particles are now ready to infect other cells.

Hiv's Immune-System Impairment Mechanism

One of the most disastrous effects of HIV infection is the loss of the immune system's CD4 T cells. These cells are responsible for recognizing foreign invaders to a person's body and initiating antibody production to ward off the infection. Without them, people are susceptible to a variety of diseases. HIV destroys the T cells slowly, sometimes taking a decade to destroy a person's immunity. However, in all the time before an HIV-infected individual shows any symptoms, the virus has been reproducing rapidly. The lymph tissue, the resting place for CD4 T cells, macrophages, and dendritic cells, becomes increasingly full of HIV, and viral particles are also released into the bloodstream.

HIV's main target is the population of CD4 T cells within a host's body. HIV kills them in one of three ways. It kills them directly by reproducing within them, then breaking them upon exit; it kills them indirectly by causing the cells to "commit suicide" by inducing apoptosis; or it kills them indirectly by triggering other immune cells to recognize the infected T cell and kill it as part of the immune system's normal function.

As infected T cells die, the immune system generates more to take their place. As new T cells become infected, they are either actively killed or induced to commit suicide. Meanwhile, the HIV virus is not completely hidden from the immune system. As with any infectious agent, HIV presents its proteins to the immune system, which develops antibodies against it. This antibody production, however, is hampered by the fact that HIV mutates rapidly, changing the proteins it displays to the immune system. With each new protein, the immune system must generate new antibodies to fight the infection. Thus, an HIV infection is a dramatic balance between a replicating, ever changing virus and the replenishing stores of T cells that are fighting it. Unfortunately, the immune system, without therapeutic intervention, eventually loses the battle.

Once the CD4 T cells are depleted, the immune system can no longer ward off the daily bombardment of pathogens that all human organisms experience. Common infectious agents thus overwhelm the system, and HIV patients become susceptible to a variety of "opportunistic" diseases that take advantage of the body's reduced ability to fight them off. AIDS doctors report at least twenty-six different opportunistic diseases specific to HIV infection. These include unusual fungal infections such as thrush. The chickenpox virus may come out of dormancy, manifesting itself as the painful disease known as shingles. An obscure form of pneumonia, called pneumocystis pneumonia, is also common in AIDS patients. In addition, patients can acquire cancers such as B-cell lymphoma, which is a cancer of the immune system. Doctors generally consider patients with fewer than 200 CD4 T cells per cubic milliliter of blood as having AIDS. (In contrast, a healthy person counts more than 1,000.)

Anti-Hiv Drug Therapy

Drugs that interfere with viral replication can slow down HIV disease. Early trials relied on the administration of one drug at a time. While patients' health improved and their T cell count rose, in time HIV mutated enough to render the drugs ineffective. Since 1995, however, doctors have found that rotating patients through three different drugs in very high doses significantly improves the health of AIDS patients. Known as "highly active antiretroviral therapy" (HAART), this therapeutic approach also reduces the amount of HIV circulating in the bloodstream to nearly undetectable levels. People infected with HIV who are treated by HAART are now living longer, healthier lives than ever before.

Targeting Life-Cycle Points

Drugs meant to knock out HIV target the activities of two HIV proteins, the reverse transcriptase and the protease. HAART requires drugs of both types. Drugs called protease inhibitors prevent the viral protease from trimming down the large proteins made late during infection. Without those proteins, the viral shell cannot be assembled. In addition, the proteins that reproduce HIV's genetic information, the reverse transcriptase and the integrase, are not functional.

Drugs that inhibit the reverse transcriptase prevent it from copying the RNA into DNA. These drugs work early in the life cycle of HIV. Reverse transcriptase inhibitors include azidothymidine (AZT), whose structure resembles the DNA nucleotide thymine. When reverse transcriptase builds DNA with AZT instead of thymine, the AZT caps the growing DNA molecule and halts DNA production, due to AZT's slight difference in structure from the thymine that DNA production requires.

Injection Drug Use and Hiv Infection

Injection drug use (IDU) contributes to considerable illness burden in both developed and developing countries. Transmission of blood-borne pathogens (e.g., HIV, hepatitis B and C virus, Human T-Cell Lymphotrophic viruses I and II, and malaria) occurs primarily through direct sharing of needles or multi-person use of syringes. More recent studies suggest potential additional risks posed by shared use of injection paraphernalia (e.g., cookers, cotton, water), which is especially a concern with respect to transmission of hepatitis B and C viruses.

Human immunodeficency virus/acquired immunodeficiency syndrome (HIV/AIDS) and injection drug use can be considered as two intertwining epidemics. Socioeconomic, legal, and cultural factors and migration contribute to the emergence of drug injection. Injection drug use has been reported in 144 countries worldwide, among which 128 have detected HIV among injection drug users (IDUs). Although IDUs presently account for 5 to 10 percent of cumulative adult HIV infections worldwide, injection drug use is the predominant mode of HIV transmission in most of Western and Eastern Europe, North Africa, the Middle East, and increasingly in parts of Asia. Taking into account direct transmission among IDUs through sharing of contaminated injection equipment, and indirect transmission to sexual partners and offspring, injection drug use accounts for 44 percent of reported AIDS cases in Europe and nearly one-third of cases in the United States and the Southern Cone of South America. In the United States, approximately half of all new HIV infections are among IDUs. In Canada, the proportion of AIDS cases attributable to injection drug use is steadily increasing.

IDU-associated HIV epidemics are characterized by a high degree of regional and local heterogeneity. Explosive epidemics have occurred in both developing and developed countries or regions, with documented HIV incidence rates reaching as high as 20 to 30 percent per year. Early examples of HIV epidemics among IDUs were documented in Manipur, India Milan, Italy, Bangkok, Thailand, and New York City, suggesting that once HIV prevalence reaches a threshold of approximately 10 percent, it can surpass 40 to 50 percent within one to four years. More recently, Vancouver, Canada, witnessed an HIV outbreak with incidence reaching 18.6 per 100 person-years, despite an extended period of low stable HIV prevalence and a high-volume needle exchange program. In the Ukraine, over 100,000 HIV infections occurred in a single year, mostly due to sharing of injection equipment. These examples serve to illustrate the extent to which IDU-associated HIV epidemics can occur with startling speed. In such cases, subsequent spread to heterosexual non-IDU populations is almost imminent, which underscores the need for swift prevention measures.

In contrast, Australia and the United Kingdom have essentially averted widespread transmission of HIV among drug users. These prevention successes did not occur by chance. The early introduction of interventions such as widespread legal access to sterile injection equipment and expansion of methadone maintenance treatment programs likely spared these regions from the tragedies described above. Preventive strategies to curtail HIV transmission among IDUs are discussed in more detail below.

Preventive Strategies to Decrease Transmission of Blood-Borne Disease

Several interventions have been developed to reduce the spread of blood-borne disease among IDUs. These include programs that promote sterile syringe acquisition, drug abuse treatment, network-oriented interventions, and community outreach. These programs are briefly summarized.

Since sterile syringes are not accessible, affordable, or legal in the majority of countries that report injection drug use, the fundamental mechanism for reducing parenteral HIV transmission among IDUs is to provide unrestricted access to sterile syringes and to promote their one-time use. Examples are syringe exchange programs (SEPs), syringe vending machines, and enabling IDUs' access to syringes through pharmacies. These interventions are consistent with the concept of harm reduction, which aims to reduce the negative consequences associated with injection drug use among persons who cannot or will not cease injecting, and their surrounding community. At SEPs, IDUs exchange sterile syringes for potentially contaminated ones. A large body of international literature suggests that SEPs can be effective in reducing the incidence of HIV, Hepatitis B, and Hepatitis C, as well as needle sharing. No evidence exists to suggest that SEPs increase drug use or crime. At many SEPs, IDUs can receive condoms, referrals to HIV testing and drug treatment programs, and screening for STDs and tuberculosis. Unfortunately, in many U.S. states where SEPs operate illegally due to syringe paraphernalia laws, these critical ancillary services are less likely to be offered. In many developing countries, even when SEPs have been successfully introduced, severe fiscal restraints limit their ability to consistently offer services to a large number of IDUs.

Drug abuse treatment, and methadone maintenance in particular, has been associated with reduced injection frequency as well as declines in needle sharing, sexual risk behaviors, and HIV seroconversion. These studies support the notion that drug abuse treatment can be effective as primary HIV/AIDS prevention. Other opiate agonist therapies that are undergoing evaluation include substitution with buprenorphine, naltrexone and levo-alpha acetylmethadol (LAAM). Clinical trials have also evaluated the prescription of heroin under continuous medical surveillance, for example, in Switzerland. However, in cities where cocaine and methamphetamine are the main drugs of abuse, little is available in terms of drug abuse treatment. In North America, less that 25 percent of IDUs are receiving drug treatment at any given time, which signals an urgent need for expanded drug treatment services, including but not restricted to methadone maintenance. Other treatmentoriented initiatives that require expansion and evaluation include programs to prevent relapse from abstinence, interim treatment of drug users on waiting lists, interventions to refer SEP attenders into treatment, and development of substitution therapies for drug users addicted to stimulants.

Network and community-level strategies that modify social norms surrounding needle sharing constitute also valuable prevention tools. Network-based strategies of HIV prevention are based upon the personal networks of IDUs. Personal networks include people an IDU may have a social relationship with: an injecting partner, a sex partner, a family member, and so on. Studies have shown that personal network-based interventions can decrease needle sharing, decrease use of shooting galleries, and increase bleach disinfection.

Community-based outreach is characterized by utilization of former IDUs and/or peers to create a liaison between the drug using community and HIV education/treatment. In the United States, outreach has been shown to impact HIV risk by decreasing the frequency of drug use and reuse of needles and increasing use of bleach for purposes of disinfection. M. S. Kumar and colleagues have shown that community-based out-reach may also be effective in an international setting. They demonstrated significant decreases in needle use frequency and needle sharing among IDUs involved in outreached efforts as compared to IDUs not involved in outreach efforts in Madras, India. D. C. Des Jarlais has shown that community outreach is a crucial component held in common by five cities that have consistently maintained low stable HIV prevalence rates among IDU populations.

Prospects for the Future

In several cities that experienced early HIV epidemics among IDUs (e.g., Milan, Italy; Geneva, Switzerland; Amsterdam, the Netherlands; and New York City), HIV prevalence has declined. This has been attributed to AIDS-related mortality, pre-AIDS mortality, improvements in HIV treatments, migration, diminishing size of some IDU populations (e.g., Amsterdam), and reduced HIV incidence as a probable consequence of combinations of the above interventions. However, in the presence of high background HIV prevalence, even low levels of needle sharing can give rise to a relatively high number of new infections. In Amsterdam, large declines in injection risk (i.e., syringe borrowing, lending, and reusing) occurred from 1986 to 1991, and annual HIV incidence declined from 8 percent to 4 percent. However, van Ameijden and colleagues reported no further reductions occurred thereafter, suggesting that a minimum level of injecting risk may persist that is difficult to prevent. Since risk reduction rather than risk elimination appears to be a realistic goal, studies are needed to determine minimum levels of acceptable injection risk for specific regions, based on a thorough understanding of local risk behaviors, HIV prevalence and incidence, mixing patterns of susceptibles, and the estimated impact of interventions. This will require collaboration across the disciplines of epidemiology, behavioral science, and biostatistics.

Apart from the aforementioned strategies of HIV prevention among IDUs, a core prevention strategy that has yet to receive adequate attention is interventions that discourage transition from noninjection to injection drug use. The rationale for this approach is that the prevalence of hepatitis B and C surpasses 50 percent among new initiates to injection drug use within one year after initiation.

There is also evidence to suggest that risk factors for HIV seroconversion among IDUs may differ significantly by gender. For example, among male IDUs, injection-related risks and homosexual/bisexual activity appear to play a predominant role, whereas among females, sexual risks are paramount. These findings suggest that prevention programs should be gender-specific as well as being ethnoculturally and locally sensitive. Future studies should pay special attention to patterns of sexual behaviors of drug users in an effort to develop practical interventions.

In summary, the characteristics of IDU-associated HIV epidemics and interventions that have been effective in reducing IDUs' risk behaviors include access to sterile injecting equipment, methadone maintenance treatment, communitybased outreach, and peer network interventions. Unfortunately, in many settings the implementation of these proven interventions is often delayed due to lack of political will or inadequate resources. The delicate balance between an epidemic that is averted and one that is merely delayed argues against complacency in the realm of prevention. These obstacles will need to be over-come if HIV epidemics among drug user populations are to be controlled or prevented.

vitamin

Definition

Vitamins are organic components in food that are needed in very small amounts for growth and for maintaining good health. The vitamins include vitamin D, vitamin E, vitamin A, and vitamin K, or the fat-soluble vitamins, and folate (folic acid), vitamin B₁₂, biotin, vitamin B₆, niacin, thiamin, riboflavin, pantothenic acid, and vitamin C (ascorbic acid), or the water-soluble vitamins. Vitamins are required in the diet in only tiny amounts, in contrast to the energy components of the diet. The energy components of the diet are sugars, starches, fats, and oils, and these occur in relatively large amounts in the diet.

Most of the vitamins are closely associated with a corresponding vitamin deficiency disease. Vitamin D deficiency causes rickets, a disease of the bones. Vitamin E deficiency occurs only very rarely, and causes nerve damage. Vitamin A deficiency is common throughout the poorer parts of the world, and causes night blindness. Severe vitamin A deficiency can result in xerophthalamia, a disease which, if left untreated, results in total blindness. Vitamin K deficiency results in spontaneous bleeding. Mild or moderate folate deficiency is common throughout the world, and can result from the failure to eat green, leafy vegetables or fruits and fruit juices. Folate deficiency causes megaloblastic anemia, which is characterized by the presence of large abnormal cells called megaloblasts in the circulating blood. The symptoms of megaloblastic anemia are tiredness and weakness. Vitamin B₁₂ deficiency occurs with

Essential Vitamins
Vitamin	What It Does For The Body
Vitamin A (Beta Carotene)	Promotes growth and repair of body tissues; reduces susceptibility to infections; aids in bone and teeth formation; maintains
	smooth skin
Vitamin B-1 (Thiamin)	Promotes growth and muscle tone; aids in the proper functioning of the muscles, heart, and nervous system; assists in digestion of
	carbohydrates
Vitamin B-2 (Riboflavin)	Maintains good vision and healthy skin, hair, and nails; assists in formation of antibodies and red blood cells; aids in carbohydrate,
	fat, and protein metabolism
Vitamin B-3 (Niacinamide)	Reduces cholesterol levels in the blood; maintains healthy skin, tongue, and digestive system; improves blood circulation; increases
	energy
Vitamin B-5	Fortifies white blood cells; helps the body's resistance to stress; builds cells
Vitamin B-6 (Pyridoxine)	Aids in the synthesis and breakdown of amino acids and the metabolism of fats and carbohydrates; supports the central nervous
	system; maintains healthy skin
Vitamin B-12 (Cobalamin)	Promotes growth in children; prevents anemia by regenerating red blood cells; aids in the metabolism of carbohydrates, fats, and
	proteins; maintains healthy nervous system
Biotin	Aids in the metabolism of proteins and fats; promotes healthy skin
Choline	Helps the liver eliminate toxins
Folic Acid (Folate, Folacin)	Promotes the growth and reproduction of body cells; aids in the formation of red blood cells and bone marrow
Vitamin C (Ascorbic Acid)	One of the major antioxidants; essential for healthy teeth, gums, and bones; helps to heal wounds, fractures, and scar tissue; builds
	resistance to infections; assists in the prevention and treatment of the common cold; prevents scurvy
Vitamin D	Improves the absorption of calcium and phosphorous (essential in the formation of healthy bones and teeth) maintains nervous
	system
Vitamin E	A major antioxidant; supplies oxygen to blood; provides nourishment to cells; prevents blood clots; slows cellular aging
Vitamin K (Menadione)	Prevents internal bleeding; reduces heavy menstrual flow

the failure to consume meat, milk or other dairy products. Vitamin B₁₂ deficiency causes megaloblastic anemia and, if severe enough, can result in irreversible nerve damage. Niacin deficiency results in pellagra. Pellagra involves skin rashes and scabs, diarrhea, and mental depression. Thiamin deficiency results in beriberi, a disease resulting in atrophy, weakness of the legs, nerve damage, and heart failure. Vitamin C deficiency results in scurvy, a disease that involves bleeding. Specific diseases uniquely associated with deficiencies in vitamin B₆, riboflavin, or pantothenic acid have not been found in the humans, though persons who have been starving, or consuming poor diets for several months, might be expected to be deficient in most of the nutrients, including vitamin B₆, riboflavin, and pantothenic acid.

Some of the vitamins serve only one function in the body, while other vitamins serve a variety of unrelated functions. Hence, some vitamin deficiencies tend to result in one type of defect, while other deficiencies result in a variety of problems.

Description

Vitamin treatment is usually done in three ways: by replacing a poor diet with one that supplies the recommended dietary allowance, by consuming oral supplements, or by injections. Injections are useful for persons with diseases that prevent absorption of fat-soluble vitamins. Oral vitamin supplements are especially useful for persons who otherwise cannot or will not consume food that is a good vitamin source, such as meat, milk or other dairy products. For example, a vegetarian who will not consume meat may be encouraged to consume oral supplements of vitamin B₁₂.

Treatment of genetic diseases which impair the absorption or utilization of specific vitamins may require megadoses of the vitamin throughout one's lifetime. Megadose means a level of about 10-1,000 times greater than the RDA. Pernicious anemia, homocystinuria, and biotinidase deficiency are three examples of genetic diseases which are treated with megadoses of vitamins.

dysmenorrhea

Dysmenorrhea (or dysmenorrhoea), cramps or painful menstruation, involves menstrual periods that are accompanied by either sharp, intermittent pain or dull, aching pain, usually in the pelvis or lower abdomen.

Painful menstruation affects approximately 50% of menstruating women, and 10% are incapacitated for up to 3 days. Painful menstruation is the leading cause of lost time from school and work among women of childbearing age. This pain may precede menstruation by several days or may accompany it, and it usually subsides as menstruation tapers off.

Although some pain during menstruation is normal, excessive pain is not. Dysmenorrhea refers to menstrual pain severe enough to limit normal activities or require medication. It may coexist with excessively heavy blood loss (menorrhagia).

• Primary dysmenorrhea refers to menstrual pain that occurs in otherwise healthy women (Wright et al. 2003). This type of pain is not related to any specific problems with the uterus or other pelvic organs.
• Secondary dysmenorrhea is menstrual pain that is attributed to some underlying disease process or structural abnormality either within or outside the uterus (for example, pelvic inflammatory disease, leiomyoma, endometriosis, adhesions, adenomyosis, uterine displacement, or a retroverted uterus). Endometriosis is the most common cause of dysmenorrhea associated with a disease process and is frequently misdiagnosed.

The incidence of menstrual pain is greatest in women in their late teens and 20s, then declines with age. Some women experience increased menstrual pain in their late 30s and 40s as their endocrine systems prepare for menopause by decreasing hormone levels and thus fertility. It does not appear to be affected by childbearing. An estimated 10 percent to 15 percent of women experience monthly menstrual pain severe enough to prevent normal daily function at school, work, or home.

Risk factors

The majority of women will suffer this degree of dysmenorrhea at least once during their reproductive years. Increased risk is associated with younger age, and past medical history of any of the conditions associated with secondary dysmenorrhea.

• Primary:
  • Nulliparity (having never given birth)
  • Obesity
  • Cigarette smoking
  • Positive family history
• Secondary:
  • Pelvic infection
  • Sexually transmitted diseases
  • Endometriosis

Primary Dysmenorrhea

Pathophysiology

Primary dysmenorrhea occurs during regular ovulatory cycles. Women with primary dysmenorrhea have increased activity of the uterine muscle with increased contractility and increased frequency of contractions. Prostaglandins are released during menstruation due to destruction of the endometrial cells and the resultant release of their contents.

Release of prostaglandins and other inflammatory mediators in the uterus (womb) is thought to be a major factor in primary dysmenorrhea (Wright et al. 2003). Prostaglandin levels have been found to be much higher in women with severe menstrual pain than in women who experience mild or no menstrual pain. Drugs which inhibit the production of prostaglandins, such as the non-steroidal anti-inflammatory drugs (NSAIDs) Naproxen, Ibuprofen and Mefenamic Acid, can provide relief for the discomfort and other associated symptoms of excessive prostaglandin release, such as nausea, vomiting, and headache.

Clinical Features

The cramping associated with dysmenorrhea usually begins a few hours before the start of bleeding and may continue for a few days. The pain is usually described as being in the lower abdomen, possibly radiating to the thighs and lower back. Other symptoms associated with primary dysmenorrhea are nausea and vomiting, fatigue, diarrhoea, lower backache, and headache.

Treatment

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen, are very effective in the treatment of primary dysmenorrhea (Andreoli et al. 2004). As earlier stated, their effectiveness comes from their ability to inhibit prostaglandin synthesis. However, many NSAIDs can cause gastrointestinal upset as a side effect. Patients who cannot take most common NSAIDs may be prescribed a cyclo-oxygenase-2 (COX2) inhibitor.

Oral contraceptives are second-line therapy unless a woman is also seeking contraception, then they would become first-line therapy. Oral contraceptives are 90% effective in improving primary dysmenorrhea and work by reducing menstrual blood volume and suppressing ovulation. It may take up to 3 months for the oral contraceptives to become effective. Norplant and Depo-provera are also effective since these methods often induce amenorrhea.

Alternative treatments

For the 10% of patients who do not respond to NSAIDs and/or oral contraceptives, a wide range of alternative therapies have been proven effective, including transcutaneous electrical nerve stimulation (TENS), acupuncture, omega-3 fatty acids, transdermal nitroglycerin, thiamine, and magnesium supplements.^{[citation needed]}

Chiropractic care has been an effective treatment approach (Chapman-Smith, 2000). Treating subluxations in the spine may cause the nerves leaving the spine to be less aggravated and so decrease symptoms of dysmenorrhea, as well as other symptoms such as chronic stomach aches and headaches. However, the Cochrane Review of 2007-04-19 ^[1] states "Authors' conclusions: Overall there is no evidence to suggest that spinal manipulation is effective in the treatment of primary and secondary dysmenorrhea."

Accupuncture is used to try to treat dysmenorrhea and studies have shown that it "reduced the subjective perception of dysmenorrhea" (Jun 2004). However, the small number of studies leaves doubt about the effectiveness of acupuncture for gynaecological conditions (White 2003).

Secondary Dysmenorrhea

Pathophysiology

The mechanisms causing the pain of secondary dysmenorrhea are varied and may or may not involve prostaglandins. Some causes of secondary dysmenorrhea are endometriosis, pelvic inflammation, leiomyoma, adenomyosis, ovarian cysts, and pelvic congestions (Hacker et al. 2004). The presence of an IUD (intrauterine device) for contraception may also be a potential cause of menstrual pain, although they usually lead to pelvic pain only around the time of insertion. Some women also find that use of internally-worn menstrual products, such as tampons and menstrual cups, exacerbate menstrual cramps and pain.

Clinical Features

The symptoms of secondary dysmenorrhea vary with the underlying cause, but generally the pain associated with secondary dysmenorrhea is not limited to the time around menses as with primary dysmenorrhea. Also, secondary dysmenorrhea is less related to the onset of bleeding in menstruation, is seen in older women, and is associated with other symptoms like infertility.

Treatment

The most effective treatment of secondary dysmenorrhea is the identification and treatment of the underlying cause of the pain, although the relief provided by NSAIDs is often helpful.

The first line of treatment is medical (e.g., prostaglandin synthetase inhibitors, hormonal contraception, danazol, progestins). If possible, the underlying disorder or anatomic abnormality is corrected, thus relieving symptoms. Dilation of a narrow cervical os may give 3 to 6 months of relief (and allows diagnostic curettage if needed). Myomectomy, polypectomy, or dilation and curettage may be needed. Interruption of uterine nerves by presacral neurectomy and division of the sacrouterine ligaments may help selected patients. Hypnosis may be useful.

Endometriosis is a common cause of secondary dysmenorrhea. In fact, approximately 24% of women who complain of pelvic pain are subsequently found to have endometriosis. This condition is often associated with infertility. If pain relief is the goal, medical options include hormonal contraception, danazol, progestational agents, and GnRH agonists.

Related Problems

• Premenstrual syndrome (PMS)
• Stress and anxiety
• Pelvic inflammatory disease
• Adenomyosis
• History of sexual or physical abuse
• Leiomyoma
• Ovarian cysts
• Endometriosis

diarrheA

Description

Diarrhea is the abnormal increase of liquid in stool and increase in the frequency of passing stool (defecation). The person with diarrhea has watery or loose stool more than three times a day. Other symptoms include cramping, pain, feeling the urge to defecate, irritation of the skin around the anus (perianal), and inability to control defecation (fecal incontinence). Approximately 10% of the patients with advanced cancer suffer from diarrhea. Diarrhea lasting fewer than two weeks is called "acute diarrhea," and diarrhea lasting for longer than two months is called "chronic diarrhea."

Diarrhea is a debilitating condition that can significantly affect quality of life. Diarrhea can prevent patients from participating in social activities and going to work. Persons with diarrhea fear soiling their clothing or bed linens, a fear that prevents them from leaving home. Loss of sleep due to nighttime diarrhea can cause fatigue, which ultimately affects the patient's ability to function normally. Uncontrolled diarrhea can lead to chemical imbalances, loss of fluids (dehydration), and even death.

Causes

Although there are many causes of diarrhea, only those associated with cancer will be discussed. The most common cause of diarrhea in cancer patients is related to constipation or its treatment. Cancer patients may experience diarrhea as a result of their treatment, or it can be due to dietary changes, infections, hormone imbalances, digestion disorders, or inflammation. Treatment-related diarrhea can be caused by chemotherapy, hormone therapy, radiation therapy, biological response modifiers (drugs that improve the patient's immune system), or surgery. In addition, cancer patients may develop temporary lactose intolerance, which causes diarrhea.

Chemotherapy drugs kill the rapidly growing cancer cells. However, certain normal cells of the body are rapidly growing and they too are affected. Rapidly growing cells are found in the intestines, as well as other parts of the body. Diarrhea occurs as a result of injury to the cells of the intestine. These effects are temporary. Chemotherapy drugs, hormones, and biological response modifiers that frequently cause diarrhea include:

• Dactinomycin
• Daunorubicin
• Diethylstilbestrol diphosphate
• Doxorubicin
• Fluorouracil
• Flutamide
• Hydroxyurea
• Interferon
• Interleukin-2 (aldesleukin)
• Irinotecan
• Methotrexate
• Nitrosoureas
• Thioguanine

Radiation therapy can cause diarrhea if the intestines are in the treatment field. Diarrhea results from the injury and destruction of the cells lining the intestines, which leads to a decrease in the uptake (absorption) of fluids and an increase in the speed with which stool moves through the intestines. Radiation therapy can cause diarrhea, and other intestinal problems, many months or years after treatment has been completed.

Diarrhea usually develops within one week following pretreatment (chemotherapy and irradiation) for bone marrow transplantation. This diarrhea usually disappears within two weeks. Also, bone marrow transplant patients with graft-versus-host disease develop severe diarrhea.

Treatments

Prevention

There are some measures that can prevent diarrhea. Patients who are receiving abdominal radiation therapy can be put into certain positions to minimize exposure of healthy intestines to radiation. Diarrhea caused by chemotherapy cannot be prevented; however, the administration of atropine during treatment with irinotecan may prevent diarrhea. Patients should stop taking dietary supplements, as these can cause diarrhea.

There are many dietary changes that can be made to prevent or reduce diarrhea. Foods to avoid include:

• whole grain breads and cereals
• fresh or frozen fruits (except banana)
• dried fruits
• fruit juices with pulp and prune juice
• raw vegetables
• canned onions, corn, olives, pickles, and Brussels sprouts
• fatty foods
• dried beans
• rich desserts
• milk and milk products
• alcohol and caffeinated coffee and tea
• spicy foods
• fried foods

Management

Of the utmost importance in the treatment of diarrhea is the replacement of fluids lost by frequent, watery stools. The patient should drink six to eight glasses of fluid daily, including clear broth, ginger ale (without the fizz), water, weak tea, and commercial formulas that contain sugars and minerals (electrolytes). Patients with severe diarrhea may need intravenous fluid replacement either at home or in the hospital.

Diarrhea can cause the perianal skin to become irritated and painful; therefore, it needs to be cleaned thoroughly after each bout of diarrhea. Baby wipes or a mild soap with water can be used to clean the irritated skin. The area should be patted dry and occasionally exposed to air. Taking a sitz bath (sitting in a bathtub of shallow water) with lukewarm water may relieve the discomfort. Petroleum jelly or other type of barrier cream may be used.

The patient should eat small, frequent meals. Foods and drinks should be taken at room temperature. Foods that can help control diarrhea include:

• bananas
• applesauce
• boiled white rice
• tapioca
• white bread
• plain pasta
• creamed cereals
• eggs
• potatoes (without skin; mashed or baked)
• fish
• chicken or turkey (without skin)

There are some medications that can slow down the movement of stool through the intestines and increase intestinal water absorption. The patient may need a combination of drugs and/or dose adjustments to achieve relief. A physician should be consulted before any over-the-counter antidiarrheal medications are taken. Anti-diarrheal medications include:

• Atropine sulfate with diphenoxylate HCl (Lomotil)
• Codeine phosphate
• Loperimide HCl (Imodium-AD)
• Octreotide phosphate (Sandostatin)

These medications should not be used if infection as the cause of diarrhea has not been eliminated.

Patients who are experiencing diarrhea due to graft-versus-host disease will continue to take their immunosuppressant drugs. They may also be treated with corticosteroids and antidiarrheal medications.

Alternative and Complementary Therapies

Peppermint tea, chamomile tea, valerian capsules, or aloe vera juice may reduce cramping and intestinal spasms. An Ayurvedic physician may recommend taking equal parts of yogurt and water with fresh ginger, or a powder of beleric myrobalan fruit. Ginger capsules may relieve intestinal spasms and pain. Glutamine supplements may speed up the healing process and relieve irritated intestines.

anti- depressant

Definition

Antidepressant drugs are medicines that relieve symptoms of depressive disorders.

Description

Antidepressant agents act by increasing the levels of excitatory neurostransmitters. The main types of antidepressant drugs in use today are:

• tricyclic antidepressants, such as amitriptyline (Elavil), imipramine (Tofranil), nortriptyline (Pamelor)
• selective serotonin reuptake inhibitors (SSRIs or serotonin boosters), such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft)
• monoamine oxidase inhibitors (MAO inhibitors), such as phenelzine (Nardil), and tranylcypromine (Parnate)
• tetracyclic compounds and atypical antidepressants which do not fall into any of the above categories

Selective serotonin reuptake inhibitors maintain levels of the excitatory neurohormone serotonin in the brain. They do not alter levels of norepinephrine. These have become the drugs of choice for a variety of psychiatric disorders, primarily because of their low incidence of severe side effects as compared with other drugs in this therapeutic class. SSRIs show similar actions and side effect profiles, but may vary in duration of action.

Tricyclic compounds, identified by their chemical structure containing three carbon rings, are an older class of antidepressants. Although generally effective, they have a high incidence of anticholinergic effects, notably dry mouth and dry eyes, which can cause discomfort. They also cause cardiac arrythmias. Because tricyclics act on both serotonin and norepinephrine, they may have some value in treatment of patients who fail to respond to SSRIs. Drugs in this class are often available at low prices, which may be significant when cost is a major factor in treatment. They have also been found useful in control of some neurologic pain syndromes.

Tricyclic antidepressants are similar, but may vary in severity of side effects, most notably the degree of sedation and the extent of the anticholinergic effects.

Tetracyclic compounds and atypical antidepressants are chemically distinct from both the major groups and each other. Although maprotilene (no brand name, marketed in generic form only) and mirtazepine (Remeron) are similar in chemical structures, they differ in their balance of activity on serotonine and norepinephrine levels.

Monoamine oxidase inhibitors (phenelzine [Nardil], tranylcypromine [Parnate]) have largely been supplanted

Antidepressant Drugs
Brand Name (Generic Name)	Possible Common Side Effects Include:
Desyrel (trazodone hydrochloride)	Allergic skin reactions, blurred vision, decreased appetite, fluid retention, headache
Effexor (venlafaxine hydrochloride)	Diarrhea, dizziness, gas, headache, insommia, rash, vomiting
Elavil (amitriptyline hydrochloride)	Constipation, idzziness, high blood pressure, fever, nausea, rash, weight gain or loss
Nardil (phenelzine sulfate)	Dry mouth, fatigue, headache, muscle spasms, tremors
Norpramin (desipramine hydrochloride)	Blurred vision, cramps, hallucinations, hair loss, vomiting
Pamelor (nortriptyline hydrochloride)	Diarrhea, fatigue, headache, decreased coordination
Paxil (paroxetine hydrochloride)	Cold symptoms, drowsiness, nervousness, stomach pain
Prozac (fluoxetine hydrochloride)	Bronchitis, drowsiness, fatigue, nausea, tremors
Sinequan (doxepin hydrochloride)	Bruising, constipation, fluid retention, itching, increased heartbeat
Surmontil (trimipramine maleate)	Disorientation, flushing, headache, nausea, vomiting
Tofranil (imipramine hydrochloride)	Bleeding sores, fever, hives, decreased coordination
Travil	Asthma, diarrhea, dizziness, fatigue, seizures
Wellbutrin (bupropion hydrochloride)	Agitation, dry mouth, headache, nausea, rash
Zoloft (sertraline)	Diarrhea, fainting, gas, headache, nervousness

in therapy because of their high risk of severe adverse effects, most notably severe hypertension. They act by inhibiting the enzyme monoamine oxidase, which is responsible for the metabolism of the stimulatory neurohormones norepinephrine, epinephrine, dopamine, and serotonin. The MAOIs are normally reserved for patients who are resistant to safer drugs. Two drugs, eldepryl (Carbex, used in treatment of Parkinson's disease) and the herb, St. John's wort, have some action against monoamine oxidase B, and have shown some value as anti-depressants. They do not share the same risks as the non-selective MAO inhibitors.

All antidepressant agents, regardless of their structure, have a slow onset of action, typically three to five weeks. Although adverse effects may be seen as early as the first dose, significant therapeutic improvement is always delayed. Similarly, the effects of antidepressants will continue for a similar length of time after the drugs have been discontinued.

paracetamol

Definition

Acetaminophen is a medicine used to relieve pain and reduce fever.

Purpose

Acetaminophen is used to relieve many kinds of minor aches and pains, including headaches, muscle aches, backaches, toothaches, menstrual cramps, arthritis, and the aches and pains that often accompany colds. It is suitable for control of pain following minor surgery, or for post-surgical pain after the need for stronger pain relievers has been reduced. Acetaminophen is also used in combination with narcotic analgesics both to increase pain relief and reduce the risk that the narcotics will be abused.

Description

This drug is available without a prescription. Acetaminophen (APAP) is sold under various brand names, including Tylenol, Panadol, Aspirin-Free Anacin, and Bayer Select Maximum Strength Headache Pain Relief Formula. Many multi-symptom cold, flu, and sinus medicines also contain acetaminophen. Persons are advised to check the ingredients listed on the container to see if acetaminophen is included in the product.

Acetaminophen is also included in some prescription-only combinations. These usually contain a narcotic in addition to acetaminophen; it is combined with oxycodone in Percocet, and is included in Tylenol with Codeine.

Studies have shown that acetaminophen relieves pain and reduces fever about as well as aspirin. But differences between these two common drugs exist. Acetaminophen is less likely than aspirin to irritate the stomach. However, unlike aspirin, acetaminophen does not reduce the redness, stiffness, or swelling that accompany arthritis.

Recommended Dosage

The usual dosage for adults and children age 12 and over is 325–650 mg every four to six hours as needed. No more than 4 g (4,000 mg) should be taken in 24 hours. Because the drug can potentially harm the liver, people who drink alcohol in large quantities should take considerably less acetaminophen and possibly should avoid the drug completely.

For children ages six to 11 years, the usual dose is 150–300 mg, three to four times a day. People are advised to check with a physician for dosages for children under six years of age.

Precautions

A person should never take more than the recommended dosage of acetaminophen unless told to do so by a physician or dentist.

Because acetaminophen is included in both prescription and non-prescription combinations, it is important to check the total amount of acetaminophen taken each day from all sources in order to avoid taking more than the recommended maximum dose.

Patients should not use acetaminophen for more than 10 days to relieve pain (five days for children) or for more than three days to reduce fever, unless directed to do so by a physician. If symptoms do not go away, or if they get worse, the patient should contact a physician. Anyone who drinks three or more alcoholic beverages a day should check with a physician before using this drug and should never take more than the recommended dosage. People who already have kidney or liver disease or liver infections should also consult with a physician before using the drug. Women who are pregnant or breastfeeding should also consult with a physician before using acetaminophen.

Smoking cigarettes may interfere with the effectiveness of acetaminophen. Smokers may need to take higher doses of the medicine, but should not take more than the recommended daily dosage unless told to do so by a physician.

Many drugs can interact with one another. People should consult a physician or pharmacist before combining acetaminophen with any other medicine, and they should not use two different acetaminophen-containing products at the same time, unless instructed by a physician or dentist.

Some products, such as Nyquil, contain acetaminophen in combination with alcohol. While these products are safe for people who do not drink alcoholic beverages, people who consume alcoholic drinks regularly, even in moderation, should use extra care before using acetaminophen-alcohol combinations.

Acetaminophen interferes with the results of some medical tests. Before having medical tests done, a person should check to see whether taking acetaminophen would affect the results. Avoiding the drug for a few days before the tests may be necessary.

Side Effects

Acetaminophen causes few side effects. The most common one is lightheadedness. Some people may experience trembling and pain in the side or the lower back. Allergic reactions do occur in some people, but they are rare. Anyone who develops symptoms such as rash, swelling, or difficulty breathing after taking acetaminophen should stop taking the drug and get immediate medical attention. Other rare side effects include yellow skin or eyes, unusual bleeding or bruising, weakness, fatigue, bloody or black stools, bloody or cloudy urine, and a sudden decrease in the amount of urine.

Overdoses of acetaminophen may cause nausea, vomiting, sweating, and exhaustion. Very large overdoses can cause liver damage. In case of an overdose, a person is advised to get immediate medical attention.

Interactions

Acetaminophen may interact with a variety of other medicines. When this happens, the effects of one or both of the drugs may change or the risk of side effects may be greater. Among the drugs that may interact with acetaminophen are alcohol, non-steroidal anti-inflammatory drugs (NSAIDs) such as Motrin, oral contraceptives, the anti-seizure drug phenytoin (Dilantin), the blood-thinning drug warfarin (Coumadin), the cholesterol-lowering drug cholestyramine (Questran), the antibiotic Isoniazid, and zidovudine (Retrovir, AZT). People should check with a physician or pharmacist before combining acetaminophen with any other prescription or nonprescription (over-the-counter) medicine.

seizures

Definition

Antiepileptic drugs are medicines that reduce the frequency of epileptic seizures.

This class of drugs includes some drugs that have other uses as well. Phenobarbital is a barbiturate. Barbiturates were once widely used as sleeping pills and are still used in anesthesia for surgery. Clonazepam, clorazepate, and diazepam are members of the benzodiazepine group of drugs and are best known for their use as tranquilizers. Phenytoin is used both to control epileptic seizures and to control irregular heart beats.

Description

There are several different types of epilepsy. Different drugs work best on different types of epilepsy. Following is a list of some of the drugs and their uses:

* topamax (Topiramate), keppra, and ACTH: for infantile spasms (IS)
* ativan: for status epilepticas
* phenobarbital: widely used for tonic-clonic but effective in all forms of epilepsy
* phenytoin (Dilantin): used in tonic-clonic and psychomotor epilepsy
* ethosuximide (Zarontin): used to treat absence seizures
* methsuximide (Celontin): used to treat absence seizures
* zonisamide (Zonegran): used to treat partial seizures
* clonazepam (Klonopin): a benzodiazepine, used to treat absence, myoclonic, and akinetic seizures
* clorazepate (Tranxene): a benzodiazepine used to treat partial seizures
* diazepam (Valium): a benzodiazepine used for treatment of status epilepticus but effective against all forms of epilepsy
* primidone (Mysoline, Myidone, Sertan): useful for tonic-clonic, psychomotor, and focal epilepsy
* valproic acid and sodium valproate (Depakene, Depakote): used to treat all types of generalized seizures
* carbamazepine (Carbatrol, Tegretol): used in treatment of tonic-clonic, mixed, and psychomotor seizures
* felbamate (Felbatol): used primarily in adults but may be used to treat seizures associated with Lennox-Gastaut syndrome
* oxcarbazepine (Trileptal): for treatment of complex-partial, simple-partial, and focal seizures
* lamotrigine (Lamictal): used primarily in adults to treat simple and complex partial seizures but may be used to treat seizures associated with Lennox-Gastaut syndrome in children

General Use

Although epilepsy is a collective term for a variety of different types of seizures, all forms of epilepsy start with a random discharge of nerve impulses into the brain. Antiepileptic drugs act by either raising the seizure threshold or by limiting the spread of impulses from one nerve to another inside the brain. As of 2004 the exact mechanism of action is not understood, but there are theories about how some of these drugs work.

Phenobarbital appears to act by slowing down all parts of the brain.

Hydantoins, the class that includes phenytoin, mephenytoin, and ethotoin, seem to work by reducing the flow of sodium into and out of nerve cells. This makes the cells less likely to send out spontaneous impulses, which are the beginning of an epileptic seizure.

Succinimides (ethosuximide, methsuximide, phensuximide) elevate the seizure threshold and make it harder for a nerve impulse to spread from one nerve to another.

Zonisamide may work in a manner similar to the hydantoins, by restricting sodium flow, but some studies contradict this theory.

Benzodiazepines may work by stimulating some brain chemicals that normally slow down nerve function, but the exact mechanism is not known.

Felbamate is similar to the tranquilizer meprobamate (Equanil, Miltown) and may work by blocking the effects of some of the brain chemicals that stimulate the nervous system.

Precautions

Antiepileptic drugs have a large number of side effects and possible adverse effects. To work best, the blood levels of drugs must be kept within a fairly narrow range. Patients should be seen by a qualified physician on a regular basis and, if required, have their blood tested routinely. Too high a blood level of these drugs is likely to cause toxic reactions, while a level that is too low may lead to seizures.

Side Effects

Most anticonvulsant medications cause some drowsiness and stomach upset. The following list gives some of the common adverse effects of the various classes of drugs. Parents should consult specific references for more comprehensive lists.

Barbiturates cause the following side effects:

* clumsiness
* dizziness
* constipation
* depression
* faintness

Benzodiazepines cause the following side effects:

* fatigue
* abnormal behavior which can include hallucinations and agitation
* slowed breathing and slowed heart rate
* increased or decreased appetite
* rash and itching

Hydantoins cause the following side effects:

* confusion
* dizziness
* growth of the gums
* severe skin reactions
* stuttering and trembling

Succinimides cause the following side effects:

* dizziness and loss of balance
* severe skin reactions
* depression
* headache
* aggressive behavior

Valproic acid and sodium valproate cause the following side effects:

* stomach and intestinal discomfort
* weight gain or loss
* hair loss
* menstrual bleeding changes
* trembling

Interactions

These drugs have many interactions. People should consult specific references for full information regarding the interactions of all drugs that may be used to treat epilepsy.

Phenobarbital and the hydantoins have a large number of other interactions, but most of the drugs involved are not commonly used in patients under the age of 18 years. The succinimides have no significant drug interactions.

Valproic acid and sodium valproate interact with many of the other drugs used to treat epilepsy. If valproates are added to an existing anti-epileptic drug regimen or other drugs are added to a regimen that contains valproate, additional dose adjustments will usually be needed.

Cimetidine (Tagamet) increases the effects of diazepam, clonazepam, and clorazepate.

Interaction Prevention

Because antiepileptic drugs have large numbers of adverse effects and drug interactions, they should be prescribed only by physicians who are experienced in their use. Parents should consult specific references for complete information on the drugs related to their child's case.

Best effects and lowest toxicity are achieved when the blood levels of these drugs are kept constant. Maintaining that constant level requires taking the drugs at the same time each day.

Excessive gum growth associated with the hydantoins can normally be prevented or minimized by good dental care.

Patients taking antiepileptic drugs should not receive additional medications without checking with a physician or pharmacist for possible drug interactions. This precaution includes over-the-counter remedies.

Parental Concerns

For liquid dosage forms, parents should always use a medicinal teaspoon or calibrated teaspoon. These are designed to deliver an exact amount of medication. Household teaspoons vary in size and should not be used for measuring medication.

Different dosage forms of the same drug may vary in their onset and duration of action. This fact is particularly relevant to phenytoin, which comes in liquid, chewable tablets, short-acting capsules and long-acting capsules. Patients should not switch from one dosage form to another without consulting their physician.

Because children may not be able to describe some of the symptoms associated with some of the adverse effects of these drugs, any evidence of change in behavior or activity should be discussed with the physician who prescribed the drug.

antiepileptic

Definition

Antiepileptic drugs are medicines that reduce the frequency of epileptic seizures.

This class of drugs includes some drugs that have other uses as well. Phenobarbital is a barbiturate. Barbiturates were once widely used as sleeping pills and are still used in anesthesia for surgery. Clonazepam, clorazepate, and diazepam are members of the benzodiazepine group of drugs and are best known for their use as tranquilizers. Phenytoin is used both to control epileptic seizures and to control irregular heart beats.

Description

There are several different types of epilepsy. Different drugs work best on different types of epilepsy. Following is a list of some of the drugs and their uses:

• topamax (Topiramate), keppra, and ACTH: for infantile spasms (IS)
• ativan: for status epilepticas
• phenobarbital: widely used for tonic-clonic but effective in all forms of epilepsy
• phenytoin (Dilantin): used in tonic-clonic and psychomotor epilepsy
• ethosuximide (Zarontin): used to treat absence seizures
• methsuximide (Celontin): used to treat absence seizures
• zonisamide (Zonegran): used to treat partial seizures
• clonazepam (Klonopin): a benzodiazepine, used to treat absence, myoclonic, and akinetic seizures
• clorazepate (Tranxene): a benzodiazepine used to treat partial seizures
• diazepam (Valium): a benzodiazepine used for treatment of status epilepticus but effective against all forms of epilepsy
• primidone (Mysoline, Myidone, Sertan): useful for tonic-clonic, psychomotor, and focal epilepsy
• valproic acid and sodium valproate (Depakene, Depakote): used to treat all types of generalized seizures
• carbamazepine (Carbatrol, Tegretol): used in treatment of tonic-clonic, mixed, and psychomotor seizures
• felbamate (Felbatol): used primarily in adults but may be used to treat seizures associated with Lennox-Gastaut syndrome
• oxcarbazepine (Trileptal): for treatment of complex-partial, simple-partial, and focal seizures
• lamotrigine (Lamictal): used primarily in adults to treat simple and complex partial seizures but may be used to treat seizures associated with Lennox-Gastaut syndrome in children

General Use

Although epilepsy is a collective term for a variety of different types of seizures, all forms of epilepsy start with a random discharge of nerve impulses into the brain. Antiepileptic drugs act by either raising the seizure threshold or by limiting the spread of impulses from one nerve to another inside the brain. As of 2004 the exact mechanism of action is not understood, but there are theories about how some of these drugs work.

Phenobarbital appears to act by slowing down all parts of the brain.

Hydantoins, the class that includes phenytoin, mephenytoin, and ethotoin, seem to work by reducing the flow of sodium into and out of nerve cells. This makes the cells less likely to send out spontaneous impulses, which are the beginning of an epileptic seizure.

Succinimides (ethosuximide, methsuximide, phensuximide) elevate the seizure threshold and make it harder for a nerve impulse to spread from one nerve to another.

Zonisamide may work in a manner similar to the hydantoins, by restricting sodium flow, but some studies contradict this theory.

Benzodiazepines may work by stimulating some brain chemicals that normally slow down nerve function, but the exact mechanism is not known.

Felbamate is similar to the tranquilizer meprobamate (Equanil, Miltown) and may work by blocking the effects of some of the brain chemicals that stimulate the nervous system.

Precautions

Antiepileptic drugs have a large number of side effects and possible adverse effects. To work best, the blood levels of drugs must be kept within a fairly narrow range. Patients should be seen by a qualified physician on a regular basis and, if required, have their blood tested routinely. Too high a blood level of these drugs is likely to cause toxic reactions, while a level that is too low may lead to seizures.

Side Effects

Most anticonvulsant medications cause some drowsiness and stomach upset. The following list gives some of the common adverse effects of the various classes of drugs. Parents should consult specific references for more comprehensive lists.

Barbiturates cause the following side effects:

• clumsiness
• dizziness
• constipation
• depression
• faintness

Benzodiazepines cause the following side effects:

• fatigue
• abnormal behavior which can include hallucinations and agitation
• slowed breathing and slowed heart rate
• increased or decreased appetite
• rash and itching

Hydantoins cause the following side effects:

• confusion
• dizziness
• growth of the gums
• severe skin reactions
• stuttering and trembling

Succinimides cause the following side effects:

• dizziness and loss of balance
• severe skin reactions
• depression
• headache
• aggressive behavior

Valproic acid and sodium valproate cause the following side effects:

• stomach and intestinal discomfort
• weight gain or loss
• hair loss
• menstrual bleeding changes
• trembling

Interactions

These drugs have many interactions. People should consult specific references for full information regarding the interactions of all drugs that may be used to treat epilepsy.

Phenobarbital and the hydantoins have a large number of other interactions, but most of the drugs involved are not commonly used in patients under the age of 18 years. The succinimides have no significant drug interactions.

Valproic acid and sodium valproate interact with many of the other drugs used to treat epilepsy. If valproates are added to an existing anti-epileptic drug regimen or other drugs are added to a regimen that contains valproate, additional dose adjustments will usually be needed.

Cimetidine (Tagamet) increases the effects of diazepam, clonazepam, and clorazepate.

Interaction Prevention

Because antiepileptic drugs have large numbers of adverse effects and drug interactions, they should be prescribed only by physicians who are experienced in their use. Parents should consult specific references for complete information on the drugs related to their child's case.

Best effects and lowest toxicity are achieved when the blood levels of these drugs are kept constant. Maintaining that constant level requires taking the drugs at the same time each day.

Excessive gum growth associated with the hydantoins can normally be prevented or minimized by good dental care.

Patients taking antiepileptic drugs should not receive additional medications without checking with a physician or pharmacist for possible drug interactions. This precaution includes over-the-counter remedies.

Parental Concerns

For liquid dosage forms, parents should always use a medicinal teaspoon or calibrated teaspoon. These are designed to deliver an exact amount of medication. Household teaspoons vary in size and should not be used for measuring medication.

Different dosage forms of the same drug may vary in their onset and duration of action. This fact is particularly relevant to phenytoin, which comes in liquid, chewable tablets, short-acting capsules and long-acting capsules. Patients should not switch from one dosage form to another without consulting their physician.

Because children may not be able to describe some of the symptoms associated with some of the adverse effects of these drugs, any evidence of change in behavior or activity should be discussed with the physician who prescribed the drug.