Seven Legal Tips For Safe Nursing Practice

DELIVERING CARE that conforms to the standards of practice for nursing protects both your patients and you. Legally, nurses are held accountable to deliver care in a manner that any prudent nurse would render in the same or similar circumstances.

Nursing standards of care are based on the latest scientific data from nursing literature. Federal and state laws, nurse practice acts, court decisions, organizations such as the American Nurses Association and The Joint Commission, nursing organizations that offer specialty certification, facility policies and procedures, and job descriptions also come into play. As nursing standards change to accommodate advancements in medicine, nursing, and the law, keeping up with them can be challenging.

To help you maintain a high standard of practice and protect against legal problems related to your nursing care, I'll spell out seven key principles you should follow when providing patient care. I'll also provide examples of how lapses in the standard of care can expose nurses to legal liability.

Follow the nursing process

The five steps of the nursing process are recognized as a universal approach to nursing practice. A failure on your part during any of these steps can lead to trouble:

* nursing assessment —collecting data regarding your patient's signs and symptoms

* nursing diagnosis —appropriately identifying the patient's problems

* planning —setting goals of care and desired outcomes and identifying appropriate nursing actions

* implementation —performing the nursing actions identified in planning

* evaluation —determining if the goals were met and the outcomes were achieved and appropriately revising the care plan based on the patient's response.

Most legal actions brought against nurses arise because a patient or a patient advocate claims that the nurse breached a standard of care and that the breach resulted in harm to the patient. Although your primary concern is patient safety, adhering to the seven key principles that follow will also help protect you legally.

1. Administer medications properly

Medication errors jeopardize patient safety and are all too frequent. They can also be costly: Besides harming patients, they can lead to expensive follow-up care, litigation, and monetary awards for damages.

Knowing the drugs you administer is a vital element in the nursing standard of practice for medication therapy. Before giving an ordered medication, you must understand its purpose and actions, the dosage appropriate for your patient's condition, the administration route, possible adverse reactions, and any contraindications.

As the last line of defense before an error reaches the patient, you must also remain vigilant for problems at other points in the medication administration process, including the ordering, dispensing, and labeling of medications. If you're unfamiliar with a medication, check a current drug reference or ask the pharmacy.

When administering a drug, make sure you follow the traditional “five rights” of medication administration:

* right patient

* right medication

* right dose

* right time

* right route (delivery method or site of administration).

A “wrong” in any of these basic steps could harm or even kill a patient. But medication safety experts say these five points are just the tip of the iceberg. Other potentially serious lapses implicated in medication errors include failure to check the medication administration record (MAR) against the order, use of banned abbreviations leading to administration of a wrong drug or dosage, mistaken interpretation of illegible penmanship, failure to obtain clarification as needed, and transcription errors.

Consider the many ways a patient could miss a medication dose or get an extra dose. For example, he may miss a dose if the order wasn't transcribed, if he or the medication wasn't available when the dose was due, if a medication order was overlooked, or if his dose was mistakenly given to another patient. On the other hand, he could receive a duplicate dose if one nurse fails to document that she gave a dose and another nurse administers a second dose. This is more likely at breaks or mealtimes, when a second nurse may temporarily assume the patient's care.

Hospitals can implement safety mechanisms such as independent double checks to help prevent errors associated with single-unit doses of high-alert medications, especially in pediatric patients. According to your facility's policy, an independent double check may call for one nurse drawing up the medication and another nurse independently determining that the medication, dose, and route are correct; both then sign the entry in the MAR or enter the details in the electronic medical record. The facility determines which medications require this extra precaution; common examples include the high-alert drugs intravenous (I.V.) heparin and insulin.

The following scenario details a medication error due to lapses in prescribing, dispensing, and administering the drug.

A physician writes an order for the antibiotic doxycycline as Vibramycin, 100 mg I.M. b.i.d. But parenteral Vibramycin can be administered by the I.V. route only, not intramuscularly (I.M.). The pharmacist who reviews the order catches the error and includes a package insert with the vial indicating that the medication must be administered I.V. However, the nurse either doesn't see or disregards the pharmacist's instruction and follows the written order. As a result, the patient gets the medication via the wrong route.

The physician writing the prescription triggered this error. The pharmacist should have contacted the physician to clarify the order and also should have advised the nurse that the drug is to be given I.V. The nurse, unfamiliar with the right route for Vibramycin, should have consulted a current drug reference. Instead, she administered the medication according to the incorrect order. 1

2. Monitor for and report deterioration

According to the nursing process, the recognized standard of care calls for continually assessing your patient. Once you've performed an initial assessment, made a nursing diagnosis, and initiated a care plan, you must continue to evaluate his condition and communicate the effectiveness of his treatment. Worsening signs and symptoms or a lack of response suggest that you need to modify the care plan.

Many legal actions brought against nurses center on an allegation of failure to monitor or recognize changes in a patient's condition. But your duty goes beyond careful monitoring and prompt documentation of any changes. Even if you've done these well, failing to recognize the significance of the changes or to communicate them clearly and promptly to the attending practitioner could endanger your patient and leave you open to liability.

In some lawsuits, nurses have been charged with failure to communicate or “failure to rescue” (not responding appropriately to the patient's deteriorating condition). The following example shows why.

A woman is admitted to the hospital with severe abdominal and lower back pain. Based on the results of diagnostic testing, her physician suspects left lower lobe pneumonia. He starts the patient on a broad-spectrum antibiotic and her condition improves. Then her pulse rate rises, and she begins experiencing distress, shortness of breath, and diffuse pain. Her nurse, however, doesn't advise the physician of the change in her condition. Two hours later, the patient goes into cardiac arrest and dies. 2

3. Communicate effectively

Besides informing a practitioner about your patient's current or changing condition, you need to clearly communicate with patients and colleagues at every point of patient care. Good communication skills are essential when:

* transferring your patient's care to another person

* speaking with and educating your patient

* interacting with the patient's family or other visitors.

Communication is a two-way street that requires good listening skills too. Listen carefully to family members, who may be the first to know that something is wrong with their child or other loved one.

A growing challenge for health care providers in the United States is that more and more patients and their family members have limited proficiency in English. Rely on a professional medical interpreter to translate your instructions or questions to your patient and his responses. Hospitals have a duty to provide these interpreters as necessary. If a competent medical language interpreter isn't provided, you could face charges of substandard nursing care. (See “Speaking Up for Medical Language Interpreters” in the December issue of Nursing2007 to learn more about this topic . )

The Joint Commission has set a standard for communication when one caregiver transfers patient care to another caregiver. According to The Joint Commission requirements, the nurse transferring care must give the nurse taking responsibility for the patient all appropriate information about his condition, how he's responded to treatment during the shift, any changes in his condition or treatment plan, and any other information that will help the next nurse plan for his care. The standard requires that communication during transfer of care be interactive so that both parties can ask questions and that interruptions be minimal. 3 (A handy way to remember what information to include when you talk with other caregivers at such times appears in Think “SBAR” when discussing care .)

The following scenario shows how poor communication can lead to legal trouble.

A neonate is receiving an infusion of calcium gluconate through an I.V. line in his right foot when the nurse notes discoloration and edema at the injection site. As the baby is being transferred to another unit, a transfer note indicates the time the infiltration was discovered and the fact that the nurse checked the area before the transfer; however, these details don't appear in the medical record. In the medical record are flow sheets on which some of the original writing is scratched out and written over.

When the baby's parents arrive and ask the staff about the injury, they're told it's a blister. With time, however, it leads to considerable scarring and loss of motion. The parents sue the nurse who cared for the baby when the infiltration occurred. 4

Think “SBAR” when discussing care

To ensure effective, comprehensive communication when you report on your patient's condition or transfer care, remember the abbreviation SBAR :

S is for situation. (Identify the patient and why he was admitted.)

B is for background. (Provide a brief and significant medical history, including any tests or treatments completed.)

A is for assessment. (Describe the patient's current condition.)

R is for recommendation. (Discuss the plan of care for the patient.)

If you're receiving a new patient, be sure to get all this information from the prior caregiver.

You can learn more and download copies of two SBAR tools at the Institute for Healthcare Improvement Web site, http://www.ihi.org .

4. Delegate responsibly

In general, today's hospitalized patients are more acutely ill than those of the past. Because experienced nurses are in short supply, nursing teams that include unlicensed assistive personnel (UAPs) are making a comeback. As an RN, you must know who has the appropriate skills and competencies to meet a patient's needs when assigning a portion of her care to someone else. When you establish a work assignment, you're still responsible for the patient's care, and you must delegate appropriately and supervise the person carrying out the assignment.

To delegate safely, you must first know what your state board of nursing allows you to assign to others. Some states don't specify which duties may be delegated, but others may spell out tasks you may delegate, such as hygiene care or insertion of an indwelling urinary catheter. The “five rights” for delegating to another caregiver provide an easy-to-remember guide: right person, right task, right circumstances, right direction, and right supervision.

The right person refers to both the nurse who's delegating and those who'll perform the task. To direct and supervise appropriately, you must be a licensed nurse and you must understand the qualifications and competencies of your staff.

The right task is one that may be safely delegated for a specific patient. Typically, safe tasks are those that recur frequently in the patient's care; involve an unchanging, standard procedure; and have minimal risk and predictable results. Don't delegate complex tasks that require nursing assessment or nursing judgment.

To determine the right circumstances , consider all relevant factors, including appropriateness of the patient setting and available resources. Even tasks that fit the criteria for “right task” may not be appropriate if circumstances such as the patient's condition don't allow for delegating them. For example, assigning a UAP to help ambulate a patient who's at high risk for falls may not be appropriate.

Giving the right direction means providing a clear, concise description of the task you're delegating, including objective limits and expectations. Here's an example: “When you take Mr. Brown's blood pressure, the acceptable range is between 120/80 and 140/80. If you get a reading outside this range, please report your findings directly to me as soon as you get the reading.”

Providing the right supervision calls for knowing the qualifications and competencies of your staff, knowing the results of the delegated task, and evaluating performance. At times, you may need to intervene in the care being given. As the supervising nurse, you remain responsible for the patient and need to evaluate her condition and response to the tasks performed.

Here's an example of inappropriate delegation posing a great risk to the patient:

A charge nurse asks a UAP to use a meter to determine a patient's blood glucose level. The UAP goes to the patient's room and apparently does as asked. At the change of shift, the charge nurse asks the UAP for the test results. The UAP reports that when she did the test, “EEEEE” appeared on the meter screen. Asked if she repeated the test, the UAP replies that she hasn't but that she did document the reading in the patient's chart. A repeat test indicates that the patient's blood glucose reading is over 800 mg/dL, and she's transferred to the intensive care unit for treatment.

Violations in the “five rights” of delegation are evident in this scenario. The UAP apparently didn't have proper education to use the blood glucose meter and wasn't the right person to perform the task under the circumstances. Was the patient's blood glucose level stable before the nurse assigned the task? Proper direction and supervision were lacking too. The charge nurse should have specified a range for the patient's blood glucose reading and told the UAP to immediately report the findings to the charge nurse if they weren't within that range. Waiting until the end of the shift to ask for the results was another serious error in judgment.

5. Document in an accurate, timely manner

Accurate, timely documentation in your patient's medical record is crucial for these reasons:

* The medical record is a legal document required by state laws and regulations.

* It's a means of communication between caregivers that ensures continuity of care.

* It's used for education and research.

* It's used to substantiate insurance reimbursement claims.

* It can be used as evidence in legal proceedings to establish whether or not the care rendered met the legal standard of care.

A basic rule of safe documentation is to know and follow your facility's documentation policies and procedures. Institutional policies typically detail the forms of documentation to use, how to make a late entry, and how to correct an error in an entry. Failure to follow facility policy can result in inconsistencies; in turn, these may compromise patient safety and create legal problems if the record ends up in court. Regardless of how professional a nurse appears on the witness stand, careless documentation can make a profoundly negative impression on a jury.

The following situation demonstrates the dangers of careless documentation.

A man injures his left leg falling off the back of a truck. A cast is applied to his leg in the emergency department, and he's admitted to the hospital for his injuries. The next day, he begins to develop numbness in his left foot. The physician examines the patient and notes in the medical record that his “toes are cool and getting more numb,” so he removes the top part of the leg cast.

The next day, the patient complains of severe pain in his left foot and the nurse alerts another physician of the change. Examining the patient and noting that he has compartment syndrome, the second physician performs a fasciotomy, but the patient's circulatory problems continue and his left leg has to be amputated.

A malpractice suit is brought against the physicians, hospital, and nursing staff. Because hourly circulation checks weren't documented in the patient's medical record, one of the decisions the court has to make is whether nursing negligence was partially responsible for the loss of his leg. 5

6. Know and follow facility policies and procedures

Institutional policies and procedures help establish the nursing standards of care you'd be held to in court. Patient-care policies and procedures must be based on current and recognized practice. They must be updated regularly, and they should be realistic.

Any deviation from a policy or procedure that harms the patient can subject you and the facility to liability exposure, so some flexibility is necessary. For example, rather than stating that patients' vital signs must be taken every 4 hours, a policy stating “within 4 hours” or “every 4 hours plus or minus 30 minutes” allows some leeway.

The nurse in the following scenario is sued after failing to follow hospital policy and procedure.

A nurse in an acute care hospital applies wrist restraints to a patient before briefly leaving his room. When she returns, the patient is next to the bed, hanging by his arms from the restraints. He subsequently develops pain in his right wrist and has X-rays, which show a fracture.

The patient sues the nurse, claiming that the restraints caused his injury. Court testimony shows that applying wrist restraints to the patient was inconsistent with hospital policy, but the patient can't prove that the restraints caused his injury. 6

7. Use equipment properly

As a nurse, you have a duty to make sure you've received adequate training on the equipment you use to provide patient care. You must understand the equipment's intended use, know how to operate it properly, and follow policies and procedures for using it if they exist. Never try guessing how to use equipment.

The following scenario demonstrates how a patient is harmed when medical equipment is misused.

A patient is undergoing hysteroscopy. The equipment is missing a clip, and the nurses improperly connect an exhaust line that's hanging loose to an outflow port. The patient dies, and the family sues the hospital.

Evidence submitted at trial indicates that when the equipment used for the procedure left the manufacturer, it was properly set up. It also shows that two of the nurses assigned to the patient's case had no training on the use of the equipment and that their lack of training may have resulted in improper unclipping of the tube. 7

Standards put into practice

By adhering to the seven principles of nursing care spelled out here, you help protect your patients, meet the standard of nursing care in your daily practice, and avoid legal problems.

Source nursingmedia.com

Acetaminophen

Pharmacy Author: Omudhome Ogbru, PharmD
Medical and Pharmacy Editor: Jay W. Marks, MD

BRAND NAME: Tylenol and others

DRUG CLASS AND MECHANISM: Acetaminophen belongs to a class of drugs called analgesics (pain relievers) and antipyretics (fever reducers). The exact mechanism of action of acetaminophen is not known. Acetaminophen relieves pain by elevating the pain threshold, that is, by requiring a greater amount of pain to develop before a person feels it. It reduces fever through its action on the heat-regulating center of the brain. Specifically, it tells the center to lower the body's temperature when the temperature is elevated. The FDA approved acetaminophen in 1951.

PRESCRIPTION: No.

GENERIC AVAILABLE: Yes.

PREPARATIONS: Liquid suspension, chewable tablets, coated caplets, gelcaps, geltabs, and suppositories. Common dosages are 325, 500 and 650 mg.

STORAGE: Store tablets and solutions at room temperature 15°-30°C (59°-86°F). Suppositories should be refrigerated below 27°C (80°F).

PRESCRIBED FOR: Acetaminophen is used for the relief of fever as well as aches and pains associated with many conditions. Acetaminophen relieves pain in mild arthritis but has no effect on the underlying inflammation, redness, and swelling of the joint. If the pain is not due to inflammation, acetaminophen is as effective as aspirin. It is as effective as the non-steroidal antiinflammatory drug ibuprofen (Motrin) in relieving the pain of osteoarthritis of the knee. Unless directed by physician, acetaminophen should not be used for longer than 10 days.

DOSING: The oral dose for adults is 325 to 650 mg every 4 to 6 hours. The maximum daily dose is 4 grams. The oral dose for a child is based on the child's age, and the range is 40-650 mg every 4 hours.

When administered as a suppository, the adult dose is 650 mg every 4 to 6 hours. For children, the dose is 80-325 mg every 4 to 6 hours depending on age.

DRUG INTERACTIONS: Acetaminophen is metabolized (eliminated by conversion to other chemicals) by the liver. Therefore drugs that increase the action of liver enzymes that metabolize acetaminophen [for example, carbamazepine (Tegretol), isoniazid (INH, Nydrazid, Laniazid), rifampin (Rifamate, Rifadin, Rimactane)] reduce the levels of acetaminophen and may decrease the action of acetaminophen. Doses of acetaminophen greater than the recommended doses are toxic to the liver and may result in severe liver damage. The potential for acetaminophen to harm the liver is increased when it is combined with alcohol or drugs that also harm the liver.

Cholestyramine (Questran) reduces the effect of acetaminophen by decreasing its absorption into the body from the intestine. Therefore, acetaminophen should be administered 3 to 4 hours after cholestyramine or one hour before cholestyramine .

Acetaminophen doses greater than 2275 mg per day may increase the blood thinning effect of warfarin (Coumadin) by an unknown mechanism. Therefore, prolonged administration or large doses of acetaminophen should be avoided during warfarin therapy.

PREGNANCY: Acetaminophen is used in all stages of pregnancy and is the drug of choice for short-term treatment of fever and minor pain during pregnancy.

NURSING MOTHERS: Acetaminophen is excreted in breast milk in small quantities. However, acetaminophen use by the nursing mother appears to be safe.

SIDE EFFECTS: When used appropriately, side effects with acetaminophen are rare. The most serious side effect is liver damage due to large doses, chronic use or concomitant use with alcohol or other drugs that also damage the liver. Chronic alcohol use may also increase the risk of stomach bleeding.

Source emedicine.com

Tramadol

Pharmacy Author: Omudhome Ogbru, PharmD
Medical and Pharmacy Editor: Jay W. Marks, MD

BRAND NAME: Ultram

DRUG CLASS AND MECHANISM: Tramadol is a man-made (synthetic) analgesic (pain reliever). Its exact mechanism of action is unknown but similar morphine. Like morphine, tramadol binds to receptors in the brain (opioid receptors) that are important for transmitting the sensation of pain from throughout the body to. Tramadol, like other narcotics used for the treatment of pain, may be abused. Tramadol is not a nonsteroidal antiinflammatory drug (NSAID) and does not have the increased risk of stomach ulceration and internal bleeding that can occur with NSAIDs.

PRESCRIPTION: Yes

GENERIC AVAILABLE: Yes

PREPARATIONS: Tablets (immediate release): 50 mg. Tablets (extended release): 100, 200, and 300 mg.

STORAGE: Store at room temperature, 15-30°C (59-86°F). Store in a sealed container.

PRESCRIBED FOR: Tramadol is used in the management of moderate to moderately severe pain. Extended release tablets are used for moderate to moderately severe chronic pain in adults who require continuous treatment for an extended period.

DOSING: The recommended dose of tramadol is 50-100 mg (immediate release tablets) every 4-6 hours as needed for pain. The maximum dose is 400 mg/day. To improve tolerance patients should be started at 25 mg/day, and doses may be increased by 25 mg every 3 days to reach 100 mg/day (25 mg 4 times daily). Thereafter, doses can be increased by 50 mg every 3 days to reach 200 mg day (50 mg 4 times daily). Tramadol may be taken with or without food.

Recommended dose for extended release tablets is 100 mg daily which may be increased by 100 mg every 5 days but not to exceed 300 mg /day. Extended release tablets should be swallowed whole and not crushed or chewed.

DRUG INTERACTIONS: Carbamazepine reduces the effect of tramadol by increasing its inactivation in the body. Quinidine (Quinaglute, Quinidex) reduces the inactivation of tramadol, thereby increasing the concentration of tramadol by 50%-60%. Combining tramadol with monoamine oxidase inhibitors (for example, Parnate) or selective serotonin inhibitors [(SSRIs, for example, fluoxetine (Prozac)] may result in severe side effects such as seizures or a condition called serotonin syndrome.

Tramadol may increase central nervous system and respiratory depression when combined with alcohol, anesthetics, narcotics, tranquilizers or sedative hypnotics.

PREGNANCY: The safety of tramadol during pregnancy has not been established.

NURSING MOTHERS: The safety of tramadol in nursing mothers has not been established.

SIDE EFFECTS: Tramadol is generally well tolerated, and side effects are usually transient. Commonly reported side effects include nausea, constipation, dizziness, headache, drowsiness, and vomiting. Less commonly reported side effects include itching, sweating, dry mouth, diarrhea, rash, visual disturbances, and vertigo. Some patients who received tramadol have reported seizures. Abrupt withdrawal of tramadol may result in anxiety, sweating, insomnia, rigors, pain, nausea, diarrhea, tremors, and hallucinations.

Source emedicine.com

Metronidazole

Pharmacy Author: Omudhome Ogbru, PharmD
Medical and Pharmacy Editor: Jay W. Marks, MD

BRAND NAME: Flagyl

DRUG CLASS AND MECHANISM: Metronidazole is an antibiotic effective against anaerobic bacteria and certain parasites. Anaerobic bacteria are single-celled, living organisms that thrive in environments in which there is little oxygen (anaerobic environments) and can cause disease in the abdomen (bacterial peritonitis), liver (liver abscess), and pelvis (abscess of the ovaries and the Fallopian tubes). Giardia lamblia and ameba are intestinal parasites that can cause abdominal pain and diarrhea in infected individuals. Trichomonas is a vaginal parasite that causes inflammation of the vagina (vaginitis). Metronidazole selectively blocks some of the functions within the bacterial cells and the parasites resulting in their death.

PRESCRIPTION: Yes

GENERIC AVAILABLE: Yes

PREPARATIONS: Tablets: 250 and 500 mg. Tablets, extended release: 750 mg. Capsule: 375 mg. Cream: 0.75% and 1%. Lotion: 0.75%. Gel: 0.75% and 1%. Injection: 5 mg/ml

STORAGE: Metronidazole should be stored at room temperature and protected from light.

PRESCRIBED FOR: Metronidazole is used to treat parasitic infections including Giardia infections of the small intestine, amebic liver abscess and amebic dysentery (infection of the colon causing bloody diarrhea), bacterial vaginosis, trichomonas vaginal infections, and carriers of trichomonas (both sexual partners) who do not have symptoms of infection. Metronidazole is also used alone or in combination with other antibiotics in treating abscesses in the liver, pelvis, abdomen and brain caused by susceptible anaerobic bacteria. Metronidazole is also used in treating infection of the colon caused by a bacterium called C. difficile. (Many commonly-used antibiotics can alter the type of bacteria that inhabit the colon. C. difficile is an anaerobic bacterium that can infect the colon when the normal types of bacteria in the colon are inhibited by common antibiotics. This leads to inflammation of the colon (pseudomembranous colitis) with severe diarrhea and abdominal pain.) Metronidazole also is used in combination with other drugs to treat Helicobacter pylori (H. pylori) that causes stomach or intestinal ulcers. Metronidazole topical gel is used for treating acne rosacea, and the vaginal gel is used for treating bacterial vaginosis.

DOSING: Metronidazole may be taken orally with or without food. In the hospital, metronidazole can be administered intravenously to treat serious infections. The liver is primarily responsible for eliminating metronidazole from the body, and doses may need to be reduced in patients with liver disease and abnormal liver function.

Various metronidazole regimens are used. Some examples are listed below.

• Amebic dysentery: 750 mg orally 3 times daily for 5-10 days
  
  
• Amebic liver abscess: 500-750 mg orally three times daily for 5-10 days
  
  
• Anaerobic infections: 7.5 mg/kg orally every 6 hours not to exceed 4 grams daily
  
  
• Bacterial Vaginosis: 750 mg (extended release tablets) once daily for 7 days. One applicator-full of 0.75% vaginal gel, once or twice daily for 5 days.
  
  
• Clostridium difficile infection: 250-500 mg orally 4 times daily or 500-750 orally 3 times daily
  
  
• Giardia: 250 mg orally three times daily for 5 days
  
  
• Helicobacter pylori: 800-1500 mg orally daily for several days in combination with other drugs.
  
  
• Pelvic inflammatory disease (PID): 500 mg orally twice daily for 14 days in combination with other drugs.
  
  
• Trichomoniasis: 2 g single dose or 1 g twice
  
  
• Rosacea: apply topical gel 0.75-1% once daily

DRUG INTERACTIONS: Alcohol should be avoided because metronidazole and alcohol together can cause severe nausea, vomiting, cramps, flushing, and headache.

Metronidazole can increase the blood thinning effects of warfarin (Coumadin) and increase the risk of bleeding probably by reducing the break down of warfarin.

Cimetidine (Tagamet) increases blood levels of metronidazole while cholestyramine reduces blood levels of metronidazole by reducing its absorption.

Metronidazole should not be combined with amprenavir for treating human immunodeficiency disease (infection with HIV) because amprenavir contains propylene glycol. Metronidazole blocks the breakdown of propylene glycol in the liver leading to accumulation of propylene glycol in blood. Accumulation of propylene glycol could cause seizures, increased heart rate, and lead to kidney failure.

Metronidazole increases the blood levels of carbamazepine, lithium and cyclosporine though unknown mechanisms. Serious reactions may occur if these drugs are taken with metronidazole.

PREGNANCY: Metronidazole is not used in early pregnancy because of potential adverse effects on the fetus.

NURSING MOTHERS: Metronidazole is excreted in breast milk. Nursing mothers, because of potential adverse effects on the newborn, should not use metronidazole.

SIDE EFFECTS: Metronidazole is a valuable antibiotic and is generally well tolerated with appropriate use. Minor side effects include nausea, headaches, loss of appetite, a metallic taste, and rarely a rash. Serious side effects of metronidazole are rare. Serious side effects include seizures and damage of nerves resulting in numbness and tingling of extremities (peripheral neuropathy). Metronidazole should be stopped if these symptoms appear.

Source emedicine.com

Methylprednisolone

Pharmacy Author: Omudhome Ogbru, PharmD
Medical and Pharmacy Editor: Jay W. Marks, MD

BRAND NAME: Medrol, Depo-Medrol

DRUG CLASS AND MECHANISM: Methylprednisolone is a synthetic (man-made) corticosteroid. Corticosteroids are naturally-occurring chemicals produced by the adrenal glands located adjacent to the kidneys. Corticosteroids affect metabolism in various ways and modify the immune system. Corticosteroids also block inflammation and are used in a wide variety of inflammatory diseases affecting many organs.

PRESCRIPTION: Yes

GENERIC AVAILABLE: Yes

PREPARATIONS: Tablets: 2, 4, 8, 16, 24, and 32 mg. Injection: 20, 40, and 80 mg/ml.

STORAGE: Tablets should be kept at room temperature, between 20° and 25°C (68-77°F).

PRESCRIBED FOR: Methylprednisolone is used to achieve prompt suppression of inflammation. Examples of inflammatory conditions for which methylprednisolone is used include rheumatoid arthritis, systemic lupus erythematosus, acute gouty arthritis, psoriatic arthritis, ulcerative colitis, and Crohn's disease. Severe allergic conditions that fail conventional treatment also may respond to methylprednisolone. Examples include bronchial asthma, allergic rhinitis, drug-induced dermatitis, and contact and atopic dermatitis. Chronic skin conditions treated with methylprednisolone include dermatitis herpetiformis, pemphigus, severe psoriasis and severe seborrheic dermatitis. Chronic allergic and inflammatory conditions of the uvea, iris, conjunctiva and optic nerves of the eyes also are treated with methylprednisolone.

DOSING: Dosage requirements of corticosteroids vary among individuals and the diseases being treated. In general, the lowest effective dose is used. The initial oral dose is 4-48 mg daily depending on the disease. The initial dose should be adjusted based on response. Corticosteroids given in multiple doses throughout the day are more effective but also more toxic than the same total daily dose given once daily, or every other day. Methylprednisolone should be taken with food.

DRUG INTERACTIONS: Troleandomycin (TAO), an infrequently used macrolide antibiotic, reduces the liver's ability to metabolize methylprednisolone (and possibly other corticosteroids). This interaction can result in higher blood levels of methylprednisolone and a higher probability of side effects. Erythromycin and clarithromycin (Biaxin) are likely to share this interaction, and ketoconazole (Nizoral) also inhibits the metabolism of methylprednisolone. Estrogens, including birth control pills, can increase the effect of corticosteroids by 50% by mechanisms that are not completely understood. For all of the above interactions, the dose of methylprednisolone may need to be lowered. Cyclosporin reduces the metabolism of methylprednisolone while methylprednisolone reduces the metabolism of cyclosporin. When given together, the dose of both drugs may need to be reduced to avoid increased side effects.

Methylprednisolone may increase or decrease the effect of blood thinners [for example, warfarin (Coumadin)]. Blood clotting should be monitored and therapy adjusted in order to achieve the desired level of blood thinning (anti-coagulation).

Phenobarbital, phenytoin (Dilantin), and rifampin (Rifadin, Rimactane) may increase the metabolism of methylprednisolone and other corticosteroids, resulting in lower blood levels and reduced effects. Therefore, the dose of methylprednisolone may need to be increased if treatment with phenobarbital is begun.

PREGNANCY: Methylprednisolone has not been adequately evaluated in pregnant women.

NURSING MOTHERS: Methylprednisolone has not been adequately evaluated in nursing mothers.

SIDE EFFECTS: Adverse effects of methylprednisolone depend on dose, duration and frequency of administration. Short courses of methylprednisolone are usually well-tolerated with few, mild side effects. Long term, high doses of methylprednisolone may produce predictable and potentially serious side effects. Whenever possible, the lowest effective doses of methylprednisolone should be used for the shortest length of time to minimize side effects. Alternate day dosing also can help reduce side effects.

Side effects of methylprednisolone and other corticosteroids range from mild annoyances to serious irreversible bodily damage. Side effects include fluid retention, weight gain, high blood pressure, potassium loss, headache, muscle weakness, puffiness of the face, hair growth on the face, thinning and easy bruising of the skin, glaucoma, cataracts, peptic ulceration, worsening of diabetes, irregular menses, growth retardation in children, convulsions, and psychic disturbances. Psychic disturbances may include depression, euphoria, insomnia, mood swings, personality changes, and even psychotic behavior.

Prolonged use of methylprednisolone can depress the ability of the body's adrenal glands to produce corticosteroids. Abruptly stopping methylprednisolone in these individuals can cause symptoms of corticosteroid insufficiency, with accompanying nausea, vomiting, and even shock. Therefore, withdrawal of methylprednisolone usually is accomplished by gradually lowering the dose. Gradually tapering methylprednisolone not only minimizes the symptoms of corticosteroid insufficiency, it also reduces the risk of an abrupt flare of the disease being treated.

Methylprednisolone and other corticosteroids can mask signs of infection and impair the body's natural immune response to infection. Patients on corticosteroids are more susceptible to infections and can develop more serious infections than individuals not on corticosteroids. For example, chickenpox and measles viruses can produce serious and even fatal illnesses in patients on high doses of methylprednisolone. Live virus vaccines, such as smallpox vaccine, should be avoided in patients taking high doses of methylprednisolone since even vaccine viruses may cause disease in these patients. Some infectious organisms, such as tuberculosis (TB) and malaria, can remain dormant in patients for years. Methylprednisolone and other corticosteroids can allow these infections to reactivate and cause serious illness. Patients with dormant TB may require anti-TB medications while undergoing prolonged corticosteroid treatment.

By interfering with the patient's immune response, methylprednisolone can prevent vaccines from being effective. Methylprednisolone also can interfere with the TB skin test and cause falsely negative results in patients with dormant TB infections.

Methylprednisolone impairs calcium absorption and new bone formation. Patients on prolonged treatment with methylprednisolone and other corticosteroids can develop osteoporosis and an increased risk of bone fractures. Supplemental calcium and vitamin D are encouraged to slow this process of bone thinning. In rare individuals, destruction of large joints can occur while undergoing treatment with methylprednisolone or other corticosteroids (aseptic necrosis). These patients experience severe pain in the joints involved, and can require joint replacement. The reason behind such destruction is not clear. Methylprednisolone can be used in pregnancy, but is generally avoided.

Source emedicine.com

Prednisone

Pharmacy Author: Omudhome Ogbru, Pharm.D.
Medical Editor: Jay Marks, M.D.

BRAND NAME: Deltasone, Orasone, Prednicen-M, Liquid Pred

DRUG CLASS AND MECHANISM: Prednisone is an oral, synthetic (man-made) corticosteroid used for suppressing the immune system and inflammation. It has effects similar to other corticosteroids such as triamcinolone (Kenacort), methylprednisolone (Medrol), prednisolone (Prelone) and dexamethasone (Decadron). These synthetic corticosteroids mimic the action of cortisol (hydrocortisone), the naturally-occurring corticosteroid produced in the body by the adrenal glands. Corticosteroids have many effects on the body, but they most often are used for their potent anti-inflammatory effects, particularly in those conditions in which the immune system plays an important role. Such conditions include arthritis, colitis, asthma, bronchitis, certain skin rashes, and allergic or inflammatory conditions of the nose and eyes. Prednisone is inactive in the body and, in order to be effective, first must be converted to prednisolone by enzymes in the liver. Therefore, prednisone may not work as effectively in people with liver disease whose ability to convert prednisone to prednisolone is impaired

PRESCRIPTION: yes

GENERIC AVAILABLE: yes

PREPARATIONS: Tablets of 2.5, 5, 10, 20, and 50 mg. Oral solution or syrup of 5mg/5ml

STORAGE: Store at room temperature 20-25°C (68-77°F), and keep away from moisture.

PRESCRIBED FOR: Prednisone is used in the management of inflammatory conditions or diseases in which the immune system plays an important role. Since prednisone is used in so many conditions, only the most common or established uses are mentioned here. Prednisone most often is used for treating several types of arthritis, ulcerative colitis, Crohn's disease, systemic lupus, allergic reactions, asthma and severe psoriasis. It also is used for treating leukemias, lymphomas, idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia. Corticosteroids, including prednisone, are commonly used to suppress the immune system and prevent the body from rejecting transplanted organs. Prednisone is used as replacement therapy in patients whose adrenal glands are unable to produce sufficient amounts of cortisol.

DOSING: The initial dose of prednisone varies depending on the condition being treated and the age of the patient. The starting dose may be from 5 to 60 mg per day and often is adjusted based on the response of the condition being treated. Corticosteroids typically do not produce immediate effects and must be used for several days before maximal effects are seen. It may take much longer before conditions respond to treatment. Prolonged therapy with prednisone causes the adrenal glands to atrophy and stop producing cortisol. When prednisone is discontinued after a period of prolonged therapy, the dose of prednisone must be tapered (lowered gradually) to allow the adrenal glands time to recover. (See side effects.) It is recommended that prednisone be taken with food.

DRUG INTERACTIONS: Prednisone may interact with estrogens and phenytoin (Dilantin). Estrogens may reduce the action of enzymes in the liver that break down (eliminate) the active form of prednisone, prednisolone. As a result, the levels of prednisolone in the body may increase and lead to more frequent side effects. Phenytoin increases the activity of enzymes in the liver that break down (eliminate) prednisone and thereby may reduce the effectiveness of prednisone. Thus, if phenytoin is being taken, an increased dose of prednisone may be required.

PREGNANCY: Corticosteroids cross the placenta into the fetus. Compared to other corticosteroids, however, prednisone is less likely to cross the placenta. Chronic use of corticosteroids during the first trimester of pregnancy may cause cleft palate.

NURSING MOTHERS: Corticosteroids are secreted in breast milk and can cause side effects in the nursing infant. Prednisone is less likely than other corticosteroids to be secreted in breast milk, but it may still pose a risk to the infant.

SIDE EFFECTS: Side effects of prednisone and other corticosteroids range from mild annoyances to serious, irreversible damage, and they occur more frequently with higher doses and more prolonged treatment. Side effects include retention of sodium (salt) and fluid, weight gain, high blood pressure, loss of potassium, headache and muscle weakness. Prednisone also causes puffiness of the face (moon face), growth of facial hair, thinning and easy bruising of the skin, impaired wound healing, glaucoma, cataracts, ulcers in the stomach and duodenum, worsening of diabetes, irregular menses, rounding of the upper back ("buffalo hump"), obesity, retardation of growth in children, convulsions, and psychiatric disturbances. The psychiatric disturbances include depression, euphoria, insomnia, mood swings, personality changes, and even psychotic behavior.

Prednisone suppresses the immune system and, therefore, increases the frequency or severity of infections and decreases the effectiveness of vaccines and antibiotics. Prednisone may cause osteoporosis that results in fractures of bones. Patients taking long-term prednisone often receive supplements of calcium and vitamin D to counteract the effects on bones. Calcium and vitamin D probably are not enough, however, and treatment with bisphosphonates such as alendronate (Fosamax) and risedronate (Actonel) may be necessary. Calcitonin (Miacalcin) also is effective. The development of osteoporosis and the need for treatment can be monitored using bone density scans.

Prolonged use of prednisone and other corticosteroids causes the adrenal glands to atrophy (shrink) and stop producing the body's natural corticosteroid, cortisol. If prednisone is abruptly withdrawn after prolonged use, the adrenal glands are unable to produce enough cortisol to compensate for the withdrawal, and symptoms of corticosteroid insufficiency (adrenal crisis) may occur. These symptoms include nausea, vomiting and shock. Therefore, prednisone should be discontinued gradually so that the adrenal glands have time to recover and resume production of cortisol. Until the glands fully recover, it may be necessary to treat patients who have recently discontinued corticosteroids with a short course of corticosteroids during times of stress (infection, surgery, etc.), times when corticosteroids are particularly important to the body.

A serious complication of long-term use of corticosteroids is aseptic necrosis of the hip joints. Aseptic necrosis is a condition in which there is death and degeneration of the hip bone. It is a painful condition that ultimately can lead to the need for surgical replacement of the hip. Aseptic necrosis also has been reported in the knee joints. The estimated incidence of aseptic necrosis among long-term users of corticosteroids is 3-4%. Patients taking corticosteroids who develop pain in the hips or knees should report the pain to their doctors promptly.

Source emedicine.com

Amoxicillin

Pharmacy Author: Omudhome Ogbru, PharmD
Medical and Pharmacy Editor: Jay W. Marks, MD

BRAND NAME: Amoxil, Dispermox, Trimox

DRUG CLASS AND MECHANISM: Amoxicillin belongs to a class of antibiotics called penicillins. Other members of this class include ampicillin (Unasyn), piperacillin (Pipracil), ticarcillin (Ticar) and several others. These antibiotics all have a similar mechanism of action. They do not kill bacteria, but they stop bacteria from multiplying by preventing bacteria from forming the walls that surround them. The walls are necessary to protect bacteria from their environment and to keep the contents of the bacterial cell together. Bacteria cannot survive without a cell wall. Amoxicillin is effective against many different bacteria including H. influenzae, N. gonorrhoea, E. coli, Pneumococci, Streptococci, and certain strains of Staphylococci.

PRESCRIPTION: Yes.

GENERIC AVAILABLE: Yes.

PREPARATIONS: Capsules: 250 and 500 mg. Tablets: 500 and 875 mg. Chewable tablets: 125, 200, 250, and 400 mg. Powder for suspension: 50 mg/ml ; 125, 200, 250, and 400 mg/5 ml. Tablets for suspension: 200 and 400 mg

STORAGE: Store Amoxil capsules as well as 125 and 250 mg dry powder at or below 20°C (68°F); tablets, chewable tablets, as well as 200 and 400 mg dry powder should be stored at or below 25°C(77°F). Store Trimox capsules and unreconstituted powder at or below 20°C (68°F) and chewable tablets at room temperature 15°-30°C (59°-86°F). Powder that has been mixed with water should be discarded after 14 days. Refrigeration is preferred but not required for powder mixed with water.

PRESCRIBED FOR: Amoxicillin is used to treat infections due to organisms that are susceptible to the effects of amoxicillin. Common infections that amoxicillin is used for include infections of the middle ear, tonsils, throat, larynx (laryngitis), bronchi (bronchitis), lungs (pneumonia), urinary tract, and skin. It also is used to treat gonorrhea.

DOSING: For most infections in adults the dosing regimens for amoxicillin are 250 mg every 8 hours, 500 mg every 8 hours, 500 mg every 12 hours or 875 mg every 12 hours, depending on the type and severity of infection.

For the treatment of adults with gonorrhea, the dose is 3 g given as one dose.

For most infections, children older than 3 months but less than 40 kg are treated with 25 mg/kg/day in divided doses every 12 hours, 20 mg/kg/day in divided doses every 8 hours, 40 mg/kg/day in divided doses every 8 hours or 45 mg/kg/day in divided doses every 12 hours depending on type and severity of the infection.

Amoxicillin can be taken with or without food.

DRUG INTERACTIONS: Amoxicillin is rarely associated with important drug interactions.

PREGNANCY: Penicillins are generally considered safe for use by pregnant women who are not allergic to penicillin.

NURSING MOTHERS: Small amounts of amoxicillin may be excreted in breast milk and may cause diarrhea or allergic responses in nursing infants. Amoxicillin is generally considered safe to use while breastfeeding. Amoxicillin is used to treat infections in the newborn.

SIDE EFFECTS: Side effects due to amoxicillin include diarrhea, dizziness, heartburn, insomnia, nausea, itching, vomiting, confusion, abdominal pain, easy bruising, bleeding, rash, and allergic reactions. Individuals who are allergic to antibiotics in the class of cephalosporins may also be sensitive to amoxicillin.

Source emedicine.com

Ibuprofen

Pharmacy Author: Omudhome Ogbru, PharmD
Medical and Pharmacy Editor: Jay W. Marks, MD

BRAND NAME: Advil, Children's Advil/Motrin, Medipren, Motrin, Nuprin, PediaCare Fever etc.

DRUG CLASS AND MECHANISM: Ibuprofen belongs to a class of drugs called non-steroidal anti-inflammatory drugs (NSAIDs). Other members of this class include aspirin, naproxen (Aleve), indomethacin (Indocin), nabumetone (Relafen) and several others. These drugs are used for the management of mild to moderate pain, fever, and inflammation. Pain, fever, and inflammation are promoted by the release in the body of chemicals called prostaglandins. Ibuprofen blocks the enzyme that makes prostaglandins (cyclooxygenase), resulting in lower levels of prostaglandins. As a consequence, inflammation, pain and fever are reduced. The FDA approved ibuprofen in 1974.

PRESCRIPTION: Yes

GENERIC AVAILABLE: Yes

PREPARATIONS: Tablets of 200, 400, 600, and 800 mg; Chewable tablets of 50 and 100 mg; Capsules of 200 mg; Suspension of 100 mg/2.5 ml and 100 mg/5 ml; Oral drops of 40 mg/ml.

STORAGE: Ibuprofen should be stored at room temperature, between 15-30°C (59-86°F).

PRESCRIBED FOR: Ibuprofen is used for the treatment of mild to moderate pain, inflammation and fever caused by many and diverse diseases.

DOSING: For minor aches, mild to moderate pain, menstrual cramps, and fever, the usual adult dose is 200 or 400 mg every 4 to 6 hours.

Arthritis is treated with 300 to 800 mg 3 or 4 times daily.

When under the care of a physician, the maximum dose of ibuprofen is 3.2 g daily. Otherwise, the maximum dose is 1.2 g daily. Individuals should not use ibuprofen for more than 10 days for the treatment of pain or more than 3 days for the treatment of a fever unless directed by a physician.

Children 6 months to 12 years of age usually are given 5-10 mg/kg of ibuprofen every 6-8 hours for the treatment of fever and pain. The maximum dose is 40 mg/kg daily.

Juvenile arthritis is treated with 20 to 40 mg/kg/day in 3-4 divided doses.

Ibuprofen should be taken with meals to prevent stomach upset.

DRUG INTERACTIONS: Ibuprofen is associated with several suspected or probable interactions that can affect the action of other drugs. Ibuprofen may increase the blood levels of lithium (Eskalith) by reducing the excretion of lithium by the kidneys. Increased levels of lithium may lead to lithium toxicity. Ibuprofen may reduce the blood pressure-lowering effects of drugs that are given to reduce blood pressure. This may occur because prostaglandins play a role in the regulation of blood pressure. When ibuprofen is used in combination with aminoglycosides [for example, gentamicin (Garamycin)] the blood levels of the aminoglycoside may increase, presumably because the elimination of aminoglycosides from the body is reduced. This may lead to aminoglycoside-related side effects. Individuals taking oral blood thinners or anticoagulants [for example, warfarin (Coumadin)] should avoid ibuprofen because ibuprofen also thins the blood, and excessive blood thinning may lead to bleeding.

PREGNANCY: There are no adequate studies of ibuprofen in pregnant women. Therefore, ibuprofen is not recommended during pregnancy. Ibuprofen should be avoided in late pregnancy due to the risk of premature closure of the ductus arteriosus in the fetal heart..

NURSING MOTHERS: Ibuprofen is not excreted in breast milk. Use of ibuprofen while breastfeeding, poses little risk to the infant.

SIDE EFFECTS: The most common side effects from ibuprofen are rash, ringing in the ears, headaches, dizziness, drowsiness, abdominal pain, nausea, diarrhea, constipation and heartburn. NSAIDs reduce the ability of blood to clot and therefore increase bleeding after an injury. Ibuprofen may cause ulceration of the stomach or intestine, and the ulcers may bleed. Sometimes, ulceration can occur without abdominal pain, and black, tarry stools, weakness, and dizziness upon standing (orthostatic hypotension) due to bleeding may be the only signs of an ulcer. NSAIDs reduce the flow of blood to the kidneys and impair function of the kidneys. The impairment is most likely to occur in patients who already have impaired function of the kidney or congestive heart failure, and use of NSAIDs in these patients should be cautious. People who are allergic to other NSAIDs, including aspirin, should not use ibuprofen. Individuals with asthma are more likely to experience allergic reactions to ibuprofen and other NSAIDs. Fluid retention (edema), blood clots, heart attacks, hypertension and heart failure have also been associated with the use of NSAIDs.

Source emedicine.com

Angiotensin Converting Enzyme (ACE) Inhibitors

Pharmacy Author: Omudhome Ogbru, Pharm.D.
Medical Editor: Jay W. Marks, M.D.

What are ACE inhibitors, and how do they work?

Angiotensin II is a very potent chemical that causes the muscles surrounding blood vessels to contract and thereby narrows the blood vessels. The narrowing of the vessels increases the pressure within the vessels and can cause high blood pressure (hypertension). Angiotensin II is formed from angiotensin I in the blood by the enzyme, angiotensin converting enzyme (ACE). ACE inhibitors are medications that slow (inhibit) the activity of the enzyme, which decreases the production of angiotensin II. As a result, the blood vessels enlarge or dilate, and the blood pressure is reduced. This lower blood pressure makes it easier for the heart to pump blood and can improve the function of a failing heart. In addition, the progression of kidney disease due to high blood pressure or diabetes is slowed.

For what conditions are ACE inhibitors used?

ACE inhibitors are used for controlling blood pressure, treating heart failure and preventing kidney damage in people with hypertension or diabetes. They also benefit patients who have had heart attacks. In studies, individuals with hypertension, heart failure, or prior heart attacks who were treated with an ACE inhibitor lived longer than patients who did not take an ACE inhibitor. Because they prevent early death resulting from hypertension, heart failure or heart attacks, ACE inhibitors are one of the most important group of drugs. Some individuals with hypertension do not respond sufficiently to ACE inhibitors alone. In these cases, other drugs are used in combination with ACE inhibitors.

Are there any differences among the different types of ACE inhibitors?

ACE inhibitors are very similar. However, they differ in how they are eliminated from the body and their doses. Some ACE inhibitors need to be converted into an active form in the body before they work. In addition, some ACE inhibitors may work more on ACE that is found in tissues than on ACE that is present in the blood. The importance of this difference or whether one ACE inhibitor is better than another, has not been determined.

What are the side effects of ACE inhibitors?

ACE inhibitors are relatively well-tolerated by most individuals. Nevertheless, they are not free of side effects, and some patients should not use ACE inhibitors. ACE inhibitors usually are not prescribed for pregnant patients because they may cause birth defects. Individuals with severe kidney problems and people who have had a severe reaction to ACE inhibitors probably should avoid them. The most common side effects are cough, elevated blood potassium levels, low blood pressure, dizziness, headache, drowsiness, weakness, abnormal taste (metallic or salty taste), and rash. It may take up to a month for coughing to subside, and if one ACE inhibitor causes cough it is likely that the others will too. The most serious, but rare, side effects of ACE inhibitors are kidney failure, allergic reactions, a decrease in white blood cells, and swelling of tissues (angioedema).

With which drugs do ACE inhibitors interact?

ACE inhibitors have few interactions with other drugs. Since ACE inhibitors may increase blood levels of potassium, the use of potassium supplements, salt substitutes (which often contain potassium), or other drugs that increase the body's potassium may result in excessive blood potassium levels. ACE inhibitors also may increase the blood concentration of lithium (Eskalith) and lead to an increase in side effects from lithium. There have been reports that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen, indomethacin, and naproxen may reduce the effects of ACE inhibitors; however, there is no conclusive evidence that this interaction, if it exists, is important.

What ACE inhibitors are available?

The following is a list of the ACE inhibitors that are available in the United States:

captopril (Capoten), benazepril (Lotensin), enalapril (Vasotec), lisinopril (Prinivil, Zestril) fosinopril (Monopril), ramipril (Altace), perindopril (Aceon), quinapril (Accupril), moexipril (Univasc), and trandolapril (Mavik).

Source emedicine.com

Getting Back to Work After a Stroke

Only Half of Stroke Survivors Make it Back Into the Workforce, Study Shows

By Stephanie Watson
WebMD Medical News

Reviewed By Elizabeth Klodas, MD

March 27, 2008 -- A stroke can have a major impact on every aspect of a person's life, including his or her job. New research shows that only about half of stroke survivors are able to return to work, and continuing disability and depression are major causes.

Though people often associate strokes with old age -- in other words, retirees -- about 20% of strokes actually occur in people of working age, the study authors say. Because of the general aging of the population and an increase in stroke survival rates, the condition can have a noticeable impact on the workforce.

The weakness, speech, and movement problems that often occur after a stroke can lead to a lengthy disability period for many patients. Often stroke survivors also develop depression and other psychiatric problems. All of these factors can contribute to the decision not to return to work.

To assess the impact of stroke on employment, researchers in Australia and New Zealand looked at 210 previously working patients (average age 55) who had had a first stroke between 2002 and 2003. Researchers assessed patients soon after their stroke, then again at one and six months afterward.

Fifty-three percent of patients were able to return to full-time work within a few months of their stroke, the researchers reported in the journal Stroke. "It can be quite heartening to families and clinicians that more than half of stroke patients go back to work," study researcher Nick Glozier, MD, PhD, associate principal director of The George Institute for International Health in Sydney, Australia, says in a news release. "But physicians should continually assess patients' mood after stroke, because it's an important predictor of whether patients will go back to work."

Depression did have a significant independent impact on work status after a stroke. Forty-five percent of patients who didn't return to work at six months were depressed, compared with 33% of those who did go back to work. Only 30% of those patients with depression following stroke reported receiving treatment for this.

"If family members pick up on someone being depressed after a stroke, ask the physician to assess them and intervene if necessary," Glozier advises. "Post-stroke depression can be successfully treated, and treatment can help the patients, their families, and society."

Other important determinants in whether patients could get back to work were the severity of the stroke and the patients' ability to care for themselves independently. Seventy-one percent of those who were working six months after a stroke were rated "independent" on a scale of self-care abilities called the Barthel Index, compared with only 32% of those who didn't go back to work. Glozier says people who are functioning well after a stroke should consider vocational rehabilitation, which can help them make the transition back into the workforce.

The authors say the next step in research is to look at ways to prevent and manage stroke-related depression to help improve patients' quality of life.

SOURCES: Glozier, N. Stroke, April 2008; vol 39. News release, American Heart Association.

© 2008 WebMD Inc. All rights reserved.

Source emedicine.com

Diabetes Mellitus, Type 2 (part 2), the treatment

Medical Care

The goals in caring for patients with diabetes mellitus include the elimination of symptoms; microvascular (ie, eye and kidney disease) risk reduction through control of glycemia and blood pressure (BP); macrovascular (ie, coronary, cerebrovascular, peripheral vascular) risk reduction through control of lipids and hypertension, smoking cessation, and utilizing aspirin therapy; and metabolic risk reduction through control of glycemia. Such care requires appropriate goal setting, regular complications monitoring, dietary and exercise modifications, medications, appropriate self-monitoring of blood glucose (SMBG), and laboratory assessment. Focus on glucose alone does not provide adequate treatment for patients with diabetes mellitus. Treatment involves multiple goals (ie, glycemia, lipids, BP).

• Implications of the UKPDS: The UKPDS was a landmark study for the care of patients with type 2 diabetes mellitus, confirming the importance of glycemic control in reducing the risk for microvascular complications and refuting previous data implicating increased macrovascular disease risk with sulfonylureas or insulin. Major findings of the study are displayed in Images 6-8. Significant implications include the following:
• • Microvascular complications (predominantly the need for laser photocoagulation on retinal lesions) are reduced by 25% when median HbA1c is 7% compared to 7.9%.
  • A continuous relationship exists between glycemia and microvascular complications, with a 35% reduction in risk for each 1% decrement in HbA1c. A glycemic threshold (above the upper limit of normal for HbA1c) below which risk for microvascular disease is eliminated does not appear to exist.
  • Glycemic control has minimal effect on macrovascular disease risk. Excess macrovascular risk appears to be related to conventional risk factors such as dyslipidemia and hypertension.
  • Sulfonylureas and insulin therapy do not increase macrovascular disease risk.
  • Metformin reduces macrovascular risk in patients who are obese.
  • Vigorous BP control reduces microvascular and macrovascular events. Beta-blockers and angiotensin-converting enzyme (ACE) inhibitors appear to be equally efficacious.
• Glycemic goal setting and achieving glycemic goals: Both the DCCT and UKPDS provide ample evidence that glycemic control is paramount in reducing microvascular complications. Unless the risk outweighs the benefit, an HbA1c target of less than 7% is appropriate. Some organizations (eg, the American Association of Clinical Endocrinologists, the International Diabetes Federation) recommend a glycemic target of HbA1c less than 6.5%.
• • The author thinks that practitioners should aim for the lowest possible HbA1c that does not cause undue harm. The limiting factor is almost always risk for hypoglycemia. Unfortunately, some physicians and their patients pursue a particular HbA1c value despite uncertain benefit (eg, patients with advanced complications) or unacceptable risk (eg, hypoglycemia unawareness, elderly patients, patients with other major systemic disease with significant risk for side effects [eg, coma, seizures, falling and breaking a hip]). Situations with an unfavorable risk-benefit ratio for intensive blood glucose lowering include advanced age, significant concomitant disease, and advanced complications.
  • Decisions about glycemic management are generally made on the basis of HbA1c measurements performed quarterly (possibly less often in patients with adequate control through lifestyle measures alone) and the results of SMBG. If a total GHb measurement is used, the actual number is 1-2% higher, but the laboratory should provide a correlation with actual HbA1c values.
• Complications monitoring: The American Diabetes Association recommends initiation of complications monitoring at the time of diagnosis of diabetes mellitus. This regimen should include yearly dilated eye examinations, yearly microalbumin checks, and foot examinations at each visit. For additional resources, please see Diabetic Microvascular Complications.
• SMBG: Daily SMBG is important for patients treated with insulin or insulin secretagogues to monitor for and prevent hypoglycemia and optimize the treatment regimen. The optimal frequency of SMBG for patients with type 2 diabetes is unresolved, but it should be sufficient to facilitate reaching glucose goals. The author often utilizes no or minimal SMBG in patients using lifestyle changes alone or agents that do not cause hypoglycemia (eg, metformin, glitazones, glucosidase inhibitors).
• Laboratory monitoring: Because diabetes mellitus is a multisystem disease, focusing solely on blood sugar is inadequate. Image 9 lists appropriate laboratory parameters in the global assessment of patients with type 2 diabetes mellitus. Obviously, patients with abnormalities need more frequent monitoring to guide therapeutic interventions. Drug-specific monitoring is also necessary (eg, serum creatinine for metformin, serum transaminases for glitazones).
• Intercurrent medical illness: Patients with intercurrent illness become more insulin resistant because of the effects of increased counter-regulatory (ie, anti-insulin) hormones. Therefore, despite decreased nutritional intake, glycemia may worsen. Patients on oral agents may need transient therapy with insulin to achieve adequate glycemic control. In patients who require insulin, scheduled doses of insulin, as opposed to sliding scale insulin, are far more effective in achieving glycemic control.
• • Recent work (ie, the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction [DIGAMI] trial) suggests improved outcomes in patients with type 2 diabetes with acute myocardial infarctions or strokes who receive constant intravenous insulin during the acute phase of the event to maintain blood glucose values of approximately 100-150 mg/dL. However, this work has not been confirmed in a recently published study (ie, DIGAMI-2).
  • In the case of cardiac ischemia, the beneficial effects may be due to reducing free fatty acids with insulin therapy.
  • In patients treated with metformin, any illness leading to dehydration or hypoperfusion should lead to temporary discontinuation of the drug because of possible increased risk of lactic acidosis.
• Surgery: Surgical patients may experience worsening of glycemia for reasons similar to those listed above for intercurrent medical illness. Patients on oral agents may need transient therapy with insulin to maintain blood glucose at approximately 100-180 mg/dL. In patients who require insulin, scheduled doses of insulin, as opposed to sliding scale insulin, are far more effective in controlling glucose. Intensive regulation of glucose (ie, maintaining glucose approximately <110>
• • For patients who can eat soon after surgery: The time-honored approach of administering one half of the usual morning neutral protamine Hagedorn (NPH) insulin dose with 5% dextrose in the IV is acceptable, with resumption of scheduled insulin (perhaps at reduced doses) within the first 1-2 days. Patients receiving insulin glargine can often receive their usual dose if they are given intravenous glucose during surgery with appropriate intraoperative and postoperative monitoring of glucose. Oral antidiabetic agents can be restarted when the patient is stable and eating. Insulin secretagogues should be used with caution in the hospital since food intake may be interrupted by diagnostic tests and procedures. Metformin may have to be started at a lower dose and gradually titrated to full dose due to gastrointestinal side effects. Since glitazones have such a long biologic effect, their omission in the hospital is usually inconsequential. The role of incretins in the hospital has not yet been defined.
  • For patients who require more prolonged periods without oral nutrition and for major surgery, such as coronary artery bypass grafting and major abdominal surgery: Constant infusion intravenous insulin is preferred. Discontinue metformin temporarily after any major surgery until the patient is clearly hemodynamically stable and normal renal function is documented. The practice of discontinuing metformin for at least 48 hours in this situation until proof of normal renal function is established is sound.
• Women of reproductive age: An increasing prevalence of type 2 diabetes mellitus has been noted in women of reproductive age. Prepregnancy planning is becoming necessary. Insulin is the only generally accepted pharmacologic therapy for women contemplating pregnancy who previously have been diagnosed with diabetes mellitus. For women with diabetes mellitus controlled by lifestyle measures alone, conversion to insulin as soon as the pregnancy is confirmed is appropriate. For women with polycystic ovary disease who ovulate and become pregnant with insulin sensitizer therapy, conversion to insulin is often mandatory as soon as pregnancy is confirmed. While metformin has been used during pregnancy in other countries, it is not so used in the United States.
• Pregnancy: Insulin is the only acceptable pharmacologic therapy during pregnancy for women with established diabetes mellitus. (Glyburide has been used for gestational diabetes mellitus patients late in the second and third trimesters, but this is not appropriate therapy for pregnant patients with established diabetes. Its safety during early gestation is not established.) For a complete discussion of this topic, see Diabetes Mellitus and Pregnancy.
• Hypertension: The role of hypertension in increasing microvascular and macrovascular risk in patients with diabetes mellitus has been confirmed in the UKPDS and Hypertension Optimization Treatment (HOT) trials. The American Diabetes Association suggests that the BP goal be less than 130/80 mm Hg. In patients with greater than 1 g/d proteinuria and renal insufficiency, a more aggressive therapeutic goal (ie, <125/75>
• Dyslipidemia: Dyslipidemia, particularly high triglycerides and low HDL-C, is more common in patients with type 2 diabetes mellitus. Data from statin trials show that event reduction is achievable in secondary prevention (ie, patients with diabetes and known CHD and LDL-C elevation). Fibrates may reduce CHD events in patients with isolated low HDL-C. Primary prevention studies have also now shown that statin therapy reduces CHD events. Whether therapy aimed more at triglyceride reduction and HDL-C elevation (ie, fibrates, niacin) is effective in CHD event reduction in primary prevention remains to be determined. The American Diabetes Association guidelines for therapy of LDL-C are presented in Image 10.

CME/CE is available for revised guidelines on the management of type 2 diabetes. See Guidelines Revised for Management of Type 2 Diabetes Mellitus.

Surgical Care

Bariatric surgery has been shown to improve diabetes control and, in some situations, normalize glucose tolerance in morbidly obese patients. It is certainly a reasonable alternative in carefully selected patients if an experienced team (providing appropriate preoperative evaluation as well as technical surgical expertise) is available.

Consultations

Primary care physicians can care for patients with type 2 diabetes mellitus adequately. The multiple facets of disease treatment (eg, nutrition, exercise, smoking cessation, medications, complications monitoring) and data management (eg, glucose levels, BP, lipids, complications monitoring) must be continually noted. Inability to achieve adequate glycemic (or BP or lipid) control usually should be a clear indication to consult a diabetes specialist. When a patient has developed advanced complications, a diabetes specialist cannot be expected to be able to lessen the burden of these complications.

Diet

For most patients, the best diet is of what they are currently eating. Time-honored attachments to a precise macronutrient composition of the diet to control diabetes are generally not supported by the research. Caloric restriction is of first importance. After that, individual preference is reasonable. Modest restriction of saturated fats and simple sugars is reasonable. However, some patients have remarkable short-term success with high-fat low-carbohydrate diets of various sorts. Therefore, the author always stresses weight management in general and is flexible regarding the actual diet that the patient consumes. Also, the practitioner should advocate a diet using foods that are within the financial reach and cultural milieu of the patient.

CME/CE is available for recently released nutritional guidelines. See American Diabetes Association Updates Guidelines for Medical Nutrition Therapy.

Activity

In general, most patients with type 2 diabetes mellitus can benefit from increased activity. Aerobic exercise improves insulin sensitivity and may improve glycemia markedly in some patients.

• The patient should choose an activity that she or he is likely to continue. Walking is accessible to most patients in terms of time and financial expenditure.
• A previously sedentary patient should start activities slowly.
• Older patients, patients with long-standing disease, patients with multiple risk factors, and patients with previous evidence of atherosclerotic disease should have a cardiovascular evaluation, probably including an imaging study, prior to beginning a significant exercise regimen.

Source emedicine.com

Pharmacologic therapy has changed dramatically in the last 10 years. New drug classes and new drugs effectively treat type 2 diabetes mellitus, allowing glycemic control previously beyond the reach of medical therapy. Traditionally, diet modification has been the cornerstone of diabetes management. Weight loss is more likely to control glycemia in patients with recent onset of the disease than in patients who are significantly insulinopenic. Medications that induce weight loss such as orlistat may be effective in highly selected patients but are not generally indicated in the treatment of the average patient with type 2 diabetes mellitus. At presentation, patients who are symptomatic may require transient treatment with insulin to reduce glucose toxicity (which may reduce beta cell insulin secretion and worsen insulin resistance) or an insulin secretagogue to rapidly relieve symptoms such as polyuria and polydipsia.

Patients with HbA1c less than 8% are usually treated initially with single oral agents. Patients with initial HbA1c greater than 9-10% may benefit from initial therapy with 2 oral agents.

Various categories of therapeutic agents effectively treat type 2 diabetes mellitus. Comparisons of studies looking at glycemic efficacy of individual agents are highly affected by 2 study conditions: level of glycemia prior to treatment and percent of study population previously untreated with drugs. These 2 factors make comparison of drug studies quite difficult because all agents are more effective in a population of patients with poor glycemic control at baseline (a large decrease in glucose concentrations occurs, but the treatment often leaves the patients with poorly controlled glucose levels), and in previously diabetes drug-naive patients.

Sulfonylureas are time-honored insulin secretagogues (ie, oral hypoglycemic agents) and probably have the greatest efficacy for glycemic lowering of any of the oral agents. The UKPDS confirmed their safety after years of suspicion from the University Group Diabetes Program (UGDP).

Meglitinides are much more short-acting insulin secretagogues than sulfonylureas, with preprandial dosing potentially achieving more physiologic insulin release and less risk for hypoglycemia. Their glycemic efficacy is possibly less than sulfonylureas.

Biguanides are old agents that reduce hepatic glucose production and may have a minor effect on glucose utilization in the periphery (ie, antihyperglycemics, hepatic insulin sensitizers). Insulin must be present for biguanides to work. Phenformin was taken off the market in the United States in the 1970s because of its risk of causing lactic acidosis and associated mortality (rate of approximately 50%). Metformin has been used successfully for the last few years with very low risk. It is the only oral diabetes drug that reliably facilitates modest weight loss. It was used in the UKPDS and was successful at reducing macrovascular disease endpoints in patients who were obese. The results with concomitant sulfonylureas in a heterogeneous population were conflicting, but overall, this drug probably improves macrovascular risk.

Alpha-glucosidase inhibitors prolong the absorption of carbohydrates. Their induction of flatulence greatly limits their use. These agents should be titrated slowly to reduce gastrointestinal intolerance. Their effect on glycemic control is modest, affecting primarily postprandial glycemic excursions.

Thiazolidinediones (glitazones) are a new class of drugs that reduce insulin resistance in the periphery (ie, sensitize muscle and fat to the actions of insulin) and perhaps to a small degree in the liver (ie, insulin sensitizers, antihyperglycemics). They activate peroxisome proliferator–activated receptor (PPAR) gamma, a nuclear transcription factor that is important in fat cell differentiation and fatty acid metabolism. Their major action is probably actually fat redistribution. These drugs may have beta cell preservation properties. Their glycemic efficacy is moderate, between alpha-glucosidase inhibitors and sulfonylureas. They are the most expensive oral agents.

Glitazones require the presence of insulin to work. They generally decrease triglycerides and increase HDL-C, but they increase LDL-C (perhaps large buoyant LDL, which may be less atherogenic). While these drugs have many desirable effects on inflammation and the vasculature, edema and weight gain may be problematic adverse effects in patients taking glitazones, especially when administered with insulin or insulin secretagogues. These effects may induce or worsen congestive heart failure in patients with left ventricular compromise and occasionally in patients with normal left ventricular function. These agents have not been tested in patients with New York Heart Association class III or IV heart failure. A recently recognized possible side effect of these agents is macular edema. Recent animal work suggests that concomitant therapy with the diuretic amiloride may reduce fluid retention related to glitazone therapy.

A recently published study (PROactive) assessed the effect of pioglitazone titrated to 45 mg/d versus placebo added to existing diabetes therapy on macrovascular outcomes. No statistically significant difference was noted between the two groups at 3 years. A later developed main secondary endpoint (all cause mortality, nonfatal myocardial infarction, and stroke) not mentioned in the original study design was reduced 16% (p=0.027). Treated patients gained 4 kg on average and had a much higher rate of heart failure and edema than patients treated with placebo. The author views this study as primarily a confirmation of concerns over weight gain, edema, and congestive heart failure with these drugs and thinks their potential antiatherosclerotic effects are still unproven.

The US Food and Drug Administration issued an alert on May 21, 2007 to patients and health care professionals of rosiglitazone potentially causing an increased risk of myocardial infarction (MI) and heart-related deaths following the online publication of a meta-analysis. For more information, see Medications.

The incretin-mimetic, exenatide, has a novel mechanism of action. Mimicking the endogenous incretin, glucagon-like peptide-1 (GLP-1), it stimulates glucose-dependent insulin release (as opposed to oral insulin secretagogues, which may cause non–glucose-dependent insulin release and hypoglycemia), as well as reducing glucagon and slowing gastric emptying. Studies have used exenatide in addition to metformin and/or a sulfonylurea. Patients may attain modest weight loss. Animal data suggest that this drug prevents beta cell apoptosis and may in time restore beta cell mass. This latter property, if proven in humans, would have tremendous therapeutic potential. This drug requires twice daily injections and is more expensive than high-dose glitazone therapy. It does have the advantage of ease of titration (only two possible doses, with most patients progressing to the higher dose) than insulin.

The newest addition to available oral hypoglycemic agents is the dipeptidyl peptidase IV (DPP-4) inhibitor, sitagliptin, which gained FDA approval in October 2006. DPP-4 degrades numerous biologically active peptides including the endogenous incretins GLP-1 and glucose-dependent insulinotropic peptide (GIP). Sitagliptin can be used as a monotherapy or in combination with metformin or the thiazolidinediones. It is a once daily drug and is weight neutral. Another DPP-4 inhibitor, vildagliptin, is currently under review at the FDA. Exenatide exhibits resistance to DPP-4 and, thus, has a longer half life than GLP-1.

Ultimately, many patients with type 2 diabetes mellitus become markedly insulinopenic. The only therapy that corrects this defect is insulin. Because most patients are insulin resistant, small changes in insulin dosage may make no difference in glycemia in some patients. Furthermore, because insulin resistance is variable from patient to patient, therapy must be individualized in each patient.

Considerable debate exists regarding the best initial oral therapy for patients with type 2 diabetes mellitus. Based on the results of the UKPDS and safety record, patients who are obese (120% ideal body weight) should be started on metformin initially, titrated to at least 2000 mg/d administered in divided doses (during or after meals to reduce gastrointestinal side effects). Patients who are markedly symptomatic may be treated with an insulin secretagogue initially to rapidly alleviate symptoms and then perhaps switched to other agents. Patients with near-normal weight may be treated with sulfonylureas or metformin initially. Short-acting insulin secretagogues (eg, repaglinide, nateglinide) can be used in patients unusually predisposed to hypoglycemia.

Failure of initial therapy usually should result in addition of another class of drug rather than substitution (reserve substitution for intolerance to a drug due to adverse effects). Considerable debate exists regarding second agents added to (or used initially in conjunction with) metformin. The time-honored approach is to add an insulin secretagogue (usually titrated to no more than the half-maximal approved dose to reduce risk for hypoglycemia). However, some experts recommend a glitazone because of the positive effects of these drugs on inflammation and the vasculature. If this strategy is used, a moderate dose of glitazone (as opposed to the highest approved dose) should be used. A therapeutic scheme utilized by the author is listed in Image 11.

The author usually only uses glitazones in cases of metformin intolerance or contraindication because of the side effects of weight gain and edema seen not infrequently with glitazones. Exceptions to the practice might include patients with marked insulin resistance of relatively normal weight, such as patients of Asian heritage. If an insulin secretagogue is being taken by the patient prior to adding a second agent, the physician should warn the patient about the possibility of inducing hypoglycemia when another agent is added. In such cases, the insulin secretagogue, not the newly added agent, should be reduced.

If 2 drugs are unsuccessful, the practitioner may consider adding a third class of oral agents. An alternative would be to add bedtime insulin, usually NPH or glargine, to the initial oral agent or 2-drug combination, or add the new injectable drug exenatide. The expense and side effect profile of glitazones make the oral triple therapy approach less of an option for the author. The new approach of adding exenatide twice daily to 1 or 2 oral agents (eg, metformin and/or sulfonylureas) is attractive because of its simplicity (ie, only 2 possible doses of exenatide with easy titration compared to insulin), but its expense may be prohibitive. If insulin is used, the insulin dose is titrated to the fasting sugar concentration, which the patient can measure at home (usually with titration to a maximum bedtime insulin dose of approximately 60 units).

Some patients need reduction of their insulin secretagogue to prevent daytime hypoglycemia as the bedtime insulin is initiated or increased and the fasting glucose concentration is decreased. If exenatide is used, the author monitors fasting and postprandial sugars, expecting a marked flattening of the postprandial rise in glucose concentrations.

Glucose patterns in patients with type 2 diabetes, particularly if they have central obesity and hepatic steatosis, often reveal that the highest preprandial glucose of the day is the fasting sugar (because of disordered hepatic glucose production overnight), with a "stair-step" decrease during the day (after the usual postmeal rise). Therefore, the physician should not necessarily be deterred from his or her present therapy by higher-than-desired morning glucose values if the HbA1c level is at target. For patients who primarily have fasting hyperglycemia, bedtime insulin is the easiest way to correct this abnormality.

When the previous approaches are unsuccessful, the patient should be switched to conventional twice-daily or multiple daily dose insulin with or without an insulin sensitizer. The author prefers metformin in this scenario if there are no problems with tolerability or contraindications. If a glitazone is used, a moderate dose should be administered to minimize fluid retention and weight gain.

A necessary condition for twice daily insulin to succeed in a regimented lifestyle, with meal times regularly spaced and insulin injections taken at essentially the same time every day including weekends and holidays. Lack of regularity in the schedule is self-defeating for this approach to therapy. The author only uses premixed insulin in patients who might have trouble mixing their insulins. The author also prefers premix containing regular insulin if a premix is administered to maintain better midday coverage. Premix with rapid-acting medications can be used if the midday meal is small. All insulin injections should be administered in the abdomen.

Conventional multiple daily dosing of insulin gives the patient the greatest flexibility. In this approach, insulin glargine or twice daily insulin detemir is generally given as the basal insulin, and rapid-acting insulin (eg, aspart, glulisine, lispro) are administered just before each meal. The basal component can be administered any time of day as long as it is given at the same time each day. Interpreting glucose patterns is probably easiest if the basal insulin is administered at or near bedtime. The basal insulin can then be titrated to the morning sugar, and the bolus premeal insulin can be titrated to the next premeal sugar and, in some cases, a postprandial (~2 h) value.

For patients trying to achieve near euglycemia, premeal glucose values of 80-120 mg/dL are the goal, with the patient going to sleep at night with a value at least 100 mg/dL. In patients with less stringent glycemic goals (eg, advanced age, advanced complications, severe concomitant disease), preprandial glucose values of 100-140 mg/dL are desired. Because of the limitations of therapies, essentially no patient is able to achieve these goals all the time if, in fact, insulin is needed to treat their disease.

Unlike in long-standing type 1 diabetes mellitus, patients with type 2 diabetes mellitus usually maintain adequate warning symptoms and signs of hypoglycemia. This situation greatly facilitates hypoglycemic therapy (ie, insulin secretagogues, insulin) in patients with type 2 diabetes.

Recent work has reminded practitioners that glycemic control is a function of fasting and preprandial glucose values and postprandial glycemic excursions. Postprandial glucose measurements may need more emphasis. This change in emphasis is fueled to some degree by the availability of short-acting insulin secretagogues, very short-acting insulin, and alpha-glucosidase inhibitors, all of which target postprandial glycemia. While postprandial sugars are a better predictor of macrovascular disease risk early in the course of loss of glucose tolerance, whether targeting after-meal glucose excursions has more of an effect on complications risk than more conventional strategies remains to be seen.

In January 2006, the first inhaled insulin (Exubera) was approved by the FDA as a rapid-acting prandial insulin. It does not produce better glycemic control than conventionally injected insulins and requires a mildly cumbersome device, skill to deliver an accurate dose (up to a few min to deliver 1 dose), and pulmonary function monitoring due to concerns about lung toxicity over time. The powder insulin comes in a 1 mg and a 3 mg packet approximately converted to 3 units and 8 units of subcutaneous aqueous insulin, respectively. Dose titration requires certain combinations of the available preparations and, thus, multiple deliveries at a time. In the author's opinion, inhaled insulin offers no advantage except convenience, but highly needle-phobic patients may find it useful. On October 18, 2007, Pfizer Inc announced that it is no longer making inhaled insulin (Exubera). The decision is not based on any safety concerns but is due to economic feasibility resulting from too few patients taking the inhaled insulin. Pfizer will work with physicians to transition patients from inhaled insulin to other treatment options over the next several months.

Intuitively, one would assume that therapies that normalize both preprandial and postprandial glycemia (or come close to normalization) would be optimal. Whether such a strategy can be achieved without untoward adverse effects and with further reductions in microvascular and macrovascular disease risk (compared to regimens used in the UKPDS) with newly available therapies is open to question. Practically speaking, most patients are fully occupied trying to do conventional glucose monitoring and insulin dose adjustment.

An outline of the therapeutic approach generally used by the author is presented in Image 11 and Image 13. An idealized scheme for glucose and insulin patterns is presented in Image 14. The author finds keeping such an idealized scheme in mind is helpful in treating and educating patients, even if the patient is trying to replicate it with less-intensive insulin therapy.

Source emedicine.com