Review of NSAIDs Effects & Side Effects for Arthritis Pain

Updated 3/2017-- all links (except to my own posts) removed as many no longer active. 

Recently I gave in and went to see a rheumatologist after more than 3 months of intense morning stiffness and swelling of my hands (especially around the PIPs and MCPs) and wrists which improved during the day but never went away.  It had gotten to the point where I could no longer open small lid jars (decreased strength), do my push-ups or pull ups (pain and limited wrist motion), and OTC products (Tylenol, Advil, etc) weren’t working.  I can’t take Aleve due to the severe esophagitis it induces.  I didn’t want to write a prescription for my self-diagnosed (without) lab arthritis.

BTW, all the lab work came back negative with the exception of a slightly elevated sed rate and very weakly positive ANA.  The rheumatologist was impressed with the swelling, pain, and stiffness and was as surprised as I by the normal lab work.  He thinks (and I agree) that I am in the early presentation of rheumatoid arthritis.  He wrote a prescription for Celebrex and told me to continue with the Zantac I was already taking (thanks to the Aleve).  The Celebrex is helping.

So I was happy to see this article (full reference below) come across by twitter feed.  H/T to @marcuspainmd: Useful review of NSAIDs effects & side effects for arthritis pain http://cot.ag/oHxQDX

A major disadvantage of NSAID use is the gastrointestinal side effects. These range from abdominal pain, nausea, diarrhea, and dyspepsia to more serious events, such as gastric or duodenal ulcers, anemia, and bleeding, or perforated ulcer. These side effects are due to the simultaneous inhibition of COX-1 and COX-2.

As many as 25% of chronic NSAID users will develop ulcer disease
2%–4% will bleed or perforate, especially those who have been designated as being in a high-risk category
The overall risk for these complications in patients taking NSAIDs was approximately 2.4.

High-risk patients are those with a history of complicated peptic ulcer disease or multiple (at least two) risk factors; moderate-risk patents are those with one to two risk factors, ie, age 65 years, high-dose NSAID therapy, previous history of an uncomplicated ulcer, concurrent use of aspirin (including low-dose), corticosteroids, or anticoagulants; and low-risk patients are those with no risk factors.

The two methods employed to prevent the development of peptic ulceration and mucosal injury in patients taking NSAIDs:

(1) prophylaxis with a proton pump inhibitor or a prostaglandin analog (such as misoprostol) or high-dose histamine 2-receptor antagonist (H2RA)
(2) with substitution of a traditional NSAID by a COX-2 inhibitor
The article on ulcer formation in COX-2 (Celebrex) vs NSAIDS:

Goldstein et al14 determined gastroduodenal damage
from endoscopy after 4, 8, and 12 weeks of treatment with celecoxib 200 mg twice daily or naproxen 500 mg twice daily in 537 patients with osteoarthritis or rheumatoid arthritis.

The cumulative incidence of gastric and duodenal ulceration for celecoxib was 9% and for naproxen was 41%. In the group that received celecoxib, the occurrence of ulcers was significantly associated with a number of factors, including H. pylori positivity, concurrent aspirin usage, and a history of ulcers.

It’s a really nice review article and is open source.



REFERENCES
Combination therapy versus celecoxib, a single selective COX-2 agent, to reduce gastrointestinal toxicity in arthritic patients: patient and cost-effectiveness considerations;  Marina Scolnik, Gurkirpal Singh; Open Access Rheumatology: Research and Reviews 2011:3 53–62

Cocaine and Ear Necrosis

Updated 3/2017-- photos and all links (except to my own posts) removed as many no longer active. 

Last week Science Daily had a brief article noting the association of contaminated cocaine with ear necrosis:   Contaminated Cocaine Triggers Decaying, Dying Skin  (photo credit) 

I’ve written about skin complications from drug abuse in the past, but this is not one I knew of.  Most common are skin and soft tissue infections (SSTIs).

The crusty, purplish areas of dead skin (purpura) that can occur with this contaminated cocaine are extremely painful and can open the door to nasty infections.  (note the lower lobe of the ear in the photo)

Apparently the cocaine is contaminated with a de-worming drug commonly used by veterinarians called levamisole,  noted by the U.S. DEA to have been found in 30% of confiscated cocaine in 2008 and 70% in 2009.

This complication from the use of the contaminated cocaine was recently reported in the June issue of the Journal of the American Academy of Dermatology (full reference below).  The report highlights six new and very similar patient cases of purpura, mostly on and around the ears, following the contaminated cocaine use.  There were six cases --  four seen in Rochester, N.Y. and two in Los Angeles. 

Although in each case an extensive battery of blood tests ruled out the usual causes of purpura, the JAAD paper authors write “because testing is not easily performed, we did not test for levamisole in the serum or blood to prove this is the causative agent.”

From the Science Digest article:

According to Mary Gail Mercurio, M.D., an author and associate professor in the Department of Dermatology at the University of Rochester Medical Center, "When we first started seeing these patients they all had a similar clinical picture, but they were really an enigma because they weren't falling into any other pattern we'd seen before. When a colleague at the National Institutes of Health mentioned levamisole contamination, we did toxicity screens and lo-and-behold, all the patients came up positive for cocaine. We had our diagnosis."

Drug enforcement officials have detected levamisole -- which was once used to treat colon cancer -- in cocaine since 2003, but have watched it increase rapidly in recent years. The Drug Enforcement Administration says that the drug, which is inexpensive, is used more and more as a diluting agent in order to stretch supplies. Study authors report that levamisole is known to increase dopamine, a neurotransmitter that helps control the brain's reward and pleasure centers, causing experts to believe it is also added to cocaine to further enhance or prolong the user's high.

Researchers don't know how levamisole causes purpura, which occurs when vessels become plugged and blood can't flow to the skin, leading to skin death and the resulting purplish, crusty appearance. Cocaine alone constricts blood vessels, which is probably the first step, but how levamisole contributes is not yet understood, Mercurio said.

The purpura can occur with both smoking and snorting of the tainted cocaine.  Treatment options include steroids to prevent inflammation, but stopping the exposure to cocaine is the best medicine.

REFERENCES

Characteristic purpura of the ears, vasculitis, and neutropenia–a potential public health epidemic associated with levamisole-adulterated cocaine; Catherine Chung, Paul C. Tumeh, Ron Birnbaum, Belinda H. Tan, Linda Sharp, Erin McCoy, Mary Gail Mercurio, Noah Craft; Journal of the American Academy of Dermatology, 09 June 2011, (10.1016/j.jaad.2010.08.024)

U.S. DEA:  Drugs of Abuse – 2011 Edition

Drug Abuse in Plastic Surgery Patients

The article (full reference below) is a reminder of drug abuse in our patients.  Many of which can create issue peri-operatively.  The article begins:

In 1957, Dr. George Crikelair detailed the impact of drug abuse on the practice of plastic and reconstructive surgery.   Five decades later, the subject remains salient: surveys administered by the White House Office of National Drug Control Policy (ONDCP) state that 41.7% of the U.S. population older than 12 has taken an illicit drug in their lifetime.  12.6% reported illicit drug use in the past year. 

….. This article seeks to impart clinical savvy regarding verbal and non-verbal cues of the seven most commonly abused drugs by detailing their pharmacology, clinical manifestations, screening and management, thus enabling plastic surgeons to provide prompt and appropriate treatment when encountering complications related to these
drugs.

I would recommend this article be read by more than just plastic surgeons.  It will either educate you or simply be a good review.  I’m not as good at picking drug abuse up as say Gruntdoc or Movin Meat or White Coat, so I found it worth my time.

To begin:

The typical urine drug screen (UDS) is based upon federal guidelines established by the Substance Abuse and Mental health Services Administration, or SAMHSA. This drug screen is referred to as the “SAMHSA-5” (and previously as the “NIDA-5”) because it detects only the five drugs required by federal workplace testing. These include cocaine, opiates, amphetamines, cannabinoids, and phencyclidine (PCP).

Synthetic opioids, such as oxycontin and hydrocodone, will not be noted on these routine screens.

The seven drugs the article reviews are:

Cocaine -- Common names: coke, blow, crack, snow, nose candy

Marijuana  -- Common names: pot, weed, grass, mary jane

Benzodiazepines  -- Common names: benzos, bars, tranks, normies, sleepers and xanies

Opioids  --  Common names: Heroin (H, smack, horse, brown/black tar), Prescription pain medication (oxy, roxy, vike, patches)

Amphetamines -- Common names: speed, uppers, dexies for amphetamine, and meth, crank, crystal, ice for methamphetamine

Gamma hydroxybutyrate --Common names: GHB, liguid Ex, G

Ecstasy  -- Common names: E, Adam, XTC, X, love drug

 

Each drug review includes pharmacology, clinical manifestations, screening, and management sections.   If you don’t have access to the journal, get your medical library to get it for you and READ the article.

 

REFERENCE

Drug Abuse in Plastic Surgery Patients: Optimizing Detection and Minimizing Complications; Cone, J.D., Harrington, M.A., Kelley, S.S., Prince, M.D., Payne, W.G., Smith, D.J.; Plast & Reconstr Surgery: POST ACCEPTANCE, 23 September 2010; doi: 10.1097/PRS.0b013e3181fad5ac

Old and Unused Drug Disposal

 Updated 3/2017-- all links (except to my own posts) removed as many are no longer active and it was easier than checking each one.

I’ve written before about this topic.  It was difficult to dispose of the unused prescription drugs when my brother-in-law died.  I was not involved in my mother’s old drug disposal, but can’t imagine it was easy (if done at all). 

Old and unused drugs don’t just happen when someone dies.  They can occur because your surgeon gave you a script for more pain pills than you needed.  This is commonly done as it is difficult to gage just how much pain someone is going to have postop.  Then there are the pills unused because you didn’t tolerate the side effects or had an allergic reaction.  Other are left over when patients are placed on new /different drugs for their conditions.

We have been reminded frequently of late that prescription drugs are now the most commonly abused drugs.  These unused drugs are a major source for that abuse.

The Drug Enforcement Administration (DEA) has initiated a prescription drug “Take-Back” campaign to help remove these old and unused drugs from our medicine cabinets.   September 25th has been designated as National Take-Back Day.

More than 2,700 sites nationwide have joined to participate in the event which will collect potentially dangerous expired, unused, and unwanted prescription drugs for destruction. 

National Take-Back Day will take place on Saturday, September 25th from 10 am to 2 pm local time.  The service is free and anonymous.  No questions will be asked about how the drugs came into the person’s possession.

Prescription and over the counter solid dosage medications, i.e. tablets and capsules accepted.  Intra-venous solutions, injectables, and needles will not be accepted.  

Collection sites in every local community can be found by going to www.dea.gov . This site will be continuously updated with new take-back locations.
In Little Rock/North Little Rock region, the sites include:
If you do not find a collection site near you, please check back frequently, sites are added every day.
Arkansas Game & Fish Commission
War Memorial Stadium Parking Lot
1 Stadium Drive, Little Rock, AR
UAMS Police Department
Reynolds Institute on Aging, First Floor
629 Jack Stephens Drive, Little Rock, AR
Cammack Village Police Department
Cammack Village City Hall
2710 N McKinley, Little Rock, AR
UALR Police
University Plaza Parking Lot
2801 S. University Ave, Little Rock, AR
Pulaski County Sheriff’s Department
Pulaski County Regional Detention Center
3201 W Roosevelt Road, Little Rock, AR
Little Rock Police Department
Pulaski County Regional Detention Facility
3201 W Roosevelt Road, Little Rock, AR
North Little Rock Police Department
NLR High School
Charging Wildcat Arena
2200 Main Street, NLR, AR
Pulaski County Sheriff’s Department
Oak Grove Volunteer Fire Department
18122 Hwy 365 N, NLR, AR

Bathing, a Source of Water Pollution from Medicines

Updated 3/2017 -- all links (except to my own posts) removed as many no longer active. and it was easier than checking each one.

I have written two posts in the past on proper disposal of unused medications.  I have always been mindful of the medicines as a source of environmental water pollution.

This past week the American Chemical Society reminded (head-slapped me) that topical medications are a source of environmental water pollution from their active pharmaceutical ingredients (APIs).   

Yes, the simple act of bathing washes hormones, antibiotics, and other pharmaceuticals down the drain into the water supply.

Ilene Ruhoy, M.D., Ph.D. and colleague  Christian Daughton, Ph.D. looked at potential alternative routes for the entry into the environment by way of bathing, showering, and laundering.  These routes may be important for certain APIs found in medications that are applied topically to the skin -- creams, lotions, ointments, gels, and skin patches.   These APIs include steroids (such as cortisone and testosterone), acne medicine, antimicrobials, narcotics, and other substances.

Ruhoy feels some APIs in topical medications have the potential of having a greater impact than those released in feces and urine.  Topical medications are un-metabolized and full-strength when washed off.  Those in feces and urine have been metabolized and are not full-strength.

APIs may go right through the disinfection process at sewage treatment plants, and enter lakes, rivers, and oceans.  Trace amounts of the active ingredients of birth control pills, antidepressants, and other drugs have been found in waterways. Some end up in drinking water – at extremely low, trace levels.

"We need to be more aware of how our use of pharmaceuticals can have unwanted environmental effects," Ruhoy said. "Identifying the major pathways in which APIs enter the environment is an important step toward the goal of minimizing their environmental impact."

Things you can do as a responsible citizen:

*  Use the topical prescription as directed, in the amount needed (more is not better, especially for the environment).

*  Do not flush prescription drugs down the toilet or drain unless the label or accompanying patient information specifically instructs you to do so.

*  To dispose of prescription drugs not labeled to be flushed, you may be able to take advantage of community drug take‐back programs or other programs, such as household hazardous waste collection events, that collect drugs at a central location for proper disposal.

*  Call your city or county government’s household trash and recycling service and ask if a drug take‐back program is available in your community.

 
Related posts
Unused and Old Medications (January 1, 2008)
Unused Prescription Medications (June 15, 2009)

 
Sources
American Chemical Society
American Pharmacy Association
White House Drug Policy

BOTOX -- Black Box Warning

 Updated 3/2017-- photos and all links removed as many are no longer active and it's easier than checking each one.

The U.S. Food and Drug Administration recently announced that safety label changes including a boxed warning and a Risk Evaluation and Mitigation Strategy (REMS) will now be required for all botulinum toxin products.  The agency took the action because of two main reasons.  The first one is the potential for serious risks that may occur from the spread of the botulinum toxin beyond the injection site.  The second reason is associated with the lack of interchangeability among the three licensed botulinum toxin products.

When the botulinum toxin spreads beyond the area of injection, symptoms similar to botulism may occur.  These symptoms include unexpected loss of strength or muscle weakness, hoarseness or trouble talking, trouble saying words clearly, loss of bladder control, trouble breathing, trouble swallowing, double vision, blurred vision and drooping eyelids.

This “spreading effect” has been reported in both children and adults.  It has been reported most often in children with cerebral palsy being treated with the products for muscle spasticity.  Treatment of muscle spasticity is an off-label use of the drug.  The “spreading effect” has been reported in patients being treated for both approved and unapproved uses.

Botulinum toxin products include:

• Botox and Botox Cosmetic (botulinum toxin type A), marketed by Allergan
• Myobloc (botulinum toxin type B), marketed by Solstice Neurosciences
• Dysport (abobotulinumtoxinA),  a new FDA-approved product marketed by Ipsen Biopharm Ltd.

All are approved by the FDA for the treatment of  cervical dystonia.  Botox Cosmetic and Dysport are approved by the FDA for treatment of glabellar frown lines.  Botox is approved for the treatment of severe underarm sweating (primary axillary hyperhidrosis), crossed eyes (strabismus), and abnormal tics and twitches of the eyelids (blepharospasm).    All other uses are considered off-label.

The FDA has not identified any definitive serious adverse event reports of a distant spread of toxin effect producing symptoms consistent with botulism when these products are used in accordance with the approved label.

It is important for those of us who use botulinum toxins to remember that the dosage strength between the products is not the same.  One unit of Botox is not equal in strength (potency) as one unit of Myobloc or Dysport. 

BOTOX® Cosmetic Insert (pdf)

Dilution Technique:  Using a 21-gauge needle and an appropriately sized syringe draw up a total of 2.5 mL/100 Unit vial or 1.25 mL/50 Unit vial of 0.9% sterile saline without a preservative…….
Injection Technique: Glabellar 

Using a 30-gauge needle, inject a dose of 0.1 mL into each of 5 sites, 2 in each corrugator muscle and 1 in the procerus muscle for a total dose of 20 Units. Typically the initial doses of  reconstituted BOTOX® Cosmetic induce chemical denervation of the injected muscles one to two days after injection, increasing in intensity during the first week.

MYOBLOC® Insert (pdf)

The recommended initial dose of MYOBLOC® for patients with a prior history of tolerating botulinum toxin injections is 2500 to 5000 U divided among affected muscles. Patients without a prior history of tolerating botulinum toxin injections should receive a lower initial dose.  The duration of effect in patients responding to MYOBLOC® treatment has been observed in studies to be between 12 and 16 weeks at doses of 5000 U or 10,000 U.

Dysport®  Insert 

The units of Dysport are specific to the preparation and are not interchangeable with other preparations of botulinum toxin.

Glabellar lines Dosage

The dosage is dependant on the severity of the lines and the specific muscle being treated.

For the corrugator and procerus muscles 40 to 60 units divided between injection sites as follows:

8 to 12 units in each of 5 sites, 2 in each corrugator muscle and 1 in the procerus muscle for a total dose of 60 units

Improvement of severity of glabellar lines generally occurs within 72 hours after treatment and persists for 3 to 6 months.

It is important for us to educate patients and their caregivers of the potential adverse effects.  Some of these effects have been reported as early as several hours and as late as several weeks after treatment.  Patients should seek immediate medical attention if they develop any of these symptoms  --  unexpected loss of strength or muscle weakness, hoarseness or trouble talking, trouble saying words clearly, loss of bladder control, trouble breathing, trouble swallowing, double vision, blurred vision and drooping eyelids.

Adverse events may be reported by health care professionals and/or consumers to the FDA's MedWatch Adverse Event Reporting program   by four ways:

• Online: www.fda.gov/MedWatch/report.htm
• Regular Mail: use postage-paid FDA form 3500 available at: www.fda.gov/MedWatch/getforms.htm and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
• Fax: 800-FDA-0178 (the same form you would mail)
• Phone: 800-FDA-1088

REFERENCES

FDA News (April 30, 2009)

BOTOX® Injections; eMedicine Article, Sept 25, 2008; Robert A Hauser, MD, MBA, Mervat Wahba, MD, Theresa McClain, MSN, ARNP

Herbal Supplements and Surgery Reviewed

Updated 3/2017-- photos and all links (except to my own posts) removed as many no longer active. and it was easier than checking each one. 

I reviewed this topic in June 2007, but the recently published article in the March/April issue of the Aesthetic Surgery Journal makes it timely to review again. The article points out that many patients don’t tell their doctors about taking the herbal supplements. Many doctors forget to ask.

Patients tend to underreport the use of complementary medicines to their conventional health care providers. In fact, 40% to 70% of responders in many investigations did not report complementary medicine use to their doctors.

It is important for both doctors and patients to ask and tell. Here is a reposting of that post.

Many people take herbal supplements these days for many reasons.

Chondroitin and glucosamine (My husband swears by them. My 14 yr old labrador, Girlfriend takes them.) are supplements that are taken together. Both are components of the normal cartilaginous matrix and are used to treat osteoarthritis.

Echinacea is often used for prevention and treatment of viral and bacterial infections. It has been shown that echinacea, both in vitro and in vivo, possessing immunostimulation properties because of enhancing phagocytosis and nonspecific T-cell stimulation.

Ginkgo biloba has become widely used for its efficacy in treating peripheral and cerebral circulatory disturbances, including claudication and memory impairment (e.g., Alzheimer’s Disease).

Garlic is taken to aid in the reduction of atherosclerosis and hypercholesterolemia. It is also taken as an antioxidant, an antibiotic, a diuretic, an antitussive, to remove “evil” spirits, strengthen the stomach and spleen, and relieve diarrhea.

Ephedra is used to promote weight loss, increase energy, and treat respiratory tract conditions, such as asthma and bronchitis. It is contained in many over-the-counter “slimming preparations.”

Many people take these supplements with no thought of "side effects" or interactions with their prescriptions.

Chondrotin and heparin are similar in chemical composition and researchers speculate that bleeding complications may arise from chondroitin use, particularly when used in combination with other blood-thinning medications.

Because echinacea does have immunostimulation properties, it is contraindicated in systemic and autoimmune diorders. The immunostimulatory effects can offset the immunosuppressive actions of corticosteroids and cyclosporin. Side effects of echinacea also include GI upset, headache, dizziness, and potential allergic reactions. Prolonged use of ecchinacea (8 weeks) has been documented to cause tachyphylaxis through an unknown mechanism. Echinacea is also an inhibitor of cytochrome P450, 3A4, and sulfotransferase and can potentiate the toxicity of drugs that are metabolized by these pathways (benzodiazepines, barbiturates).

Gingko biloba has the ability to inhibit platelet-activation factor and possesses an anti-inflammatory effect. Gingko biloba has induced spontaneous hyphema (bleeding from the iris in the anterior chamber of the eye), subarachnoid hemorrage, and spontaneous bilateral subdural hematomas. It should not be used with other anticoagulants. Other side effects of gingko include headache, GI symptoms, and allergic skin reactions.

The active ingredient in garlic is allicin, which has been reported to inhibit platelet aggregation. It should not be taken with other coagulation inhibitors (e.g. warfarin, heparin, nonsteroidal anti-inflammatory inhibitors, and aspirin). Other side effects of garlic include halitosis, nausea, hypotension, headache, bloating, and possible allergic reaction.

Ephedrine, a chemical contained in ephedra, has medical uses, mostly in operating rooms and intensive care units. It is sympathomimetic agent and causes positive inotropic and chronotropic responses to raise blood pressure and heart rate, respectively; dilates bronchioles; and increases metabolic rate. Side effects such as psychiatric disturbances, heart attack, cardiac dysrhythmias associated with volatile general anesthetic agents (e.g., halothane) and cardiac glycosides (e.g., digitalis), stroke, and even death. Of note, patients taking ephedra under general anesthesia can have severe hypotension that can be controlled with phenylephrine instead of ephedrine.

It has become important to ask patients about supplements. It is important to caution them to stop them prior to surgery. Gingko biloba should be discontinued at least 36 hours before surgery. Garlic should be discontinued at least 1 week prior to surgery. The exact time for chondrotin is unknown, so recommendations are based on guidelines from the American Society of Anesthesiologists, which advises that all herbal medicines without formal study be discontinued at 2 to 3 weeks before an elective surgical procedure. Echinacea should be discontinued 2-3 weeks prior to surgery. Ephedra should be discontinued at least 24 hours prior to surgery.

Herbal supplements are being studied as medications, but still too much is unknown. If you are the patient, tell your doctor which ones you are taking. If you are scheduled for an elective surgery, stop taking the supplements for 2-3 weeks prior to surgery.

Some references:
1. Kleiner, S. M. The true nature of herbs. Phys. Sports Med. 23: 13, 1995.

2. Eisenberg, D. M., and Kessler, R. C. Unconventional medicine in the United States: revalence, costs and patterns of use. N. Engl. J. Med. 328: 246, 1993.

3. Kaye, A. D., Kucera, I., and Sabar, R. Perioperative anesthesia clinical considerations of alternative medicines. Anesthesiol. Clin. North Am. 22: 125, 2004

4. Ang-Lee, M. K., Moss, J., and Yuan, C. Herbal medicines and perioperative care. J.A.M.A. 286: 208, 2001

5. Heller, Justin B.S.; Gabbay, Joubin S. M.D.; Ghadjar, Kiu; Jourabchi, Mickel; O'Hara, Catherine B.A.; Heller, Misha B.S.; Bradley, James P. M.D. Top-10 List of Herbal and Supplemental Medicines Used by Cosmetic Patients: What the Plastic Surgeon Needs to Know. Plastic & Reconstructive Surgery. 117(2):436-445, February 2006.

6. Broughton, George II M.D., Ph.D., Col., M.C., U.S.A.; Crosby, Melissa A. M.D.; Coleman, Jayne M.D.; Rohrich, Rod J. M.D. Use of Herbal Supplements and Vitamins in Plastic Surgery: A Practical Review. Plastic & Reconstructive Surgery. 119(3):48e-66e, March 2007.

7. Perioperative Risks and Benefits of Herbal Supplements in Aesthetic Surgery; Aesthetic Surgery Journal, March/April 2009; vol 29: pp 150-157; Rowe, D.J.

Sulfonamide Associated Hepatic Failure

Updated 3/2017-- all links (except to my own posts) removed as many no longer active. and it was easier than checking each one. 

First off, let me say I have never seen this complication of sulfonamides.  I was only vaguely aware that it existed.  A patient came in to discuss a cosmetic procedure.  Like always, I was going through the allergy section.  She had marked yes on the sulfa drugs.  I asked what kind of reaction.   I want to know if it was a true problem or just an unwelcome side effect.

She then told me about her son who died of acute hepatic failure from a reaction to Bactrim (Sulfamethoxazole/Trimethoprim), and how a few years after his death she got very ill after taking Bactrim.  So now their family refuses to take sulfa drugs.  It prompted me to do a review.

Sulfamethoxazole/Trimethoprim (SMX/TMP) is a commonly used antibiotic for respiratory, gastrointestinal and urinary tract infections caused by a range of aerobic gram-positive and gram-negative bacteria. It also has activity against Listeria monocytogenes, Nocardia and Pneuomcystis jiroveci.

SMX/TMP is generally well tolerated in non-HIV-infected patients.  Adverse reactions occur in this group in approximately 6 to 8 percent of individuals. In comparison, the adverse reaction rate is as high as 25 to 50 percent in HIV-infected patients and many of the reactions are severe.

The most common adverse reactions include nausea, vomiting, anorexia, dermatological reactions such as pruritis, urticaria and less commonly Steven Johnson Syndrome.

Life-threatening adverse reactions include neutropenia, exfoliative dermatitis (a severe skin disorder with generalized erythema and scaling) and toxic epidermal necrolysis (an acute severe reaction with widespread erythema and detachment of the epidermis). Acute liver failure has only been reported in a few cases worldwide, and has been attributed to the sulphonamide component of the drug.

The sulfamethoxazole component of SMX/TMP is responsible for most of its' side effects including liver failure.
Three forms of SMX/TMP induced liver damage have been described.
1) hepatocellular
2)  mixed hepatocellular cholestatic
3) bile duct injury with ductopenia or Vanishing Bile duct syndrome

The onset of symptoms usually occurs within a few days of exposure, but can take up to a 1–2 months.  Patients will usually present with  nausea, vomiting, jaundice, and pruritis (if cholestatic).  Liver function tests (LFTs)  may show a hepatocellular or cholestatic pattern depending on the type of injury. Patients might have other feature of an allergic reaction such as skin rash, eosinophilia. 

Diagnosis is suspected from the clinical presentation, and absence of other causes.

The severity of SMX/TMP induced liver injury can range from mild symptoms with elevated liver enzymes to fulminant hepatic failure with hepatic encephalopathy and coagulopathy. Outcome can be favorable with spontaneous resolution or unfavorable leading to death.

Treatment is generally supportive, liver transplantation has been successful for both fulminant hepatic failure and vanishing bile duct syndrome

REFERENCES

Acute Liver Disease Associated with Erythromycins, Sulfonamides, and Tetracyclines; Annals of Internal Medicine, Vol 119, Issue 7, Part 1, pp 576-583, Oct 1993;  Jeffrey L. Carson; Brian L. Strom; Amy Duff; Anand Gupta; Michele Shaw; Frank E. Lundin; and Kiron Das

Case Report: Sulfamethoxazole/Trimethoprim induced liver failure: a case report; Cases Journal 2008, :44doi:10.1186/1757-1626-1-44; Salaheldin Abusin, Swapna Johnson
Harrison’s Online; Chapter 299 (Merck’s)-- Trimethoprim-Sulfamethoxazole Hepatotoxicity (Idiosyncratic Reaction)

Latisse for Longer, Darker Lashes

Updated 3/2017-- all links (except to my own posts) removed as many no longer active. and it was easier than checking each one. 

Have you ever wished you had longer, darker lashes?  Well, now there is an FDA approved drug that can help you with your wish.  Friday, December 26, 2008, Allergan Inc. made the announcement.

The drug, Latisse, can be obtained by prescription only, so will be available through a doctor’s office.  

The primary ingredient in Latisse, bimatoprost, is a prostaglandin analog that is present in hair.  It is thought to help in the development and regrowth of hair follicles.

Latisse is applied once-daily to the base of the upper eyelashes with a sterile, single-use-per-eye disposable applicator.  Users may begin to see results as early as six to eight weeks.  However, it takes 16 weeks to see the full results. 

• Latisse should not be applied to the lower lid. 
• Lashes on each eye lid may not grow in the exact same way. 
• Continued use of the drug is necessary to maintain the effect.  Lashes will gradually return to pretreatment state if the use of Latisse is discontinued.

Contraindications and Side Effects

The only known contraindication for use of Latisse is hypersensitivity to the drug.

Approximately 4% of users of Latisse will have side effects such as an itching sensation in the eyes and/or eye redness.

Pigmentation of the eyelids and iris may occur.

Other less common side effects which typically occur on the skin close to where Latisse is applied, or in the eyes include skin darkening, eye irritation, dryness of the eyes, and redness of the eyelids.

Precautions

If you develop a new eye condition (e.g., trauma or infection), change in vision, have eye surgery, or develop any eye reactions (e.g. conjunctivitis and eyelid reactions), you should immediately seek your doctor's advice  and consider discontinuing use of Latisse.

Other posts you may find interesting:

Eyebrow Reconstruction

Hair for Charity

Hair Transplantation

Permanent Hair Removal

Antibiotic TX for Seawater Injuries

Updated 3/2017-- photos and all links removed as many are no longer active and it's easier than checking each one.

I wanted to share this article (reference below) as many of us may either see these patients as tourists or after they return from vacation. It is nice to have a logical choice for empiric antibiotic therapy. 

The proposal of the article was "that the analysis of seawater pathogens will act as a guide for rational empiric antibiotic therapy, either as prophylaxis at the time of penetrating injury or as early treatment of a developing infection." To do this, 50 ml samples of seawater were collected from 25 preselected locations along a 12-km segment of the southern portion of the Galveston beach area in Texas. These water samples were taken over four seasons, the fall and winter of 2002 and the spring and summer of 2003.

"Despite variations in water temperature and beachgoer population size, the seasonal variations of bacterial species were minimal. Throughout all four studies, the most effective antibiotics against most Gram-positive microorganisms were penicillin, ampicillin, vancomycin, and levofloxacin, whereas the most effective antibiotics against all Gram-negative microorganisms were levofloxacin, lomefloxacin, and cefepime. Because all four studies contained similar trends in both Gram-positive and Gram-negative microorganisms, these authors believe that it is necessary to prescribe initial antibiotics that provide dual coverage of Gram-positive and Gram-negative organisms to patients with seawater-contaminated wounds, regardless of the season. Although the majority of organisms analyzed showed some sensitivity to levofloxacin, this drug has somewhat limited Gram-positive coverage that the addition of penicillin will address more appropriately. Thus, prescribing a combination of penicillin or ampicillin with levofloxacin to patients with seawater-contaminated penetrating wounds at any time throughout the fall, winter, spring, or summer should provide the necessary coverage to promote proper wound healing and functional recovery of the injured site. As is usually practiced, antibiotic therapy should be administered for a period of 5 to 7 days, with further changes being made based on the treating physician's clinical judgment. Using this regimen will also cover the dangerous Vibrio species and aid in preventing the morbidity and mortality associated with such infections."

The decision to treat any wound with antibiotic therapy should be based on clinical judgment. Abrasions and superficial injuries may only require debridement and copious irrigation. Lacerations and penetrating wounds that have a clearly visible base and no signs of infection in the wound or surrounding tissues may be irrigated and closed primarily using clinical judgment. However, seawater-contaminated wounds that are penetrating deeper than the dermis and associated with erythema and/or edema in the surrounding tissue will most likely benefit from dual-coverage prophylactic antibiotic therapy pending culture results.

REFERENCES

Empiric Antibiotic Therapy for Seawater Injuries: A Four-Seasonal Analysis; Plastic & Reconstructive Surgery. 121(4):1249-1255, April 2008; Jennifer S. Kargel, B.S.; Vanessa M. Dimas, B.S.; Dennis S. Kao, M.D.; John P. Heggers, Ph.D.; Peter Chang, M.D., D.M.D.; Linda G. Phillips, M.D.

Drugs in our Water Supply

 Updated 3/2017-- all links removed as many no longer active.

The news today is full of the headlines -- "Pharmaceuticals in Drinking Water".

As I mentioned in my post on "Unused Medicines", the question of what to tell patients to do with unused medicines has changed since I was in medical school. We were taught to tell patients to flush them. That is not a good idea. But what do we tell them? It seems that the new advise is not always always clear. The two best sites I found were the American Pharmacy Association and the White House Drug Policy.

The Federal Guidelines state:

• Take unused, unneeded, or expired prescription drugs out of their original containers and throw them in the trash.
• Mixing prescription drugs with an undesirable substance, such as used coffee grounds or kitty litter, and putting them in impermeable, non-descript containers,such as empty cans or sealable bags, will further ensure the drugs are not diverted.
• Flush prescription drugs down the toilet only if the label or accompanying patient information specifically instructs doing so ( see list below).
• Take advantage of community pharmaceutical take-back programs that allow the public to bring unused drugs to a central location for proper disposal. Some communities have pharmaceutical take-back programs or community solid-waste programs that allow the public to bring unused drugs to a central location for proper disposal. Where these exist, they are a good way to dispose of unused pharmaceuticals.

The FDA advises that the following drugs be flushed down the toilet instead of thrown in the trash:
Actiq (fentanyl citrate)
Daytrana Transdermal Patch (methylphenidate)
Duragesic Transdermal System (fentanyl)
OxyContin Tablets (oxycodone)
Avinza Capsules (morphine sulfate)
Baraclude Tablets (entecavir)
Reyataz Capsules (atazanavir sulfate)
Tequin Tablets (gatifloxacin)
Zerit for Oral Solution (stavudine)
Meperidine HCl TabletsPercocet (Oxycodone and Acetaminophen)
Xyrem (Sodium Oxybate)Fentora (fentanyl buccal tablet)