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Psychiatry, Infections, drugs Which of the following is TRUE about the oral anticoagulants used to prevent stroke due to atrial fibrillation? A.Pradaxa (dabigatran) 150 mg BID prevents more strokes than warfarin. B.Xarelto (rivaroxaban) 20 mg once a day works about as well as warfarin. C.Both Pradaxa and Xarelto ca use fewer intracranial bleeds than warfarin...but more GI bleeds. D.All of the above Answer • D.All of the above Which of the following is TRUE about treating ADHD? A.Methylphenidate is appropriate for some children as young as 4 years old. B.Methylphenidate 1 mg is equivalent to 2 mg of amphetamine salts. C.Stimulants significantly increase cardiovascular risk in otherwise healthy kids. D.Stimulants are metabolized faster in preschoolers than older children. Answer • A.Methylphenidate is appropriate for some children as young as 4 years old. • New guidelines and drug shortages will raise new questions about treating ADHD in children. The new guidelines now recommend treating kids as young as 4...IF they have severe symptoms that impair function AND behavioral therapy isn't enough. Until now the cutoff was 6-year-olds. If you need to treat a 4- or 5-year-old, use low-dose methylphenidate. Stimulants are metabolized slower at this age. Reassure parents any increased cardiovascular risk from stimulants is likely very small...if it exists at all...in otherwise healthy kids. Continue to monitor BP and pulse. Avoid stimulants in children with serious heart problems, such as arrhythmias, cardiomyopathy, etc. The Adderall (amphetamine salts) and methylphenidate shortages are causing lots of problems. These will continue at least through the rest of 2011. Two culprits...manufacturing problems...plus delays caused by cumbersome regulations that limit quantities of controlled substance raw materials. If needed switch patients to an available med. A rule of thumb: Use about 1 mg methylphenidate for 0.5 mg of amphetamine salts, dextroamphetamine, or dexmethylphenidate (Focalin)...but responses vary. To switch from Adderall to dextroamphetamine or methylphenidate, start with the same total daily dose and titrate as needed. To switch from methylphenidate to Adderall, cut the daily dose in half and monitor for response and side effects. To switch to a different oral methylphenidate product, use the same daily dose...divided appropriately. An exception is Concerta...use 18 mg/day of Concertafor 15 mg/day of methylphenidate. When in doubt, start with the new product's starting dose. To HEAR our experts enlighten you on the controversy of when to treat ADHD in kids, see our PL Detail-Document and listen to PL Voices. You can also get our PL Chart, Comparison of Drugs for ADHD, for treatment options, dosing, duration, and cost. • You'll hear that vitamin E INCREASES the risk of prostate cancer. This is a surprise...but based on reliable evidence. Vitamin E was often recommended to PREVENT prostate cancer...based on several older studies. The latest big randomized trial suggests the opposite. It shows one more case of prostate cancer for every 625 men taking 400 units per day of vitamin E for one year. There are also cardiovascular concerns. Vitamin E may increase the risk of hemorrhagic strokes...and taking 400 units/day may increase the risk of heart failure in patients with diabetes or heart disease. Vitamin E proponents will point out that the new findings are for SYNTHETIC vitamin E. They're right. Keep in mind this is the form most users get. And there's no solid proof that NATURAL vitamin E is safer or more effective than the synthetic versions. Discourage using vitamin E to prevent cancer or heart disease. Don't go out of your way to discourage using regular multivits... as long as they do not contain large amounts of synthetic vitamin E • TESTOSTERONE If you prescribe AndroGel or Androderm (testosterone), you'll likely get a call about the strength. AndroGel now comes in a higher concentration so patients can use less gel. Using 2 pumps of the new AndroGel 1.62% is similar to using 4 pumps ofAndroGel 1%. The new strength will be priced a little LOWER to entice patients to switch. But they both still cost over $300 a month...and a generic is 2 or more years away. If you write for AndroGel, be sure to specify 1% or 1.62%. Tell men to apply the new AndroGel 1.62% only to their upper arms and shoulders for better absorption...instead of to their abdomen, too, like AndroGel1%. Also tell them to avoid bathing for 2 hours after applying AndroGel 1.62%...or 5 hours for AndroGel 1% due to the larger amount. Androderm now comes in smaller, lower-strength patches...the original patches will be discontinued at the end of this year. Use the new 2 mg patch instead of the older 2.5 mg patch...and the new 4 mg patch instead of the 5 mg patch. Check serum testosterone 2 weeks after the switch to make sure the new dose is appropriate. Get our latest PL Chart, Comparison of Testosterone Products, with all dosage forms including injectable, buccal, and others. Which of the following is TRUE about vaccinations for pregnant women? A.Tdap can now be given to pregnant women after 20 weeks gestation. B.Two doses of Tdap should be given during pregnancy. C.Flu vaccine with thimerosal is proven to be harmful during pregnancy. D.FluMist is appropriate for pregnant women. Answer • A.Tdap can now be given to pregnant women after 20 weeks gestation • You'll see a new emphasis on giving Tdap and flu vaccines to pregnant women...to protect moms AND their newborns. Tdap (Adacel, Boostrix) used to be given to the mom right AFTER delivery if needed. But that leaves newborns unprotected until they start getting pertussis vaccinations at 2 months. Vaccinate pregnant women after 20 weeks gestation if they haven't previously gotten Tdap and only need a booster. When a pregnant woman's vaccine history is unknown or incomplete, give a 3-shot series: one dose right away...another at 4 weeks...and the last at 6 to 12 months. Use Tdap for the first vaccine after 20 weeks gestation...and Td for the other two injections. Injectable influenza vaccine (Fluzone, etc) can be given during ANY trimester. Don't use FluMist...it's not recommended during pregnancy because it's a live vaccine. Some states require using a thimerosal-free vaccine for pregnant women and children...even though there's no proof thimerosal is harmful. If you need to avoid thimerosal, use one of the prefilled syringes...EXCEPTFluvirin which has trace amounts of thimerosal. Consider reporting immunizations to your state's Immunization Information System...even if it's not required. Providers are being encouraged to use these vaccine registries...and using them counts as one of the "meaningful use" criteria for electronic health records • GERIATRICS Most current electronic systems don't alert you about too many anticholinergics in an elderly patient...but they should. Even a single anticholinergic med can increase the risk of cognitive impairment by up to 50%...even more in patients who've had a stroke or have a family history of dementia. Anticholinergics are also linked to higher hospitalization rates. Think about each patient's anticholinergic burden...and whether meds can be stopped, switched, or given in a lower dose. Antihistamines. Avoid first-generation antihistamines (diphenhydramine, etc)...including "PM" OTCs, such as Tylenol PM. Instead, use a second-generation antihistamine (loratadine, etc) or nasal steroid for allergies...or low-dose trazodone for insomnia. Antidepressants. Try to avoid tricyclics (amitriptyline, etc) or paroxetine. Instead, use one of the other SSRIs (sertraline, etc) for depression...and consider using gabapentin for neuropathic pain. Overactive bladder agents. Their minimal benefits usually don't outweigh their significant anticholinergic effects. And there's no proof the newer ones have less effect on cognition. Try to avoid bladder control drugs in patients who already have poor cognition...or those whose quality of life isn't likely to benefit. Keep in mind that these anticholinergics are sometimes added for incontinence that's caused or exacerbated by a cholinesterase inhibitor (Aricept, etc). A great example of using one drug to treat the effects of another. Re-evaluate whether either one is really needed. • The new generic olanzapine (Zyprexa) means you'll see even more patients on atypical antipsychotics. In some situations this is appropriate...in others it's not. About 60% of atypical usage is off-label. Evidence of effectiveness varies by drug and indication: Insomnia. Low doses of quetiapine (Seroquel, etc) and others are often used because they can be sedating. But there's no evidence they're effective for insomnia and they have serious side effects. Try zolpidem, trazodone, and others first. Generalized anxiety disorder. Consider trying quetiapine if patients don't respond to an SSRI (sertraline, etc) or SNRI (venlafaxine, etc). There's no evidence that any of the other atypicals are effective for anxiety. Depression. Olanzapine, Abilify (aripiprazole), and Seroquel XR are approved to use with an antidepressant for depression...and there's good evidence for risperidone. But they have only a modest benefit and serious side effects. Try an adequate trial of antidepressants first. Dementia. Antipsychotics increase strokes and mortality in elderly dementia patients. Save them for patients who are a risk to themselves and others due to aggression, hallucinations, or delusions. Consider using one-quarter to one-half the usual starting dose of risperidone, olanzapine, or Abilify...they have the most evidence. Use quetiapine for patients with Lewy body dementia or Parkinson's. Monitor blood glucose and lipids at baseline, 12 weeks, and then periodically for patients on an atypical. Also check weight every month for 3 months, then every 3 months. Keep in mind that olanzapine is one of the worst offenders for causing metabolic problems • Dosing and drug interactions with colchicine (Colcrys) for acute gout are still causing confusion. We're all used to the old way of dosing colchicine for acute gout...two tabs initially then one tab every hour until either diarrhea starts or the pain stops. But this causes too much toxicity...and even some deaths. When FDA approved Colcrys, they also approved safer dosing. The new dosing for a gout flare is to give two 0.6 mg tablets followed by just ONE tab one hour later. Give even lower and less frequent doses if colchicine is used with other drugs that inhibit its metabolism. For example, give just one tab per attack with cyclosporine...one tab followed by a half tab with strong 3A4 inhibitors (clarithromycin, etc)...and two tabs with moderate 3A4 inhibitors (verapamil, etc). Tell patients not to repeat these colchicine doses for at least 3 days. For severe renal or hepatic impairment, give a 3-tablet course...and wait at least 2 weeks before repeating the course. Don't give colchicine plus cyclosporine or a strong 3A4 inhibitor to a patient with renal or hepatic impairment. This can be fatal. Continue to use NSAIDs or corticosteroids first-line for acute gout. They're usually better tolerated and cost less...at least until generic colchicine is available again • Reps will promote using Byetta WITH Lantus for type 2 diabetes. Adding Byetta (exenatide) to Lantus (insulin glargine) lowers A1C by 1.7%...compared to 1% for Lantus alone. Think of it as an alternative to adding a short-acting prandial insulin (Humalog, etc)...when a basal insulin isn't enough. Byetta doesn't increase hypoglycemia risk...and it can help reduce the weight gain associated with insulin. In fact, patients on the combo for 30 weeks LOSE about 4 pounds...compared to GAINING 2 pounds with just Lantus. But about one in 12 patients will stop Byetta due to nausea, vomiting, diarrhea, or other side effects. And Byetta costs about $340/month...compared to up to $190/month for prandial insulin plus extra for glucose monitoring. Add either Byetta or a prandial insulin when basal insulin and oral meds aren't enough for type 2 diabetes. Lean towards Byetta to reduce weight gain or hypoglycemia. When starting Byetta, consider lowering the basal insulin dose by 20% if the patient's A1C is 8 or less. Keep in mind that Byetta isn't appropriate for patients already using prandial insulin Which of the following is TRUE about treating UTIs in the elderly? A.Nitrofurantoin is a good option for uncomplicated UTIs if renal function is okay. B.TMP/SMX can cause hyperkalemia when combined with an ACE inhibitor or ARB. C.Quinolones are preferred for complicated UTIs. D.All of the above Answer • D.All of the above • URINARY TRACT INFECTIONS Which antibiotics should you use for urinary tract infections in elderly patients? It depends on whether it's a complicated UTI or not. We know all UTIs in older MEN are considered complicated due to possible prostate involvement. UTIs in women can also be complicated due to a catheter, obstruction, immunosuppression, etc. Antibiotic selection also depends on kidney function, side effects, and possible drug interactions. TMP/SMX is first-line for uncomplicated infections...if local resistance is <20%. Use TMP/SMX DS twice daily for 3 days...and half the dose if kidney function is impaired (CrCl 15 to 30 mL/min). Watch for possible hyperkalemia if TMP/SMX is combined with an ACEI, ARB, or potassium...or increased INR with warfarin. Nitrofurantoin 100 mg BID for 5 days is a good option for uncomplicated UTIs...IF renal function is okay. Avoid nitrofurantoin in women with a CrCl <60 mL/min...or for a complicated UTI. Quinolones are the best choice for complicated UTIs and kidney infections...or if patients can't take TMP/SMX or nitrofurantoin. Avoid moxifloxacin or gemifloxacin...they don't get into the urine. Avoid quinolones if local resistance is over 10%...and adjust the dose for impaired renal function. Keep in mind possible adverse CNS effects...tendon rupture...hyper- or hypoglycemia...or increased INR in warfarin patients. Beta-lactams (amoxicillin, etc) are usually less effective for UTIs. Use them only if other antibiotics aren't an option. Give antibiotics for 3 to 5 days for uncomplicated UTIs... 7 to 14 days for complicated UTIs...and 6 to 12 weeks for men with prostate involvement. Don't screen for or treat asymptomatic bacteriuria in most cases. There's no benefit...and it increases resistance Which of the following is TRUE about using NSAIDs in patients with uncomplicated hypertension? A.Even occasional use of NSAIDs should be avoided. B.Combining an NSAID with an ACE inhibitor or ARB can worsen BP and renal function. C.Some NSAIDs are more likely to increase BP than others. D.Naproxen is the most likely to increase cardiovascular risk. Answer • B.Combining an NSAID with an ACE inhibitor or ARB can worsen BP and renal function. • NSAIDS Is it okay for patients with uncomplicated hypertension to take NSAIDs...ibuprofen, celecoxib, etc? Many can...but you need to be careful. On average, NSAIDs increase BP by around 5 mmHg in patients with hypertension...but some patients are more susceptible than others. Elevations are more likely in the elderly...obese men...and patients with diabetes, heart failure, or kidney or liver disease. Tell patients with uncomplicated hypertension that occasional use of NSAIDs is usually okay...but daily use for just one week can reduce BP control. Monitor BP if a hypertensive patient starts a chronic NSAID. Explain that NSAIDs can also make BP meds less effective. Be careful about combining an NSAID with an ACE inhibitor or ARB...the combo can worsen BP and renal function. And watch for the "triple whammy"...an NSAID plus an ACEI or ARB plus a diuretic. This combo can push a patient into acute renal failure. Consider using a calcium channel blocker if a patient needs an antihypertensive that is less affected by NSAIDs. Don't expect one NSAID to increase BP more or less than the others. Suggest naproxen if a chronic NSAID is needed for a patient with cardiovascular disease...not just hypertension. Naproxen seems to be the least likely to increase cardiovascular risk Which of the following is TRUE about the new generic atorvastatin (Lipitor)? A.It lowers LDL more than simvastatin. B.It has fewer interactions than simvastatin. C.Atorvastatin 80 mg lowers LDL about as much as Crestor 20 mg. D.All of the above Answer • D.All of the above • Atorvastatin will unseat simvastatin as the most popular generic statin...especially with simvastatin's new dosing restrictions. Simvastatin now needs to be limited to 40 mg/day due to the increased risk of myopathy with higher doses. Use an even lower simvastatin dose if you give it with amlodipine, diltiazem, verapamil, amiodarone, or ranolazine. And try not to use it at all with gemfibrozil or strong 3A4 inhibitors (clarithromycin, etc). Consider switching to atorvastatin as your statin of choice... it lowers LDL more than simvastatin and has fewer interactions. Atorvastatin can even replace Crestor (rosuvastatin) in many cases. Atorvastatin 80 mg and Crestor 20 mg both lower LDL about 55%. When switching, use atorvastatin 20 mg for simvastatin 40 mg or Crestor 5 mg. You may hear reps talking up Livalo's (pitavastatin) lack of drug interactions. There's some truth to this. But when interactions are a concern, use Crestor or pravastatin. They have a longer track record...and Crestor lowers LDL more thanLivalo. Keep in mind that LDL-lowering is just treating a lab number. It's patient OUTCOMES that matter. For secondary prevention, statins prevent one death for every 48 patients treated for 3 to 5 years. For primary prevention, statins prevent one nonfatal CV event for every 60 patients treated for 4 years. The price of generic atorvastatin won't drop much until more generics come out in 6 months. But tell Lipitor patients who pay a co-pay for Rxs that they'll likely pay less by getting the GENERIC. Until the generic price drops, suggest that patients who pay more than $50/month keep using their Lipitor co-pay card...the program runs through 2012. To get the scoop on how atorvastatin really stacks up to Crestor and fact vs fiction on simvastatin interactions, see our PL Detail-Document and click to listen to PL Voices. You'll hear an interesting audio snippet of our experts' lively discussion. Which of the following is TRUE about using bisphosphonates for osteoporosis? A.Bisphosphonates can be stopped after 3 to 5 years for most patients. B.Bisphosphonates should be continued in patients at high risk for fractures. C.Bisphosphonates only stay in the bone for a few days. D.Both A and B Answer • D.Both A and B • You'll hear more controversy about how long patients should take bisphosphonates (Fosamax, etc) for osteoporosis. Many patients get put on a bisphosphonate to prevent fractures and are left on it indefinitely. But long-term use may be associated with problems...jaw osteonecrosis and atypical femur fractures. Keep in mind that bisphosphonates persist in the bone for years and may continue to prevent fractures even after they're stopped. For example, women who stop alendronate after 5 years have a similar risk of nonvertebral fractures as those who continue it for 10 years. And stopping zoledronic acid (Reclast) after 3 years prevents fractures almost as well as taking it for 6 years. Consider stopping the bisphosphonate after 3 to 5 years for most patients. But continue it or switch to another osteoporosis med for patients at high fracture risk, such as those with a recent fracture... on chronic corticosteroids...or if bone density continues to drop. Consider checking bone density or bone turnover markers 2 to 3 years after stopping a bisphosphonate. If these indicate bone loss, restart the bisphosphonate...or start raloxifene, calcitonin, Forteo, or Prolia. Continue to encourage patients to get about 1200 mg/day of elementalcalcium...and 800 to 2000 units/day of vitamin D. Which of the following is TRUE about using tadalafil (Cialis) for benign prostatic hyperplasia (BPH)? A.It improves urine flow. B.It works better than an alpha-blocker (tamsulosin, etc) for BPH. C.It may be appropriate for men with erectile dysfunction and mild BPH symptoms. D.It should never be combined with an alpha-blocker. Answer • C.It may be appropriate for men with erectile dysfunction and mild BPH symptoms. • Reps will promote daily Cialis (tadalafil) for benign prostatic hyperplasia (BPH)...not just erectile dysfunction. Cialis and other phosphodiesterase-5 inhibitors seem to enhance smooth muscle relaxation in the prostate, bladder, and urethra. But don't expect a large improvement in BPH symptoms. Cialis modestly improves urinary frequency, urgency, and straining...but not urine flow rate. And you have to treat 6 men for one to benefit. Continue to start with alpha-blockers (tamsulosin, etc) for BPH...they're likely to be more effective and they cost less. Consider using daily Cialis for men with both erectile dysfunction and mild BPH symptoms. Or consider adding daily Cialis if a man with both erectile dysfunction and BPH isn't getting adequate relief from an alphablocker. The combo might work better than either drug alone for BPH. When adding Cialis to an alpha-blocker, start with just 2.5 mg a day to reduce hypotension...and titrate to 5 mg. Cialis 5 mg/day costs about $150 a month. Expect insurers to require a prior authorization to verify that it's for BPH. • MEN'S HEALTH Saw palmetto will fall out of favor for treating BPH symptoms. You'll still hear staunch believers claim it works and cite lots of older studies...but it's not standing up to close scrutiny. Two NIH-sponsored trials now suggest that saw palmetto is NOT better than placebo for BPH symptoms...even at high doses. In fact, our Natural Medicines Comprehensive Database is downgrading its rating of saw palmetto to "Possibly INeffective." Evaluating supplements is tricky...results apply mainly to the specific formulation tested. Amazingly, the recent NIH study used a saw palmetto product that is NOT available in the U.S. Tell men not to rely on saw palmetto for BPH. Explain that benefits are modest at best. But don't be overly concerned if they want to try it...there's no evidence of serious adverse effects. Listen to our audio clip, PL Voices, to hear our experts explain why there's been a shift in thinking about saw palmetto... and tips on how to pick high-quality supplements in general. • DIABETES You'll hear claims that gliptins (Januvia, etc) decrease cardiovascular risk in diabetes patients. This is based on a new meta-analysis that suggests gliptins don't increase cardiovascular risk...and MIGHT even decrease it. Don't buy it. It hasn't been peer-reviewed and published. So far, NONE of the diabetes meds are proven to lower CV risk. Metformin seems to have the most favorable cardiovascular profile...but there's not enough evidence to say it's cardioprotective. Pioglitazone (Actos, etc) and rosiglitazone (Avandia) increase heart failure risk...rosiglitazone likely increases MI risk. Gliptins lower A1C by about 0.7% and cost about $8/tab. Save them as a second- or third-line option for patients close to their A1C goal. Juvisync (sitagliptin/simvastatin) will be the first gliptin and statin combo...and will cost the same as Januvia alone. Consider Juvisync for patients on Januvia who also need a statin...and for whom simvastatin is an appropriate choice. Which of the following is TRUE about adding a GI protectant to an NSAID? A.Famotidine 80 mg/day can help prevent NSAID-induced ulcers. B.PPIs are more effective than H2-blockers for preventing NSAID-induced ulcers and bleeding. C.Misoprostol is an alternative to using a PPI. D.All of the above Answer • D.All of the above • You'll hear reps claim the new Duexis is safer than plain NSAIDs. But it's usually not the best choice. Duexis is a combo of ibuprofen 800 mg and famotidine 26.6 mg for TID dosing. This provides about 80 mg/day of famotidine...the dose that has been shown to reduce NSAID-induced ulcers. One ulcer is prevented for every 10 patients taking Duexis compared to ibuprofen alone...but it's not proven to prevent GI bleeds. PPIs are more effective than H2-blockers for preventing NSAID-induced ulcers...AND they're proven to prevent GI bleeds. But PPIs aren't benign. Chronic PPIs are associated with a higher risk of pneumonia, C. diff diarrhea, hypomagnesemia, and fractures. Choose a strategy for NSAID users based on their risks. Use a PPI or misoprostol for those at moderate GI risk due to one or two risk factors...age over 65, high-dose NSAIDs, prior uncomplicated ulcer, or use of aspirin or another antiplatelet drug. Vimovo (naproxen/esomeprazole) is the only NSAID/PPI combo... but it costs more than giving a generic NSAID and PPI separately. Consider using an H2-blocker for patients at moderate GI risk who can't take a PPI or misoprostol. Give famotidine 40 mg BID plus a generic NSAID instead of Duexis. Duexiscontains more ibuprofen than most patients need...and it costs about $150 per month. Consider using celecoxib alone instead of a traditional NSAID plus GI protectant for patients at moderate GI risk...and low CV risk. Use naproxen if an NSAID is needed for patients at high CV risk... and add a GI protectant for those at moderate GI risk. Use celecoxib plus a PPI or misoprostol for patients at high GI risk due to 3 or more risk factors...concomitant warfarin or corticosteroids...or a prior complicated ulcer. This combo has the safest GI profile...but avoid NSAIDs altogether if possible. • NEUROPATHIC PAIN You'll soon see Gralise (gra-LEEZ), a new extended-release gabapentin for postherpetic neuralgia (PHN). Gralise is the second ONCE-daily gabapentin...after the approval of Horizant for restless legs syndrome earlier this year. Gralise tabs are similar to Glumetza (metformin ER). These swell to stay in the stomach longer and gradually release the drug. Continue to use a tricyclic first-line for post-shingles pain. If tricyclics aren't enough or aren't tolerated, go to gabapentin, pregabalin (Lyrica), duloxetine (Cymbalta), opioids, a lidocaine patch, or capsaicin. Combining a tricyclic and gabapentin can work better than either one alone. Gabapentin and pregabalin are only modestly effective for postherpetic neuralgia. Choose one based on cost or convenience. Gralise costs about $180/month...compared to $240 for Lyrica and $40 for gabapentin immediate-release capsules. But keep in mind that Gralise is given once a day...compared to 2 to 3 times a day for Lyrica or 3 times a day for regular gabapentin. If you start a patient on Gralise, prescribe the 30-day starter pack to slowly titrate the patient from 300 mg to 1800 mg/day. Tell patients to take Gralise in the evening with dinner. Which of the following is TRUE about drugs to avoid in patients with glaucoma? A.Anticholinergic drugs can worsen glaucoma by constricting the pupil. B.Anticholinergics are only a problem for patients with narrow-angle glaucoma. C.Corticosteroids can worsen narrow-angle glaucoma. D.It's not necessary to monitor intraocular pressure in patients using ophthalmic steroids long-term. Answer • B.Anticholinergics are only a problem for patients with narrow-angle glaucoma. • OPHTHALMOLOGY Glaucoma patients often ask which drugs to avoid...and if they don't ask, they should. Many drugs have warnings not to use them in glaucoma patients. But these warnings are usually for patients with NARROW-angle glaucoma...which is much less common than OPEN-angle glaucoma. Anticholinergic drugs can dilate the pupil and worsen the obstruction in patients with narrow-angle glaucoma...increasing the risk of acute angle closure. Try to avoid anticholinergics or use the lowest effective dose. This includes many antihistamines, tricyclics, antipsychotics, antispasmodics, overactive bladder drugs, etc. Also warn patients to get immediate treatment if they develop eye pain plus redness, blurred vision, halos around lights, etc. Reassure patients with OPEN-angle glaucoma that anticholinergic drugs will not make it worse. Corticosteroids are another story...these can increase intraocular pressure and cause or worsen open-angle glaucoma. Check intraocular pressure when ophthalmic steroids are used for 10 days or longer, especially in high-risk patients. • EDEMA Questions come up about how to handle drug-induced edema. Peripheral edema often prompts clinicians to jump straight to a workup for thromboembolism or heart, renal, or hepatic failure. But first look for meds that can cause it. Dihydropyridine calcium channel blockers (amlodipine, etc) cause dose-dependent edema. But it's not caused by fluid overload, so diuretics usually don't help. Try to lower the dose...or ADD an ACE inhibitor or ARB. If that doesn't work, switch to a different antihypertensive... even verapamil or diltiazem cause less edema. Pioglitazone (Actos, etc) can cause edema...especially with higher doses. Avoid it in patients with class 3 or 4 heart failure. In other patients, try a lower dose...or switch meds. Consider trying spironolactone or hydrochlorothiazide if needed. They might help...but keep in mind they can sometimes worsen edema. Gabapentin, pregabalin, or dopamine agonists (pramipexole, etc) can cause dose-dependent peripheral edema. Try to lower the dose or switch meds. Diuretics might help some patients...but don't count on them. • MAGNESIUM Concerns about PPIs and hypomagnesemia are raising questions about when and how to use magnesium supplements. PPIs may lower mag levels...possibly due to reduced absorption. Consider checking serum magnesium in patients on long-term PPIs... especially if they have muscle cramps, tremors, palpitations, etc. Also check serum magnesium in patients taking PPIs with drugs that can lower mag, such as diuretics or cisplatin...or in those on digoxin, because hypomag can lead to dig toxicity. But keep in mind that serum levels don't always correlate well with total body stores. Some insurers require an ICD-9 code on the lab slip. Use 275.2 for hypomagnesemia...or 995.20 for a drug adverse effect. Consider checking potassium and calcium at the same time. Hypokalemia and hypocalcemia can be hard to correct if magnesium is low. If a supplement is needed, lean toward one that's better absorbed, such as mag lactate (Mag-Tab SR, etc), mag chloride (Slow-Mag, etc), or mag aspartate (Maginex, etc). Mag oxide (Mag-Ox, etc) has more elemental magnesium than the others...but has poorer absorption. Explain that better absorption may mean less diarrhea. Use 200 to 400 mg/day of elemental magnesium for hypomagnesemia. For 200 mg/day, this works out to about 3 tabs of Mag-Tab SR or Slow-Mag or 4 tabs ofMaginex. Suggest dividing the dose to improve tolerability. Use IV magnesium sulfate for severe deficiencies. If low magnesium doesn't resolve with a supplement in a patient on a PPI, stop the PPI and switch to an H2-blocker if needed. Be careful using magnesium supplements in patients with renal insufficiency...to avoid HYPERmagnesemia. • INFECTIOUS DISEASES New guidelines will help improve the treatment of community-acquired pneumonia in children. Select an antimicrobial for outpatients based on their age, immunization status, and suspected pathogen. Typical bacterial pathogens are common...especially in school-age kids and adolescents. Use amoxicillin 90 mg/kg/day for 10 days...up to 4 g/day to cover Strep pneumoniae. Use amoxicillin/clavulanate (Augmentin, etc) to add H. influenzae coverage when kids aren't fully vaccinated for Hib. Atypical bacterial pathogens such as M. pneumoniae tend to be more common in school-age kids and adults. Suspect Mycoplasma in kids with slowly progressing symptoms...malaise, muscle aches, sore throat, and lowgrade fever with a nonproductive cough. Use azithromycin 10 mg/kg the first day then 5 mg/kg for 4 days... up to 500 mg the first day and 250 mg/day for 4 days. Viruses are usually the culprit in infants and preschoolers... especially if they have gotten their pneumococcal and Hib vaccines. For flu pneumonia, use oseltamivir (Tamiflu)...or zanamivir (Relenza) for kids 7 years and older if an alternative is needed. Which of the following is TRUE about using the new oral anticoagulants for atrial fibrillation? A.They're an alternative to warfarin if INR control is poor or monitoring isn't feasible. B.Dabigatran (Pradaxa) causes less bleeding than warfarin. C.Rivaroxaban (Xarelto) is more effective than warfarin. D.The new anticoagulants are all given once a day. Answer • A.They're an alternative to warfarin if INR control is poor or monitoring isn't feasible. • ANTICOAGULANTS You'll hear controversy over which ORAL anticoagulant to use to prevent strokes in patients with atrial fibrillation. Warfarin was our only option for over 50 years...but you'll get more questions about how the new ones stack up. Warfarin is obviously the gold standard. You know its limitations...INR monitoring, dose adjustments, and many interactions. But advocates call it "the devil we know" because we're familiar with its long-term safety...and it's the only one with an antidote. It's also the cheapest...about $80/month including INR monitoring once a month. Dabigatran (Pradaxa) is a direct thrombin inhibitor...and the first of the new oral anticoagulants that don't need INR monitoring. It prevents more strokes than warfarin...about 5 more strokes per 1000 patients per year...with a similar overall bleeding risk. But it needs to be given twice daily...and costs about $240/month. Rivaroxaban (Xarelto) is the first oral factor Xa inhibitor...and will likely be approved for atrial fib soon. Reps will tout that it only needs to be given once a day. But rivaroxaban doesn't work any better than warfarin...and it costs about the same as dabigatran. Apixaban (Eliquis, ELL-eh-kwiss) will be the next oral factor Xa inhibitor...likely out late next year. It's the one many are waiting for...it seems more effective AND causes less bleeding than warfarin. Continue to feel comfortable using warfarin for atrial fib...especially in longtime users with good INR control. Use a newer agent if INR control is poor...or monitoring isn't feasible. For now, lean towards dabigatran. To switch, wait until the INR is below 2 before starting dabigatran. Be careful about using dabigatran in the elderly due to bleeding concerns...especially if underweight or renal function is poor. Which of the following is TRUE about the new dosing limits for citalopram (Celexa, etc)? A.Doses should not exceed 40 mg/day for anyone. B.Doses should not exceed 20 mg/day for most patients over age 60. C.Higher doses increase the risk of QT prolongation and torsades. D.All of the above Answer • D.All of the above • ANTIDEPRESSANTS FDA now says citalopram doses should not exceed 40 mg/day for anyone...or 20 mg/day for most patients over age 60. Higher doses of citalopram (Celexa, etc) increase the risk of QT prolongation and torsades. Be careful about using citalopram in patients at risk due to underlying cardiac disease or low serum potassium or magnesium. Avoid citalopram or monitor ECG if citalopram is used in patients with heart failure...bradyarrhythmias...or on other meds that can prolong the QT interval. Don't exceed citalopram 20 mg in most patients over age 60...or those with liver impairment. Also avoid going over 20 mg when combined with CYP2C19 inhibitors...omeprazole, cimetidine, etc. If these lower doses aren't adequate, switch to another antidepressant. Sertraline, paroxetine, and fluoxetine seem less likely to cause QT prolongation. Don't exceed 20 mg/day of escitalopram (Lexapro). Usual doses aren't associated with significant QT prolongation...but the risk increases with higher doses. • ANTIDEPRESSANTS Reps are filling up sample closets, hoping prescribers will use Deplin to improve the efficacy of antidepressants. Deplin contains L-methylfolate...the active form of folic acid. The manufacturer can make medical claims for Deplin because it's marketed as a medical food. Medical foods are a commonly misunderstood category of products. They're not Rx drugs, not OTCs, not dietary supplements, and not homeopathics. Medical foods often have a package insert and say "Rx only" on their label...but they are NOT approved by FDA like traditional Rx drugs. There's a link between folate deficiency and depression...possibly because folates are needed to make serotonin, norepinephrine, and dopamine. Some preliminary evidence also suggests that adding folate can increase antidepressant efficacy. Deplin claims to be more effective than folic acid because it's already in the active form. But there's no proof that Deplin is more effective...and it costs more. Generic folic acid might be worth a try before going to other augmenting agents...antipsychotics, buspirone, thyroid, lithium, etc. Use at least 500 mcg/day of folic acid for augmentation. Keep doses under 800 mcg/day in the elderly due to concerns about cancer with higher folate doses in the elderly. Which of the following is TRUE about using azithromycin to prevent COPD exacerbations? A.Azithromycin 250 mg/day seems to reduce the risk of acute exacerbations. B.This dose does not increase bacterial resistance. C.Azithromycin can worsen eyesight. D.Thirty-day mortality is higher after a heart attack than a COPD exacerbation. Answer • A.Azithromycin 250 mg/day seems to reduce the risk of acute exacerbations. • RESPIRATORY / ALLERGY You'll hear debate about whether to use chronic azithromycin to PREVENT recurrent COPD exacerbations. Preventing acute COPD exacerbations is a BIG deal. Each exacerbation worsens lung function and quality of life...plus the 30-day mortality rate is higher after a severe COPD exacerbation than an MI. Adding azithromycin 250 mg/day to standard COPD therapy reduces the risk of acute exacerbations...but may worsen hearing. There will be one less exacerbation for every 3 COPD patients on oxygen or with prior exacerbations that take azithromycin for one year...but one in 20 patients will experience slight hearing loss. The theory is that this benefit is mostly due to azithromycin's antiinflammatory and immunomodulatory effects. But the big concern is bacterial resistance. Patients on chronic azithromycin are less likely to be colonized with respiratory pathogens...but if they are, it's more likely to be with macrolideresistant strains. Consider azithromycin for patients with severe COPD and frequent hospitalizations for acute exacerbations. Don't use a macrolide for an acute exacerbation if the patient is on chronic azithromycin. Instead, use a quinolone, cephalosporin, or amoxicillin/clavulanate. Which of the following is TRUE about managing hypothyroidism during pregnancy? A.Levothyroxine doses should be decreased by 50% during pregnancy. B.Levothyroxine doses should be increased by 25% to 30% as soon as pregnancy occurs. C.TSH should be monitored every 8 weeks. D.Women should wait one year after delivery to resume their pre-pregnancy dose. Answer • B.Levothyroxine doses should be increased by 25% to 30% as soon as pregnancy occurs. • New guidelines will call for tighter and more aggressive control of hypothyroidism before and during pregnancy. Levothyroxine needs rapidly increase when a woman becomes pregnant...leaving many women undertreated in early pregnancy. Hypothyroidism during pregnancy increases the risk of miscarriage, preterm birth, low birth weight, and cognitive deficits. Treatment should begin BEFORE a woman becomes pregnant. Titrate levothyroxine doses to achieve a TSH less than 2.5 mIU/L when a woman is planning to become pregnant. As soon as pregnancy is confirmed, increase the levothyroxine dose by 25% to 30%. One way to do this is to have the woman take an extra dose of levothyroxine two days per week as soon as she misses a period or has a positive home pregnancy test. Monitor TSH every 4 weeks during the first half of pregnancy...and then at least once between 26 and 32 weeks of gestation. Aim for a TSH of 2.5 mIU/L or less in the first trimester...and 3.0 mIU/L or less during the second and third trimesters. After delivery, have women resume their pre-pregnancy levothyroxine dose...and check TSH in 6 weeks. Tell women they may need extra levothyroxine for several months after delivery. Remind women not to take levothyroxine and prenatal vitamins at the same time due to decreased levothyroxine absorption. Recommend taking levothyroxine first thing in the morning on an empty stomach...and the prenatal vitamin at least 4 hours later with lunch or dinner. • You'll hear about two new opioid formulations, Oxecta and Lazanda. Oxecta (OX-ec-tah) is a new tamper-resistant, immediate-release oxycodone tab. It's formulated to discourage potential abusers from crushing, chewing, snorting, or injecting the opioid. The tab breaks into chunks instead of a powder if crushed...and turns into a gel if mixed with liquid. It also contains sodium laurel sulfate, which irritates the nose if it's snorted. But this won't stop people from taking large doses orally. Caution NOT to use Oxecta in feeding tubes...it can clog them. Lazanda (la-ZAHN-duh) is the first fentanyl nasal spray. It's for breakthrough pain in opioid-tolerant cancer patients...those on at least 60 mg/day of oral morphine or a 25 mcg/hr fentanyl patch for at least one week. Lazanda is absorbed a little faster than Actiq (fentanyl lozenge)...but has a similar onset for pain relief. Start all new Lazanda patients with ONE 100 mcg spray and titrate up for pain control. Emphasize proper storage and disposal. Advise patients to keep the Lazandabottle in the child-resistant container between uses...and to empty any unused solution into the carbon-lined pouch to bind the drug before disposal. You'll need to take an FDA-required training program and complete an enrollment form before you can prescribe Lazanda. You can link to these from ourPL Detail-Document...or go to LazandaREMS.com. • CARDIOLOGY There are MORE safety concerns with dronedarone (Multaq). This time it has to do with the TYPE of atrial fibrillation. Multaq improves CV outcomes in some patients with PAROXYSMAL or PERSISTENT atrial fib. These resolve spontaneously or with cardioversion. So researchers hoped that Multaq would also benefit patients with PERMANENT atrial fib. This type continues long-term despite attempts at cardioversion...or it's decided not to try cardioversion. But new evidence suggests that patients on Multaq for permanent atrial fib actually have a higher risk of death and cardiovascular events. Don't use Multaq or other antiarrhythmics for permanent atrial fib. None of them improve outcomes. Instead, use anticoagulation to help prevent strokes...and rate control with a betablocker, verapamil, diltiazem, or digoxin. Tell patients that it's often okay to stay in atrial fib...especially if they don't have symptoms. Don't be too quick to start Multaq for paroxysmal or persistent atrial fib either. It's not as effective as amiodarone...and may not be much safer. Multaq may lead to heart, liver, or kidney failure...and possibly increase INR in patients taking warfarin. Multaq doubles mortality in patients with severe heart failure. Lean toward amiodarone over dronedarone for patients with paroxysmal or persistent atrial fib who need rhythm control...especially if they have heart failure or severe left ventricular hypertrophy. Which of the following is TRUE about managing behavior problems in elderly patients who have dementia? A.Mood stabilizers (valproate, etc) are proven to be beneficial. B.Benzodiazepines are a good choice for agitation. C.Antipsychotics increase stroke risk and mortality. D.Psychotropic med regimens should be re-evaluated once a year. Answer • C.Antipsychotics increase stroke risk and mortality. • GERIATRICS It's challenging to manage elderly dementia patients who have behavior issues...agitation, aggression, delusions, etc. About 20% of elderly dementia patients experience delusions or hallucinations at some point...and many become agitated or aggressive. First rule out some common causes...pain, infection, constipation, incontinence, dehydration, or adverse med effects. Nonpharmacologic options can help manage agitation or aggression...and they're safer than meds. Suggest a calm environment...soothing rituals...reducing noise or sudden changes in surroundings or caregivers...etc. Reserve meds for behavior problems that affect safety. Start LOW...one-quarter to one-half the usual starting dose...and increase SLOWLY if needed. Antidepressants might be worth a try. Consider an SSRI (citalopram, etc) for agitation...or trazodone for agitation with insomnia. Mood stabilizers (valproate, etc) are controversial because of conflicting evidence on whether they're effective. If you try them, watch for side effects...nausea and sedation with valproic acid...and rash, dizziness, and sedation with lamotrigine. Antipsychotics are very controversial...they increase stroke risk and mortality. There's one more death for every 52 frail nursing home dementia patients treated with an antipsychotic for 10 weeks. Save them for patients with disabling delusions, hallucinations, or paranoia...and aggressive behavior that's harmful to themselves or others. But discuss the risks first. Try to avoid antipsychotics in patients with Lewy body dementia. These patients often have fluctuating cognition, parkinsonism, hallucinations, and severe sensitivity to antipsychotics. Use a very low dose of Seroquel (quetiapine) if necessary. Benzodiazepines should usually be avoided. Explain that they can actually INCREASE agitation by worsening cognition. Re-evaluate psychotropic meds at least quarterly...and attempt to wean patients off therapy as their condition permits. • DRUG INTERACTIONS Computers often give an "interaction alert" when potassium chloride tabs or caps are combined with an anticholinergic drug. These alerts are common for potassium chloride (Micro-K, etc) and ORAL anticholinergics...oxybutynin, amitriptyline, etc. But now alerts are popping up with INHALED anticholinergics...ipratropium (Atrovent, etc) and tiotropium (Spiriva). Plus they're showing up as a severe interaction...because anticholinergics are listed as a contraindication in the KCl labeling. That's why you may also be getting calls from pharmacies. But this is based more on theory than actual evidence. It's true that potassium chloride can cause GI irritation. The concern is that anticholinergics might increase this risk by slowing GI motility...but there's no convincing evidence this happens. Don't worry about this interaction alert with INHALED agents...they're not likely to affect GI motility. But, before you give the okay to use potassium with ORAL anticholinergics, think twice about whether the patient is at risk for GI problems due to older age...prior GI bleeding...gastroparesis...etc. Consider switching high-risk patients to a non-anticholinergic med...or switching to a potassium chloride liquid or powder. Tell patients to take KCl tabs or caps with a full glass of water and stay upright for at least 10 minutes...to avoid esophagitis. • CORTICOSTEROIDS We're getting questions about whether hyperglycemia can occur with non-oral corticosteroids...topical, inhaled, or local injections. Hyperglycemia is less likely when corticosteroids are given by these routes instead of systemically...but can still occur in susceptible patients. Topical steroids can cause hyperglycemia when used in chronic or high doses...especially for diffuse conditions such as psoriasis. Monitor blood glucose in patients using high-potency steroids...large steroid doses...or when treatment exceeds 6 months. Be especially vigilant if patients are at risk for diabetes. Inhaled steroids can increase the risk of hyperglycemia when used in high doses, such as fluticasone 1000 mcg/day or more. If hyperglycemia occurs, try to lower the steroid dose and add a bronchodilator or other agent if needed. Steroid injections into joints can cause hyperglycemia for about 2 to 5 days in patients with diabetes...and longer for long-acting steroid formulations. Epidural injections can increase blood glucose up to 2 weeks. But DON'T proactively adjust diabetes meds for most patients. Instead, advise those monitoring their blood glucose to call if it gets too high, such as a fasting glucose above 200 mg/dL for type 2...and above 150 mg/dL for type 1 diabetes. If you'd like to hear our team discuss how to treat these cases of Which of the following is TRUE about stopping antiplatelet drugs? A.Clopidogrel (Plavix) should be stopped 6 months after placement of a drug-eluting stent. B.Antiplatelet drugs usually don't need to be stopped for procedures with a low bleeding risk. C.Clopidogrel should be stopped at least 10 days before surgery. D.Patients should take 325 mg/day of aspirin with ticagrelor (Brilinta). Answer • B.Antiplatelet drugs usually don't need to be stopped for procedures with a low bleeding risk. • CARDIOLOGY Patients often don't realize the risk of stopping aspirin, clopidogrel, or other antiplatelet drugs too soon. Patients on aspirin for secondary prevention...or on aspirin plus clopidogrel for acute coronary syndrome or after a stent...sometimes stop these drugs on their own with dire consequences. For example, stopping aspirin in patients with a prior MI leads to 4 extra MIs per 1000 patients per year. Stopping clopidogrel within 30 days after a drug-eluting stent results in 25% of patients having a stent thrombosis instead of just 1%. Talk with patients to help them understand the importance of continuing with their antiplatelets. For stents, continue aspirin plus clopidogrel (Plavix), prasugrel (Effient), or ticagrelor (Brilinta) for AT LEAST one MONTH after a bare-metal stent...or at least one YEAR after a drug-eluting stent. Cardiologists often continue dual antiplatelets longer...especially for higher-risk patients. If you have questions about when to stop, discuss the pros and cons with the cardiologist. But...and this is very important...continue aspirin INDEFINITELY. Use just 81 mg/day of aspirin for most patients...especially those on ticagrelor. Higher aspirin doses make ticagrelor LESS effective. Keep in mind that antiplatelet drugs usually DON'T need to be stopped for procedures with a low bleeding risk...minor surgery, dental extraction, cataract surgery, endoscopy, etc. For stent patients, try to postpone procedures with a high bleeding risk until clopidogrel, prasugrel, or ticagrelor is stopped. If they can't wait, consider continuing the drug through the procedure, if possible...or stopping the drug for a brief time. Continue aspirin for all but the riskiest surgery. If the drug must be stopped, stop clopidogrel, ticagrelor, or aspirin 5 days prior...and prasugrel 7 days before surgery Which of the following is TRUE about combining simvastatin (Zocor, etc) and amlodipine (Norvasc, etc)? A.The combo can increase the risk of myopathy. B.Patients on amlodipine should not take more than simvastatin 20 mg/day. C.Amlodipine also significantly increases levels of atorvastatin (Lipitor). D.Both A and B Answer • D.Both A and B • STATINS New alerts will raise new questions about the interaction between simvastatin (Zocor, etc) and amlodipine (Norvasc, etc). Some prescribers are surprised...because amlodipine is only a weak inhibitor of simvastatin metabolism by CYP3A4 enzymes. But the combo IS associated with a higher risk of myopathy. There's possibly another mechanism at work...such as inhibiting transport proteins that carry simvastatin into liver cells for metabolism. Follow the new FDA guidelines and don't prescribe more than simvastatin 20 mg/day in patients taking amlodipine. Switch patients who need simvastatin 40 mg to pravastatin 80 mg...atorvastatin (Lipitor) 20 mg...or rosuvastatin (Crestor) 5 mg. Amlodipine isn't likely to significantly increase levels of these statins Which of the following is TRUE about using spinosad (Natroba) for head lice? A.It can be used for infants. B.A second treatment is always required. C.It seems to work better than OTC permethrin (Nix, etc). D.It's not well tolerated. Answer • C.It seems to work better than OTC permethrin (Nix, etc). • HEAD LICE Reps will promote Natroba (nah-TRO-buh), a new Rx topical suspension for head lice. They'll point out that Natroba (spinosad) seems to work better than OTC permethrin (Nix, etc)...and it's well tolerated. It's true that Natroba kills lice AND nits...and it's not absorbed. But this comes at a cost. Natroba costs $220...compared to about $10 to $20 for Nix, $160 for malathion, and $160 for Ulesfia, depending on hair length. Continue to use OTC permethrin or pyrethrins first-line. They're inexpensive and usually effective...and permethrin can be used in children as young as 2 months. If these don't work or resistance is a problem in your area, prescribe Natroba, malathion (Ovide, etc), or Ulesfia (benzyl alcohol). Keep in mind that Ulesfia is for ages 6 MONTHS and older...Natroba is for 4 YEARS and up...and malathion is for 6 YEARS and up. Tell parents that only one treatment is usually needed with Natroba or malathion. Recommend retreatment in 7 days with Ulesfia...or 7 to 9 days with permethrin or pyrethrins. If these options fail, consider Rx oral ivermectin (Stromectol) if the child weighs at least 15 kg. It kills lice within 24 hours • You'll start hearing lots more about the comparisons between warfarin, dabigatran (Pradaxa), and rivaroxaban (Xarelto). Now that both Pradaxa and Xarelto will be marketed for atrial fib, people will ask if these are better than warfarin. Keep these drugs' pros and cons in perspective. Efficacy. Pradaxa may have a slight advantage. Pradaxa 150 mg BID prevents about 5 more strokes per 1000 patients/year than warfarin. Xarelto 20 mg once a day works about as well as warfarin...but this is in higher-risk patients than those in the Pradaxa trial. Side effects. Pradaxa, Xarelto, and warfarin have about the same overall risk of bleeding. But Pradaxa and Xarelto seem to cause FEWER intracranial bleeds...and MORE GI bleeds...than warfarin. Dyspepsia is a problem with Pradaxa. Cost. Pradaxa and Xarelto each cost about $260/month. Warfarin costs about $80/month even when you add in INR monitoring once a month. Continue to use warfarin for many atrial fib patients. Go to one of the newer anticoagulants if INR control is poor...or warfarin interactions are a concern...or monitoring isn't feasible. For now, lean towards Pradaxa before Xarelto. Pradaxa is more effective than warfarin in some patients. Use Xarelto for patients who can't tolerate Pradaxa due to dyspepsia...or have trouble with Pradaxa's BID dosing. Monitor renal function with the new anticoagulants...and lower the dose if needed. Use Pradaxa 75 mg BID for a CrCl between 15 and 30 mL/min. UseXarelto 15 mg/day for a CrCl between 15 and 50 mL/min. Don't ROUTINELY use aspirin for atrial fib. New evidence suggests that it's not much better than placebo...but it still increases bleeding. Consider aspirin for younger patients without any additional stroke risk factors...or patients who won't take an anticoagulant. If you want to be the smartest person in your area about the new anticoags for atrial fib, go to our PL Detail-Document...and listen to our experts talking on PL Voices. Also see our PL Chart, Comparison of Oral Antithrombotics, for their indications, dosing, interactions, etc. • Many of the antipsychotics can prolong the QT interval...but not all of them are associated with torsades or sudden death. Torsades with Seroquel is very rare...and usually linked to an overdose. But the problem is that you can't predict who will get it. Patients who develop torsades usually have multiple risks...a long QT interval,heart disease, older age, female gender, low serum potassium or magnesium, or slow heart rate. Watch for patients on multiple meds that can prolong the QT interval...and meds that interact to boost levels of these QT drugs. For example, don't combine Seroquel (quetiapine) with other QT prolongers...macrolides (clarithromycin, etc), quinolones (moxifloxacin, etc), tricyclics, Geodon (ziprasidone), methadone, or amiodarone. And proceed carefully if patients are on meds that can lower potassium or magnesium, such as diuretics or laxatives...or meds that can slow heart rate, such as beta-blockers. In risky patients, consider using an alternate antipsychotic that's not linked to torsades, such as Zyprexa (olanzapine)...Abilify (aripiprazole)...Latuda(lurasidone)...or Saphri s (asenapine). Avoid haloperidol, pimozide, thioridazine, or chlorpromazine in high-risk patients. These are an even bigger torsades risk than Seroquel • GERIATRICS You'll hear about using "START" and "STOPP" instead of Beers to evaluate appropriate med use in the elderly. The Beers list is often used to identify drugs to avoid in the elderly. The START and STOPP criteria take it a step further. They provide more context by listing situations where specific drugs should be USED...and when specific drugs should be AVOIDED. START (Screening Tool to Alert doctors to Right Treatment) lists 22 situations where meds are indicated. It focuses on common quality- of-care indicators...warfarin for atrial fibrillation, ACE inhibitors for heart failure or post-MI, metformin for diabetes, etc. STOPP (Screening Tool of Older Persons' potentially inappropriate Prescriptions) lists 65 risky drug interactions with diseases or other drugs...plus therapeutic duplications. For example, it advises not to use benzodiazepines in a patient who has fallen in the past 3 months...or NSAIDs without a PPI or H2-blocker in a patient with a history of ulcers or GI bleeding. The Beers list is controversial because prescribers are sometimes dinged for using a Beers drug in an elderly patient...even when it IS appropriate...such as amitriptyline for neuropathic pain...amiodarone for atrial fibrillation...or naproxen forarthritis. STOPP includes some of the same drugs, but provides more guidance. For example, it suggests avoiding tricyclics for patients with glaucoma, cardiac conduction problems, dementia, constipation, or benign prostatic hyperplasia...but NOT neuropathic pain. Don't fall into the trap of using these tools as the final word. None of them are appropriate for blanket prescribing protocols or blanket formulary decisions. Use them to help identify POTENTIAL problems...and then look at the whole picture. Consider the patient's medication history, chronic diseases, functional status, and prognosis • INFECTIOUS DISEASES Experts are concerned about a new strain of ceftriaxone-resistant gonorrhea. Once gonorrhea is resistant to ceftriaxone, we will have run out of simple andreliable antibiotic options. The ceftriaxone-resistant strain is already in Japan. U.S. strains are becoming less susceptible to cephalosporins and azithromycin...but they still work for now. Use dual antibiotic therapy for gonorrhea to help reduce resistance...not just because it also treats chlamydia. Use ceftriaxone 250 mg IM...PLUS azithromycin 1 g PO instead of doxycycline. Strains that are more resistant to cephalosporins are usually resistant to doxycycline. Don't be tempted to use higher ceftriaxone doses to prevent or overcome resistance...there's no evidence that this is helpful. Give cefixime instead of ceftriaxone if an oral option is absolutely necessary...but watch for treatment failures. If cefixime doesn't work, use ceftriaxone 250 mg plus azithromycin 2 g...and retest in one week to make sure it works. For patients with severe penicillin allergies, use a single 2 g dose of azithromycin...and retest in a week. • ACETAMINOPHEN You'll see changes to OTC Tylenol and other acetaminophen products to increase safety...starting this fall. Tylenol products for adults will have a lower maximum dose. Extra-strength Tylenol labels will say not to take more than six 500 mg tabs or 3000 mg/day...instead of 8 tabs or 4000 mg/day. Regular-strength Tylenol products will recommend no more than ten 325 mg tabs or 3250 mg/day...starting next year. Extended-release Tylenol dosing won't change. It will still recommend up to six 650 mg caps or 3900 mg/day. This is part of the trend to limit acetaminophen doses to reduce the risk of acute liver failure. Advise patients not to exceed 3000 to 4000 mg/day of acetaminophen...from all sources. CONCENTRATED infant drops (80 mg/0.8 mL) will be phased out. The new infant drops will be the same concentration as the children's liquid (160 mg/5 mL). Always give acetaminophen doses in mgs to avoid confusion. Some of the older infant drops will remain on store shelves until next year...and in home medicine cabinets even longer. Important: Keep in mind that telling a parent to give a half teaspoonful of Tylenoldoes NOT assure that they'll use the 160 mg/5 mL product. Caution them that if they use the concentrated drops they may have at home, their baby could get triple the proper dose. Dosing for kids as young as 6 months will appear on children's products...and will be based on age AND weight. For ages 4 to 23 months, recommend 10 to 15 mg/kg every 4 to 6 hours...up to 5 doses per day. • ANTICOAGULANTS The new oral anticoagulants are bringing up questions about how to reverse bleeding due to Pradaxa or Xarelto. There are currently no antidotes for Pradaxa (dabigatran) or Xarelto(rivaroxaban)...like vitamin K for warfarin. But there are things you can do. Stopping the anticoagulant and waiting 1 to 2 days in patients with healthy renal function is enough prior to most surgeries. But this may not be fast enough for bleeding or emergency surgery. So far there are no specific guidelines...so for now, follow these common-sense best practices to control bleeding. Start with activated charcoal to absorb any residual drug if a dose was taken within 2 hours. Maintain adequate diuresis...especially for Pradaxa since it's primarily renally excreted. Consider hemodialysis if feasible for Pradaxa...about 60% of the drug is removed in 2 to 3 hours. Xarelto is NOT dialyzable. Give red blood cells and fresh frozen plasma as appropriate. Consider activated prothrombin complex concentrates (aPCC) or recombinant factor VIIa as a last resort for life-threatening bleeding. There's not much evidence to support their use...and they increase thrombosis risk. Plus, factor VIIa costs $5000 to $25,000 per treatment. Keep in mind that clotting factors (fresh frozen plasma, aPCC, etc) aren't likely to be wholly effective. That's because these newer anticoagulants INHIBIT clotting factors...not DEPLETE them. Be especially careful using Pradaxa or Xarelto in elderly patients with poor renal function...due to the higher risk of bleeding. Which of the following is TRUE about treating migraine headaches in children? A.Migraines are rare in children. B.Ibuprofen is often effective if given in adequate doses. C.Sumatriptan tablets work better than the nasal spray for kids. D.Almotriptan (Axert) is approved for ages 6 and up. Answer • B.Ibuprofen is often effective if given in adequate doses. • MIGRAINES We're getting questions about whether it's okay to use triptans (sumatriptan, etc) for migraines in CHILDREN. Yes. Migraines are common in kids...especially teens. Acetaminophen sometimes helps...ibuprofen is usually better. Use ibuprofen 7.5 to 10 mg/kg/dose...up to 800 mg/dose in older teens. When OTC analgesics aren't enough, use a triptan...except in the rare case that a child is at risk for heart disease. For adolescents, start with almotriptan (Axert) 6.25 mg...rizatriptan (Maxalt) 5 mg...sumatriptan (Imitrex) nasal 5 mg...or zolmitriptan (Zomig) nasal 5 mg. These have the most evidence in adolescents...and almotriptan is actually approved for ages 12 and up. In kids age 6 to 11, lean towards Maxalt 5 mg or Imitrex nasal 5 mg...because these have the most evidence in younger kids. Sumatriptan TABLETS are less expensive than the nasal spray...but they may not work as well, possibly due to slower absorption. The important point is to try another triptan if one doesn't work. Explain that some patients respond to one triptan but not another. Advise patients to take the triptan at the first sign of a headache...and repeat in two hours if needed. Advise parents to contact their child's school for the policy on med administration...these vary between schools. To help prevent migraines, recommend avoiding common culprits...not enough sleep, skipped meals, too much caffeine or stress, etc. Consider PROPHYLAXIS if headaches are frequent or severe enough to interfere with daily activities. For most kids, start with amitriptyline, nortriptyline, cyproheptadine, divalproex (Depakote, etc), topiramate (Topamax, etc), or propranolol. Which of the following is TRUE about treating more advanced Parkinson's disease? A.Decreasing the levodopa dosing interval may help reduce off time. B.Switching to sustained-release carbidopa/levodopa will reduce off time. C.Increasing the levodopa dose will help dyskinesias. D.Selegiline is proven to work better than rasagiline (Azilect) for reducing off time. Answer • A.Decreasing the levodopa dosing interval may help reduce off time • You'll see more approaches to treating Parkinson's disease AFTER the "honeymoon" is over. It's relatively easy to control symptoms in the early years with low doses of carbidopa/levodopa...or a dopamine agonist, such as pramipexole (Mirapex, etc) or ropinirole (Requip, etc). But when drug efficacy decreases, consider these approaches to control movement problems in more advanced Parkinson's. "Wearing off" often occurs after about 5 years of levodopa...where its effects start to "wear off" sooner after the last dose. To reduce "off" time, decrease the levodopa dosing INTERVAL by 30 to 60 minutes. Don't count on switching to sustained-release levodopa (Sinemet CR, etc) to reduce off time...it doesn't help. Next try adding a dopamine agonist. This extends "on" time and prevents "deep" offs. Or add a COMT inhibitor or MAO-B inhibitor. For a COMT inhibitor, use Comtan (entacapone) or the combo product Stalevo(carbidopa/levodopa/entacapone). Explain that the combo usually costs less than the separate tabs. Try to avoid Tasmar (tolcapone)...it's linked to liver failure. For an MAO-B inhibitor, use either selegiline or rasagiline (Azilect). Rasagiline has better evidence for reducing off time...but selegiline costs less. Dyskinesias occur when patients get too much dopamine. Decreasing the levodopa dose may help...but may mean more Parkinson's symptoms, such as tremor, stiffness, and rigidity. Instead, try decreasing the levodopa dose...and adding a dopamine agonist. Dopamine agonists cause fewer dyskinesias than levodopa...and also help decrease Parkinson's symptoms. Or add amantadine...but watch for CNS side effects. Keep in mind that COMT inhibitors can contribute to dyskinesias by boosting levodopa's effects. Reduce the dose or stop the COMT inhibitor if necessary. • DIABETES Patients are asking about a new "bloodless" glucose meter. This comes from misleading TV ads for diabetes supplies. These ads are actually referring to "alternate site" meters. It's true that patients don't need to stick their fingers...but they do need to get blood from their arm or another site. Tell patients that there aren't any bloodless glucose meters on the market...but many of the newer ones need only a tiny drop of blood. Explain that alternate site testing isn't reliable when blood glucose is changing...after eating, after exercise, or when they're hypoglycemic. Recommend fingertip testing at these times. GlucoWatch WAS a bloodless meter...but it's no longer available. It measured glucose through the skin...but it was plagued by problems. Tell patients that researchers are trying to invent a bloodless meter to measure glucose in tears, breath, or through the skin. • EDEMA Questions often come up about how to handle peripheral edema due to dihydropyridine calcium channel blockers (amlodipine, etc). These often cause edema...especially at higher doses. It's not due to fluid overload, so diuretics usually don't help. Try lowering the dose. Most of the antihypertensive effect is at lower doses, so cutting the dose in half doesn't also cut the BP benefit in half. Or try ADDING an ACE inhibitor or ARB to counteract the edema and augment the antihypertensive effect. Switch to a different antihypertensive, if needed. Verapamil or diltiazem is less likely to cause edema than a dihydropyridine. Watch for drugs that can increase dihydropyridine levels and, therefore, the risk of edema. For example, amlodipine levels can be increased by strong 3A4 inhibitors (clarithromycin, etc). Multi-axial system • The DSM-IV organizes each psychiatric diagnosis into five dimensions (axes) relating to different aspects of disorder or disability: • Axis I: Clinical disorders, including major mental disorders, and learning disorders, Substance Use Disorders • Axis II: Personality disorders and intellectual disabilities (although developmental disorders, such as Autism, were coded on Axis II in the previous edition, these disorders are now included on Axis I) • Axis III: Acute medical conditions and physical disorders • Axis IV: Psychosocial and environmental factors contributing to the disorder • Axis V: Global Assessment of Functioning or Children's Global Assessment Scale for children and teens under the age of 18 The condition of a patient with depressed mood on most days for ≥2 yr plus ≥2 of the following: changes in appetite, sleep, or energy, lowered self esteem, poor concentration, or hopelessness should be diagnosed as: A) Major depression B) Dysthymic disorder C) Bipolar disorder D) Cyclothymic disorder Answer • B) Dysthymic disorder Major depression • 2 wk of depressed mood plus 4 SIG E CAPS (mnemonic for • increased or decreased Sleep • Decreased Interest • Guilt • decreased Energy • Decreased Concentration • increased or decreased Appetite • Psychomotor agitation or retardation • thoughts of or attempts at Suicide) • and without history of mania or hypomania; • dysthymic disorder—depressed mood on most days for 2 yr plus 2 of changes in appetite, sleep, energy, lowered self-esteem, poor concentration, or hopelessness The definition of mania includes which of the following? More than 1 wk of persistently elevated, expansive, or irritable mood Increased activity and decreased need for sleep Grandiosity Disorganized speech Indiscretion A) 2,3,4,5 B) 1,2,4,5 C) 1,2,3,5 D) 1,3,4,5 Answer • C) 1,2,3,5 Bipolar disorders (BPDs) • • • • • • • • • • • • • • • • BPD I requires 1 episode of mania BPD II requires 1 episode of hypomania Cyclothymic disorder —rapid fluctuation between depression and hypomania mania—1 wk of persistently elevated, expansive, or irritable mood with 3 (or 4 if mood irritable only) of DIGFAST (mnemonic for Distractibility Indiscretion Grandiosity Flight of ideas increased Activity decreased need for Sleep increased Talkativeness or pressured speech) and must cause marked impairment in occupational or social functioning or necessitate hospitalization hypomania—4 days of elevated, expansive, or irritable mood plus 3 (or 4 if mood irritable only) of DIGFAST marked impairment in occupational or social functioning not required cyclothymic disorder —2 yr of numerous episodes of depressive symptoms and hypomanic symptoms without full-blown major depressive or manic episodes mood disorder due to general medical condition — medical illness physiologically causes depression, eg, depression due to hypothyroidism or pancreatic cancer; substanceinduced mood disorders — eg, mania due to steroids or methamphetamine • • • • • • • • • • • • Schizophrenia 2 of delusions (fixed false believes), hallucinations, disorganized speech, disorganized or catatonic behavior, and negative symptoms plus 6 mo of continuous disturbance with 1 mo of active symptoms and significant impairment in self-care and occupational and social functioning brief psychotic disorder — psychotic symptoms lasting 0 to 30 days schizophreniform disorder —symptoms lasting 1 to 6 mo Subtypes: Paranoid disorganized (disorganized speech or behavior) Catatonic undifferentiated (mainly positive symptoms), or residual (negative symptoms predominate) catatonia— treat first-line with trial of intravenous (IV) lorazepam (2 mg); if benzodiazepines not effective, switch quickly to electroconvulsive therapy (ECT) differentiated from neuroleptic malignant syndrome (NMS) by FEVER mnemonic for Febrile, Elevated creatine phosphokinase (CPK), Vital sign instability, Elevated white blood count, and Rigidity (catatonic patients have only rigidity) Schizoaffective disorder • both psychotic and mood symptoms that may occur separately • 2 types, bipolar or depressive • symptoms present regardless of mood (unlike major depression or bipolar disorder with psychotic features, in which psychosis occurs only during mood disturbance) • Delusional disorders: • 1 mo of nonbizarre delusion with no impairment of function or odd behavior; subtypes—erotomanic, grandiose, jealous, persecutory, somatic, mixed, and unspecified • do not respond well to medication or psychotherapy A panic attack is defined as a discrete period of fear peaking in: A) 10 min B) 30 min C) 60 min D) 90 min Answer • A) 10 min Panic disorder • recurrent panic attacks with 1 mo of concern about having another attack or consequences of attack and significant change in behavior • panic attack—discrete period of fear peaking in 10 min with • 4 of palpitations, diaphoresis, trembling, dyspnea, sense of choking, chest pain, nausea, dizziness, derealization or depersonalization, fear of losing control or dying, paresthesias, chills, and hot flushes • classified as with or without agoraphobia • Generalized anxiety disorder (GAD): • 6 mo of excessive anxiety on most days (not due to features of another axis 1 disorder) • 3 of WORRY WART • (for Wound up or irritable • Worn out or easily fatigued • Absent minded or poor concentration, • Restless • Tense, or Sleepless) Which of the following statements about obsessive compulsive disorder is correct? A) The obsessions and compulsions are recognized by patients as excessive and egodystonic B) The obsessions and compulsions arise from the patient's desire for rules and orderliness and are ego-syntonic C) Patients believe that the obsessive thoughts are inserted into their minds by others D) None of the above Answer • A) The obsessions and compulsions are recognized by patients as excessive and ego-dystonic Obsessive compulsive disorder (OCD) • obsessions, compulsions, or both, recognized by patient as excessive and ego-dystonic, and that cause marked distress and interfere with function • not restricted to another axis 1 diagnosis, eg, trichotillomania (compulsion of pulling hair), hypochondriasis (obsession about serious illness), or paraphilia (compulsions around sexual acting out) • obsessions —recurrent, persistent, intrusive, inappropriate thoughts that cause distress • Patient recognizes thoughts as products of own mind • compulsions— repetitive behaviors that patient must perform in response to obsession or rigid rule Posttraumatic stress disorder (PTSD) • • • • • • • • • • • • • • patient experienced, witnessed, or confronted with event that involved actual or threatened death or serious injury response involves fear, helplessness, or horror; >1 mo of symptoms in 3 areas (re-experience, hyperarousal, and avoidance) re-experience—1 symptom required Recurrent recollections, nightmares, flashbacks (waking re-experience), or intense distress after exposure to cues hyperarousal—2 symptoms required insomnia, irritability, poor concentration, hypervigilance, or exaggerated startle response avoidance—3 symptoms required; avoidance of thoughts, feelings, conversations, people, or places or activities associated with event difficulty remembering aspects of event loss of interest in usual activities detachment or estrangement restricted affect sense of foreshortened future if symptoms present for <1 mo, diagnosis acute stress disorder The diagnosis of somatization disorder requires 4 sexual symptoms, 2 gastrointestinal symptoms, 1 pain symptom, and 1 pseudoneurologic symptom. A) True B) False Answer • B) False Somatoform disorders • • • • • • • • • • somatization disorder—multiple physical complaints beginning before 30 yr of age with treatment sought and impaired functioning diagnosis requires 4 pain symptoms, 2 gastrointestinal symptoms, 1 sexual symptom, and 1 pseudoneurologic symptom conversion disorder—1 symptom affecting motor or sensory function; hypochondriasis—preoccupation with belief in presence of serious illness belief persists 6 mo after evaluation and reassurance body dysmorphic disorder—preoccupation with imagined or minor defect in appearance factitious disorder— intentional feigning of signs and symptoms of illness motivated by desire to have illness and receive care or sympathy more common in women Munchausen variant more common in men malingering—intentional feigning of signs and symptoms of illness motivated by desire to avoid something (eg, work, military service) or obtain medications, shelter, or financial compensation Pain disorder—unexplained pain • • • • • • • • • Eating disorders anorexia nervosa—refusal to maintain normal body weight intense fear of gaining weight disturbed perception of body weight or shape often presents with amenorrhea Bulimia nervosa—recurrent episodes of binge eating and purging 2 times per week for 3 mo patients usually depressed, but do not treat with bupropion (Wellbutrin, Aplenzin, or Zyban) because of risk for seizures Paraphilias: 6 mo of recurrent, intense sexual fantasies, urges, or behaviors focused on specific act or subject include exhibitionism, fetishism, frotteurism, pedophilia, sexual masochism or sadism, transvestic fetishism, voyeurism, and not otherwise specifie Choose the correct statement(s) about patients with borderline personality disorder.They may show suicidal behavior They typically have a history of stable but abusive relationships They have an intense fear of abandonment Dialectical behavioral therapy is the treatment of choice They often show emotional lability A) 1,2,3,4 B) 2,3,4,5 C) 1,3,4,5 D) 1,2,4,5 Answer • C) 1,3,4,5 Personality disorders • • • • • • • • • • • • • • • • • • pervasive behavior not time limited How patient’s world outlook framed Cluster A: paranoid (4 symptoms required) schizoid (lack of interest in human relationships) schizotypal (unusual beliefs with eccentric behavior) Cluster B: borderline—5 symptoms required, typified by history of unstable relationships emotional lability, or suicidal or parasuicidal behavior intense fear of abandonment (often associated with difficult childhood) treat with dialectical behavioral therapy (DBT) histrionic—patient shows superficial emotional lability and desire for attention narcissistic—patient believes in own specialness, needs attention, arrogant, entitled, exploits others, and needs power antisocial—patient lacks concern for anyone’s safety, rules, or social constructs conduct disorder in child Cluster C: avoidant—patient desires relationship but cannot participate in one because of fear of rejection dependent—unable to live without someone’s care obsessive compulsive— patient desires rules and orderliness ego-syntonic rather than egodystonic Choose the correct statement(s) about differences among selective serotonin reuptake inhibitor (SSRI) antidepressants. A) Fluoxetine has the longest half-life B) Paroxetine is the most sedating C) Fluvoxamine has the most significant interactions with cytochrome P450 D) A, B, and C Answer • D) A, B, and C Antidepresents • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • Selective serotonin reuptake inhibitor (SSRI) antidepressants: fluoxetine (Prozac, Sarafem, Selfemra), citalopram (Celexa), escitalopram (Lexapro), paroxetine (Paxil, Pexeva), sertraline (Zoloft), and fluvoxamine (Luvox) 3 to 6 wk needed for response relatively safe in overdose side effects common but not severe and diminish with time Sexual dysfunction most long lasting Differences among SSRIs: half-life— longest for fluoxetine (84 hr); shortest for fluvoxamine level of activation — sertraline and fluoxetine most activating citalopram and escitalopram intermediate paroxetine most sedating Interactions with cytochrome P450—fluvoxamine has most; citalopram and escitalopram have none Duration of treatment: administer antidepressants 6 mo (ideally1 yr) after resolution of symptoms to prevent relapse Serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressants: venlafaxine (Effexor) has greater affinity for serotonin, and duloxetine (Cymbalta) inhibits both equally Tricyclic antidepressants (TCAs): imipramine first available antidepressant; highly efficacious but side effects (anticholinergic effects and orthostatic hypotension) limit patient adherence easily fatal in overdose desipramine and nortriptyline have least anticholinergic potential doxepin, protriptyline, and amitriptyline have most nortriptyline has lowest risk for orthostasis clomipramine most serotonergic (often used in OCD) doxepin most sedative on overdose, TCAs block fast sodium channel, causing cardiac toxicity and fatal arrhythmias (treat with IV sodium bicarbonate) Monoamine oxidase inhibitor (MAOI) antidepressants: more efficacious but more side effects phenelzine (Nardil) and tranylcypromine (Parnate) irreversibly inhibit MAOA and MAOB increasing synaptic monoamines; risks include hypertensive crisis and serotonin syndrome patient must adhere to tyramine-free diet drug interactions —with serotonergic (serotonin syndrome) or sympathomimetic drugs (hypertensive crisis) 2-wk washout period required before reintroducing any serotonergic drug antibiotic linezolid weakly inhibits MAOA and can cause hypertensive crisis and serotonin syndrome Other antidepressants: mirtazapine (Remeron)— antagonist of inhibitory 2 receptors; increases release of serotonin and norepinephrine; strong antihistamine adverse effects include somnolence and weight gain bupropion—increases dopamine and norepinephrine rarely associated with sexual dysfunction; increases risk for seizures (especially in patients with eating disorders) adjunct treatment for sexual dysfunction induced by SSRIs Anxiolytics: SSRIs and SNRIs used first-line Some antiepileptic and neuroleptic medications are commonly used as mood stabilizers for patients with bipolar disorder. A) True B) False Answer • A) True • • • • • • • • • Mood stabilizers: for patients with BPD, do not start unopposed antidepressant (may push patient into mania) start mood stabilizer first antiepileptics commonly used include valproate, carbamazepine, and oxcarbazepine lithium — start at 300 mg twice daily, monitor, and titrate to therapeutic level (0.7 to 1.2 mEq/L) adverse effects—renal injury with diabetes insipidus, thyroid injury, hyperparathyroidism, tremor, dry mouth, nausea, and benign leukocytosis toxicity characterized by confusion, nausea and vomiting, tremor, ataxic gait, blurred vision, orthostasis, hyperreflexia, and fasciculations treat with aggressive IV fluids if blood level <2.5 mEq/L or hemodialysis if blood level >2.5 mEq/L; monitor levels closely, even after dialysis; drug interactions— nonsteroidal antiinflammatory drugs (NSAIDs), thiazide diuretics, and angiotensin-converting enzyme (ACE) inhibitors activated charcoal does not affect lithium overdose but useful if patient A patient who shows elevated creatine phosphokinase, vital sign instability, elevated white blood count, and rigidity is likely to have which of the following disorders. A) Catatonia B) Serotonin syndrome C) Neuroleptic malignant syndrome D) None of the above Answer • C) Neuroleptic malignant syndrome Neuroleptics • • • • • • • • • • • • • • • • • • typical (eg, haloperidol, chlorpromazine, fluphenazine) atypical (eg, risperidone, quetiapine, olanzapine, ziprasidone) block dopamine; atypicals less specific and act on serotonin, acetylcholine, and histamine as well as dopamine; first-line treatment for psychotic disorders but indicated in others; some atypicals approved as mood stabilizers in BPD (ie, ziprasidone, olanzapine, quetiapine, aripiprazole, and risperidone) Intramuscular injection (ensures compliance): long-acting— decanoate preparations of haloperidol and fluphenazine, risperidone (Risperdal Consta), and paliperidone (Invega Sustenna); short-acting — haloperidol, chlorpromazine, olanzapine (Zyprexa), ziprasidone (Geodon) Intravenous:— none approved for IV injection, but IV haloperidol standard of care for delirium Adverse effects: typicals — extrapyramidal (ie, dystonia and parkinsonism), akathisia, tardive dyskinesia Prolongation of QTc interval, and NMS atypicals — weight gain, metabolic syndrome, and diabetes mellitus, prolongation of QTc interval, and NMS clozapine—most efficacious but increases risk for life-threatening agranulocytosis requires federal permission for prescribing; must document failure of other treatments and use federal national registry regular monitoring of white blood cell count and absolute neutrophil count required NMS—differentiated from serotonin syndrome by presence ofrigidity in NMS and clonus in serotonin syndrome discontinue agent and provide supportive car Electroconvulsive therapy is indicated for which of the following conditions? A) Major depression B) Bipolar disorder C) Catatonia D) A, B, and C Answer • D) A, B, and C Electroconvulsive therapy • indicated for major depression (especially if patient cachectic or psychotic), BPD, acute exacerbation of schizophrenia, or catatonia • paralyzes patient and induces seizure lasting 25 sec • very efficacious with no absolute contraindications; relative contraindications include coronary artery disease, hypertension, arrhythmias, space-occupying intracranial lesions, cerebral aneurysms, history of recent stroke, or pregnancy • adverse effects—postictal confusion (typically clears in days to weeks) • anterograde and retrograde amnesia (lasting 6 mo) Psychodynamic psychotherapy • psychoanalysis to achieve understanding of previously unconscious conflicts • Cognitive behavioral therapy: assumes thoughts and feelings influence each other; very effective for depression, anxiety, and • treatment of choice for OCD • Dialectical behavioral therapy: specifically intended for borderline personality disorder • focuses on mindfulness • regulation of emotion, • and radical acceptance • Important stages: behavior change—precontemplation, contemplation, preparation, action, maintenance, and relapse; grief— • denial, anger, bargaining, depression (not in linear progression), and acceptanc For most uncomplicated abscesses or boils, antibiotics (ABX) are recommended as the first line of treatment. (A) True (B) False Answer • (B) False • Case 1: 32 yr-old man with 3 days of enlarging painful lesion on left thigh attributed to spider bite • afebrile; remainder of vital signs (VS) normal • area of induration with surrounding erythema and some purulent drainage noted • Management of skin abscesses: for most uncomplicated abscesses or boils, incision and drainage (I&D) alone likely adequate • controversial whether antibiotics (ABX) provide additional benefit (multiple observational studies plus 3 recent randomized controlled trials [RCTs] of uncomplicated skin abscesses report high clinical cure rates with and without ABX • however, data from 2 RCTs suggest ABX may also help prevent recurrent infections) • ABX therapy recommended for abscesses associated with — severe or extensive disease (rapidly progressive or with associated septic phlebitis) • signs and symptoms of systemic illness; associated comorbidities or immmunosuppression; extremes of age; area difficult-to-drain; failure of previous I&D • Microbiology of purulent skin and soft tissue infections (SSTIs): in study of patients presenting to 11 emergency departments (EDs) throughout United States, methicillinresistant Staphylococcus aureus (MRSA) accounted for 59% of SSTIs, while Beta-hemolytic Streptococcus (BHS) accounted for only 3% • Treatment of purulent cellulitis: empiric therapy for community acquired (CA)-MRSA recommended • therapy for BHS unlikely to be necessary • recommended duration of therapy 5 to 10 days • Empiric oral ABX therapy for uncomplicated purulent SSTIs: options trimethoprim-sulfamethoxazole (TMPSMX), doxycycline or minocycline, clindamycin, and linezolid • rifampin not recommended for routine treatment of SSTI Case 2 • • • • • • • • • • • 28-yr-old woman with erythema of left foot for last 48 hr no purulent drainage, exudates, or abscess afebrile; other VS also normal Treatment of nonpurulent cellulitis empiric therapy for BHS recommended therapy for CA-MRSA recommended if patient fails to respond to Beta-lactam ABX, and should be considered in patients with systemic toxicity; options for empiric treatment — cephalexin (eg, Keflex, Panixine, Biocef), dicloxacillin, clindamycin, and linezolid if no response to cephalexin or dicloxacillin, add ABX effective against MRSA Treatment of complicated SSTIs: mainstay of therapy surgical debridement; empiric therapy for MRSA recommended pending data from cultures options for ABX therapy—vancomycin, linezolid, daptomycin, telavancin, ceftaroline, and clindamycin tigecycline associated with increased risk for mortality (not recommended; consider alternative agent); recommended duration of therapy 7 to 14 day The recommended duration of ABX therapy for purulent cellulitis is _______ days. (A) 5 to 10 (C) 14 to 21 (B) 7 to 14 (D) 3 Answer • (A) 5 to 10 Which of the following options for ABX treatment of complicated skin and soft tissue infections (SSTIs) is associated with an increased risk for mortality? (A) Vancomycin (C) Linezolid (B) Daptomycin (D) Tigecycline Answer • (D) Tigecycline Current guidelines suggest firstline treatment of recurrent SSTIs is: (A) Focus on personal hygiene and wound care (B) Decolonization with topical ABX (C) Decolonization with oral ABX (D) B or C Answer • (A) Focus on personal hygiene and wound care Case 3 • • • • • • • • • • • • • • • • case 1 patient returns 4 wk later with another abscess on opposite thigh notes that after I&D of first abscess, did not keep wound covered, and occasionally touched site to make sure healing properly site of old abscess clean with well-healed scar patient undergoes I&D and receives 1 wk of TMP-SMX Management of recurrent SSTIs: pathogenesis of recurrent SSTIs unclear however, likely complex interplay between host, environment, and pathogen current guidelines recommend focusing first on personal hygiene, wound care, and environmental hygiene if these measures fail or with evidence of ongoing household transmission, consider decolonization with topical ABX caveat —mupirocin appears to decrease S aureus colonization among nasal carriers in short term, but no studies show impact on prevention of recurrent SSTIs Decolonization: regimens to consider—intranasal mupirocin twice daily for 5 to 10 days mupirocin for 5 to 10 days plus topical skin antiseptic (eg, chlorhexidine) for 5 to 14 days mupirocin for 5 to 10 days plus dilute bleach baths (one-quarter cup to one-quarter tub of water) for 15 min twice weekly for 3 mo oral ABX for decolonization —Cochrane review found oral ABX provide no benefit in eradicating MRSA among patients in health care settings systematic review found rifampin plus antistaphylococcal antibiotic superior to antistaphylococcal agent alone in reducing S aureus colonization however, no studies have evaluated impact of therapy on rates of infection guidelines suggest using oral ABX for decolonization only as last resort (watch for drug interactions, potential side effects, and development of resistance Imaging with _______ has low sensitivity for diagnosing necrotizing SSTIs, but may be helpful if gas is present. (A) Computed tomography (C) Plain films (B) Ultrasonography (D) Magnetic resonance imaging Answer • (C) Plain film • • • • • • • • • • • • • • • Case 4 39-yr-old man with 1-day history of leg pain and erythema (worsening pain/swelling over 24 hr) development of bulla formation febrile, tachycardic, and slightly hypotensive has white blood cell count with left shift Necrotizing SSTIs: can be monomicrobial (most common pathogen group A Streptococcus) or polymicrobial risk factors include intravenous (IV) drug use, diabetes, obesity, and chronic immunosuppression (but often have no precipitating factor) Clinical presentation—patient often presents with nonspecific complaints on physical examination (PE), can be difficult to distinguish from cellulitis (sometimes only mild local erythema found pain out of proportion clue to deeper necrotizing infection); diagnosis— can be challenging many characteristic findings (eg, bullae, induration, fluctuance, crepitus, necrosis) occur later in presentation most common findings (tenderness, warmth, erythema, fever, and tachycardia) often seen with “run of the mill” SSTIs plain films have low sensitivity, but may be helpful if gas present computed tomography and ultrasonography may identify other diagnoses; magnetic resonance imaging fairly sensitive but has low specificity management—if necrotizing SSTI suspected, consider early surgical consultation and treat empirically (antimicrobial therapy with piperacillin-tazobactam or carbapenem, plus clindamycin and vancomycin Bites from _______ are associated with the highest risk for infection. (A) Dogs (B) Cats (C) Humans (D) Rabbit Answer • (B) Cats Case 5 • • • • • • • • • • • • • • • • • • • • • 21-yr-old man bitten by dog receives several deep puncture wounds on hand Animal bites: risk factors for infection —biting species (cats associated with highest risk, followed by humans; dogs associated with relatively low risk) location (hand, foot, joint, or other vulnerable areas [eg, face]) wound type (deep puncture wounds, crush injuries) interval to medical care (treatment delay >12 hr) host factors (eg, advanced age, underlying comorbidities or immunosuppression, steroid use) microbiology—infections typically polymicrobial most common pathogen in dog and cat bites Pasturella recommended empiric treatment regimen—amoxicillin-clavulanate (Augmentin) (plus anti-MRSA agent, if indicated) with penicillin allergy, consider ciprofloxacin plus clindamycin or Moxifloxacin consider prophylaxis if—bites moderate to severe, or on face or hands patient immunocompromised bitten by cat risk for rabies—in assessing risk after bite, consider local epidemiology if bite from dog, cat, or ferret, prophylaxis recommended if rabies suspected if bite from skunk, raccoon, fox, or bat, consider animal rabid unless proven negative by laboratory test (immediate prophylaxis recommended) bites from rabbits and small rodents typically do not require prophylaxis; recommended postexposure prophylaxis regimen —clean wound with virucidal agent Rabies immunoglobulin (administer full dose around wound and remaining volume intramuscularly at site distant from vaccine Vaccinate for 4 days Case 6 • 53-yr-old ED physician with 9-day history of progressive cellulitis of left forearm • initially noted pustule and performed I&D on himself • despite taking cephalexin and clindamycin for 4 days, developed progressive erythema and drainage • started IV vancomycin and ceftriaxone, with no improvement after 3 days • Nocardia brasiliensis—found in soil and environment worldwide • incubation period 1 to 6 wk; infection often associated with mild systemic symptoms • diagnosis made by biopsy and culture • treatment TMP-SMX for 4 to 6 mo • • • • • • • • • • • • Case 7 26-yr-old man with 6-wk history of papule on right hand that progressed to ulcer patient presented to ED and urgent care multiple times and received several courses of ABX with no improvement diagnosed with Leishmania panamensis infection Management of nodular lymphangitis: biopsy critical for diagnosis (pathology for fungi and mycobacteria; cultures for bacterial, fungal, and mycobacterial disease) consider empiric therapy if index of suspicion high based on etiology and patient history organisms to consider include Francisella tularensis, N brasiliensis, Mycobacterium marinum, Sporothrix schenkii, and L panamensis “Masqueraders” of infectious cellulitis contact dermatitis Drug reactions deep venous thrombosis Sweet syndrome Underlying malignancy The population-adjusted incidence of sepsis has been _______ in the United States. (A) Decreasing (B) Stable (C) Increasing Answer • (C) Increasing Sepsis • occurs when systemic inflammatory response syndrome (SIRS) overlaps with infection (defined by visual inspection or culture) • most commonly caused by bacteremia • Impact of sepsis in United States: retrospective study of patients hospitalized for sepsis between 1979 and 2000 found mortality rate declined from 28% during first 6 yr of study to 6% during last 6 yr (mortality still quite high; 20% of severely affected patients die; tenth-leading cause of death in United States) • population-adjusted incidence of sepsis increasing Multiplex polymerase chain reaction is easier to use for detecting pathogens in _______ infections than in _______ infections. (A) Bacterial; fungal (B) Fungal; bacterial Answer • (A) Bacterial; fungal • • • • • • • • • • • • • Diagnosis of sepsis establish source—look for epidemiologic clues obtain gram stains (from urine, sputum, and superficial sites) and cultures (from all sites) targeted imaging; Source control— critical step in early management (diagnostic and therapeutic) data from cultures always delayed potential additional diagnostic aids —procalcitonin (may have role in monitoring therapy and/or limiting duration of ABX) multiplex polymerase chain reaction (PCR; can potentially decrease time to pathogen diagnosis easier to use in detecting bacterial [vs fungal] pathogens) Importance of appropriate initial ABX therapy: several studies have demonstrated significant increase in mortality when inadequate ABX used at start of treatment for sepsis Infection-specific considerations in choosing ABX therapy: consider source, susceptibility of pathogen (know local antibiogram and trends in hospital epidemiology), host factors (eg, asplenia, neutropenia, history of solid organ transplantation), and recent antibiotic exposure Comments: between 1979 and 2001, rise in gram-positive and gram-negative bacterial infections mirrored that in sepsis however, from late 1990s to 2001, incidence of fungal infections rose substantiall All the following are risk factors for nosocomial infections, except: (A) Increasing age (C) Male sex (B) Immunosuppression (D) Recent antibiotic exposur Answer • (C) Male sex Risk factors for nosocomial infections • (vancomycin-resistant enterococci [VRE], MRSA, gram-negative rods, or Candida): health care exposure • increasing age • Immunosuppression • exposure to invasive devices • recent antibiotic exposure Combination vs monotherapy • area of some controversy; 2004 and 2005 meta-analyses found no overall benefit with combination therapy vs monotherapy for treatment of gram-negative bacteremia • however, in recent study of gram-negative sepsis, results showed no survival advantage overall, but subgroup analysis found combination therapy beneficial in patients with septic shock or neutropenia • in another recent study of patients with culture-proven, bacterial septic shock, propensity-matched analysis found combination therapy associated with lower 28-day mortality and greater number of ventilator- and vasopressor- or inotrope-free days; • Hypothesized mechanisms of benefit—1 agent increases likelihood of pathogen susceptibility • prevention of emergence of resistant organisms • potential immunomodulatory effects of second agent • synergistic antimicrobial effect of combination (leading to more rapid killing of pathogen) • • • • • • • • • • • • • • • • • • Drug-dosing considerations in critically ill patients: pharmacokinetics —penetration into various body fluids activity of drug in anaerobic environment (eg, abscess) Presence of foreign material organ dysfunction that may necessitate dose adjustment pharmacodynamics —degree of serum protein binding pattern of killing degree of persistent effect patients with sepsis typically have increased volume of distribution and variations in clearance Beta-lactams: pattern of activity time above minimal inhibitory concentration (MIC; ideally, should to be 4 to 5 times above MIC 40% to 70% of time) achieved by increasing frequency of dosing or changing to continuous or extended infusions retrospective cohort study of patients with Pseudomonas infection found extended (vs regular) dosing resulted in much lower mortality rate in patients with Acute Physiology and Chronic Health Evaluation (APACHE) score 17 at speaker’s institution, piperacillin-tazobactam infusions extended to 4 hr and carbapenem infusions to 3 hr Aminoglycosides: peak-to-MIC ratio most important factor in proper dosing once-daily dosing most effective small study from late 1990s showed >90% probability of response (fever and leukocytosis) by day 7 if ratio of maximum concentration (Cmax ) to MIC >10 lower incidence of nephrotoxicity at day 5 with once-daily dosing drug monitoring necessary in critically ill patients due to clearance variation Which of the following interventions is included in the acute-care (first 6 hr) bundle for sepsis care? (A) Administer low-dose corticosteroids (B) Achieve glucose control between >70 mg/dL and <150 mg/dL (C) Measure serum lactate (D) Consider administering activated protein C Answer • (C) Measure serum lactate Timing of administration of ABX and patient survival • • • • • • • • • • • • • • • • • • • • • • • • Study found administration of ABX within first hour of documented hypotension associated with 20% mortality rate each 1-hr delay in ABX administration associated with 7% increase in mortality Early goal-directed therapy (EGDT) for sepsis-induced hypoperfusion goal of EGDT to complete series of interventions in first 6 hr after presentation in order to maximize oxygen delivery and minimize organ dysfunction interventions include aggressive fluid resuscitation, transfusion to hemoglobin >12 g/dL, use of pulmonary artery catheter for hemodynamic monitoring, sedation, and ventilation paralysis, as needed in one study, EGDT shown to reduce mortality rate from 46% to 30% criticisms of study —with bundled approach, difficult to separate relative value of each intervention single-center trial controls “overly sick” ongoing concern and reluctance to place pulmonary artery catheter and transfuse per protocol because of potential complications Currently 3 large ongoing multicenter trials looking at each intervention and their incremental benefit (data not yet published) Bundled approach to sepsis care: currently divided into 2 components acute-care bundle — to be completed within first 6 hr measure serum lactate obtain blood cultures and administer ABX treat hypotension and/or elevated lactate (IV fluids; vasopressors) if persistent hypotension or lactate >4 mmol/L, implement transfusion and pulmonary artery monitoring for hemodynamics longer-term-care bundle —to be completed within first 24 hr administer low-dose corticosteroids glucose control between >70 mg/dL and <150 mg/dL (controversial) maintain low tidal volume (6 mL/kg) with ventilation consider activated protein C caveat —much of this subject to change new sepsis guidelines due in 2012 (should incorporate data from ongoing studies) Which of the following is(are) a symptom(s) of depression? A) Social withdrawal B) Pessimism C) Fearful affect D) All the above Answer • D) All the above Late-life depression • • • • • • • • • • • • • • • • • • • frequently underdiagnosed and undertreated due to misconception that depression part of normal aging definition — pervasive sadness, depressed mood, loss of interest in normal activities, feeling that life no longer worth living suicide— most adverse consequence of untreated depression duration — months or years Presentation: often coincides with medical illness and general deterioration of health often underdiagnosed due to attribution of depression to natural consequences of concomitant illness (eg, cardiovascular disease [CVD]) consequences — prolonged suffering for patient and family reduced quality of life poorer prognosis for general medical illness increased costs increased risk for suicide and mortality Diagnosis: difficult in context of other illnesses (ie, symptoms may overlap) observer-rated scales used more often in elderly than in younger patients appearance — fearful or sad affect behavior — social withdrawal, deterioration in self-care, or decreased conversation irritability or sadness considered first primary symptom of depression on some scales thought content — brooding, self-pity, pessimism, increased sense of failure and/or punishment, feeling helpless, low self-esteem, wish to die practice tips— do not allow empathy to interfere with diagnosis major depressive disorder not consequence of illness Medications for patients with depression and physical illness • • • • • • • • • • • Cochrane Review (2010) — over 51 published placebo-controlled trials of elderly patients with concomitant illnesses (eg, cancer, diabetes); medications more effective than placebo longer studies — better response seen with 12 to 14 wk vs 6 to 8 wk duration safety and efficacy of tricyclics— comparable to selective serotonin reuptake inhibitors (SSRIs) Medications associated with development of depression: Reserpine Steroids certain drugs used for cancer treatment (eg, interferon) polypharmacy—medications not typically associated with depression when used alone may cause depression when used in combination eliminate medications as appropriate (first line of treatment) cognitive deficits and depression often resolve without addition of antidepressant medication Depression can be an early indicator of Alzheimer disease in elderly patients. A) True B) False Answer • A) True Cognitive disorders • • • • • • • depression often early sign of deteriorating cognitive disorder, eg, Alzheimer disease (AD) Similar rates of depression seen in subcortical dementias, eg, Parkinson disease, vascular dementias vascular depression— first onset generally at >60 yr of age consider hidden neurologic disorder or vascular risk factors (eg, hypertension, CVD, cerebrovascular disease) often associated with reduced depressive ideation and increased somatic symptoms, psychomotor retardation, and cognitive dysfunction does not respond as well to medication as nonvascular depression depression with executive dysfunction —considered to have frontostriatal origin characterized by psychomotor retardation, reduced interest in activities, anhedonia rather than sadness, impaired instrumental activities of daily living, limited insight, and impaired executive functioning (eg, setting goals, planning activities, initiating and sustaining effort, monitoring performance Treatment for depression with cognitive impairment in elderly • • • • • • • • antidepressants— studies show marginal efficacy (possibly attributable to high response rates in groups receiving placebo speaker postulates that this effect due to frequent follow-up visits with caring clinician) problemsolving therapy— shown to be highly effective in studies by Arean et al and Alexopoulos et al aimed at relieving stress by teaching patients how to cope with everyday difficulties after 6 wk, problem-solving therapy more effective than supportive therapy prolonged effects observed in patients followed beyond 12 wk donepezil— cholinesterase inhibitor used to improve cognition in patients with cognitive dysfunction when given to patients with minimal cognitive impairment who had responded to antidepressant medication (in study by Reynolds), cognition improved (less progression to dementia), but likelihood of recurrence of depression increased Which of the following symptoms is not associated with vascular depression? A) Increased depressive ideation B) Increased somatic symptoms C) Psychomotor retardation D) Cognitive dysfunction Answer • A) Increased depressive ideation Which of the following treatments has been shown to be highly effective in improving depression in elderly patients with comorbid cognitive impairment? A) Antidepressant medications B) Problem-solving therapy C) Memory enhancers D) None of the above Answer • B) Problem-solving therapy Multiple losses and bereavement • elderly lose jobs, money, homes, abilities, health, and loved ones; • bereavement — relationship with depression controversial • Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) — cautions against treating depression within 2 mo of loss of loved one and diagnosing major depression after bereavement • however, depression after bereavement common and as persistent as any other type of depression with similar outcomes, treatment responses, and recurrence rates • “fallacy of misplaced empathy” — inappropriate to dismiss signs of major depressive episode as “normal” in patients despondent because of loss (treat accordingly Which of the following is a characteristic of normal grief rather than depression? A) Dysphoria that occurs in waves B) Guilt focused on deserving to be depressed C) Feeling that nothing is enjoyable D) Being inconsolable Answer • A) Dysphoria that occurs in waves • • • • • • • • • • • • • • • • • Distinguishing between normal grief and major depressive disorder normal grief — dysphoria in waves, often precipitated by reminders of deceased, but mixed with happy pleasant memories not inconsolable wants to be with others and talk major depression — pervasive feeling that nothing enjoyable guilt focused on deserving to be depressed (rather than letting down person who died) suicidal ideation or feeling undeserving of life (rather than wishing to be reunited with deceased) diagnostic tip — consider severity of depression and history not determined by time since loss of loved one Treatment for bereavement-related depression: no randomized controlled trials (RCTs) of psychotherapy literature suggests positive effects; several studies demonstrate efficacy and safety of medication study by Zisook et al — patients who met criteria for major depression given bupropion within 8 wk of losing spouse depression and symptoms of grief diminished over time Psychotherapy: historically considered ineffective in past 10 to 15 yr, controlled trials have proven otherwise indications — acute treatment of major depression after remission to prevent further episodes prophylactic treatment with problem-solving therapy or SSRIs after stroke associated with lower rates of depression, compared to placebo • • • • • • • • • • • • • • • • • • • • • • • • Antidepressants tricyclics — mainstay in 1960s and 1970s desipramine least anticholinergic and nortriptyline least likely to cause orthostatic hypotension (OH) effective in elderly, but anticholinergic side effects can adversely affect cognition also associated with potentially detrimental antihistaminic and cardiovascular effects SSRIs — introduced in late 1980s safer and more tolerable than tricyclics; serotonin-norepinephrine reuptake inhibitors (SNRIs) — also effective mirtazapine may be beneficial in frail underweight elderly due to potential side effect of weight gain efficacy — study by Nelson showed that response to antidepressants shows greater divergence from response to placebo with longer (10-14 wk) duration of treatment; patients with early onset of depression, more severe depression, and/or more recurrent depression attain better response weigh modest benefits of antidepressants against potential safety issues (eg, increased risk for bleeding, hyponatremia, decreased bone density) treatment tip — “start low, go slow,” but increase dose until patient responds or fails to tolerate Other effective modalities: exercise — for minor and major depression not as strongly recommended for major depressive disorder, but some data suggest benefit bright light — for major and minor depression electroconvulsive therapy (ECT) — for more resistant depression transcranial magnetic stimulation (TMS) — approved by Food and Drug Administration, but effects not as robust as ECT Collaborative care: depression in primary care settings often undertreated or not treated effectively outcomes of collaborative care models, eg, Improving Mood Promoting Access to Collaborative Treatment (IMPACT) consistently superior to those of traditional approaches findings— higher patient satisfaction sustained effects crosses cultural boundaries associated with fewer thoughts of suicide cost — $522 per patient savings tremendously outweigh alternative should be standard of care Results of randomized controlled trials do not always apply to elderly patients with dementia because: A) Patients with dementia are commonly excluded from the trials B) Patients >80 yr of age are commonly excluded in the trials C) Patients with multiple comorbidities are commonly excluded from the trials D) All the above Answer • D) All the above All the following are conditions commonly comorbid with dementia, except: A) Diabetes B) Hypertension C) Ulcerative colitis D) Congestive heart failure Answer • C) Ulcerative colitis Which of the following is not a complication of late-stage dementia? A) Behavioral disturbances B) Gait disorders and falls C) Weight loss D) Hair loss Answer • D) Hair loss A noisy chaotic environment can trigger agitation in patients with dementia. A) True B) False Answer • A) True Which of the following statements about management of agitation in advanced dementia is incorrect? A) Undiagnosed pain may be the underlying cause B) Medication is the first line of treatment C) Focus treatment on symptoms that place patient or others at risk D) Do not treat trivial or annoying behaviors Answer • B) Medication is the first line of treatment Menopause can produce symptoms as a result of declining hormone levels. Which one of the following sentences is TRUE concerning the use of testosterone in postmenopausal women? Testosterone production declines approximately 90% with the onset of menopause. Testosterone improves sexual functioning and reduces the vasomotor symptoms associated with menopause. The Nurses’ Health Study showed no link between combined estrogen/testosterone therapy and increased risk of breast cancer. Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are not reasonable alternatives for testosterone when considering androgen therapy in postmenopausal women. Because of its effect on the lipid profile, testosterone has been determined to be safe in postmenopausal women with • • • • • • • • • Menopause can produce severe and disabling symptoms in some women, and many studies have sought to evaluate the effectiveness of therapies in alleviating these symptoms. Those most commonly described are vasomotor symptoms, loss of libido, vaginal dryness/atrophy, depressed mood, poor sleep, cognitive disturbances and an overall decrease in quality of life. Not only do estrogen levels decline with menopause, but so do androgen levels. There is approximately a 50% reduction in androstenedione and subsequent testosterone production. A few studies have found that reduced levels of testosterone result in a decrease in sexual desire and functioning that improves with the addition of androgen therapy. Low circulating levels of testosterone have also been correlated with hip fracture and reduced bone density. Because of such results women have been started on testosterone therapy since the 1970s, despite lack of approval by the Food and Drug Administration (FDA). Doses of testosterone at higher-than-physiologic levels do appear to improve sexual functioning, libido and sexual arousal while also improving bone composition, muscle strength and quality of life. A review (Alexander, et al.) of randomized controlled trials determined that testosterone with estrogen replacement improved overall sexual functioning, but the number of women responding was variable, as were the dosing and regimen used in the trials reviewed. The addition of testosterone does improve bone density. However, there is little evidence that use of testosterone is useful in managing vasomotor symptoms except when combined with estrogen. Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) decline with age along with testosterone. While replacing these substances increases testosterone levels, vasomotor symptoms, mood and sleep disturbances do not improve. The use of testosterone and androgens has potential risks. Adverse side effects with high doses of androgens include acne, hirsutism and a reduction in HDL levels. Long-term cardiac effects resulting from lowered HDL levels are unknown and pose a theoretical concern, although no long-term studies have explored the cardiovascular risks or safety. Virilization is rare but can occur in women taking doses that are higher than exist physiologically. Women receiving estrogen and testosterone hormone replacement therapy in the Nurses’ Health Study from 1978-2002 were found to have a greater risk of breast cancer with each year of use (17.2% increased; 95% confidence interval [CI] 6.7-28.7%). The evidence regarding the use of testosterone in menopause is conflicting and its safety uncertain; therefore, a thorough review of individual risks and potential benefits should be undertaken before initiating testosterone therapy. The North American Menopause Society recommends that testosterone therapy only be considered and started in women who suffer from decreased sexual functioning that causes personal distress with no identifiable cause (SOR C; Ref. 5). DHEA and DHEAS are not recommended, since little evidence supports their use and the FDA does not regulate these over-the-counter formulations for content or purity. Continued monitoring is recommended once a woman chooses to begin therapy and should focus primarily on monitoring for potential side effects such as virilization, breast cancer and altered lipid levels. Baseline liver function tests and lipid levels are recommended and should be obtained again at 3 months and annually if stable. Contraindications to testosterone therapy are similar to those for estrogen. These include breast or uterine cancer or women with cardiovascular or liver disease. A 45-year-old male patient comes to the office for a routine physical. During the history taking, the patient states his wife has said he has bad breath. He has tried mouthwashes and increasing his fluid intake, but his wife says they have not helped. Breath mints seem to cover his bad breath but do not eliminate it. Which one of the following would be the BEST recommendation regarding the patient’s halitosis? Obtain a H. pylori antibody test. Prescribe empiric therapy with oral antibiotics. Recommend aggressive oral hygiene with frequent flossing and tongue brushing. Schedule an esophagogastroduodenoscopy (EGD) to evaluate the patient for gastrointestinal reflux disease. Schedule a computed tomography (CT) of the sinuses and upper airway.