neuropathic pain, Ceiliac disease

1. neuropathic pain, Ceiliac disease

2. EVALUATION OF SYNCOPEWhich one of the following features is predictive of seizure rather than syncope?  (check one) A. Presyncope spells before loss of consciousness.  B. Diaphoresis before a spell.  C. Loss of consciousness with prolonged standing.  D. Witnessed abnormal posturing

3. Answer •  D. Witnessed abnormal posturing. 

4. EVALUATION OF SYNCOPEWhich of the following clinical features predict an adverse one-month outcome following an episode of syncope?  (check all that apply) A. Anemia.  B. Brain natriuretic peptide level ≥ 300 pg per mL (300 ng per L).  C. Absence of chest pain.  D. Bradycardia. Correct.

5. Answer •  A. Anemia.  B. Brain natriuretic peptide level ≥ 300 pg per mL (300 ng per L).   D. Bradycardia.

6. EVALUATION OF SYNCOPEWhich of the following generally should be considered in patients without cardiac disease who have a syncopal event?  (check all that apply) A. Hospital admission for monitoring and evaluation.  B. Standard 12-lead electrocardiography.  C. Electrophysiology.  D. Orthostatic vital signs. 

7. Answer • B. Standard 12-lead electrocardiography.  D. Orthostatic vital signs. 

8. Syncope • Syncope is a transient and abrupt loss of consciousness with complete return to preexisting neurologic function. • It is classified as neurally mediated (i.e., carotid sinus hypersensitivity, situational, or vasovagal), cardiac, orthostatic, or neurogenic. • Older adults are more likely to have orthostatic, carotid sinus hypersensitivity, or cardiac syncope, whereas younger adults are more likely to have vasovagal syncope. • Common nonsyncopal syndromes with similar presentations include seizures, metabolic and psychogenic disorders, and acute intoxication. • Patients presenting with syncope (other than neurally mediated and orthostatic syncope) are at increased risk of death from any cause. • Useful clinical rules to assess the short-term risk of death and the need for immediate hospitalization include the San Francisco Syncope Rule and the Risk Stratification of Syncope in the Emergency Department rule. • Guidelines suggest an algorithmic approach to the evaluation of syncope that begins with the history and physical examination. • All patients presenting with syncope require electrocardiography, orthostatic vital signs, and QT interval monitoring. • Patients with cardiovascular disease, abnormal electrocardiography, orfamily history of sudden death, and those presenting with unexplained syncope should be hospitalized for further diagnostic evaluation. • Patients with neurally mediated or orthostatic syncope usually require no additional testing. • In cases of unexplained syncope, further testing such as echocardiography, grade exercise testing, electrocardiographic monitoring, and electrophysiologic studies may be required. • Although a subset of patients will have unexplained syncope despite undergoing a comprehensive evaluation, those with multiple episodes compared with an isolated event are more likely to have a serious underlying disorder.

9. Syncope • Patients with syncope and evidence of heart failure or structural heart disease should be admitted to the hospital for monitoring and evaluation. • C • All patients presenting with syncope should have orthostatic vital signs and standard 12-lead electrocardiography. • C • Laboratory testing in the evaluation of syncope should be ordered as clinically indicated by the history and physical examination. • C • Indications for electrophysiology include patients with coronary artery disease and syncope, coronary artery disease with an ejection fraction less than 35 percent, and possibly nonischemic dilated cardiomyopathy. • C • Patients at low risk of adverse events (i.e., those with symptoms consistent with vasovagal or orthostatic syncope, no history of heart disease, no family history of sudden cardiac death, normal electrocardiographic findings, unremarkable examination, and younger patients) may be safely followed without further intervention or treatment. • B

10. Causes of SyncopeType of syncopeMean prevalence of syncope (%)*Cardiac • Arrhythmia • 14 (4 to 38) • Structural disease • 4 (1 to 8) • Neurally mediated • Carotid sinus • 1 (0 to 4) • Situational • 5 (1 to 8) • Vasovagal • 18 (8 to 37) • Neurologic • 10 (3 to 32) • Orthostatic • 8 (4 to 10) • Psychogenic • 2 (1 to 7) • Unknown • 34 (13 to 41)

11. Risk Stratification in Patients with SyncopeHigh-risk (hospital admission recommended)* • Clinical history suggestive of arrhythmia syncope (e.g., syncope during exercise, palpitations at time of syncope) • Comorbidities (e.g., severe anemia, electrolyte abnormalities) • Electrocardiographic history suggestive of arrhythmia syncope (e.g., bifascicular block, sinus bradycardia < 40 beats per minute in absence of sinoatrial block or medications, preexcited QRS complex, abnormal QT interval, ST segment elevation leads V1 through V3 [Brugada syndrome], negative T wave in right precordial leads and epsilon wave [arrhythmogenic right ventricular dysplasia/cardiomyopathy]) • Family history of sudden death • Older age† • Severe structural heart or coronary artery disease • Low-risk (outpatient evaluation recommended)‡ • Age younger than 50 years† • No history of cardiovascular disease • Normal electrocardiographic findings • Symptoms consistent with neurally mediated or orthostatic syncope • Unremarkable cardiovascular examination

12. APPROACH TO SEPTIC ARTHRITISA 55-year-old woman presents for follow-up after hospitalization for septic arthritis in her finger from a cat bite. Which one of the following pathogens is the most likely cause of infection?  (check one) A. Brucella species.  B. Pasteurellamultocida.  C. Pseudomonas aeruginosa.  D. Mycobacterium marinum. 

13. Answer • B. Pasteurella multocida. 

14. APPROACH TO SEPTIC ARTHRITISWhich of the following are risk factors for septic arthritis?  (check all that apply) A. Recent joint surgery.  B. Age older than 80 years.  C. Human immunodeficiency virus infection.  D. Rheumatoid arthritis. 

15. Answer •  Recent joint surgery.  B. Age older than 80 years.  C. Human immunodeficiency virus infection.  D. Rheumatoid arthritis. 

16. Prompt diagnosis and treatment of infectious arthritis can help prevent significant morbidity and mortality. • The acute onset of monoarticular joint pain, erythema, heat, and immobility should raise suspicion of sepsis. • Constitutional symptoms such as fever, chills, and rigors are poorly sensitive for septic arthritis. • In the absence of peripheral leukopenia or prosthetic joint replacement, synovial fluid white blood cell count in patients with septic arthritis is usually greater than 50,000 per mm3. • Isolation of the causative agent through synovial fluid culture is not only definitive but also essential before selecting antibiotic therapy. • Synovial fluid analysis is also useful to help distinguish crystal arthropathy from infectious arthritis, although the two occasionally coexist. Almost any microorganism can be pathogenic in septic arthritis; however, septic arthritis is caused by nongonococcal pathogens (most commonly Staphylococcus species) in more than 80 percent of patients. • Gram stain results should guide initial antibiotic choice. Vancomycin can be used for gram-positive cocci, ceftriaxone for gram-negative cocci, and ceftazidime for gram-negative rods. • If the Gram stain is negative, but there is strong clinical suspicion for bacterial arthritis, treatment with vancomycin plus ceftazidime or an aminoglycoside is appropriate. • Evacuation of purulent material with arthrocentesis or surgical methods is necessary. Special consideration should be given to patients with prosthetic joint infection. In this population, the intraarticular cutoff values for infection may be as low as 1,100 white blood cells per mm3 with a neutrophil differential of greater than 64 percent.

17. Suspicion of septic arthritis should be pursued with arthrocentesis, and synovial fluid should be sent for white blood cell count, crystal analysis, Gram stain, and culture. • C • In addition to antibiotic therapy, evacuation of purulent material is necessary in patients with septic arthritis; arthrocentesis and surgical methods are appropriate. • C • Intraarticular white blood cell cutoff values for infection as low as 1,100 per mm3 (1.10 × 109 per L) with a neutrophil differential of greater than 64 percent can help diagnose prosthetic joint infection. • C

18. Which of the following is most likely to cause neuropathic pain? A) Sprains B) Postoperative incision site C) Fibromyalgia D) Arthritis

19. Answer • C) Fibromyalgia

20. Pain types: nociceptive— somatic pain; associated with, eg, sprains, strains, postoperative incisional pain, arthritis; localized pain; easier for patients to pinpoint; often easier to treat; treated with acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose opioids, ice, and heat; • neuropathic — vividly described by patients; associated with, eg, nerve entrapment, shingles, complex regional neuropathic pain syndromes, fibromyalgia, peripheral neuropathies, central neuropathic pain syndromes, cancerassociated syndromes • mixed — important to identify and treat dominant type • patient may continue to report severe pain from subdominant type • Pain sensitivity: paresthesia — nonpainful abnormal sensation • allodynia — pain caused by stimuli that normally do not provoke pain • hyperalgesia — increased pain response to stimuli that normally do not cause that level of pain • hypoalgesia — characterized by numbness

21. Opioid-induced hyperalgesia can occur with: A) Maintenance therapy B) High escalating doses C) Low doses D) All the above

22. Answer • D) All the above

23. Opioids for neuropathic pain: limit to prevent addiction • crucial to use adjunctive medications that change chemical mediators • many patients present on high doses of opioids • use of opioids as sole therapy can worsen pain and lead to cycle of increased use • Hyperalgesia: can occur with any type of pain but classically associated with neuropathic pain • often due to upregulation in central nervous system of N-methyl-D-aspartate • (NMDA) receptor; glutamate-activated and upregulated by, eg, opioid, fear, disease process, or unrelieved pain • upregulation results in hypersensitization of nervous system • opioid-induced hyperalgesia — 3 forms • 1) with maintenance therapy (eg, patient with classic chronic pain started on opioid, and dose increased over time) • results in slow upregulation and mild stimulation of excitatory glutamate system • 2) with high escalating doses of opioid (eg, end-of-life patient given high amount of opioid for pain) • escalating dose of morphine or hydromorphone (eg, Dilaudid, Palladone) • results in accumulation of metabolite (3-glucuronide) that can cause excitatory intoxication within hours or days • (must switch opioids and clear metabolite with fluid) • 3) with low doses of opioid; shown in animal models (not • clearly seen in humans)

24. Models of neuropathic pain: • diabetic neuropathy and postherpetic neuralgia classic • devastating effects on quality of life of older patients • eg, in patients with pain due toc shingles, average number of general practice visits, 19 (number of drugs, 14) • polyneuropathies — eg, diabetes, neurotoxicity from chemotherapy, alcoholism, or HIV disease • one-third of cases idiopathic • in some patients, numbness and loss of balance more problematic than pain (drugs ineffective) • efficacy of drugs seen in 30% to 50% • Patients with symptomatic pain at new diagnosis of diabetes, 8% (30%-50% after 25 yr) • poststroke pain associated with ectopic abnormal discharge of pain sensations • phantom pain can be associated with, eg, mastectomy, colon resection, tooth extraction (early treatment beneficial

25. Choose the correct statement about the risks of nonsteroidal anti-inflammatory drugs (NSAIDs). A) Adverse effects occur only with high doses B) Gastrointestinal bleeding is always preceded by gut pain C) May decrease bone healing when used too soon postoperatively D) Younger patients should be monitored every 1 to 2 yr

26. Answer •  C) May decrease bone healing when used too soon postoperatively

27. Nonsteroidal anti-inflammatory drugs • not classically used for neuropathic pain • central and peripheral action • most interact centrally with opioid system, serotonergic system, and cen- tral nitric oxide mechanisms • weigh risks and benefits • In younger patients (25-50 yr of age), low-dose NSAID as part of multimodal approach can be effective • prostaglandins thought to sensitize peripheral nociceptors in dorsal horn • may take months to perceive benefit • options include nonselective, selective, and topical forms • consider ibuprofen, 200 to 400 mg 3 times daily • risks—(even with low doses) include gastrointestinal (GI) bleeding, renal toxicity, and exacerbation of congestive heart failure • monitor younger patients every 6 mo to 1 yr • decreased bone healing when used too soon postoperatively • cardiovascular events in elderly at-risk populations • GI bleeding can be spontaneous without pain in gut • avoid use in frail elderly patients; • topical—eg, creams, transdermal patches • consider in older patients • produce lower blood levels; effective only on area where applied; may be effective in • patients with mixed type of pain (nociceptive and neuropathic

28. All the following are associated with dexamethasone,except: A) Cataracts B) Hypoglycemia C) Muscle wasting D) Insomnia

29. Answer •  B) Hypoglycemia

30. Amitriptyline A) Indicated for diabetic neuropathy and fibromyalgia B) Risks include orthostasis, falls, and constipation in elderly, and weight gain, increased appetite, and sexual dysfunction in younger patients C) Approved by Food and Drug Administration for postherpetic neuralgia; bioavailability decreases dramatically with doses >600 mg D) Binds to kappa-opioid receptors and mimics dynorphin effect effectively

31. Answer • B) Risks include orthostasis, falls, and constipation in elderly, and weight gain, increased appetite, and sexual dysfunction in younger patients

32. Antidepressants • TCAs— nortriptyline better tolerated than amitriptyline • desipramine more activating than sedating • selective serotonin reuptake inhibitors (SSRIs) — not shown highly beneficial in neuropathic pain • may be effective for migraines and chronic tension headaches; • use of TCAs — effective due to many mechanisms of action (eg, effect on NDMA receptor) • if younger patient can tolerate NSAID, consider pushing TCA dose to 150 to 200 mg for • greater benefit • studies suggest effective whether patient depressed or not • benefit usually seen with lower dose (100 mg; 50 mg in elderly) in 4 to 16 wk; • side effects worst during first week (and pain relief least), then diminish as efficacy increases • efficacy similar between agents • meta-analysis suggests number needed to treat (NNT) to benefit 1 patient with 50% reduction in pain, 3 (with SSRIs, 7); NNT for adverse effect, 1 in 19 • side effects include orthostasis, risk for falls, and constipation (especially in elderly) • not highly useful in patients >65 yr of age; beneficial in younger patients • important to select appropriate drug • amitriptyline associated with most adverse effects, then doxepin, nortriptyline, and desipramine • younger patients typically bothered by weight gain, increased appetite (adding chromium picolinate may be helpful), and sexual dysfunction; • atypical agents — some evidence of efficacy with venlafaxine (patients more energetic with higher doses needed for pain relief) • one study showed good efficacy of bupropion; duloxetine indicated for diabetic neuropathy and fibromyalgia (due to risk for side effects [eg, nausea, liver problems], not used as first-line agent by speaker) • venlafaxine and duloxetine acceptable for postherpetic neuralgia, but efficacy of TCAs higher

33. Duloxetine A) Indicated for diabetic neuropathy and fibromyalgia B) Risks include orthostasis, falls, and constipation in elderly, and weight gain, increased appetite, and sexual dysfunction in younger patients C) Approved by Food and Drug Administration for postherpetic neuralgia; bioavailability decreases dramatically with doses >600 mg D) Binds to kappa-opioid receptors and mimics dynorphin effect effectively

34. Answer •  A) Indicated for diabetic neuropathy and fibromyalgia

35.  Gabapentin A) Indicated for diabetic neuropathy and fibromyalgia B) Risks include orthostasis, falls, and constipation in elderly, and weight gain, increased appetite, and sexual dysfunction in younger patients C) Approved by Food and Drug Administration for postherpetic neuralgia; bioavailability decreases dramatically with doses >600 mg D) Binds to kappa-opioid receptors and mimics dynorphin effect effectively

36. Answer • C) Approved by Food and Drug Administration for postherpetic neuralgia; bioavailability decreases dramatically with doses >600 mg

37. Anticonvulsants: older agents associated with drug interactions and side effects • newer agents— expensive; partial to “decent” efficacy in studies of neuropathic pain; carbamazepine (eg, Tegretol, Carbatrol, Epitol) and clonazepam shown beneficial; phenytoin; valproic acid can be used at end of life for sedating and calming effects (can be given rectally); • gabapentin— available in generic form; studies controversial; 30% to 50% reduction in pain in 1 in 2 or 3 • Patients • consider lamotrigine, pregabalin, and topiramate (if one agent ineffective, consider trying another agent) • gabapentin approved by Food and Drug Administration (FDA) for postherpetic neuralgia • limited intestinal absorption (800-900 mg absorbed in single dose; bioavailability decreases dramatically with doses >600 mg) • Tolerable when titrated up slowly • in younger patients, start at 300 mg once daily at bedtime (does not disrupt sleep architecture), then slowly increase to 3 times daily (if needed, give 600 mg 3 times/day slowly) • for older patients, start slowly with 100 mg once daily at bedtime for 1 wk, then increase to 200 mg once daily at bedtime (if still no benefit, add 100 mg in morning) • study showed 30% reduction in pain in 33% of patients (dizziness and somnolence in 25%, • edema in 10%) • study saw 33% of patients with poorly controlled diabetes and significant pain had 25% reduction in pain • hyperexcitable nervous system — in patients on opioids, eg, oxycodone (eg, OxyContin, Oxydose, OxyFAST, Roxicodone) with escalating pain; start low-dose anticonvulsant or TCA and slowly taper opioids to reduce by • 50% • ask, “are you better off today than you were 2 or 4 yr ago with your pain?” • pregabalin — mechanism similar to gabapentin option when other agents fail • more linear dosing with quicker onset • 75 mg twice daily recommended (speaker recommends starting at 25-50 mg/day to reduce dizziness); • efficacy — varies between types • NNT with carbamazepine lowest of any anticonvulsant, particularly for trigeminal neuralgia (may not be useful in other neuropathic pain due to need for higher doses and increased risk) • valproic acid associated with more sedation and decreased functionality • topiramate used more for migraine than neuropathic pain • gabapentin, lamotrigine, and pregabalin reasonable • mexiletine not commonly used for neuropathic pain (except in resistant cases) due to risk

38. Using _______ lidocaine patches at once can lead to adverse effects (eg, arrhythmia). A) >1 B) >2 C) >3 D) >4

39. Answer •  D) >4

40. Response to opioids • some evidence of efficacy • use of opioid alone can lead to more pain • some short-term (eg, 3-6 mo) studies show average NNT ranges from 2.1 to 3.0 (3.5- • 3.9 with tramadol) • Selecting opioids: morphine — consider effect of metabolite with high doses in patients with poor renal function, or end-of-life patients with insufficient fluid (problem unlikely in patients 45-50 yr of age on lower doses) • methadone — studies comparing efficacy with morphine conflict • oxycodone — binds to kappa-opioid receptors and may mimic dynorphin effect more effectively (not proven) • tramadol — blocks reuptake of catecholamines; escalating doses associated with risk for serotonergic syndrome, especially in combination with other drugs, eg, SSRIs • Using opioids: use adjuvant; do not expect 100% pain relief • start at reasonable dose (acceptable to titrate up • if benefits do not justify use, then taper and stop) • methadone — some benefit in neuropathic pain, but more complex and risky • use conversion tables; long half-life; associated with cardiac toxicity • can be beneficial when monitored and converted properly • watch for drug interactions, accumulation, and cardiac risk

41. Topical approaches • ketamine compounded in pluronic lecithin organogel shown beneficial • topical agents effective locally where applied • lidocaine patch (eg, Lidoderm Patch) — using >4 patches at once can lead to adverse effect (eg, arrhythmia) • recommended to apply new patch after 12 hr • speaker leaves patch on continuously for 2 to 5 days (off-label use) • if this causes itchiness or rash, remove patch for few hours and wash area • if rash continues, inhaled corticosteroid, eg, beclomethasone [eg, QVAR, Beconase, Vancenase] applied on skin helpful • takes 7 to 10 days • blood levels low unless 4 to 5 patches used • indicated for postherpetic neuralgia • can be used in diabetes for localized burning feet (off-label use) • effective in patients with healed amputated toes (in addition to oral therapy) and neuropathic cervical neck pain (off-label use) • Topical capsaicin highly beneficial (depletes substance P; NNT in postherpetic neuralgia, 3.2 [6.7 in generalized peripheral neuropathic pain]) • compounded products — useful, but little evidence; localized effect on nerve fiber; gels cause absorption of drug and can lead to systemic side effects (eg, paranoia, hallucinations, and mind-body dissociation with ketamine

42. Choose the correct statement about antipsychotic agents for treatment of pain. A) Directly affect neuropathic pain with high efficacy rates B) Studies show haloperidol more effective for trigeminal neuralgia than for migraine C) No responses shown to quetiapine D) One study showed olanzapine effective for end-of-life pain, but only when pain driven by fear

43. Answer • D) One study showed olanzapine effective for end-of-life pain, but only when pain driven by fear

44. Cannabinoids have been shown to: A) Improve pain B) Be more effective for pain than NSAIDs C) Improve function (eg, return to work) D) Cause severe hyperalgesia 

45. Answer •  A) Improve pain

46. Agents that affect NMDA receptors: methadone and ketamine effective • ketamine most effective but with highest risk for side effects • only small studies in stroke pain, fibromyalgia, ischemia, and phantom pain • more effective for allodynia and hyperalgesia than traditional analgesics; • speaker uses for patients with hyperexcitable nervous system • when using ketamine, decrease opioid dose by 50% to reduce risk for opioid toxicity • use low doses of oral and topical therapies for nonmalignant pain • Cannabinoids: shown effective for pain, but not shown more effective than other agents; not shown to improve function (eg, return to work) • Neuragen PN: available over-the-counter; geranium oil • for burning feet of diabetes; $25 to $30; use 1 to 2 drops

47. According to the National Institute on Alcohol Abuse and Alcoholism, _______ drinks per week constitutes "heavy drinking" in men. A) 7 B) 10 C) 12 D) 15

48. Answer •  D) 15

49. Crack cocaine is available only as a hard-based form, while methamphetamine is available only as a powder. A) True B) False

50. Answer •  B) False