Final Exam Workshops Review sheet PDF

PUD Drugs that can cause Aspirin (and other antiplatelet drugs) disease Smoking Anticoagulants SSRIs Bisphosphonates → associated with esophageal ulceration...

PUD Drugs that can cause Aspirin (and other antiplatelet drugs) disease Smoking Anticoagulants SSRIs Bisphosphonates → associated with esophageal ulceration Methotrexate → thins epithelial lining Corticosteroids (maybe – these are controversial) → do not necessarily cause ulcers, but delays healing of ulcers and increase risk of developing an ulcer with concomitant use of NSAIDs NSAIDs → interfere with prostaglandins and mucosal repair To consider: Gastric vs. duodenal ulcers NSAID-induced ulcer can be local or systemic o Local: direct irritation of gastric epithelium o Systemic: interfere with prostaglandin production → most of the ulcers we see will be systemic because these can occur no matter the route of administration, i.e., oral H. Pylori induced ulcers: o More duodenal than gastric o Symptom: epigastric pain o Occurs more superficially o GI bleeding less severe NSAID induced ulcers: o More gastric than duodecal o Symptom: often asymptomatic o Occurs more deeply o GI bleeding is typically severe o Note: 2-4% of patients that chronically use NSAIDS will develop an ulcer o These include NSAIDS used alone or NSAIDS in combination therapy (i.e., in migraine medication) Risk Factors H. Pylori PUD: Age over 60 years Lower socioeconomic class (developing countries) Children under 10 years NSAID PUD: Age over 65 years Previous peptic ulcer in the past (depends on type of NSAID they are taking) If they have a chronic disease Not clear if alcohol or smoking causes ulcers, but it definitely slows healing rate NSAID properties that increase risk of PUD: If the patient is on a high dose of an NSAID If they are taking multiple NSAIDs (i.e., ASA + naproxen) Non-COX-2 selective NSAID Duration of activity of the drug is longer (i.e., meloxicam) Clinical Presentation Episodic dyspepsia (epigastric pain/burning) Abdominal pain Nausea, vomiting, anorexia Rarely: life-threatening upper GI bleeding Diagnosis Definitive diagnosis is done with endoscopy and biopsy Decreased hemoglobin due to bleeding Serology testing: detecting H. Pylori IgE in the serum Urea breath test Location of ulcer: duodenal more likely to be H. Pylori and gastric more likely to be NSAID- induced  Is the ulcer bleeding? NSAID-induced ulcers are more likely to be asymptomatic and bleeding whereas H. Pylori ulcers are more likely to be symptomatic and less likely to bleed Differential Diagnosis If she came in with epi-gastric pain: need to rule out cardiac pain (pain into left arm or jaw or chest pain when they do little activity), if they have chest pain they need to get checked out Ask if she has dysphagia, vomiting, looking for any esophageal or gastric cancers Why is drug therapy Complications if ulcer is left untreated: required? Can cause an obstruction (depending on where the ulcer is) Bleeding can lead to hematemesis, melena, and massive upper GI bleeds → less common for H. Pylori ulcer but very common for gastric ulcers Ulcers can progress The patient will continue to have epigastric pain Efficacy endpoints (goals Resolution of ulcer within 2 weeks of treatment of therapy) Eradication of H. pylori infection within 2 weeks of treatment Resolution of epigastric pain within 1-2 weeks of treatment Prevent recurrence of Infection/ulcer in the future Therapeutic regimens (3- Pharmacological treatment is first-line, and non-pharms adjunctive 4 reasonable options) H. Pylori-induced ulcer: PPI + bismuth subsalicylate + metronidazole + tetracycline (Bismuth quadruple therapy) PPI + amoxicillin + clarithromycin + metronidazole (Non-bismuth quadruple therapy) PPI + amoxicillin + clarithromycin (LOSEC1-2-3-A) PPI + metronidazole + clarithromycin (LOSEC1-2-3-M) PPI + amoxicillin + levofloxacin NSAID-induced ulcer: Proton Pump Inhibitors (PPI), i.e., omeprazole, lansoprazole, pantoprazole Histamine 2 Receptor Antagonists (H2RA), i.e., ranitidine, famotidine Antacids, i.e., sodium bicarbonate, calcium carbonate Mucosal protective agents, i.e., misoprostol Compare efficacy H. Pylori-induced ulcer; Quadruple therapy is recommended first line therapy, and more specifically the bismuth quadruple therapy due to the increase in clarithromycin resistance Triple therapy should only be used when clarithromycin resistance is less than 15%, which is not the case in North America In Canada, the least amount of bacterial resistance is to amoxicillin, therefore we want amoxicillin in our choice and avoid clarithromycin No difference between efficacy of PPIs and they can all be used BID PPIs start to have their full effect in 2-3 days and the minimal effective course of treatment is 7- 10 days for all regimens, but 14 days is the recommended time frame BEST: Bismuth quadruple therapy Second BEST: non-bismuth quadruple therapy WORST: triple therapy with clarithromycin NSAID-induced ulcer: PPIs: fastest at healing ulcers (2-4 weeks) due to inhibiting 90-95% of acid secretion in a 24-hour period. Begin to have their full effect in 2-3 days H2RAs: treat ulcers in approx. 8 weeks due to inhibiting 60-70% of acid secretion in a 24-hour period Antacids: provide temporary relief of symptoms, however will take more than 12 weeks to heal an ulcer Mucosal protective agents: will take approximately 8+ weeks to heal an ulcer BEST: PPI Second BEST: H2RA WORST: Antacids Compare toxicity H. Pylori-induced ulcer:  Metronidazole: Taste disturbance Tetracycline: photosensitivity Amoxicillin and other antibiotics: rash, nausea, diarrhea Bismuth: dark stool, tongue discolouration PPI: o Short-term: headache, nausea, constipation o Long-term: pneumonia as PPIs can change how you aspirate NSAID-induced ulcer: all generally well-tolerated PPI: generally well tolerated; nausea, constipation, diarrhea, rash H2RA: generally well-tolerated, but cimetidine has CNS side effects Antacids: constipation, diarrhea, can lead to metabolic alkalosis Mucosal protective agents: headache, nausea, diarrhea, rash Compare drug H. Pylori-induced ulcer: interactions PPI: decrease calcium absorption, which puts patient at greater risk for osteoporosis; interferes with absorption of vitamin B12, iron, Mg; inhibits CYP2C19 which delays activation of clopidogrel; drugs that require an acidic environment to be absorbed such as antifungals Calcium and iron interfere with absorption of tetracycline Bismuth: interacts with ACE inhibitors Clarithromycin : inhibitor of CYP3A4, therefore many potential drug interactions NSAID-induced ulcer: PPI: decrease calcium absorption, which puts patient at greater risk for osteoporosis; interferes with absorption of vitamin B12, iron, Mg; inhibits CYP2C19 which delays activation of clopidogrel; drugs that require an acidic environment to be absorbed such as antifungals H2RA: antacids, ethanol, warfarin, drugs that require acidic pH, drugs metabolized by CYP450; ranitidine has far less interactions than cimetidine Antacids: significant binding of other drugs (cations), should be taken 2-3 hours apart from other drugs; ACE inhibitors, ASA, NSAIDs, levothyroxine Compare cost and H. Pylori-induced ulcer: convenience All relatively cost-friendly and all have options that are covered Quad therapy is less convenient, but more effective than triple therapy (and efficacy is always more important) PPIs should always be taken before a meal NSAID-induced ulcer: PPI: daily or BID dosing 30 mins before meals; some require prescription and some are OTC; some are covered by ODB and some are not H2RA: daily or BID dosing (usually before bed); require prescription and available OTC; cheaper than PPIs Antacids: need to be taken almost every hour; less expensive than H2RAs and PPIs; OTC Mucosal protective agents: dosing QID; expensive; need to be taken with food DTP + drug Recommendation: recommendation + H. Pylori-induced: Bismuth quadruple therapy orally for 14 days, and continue PPI for 6 weeks duration after NSAID-induced: PO PPI for 6-8 weeks (in the workshop, we picked lansoprazole as the PPI) Notes: If patient is a child, famotidine (H2RA) can be used If patient is pregnant, avoid misoprostol at all costs If patient has penicillin allergy → go with bismuth quadruple therapy  GERD Drugs that can cause Aggravating factors that decrease lower esophageal sphincter disease Food: fatty foods, peppermint, chocolate, caffeine, garlic, onions, chili peppers Drugs: anticholinergics, Alcohol, barbiturates, Nicotine, Estrogen, Progesterone, Dihydropyridine calcium channel blockers (amlodipine), Theophylline, tetracycline have direct irritant effects, Not a cause of GERD but it can cause the symptoms Aggravating factors that cause direct esophageal mucosal irritation Food: spicy foods, orange/tomato juice, coffee Drugs: bisphosphonates, ASA, NSAIDs, Iron, KCl, ethanol, quinidine Medications that can worsen GERD by weakening or relaxing the esophageal sphincter leading to increased acid reflux include: Anticholinergics → Ex. Oxybutynin Tricyclic antidepressants → Ex. amitriptyline, doxepin, etc. Calcium channel blockers, statins, ACE inhibitors and nitrates used for high blood pressure and heart disease Narcotics → Ex. codeine Progesterone → Decreased lower esophageal sphincter pressure Sedatives or tranquilizers including benzodiazepines → Ex. Diazepam and temazepam Theophylline → Ex. Elixophyllin, Theochron Aspirin → direct irritant to the esophageal mucosa Risk Factors Conditions that can increase risk of GERD include: >40 years age more common in men and pregnancy cases presence of non-erosive reflux disease increase in western countries - fatty foods delaying gastric emptying family history infants bulging of the top of the stomach up into the diaphragm (hiatal hernia) pregnancy (hormonal changes) connective tissue disorders, like scleroderma delayed stomach emptying Factors that can aggravate acid reflux include: smoking obesity eating large meals or eating late at night eating certain foods (triggers) such as fatty or fried foods -> fatty foods delay gastric emptying drinking certain beverages, such as alcohol or coffee taking certain medications, such as aspirin Clinical Presentation Symptomatic (with or without tissue injury) Heartburn, regurgitation, belching Dysphagia (difficulty swallowing); Odynophagia (painful swallowing) Diagnosis based on typical symptoms and empiric trial of acid-suppressive therapy (done first)  if fail empiric: more invasive (but usually don’t have this referral to gastroenterologist) o endoscopy (ogd) o ambulatory pH monitoring o pillcam ESO Differential: Chest pain → need to make sure it’s nothing related to the heart Ask PT about any pain in the left arm or jaw Is it chest pain or is it dyspepsia? The risk factors for CVD and GERD are the same Cardiac risk factors: hyperlipidemia PUD → GERD tends to be correlated to having meals and it comes at night time when you lie down PUD isn’t as temporal, it is constant pain Why is drug therapy The main reason to treat GERD: required? Improve symptoms and quality of life not treating to prevent complications b/c it’s very rare (baret’s esophagus risk factor for cancer) not all pts with GERD have esophagitis (would need to scope; not done much unless persistent symptoms) can have bad esophagitis and no symptoms → Main point: not treating to prevent esophagitis because this correlation doesn’t exist Alarm symptoms: dysphagia painful swallowing heartburn + these symptoms (might be more malignant) Efficacy endpoints Reduce difficulty falling asleep due to indigestion within 1 week (goals of therapy) Reduce heartburn/burning sensation in throat within 1 week Reduce/prevent recurrence of symptoms (frequency/duration) throughout the duration of therapy Prevent complications of untreated GERD (Barett’s esophagus or esophageal adenocarcinoma) Therapeutic regimens Nonpharmacological therapy is considered both first line and adjunctive (3-4 reasonable Evidence based non-pharms: options) o Weight loss o Smoking cessation o Raising head of bedframe → increasing intraabdominal pressure o NO food before bed Pharms: o Antacids o H2 receptor antagonists (e.g. famotidine) o Proton Pump Inhibitors (e.g. pantoprazole, lansoprazole, esomeprazole, rabeprazole) o Motility Agents (dopamine antagonists–metoclopramide/domperidone) Compare efficacy PPIs are more effective than H2RAs, providing twice the healing rates for esophagitis and more successful long-term symptom relief In terms of efficacy, PPIs are shown to be the most effective for GERD compared to H2RAs in providing more rapid relief symptoms, twice the healing rates of esophagitis and prevention of recurrences. As such, they are considered to be the first line therapy in most GERD patients. - 83% improvement in symptoms vs 60-70% in h2ra vs 20% in antacids - motility usually used in combination -> if there is a GI motility issue and if PPIs not working alone. Domperidone: helps with motility and improves it but motility is not the only problem, contributing factor but not the major pathogenesis Antacids: for immediate relief not long-term: east effective for long-term, not healing esophagitis  Summary: BEST: PPI → reduce symptom, prevent reoccurrence, heal esophagitis Second: H2RA → if there is a GI motility issue and if PPIs not working alone. Worst: Antiacids → limited to use for mild symptoms (does not heal esophagitis or prevent recurrences) not for long-term use ONSET: BEST: Antacids/alginates and H2RAs provide rapid immediate relief (for “on demand” use–just not PPI) PRN use WORST: PPI’s - take 1-4 days to work (not good if immediate relief is needed) NOT short term Compare toxicity Antacids aluminum and calcium based antacids = constipating magnesium = more for diarrhea balance aluminum and magnesium in the antacids PPI generally well tolerated long term use we are more worried about PPIs are overused in the community. For GERD, some people may be on the medication for a long time, so it is worrisome. For PUD it is only used for a short time (around 14 days) pneumonia and C diff are associated effects absorption of iron, b12, Ca+ o anemia (iron/b12) o resulting in osteoporosis (ca+) H2RA: well tolerated in general BUT don’t use cimetidine due to unique side effects and also QID (inconvenient) o more CNS effects too o enlargement in breasts–not good in men Compare drug In terms of drug interactions, PPIs are the most at risk of drug interaction since they interfere with CYP3A4 interaction and CYP2C19 metabolism and therefore potentially many drugs compared to H2RAs. However H2RAs do interact with RD’s current medication, antacid. PPI omeprazole - cyp2c19 - decreases absorption of drugs requiring acid medium (clopidogrel) Motility agents - CYP3a4 and not used with Parkinson disease (metoclopramide) Antacid - decreases absorption of antibiotics and irons Compare cost and COST: convenience Both PPIs and H2RAs have expensive and cheap options that are available OTC (not covered) or Rx (might be covered from work). Antacids and H2RAs are cheapest, PPIs are second CONVENIENCE: PPI: daily → most convenient H2RA: BID or QID → second convenient ANtiacids: around the clock → least convenient DTP + drug NOTE: recommendation + Famotidine (H2RA) can be used in children duration Avoid misoprostol if pregnant Normal treatment would be: Any PPI 30 mins before breakfast once a day for 8 weeks Recommend stop taking antacids since they are ineffective - however if symptomatic, can take antacids PRN for 2-3 days until PPIs reach maximal efficacy  Osteoarthritis Drugs that can cause There aren’t any drugs that directly cause osteoarthritis, however, a number of drugs can lead to joint disease aches and back pain. Patients on steroids for a long time have reduced cartilage in the knee so it’s contraindicated in OA Risk Factors 1. Obesity – more compression on joints, 1 kg increase in weight increases your chance of OA by 10% 2. Age > 60 years 3. Sex – more in men under 50 yo due to sports. Hip, knee and hand OA more in females > 50 yo 4. Occupation 5. Sports 6. History of joint trauma 7. Genetic predisposition (weak) Clinical Presentation Asymmetrical joint pain* Localized pain, deep aching** Pain worsens with activity Morning stiffness that lasts < 30 mins and is hard to get out of bed Related to weather Limited joint motion Limits daily activities à morbidity and disability Diagnosis Physical Asymmetrical: monoarticular or oligoarticular Commonly the proximal and distal interphalangeal joints Not associated w/ tenderness Diagnostic Imaging X-rays – looking at joint space narrowing and osteophyte formation → doesn’t help with monitoring because only shows changes when severe damage has occurred Goal of diagnosis 1. Primary vs. secondary Primary No identifiable cause Localized OA vs generalized OA Known cause Secondary Due to RA, trauma, metabolic disorder or congenital factors 2. Severity 3. Response to previous therapy Differential diagnosis OA vs RA → no systemic involvement, no fever or malaise, more localized OA vs gout → stiffness in morning, gout is mainly in lower extremities, test uric acid levels, gout is debilitating sharp pain but OA is localized deep aching pain OA vs OP → OA risk factor is high BMI, OP risk factor is low BMI Why is drug therapy OA bad → increased morbidity and disability required? Therapeutic regimens (3-4 NPCT delay progression, PCT manage pain reasonable options) Management starts with NPCT and maintained as adjunctive For hand or knee – first line is topical analgesia For hip, hand and knee – first line is oral NSAIDs NPCT PT education  Diet (weightloss) Exercise (swimming, cycling, tai chi) Physical and occupational therapy Surgery Assistive devices to minimize falls and fractures PCT 1. Oral Analgesics · Acetaminophen · Tramadol – no working · Opioids 2. NSAIDs (for all OA) · Ibuprofen · Naproxen 3. Topical Analgesics (hand and knee) · Diclofenac · voltaren · capsaicin 4. Adjunct therapy – duloxetinefor kneeor if PT is also depressed and/or has neuropathic pain 5. Intra-articular injections (mainly hip and if necessary for knee) 6. Nutritional Supplements → no goodo 7. Glucosamine/Chondroitin → no goodo Compare efficacy Topical · Similar to oral NSAIDs · Long time for pain relief Oral analgesic Acetaminophen: not as effective as oral NSAIDs, was shown to be beneficial in the short term use but ineffective long term. Oral NSAID Provides better pain relief compared to acetaminophen - it further reduces inflammation which reduces pain stimulated by nociceptors Opioid Tramadol Not very efficacious, never used in monotherapy Corticosteroid or hyaluronic acid (injection) Recommended for hip osteoarthritis, beneficial at alleviating pain and stiffness by osteoarthritis. it also reduces inflammation Glucosamine and chondroitin Not effective in treatment of osteoarthritis Compare toxicity Topical No systemic adverse effect Local burning and stinging more local adverse reactions Oral analgesic Less risk of gastrointestinal and CVD AE over oral NSAIDs Less risk of gastrointestinal and CVD AE over oral NSAIDs  Oral NSAID NSAIDS induce ulcers, renal complications, increased risk of CV events, especially with COX-2 higher risk for GI, renal and CV adverse effects i.e. MI, stroke, HF, HTN Opioid Dependence, N&V, seizure Duloxetine Nausea, dry mouth, constipation, IA Inj Hyperglycemia, edema, elevated blood pressure, flushing, dyspepsia and hypercortisolism Inj site infection max 3 injection/joint/year Glucosamine and chondroitin Nausea and diarrhea, constipation or hartburn Compare drug interaction Topical Don’t use other topical analgesics Oral analgesic Acetaminophen and alcohol don’t mix and it is hard on liver Oral NSAID COX-2 inhibitors have less GI risk then NSAIDS Increased risk of bleeding with anticoagulants (e.g., warfarin) or antiplatelet drugs (e.g., clopidogrel) because of CYP 2C9 Beta blockers and anti-hypertensives Opioid Loss of seizure control due to CYP 3A4 Drugs that increase serotonin Duloxetine Don’t use with MAOI or CYP 1A2 inhibitors IA Inj Interaction with strong CYP3A4 inhibitors with triamcinolone acetonideInteraction with strong CYP3A4 inhibitors with triamcinolone acetonide Glucosamine and chondroitin → no known interactions Compare cost and Injections are less convenient cause you have to go to the physician convenience Oral agents are cheaper and OTC DTP + drug NPCT like weight loss + exercise recommendation + Celecoxib 100 mg PO BID or 200 mg PO daily and continue/initiate PPI Rabeprazole 20 mg po duration once daily IA injection of methylprednisolone (20-80mg) for a large joint every 3 months Algorithm First line therapies (this doesn’t include the acetaminophen initially given) Oral NSAIDs, intra- articular corticosteroids (for hip mainly), topical NSAIDs (for knee and hands) o NSAIDs are toxic but more efficacious These are first line therapies because they are the most efficacious Major toxicities of oral NSAIDS: ulcers, CV events (MI & stroke with cox2 and with all NSAIDS they can exacerbate hypertension and thrombosis), renal (fluid retention and exacerbate HF)  Topical NSAIDs toxicities: mostly local and much less of systemic side effects Intra-articular corticosteroids - hyperglycemia (initial flare at injection site after injection) - high blood pressure o Less convenient - need to go to physician o Want to monitor glucose** (even for diabetes) Second line agents Tylenol (acetaminophen) because its like a placebo (even though they are safe they are less effective) - no better than a placebo - only short term; ineffective long term Tramadol, duloxetine -second line because limited evidence of efficacy, safety risk o Serotonin syndrome, steven johnson’s syndrome  GOUT Drugs that can cause Drugs that precipitate gout disease Diuretics, levodopa, cyclosporine, niacinamide, low dose salicylates, ACE inhibitors → reduce renal clearance of uric acid Aspirin (acetylsalicylic acid raises uric acid in the blood?) Cytotoxic drugs (i.e., chemo) → increase uric acid production through cell lysis Other factors Drugs that precipitate attacks via other mechanisms: alcohol Alcohol may contribute - increase purine production - increase [uric acid] Precipitants of acute attacks include acute illness, surgery, trauma, alcohol, high purine diet and drugs Risk Factors Risk factors: (factors that increase the risk of developing gout) Male sex (especially over 40 years old) → but risk evens out for women after menopause People that consume large amounts of alcohol People that consume lots of foods high in purines and products containing high-fructose corn syrup Obesity Previous trauma to the toe Other metabolic syndromes such as diabetes Precipitating factors: (factors that trigger gout) Stress Trauma Infection Surgery Alcohol Sugary food/beverages Medications (as noted above) Increased uric acid Clinical Presentation Signs and symptoms: Acute inflammatory monoarthritis (excruciating pain and inflammation at the joint) → RAPID onset of intense pain Onset usually at night or early morning (because water is reabsorbed from joint space, creating a super-saturated solution of monosodium urate) Duration is typically 3-14 days if left untreated More lower extremity involvement 85% of initial attacks involve a single joint Any joint can be involved (ankles, knees, wrists, fingers, elbows), but most often it is the big toe Most common presentation: fever, intense pain, erythema, warmth, swelling, and inflammation of involved joints Usually only involved one main joint Diagnosis Officially based on visualization of crystals in joint fluid by aspiration But, since the joint is in so much pain, we do not want to stick a needle in it. Instead, we use the “clinical triad”: o Inflammatory monoarthritis o Elevated uric acid levels o Response to treatment (usually colchicine) Lab tests: high UA, leukocytosis Long-standing gout: x-ray asymmetric swelling is unremarkable in comparison to someone experiencing an initial acute gout attack We diagnose based on: clinical presentation and high UA levels Why is drug therapy If left untreated, gout attack will resolve in 3-14 days on its on required? However, patient will continue to be in excruciating pain for several days, therefore we want to treat in order to:  o Improve quality of life of patient, i.e., reduce pain o Prevent complications, i.e., severe degenerative arthritis, urate or uric acid nephropathy, infection We also want to prevent recurrence of gout by implementing non-pharm strategies Efficacy endpoints Improve pain within 24-48 hours, with resolution of attack within 1 week (goals of therapy) Reduce redness, pain, swelling, inflammation within 1 week Improvement of limping within 1 week ONLY if non-pharms are part of our intervention: prevent recurrent gout attacks within 1 year → as this is not tied to the drugs prescribed to terminate an acute attack Therapeutic regimens Acute gout: (3-4 reasonable NSAIDs options) Oral colchicine Corticosteroids (oral, intramuscular, intra-articular) Chronic gout: Xanthine oxidase inhibitors (allopurinol for prophylaxis, febuxostat) Uricosurics (probenecid - not available in Canada) Compare efficacy Acute gout: All three classes (NSAIDs, colchicine, and corticosteroids) will be effective as a first-line therapy → all equally effective Colchicine needs to be started within 36 hours of onset of attack to be effective NSAIDs are the main treatment for acute attacks (not one specific NSAID → depends on patient and if there are any contraindications) due to their ability to reduce pain and inflammation quickly Corticosteroids have risk of rebound, therefore may need a longer tapering off period NSAIDs and colchicine have a faster onset (few hours) and max effect within a day; corticosteroids such as prednisone take longer to have effect, therefore not ideal since we are trying to reduce pain quickly For severe cases, we can use a combination of these therapies Chronic gout: Efficacy of allopurinol and febuxostat are similar. At higher doses, febuxostat is more effective, but it also has a lot more serious side effects, so we avoid it Compare toxicity Acute gout: In this case, we are only concerned about short term side effects (therefore do not talk about high- dose NSAID-induced ulcers) Oral NSAIDs are associated with stomach upset, need to consider dosing adjustments in kidney failure Corticosteroids can affect blood pressure and blood sugar levels (important to monitor for diabetics) Injections have more local side effects than systemic, i.e., swelling and pain at injection site Colchicine has the lowest risk of side effects if used at low doses. At high doses, colchicine has been associated with headache, nausea, and cramping Chronic gout: Allopurinol: rash, hypersensitivity reactions common in certain ethnicities → can lead to severe rash Febuxostat: black box warning indicating increased risk of stroke and MI Compare drug Acute gout: interactions NSAIDs: increased risk of bleeding if a patient is on anticoagulant (i.e., warfarin) or antiplatelet agent (i.e., clopidogrel); may decrease effect of antihypertensive medications; if patient is on lithium, may alter water/sodium balance; if patient is also taking SSRI, risk of GI bleeding Colchicine: increase plasma levels of HMG Co-A reductase inhibitors; if patient is taking a CYP3A4 inhibitor (antiretrovirals, clarithromycin, erythromycin, itraconazole, ketoconazole, verapamil) or Pgp inhibitors (i.e., cyclosporine) → decrease dose of colchicine; interaction with grapefruit juice; decreased efficacy of certain antihypertensive drugs Corticosteroids: significant interaction with warfarin, CYP3A4 inhibitors and inducers affect plasma concentrations of corticosteroids, they increase blood sugar levels Injectable corticosteroids: less likely to have drug interactions because they act locally  Chronic gout: Allopurinol: using with ACE inhibitors increases hypersensitivity reactions such as SJS; antacids reduce absorption of allopurinol; elevates carbamazepine serum concentrations Febuxostat: SERIOUS toxicity reactions associated with azathioprine and mercaptopurine; be careful when administering in combination with colchicine or NSAIDs → may require lower dose of febuxostat Compare cost and Acute gout: convenience NSAIDs are OTC, which is more convenient whereas corticosteroids and colchicine require a prescription. However, if you buy NSAIDs OTC, they will not be covered by insurance Dosing for NSAIDs is simpler than for colchicine and corticosteroids All have oral options (and we would not give an injection in this case because it would be too painful for the patient) Overall fairly cheap, therefore cost is not a determining factor in this case Chronic gout: Both allopurinol and febuxostat are once daily dosing and dose can be titrated up Allopurinol is much cheaper than febuxostat Allopurinol is covered by ODB and febuxostat has some off-formulary interchangeable DTP + drug Acute gout: recommendation + Colchicine 1.2 mg STAT and on day 3, start 0.6 mg daily or 0.3 mg BID for 4 days (but this only duration works if attack started less than 36 hours ago) Or naproxen 750 mg STAT and 250 mg TID for 7 days Recommend non-pharms such as weight loss, healthy eating habits, decreasing alcohol consumption, smoking cessation Chronic gout: Allopurinol 50-100 mg daily, then titrate up by 50-100 mg every 2-5 weeks for a max of 800 mg daily Can be given along with low-dose naproxen or colchicine Decrease dose if they have renal impairment (CLcr below 30 mL/min)  Osteoporosis Drugs that can cause Glucocorticoids (> 3 months) - 12% bone loss in the first year of using prednisone or disease hydrocortisone 7.5 mg but can also be due to chronic use of other glucocorticoids between 2.5 and 7 mg o ↓ calcium absorption → body takes calcium from bone by ↑ bone resorption and ↓ bone formation → ↓ BMD and ↑ fracture risk Anti-androgen: decrease sex hormone production → ↓ BMD and ↑ fracture risk o Gonadotropin-releasing hormone agonist – prostate cancer Aromatase inhibitors: ↓ estrogen → ↓ BMD and ↑ fracture risk o Typically given for breast cancers Less common: PPIs, anticonvulsants, glitazones (used for diabetes), progesterones (for HRT and contraception), SGLT2 inhibitors – cause natriuresis and diuresis Risk Factors in Low body weight or major body weight loss (more than 10%) → low BMI > 50 yo men Post-menopausal women Prior fractures History of falls Family history Hyperthyroidism or hyperparathyroidism → need to assess PTH levels Chronic kidney or liver diseases Multiple myeloma Lifestyle: sedentary, smoking, excess alcohol, low Ca/Vit D intake Clinical Presentation Height loss due to vertebral or compression fractures → loss of 2 cm or more over 3 years Low BMD Fragility fractures Back pain Kyphosis → dysphagia Diagnosis Difficult to identify unless a fracture has already occurred so regular screenings are done to identify and manage modifiable risk factors Use diagnostic imagingto assess for lateral, thoracic or lumbar fractures (especially if PT lost height) Biochemical tests: Calcium, TSH, Cr, 25-OH-vit D, SPEP BMD: T-score and Z-score o -1 ≤ T-score ≤ -2.5 → osteopenia o T-score ≤ -2.5 → OP o T- score is your BMD compared to a young healthy adult of the same sex o Z-score is your BMD compared to same sex and age Presence of fragility fracture (i.e. injury from a fall from standing height) brings score lower and is indicative of severe OP Physical examinations for vertebral fractures o Height loss o Rib to pelvis distance ≤ 2 fingers o Occiput-to-wall distance > 5 cm → asses for kyphosis o Get-Up-and-Go Test → assess fall risk Fracture risk assessment o 10-year fracture-risk tools: CAROC → age + sex + T-score at femoral neck from BMD Results: low 20% risk If PT is in low and/or moderate risk you look at other risk factors FRAX (country-specific) → age + sex + BMD + clinical risk factors o 1-year fracture-risk tool: Fracture Risk Scale (FRS) → mainly for LTC residents Differential diagnosis OP vs multiple myeloma → SPEP test to rule out malignancies  Metastatic bone disease Osteomalacia (low matrix to mineral due to nutrient deficiency) Why is drug therapy Increases the risk of future fractures →Break your hip once and you need a cane, break it again required? you neeed a walker, break it again and you need a wheelchair, break it again and you’re bed bound → so huge impact on their quality of life ↑ Risk of: Hospitalization, LTC, Death, and Subsequent fracture / falls → if injure, then lack of mobility, and recurrent hip fractures leads to progressive mobility decreases Impact on quality of life: Loss of confidence Fear of falling