UNINTENDED EFFECTS OF MEDICATIONS & IMPLICATIONS FOR PHYSIOTHERAPY ASSESSMENT … · 2019-09-26 ·...
Transcript of UNINTENDED EFFECTS OF MEDICATIONS & IMPLICATIONS FOR PHYSIOTHERAPY ASSESSMENT … · 2019-09-26 ·...
UNINTENDED EFFECTS OF MEDICATIONS & IMPLICATIONS
FOR PHYSIOTHERAPY ASSESSMENT AND TREATMENT
Cheryl A Sadowski, B.Sc(Pharm), PharmD, BCGP, FCSHPFaculty of Pharmacy and Pharmaceutical Sciences
University of Alberta
Allyson Jones, MScPT, PhD, Dept Physical TherapyFaculty of Rehabilitation Medicine
University of Alberta
Ziqi Wang, PharmD StudentFaculty of Pharmacy & Pharmaceutical Sciences
University of Alberta
Presenters
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Learning Objectives1. Identify musculoskeletal adverse effect(s) and associated risk factors for
adverse effects of the following medications:■ Fluoroquinolones (FQs)■ Statins■ Finasteride■ DPP-4 inhibitors (DPP-4i)
2. Identify the adverse effects and contributing factors to fall risk of the following medication classes:
■ Antidepressants■ Benzodiazepines■ Antipsychotics■ Opioids
3. Recognize the clinical presentation of drug-induced adverse effects 4. Recognize the importance of asking for medication history5. Determine when referral to another medical professional is necessary
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Introduction■ Physiotherapists in Alberta have
expressed an interest in learning about medications.
■ Knowledge gap: – How to identify and recognize the
clinical presentation of medication-related effects
■ Bridging the knowledge gap:– Continuing education for
physiotherapists on effects of medications that may contribute to musculoskeletal complaints and disability
Image source: http://www.compendian.com/2015/03/can-you-fill-the-knowledge-gap-when-you-have-unexpected-vacancies
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Webinar Outline■ Module 1: Musculoskeletal Adverse Effects of Medications
– 1a: Tendinopathies– 1b: Myalgias and Arthralgias
■ Module 2: Falls and Psychotropic Medications– 2a: Falls and Antidepressants– 2b: Falls and Benzodiazepines– 2c: Falls and Antipsychotics
■ Module 3: Overview of Opioids
Image source:https://www.goodrx.com/blog/tooth-infection-symptoms-treatments-antibiotics/https://www.pinclipart.com/pindetail/TxTbTw_neck-clipart-muscle-ache-muscle-and-joint-pain/https://www.nurseathome.com.au/services/fall-risk-icon-2/
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Module 1a: Tendinopathies
CASE 1:
■ Client: Cathy, 45y F
■ Occupation: sales clerk
■ HPI:
– severe & sharp pain along posterior left heel, dull pain at rest
– pain started abruptly, most severe when weight bearing
– denies previous history of heel pain, recent trauma, injury or strenuous exercise
■ Examination:
– extreme tenderness of left Achilles tendon, most prominent with plantar flexion
– tendon is warm, red, and stiff
Image source: https://heelpaincenteroftampabay.com/achilles-tendonitis/
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Module 1a: Tendinopathies
CASE 1■ After performing the Thompson test to rule out the possibility of
tendon rupture, how would you proceed?
a) give ultrasoundb) refer for imagingc) ask for complete medication historyd) recommend over-the-counter (OTC) pain medication(s)e) all of the above
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Module 1a: Tendinopathies
CASE 1■ After performing the Thompson test to rule out the possibility of
tendon rupture, how would you proceed?
a) give ultrasoundb) refer for imagingc) ask for complete medication historyd) recommend OTC pain medication(s)e) all of the above
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Module 1a: TendinopathiesCASE 1Medication History:■ Achilles Tendonitis:
– ibuprofen (Advil®): 400mg every 6 hours as needed for pain (started yesterday)■ Asthma:
– budesonide-formoterol (Symbicort®): 100/6mcg 2 puffs twice daily x 10 years– salbutamol (Ventolin®): 200mcg 1-2 puffs every 4-6 hours as needed x 12
years■ Urinary Tract Infection:
– ciprofloxacin (Cipro®): 500mg twice daily (finished 3/5 days)
Image sources:https://www.londondrugs.com/advil-extra-strength-liqui-gels---80s/L4322939.htmlhttps://www.ukmeds.co.uk/symbicorthttps://www.indiamart.com/proddetail/salbutamol-inhalers-15073306312.htmlhttps://www.webmd.com/drugs/2/drug-1124-93/cipro-oral/ciprofloxacin-oral/details
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Module 1a: Tendinopathies
CASE 1
■ Which of the medications could be contributing to Cathy’s Achilles tendonitis?
a) ibuprofen (Advil®)
b) budesonide/formoterol (Symbicort®)
c) salbutamol (Ventolin®)
d) ciprofloxacin (Cipro®)
e) Cipro® and Symbicort®
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Module 1a: Tendinopathies
CASE 1
■ Which of the medications could be contributing to Cathy’s Achilles tendonitis?
a) ibuprofen (Advil®)
b) budesonide/formoterol (Symbicort®)
c) salbutamol (Ventolin®)
d) ciprofloxacin (Cipro®)
e) Cipro® and Symbicort®
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Module 1a: Tendinopathies(Fluoro)Quinolones Statins Corticosteroids Aromatase inhibitors
Example
medications
Oral:moxifloxacin (Avalox®)norfloxacin (Noroxin®)
Oral and IV:ciprofloxacin (Cipro®)levofloxacin (Leviquin®)ofloxacin (Floxin®)
Oral:
atorvastatin (Lipitor®)
lovastatin (Mevacor®)
pravastatin (Pravachol®)
rosuvastatin (Crestor®)
simvastatin (Zocor®)
Oral:
• dexamethasone (Decadron®)
• methylprednisolone (Depo-
Medrol®)
• prednisone (Deltasone®)Inhaled (single entity):
• beclomethasone (QVAR®)
• ciclesonide (Alvesco®)
Inhaled (combination products):
• budesonide (Symbicort®)
• fluticasone (Advair®, Breo Ellipta,
Trelegy Ellipta)
• mometasone (Zenhale®)
Oral:
anastrozole (Arimidex®)
exemestane (Aromasin®)letrozole (Femara®)
Indication(s) Infections caused by
susceptible Gram-
positive and Gram-
negative bacteria
(generally respiratory or
urinary infections).
Dyslipidemia, vascular
protection in coronary
artery disease and/or
acute coronary syndrome
Oral: adrenal insufficiency, chronic
allergy and inflammatory conditions
(gout rheumatoid arthritis)
Inhaled: chronic respiratory diseases
(asthma, COPD)
Hormone treatment for
breast cancer in
postmenopausal women.
Table 1a: Medication classes associated with tendinopathies
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(Fluoro)Quinolones Statins Corticosteroids Aromatase inhibitors
Median
time of
injury
onset
9 days (reported as early as
2 hours after initiation and
as long as 6 months
following discontinuation)
8-10 months 4 months-several years 2 weeks-19 months
Risk
factors
Age > 60 years
Concomitant glucocorticoid
therapy
Pre-existing tendinopathy
Renal failure or
hemodialysis
Renal transplantation
Strenuous physical activities
Age > 80 years
Strenuous physical activity
History of tendinopathy
Concomitant quinolone therapy
Long-term use
Concomitant quinolone
therapy
History of prior
chemotherapy
Obesity
Prior menopausal
hormone replacement
therapy
Reported
sites
involved
Achilles tendon (90% of
cases)
Other (10% of cases):
rotator cuff, extensor carpi
radialis brevis, finger and
thumb flexors, quadriceps
Achilles tendon (52-56% of
cases)
Other (44-48% of cases): rotator
cuff, distal biceps, extensor carpi
radialis brevis, finger extensors
and flexors, quadriceps
Achilles tendon
Patellar tendon
Quadricipital tendon
Hand and wrist tendons
Incidence 0.1-0.4% 2.1% Not reported Not reported
Module 1a: TendinopathiesTable 1a: Medication classes associated with tendinopathies (adapted from Kirchgesner et al.)
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Module 1a: TendinopathiesFluoroquinolone-Induced Tendinopathy ▪ Health Canada Safety Review (2017):
- Triggered by FDA Safety Review on fluoroquinolones
- Case reports on systemic fluoroquinolones (IV and oral) have described persistent and disabling tendinopathy lasting >30 days post-discontinuation
▪ Management:- Discontinue fluoroquinolone(s) if
tendon pain, swelling, or inflammation are present
- Avoid exercise and use of the affected area
Image source: Health Canada
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Module 1a: Drug-Induced Tendinopathies
CASE 1 WRAP-UP▪ Cathy is experiencing tendonitis that is likely drug-
induced:
✔ taking a fluoroquinolone antibiotic (ciprofloxacin; Cipro)
✔ using a corticosteroid-containing inhaler (budesonide/formoterol; Symbicort)
▪ Encourage Cathy to see her prescriber (pharmacist, physician or nurse practitioner) for immediate discontinuation of fluoroquinolone and switching to a different antibiotic to finish her course of therapy
▪ Continue with regular physiotherapy treatment (eg. pain management) and re-assess in 1 month
Image sources:• https://www.ukmeds.co.uk/symbicort• https://www.webmd.com/drugs/2/drug-
1124-93/cipro-oral/ciprofloxacin-oral/details
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Module 1b: Myalgias and Arthralgias
CASE 2■ Client: Michael (58yo M)■ Occupation: accountant■ HPI:
– new onset of dull pain in thighs – thighs feel heavier, sore and cramp
especially when climbing stairs– no recent illness, fever, muscle trauma, or
strenuous activity■ Examination:
– diffuse tenderness in thigh muscles– no tenderness, swelling or redness in knee
or ankle joints
Image source: https://www.nextavenue.org/knee-pain-gout-lyme-arthritis/
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Module 1b: Myalgias and Arthralgias
CASE 2:
■ PMHx:– Osteoarthritis:
■ acetaminophen (Tylenol®): 500 mg tablets every 6 hours when needed x 2 years
■ diclofenac (Voltaren®): 2% cream applied twice a day on both knees x 2 years– Diabetes:
■ sitagliptin (Januvia®): 25mg once daily x 1 year– BPH:
■ finasteride (Proscar®): 5 mg once daily x 1 year– High cholesterol:
■ atorvastatin (Lipitor®): 40mg once daily for primary prevention of cardiovascular events, started 1 month ago
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Module 1b: Myalgias and Arthralgias
CASE 2
■ Which of the medication(s) could be contributing to Michael’s myalgia?
a) acetaminophen (Tylenol®)
b) atorvastatin (Lipitor®)
c) diclofenac (Voltaren®)
d) finasteride (Proscar®)
e) sitagliptin (Januvia®)
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Module 1b: Myalgias and Arthralgias
CASE 2
■ Which of the medication(s) could be contributing to Michael’s myalgia?
a) acetaminophen (Tylenol®)
b) atorvastatin (Lipitor®)
c) diclofenac (Voltaren®)
d) finasteride (Proscar®)
e) sitagliptin (Januvia®)
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Module 1b: Myalgias and Arthralgias
Statin Associated Muscle Symptoms (SAMS) ■ Myopathy:
– May include muscle pain, aching, fatigue, weakness or stiffness
■ Incidence: – 1-5% in clinical trials and up to 25% in
observational studies■ When does SAMS occur?
– Usually <1 month of initiating statin therapy or after a recent dose increase
■ Which muscle groups are affected?– Bilateral large proximal muscle groups (e.g.
shoulders, lower back, gluteus muscles, quadriceps)
Image source: https://www.healthline.com/health/high-cholesterol/natural-statins
Module 1b: Myalgias and Arthralgias
Statin Associated Muscle Symptoms (SAMS)
Statins most likely to
cause SAMS
Atorvastatin (Lipitor®)
Lovastatin (Mevacor®)
Simvastatin (Zocor®)
Medications involved in
CYP3A4 interactions
with statins
Anti-infective medications (eg. azole antifungals, macrolide antibiotics)
Cardiac medications (eg. antiarrythmics, calcium channel blockers)
Cholesterol lowering medications (eg. fibrates)
HIV medications (eg. protease inhibitors)
Other medications (eg. DPP-4 inhibitors, warfarin)
Non-medication
CYP3A4 interactions
with statins
Excessive alcohol
Grapefruit juice
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Module 1b: Myalgias and Arthralgias
Statin Associated Muscle Symptoms (SAMS)
Modifiable risk factors
• Higher dose of statin• Reduced muscle mass• Reduced body mass index• Hypothyroidism• Diabetes mellitus• Drug interactions
Non-modifiable
risk factors
• Age > 80 years• Female• Physical disability• History of pre-existing or unexplained
muscle aches/joint pains• Family history of myopathy
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Module 1b: Myalgias and ArthralgiasStatin Associated Muscle Symptoms (SAMS) ■ Although rare, myalgia may be a symptom of rhabdomyolysis■ Suspect rhabdomyolysis and send client to emergency when “classic
triad” of symptoms present.
Muscle pain (mild to severe)
Weakness and swelling of affected
muscle(s)
Dark, tea colored (brown or black)
urine
Rhabdomyolysis
Image source: https://depositphotos.com/117690064/stock-photo-hospital-emergency-sign.html
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Module 1b: Myalgias and ArthralgiasCASE 2 WRAP-UP■ Michael is likely experiencing statin-induced myalgia
– atorvastatin 40mg was started <4 weeks ago
■ Michael has the following risk factors for statin-induced myalgia:
– Type II diabetes mellitus
– Pre-existing joint pain from osteoarthritis
– Potential drug interaction between sitagliptin (Januvia®) and atorvastatin
■ Refer Michael to prescriber for switching to different statin that does not interact with sitagliptin (eg. rosuvastatin)
Image sources:https://www.zavamed.com/uk/lipitor.htmlhttp://rxmedicaments.com/en/57-januvia-100mg-tablets.html
CYP3A4
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Module 1b: Myalgias and Arthralgias
Finasteride Associated Muscle Adverse Effects■ Finasteride (Proscar®/Propecia® ) is an oral
medication typically used for benign prostatic hypertrophy (BPH) and less frequently for androgenic alopecia
■ Health Canada Safety Review (2017): – Case reports have described muscle
disorders including myalgia, weakness, atrophy and stiffness
■ Management– clients presenting with myalgia or muscle
weakness following finasteride exposure should be referred to medical professional for alternative drug therapy
Image source: http://www.sturology.com.au/benign-prostatic-hyperplasia-bph/
Image source: http://2018.igem.org/Team:NYMU-Taipei/Description
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Module 1b: Myalgias and Arthralgias
DPP-4 Inhibitor Associated Arthralgia■ Dipeptidyl peptidase-4 inhibitors (DPP4i) is a class of oral
glucose-lowering drugs used in type 2 diabetes mellitus. – Examples: sitagliptin (Januvia), saxagliptin (Onglyza),
linagliptin (Trajenta)■ Health Canada Safety Review (2017):
– Case reports linking DPP4i to severe, disabling arthralgia within >30 days of initiation
– Some cases occurred in those with gout, rheumatoid arthritis, Crohn’s disease or obesity
■ Management– Monitor for arthralgia in clients who are predisposed
to or have pre-existing joint conditions (see above)– Refer to prescriber for discontinuation if such cases
arise
Image sources: https://www.ukmeds.co.uk/trajentahttps://www.ukmeds.co.uk/onglyzahttp://rxmedicaments.com/en/57-januvia-100mg-tablets.html
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Module 2: Falls and Psychotropic Drugs
CASE 3■ Client: Edith (66yo F) ■ HPI:
– nearly had a fall when walking down steps of her front entrance
– felt dizzy and lightheaded (resolved after sitting for 5 minutes)
– no injuries and no previous history of falls– when sitting, BP ~130/80mmHg – when standing, BP ~110/70mmHg
■ Ambulation:– mobilizes independently without mobility aids– no pre-existing gait or balance impairment Image source:
https://www.hgtv.com/design/make-and-celebrate/handmade/the-dos-and-don-ts-of-painting-concrete-steps
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Module 2: Falls and Psychotropic Drugs
CASE 3■ PMHx:
– Major Depressive Disorder: ■ escitalopram (Cipralex®): 20mg once daily x 5 years
– Generalized Anxiety Disorder: ■ lorazepam (Ativan®): 1mg once daily as needed (3-4x/week) x 5
years– Insomnia:
■ amitriptyline (Elavil®): 10mg daily at bedtime (started 1 week ago)
Image sources:https://www.drugs.com/escitalopram-images.htmlhttps://www.innovicares.ca/en/cipralexhttps://www.myanxietymeds.com/product/ativan/https://onhealthy.net/product/elavil/https://www.pharmacy-xl.com/antidepressants.html
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Module 2: Falls and Psychotropic Drugs
CASE 3
■ What are some of Edith’s risk factors for a fall?a) age >65yob) amitriptyline (Elavil®)c) escitalopram (Cipralex®)d) lorazepam (Ativan®)e) all of the above
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Module 2: Falls and Psychotropic Drugs
CASE 3
■ What are some of Edith’s risk factors for a fall?a) age >65yob) amitriptyline (Elavil®)c) escitalopram (Cipralex®)d) lorazepam (Ativan®)e) all of the above
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Module 2: Falls and Psychotropic Drugs
“Psychotropic drugs such as benzodiazepines, certain antidepressants and antipsychotics should be avoided as first-line treatment options for seniors in most situations because of their potential to increase the risk of falls, fractures and cognitive impairment.”
– Canadian Institute of Health Information (CIHI, 2016)
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Module 2a: Falls and AntidepressantsSelective Serotonin Reuptake Inhibitors
(SSRIs)
Tricyclic Antidepressants
(TCAs)
Examples • citalopram (Celexa®)
• escitalopram (Cipralex®)
• sertraline (Zoloft®)
• amitriptyline (Elavil®)
• doxepin (Sinequan®)
• nortriptyline (Aventyl®)
Health Canada
Use(s)
Major depressive disorder, obsessive
compulsive disorder, anxiety & panic
disorders
Major depressive disorder, insomnia
Off-label Use(s)
Chronic fatigue syndrome, fibromyalgia Fibromyalgia, neuropathic pain
Fall Risk Odds
Ratio All antidepressants: OR = 1.57 (95% CI 1.43-1.74)
SSRIs: OR = 1.57 (95% CI 1.85-2.20)
TCAs: OR = 1.41 (95% CI 1.07-1.86)
Adverse Effects
Contributing to
Fall Risk
CNS effects: insomnia with increased
daytime drowsiness, potential to cause
movement disorders
• CNS effects: sedation, confusion
• Cardiac effects: orthostatic hypotension, rhythm
and conduction disturbances
• Anticholinergic effects: blurred vision, dizziness
Table 2a: Association of antidepressants with fall risk in older adults >60 years
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Module 2a: Falls and Antidepressants
Which neurotransmitter(s) is/are affected by SSRIs?a) Dopamineb) Serotoninc) Norepinephrined) Serotonin and dopaminee) Serotonin and norepinephrine
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Module 2a: Falls and Antidepressants
Which neurotransmitter(s) is/are affected by SSRIs?a) Dopamineb) Serotoninc) Norepinephrined) Serotonin and dopaminee) Serotonin and norepinephrine
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Module 2b: Falls and Benzodiazepines
Benzodiazepines (BZDs)
Example BZDs Short acting (<12 hours):
alprazolam (Xanax®)
oxazepam (Serax®)
temazepam (Restoril®)
Intermediate acting (12-24h):
bromazepam (Lectopam®)lorazepam (Ativan®)
Long acting (>24 hours):
clonazepam (Rivotril®)diazepam (Valium®)nitrazepam (Mogadon®)
Indication(s) Anxiety and panic disorders, insomnia, sedation, seizure disorders, alcohol withdrawal
Off-label use(s) Agitation, restless legs syndrome, muscle spasticity
Fall Risk Odds
Ratio All BZDs: OR = 1.57 (95% CI 1.43-1.74)
Short & intermediate-acting BZDs: OR = 1.27 (95% CI 1.04-1.56)
Long-acting BZDs: OR = 1.81 (95% CI 1.05-3.16)
Adverse Effects
Contributing to Fall
Risk
CNS effects: dizziness/vertigo, sedation, balance & coordination impairment
Note: older adults may have decreased drug metabolism and elimination that may prolong
effects of BZDs
Table 2b: Association of benzodiazepines (BZDs) with fall risk in older adults >60 years
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Module 2b: Falls and Benzodiazepines
Is it safe for a client to stop taking a benzodiazepine without consulting prescriber?❑Yes❑No❑ It depends
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Module 2b: Falls and Benzodiazepines
Is it safe for a client to stop taking a benzodiazepine without consulting prescriber?❑Yes❑No❑ It depends
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Module 2b: Falls and Benzodiazepines■ Benzodiazepines (BZD):
– one of the top 10 most commonly prescribed classes of medications in older adults in 2016
■ Other non-BZD sedative hypnotics are also associated with increased fall risk:
– Z-drugs: zopiclone (Imovane®) and zolpidem (Sublinox™)
■ BZDs and non-BZD sedative hypnotics may both impair body balance and standing steadiness even after single dose administration.
Image source:https://www.cihi.ca/en/land/data-in-action/in-health-care-more-is-not-always-better
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Module 2c: Falls and Antipsychotics
Antipsychotics
Example
medications
Typical (1st generation)
• chlorpromazine (Largactil®)• flupenthixol (Fluanxol®)• haloperidol (Haldol®)• perphenazine (Trilafon®)
Atypical (2nd generation)
• risperidone (Risperdal®)• quetiapine (Seroquel®) • olanzapine (Zyprexa®)• ziprasidone (Zeldox®)• paliperidone (Invega®)• ariprazole (Abilify®)• clozapine (Clozaril®)
Indication(s) Bipolar disorder, behavioural symptoms of dementia, schizophrenia
Off-label Use(s) Situational aggression, delirium, insomnia
Fall Risk Odds Ratio
(OR) All antipsychotics: OR 1.54 (95% CI 1.28-1.85)
Adverse effects CNS effects: sedation, hypotension, movement-related effects (eg. tardive dyskinesia,
tremors, stiffness)
Table 2c: Association of antipsychotics with fall risk in older adults >60 years
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Module 2d: Falls and Other Drugs
CV DRUGS OTHER DRUGS
Significant
association with
increased fall risk
Loop diuretics
• OR = 1.36, 95% CI 1.17-1.57
Opioids
• OR = 1.60, 95% CI 1.35-1.91
Antiepileptics
• OR = 1.55, 95% CI 1.25-1.92
Non-significant
association with
increased fall risk
Digoxin
Antihypertensives
Anti-Parkinson drugs
Non-Steroidal Anti-Inflammatory
drugs (NSAIDs)
Proton Pump Inhibitors (PPIs)
Table 2d: Associations of cardiovascular (CV) and other drugs with fall risk in older adults >60y
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Module 2: Falls and Psychotropic Drugs
■ Regardless of the psychotropic(s) used, there should be increased caution regarding falls in clients who are:
– Older adults (age >65yo)– Starting psychotropic drug(s)– Taking multiple psychotropic drugs or > 4 medications– Taking medication for >4 weeks– Living in long term or residential care (eg. seniors with
dementia)
■ Provide fall risk screening and education to all older adults taking psychotropic medications
■ Resource: Finding Balance https://findingbalancealberta.ca/resource-catalogue/ Image source: https://www.mysafetysign.com/fall-
hazard-signs
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Module 2: Falls and Psychotropic Drugs
CASE 3 WRAP-UP■ Edith has multiple risk factors for falling including:
– advanced age (>65 years)– taking an SSRI (escitalopram)– taking a TCA (amitriptyline) – taking a BZD (lorazepam)
■ Recommend fall prevention strategies including balance and strengthening exercises
■ Measure or ask for standing and supine BP at each visit and educate Edith on how to minimize dizziness and lightheadedness from orthostatic hypotension
■ Refer Edith to prescriber for potential deprescribing
Image source:https://www.medscape.com/viewarticle/851897
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Module 3: Overview of OpioidsCASE 4: ■ Client: Ashley 50y F■ Occupation: administrator■ HPI:
- involved in rear-end vehicle collision 1 month ago- experienced WAD Grade II whiplash (presence of
neck stiffness, neck pain rated 7/10, decreased ROM)- although neck stiffness has decreased since
accident, experiencing persistent and bothersome neck pain that has impacted her ability to sleep and work
- Examination- stiffness and tenderness of neck muscles,
hypersensitive to palpation- decreased ROM during neck flexion, extension and
rotation
Image source: https://physiotherapykingston.ca/back-neck-pain-different-types-pain-mean/
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Module 3: Overview of Opioids
CASE 4Medication History:■ Neck stiffness and pain
– cyclobenzaprine (Flexeril®): 10mg once every evening x 4 weeks
– naproxen (Aleve®): 500mg twice daily as needed for pain x 4 weeks, stopped yesterday
– codeine phosphate 30mg /acetaminophen 300mg / caffeine 15mg (Tylenol® #3): 1 tablet up to four times daily as needed for pain, started yesterday
Image source:https://drugsdetails.com/flexeril-and-tylenol-interactions/https://www.webmd.com/drugs/2/drug-3179/tylenol-codeine-3-oral/details
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Module 3: Overview of Opioids
Traditional opiates Synthetic opioids
Examples
(with brand
names)
codeine (Tylenol® #3*)
morphine (Kadian®, M-Eslon®, MS-Contin®)
fentanyl (Actiq®, FentoraTM, Duragesic®)
hydromorphone (Dilaudid®)
oxycodone (Oxyneo®, Percocet®*)
tramadol (Durela®, Tramacet®*, Zytram XL®)
Indications 2nd or 3rd line option for treatment of pain (acute/chronic, cancer & non-cancer)
End-of life care
Typical
starting dose
<50 Morphine Equivalents (MEQ)
Adverse effects
CNS effects: impaired cognition, impaired coordination, sedation, dizziness
GI effects: chronic constipation, nausea, vomiting
Other effects: endocrine abnormalities (hyperprolactinemia, hypogonadism), respiratory
depression
*Tylenol #3 and Tramacet are combination products containing acetaminophen
Table 4.1: General information on opioids and adverse effects
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Module 3: Overview of Opioids
CNS Adverse Effects Examples of Follow-up Actions
Impaired cognition Periodic assessment, mini-mental state examination
Impaired coordination Heel-toe gait testing; UE alternating pronation/supination
Sedation Consider monitoring with Epworth Sleepiness Scale (for excessive
daytime somnolence) and with family and other witness accounts
such as prescribers
Consider possibility of drug interaction (e.g. benzodiazepines) and
review dosages and need
Table 4.2: Management of Opioid-Related Adverse Effects (adapted from McDough)
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Module 3: Overview of OpioidsOpioids and Falls■ A significant increase was shown in the most recent meta-analysis of opioids by
Seppala et al., (OR=1.60, 95% CI 1.35-1.91) in adults >60 years
■ previous meta-analyses and some other studies have not shown significant associations between opioids and fall risk
■ Fall risk and fall-related injuries is significantly increased in adults who initiate opioids
– OR = 5.14 (95% CI 4.76-5.55) in the first week of opioid treatment– OR = 1.23 (95% CI 1.10-1.38) in the fourth week
■ The proposed fall risk increasing mechanisms include CNS effects of opioids (impaired cognition, impaired coordination, sedation, dizziness)
■ Caution and close monitoring is warranted in older adults taking >1 opioids, especially if they are opioid naïve, taking other fall-risk increasing medications or taking >4 medications (polypharmacy)
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Module 3: Overview of Analgesics
Comparator Pain Rating Using Visual Analog Scale
(VAS) vs opioid therapy
Physical Function (at (>4
weeks) Using Physical
Component Score of SF-36
compared to opioid therapy
NSAIDs Little to no difference ”…little to no difference in
physical function…”Anticonvulsants Greater proportion of patients on opioids
who achieve a 1cm reduction on a 10cm
VAS
Tricyclic
Antidepressants
Little to no difference
Nabilone Little to no difference
Table 4.3: Effects of opioids vs. other analgesics on pain and function (adapted from 2017 Canadian Guidelines for Opioids for Chronic Non—Cancer Pain)
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Module 3: Overview of Opioids
■ Should a trial of opioids be initiated or should established non-opioid therapy (eg. NSAIDs, anticonvulsant, tricyclic antidepressants, nabilone) be continued in clients with persistent & problematic pain?
❑Optimize non-opioid first, then add opioid
❑Add opioid to before maximizing non-opioid to avoid toxicity
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Module 3: Overview of Opioids
■ Should a trial of opioids be initiated or should established non-opioid therapy (eg. NSAIDs, anticonvulsant, tricyclic antidepressants, nabilone) be continued in clients with persistent & problematic pain?
❑Optimize non-opioid first, then add opioid
❑Add opioid to before maximizing non-opioid to avoid toxicity
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Module 3: Overview of Opioids
Reference: http://nationalpaincentre.mcmaster.ca/documents/Opioid%20GL%20for%20CMAJ_01may2017.pdf
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Module 3: Overview of OpioidsCASE 4 WRAP-UP
■ Based on the McMaster pain guidelines, Ashley qualifies for a trial of opioids
■ Her dose of Tylenol #3 is within the recommended range of <50 MEQ for opioid initiation
■ Fall risk may be increased since due to recent initiation of an opioid
■ Follow-up in 2-4 weeks– assess pain and function– If she is experiencing CNS adverse effects,
determine if there are actions within your scope of practice that can be taken to mitigate these adverse effects
Image source: https://www.ctvnews.ca/it-s-time-to-phase-out-codeine-doctors-urge-1.559426
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Conclusion
■ Medication may play a role in worsening function in older adults.
■ Physiotherapists have the potential to identify clients experiencing adverse effects that may be hindering participation or effectiveness of physiotherapy interventions.
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Questions
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Module 1 ReferencesHealth Canada Safety Reviews■ Summary Safety Review on Fluoroquinolones – Assessing the potential risk of persistent and disabling side
effects. (2017). Retrieved from: https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/safety-reviews/summary-safety-review-fluoroquinolones-assessing-potential-risk-persistent-disabling-effects.html.
■ Summary Safety Review on Dipeptidylpeptidase-4 (DPP-4) inhibitors – Assessing the risk of joint pain (arthralgia). (2017). Retrieved from: http://www.hc-sc.gc.ca/dhp-mps/medeff/reviews-examens/dipeptidylpeptidase-eng.php.
■ Summary Safety Review on Finasteride – Assessing the Potential Risk of Serious Muscle-Related Side Effects. (2017). Retrieved from: https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/safety-reviews/summary-safety-review-finasteride-assessing-potential-risk-serious-muscle-related-side-effects.html.
FDA Safety Reviews■ FDA Drug Safety Communication: FDA updates warnings for oral and injectable fluoroquinolone antibiotics due to
disabling side effects. (2018). Retrieved from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-updates-warnings-oral-and-injectable-fluoroquinolone-antibiotics
■ FDA Drug Safety Communication: FDA warns that DPP-4 inhibitors for type 2 diabetes may cause severe joint pain. (2015). Retrieved from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-dpp-4-inhibitors-type-2-diabetes-may-cause-severe-joint-pai
Other■ Kirchgesner, T., Larbi, A., Omoumi, P., Malghem, J., Zamali, N., Manelfe, J.,...Dallaudiere, B. Drug-induced
tendinopathy: from physiology to clinical applications. (2014). Joint Bone Spine. 81(6): 485-492. ■ Tomlinson,S.S., & Mangione,K.K. Potential Adverse Effects of Statins on Muscle. (2005). Physical Therapy.
85(1):459–465■ Sathasivam, S., & Lecky, B. (2008). Statin induced myopathy. BMJ. 337:a2286. doi:10.1136/bmj.a2286■ Thompson, P.D., Panza, G., Zaleski, A., & Taylor, B. (2016). Statin-associated side effects. Journal of the American
College of Cardiology. 67(20).
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Module 2 ReferencesMeta-Analyses and Systematic Reviews Re: Fall Risk■ de Vries, M., Seppala, L. J., Daams, J. G., van de Glind, Esther M. M., Masud, T., van der Velde, N., . . . van der Velde, N. (2018). Fall-
risk-increasing drugs: A systematic review and meta-analysis: I. others. Journal of the American Medical Directors Association, 19(4), 371e9.
■ Seppala, L. J., Wermelink, Anne M. A. T., de Vries, M., Ploegmakers, K. J., van de Glind, Esther M. M., Daams, J. G., . . . van der Velde, N. (2018). Fall-risk-increasing drugs: A systematic review and meta-analysis: II. psychotropics. Journal of the American Medical Directors Association, 19(4), 371.e17.
■ Seppala, L. J., van de Glind, Esther M. M., Daams, J. G., Ploegmakers, K. J., de Vries, M., Wermelink, Anne M. A. T., . . . van der Velde, N. (2018). Fall-risk-increasing drugs: A systematic review and meta-analysis: III. others. Journal of the American Medical Directors Association, 19(4), 372.e8.
Other Articles Re: Fall Risk■ Drug Use Among Seniors in Canada (2016). Canadian Institute for Health Information Institute (CIHI).■ Darowski, A., Chambers, SA.C.F. & Chambers, D.J. (2009). Antidepressants and falls in the elderly. Drugs & Aging. 26(5): 381-
394. ■ Griffin, C. E., Kaye, A. M., Bueno, F. R., & Kaye, A. D. (2013). Benzodiazepine pharmacology and central nervous system-
mediated effects. The Ochsner journal, 13(2), 214–223.■ Mets, M.A.J., Volkerts, E.R.,. Olivier, B., & Verster, J.C. (2010). Effect of hypnotic drugs on body balance and standing
steadiness. Sleep Medicine Reviews. 14(4): 259-267.■ Treves, N., Perlman, A., Kolenberg Geron, L., Asaly, A., & Matok,L. (2018). Z-drugs and risk for falls and fractures in older adults
– a systematic review. Age and Ageing. 47(2): 201-208.■ Fraser, L., Liu, K., Naylor, K.L., Hwang, J., Dixon, S., Shariff, S.Z., & Garg., A.X. (2015). Falls and fractures with atypical
antipsychotic medication use: a population based cohort study. JAMA Internal Medicine. 175(3):450-452.
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Module 2 References
General Information on Medication Classes:■ Antipsychotic medications. Centre for Addiction and Mental Health (CAMH). Retrieved
from: https://www.camh.ca/en/health-info/mental-illness-and-addiction-index/antipsychotic-medication
■ Benzodiazepines (CPhA Monograph). (2015). Canadian Pharmacists’ Association. Retrieved from: https://www-e-therapeutics-ca
■ Selective serotonin reuptake inhibitors (CPhA Monograph). (2014). Canadian Pharmacists’ Association. Retrieved from: https://www-e-therapeutics-ca
■ Tricyclic antidepressants (CPhA Monograph). (2018). Canadian Pharmacists’ Association. Retrieved from: https://www-e-therapeutics-ca
■ The association between medications and fall risk. (2016). Alberta College of Physicians and Surgeons. Retrieved from: http://www.cpsa.ca/the-association-between-medications-and-fall-risk/
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Module 3: Overview of Opioids
References
■ http://nationalpaincentre.mcmaster.ca/documents/Opioid%20GL%20for%20CMAJ_01may2017.pdf
■ https://www.nps.org.au/australian-prescriber/articles/safe-prescribing-of-opioids-for-persistent-non-cancer-pain
■ https://www-sciencedirect-com.login.ezproxy.library.ualberta.ca/science/article/pii/S1525861017307855?via%3Dihub
■ https://www.ncbi.nlm.nih.gov/pubmed/23345030
■ RxTx. Opioid monograph
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Opioids and Physical Function (extra info)
■ https://www-sciencedirect-com.login.ezproxy.library.ualberta.ca/science/article/pii/S1526590017308003?via%3Dihub
– Adults >60 years– Compared to placebo, opioids improved function (standardized mean difference = −.27, 95% CI = −.36 to −.18)
on the WOMAC disability subscale which was not associated with daily dose or treatment duration. (Megale et al.)
■ https://jamanetwork.com/journals/jama/fullarticle/2718795– Adults (median age 58 years, range 51-61yo)– Systematic review and meta-analysis of opioids for non-cancer pain– Compared to placebo, opioids Improved physical functioning (weighted mean difference = 2.04 points, 95% CI,
1.41 to 2.68 points] on the 100-point SF-36 PCS but not meet criterion for clinically important difference– More opioid-users achieved clinically important difference in physical functioning than non users (risk
difference = 8.6%, 95% CI 5.9-11.2%)
■ https://link-springer-com.login.ezproxy.library.ualberta.ca/article/10.1007%2Fs11606-015-3579-9– Males > 65 years with persistent musculoskeletal pain– Secondary analysis– Risk of falling did not differ significantly between opioids users and non-user groups– Physical performance was worse at baseline for opioid users (composite of grip strength, chair stands, gait
speed and dynamic balance)– No difference in annual decline in physical performance (composite of grip strength, chair stands, gait speed
and dynamic balance)– Conclusion: more research needed to determine if opioids impact falls and function in older adults with
chronic pain59