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

2

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

40

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

44

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)

46

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)

47

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)

48

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

52

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.

53

Questions

54

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