OTC Analgesics Flashcards
Common dosing of morphine for moderate to severe pain?
For moderate to severe pain, morphine might be
started at 5-10 mg Q4H.
Describe the morphine equivalents (10 MEQ) of the available OTC analgesics. What does MEQ of 10 mean?
We need this amount of each agent to get to the
same painkilling level as 10 mg morphine.
What is an issue with Tylenol-3’s for analgesia?
Codeine – 2D6 – Metabolized to morphine – pro-drug – Not consistetnt across the population – based on genetics and race
T3s are terrible - slow metaboizer may not even help; rapid metabolizer okay for pain control
What are the available NSAID’s and there OTC limiting dosing? What does this mean as comapred to acet at OTC doses in comparison of MEQ 10? Exception?
1200 mg ibup
440 mg naproxen
This means theoretically they are LESS effective than acet at OTC doses
However, many patients say NSAIDs work better for them (anti-inflammatory action)
What are some recommendations for dosing of Ibuprofen and Naproxen?
What is unique about OTC analgesics compared to morphine? AT what values does this effect occur at?
Ceiling Effect of Analgesia
Morphine has no celining effect: Can lead to respiratory depression and therefore body develops tolerance to it so greater doses can be used –> Common in pallitative care as do not want to play catch up
Ibuprofen –> Max analgesia achieved at 400 mg dose. Individual doses greater than 400 mg do not provide further analgesia
ASA/ACET –> Individual doses greater than 1000 mg do not result in further analgesia
Acet –> 1000 mg –> No anti-inflammatory action
Describe OTC dosing in dental pain and if the ceiling effect is maintained for analgesia and inflammation? Certain Disease States?
Ceiling effect of analgesia is maintained; however, dental pain includes an inflammatory component
If inflammation is present, all best are off as higher doses can help to achieve anti-inflammatory effects
Pain mangement for osetoarthritis may have a ceiling effect, but dental and rheumatoid can go into higher doses for analgesia and anti-inflammatory
Describe non-opiod analgesics and there anti-inflammatory dosing. Key points to consider regarding usage of NSAID’s?
Nonopiods exhibit a ceiling effect for their analgesia response but optimal doses should be established before it is assumed that an NSAID has failed
Acetaminophen does not have an anti-inflammatory effect; however, a combination of an NSAID and acetaminophen provide greater analgesia efficacy than does either agent alone
Is ibuprofen at OTC doses harder on the stomach at OTC doses? Describe the rate of benefit?
NO
Adverse effects of OTC analgesics are generally no different from placebo
Chances of getting help for acute pain range from 70% at best to 20% at worst
Describe the rates of adverse effects related to tolerability of oTC analgesics?
Ibuprofen: 13.7%
Acetaminophen: 14.5%
ASA: 18.7%
The overall tolerability of OTC ibuprofen 1200 mg/day was equal to acet 3000 mg daily but superior to ASA 3000 mg/day
Chance of all side effects here; RX doses all bets are off
Describe the rates of GI adverse effects of OTC Ibuprofen and Acet. How can a pharmacist frame this to a patient?
At OTC doses, ibuprofen does NOT have more side effects !!
Almost every pharmacist gives acet more credit for less s/e
Frame these as ‘nuisance side effects’
–> 10% acet, 10% ibu, 10% placebo
Placebo is around 10% for these adverse effects
Describe the evidence of Ibuprofen and GI adverse effects compared to placebo? Ibu and Acet?
Symptomatic GI side effects with Ibuprofen are comparable with placebo and treatment is well tolerated and largely free of gastric damage
Large trials of ibuprofen and acetaminophen, the risk of GI bleeding was low with no statistically significant difference in GI bleeding between the two
Describe the overall adverse effect profile of acet and ibuprofen.
Ibuprofen and acetaminophen have similar reported adverse effects
There is comparable safety for ibuprofen and acetaminophen at OTC doses
Describe the incidence rates of adverse effects of Ibuprofen statistics? Exception?
3-9% –> Nausea, epigastric pain and heart burn
Less than 1% –> Gastric or duodenal ulcer (Higher doses and longer term usage)
Is heartburn/epigastric pain the same as an ulcer?
Heartburn is not the same as an ulcer
One can have an ulcer and be asymptomatic
One can have painful symptoms but no pathology in the stomach
The linkage between the symptoms and pathological mechanisms is weak and is not a 1:1 or linear ratio
Therefore, can not say heartburn is the same as an ulcer
What are some signs and symptoms of a stomach ulcer?
Nausea
Blood in Vomit
Indigestion
Loss of appetite
Pain in Stomach
Stool Discoluration
What is a critical counselling point to include when counselling someone on OTC acteaminophen?
Do you use any other products that might have acetaminophen?
Describe the effect of taking an NSAID with food? Does it prevent GI adverse effects?
Fluid or food helps clear a pill from the esophagus
It can help reduce some local damage to stomach
It will NOT prevent GI damage via systemic PG inhib (systemic effect)
Food can actually delay onset of action (if need fast action, take without food)
If someone wants a faster analgesic response, are gel caps more useful than tablets for Ibuprofen?
Could be useful for some patients; however, often not relevant
Different delievery mechanism; gel caps are 2 minutes faster
Why does taking food with Ibuprofen not protect from GI ulcers?
Ibuprofen is a non-selective NSAID and therefore is blocking both COX-1 and COX-2 to varying degrees
COX-1 is required for gastric production through mucous protection; therefore, blocking COX-1 can lead to GI damage
Systemic effect; food will not prevent the systemic effect
What is a concern with NSAID administration with food?
Food will not provide systemic protection from COX-1 inhibition
Food may lead to a slower onset of action
If someone wants fast analgesia, taking an NSAID without food may be the appropriate course of action
Describe Enteric Coated Aspirin and its absoprtion and use?
EC ASA delays maximum pain relief as long as 3 to 4 hours
Therefore, this product will not provide fast relief of headaches or other symptoms
Does enteric coating lower the risk of GI bleeding?
Enteric Coating ASA is just as likely to cause stomach bleeding and therefore is not safer than regular aspirin
Is the coating of ASA always for delayed release?
No
Sometimes ‘coatings’ are on the tablet to simply make it taste better getting by the mouth (Not ER or XR here, just taste)
Regarding NSAID’s, what stance does a pharmacist commonly focus on?
Take an approach with s/e, C.I., risks, fine print
Risk people, need to lower the risk
Shift focus to this person needs help
Describe the decision of using Ibuprofen and the risks in a patient?
Describe the BEER’s List stance on NSAID use in geriatric patients?
Adults aged 65 years and older
Experts found that older adults should avoid even short term use of NSAIDs for pain, emphasizing their high risk when used in combination with:
1) Steroids
2) ANticoagulants
When no alternatives exist, pt’s should be placed on misoprostol or a proton pump inhibitor while taking NSAID’s
BEER’s List and NSAID and Risk Factors for GI Bleed
No safe dose of an NSAID for seniors over the age of 65 years old
Incraesed risk with:
1) Steroids
2) SSRI’s (7-fold increase)
3) ANti-coagulants (DOAC”s better than warfarin but can still cause GI bleed)
Describe the use of NSAIDs in CV and GI risks in reviews and what a pharmacist should do in this situation?
Almost all the big reviews focus on GI and CV risk, yet fail to mention that by not treating, PAIN is not treated, and that may be worse for the patient
Need to balance the benefits and the risks
Describe the analgesic combinations marketed for nightime pain releief? What is added? Are these agents good?
NSAIDs or acetaminophen in combination with either:
1) Methocarbamol: Muscle relaxent –> Does nothing for muscle relaxing, just dizziness and sedation
2) Diphenhydramine –> BEERs list and incraesed fall risk –> Not a good sleep aid
Describe the incidence of insomnia and pain?
It is estimated that 60-80% of pain patients experience symptoms of insomnia
What are the mechanisms for pain occuring at night?
Lower levels of anti-inflammatory hormone cortisol at night
Staying still in one position might cause the joints to stiffen up
Describe the prevalence of the nature of pain
Describe the prevalence of pain severity?
How can pain be evaluated in children? Is this common in pharmacy practice?
Evaluating behavioural signs such s facial expressions, crying, irritablity, poor feeding, sleep disturbance, and inactivity
Level of asessment not commonly done at the community pharm level
First Line medications for analgesia in children
Acetaminophen and Ibuprofen
Comparable safety profile
Go for flavour here or what they have used before
Analgesics for headache including migraines
NSAIDs or Acet
ALSO TRIPTANS
Describe the difference between a headache and migraine
Is Advil 12 hour a major improvement?
12 Hour – Simplicity
300 mg on outside and 300 mg inside
CONVENIENCE – TOTALLY fine
Are Tylenol liquid gels a major improvement?
Five mins faster than tabs next to it
Not a major advancement
What use to be the drug of choice for osteoarthritis? Is it still the drug of choice?
Acetaminophen use to be the drug of choice
Now is on the verge of no longer being DOC
Describe the prevalence of osteoarthritis
60% of people with arthritis are women
6 million Canadians
1/6 men have arthritis
Arthritis can effect people of any age; however, the likelihood increases with age with nearly 1 in 2 seniors over the age of 65 having arthritis
Average age at diagnosis of arthritis
50 years old
Average age at first symptoms of arthritis
47.5 years old
Is Acetaminophen useful for arthritis?
Acetaminophen only provides minimal improvements in pain and function with no increased risk of adverse events overall
The effects on pain and function do not differ according to the dose of acetaminophen
Verge of being placebo
Is the effect of acetaminophen in osteoarthritis dose related?
NO NOT DOSE RELATED
Describe what a pharmacist should do if someone is wanting acet for osteoarthritis?
Some people do seem to get value out of this, but numbers are shrinking and not good
If it works for someone, good enough
For first recommendation, if go with this:
Try for 2 weeks and see if it helps – if it doesn’t work, we will try something different
Where NSAID’s kick in - need to go to this to help with pain or do nothing
What is the drug of choice for osteoarthristis? When would it be used?
Topical Diclofenac should be considered first line
One or two joints – topical diclofenac
Both hips, elbows, and phalanges – tough to manage with topical
- Topical – best for isolated joints
- At some point, will probably need to consider oral
What agent and dose had the lowest effect on osteoarthritis pain?
Paracetamol 4000 mg/day had the lowest effect on OA pain
Acet is not looking like a valuable therapy for…..
Arthritis and Low Back Pain
What is the drug of choice for dysmenorhhea?
NSAIDs are the drug of choice
Why are NSAIDs the drug of choice for dysmenorhhea?
Menstrual cramps are causes by contractions in the uterus by prostaglandins
What is dysmenorhhea?
Cramping pain in the lower abdomen that can start from 1-2 days before your period and can last up to 2-4 days
Describe the prevalence of dysmenorhhea?
Most commonly reported menstrual disorder
More than one half of women who menstruate have some pain for 1-2 days each month
Can acet be used for dysmenorhhea?
NSAIDs are preferred, but acet is an option too
Describe the avilable agents for dysmenorrhea. Are all useful for dysmenorhhea?
Midol: Acet 500 mg, Caffeine 60 mg, and pyrilaminate maleate 15 mg
- Caffeine is a diuretic here, so for PMS not Dys
Maxidol: NAproxen 220 mg
Advil: Ibu 200 mg
What is the purpose of caffeine with an analgesic?
caffeine – Diuretic
need 100 mg to be analgesic with the Ibu or Acetaminophen
How much caffeine is in a cup of coffee? Who is acffeine useful as an analgeisc in? WHich condition in females?
100 mg in a cup of coffee
- PMS
- Caffine drinker – stabilized intake and outake –>will pee it out in a couple of hours
- Cafeine Naieve Individuals (those who do no consume caffeine) - enhance analgesic effect through vasoconstrictive properities
How can one manage toothaches?
Acet and Ibu combination may be effective here
What is a strategy that can be used to manage post-operative dental pain? Issue:
Ibuprofen (400-600 mg) every four to six hours (2400 mg/day max)
AND
Acetaminophen (650-1000 mg) every six hours (max of 4000 mg/day)
HOWEVER:
OTC max of Ibu is 1200 mg/day
600 mg Ibuprofen and 1000 mg Acetaminophen administered every 6 hours (four times daily) for 24 hours
2-4-24 Rule (2 drugs, 4 doses, 24 hours)
Describe the combination product Advil plus Acetaminophen. Issue:
Ibuprofen 125 mg
Acetaminophen 250 mg
Two tablets every 8 hours (6 max/day)
Number look low here
Describe the concept of the combination of Advil plus acetaminophen?
The concept here is that lower doses in the fixed-dose combo gets just as good (or better) relief, with less frequent dosing, and not a jump in side effects.
Describe the formulation of combogesic?
Acet 325 mg
Ibup 97.5 mg
When would one select Aleve over another NSAID?
Dosing less frequent –> BID
Value: More CV protection –> As far as grey areas, a little more safer in the CV front
– Can be worse for GI
- Ibu is better for GI than Aleve; but more risk with CV
Describe Tylenol Ultra Relief. Who is it useful for? When is it useful? Side effect?
Acetaminophen 500 mg
CAffeine 65 mg
Need 2 tablets here to get benefit
Caffeine naieve people may get some diuresis
Migraines –> Good choice to include for relief of pain
Efficacy of caffeine as an analgesic Efficacy. In what conditions?
Compared with analgesic medication alone, combinations of caffeine with analgesic medications, including acetaminophen, ASA, and Ibuprofen, showed significantly improved efficacy in the treatment of TTH and Migraine
Favourable tolerability in most
Dosing of caffeine in in TTH and Migraines
Caffeine doses of 130 mg enhance the efficacy of analgesics in TTH and doses of > 100 mg enhance benefits in migraine.
100 mg is close enough for benefit
What is medication overuse headache?
When more medications lead to more headaches
Concern of Caffeine in Combination with Analgesics
Analgesic combos containing caffeine are more likely to induce Medication Overuse Headaches than simple NSAIDs alone.
Caffeine-containing formulations are therefore reserved as 2nd options for Tension Headache and should not be used more than 9 days per month.
THINK OF 10 DAYS of USE PER MONTH
Days of therapy with meds; not how much drug you take
What is the number of days of therapy with an analgesic and/or caffeine when one should be worried about medication overuse headaches?
Think of 10 – painkilling person taking the drugs for 10 days a month
Worried about medication overuse headaches here
What types of medications can lead to medication overuse headaches?
Most headache medications have the potential to cause medication overuse headaches
NSAIDS, Acetaminophen with caffeine are the most common culprits
Most refs do NOT agree that NSAIDs get a pass on this, with one saying that virtually all acute headache meds can cause them.
Is medication overuse headaches a concern with all individuals taking NSAIDs?
A pre-existing headache disorder seems to be required to get MOH.
Migraine and TH have high potential for adding these on.
It is generally not observed in people taking analgesics for reasons other than headaches, such as arthritis or back pain.
When would we be concerned about medication overuse headaches regarding conditions?
If have a neurological disorder (arthritis + migraines/tension headaches)
In general, what OTC analgesics are less lethal in overdose?
NSAID’s – Lower concern; a lot of it is just supportive care
ASA and ACET – more worried
ACET is a major concern
Acetaminophen overdose is a……..
Serious medical emergency
When is hepatotoxicity observed in adults and adolescants regarding acetaminophen?
Describe acetaminophen concern for overdose in pediatrics?
What is the recommended maximum dose of acetaminophen in Canada and the USA?
USA: 3 g/day
Canada: 4 g/day
What value of a daily dose of acetaminophen is a cause for concern?
The expert said that “a bit more than 4000 mg = trouble” is NOT true.
The problems start with people getting 8000 or 10000 mg in a day. He feels that 6000 mg is clearly safe.
So, he is fine if the max stays at 4000 mg b/c some buffer room above itis in place.
Describe the dosing of Tylenol products in Canada
Describe the risk of overdose of Ibuprofen
Reports of complications following ibuprofen overdose particularily in children are rare
The vast majority of individuals who overdose on ibuprofen alone have no, or only mild symptoms
Fatal overdose in adults is extremly rare
Describe a critical drug interaction of NSAIDs in comparison to Acetaminophen. Is acetaminophen more safe than NSAIDs?
Several reports of an interaction with acetaminophen
Doses at > 2.25 g per week starting point for concern
Doses > 2.5 g per week could be impactful
More frequent monitoring is suggested
Warfarin use is dropping (but it still is out there)
Mechanism appears to not be due to a plasma protein binding interaction
What should a pharmacist recommend if someone is on warfarin and taking acetaminophen?
Patients taking warfarin who are at high risk of bleeding require close INR monitoring when starting and stopping courses of acetaminophen
Describe the benefits of DOACs. Is there a drug interaction with NSAIDs?
Lower bleeding risk
Less monitoring
Fixed dose
Less drug interactions
But NSAID + DOAC does increase bleed risk
Far less of pharmacodynamic drug interaction
Describe the association between acetaminophen use and preganncy?
Acetaminophen during pregnancy has been associated with neurodevelopmental and behavioral disorders such as ADHD and increase risk of wheezing and incidence of asthma among offspring
Does acetaminophen cause asthma or worsen existing asthma? Mechanism? When does this occur if it does?
Acetaminophen does not worsen asthma
May cause asthma
Possible mechanism: Reduces the body’s level of natural free radical scavenger (glutathione)
There is some concern for this connection while other dispute the connection
Exposure via pregnancy or during early infancy
Does acetaminophen make a child’s asthma worse?
No
Acetaminophen does not make asthma worse
Found no difference in the number of asthma exacerbations
Does acetaminophen in pregnancy lead to ADHD?
Use of acetaminophen in pregnancy is safe after talking with your healthcare provider because there is no clear evidence of a direct relationship between acetaminophen and irregular fetal development
Reports are weak; can still use acet safely in pregnancy
ADHD –> NOOOOOOO
ADHD and autism lawsuits againts acetaminophen lacked admissible proof to support their claims
Acetaminophen and Pregnancy FDA Category. Indication and safety in preganncy?
Pregnancy Category B
Acetaminophen still first line for fever and pain in pregnancy
Acetaminophen is used by 69.9% of women during the first and second trimesters of pregnancy
May actually prevent negative health consequences for the fetus
Does regular acetaminophen use increase blood pressure?
Taking 3-4 g of acetaminophen per day for 2-4 weeks incraeses systolic blood pressure by 3-4 mmHG.
What are the symptoms of an asthma exacerbation?
What happens to an asthmatic if you are sensitive to an NSAID?
When they take ASA or an NSAID symptoms of an asthma exacerbation occurs between 30-120 minutes after taking the NSAID
What type of condition is NSAID induced asthma exacerbation? (age)
The condition develops in adulthood, typically between the ages of 20-50 years old.
The average onset is 34 years old
What are some major causes of an asthma exacerbation in adults?
Viral
Allergen
Exercise
Describe the rates of ASA-allergy. Do most people know if they have an ASA-allergy? Cross sensitivity with other NSAIDs?
Most people won’t get their first dose of ASA until they are about 60
Not due to salicylate group
Describe which NSAID’s to use in those with asthma?
IF the person is ASA-sensitive, do not use
IF the person is NOT ASA-sensitive, these agents CAN be used
IF the person does not know their status ….
Many patients erroneously believe they are ASA-allergic
ASA-induced asthma may only be seen in adulthood (Good chnace we can recommend these products in children)
Can a child with asthma be given an NSAID?
NSAIDs can safely be given to children with asthma
No need to avoid medications unless it is known that they are an asthma trigger for you
Condition of adulthood: 10-20% of adults with asthma have sensitivity to ASA and NSAIDS’s
NSAID induced asthma exacerbation appears to be due to what pathological process?
COX-1 Inhibition
Can use celecoxib here (selective COX-2 Inhibitor)
COX-2 inhibitors provide a potnetially safer alternative for treatment of inflammatory conditions in patients with aspirin-exacerbated respiratory disease
What is ASA 81 mg commonly used for?
Commonly used for secondary prevention rather than primary prevention
What are some warnings listed on Advil and Aleve for the use of ASA 81 mg with these agents?
Avoid taking IBU/Naproxen if taking low dose ASA 81 mg without talking to to a physician/pharmacist
Describe how ASA 81 mg leads to cardio-protection?
ASA hits COX-1 receptor as a Non-selective NSAID
- Now means that the platlet is less sticky – can save your life perhaps
What happens if Ibuprofen is administered with ASA 81 mg?
Ibuprofen on there first; sticks there as far as receptor blocking ASA form getting to the receptor
ASA cannot deactivate COX-1 receptor
What is a risk of taking Aleve and Ibuprofen beyond the loss of cardioprotection?
The risk of GI issues (bleeding risk) incraeses with regular use of either agent in combination with ASA
How can the interaction of ASA 81 mg and IBU be avoided? What complicates this strategy?
Single doses should be given 2 HR after the ASA or 8 hours before the ASA
Multiple daily doses will be a problem
Is Naproxen (Aleve) also likely to interact with ASA 81 mg?
Less likely to interact but still some evidence of an interaction
Avoid if regular use is planned
Single doses should be given 2 hours after the ASA or 8 hours before the ASA
Multiple daily doses will be a problem
When are we more worried about the interaction of ASA and Ibu/Naproxen?
Cut the loses with the 2 HR after the ASA and 8 hours before the ASA
If short term, not an issue
Long term worried as not will be getting value of ASA 81
Does acetaminophen have the same interaction with ASA 81 mg as does IBU and Naproxen?
May not be an option for osteo or low back pain (limited efficacy)
Headaches –> May be useful for benefit/relief
What are the main strategy(ies) that a pharmacist should consider if an individual is taking ASA 81 mg and has pain?
Increase the dose of ASA
G.I. risk will increase but still may be the best option
GI risk is evident but also evident with IBU and Naproxen
CV - Same drug as ASA 81 mg and go with a higher dose to maintain cardio-protection
Topical Diclofenac
Not for headaches, but may be useful for joint pain as example
Overall, ASA 81 mg and taking IBU and Naproxen main concern duration
If ibu and naproxen used periodically, can probably do that – take odd tablet and not worry – regular use is the issue here
Describe the use of analgesic usage in pregnancy
Pregnant women are at risk for under-treatment of pain b/c of concerns
OTC analgesics are some of the most commonly used agents in pregnancy, whether self- or MD-recommended
Few analgesic drugs have been demonstrated to be absolutely contraindicated during pregnancy
What FDA Category is acetaminophen in pregnancy?
FDA Category B
Commonly used in all stages of pregnancy
Describe the issue of NSAID usage in pregnancy.
Prostaglandins maintain the patency of the ductus arteriosus until birth
Before you are born, it allows blood to bypass the baby lungs
Flow to the lungs in not yet needed
After your are born the ductis arteriosus closes and blood is now shunted to the baby’s lungs
What pregnancy category is Ibuprofen according to the FDA?
Category C up to 30 weeks
Category D at greater than 30 weeks
What are the risks of Ibuprofen in pregnancy?
Causes premature closure of the PDA
Increased bleeding risk at term
Describe the safety of Naproxen usage in preganancy?
Every pregnancy starts out with a 3-5% chance of having a birth defect
Naproxen did not show an increased chance of bith defects
Naproxen is not recommended for use after week 20 of pregnancy
Leads to premature closure of the PDA (Patent Ductus Arteriosus)
What is another concern stated by the FDA and Health Canada regarding NSAID use in pregnancy?
Avoid NSAIDs in pregnancy at 20 weeks or later as they can result in low amniotic fluid
Describe the effects of the COX enzymes?
Starts with arachadonic acid and is mediated by thromboxanes and cytokines
Describe the MOA of COXIBS in comaprison to OTC NSAIDs. Examples.
Only block COX-2 enzymes
OTC Nsaids
Block COX 1 and 2 to varying degress –> Naproxen, Diclofenac, Ibuprofen
What enzyme is responsible for pain killing?
Blocking the COX-2 receptor is considered the enzyme for pain killing
Describe the GI safety of NSAIDs regarding adverse effects
Occurrence of severe damage (ulceration, bleeding) is rare at OTC dosing of Ibuprofen and Naproxen
Heartburn and dyspepsia occur with OTC ibuprofen but the rate is similar to acetaminophen or even placebo
At RX doses, the risks jump alot
What can be done to help prevent GI issues from occuring with NSAID’s?
H2RA’s do not help with preventing GI issues (12 hours to onset)
Must be PPI’s –> Add on for long term usage of an NSAID
Describe the gastrointestinal safety of Ibuprofen
GI a/e with the use of NSAID is comparitevely low
Serious GI adverse effects occur in 1% of patients each year in the use of high doses with long term tx
OTC Doses –> Rates similar to that of acetaminophen
Out of all NSAID’s, Ibuprofen appears to have one of the best GI tolerability profiles
What are some comobination products of NSAIDs with gastro-protective agents?
Vimovo –> Naproxen and Esomperazole
Duexis –> Ibuprofen and famotidine
–> Reduces the risk of ulcers by 50% compared to ibuprofen alone
OTC Scenarios: Advil + Zantac (famotidine)
How long should a PPI be used for if taking an NSAID? H2RA?
PPI for three weeks is a good move
Short Term –> H2RA may be a good move but PPI looks like a better move
Describe the prevalence of CV disease death in Canada and relevant statistics
2021 –> 194/100,000 Canadians died from major CV disease
Roughly 6.1/1000 adults aged 20 years and older recived diagnosis of Ischemic heart disease
2.3/1000 adults had a first heart attach
5.2/1000 Canadians aged 40 years and older recieved a diganosis of HF
Describe the risk of NSAIDs and a Heart Attack
Above average risk of heart problems and taking an NSAID:
Diclofenac, celecoxib, or ibuprofen:
Estimated that 7 to 8 extra CV events (such as heart attack) would occur each year among 1000 people taking these medications
For those taking Naproxen, no incraesed risk was observed
THIS IS CONSIDERED A SMALL ADDED RISK
More important risk factors included smoking, eating an unhealthy diet and not exercising enough
Compare the safety of Advil and Aleve
Describe the risk of NSAID and CV risk regarding a comparison of the agents
All NSAID’s including both traditional and COX-2 selective NSAIDs increase the risk CV adverse events
It is not possible to differentiate or rank NSAIDs by their CV risk
CV adverse events occur with both short-term and long-term use
Use NSAIDs at the lowest effective dose for the shortest time possible
Are NSAIDs still prescribed in individuals with CV risk?
Although NSAID use is discourage in patients with CV disease, pain-releief medication is often required and, in the absence of analgesics that are at least as effective but safer, NSAIDs are frequently prescribed
Describe an overall approach that can be used to manage pain in someone with CV adverse event history
1) Non-drug measures first (warm compress, TLC, massage)
2) Topical Diclofenac if isolated joints
3) Tylenol (Short leash here)
4) NSAID –> Need to inform patient to tell there doctor they are taking to monitor for GI and CV risk
–> IBU vs NAproxen –> Little nuance here:
Check in and see if its working:
If not –> STop
If it is –> Lower the dose
Describe the overall concept of CV disease for pharmacists regarding NSAID usage in these patients
The risk of having a heart attack or stroke is extremely small over s short course of therapy (less than one month) such as would be the case in treating acute pain from a musculoskeletal injury
In people without known CVD, the increase risk is minimal
Advise an alternative treatment; however, many patients with CVD can be safely treated with a short course of NSAIDs
Chronic or daily us will be more a concern and warrant questioning
What are some of the drug interactions associated with NSAIDs?
Prednisone 5 mg –> No NSAID
Anti-coags:
Warfarin: INR changes and increased GI bleed risk
DOACs: Less pharmacodynamic drug interaction but someone should be monitoring bleed risk
Will likely increase blood pressure
SSRI’s: Increase risk of GI bleed 7-fold –> Increased risk with NSAID
ASA –> CV protection loss due to platlet binding
Is acetaminophen safe for a hangover?
Yes acetaminophen is safe for a hangover
Describe the acetaminophen metabolism pathway in regards to alcohol consumption
Chronic alcohol and Tylenol is not a good option
Have less glutathione –> all leaning towards to NAPQI and liver damage
Not a problem for hangover to take Tylenol
Chronic aspect leading to issues
NAPQI –> glutathione –>move it over to non-toxic metabolites
Alcohol – not eating as good as they should be chronically; so less glutahione
What does the acetaminophen box say regarding use of alcohol? Is this factual?
If you consume 3 or more alcoholic drinks every day, ask your MD whether you should take acetaminophen.
Acetaminophen may cause liver damage.
Not the reality
What is the true reality regarding acetaminophen usage in individual who use alcohol?
Patients with cirrhosis have lower clearance of acet SO:
Use < 2 g per day including those who continue to drink (still considered safe)
If taken in appropriate doses, acetaminophen is one of the safest analgesics for patients with cirrhosis
Once exceed 2 g/day –> NAPQI accumulation
Are we concerned about hepatotoxicity in acute alcohol ingestion?
Acute alcohol ingestion is not a risk factor for acetaminophe hepatotoxicity.
In fact, it may even be protective (by competing for Cyp2E1).
Are we concerned about hepatotoxicity in chronic alcohol ingestion? Why are why not?
Chronic alcohol ingestion may potentiate hepatoxicity by:
1) Up-regulating CYP 2E1 (which will create more NAPQI)
2) Decreasing available stores of heaptic glutathione
3) MAlnourishment
What is another risk of alcohol with NSAIDs beyond effects on the liver?
Increased risk of GI bleed
What are some issues that make NSAID use in elderly patients more concerning?
Decreased renal function
More medications
More conditions
More bleed risk
More CV issues
More Pain too
What is an algorithm to decide whether to use an NSAID in an elderly patient?
TLC therapies first
Topicals (drug of choice) –> then someone pushes button go to something
OTC doses
RX Doses: Coxibs to reduce GI risk
Try Tylenol – not looking good for OA or back pain
When are we worried about the use of NSAIDs in sports?
Only concerned if the individual is dehydrated
Kidney problems are unlikely to be a concern if they are not dehydrated
Prostaglandins are required to maintain renal perfusion, therefore a decrease in PG and less fluid will lead to decreased renal perfusion
Fully dehydrated and NSAID –> BAD
Are NSAID’s useful for the treatment of injuries from activity/sports? What is the trajectory of the treatment of acute injury?
NSAID’s are questionable in reducing swelling associated with phsycial injury but they can improve pain
New Thinking: Need the inflammation to help remodel the joint for long term functions
NSAIDs and cold compress may not be good for the long term front regarding remodelling
For an acute injury (e.g. sprain ankle), NSAIDs are better than acet due to the anti-inflamm action; however, OTC doses may not be anti-inflammatory
Trajectory is leaning from RICE to MCE (RI is on the verge of not being considered anymore)
Describe the statistics regarding low back pain and the efficacy of treatment? Take away?
75% will recover with simple treatment
25% will have future further espiodes
The value of analgesics are really being re-thought in this area
Is bed rest a good therapeutic management for low back pain?
No
Want to power through and maintain movement as movement can help remodel
From a pharmacist perspective, what types of back pain are we involved in?
Low back pain
High back pain can be caused by many conditions (compressed vertebrae, syndromes) and this is not us
–> Physio, chiropractice and medicine territory
What are some causes of back pain? Are we able to distinguish these? If so, which ones?
Sciatica – Can guide us on what not to use
Important nerve for ambulation
Pain down the back length of the lower keg
When are NSAIDs useful for back pain?
Add on for acute is likely useful
Pain meds have a limited role in most cases of lower back pain
Describe the etyiology of back pain
Chronic low back pain has generally been considered to be the result of an injury
Overly simplistic
Complex interaction of pain, perception, emotions, attitude, stress, phsycial activity and HCP relations
Tremendous amount of back pain is not due to injury- no trauma there
Describe a common type of back pain regarding pain etyiology. Role of NSAIDs?
Nociplastic Pain
Pain without any damage or inflammation to that region of the body
Encompasses a lot of chronic pain, especially low back pain
Not neuropathic or somatic (injury) –> Perceptions in the brain
Since no inflammation, NSAID’s are useless
What is the likelihood of someone having lower back pain?
Most people will have at least one episode of lower back pain in their life
Is back pain common? Ages?
Back pain is increadibly common
Most people start noticing back pain between the ages of 40 and 60
Some start to feel the effects of an aging spine as young as 30
Describe the available OTC analgesics and their associated max doses/day and their efficacy regarding analgesia and anti- inflammation?
ASA is only NSAID that will have anti-inflammatory action but not doing this anymore
Describe the mechanism of action of Acetaminophen. Indication?
Works in the central nervous system (in the brain) via a PG effect
Indication: Anti-pyretic and relief of mild to moderate pain
Is acetaminophen anti-inflammatory?
No: Acetaminophen is not anti-inflammatory
Describe the role of acetaminophen in low back pain and OA?
Acetaminophen is not effective for low back pain and provides no clinically meaningful impact on osteoarthritis
What is the treatment strategy regarding analgesic use in low back pain/osteoarthritis?
Describe the therapeutic ladder of ASA
Describe the OTC dosing of Naproxen and Ibuprofen in comparison to anti-inflammatory dosing
What are some concerns with NSAID? What is another risk factor for pharmacists to consider?
Geriatrics
Cardiovascular
GI
Asthma
Renal
DOING NOTHING IS ALSO A RISK FACTOR
Describe the available muscle relaxent OTC analgesic combos available. Ingredients and strength? Is xtra-strength useful?
CNS effects –> Extra strength –> No change in methocarbamol dose
Are OTC muscle relaxents effective for lower back pain? WHy or why not?
Methocarbamol – buying it for a buzz
CNS effects –> Extra strength –> No change in methocarbamol dose
Notoriously consisted not a muscle relaxant –> no antispasmodic effect
Just makes you drowsy –> not anti-spasmodic and not muscle relaxing
Adds on side effect with little value
What is the best available Robax agent on the Canadian market?m
Methocarbamol + ASA is the best one –> inflammation is little in back pain
ASA would be the best of the right dosage; however, may not have an effect as more complexity than just inflammation
What is the main purpose of Tylenol or Motrin adding methocarbamol into their formulations?
Motrin Muscle and Body –> IBU 200 and Methocarb 500
Tylenol Body Pain and Night –> Acetaminophen and Methocarbamol
Helps you go to sleep as a little sedating; that is all
Are the following agents any better than the other OTC analgesics?
Same medication; no difference from the regular OTC analgesics
What is lidocaine useful for? Concerns?
Possibility of use for neuropathic pain but concern over whether it actually reaches the tissues or not
What is lidocaine?
Topical anasthetic
Lidocaine by Deep Relief in Canada Indications:
How is it applied?
Inset bites are indicated but back pain is not i dedicated
Numbness for sure
Vaccine and epidural pain –> Can help with initial pain
Applied TID to QID
What is the depth of nerves that lidocaine is able to effect and work on?
Works primarily on the. nerves at the surface of the skin
Maximal penetration depth of topical lidocaine is from 8-10 mm
3 mm after 60 minute application
5 mm after a 120 min application
Can lidocaine be used for peripheral neuropathy?
Potentially –> PHysicians call here; not us as pharamcists
For lower back pain, would lidocaine be an effective agent? Alternatives?
Need some penetration for low back pain treatment
Choose topical diclofenac here rather than lidocaine
Describe the proposed mechanism of lidocaine
Describe another formulation of lidocaine and its usage? Application, onset, time to maximum effect?
EMLA Patch
Can be utilized for injection needle pain
The onset is less than 25 mins
Application time for adequate analgesia is at least 1 hour
Maximum effect is reached at 2-3 hours of application and lasts for 1-2 hours after removal
Describe the effectiveness of the EMLA lidocaine patch
The duration of analgesia is influences by the vascularity of the local area
More vasculatiure, more clearence, effect is shortened
When applied for 60 mins, the depth of the anaesthetic effect was found to be 3 mm and 5 mm for a 120 mins applictaionn
Describe the depth of anasthetic effect for EMLA patch
1-2 mm when applied for 60 mins
2-3 mm when applied for 120 mins
6 mm when applied for 3-4 hours
What is Zostrix? Indication and MOA (simple)? Main a/e?
Capsaicin 0.075% (pepper compound)
Generally for post-herpectic neuralgia
Needs consistent use to decraese substance P –> applied TID
Irritating to the skin when applied
Describe the mechanism of action of Zostrix in depth
Substance P is a transmitter that is making pain occur
Zostrix is working to decraese substance P in blood vessels and from mast cells
Reduced substance P at the distal level and dulling the nerves
What are some of the available topical external analgesics?
Counter-irritants
- Methyl Salicylate
- Menthol
- Triethanolamine
Topical NSAID’s
- Topical diclofenac (Voltaren)
What is the MOA of topical external analgesics?
Counter Irritation
Massage/Blood flow
Posychological (odour)
Describe the mechanism of action of counter irritants
Counter-irritants
They actually irritant the skin.
If I irritate the skin on top of the muscle, sends signal to brain.
Original pain signals from muscle underneath.
Thought is that brain cannot handle both signals: fool the brain
What are the main counter irritant agents? Brand Names and how do they work?
Methyl Salicylate
Menthol –> Icy/Hot, Deep cold
Icy Hot:
First half-hour –> Menthol hits the cool receptors quickly (not actually lowering the temperature)
–> Physiolofical and psychological effect
After 30 minutes, becomes warm as other tissues become irriated and incraeses blood flow (not an actual temperature change)
Deep Cold works in thye same manner
What is triethanolamine? Product name? Is xtra strength any better than regular strength?
RUB-A535
No odour versions –> Triethanolamine –> Smell is up to the patients
Do not worry about extra vs reg. strength
Low expectations of how effective this agent would be
Same mechanism as a counter irritant; just no odour
What counter-irritant is used for heating? WHich is used for deep cold? Recommendation? Describe the indications of menthol?
Methyl salicylate is not hitting the cool receptors like menthol
Just try one of them to see if helpful
IS the combination of multiple counter irritants useful? Example?
3 is not better than one or two; patient choice here
Biofreeze product medication
Just another menthol product
What is a critical counselling point if someone is to use a counter-irritant medication?
Do not use a heating pad at the same time with any counter-irritant products
Describe the approach to therapy for sore muscles and a sore back? Counter irritants? Topical NSAID’s?
Counter irritants are more likely to be effective on larger muscles rather than back pain
Worth a try for sure
Lower expectations and delays use of NSAID
Often may choose to go with topical diclofenac before RUB A535
Describe the available topical OTC NSAIDs that may be beneficial to use
Topical Diclofenac 1% (Voltaren)
What does the manufacture of voltaren sat about use of the product?
Useful for:
1) Muscle/joint injuries
2) Sprains and strains
3) Back muscle pain
Describe the available formulations of topical diclofenac? Strength and application? Which agent should we choose?
Voltaren Extra STrength 2.32%
- Applied BID; more convenient; more efficacy as driving more into the skin
Volatren Regular STrength 1.16%
- APplied TID
Often recommed the regular capped voltaren a shigh price to pay for the special cap
Where does voltaren emugel fit into lower back pain therapy?
1) Topical NSAID
2) Oral NSAID
3) RUB A535
More proof for OA knee and hand then the back area
–> Most studies have been done on the knee
Less side effects than oral NSAIDs
–> The low systemic absorption of voltaren emugel (6% systemic absorption) is associated with a low incidence of systemic side effects
Chronic low level back pain; may be more useful than oral
Drug of choice in patients >75 years old
Describe the dosing of the regular strength Volatren Emugel? Do we use this recommendation?
No dosing card
Apply the gel 3 to 4 times daily
The amount needed will vary depending upon the size of the painful or swollen are:
2-4 g (1 g equala a strip approximately 2 cm long) gel will be sufficient to cover a 400-800 cm^2 area
Never doing this kind of deatil
When recommending Voltaren emugel, how much should we recommend?
Almost all patients will go with their own judgment
Suggesting a _______ amount will be fine for vast number of cases
For chronic low back pain, how much voltaren emugel should we recommend? Other joints?
1 FTU is fine for most cases
Covers the area of the back and front of hands
2 cm strip is often fine T-QID (not doing this)
Other joints, just a dab (example: knuckles, just pea sized dabs)
Voltaren Rx Agent and ISsues
Diclofenac 25 mg
Oral Tablet
Local and PG issues occuring here
What is the main adverse effect of voltaren emugel?
Local skin irritation
Unlikely to have systemic PG issues
Is the easy to open cap or no mess applicator of volatren a good move?
No
Manufacturing move
25 grams less when go the easy to open cap
No mess applicator –> Lift it, squeeze against the skin, moves back, don’t get anymore
–> Still messy, pad not looking great after one month
Is the dosing card of voltaren emugel useful for the xtra strength volatren? Issue?
Extra strength topical gel is measured to give an accurate dose
Ususal dosing card is supplied with the medication to measure a 2g doses and apply the gel to the affected area 2 times daily
Basically everyone is instructed to use the same amount
2 FTU’s is what everyone is getting here
Way too much
What is the dosing of volatren extra strength?
BID
No mention of altering the dose according to the dosing card
Describe the role of anti-depressants in chronic low back pain
ANtidepressants are the most prescribed medication for chronic low back pain
Systematic Review –> Antidepressants have a limited role –> Ineffective or had very small beneficial effects
Recommendation for Duloxetine (other SNRI’s) –> Norepi effect
Leap of hope aspect here
SSRI’s do not have a large role here
Describe the role of anti-depressants in OA and sciatica
SNRI’s offered nonclinically relevant benefits with people with osteoarthritis
questioned SNRI’s and TCA’s for sciatica
TCA’s for neuropathic pain
Sciatica –> DUloxetine on MD”s radar
Describe the role of SNRI’s and TCA’s in chronic back pain
Back Pain specifically –> Duloxetine (SNRI) does help, while TCAs were inconclusive
Liked nortriptylline better than amitriptylline
All based on neuropathic pain
Descriptive symptom of sciatica
Sharp pain down the back of leg to the knee
–> Neuropathic pain
What is shingles? RAte? Main intial Sx presnetation ?
Shingles is the re-activation of the herpes zoster virus (chicken pox)
Chicken Pox as a kid –> 20-30% chance of reactivation
Symptoms and rash tend to be unilateral
What is a preventative strategy for shingles?
Get vaccinated
Small price to pay for not having neuropathic pain later on
Is shingles a single phase condition?
No
Acute and chronic phase
Acute phase treatment of SHingles
ANtivirals within 72 hours of the rash’s initial appearance (higher dose than cold sores)
Analgesics - can use for acute phase (first 3 weeks)
For itch –> Cool compress, calamine
How long does the acute phase of shingles commonly last?
3 weeks –> Can use analgesics in this time
Should clear within 3 weeks
Describe the chronic phase of shingles and its assosictaed treatment
Rash has now healed - month later
Pain occuring due to damage to nerves by herpes zoster virus
Analgesics –> Not great as neuropathic pain here
TCA’s on the radar for neuropathic pain
Gabapentin/Lyrica/Carbamazepine
Capsaicin –> Topen agent –> Tough on the skin an dno guarntee if working
1/3 of patients do not like this aget –> need to use consistently; not PRN
Post-herpetic Neuralgia - OTC agent
Zostrix
Not for acute shingles (rash phase) but option if in a chronic phase
Applied TID where the pain appears to be (no rash to guide you)
Not dosed PRN - needs consistent applicatiion in order to depelete susbtance P
Zostrix Ingredient and Adverse EFfects
Capsaicin
Burning, stinging, and skin redness
Intolerable in 1/3 to 1/4 of patients
What is the most common cause of sciatica
The most common cause of sciatica is a bulging disk or hernaited disk
Oral NSAIDs for Neuropathic PAin
NSAID’s are not usually effective in treating neuropathic pain
No difference in NSAIDs and placebo nregarding adverse effects or pain
If nerves being fired –> NSAIDs not helping
If a high suspicion of sciatica in addition to back pain - not pharamcist territory
Save money on avoiding NSAIDs and avoid adverse effects
