Analgesics Flashcards
What type of analgesics are capped at OTC dosing?
NSAIDS
Ibubrofen OTC Cap
1200 mg/day
Naproxen OTC cap
440 mg/day
OTC Capping of NSAIDS vs Acet?
This means theoretically they are LESS effective than acet at OTC doses
However, for pain many say ibup works better for them
Pediatric NSAID’s to Use
Ibu –> YES
Naproxen, ASA –> NO
Ibuprofen Adults Timing
- Every 8 to 12 hours –> Mainly just BID
OTC analgesics exhibit a…….
Ceiling Effect of Pain Relief
Does Morphine pain relief ever flatten out?
NO
Ibu pain relief maxes out at….
400 mg/dose
ASA and Acet pain relief max out at…..
1000 mg/dose
In cases of inflammation, ibu doses would need to….
- Go beyond OTC cap of 1200 mg –> get anti-inflammatory action
Dosage of Ibu for Headache vs. Dental Pain
Headache - 400 mg TID
Dental Pain with Inflamm. –> 400-800 mg TID
Which OTC analagesic is the most convienient? WHy?
Naproxen (Aleve) –> BID Dosing
Are liquid gel capsules better than regular tablets?
Liquid Gels –> A little bit quicker
- Potentially carve off 2 minutes
- Not of major benefit –> If pt wants, go for it
What are the typical s/e warnings on the packaging of Ibu?
Hives - Not anaphylatic –> Rash is common
Swelling, wheezing –> Worry
Stomach Irritation
Increased risk of heart attack and/or stroke if use more than directed or for longer than directed
Is Ibu at OTC doses harder on the stomach than acet?
NO, not at OTC doses
What are the s/e of ibu and acet? Conclusion? What should we call these s/e?
Nauseau, Abdomina Pain, Dyspepsia
So, 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’ –>no one wants them but people get them
Not pathological trajectories for serious issues
When is ibu harder on the stomach/ more s/e than acet?
RX Doses
Ibuprofen S/e
Nauseau, epigastric pain, heartburn and rash (maculopapular, hives)
At OTC levels, are major intestinal s/e common? What are they?
- Gastric or duodenal ulcers
–> Epigastric pain and heartburn do not lead to gastric ulcers - OTC Levels –> Very safe agents
When giving a patient acet, what is it important for the pharmacist to ask about?
- Ask whether they currently take any other products with acetaminophen
- Remind them to stay withing dosing guidelines
Does taking analgesics with food help?
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
Food can actually delay onset of action
NSAIDS work by…. (simple)
cox-1 prostaglandin synthesis inhibition
- System effect of knocking back prostaglandins
When should NSAIDS not be taken with food?
Acute Pain when a rapid onset of effect is desired, recommend taking NSAID on an empty stomach with a full glass of water
Food delays the analgesic effect of NSAIDS and there is no reliable evidence that taking NSAIDs with food prevent adverse gastrointestinal effects
Is enteric coating of NSAIDS useful for gastric sx? What are some coatings for?
- Extended release or enteric coating do not help with gastric sx
- NSAIDs are a systemic effect of knocking back prostaglandins. Does not matter where it dissolves, as a systemic effect
- Some coatings on the tablet are there to make it taste better
What is an issue with extended release/enteric coating?
Delays maximum pain relief for as long as 3-4 hours
- Does not provide fast relief of headaches
Eenteric ASA vs. Regular G.I. Bleeding Risk
- Enteric coated ASA is just as likley to cause stomach bleeding
Pharmacists should balance the use of medicine by analyzing…..
The risk of the medicine vs. the benefit of the medicine
Ibu Decision for a Pt
- 5% chance of GI problems when used
- 100% chance of pain when not used
Acetaminophen is placebo for…..
Back pain and arthritis
Pharmacists often focus on…… risks, yet fail to mention that……
GI and CV risk, yet fail to mention that by not treating, PAIN is not treated, and that may be worse for the patient
What is the number one cause of liver toxicity? Number one cause?
Drug-Induced
Acetaminophen
- Especially in combo with alcohol
Ibu vs. Acet Toxicity: Which one is more damaging to the liver?
Acet
In regards to pain, what other sx/issue is often closely related?
Insomnia
Nightime Analgesics often have….. for what effect?
Diphenhydramine –> Sedation
When does pain often get worse? Why?
- Pain often gets worse at night
- Cortisol lowers at night, and staying in one position might cause the joints to stiffen up
What are some of the major causes of pain?
Muscle/Back/Joint Pain
Headache/Migraine
Cold/Flu
How should one asses pain in a child? Treatment?
Evualuate behavioural changes (e.g. facial expressions, mood, crying, inactivity)
- fever –> Tx if affecting behvaviour
- pain –> Tx
Acet or Ibu (or combo)
Headaches Tx?
Migraine Tx
- NSAID’s or Acet
- Triptans Migraine
Osteoarthritis DOC
NSAID’s
Lower Back Pain Tx
NSAID always
What is the drug of choice for dysmenorrhea? Why?
NSAIDS
- Prostaglandin derived syndrome
- Contractions in uterus by prostaglandins
What is dysmennorhea?
Cramping pain is the lower abdomen that can start from 1-2 days before your period begins and can last for 2-4 days
Dysmenorrhea Prevalence?
- Most commonly reported menstrual disorder
- More than one half of women
Is caffeine required for dysmenorrhea?
DO NOT need caffeine
- Midol, Maxidiol –>Used for PMS; NSAIDS still better
What analgesic should be used for toothaches? What rule to follow?
- Acet or Ibu –> Also combination
- Ibu –> anti-inflamm but not at OTC doses
2-4-24 Rule –> 2 drugs, 4 doses, 24 hours
Combination products of Acet and Ibu? Dose?
Combination makes sense –> Overall safe
- Not at therapeutci doses of either agent
Acet 250
Ibu 125
2 tabs Q8h (max 6/day)
Is combogesic a recommended product?
No –> Not at therapeutic doses of acet or ibu
Should anagelesics be combined with caffeine? When?
Compared with analgesic medication alone, combinations of caffeine with analgesic medications, including acetaminophen, acetylsalicylic acid, and ibuprofen, showed significantly improved efficacy in the treatment of patients with tension type headache (TTH) or migraine, with favorable tolerability in the vast majority of patients.
Adverse effects of Caffeine Anagesics
Nervousness
Nauseau
Abdominal pain/discomfort
Dizziness
Caffeine Doses for Tension Headache and Migraine
caffeine doses of 130 mg enhance the efficacy of analgesics in TTH
doses of > 100 mg enhance benefits in migraine
Is caffeine useful for people who intake caffeine already?
No. More beneficial in those who do not use a lot of caffeine
What is the problem with caffeine-analgesic combos? When does this occur? Counselling?
If used often, meds may cause the headaches
More than 15 days of use per month
Caffeine are more likely to induce medication overuse headaches –> should not be used more than 9 days per month
Caffeine-Analagesic vs. NSAID’s Headaches?
Analgesic combos containing caffeine are more likely to induce Medication Overuse Headaches than simple NSAIDs alone
Caffeine Containing Formulations are what line of tx for what?
Caffeine-containing formulations are therefore reserved as 2nd options for Tension Headache and should not be used more than 9 days per month.
Medication Overuse Headaches Tx
While stopping headache medicines to treat these headaches seems counter-intuitive, studies have shown this is the only reliable way to treat MOH
Usage of caffeine containing analgesics is for….. Not……
CNS Conditions –> Headaches
Not arthritis
What people are prone to medication-overuse headaches?
- Only people prone to headaches develop this syndrome
- Generally not seen in people taking analgesics for reasons other than headaches such as arthritis or back pain
Why is codeine not used much anymore?
- Dosages are not ideal
- Codeine is a pro-drug that is converted by 2D6 to morphine
- Depending on genetic background, people metabolize codeine to morphine differently
To sell codeine products, pharmacists require a….
Training Program
In regards to overdose on analgesics, what agents are worrying?
Acet and ASA –> Worrying
Ibu, Naproxen –> NSAID’s –> Far less of a problem in overdose
Acet Overdose is considered a……
Medical Emergency
Hepatic Toxicity in acet overdose can occur at….
Hepatic toxicity in adults/adolescents at 7.5-10 g in < 8 hr
- 24 reg/15 Xtr
Fatalities are rare when acet overdose’s are under…..
Less than 15 g
(45 reg/30 xtr)
What is the Paeds dose of acet?
10-15 mg/kg q4-6H (75 mg/kg in a day)
Paeds overdose concern of acet?
Levels drawn if 150-200 mg/kg ingested
What is the max dose of acet per day in Canada? USA?
Canada - 4 g
America -3 g
What dose of acet/day becomes a worry for overdose?
8000-10,000 mg/day
- 6000 mg appears to be safe
Is Ibuprofen overdose more dangerous than acet? What should happen?
No
- Mild sx and rarely fatal
- Get to hospital, take the bottle, number of tablets, vomitting times
What is the drug of choice in anti-coagulated patients? Why?
- Acetaminophen
- NSAID’s bounce the anticoagulant drug (e.g. Warfarin) off of plasma proteins causing more free drug that can go and do its effects
- NSAID’s exhibit plasma protein binding
Does acet have a drug interaction with warfarin? Doses?
- Several reports of an interaction
Doses at > 2.25 g per week starting point for concern
Doses > 2.5 g per week could be impactful
If a patient is on warfarin and taking acet, they should have…..
More frequent monitoring –> Close INR monitoring when starting and stopping courses of acet
Is there a drug interaction with NSAID’s and newer anticoags?
DOACS –> Rivaroxaban
- Safer with newer agents, but anticoags thin out blood so throwing on an NSAID can cause a G.I. bleed as well as bleed easier
Can a child get asthma via acet? Mechanism?
- Potentially –> Concern for this connection when exposure is in:
a) Pregnancy
b) Early Infancy
It reduces the body’s levels of a natural free radical scavenger (glutathione) (acts to modulate asthma response)
Acet Usage in pregnancy has been linked to______ in offspring
- ADHD
- Increased risk of wheezing and incidence of asthma
NSAID Usage in Asthma Guidelines?
Broken down into whether the individual has ASA-sensitive asthma or not
- Not ASA-sensitive –> Can take Ibu as directed
- ASA-sensitive –> Ibu can trigger sx of asthma or allergy. Symptoms of severe allergic rxn usually dvelop a few hours after taking the drug
What happens to an asthmatic if they are ASA-sensitive and take an NSAID?
Coughing
Wheezing
Tightness in Chest
Nasal Congestion
Headache
Sinus Pain
Sneezing
- Exacerabations in asthma after taking Ibu
- Caused by allergens, cold, or exercise
Aspirin allergy in the general population vs in Asthmatics (What other conditions)? Why does this occur?
1-2 % in General population
- 10 fold increase in asthmatic, allergic rhin, and utricaria –> 10-30%
- Increase is due to blocking Cox-1 –> Prostaglandins are important mediator sin asthma
If someone is ASA-sensitive, is there cross sensitivity to other NSAIDS?
YES
Ibu - Cross sens. 98%
Naproxen - Cross sens. 100%
When is ASA-induced asthma often seen?
Usually only seen in adulthood
Acetaminophen Usage in Asthma? Use or no?
It is believed that the metabolite of acetaminophen depletes glutathione levels in the respiratory tract and thus leads to vulnerability to oxidative stress.
This process might cause airway inflammation, bronchoconstriction, and subsequent symptoms of asthma
If a person is ASA-Sensitive, NSAID?
NO
If not ASA-sensitive, NSAID?
NSAIDS can be used
Should asthmatics avoid NSAIDS?
Not necessarily - Do not need to avoid unless you know they are asthma triggers for you
What is the legal call in asthma NSAID usage?
Do not use
What is ASA 81 used for? What is used in determining if someone should be put on this agent?
- A low dose ASA for doctor supervised daily prevenetative tx (secondary prevention of heart attack rather than primary)
- Balance of preventing a heart attack vs. risk of a G.I. bleed
What does ASA-81 do (simple?
Makes platlets less sticky
Is there a drug interaction between NSAID’s and ASA-81 mg? Mechanism?
YES –> Somewhat
If ASA 81 is on the COX-1 receptor on a platlet, the platelets are less sticky and will not form a clot. This is cardio-protective.
If another NSAID (e.g. Ibu) is adminstered, can bind to the COX-1 receptor rather than ASA –> Ibu is not cardio-protective, so neutralizes the benefit of ASA
G.I. Risk Increases in ASA when….
- GI issues increases with regular usage of an NSAID and ASA
If someone who has pain is on ASA-81, what strategies should they use to use an NSAID and ASA? When should this be used?
- Single doses of NSAID should be given 2 hours after the ASA or 8 hours before the ASA
- Multiple daily doses will be a problem
- If a one off headache, go for it. Long term usage and effects is a worry.
Is ibu or naproxen more likely to inetract with ASA?
Naproxen is less likely to inetract; however, still some evidence. Avoid if regular use is plannned
Can a person on ASA just take more ASA to get pain coverage as well?
YES
- GI risk will rise (not by much) but may still be a good option
- Cannot interact with itself on the platelet
- If taking this twice a day, getting the cardio protective function as well as the pain coverage
- Up the dose when experience a headache
What is another option for people taking ASA-81? What conditions?
- Voltaren –> Topical Diclofenac
- Not for headaches
- DOC for joint pain and people on ASA-81
Pregnant Woman are at risk of…. What are the most common agents used in pregnancy? Are they safe?
Under-tx 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 is the analgesic in pregnancy system? What do they mean?
Category A (air and water)
- Adequate and well-controlled studies have failed to demonstrate risk to the fetus
Category B
- Animal reproduction studies have failed to demonstrate risk to the fetus; there are no adequate and well-controlled studies in pregnant women
Category C
- Animal reproduction studies have shown an adverse effect on the fetus; there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks
Category D
There is positive evidence of human risk, but potential benefits may warrant use of the drug in pregnant women despite potential risks
Category X
Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits
Acetaminophen Pregnancy Safety
- Category B
- Commonly used in all stages
- Appears to be no risk at std doses (ADHD and asthma on radar screen)
What does PDA stand for? What does it do? How do NSAIDs effect the PDA?
Patent Ductus Arteriosus
- In a fetus, de-oxygenated blood does not need to go to the lungs through the bronchial pulmonary arteries
- The PDA allows blood to bypass the baby lungs (before born)
- After you are born, the pda closes and blood now shunts to the baby’s lungs
- The patent ductus arteriosus opening is maintained by prostaglandins until birth
- NSAID’s decrease prostaglandin production, therefore may be an early closure of that duct. Blood fires to the lungs causing trouble for the fetus.
Ibu in Preganancy Category. Why?
Category C up to 30 weeks
Category D greater than 30 weeks
- Causes premature closure of PDA
- Increased risk of bleeding at term
Naproxen in Pregnancy Category. Why?
FDA Category C
Avoid late in pregnancy b/c of PDA closure= Category D
Risk in 1st trimester too – spontaneous abortion (Absolute risk, tho, appears to be low)
ASA Pregnancy Category
FDA Category C
Category D in 3rd trimester
Describe the process of inflammation?
Arachadonic Acid –> Cox-2 –> Inflammation (part of the healing process)
What is COX-1 enzyme responsible for?
Helps protect GI
Negative impact on the CV
What is the COX-2 enzyme responsible for?
- Causes inflammation
- Positive CV impact
What enzymes do NSAID’s target?
COX Enzymes
- Effect them to varying degrees
G.I. Safety of NSAID’s. Comparison to acet?
Occurrence of severe damage (ulceration, bleeding) is RARE at OTC dosing for both ibuprofen and naproxen
Heartburn and dyspepsia occur with OTC ibuprofen, but the rate is similar to acetaminophen
When does the risk of G.I. safety increase? Why?
At Rx doses, risks jump a lot (blocking Cox-1 and Cox-2 more significantly)
What is an important counsleling tip for NSAID usage?
- Use the smallest amount you can
Are combination products useful for GI safety?
May lead to have less G.I. effects as lowering the acid in the stomach (PPI’s)
What enzymes do Ibu and Naproxen block? What drug is selective?
Ibu and Naproxen are going to block both COX-1 and COX-2 to varrying degrees
NSAID’s in general are broad spectrum
Celabrix –> Just COX-2
What is the NSAID and CV risk summary?
All NSAIDs include both traditional and COX-2 selective NSAIDs increase the risk of CV adverse events
It is not possible to differentiate or rank NSAIDS by their CV risk
CV events occur with both short term and long term use
Use NSAIDs at the lowest effective dose for the shortest time possible
Ibu and Naproxen - Which is safety for GI and CV?
Ibu - GI
Naproxen - CV
What are some drug interactions of NSAID’s? Risk?
Drugs that neg. affect the GIT - Increase GI risk/bleed
Anticoagulants - Increase bleeding risk
Blood Pressure Meds - Increase CV risk (bleed)
SSRI’s - Increase GI risk (bleed)
ASA 81 - Increase GI risk
Alcohol - Increase GI risk
Describe the pathway of alcohol and acetaminophen usage?
Acet can through conjugation become non-toxic conjugated metabolites
Acet can also be metabolized by P450 to NAPQ which causes damage to cells. (Chronic Alcohol - Enzyme Induction) (Acute Alcohol - Enzyme Inhibition)
NAPQ can be converted to non-toxic metabolites by glutathione. Glutathione can be depleted by chronic alcohol.
Should acetaminophen be used in liver disease/alcohol?
Pharmacist - DO not use
Patients with cirrhosis have in your situation have lower clearance of acet, so use < 2 g per day including those who continue to drink
Acetaminophen and Alcohol Safety
Acute alcohol ingestion is not a risk factor for acetaminophen hepatotoxicity. In fact, it may even be protective.
Chronic alcohol ingestion, on the other hand, may potentiate hepatotoxicity by up-regulating cyp2E1 (which will create more NAPQI metab) decreasing avail stores of hepatic glutathione malnourishment
What is another issue with NSAID and Alcohol?
Alcohol - Increased risk of GI bleed
Alcohol slowly takes the lining off the stomach
Why is it a concern for the elderly taking NSAID’s?
decreased renal
more medicines
more conditions
more bleed risk
more CV issues
NSAID’s in Sports
- Problem with NSAID’s if dehydrated, 60 years or older, kidney problems, or taking ACE, ARB, or diuretics
NSAIDS can be a problem with sports if you are dehydrated or long endurance athletes
What do prostaglandins do in dehydration?
Dehydration state –> Prostaglandins help profuse the kidneys –> less profusion 9decraesed renal blood flow) –> Kidney issues
NSAIDs in acute injury
- May need the inflammation for remodelling
