Analgesics in MOS 1 Flashcards
What are the most effective NSAIDs for pain after oral surgery (currently recommended)?
- ibuprofen
- diclofenac
What comprehensive advice can be given to prescribers of NSAIDs?
prescribe the lowest effective dose for the shortest possible duration
How many NSAIDs are on the global market ?
over 50
Suggest a reason why diclofenac presriptions are more common than ibuprofen
this is due to only small doses of diclofenac being available OTC
Ibuprofen is an effective analgesic in the control of post-operative dental pain. True or false
True
Aspirin is mainly used for…
cardiovascular treatment
What is the half-life of aspirin ?
15 minutes
What is the half life of naproxen?
12-15 hours
What is the benefit of using ibuprofen over fenoprofen?
it has less gastrointestinal side effects
What are the uses of dexketoprofen?
mild to moderate pain
Ketoprofen and dexketoprofen have similar anti-inflammatory properties to ibuprofen. True or False
true
Diclofenac and acelofenac have a similar efficacy to …
naproxen
Diclofenac potassium is _________ release
immediate
Diclofenac sodium is ____ release
slow
Diclofenac potassium was developed to manage what type of pain?
migraine pain
What type of diclofenac is more frequently prescribed?
diclofenac sodium
What preparation of diclofenac is more useful for management of post-operative pain?
diclofenac potassium
What is the main use of Etodolac?
licensed for symptomatic relief of arthritis
What is the half life of etodolac ?
7 hours
Indometacin has equal or superior efficacy to naproxen, however, it has a higher incidence of side effects. List some of these side effects
- headache
- dizziness
- GI disturbances
What is the half life of indometacin ?
4.5 - 6 hours
Mefenamic acid has ____ anti-inflammatory properties.
minor
What is the half life of mefenamic acid ?
3-4 hours
Mefenamic acid is often associated with what side effects?
- diarrhoea
- haemolytic anaemia
What is meloxicam currently licensed for use on?
- short term pain relief in osteoarthritis
- long term treatment of rheumatoid arthritis and ankylosing spondylitis
What is the half life of meloxicam ?
13-20 hours
Phenylbutazone is used for …
ankylosing spondylitis
Why is the use of phenylbutazone restricted to specialist treatment of severe cases where other treatments have failed?
this is because it is associated with serious side effects
What permits the once daily administration of piroxicam?
long duration of action
What is the half life of piroxicam ?
30-86 hours
What are the adverse effects of piroxicam ?
- more GI disturbances than other NSAIDs
- severe skin reactions
Tenoxicam also has a long duration of action that permits 1x daily administration. True or false
true
Ketorolac and parecoxib are licensed for __________ management of post operative pain
short term
Parecoxib is _____ selective
COX-2
Celecoxib and etoricoxib are ____ selecitive
COX-2
Celecoxib and etoricoxib are licensed for treatment of …
- arthritis
- ankylosing spondylitis
What coxib is licensed for treatment of acute gout?
etoricoxib
Outline the available formations of ibuprofen
- 200mg, 400mg, 600mg, 800mg slow release tablets
- 100mg/5ml oral suspension (available sugar free preparations)
- 600mg effervescent sachets
- topical preparations
What is the recommended dose of ibuprofen for adults and children over 12 years old?
300-400mg 3-4x daily
increased if necessary to a maximum 2.4g daily, administered by mouth
Diclofenac potassium is on the DPF. True or false
false
Diclofenac potassium has fewer routes of administration and is more expensive. True or false
True
What formulation of diclofenac potassium is available OTC?
12.5mg tablet for 3 day usage
What are the available formulations of diclofenac sodium?
- 12.5mg, 25mg and 50 mg tablets
- 75mg and 100mg slow release formulations
- dispersible tablets (50mg equivalent)
- 12.5mg, 25mg, 50mg and 100mg suppositories
- 75mg IM injection
- 75mg IV infusion
- Topical preparations
What is the recommended dose of diclofenac sodium for adults ?
75-150mg per 24 hours in 2 or 3 divided doses
administered via mouth or rectum
What is the role of COX enzyme?
processing arachidonic acid into prostaglandins and thromboxane
What are the isoforms of the COX enzyme ?
- COX-1
- COX-2
What are the constitutive roles COX-1 enzymes ?
- GI protection
- platelet aggregation
- blood flow regulation
- CNS function
What are the constitutive roles of COX-2 enzymes?
- renal function
- CNS function
- tissue repair and healing (including GI tract)
- reproduction
- uterine contraction
- blood vessel dilation
- inhibition of platelet aggregation
State an adverse effect that results from NSAID use
loss of gastric protection
consequent GI ulceration and bleeding
How do NSAIDs produce their analgesia?
analgesia is produced as a result of inhibition of prostaglandin production
Where does NSAID absorption take place?
- upper parts of the small intestine
- small amount occurs in the stomach
Suggest possible reasons that lead to slower onset of analgesia following administration of oral NSAIDs
- food intake
- gastrostasis caused by acute pain
these both delay delivery of the drug to the small intestine
taking them with food can delay onset of analgesia however it is recommended to take them with food as they can irritate gastrointestinal lining
When are suppository formulations of NSAIDs made use of ?
suppository (rectum)
in children when swallowing is impractical
What is the half life of ibuprofen?
2 hours
What time is the peak plasma concentration of ibuprofen reached when taken on an empty stomach?
45 minutes
What time is the peak plasma concentration of ibuprofen reached when taken with food?
1-2 hours
How is ibuprofen excreted ?
via the kidneys
What is the half life of diclofenac?
1-2 hours
When is the peak plasma concentration of diclofenac reached?
20-60 minutes following drug administration
Diclofenac undergoes first pass metabolism. True or false
True
transported via the portal vein to liver where it is metabolised before it enters systemic circulation
What does a ceiling effect refer to?
this is where additional doses of the drug offer no further analgesic benefits
Give examples of analgesic drugs that have a ceiling effect
- NSAIDs
- paracetamol
What is the benefit of using COX inhibiting nitric oxide donators (CINODs)?
- provide analgesis through COX inhibition
- they have gastrointestinal safety through the protective effects of controlled NO donation
Celecoxib has a ____ COX-2 selectivity
moderate
Diclofenac has a slight selectivity towards ____ inhibition
COX-2
Parecoxib is an injectable prodrug of _________.
valdecoxib
converted in the liver
What risks are associated with parecoxib ?
- slightly elevated risk of renal dysfunction
- hypertension
The full analgesic effect of NSAIDs is often reached within …
a week
When can you expect to achieve the anti-inflammatory effect of NSAIDs?
up to 3 weeks
If the analgesic/anti-inflammatory responses are not obtained within their expected time frames, what should you do?
try another NSAID
What does the “number needed to treat” (NNT) measure?
the efficacy of an analgesic
What does the NNT represent?
- represents the number of patients given an analgesic who achieve at least 50% pain relief compared to placebo
What does a smaller NNT number represent ?
a more effective analgesic
What is the benefit of using COX-2 selective agents/
- limiting GI toxicity and bleeding
Based on cochrane data, which COX-2 selective NSAID has been shown to have the lowest NNT? What must you take into consideration with regards to this NNT?
Etoricoxib
(1.6 NNT)
This NNT is based on data from only 4 trials compared to 49 for ibuprofen 400mg with 10x the number of participants
What is the half-life of etoricoxib?
22 hours
Etoricoxib is licensed for use in post-operative pain in the UK. True or false
false
Impaired coagulation and perioperative bleeding from NSAIDs are not considered to be a problem for patients undergoing oral surgery. True or false
true
Anti-inflammatory drugs (coxibs specifically ?) may be associated with increased cardiovascular disease risk. True or false
True
What COX-2 inhibitor was removed from the market in 2004 owing to its role in risk of cardiovascular events?
Rofecoxib
The issue of increased cardiovascular disease risk with the use of NSAIDs is particularly relevant for what kinds of patients?
patients who need long term drug use such as those with arthritis pain
State the high risk factors where NSAID prescription should be avoided
- history of MI
- unstable angina
- congestive heart failure
- suspected or known atherosclerotic disease
All NSAIDs are thought to weakly increase the risk of thrombotic events when used long term , with the possible exception of …
naproxen
Outline from the highest to lowest risk, the NSAIDs that are associated with significant GI toxicity
Ketoprofen>ketorolac>diclofenac>naproxen>ibuprofen
In order to minimise the risk of GI toxicity observed in non-selective NSAIDs, what drug class can be prescribed/taken concomitantly?
PPI (e.g. omeprazole)
List risk factors for GI complications in patients taking NSAIDs
- age >65 years
- previous ulcer history
- helicobacter pylori infection
- severe comorbidities
Treatment related risk factors
* NSAID dose
* combination of >1 NSAID
* concomitant use of aspirin
* concomitant use of corticosteroids
* concomitant use of anticoagulants and antiplatelet agents
What are the potential adverse effects NSAIDs can cause in kidneys?
((loss of protective prostaglandins))
* renal insufficiency
* anagelsic associated nephropathy
In adults with normal renal function preoperatively, what is the effect of NSAIDs used for post operative pain management on renal function ?
small, transient reduction in renal function
this renal reduction is clinically unimportant
Aspirin must be avoided in children under 12 due to the risk of developing…
Reyes syndrome
What is the recommended dose of ibuprofen for children between 3-6 months (body weight over 5kg) ?
50mg 3x daily
maximum 30mg/kg daily divided in 3-4 doses
What is the recommended dose of ibuprofen for children between 6 months -1year?
50mg 3x daily
maximum 30mg/kg daily divided in 3-4 doses
What is the recommended dose of ibuprofen for children between 1- 4 years ?
100mg 3x daily
maximum 30mg/kg daily divided in 3-4 doses
What is the recommended dose of ibuprofen for children between 4-7 years old?
150mg 3x daily
maximum 30mg/kg daily in 3-4 doses
What is the recommended dose of ibuprofen for children between 7-10 years ?
200mg 3x daily
up to 30mg/kg daily, maximum 2.4g in 3-4 divided doses
What is the recommended dose of ibuprofen for children between 10 -12 years ?
300mg 3x daily
up to 30mg/k, maximum 2.4g, in 3-4 divided doses
What is the recommended dose of diclofenac for children (6months -18 months) by mouth?
0.3-1mg/kg (maximum 50mg) 3x daily
What is the recommended dose of diclofenac for children 8-12 kg in body weight by rectum?
12.5mg 2x daily for maximum of 4 days
What is the recommended dose of diclofenac for children >12 kg in body weight by rectum?
1mg/kg (maximum 50mg) 3x daily for a maximum of 4 days
The use of NSAIDs in the 3rd trimester of pregnancy can cause…
increased risk of closure of fetal ductus arteriosus in untero and persistent pulmomary hypertension in the newborn
delayed labour onset + increased labour duration
Regular use of NSAIDs in the early stages of pregnancy is associated with …
increased risk of miscarriage
NSAIDs are readily transferred into breast milk. True or false
False
they are not readily transferred
therefore considered safe for short term use
How can you achieve aspirin desensitisation in aspirin sensitive asthmatics?
- incremental doses of aspirin
- topical administration of soluble lysine- aspirin
What is the major known interaction between NSAIDs and corticosteroids ?
increased risk of peptic ulceration
What is the major known interaction between NSAIDs and aminoglycosides, lithium, methotrexate and digoxin ?
reduced renal excretion
What is the major known interaction between NSAIDs and aminoglycosides, ciclosporin and diuretics?
increased nephrotoxicity
What is the major known interaction between NSAIDs and ACE inhibitors and beta blockers?
decreased anti-hypertensive efficacy
What is the major known interaction between NSAIDs and warfarin ?
increased severity of GI bleeding
What is the major known interaction between NSAIDs and diuretics ?
impaired diuresis
What is the major known interaction between NSAIDs and pheytoin?
reduced metabolism
The routine use of COX-2 selective NSAIDs for post operative surgery is not advised; where there is risk with prescribing NSAIDs (e.g. GI bleed/drug interactions) what is recommended to prescribe?
- paracetamol + weak opiate e.g. codeine or tramadol
When do severe side effects (GI bleed/thrombotic event) of NSAIDs tend to occur?
tend to occur with long term use of the drugs for chronic inflammatory conditions e.g. arthritis