pharma sheet # 21 - Zaina Toffa7a

بسم الله الرحمن الرحيم

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http://www.freefileconvert.com/converted/4cfbd8c7e18bb/pharma_zaina_ayman.doc
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The dr. started the lecture by answering last lectures question which was: why do we use [Diclofenac K or Na] in particular to treat mild muscle pain, skeletal muscle injury pain arthritis pain [Voltaren tablets, or بودرة حل = fast Voltaren]? Why we use this one not Profen nor aspirin? It's the same reason why we find Diclophenac gel and sprays [Voltaren gels] in football games and there's no such thing as Profen gels! The answer lies in the synovial fluid; for the half life of the drug in the synovial fluid is much longer than the half life of the same drug in the blood.
Let's say we gave a patient Diclophenac and we measured its half life in the blood, we'd find it around 2:30 to 4 hours max! But at the same time Diclophenac would still be acting as an analgesic for 6 to 8 hours! The reason for this is that the amount of drug which we normally measure is in the blood and Diclophenac has a nice property which is it's normally concentrated in the synovial fluid. So the amount of Diclophenac in the blood isn’t an indication for its amount within the body.
Now why do we use Profen not Diclophenac in dentistry?
It's because Profen is an anti-inflammatory drug and it's stronger in this aspect than Diclophenac. Diclophenacs' activity is inhibition of COX2 mostly and COX2 is much weaker than Ibuprofen.
Diclophenac is used for short term treatment of: acute muscles injury, tendinitis and dysmenorrhoea. This is all coming from the fact that it's concentrated in the synovial fluid.
. Drug 2: Etodolac
It's a non-steroidal anti-inflammatory drug.
It causes significantly less gastrointestinal irritation; due to its selectivity towards COX2 10times more than COX1.
We want COX1 to remain active while we block COX2 since COX1 is responsible for inhibition of GI irritation.
**One important point is that we don’t call this drug a COX2 selective drug because it still affects COX1 to some extent. So there's a difference in selectivity.
If you want to treat a patient for a long time = more than 3 months [chronic pain] and this patient, let's say, is more susceptible or has a history of GI ulceration, you use this drug but very cautiously! Tell him to report any undesirable side effects. This drug is the least with GI irritation but it's not the best one… it's weaker than ibuprofen for instance. You can reach to the level of Profens' action by increasing the dose.
Revision:
• Aspirin: one of the most used drugs of all time. Usage as an analgesic became less in dentistry but it's present and dentists are allowed to use it as a level of 650 [ 325 mg, 3-4 times a day, 2 tablets together ]. Aspirin has a lot of interactions when it comes to dental procedures like bleeding and development of ulcers so if your patient is taking Aspirin don’t give him NSAID and if u gave him NSAID you have to give it after Aspirin since Aspirin have to be take first thing in the morning.
• The drug of choice in pregnancy and children is Acetaminophen [Paracetamol].
Acetaminophen is better than NSAID in 2 things [3ala mostawa el analgesia]: 1- its side effects and 2- its speed of action. Acetaminophen is fast in action than any NSAID. If you took Profen and acetaminophen the later will work faster [15mins] and Profen will take [25mins] to work.
Sometimes we give Acetaminophen and Profen together for faster n better action but this doesn’t mean we are giving 2 NSAIDs coz acetaminophen and Paracetamol are not NSAID, they're just from the group. Never give 2 NSAID together.
• Profen, Naproxen, Oxaprazen, Ibuprofen and Floraprofen.
Naproxen: is taken twice daily, never give it to children while you can give profen to children! < Important point!
Oxaprazen: is taken once daily coz it works 24hrs.
All the case studies we discussed were about Profen coz it's the most clinically
Experienced.
• Indomethacin: it’s a very bad drug since it causes confusion and psychiatric problem and it has a contraindication with psychiatric and epilepsy patients and even hematological problems. That’s why we stay away from it unless the patient has one of 2 things: 1- unresponsive arthritis to NSAIDs, 2- acute gout.
Dentists should prescribe this drug, but if the patient was using it he's going to be more susceptible to inflammation.
• Diclophenac Na: is very popular. It's concentrated mostly in the synovial fluid but it's not stronger than profen when it comes to dental pain, but it can do the job anyways.
Q: why nowadays we find Diclophenac K? What's the difference between it and Diclophenac Na? When do we prescribe Na n when K?
A: Na is the main mediator for the blood volume in the body; it's responsible for re-absorption and excretion of water in the nephrone. We prescribe it for patients with hypertension coz most of these patients take diuretics which affects the K.
• Etodolac: use when there's a long term treatment of pain. We use it coz it has less selectivity towards el COX1.
Note: remember ALWAYS that we are dealing with drugs that have Nephrotoxic effect. Nephrotoxicity comes from the fact that these drugs affect the prostaglandins and disturb the homeostasis of kidney like blood flow and filtration. If these drugs were give more than 3 months they could cause kidney problems. Always advice your patient to never take drugs unless you need them, coz there are lots of Jordanian people who take profen everyday.
• Diflunisal: Dentists prescribe it when they extract wisdom teeth. It's very effective towards acute pain. Use it when there's a doubt profen could relieve this kind of pain. It's not that popular coz it's still new, not that much clinically experienced in dentistry.


Let us talk the loading dose for a bit.
In Naproxen the patient can take 2 tablets on day one [1350] then he has to use a lower dose on the following days [the building up principal]. The same thing happens with Diflunisal; to make it work faster plus to not give him acetaminophen with it, this way we give him one drug only. We increase the dose at first coz there's a lag phase 30 mins to 1 hour. We give him initially 500-1000 mg followed by 250 mg every 8-12 hours. it’s a similar drug to Naproxen. It also has a mild sedative effect that’s why dentists like it a lot.
Again, we do this to 1. Fast action 2. Rapid building up for steady state.
A question by student: when we give the patient a drug n we find it not that effective, should we increase the dose or increase number of times taken daily?
Answer: initially, we increase the dose fast [instead of 500mg, give him 100] but not always since there are drugs which if u increase the dose they won't work or they might have severe side effects. The loading dose principal came with clinical experience. So, give him initially high dose build the drug up in his body fast then lower the dose coz it's already there in his body. Now increasing the dose or increasing numbers of time taken depends on the drug. For example, when it comes to Profen, if the patient isn’t responding for 400mg, give him 600 or 800mg coz you're playing in the safe side still. Profen is very safe so you can manipulate with the dose from 200 till 800! Unlike Aspirin and Indomethacin.

Last topic in NSAIDs =)
Remember how much these drugs affected the stomach? Now we're going to talk about drugs COX2 selective NSAIDs. Very similar to the story of Etodolac.
A student asked: is COX1 only found in the stomach?
Doctor: COX1 is found in lots of places in the body. For instance, its important in tissue homeostasis, but it's effect on the stomach is mostly shown when using NSAIDs>> no more protection against irritation of the stomach.

Now back to COX2-selective type-NSAIDs.
They're dangerous. An example for them is [Celecoxib - Celebrix]. It's used in rheumatic arthritis and as an analgesic in dentistry. Remember this idea about Celebrix, never use it unless you need it, in situations like: patient with peptic ulcer.
Adverse effects: abnormal taste, stomatitis, xerostomia [just like profen] and teeth disorders.
Rofecoxib [Vioxx] 2004 story…
This drug came out on 2000-2001 and became the most prescribed drug in dentistry. Why?
Because dentists mostly prescribe NSAIDs and this drug solved the issue of ulceration completely. So instead of asking the patient if he has ulcers or a history ulcer, just give him this drug and get it over with. On 2003 there was 2.5 billion revenue just from this drug. On 2004, lots of death incidents were reported among patients, with and without heart problems, using Vioxx. By the end of 2004 Vioxx was removed from the market coz it was believed that it's the reason behind causing heart attack and MI which lead to the death of these patients.
On 2005, people started having doubts. Since Vioxx induced such problems, maybe all NSAIDs induce such problem. Scientists did a lot of researches 2009 and compared all these drugs to Rofecoxib which was removed earlier from the market since it was reported to be toxic.
Going back to 2000 when Rofecoxibwas released, the results of its IRR [incidence rate ratio]-before it went into the market -stated that this drug may increase the chances if MI, angina and heart failure! But still they sold that drug to people. Already this drug was known to be toxic!! Why did they sell it? Greed probably! But no one really knows. Shame!
IRR of Naproxen stated that it’s the best drug for patient with heart problems [least toxic towards them]. This is the second reason why Naproxen is very common. The first reason was that it's taken every 12 hours.
Here the doctor showed us research papers from 2009 and read from them.
i. Other reference wrote that the individual who took the Diclophenac has a 50% increase risk of MI, stroke or death from any cause compared with Naproxen users.
ii. The author pointed out that Diclophenac is widely used outside the US and has been the reference drug in several COX2 inhibitor outcome trials and this exceed risk was reported with high dose as well as low dose.
iii. profen using individuals have a 25% increase risk of MI, stroke or death end point compared to the Naproxen. But that doesn’t mean that all users are going to have heart attacks, it just means that there's a risk should be taken into consideration.
iv. Comparison with the high dose Naporxen use, user of high dose of Cerebrix and Rofecoxib had increase risk of heart disease but less.
To sum up, the end result of this table is that the patients with heart problems > treat them with Naproxen and never use anything else from the NSAIDs. Go as far as you can from Diclophenac when dealing with old people.
FDA has announced a product labeling change for all NSAIDs including COX2 selective drugs Cerebrix and OTC [over the counter] medication. These changes are the result of arthritis and drug safety advisory. The FDA has asked that all labeled be revised to include information related to the potential of increase cardiovascular problems. It's a warning black box similar to the box on cigarettes box [smoking cause lung cancer].
Another 2009 case study: Naproxen best NSAID for heart disease patients. It's new and interesting and I quote: IT DEREVES YOUR EYES ;) might be useful in your life.
-=I want to apologize for any unintentional mistakes! Corrections are welcomed=-
Done by : Zaina Ayman =]