pharma sheet # 20 - Karam Elias

بسم الله الرحمن الرحيم

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بسم الله الرحمن الرحيم

-Non steroidal anti-inflammatory drugs.
- 2 types of agents
We talked about aspirin  indication toward dentistry is little, but there is very strong dug interaction.

Note:
You should know that pain or analgesics are drug (A) all of them you [as a dentist] can prescribe them (because you are dealing with pain)….. So you will need to decrease the pain of the patient that is suffering from a dental pain.(any type of pain).
First drug we talked about is:
1) Aspirin  interaction or prescription from dentists is low, because it’s a little bit old and it has complications more than other drugs.
Aspirin cause:
I. Increase the risk of Reye syndrome in children.
II. GI bleeding is high relatively (every patient who take aspirin will lose 8ml of blood at low doses {325…} and it’s usually with defecation).
So, it’s a very bad drug…… but why it’s still present?
Because of arthritis and it has high anti-inflammatory activity.

**it’s popular now because it has been proven that it has an application in prevention of heart attack and MI (heart diseases).

**So you need to know how to interact with this drug.
**also we said that you have to give aspirin in the morning, and then you give the NSAIDs so no interaction develops on the same side of activity. [Pharmacological interaction or antagonism].


2) Acetaminophen (paracatemol, panadol) which is a very important and popular drug.
**drug of choice for children  because it doesn’t have side effects.

NOTE:
Always keep children away from side effects… 29lan keep children away from drugs.
-similarly we apply this to pregnancy; keep pregnant women away from any drug {should be drugs free}.

**acetomphine  you can give it to a pregnant women because it has no side effects on the level of tetrogenic and on closing of arteries (action of aspirin & )

** It’s a safe drug, one of the most drugs that are used in the world.
**acetomphine is not part of NSAIDs but we considered it to make comparison
-weak anti-inflammatory activity.
-weak COX1 & COX2 inhibitor (imp).
So the efficacy of acetaminophen is always lower than other NSAIDs, but what is the solution?
We add another drug to it low dose of codeine, hydrocodine or hydroxycodine.(one of them).
This will give us additive effect & it will increase the efficacy of the tablets we take.

Remember:
Don’t take one tablet of paracetamol, you have to take 2 tablets, because the 1st tablet gives a low level that doesn’t reach threshold of pain, so when you take 2 tablets it will reach the threshold of pain … & at the end the maximum efficacy will be low.
So we give it with codeine or hydrocodine.
**you will take 2 drugs: paracetamol & codeine.
 We’ll talk about codeine side effects later on, so you have to understand this.
Codeine is sedative…. Make the patient tired & sleepy (there is some side effects)


Note:
When you prescribe a tablet to a patient that contains more than one drug, you need to take care of the possible side effects of the 2 drugs!
When we’ll talk about opoids things will be clearer. {Opoids have a sedative effect}.

For eXample:
If the patient is alcoholic, there is a high interaction between alcohol & codeine, which will cause CNS depression.


NOW, we will talk about a group of drugs which are very important in our life:-

*propionic acid derivatives:
Their chemical name is not important.
-Ibuprofen, naproxen, fenobrufen, katobrufen, oxapaszoin, and fluroprofen. All of them are one group (one chemical).


 ReviSion:
-Most drug was used before  aspirin.
-Most drug is being used nowadays  acetaminophen
-Most drug is being used in dentistry Ibuprofen.


**Why Ibuprofen is being used in dentistry?
a) The efficacy is more for ibuprofen than that to acetaminophen.
b) It’s better than aspirin (even its efficacy is better than aspirin).
c) Very nice anti-inflammatory activity (dosing effect  high dose… high activity of ibuprofen). We talked about it.

**We have choices in ibuprofen
Meaning  if a patient has normal pain you can start with him by 200mg, 3 times a day.
If the pain increased more  400mg, 3 times a day.
If the pain is severe, you can give him 800 mg 3 times a day.
Note that we are talking about dosing. Ibuprofen has a wide range of applications & there is an important idea in pharmacology which is experience:
-flurobrufen is better than ibuprofen.
-ketobrufen is better than ibuprofen.
On the level of analgesics But brufen is the most drug that is used (which we call it pharmacological experience) 
-Most drug used.
-most drug safe.
-Most drug popular.
From these agents.



Note that  ketobrufen, flurobrufen are better at the level of analgesics  potency is more.
Potency of ketobrufen is more than ibuprofen
Potency of flurobrufen is more than ibuprofen


Naproxen:
A nice drug, but its experience is low!
*Most experience for dentistry is brufen. Generally speaking, burfen is given in dentistry.

** All of these drugs that we are talking about are:
Antipirotic , we can give it to children more than 1 year  you can give them brufen.


Notes:
• Dose of brufen is 4-6 hours, 3 times a day generally, but at night the situation of patients differ (depend on metabolic activity).
• Note more than (7-10 days), more specifically 5 days only, why??? Because all NSAIDs antagonize the antihypertension drugs (aspirin & all NSAIDs but not acetaminophen) so we try to keep the patient away from the drug.
• On long term NSAIDs usage  renal problems will develop (nephrotoxicity)
• So, the usages of analgesics drugs should not be more than 7 days or maximum 10 days {the Dr. said 5 days especially for dental pain, no more than 5-7 days maximum).
• Half life of brufen is short that is why naproxen is better.
• Naproxen half life is 12 hours …twice a day.
• Ibuprofen half life 4-6 hours … 3 times a day (3-5 times depending on the dose) makes a very nice curve in the body.
• Oxaprazin has the longest half life among NSAIDs, given once a day, used with patient who has no compliance :
1) Patients with psychiatric problems (dose not take his drug).
2) Patient with amnesia.
3) Patients with Alzheimer (old patients).
So sometimes patients don’t take their medicine (eX: brufen every 4-6 hours), we give them oxaprazin (even though it’s not better than brufen) but it’s a good choice, because it has the longest half life & administrated once daily.


 Revision:
-oxaprazin …. Once daily.
-naprozin … twice daily (every 12 hour).
- ibuprofen … 3 times a day (6 hours usually).
-All other drugs are given 3 times a day.

NOTE:
Antihypertensive drugs with NSAIDs should not be given together BUT no interaction between the antihypertensive drugs & aspirin…because the aspirin is given in low doses (81 mg) so..no interaction with these agents
But Most of the NSAIDs have a relationship with prostaglandins which have a relationship with long term equilibrium (or control) of hypertension.
SO… any patient with hypertension should not take these agents for more than 7 days.


**MOST COMMON SIDE EFFECTS:
*Gastrointestinal bleeding (like aspirin)
BUT the percentage is lower... so the advantage of brofen is that bleeding of GI is lower than the bleeding that is caused by aspirin... (Not equal  aspirin has more side effects).

NOTE:
-Ladies usually use ibuprofen for dysmenorrhea (very effective)…why? Nobody knows …all this is clinical experience .
WHY they do not use ketoprofen, diclfenac ,voltaren  because of people experience.
-(not required)…
Flurobrufen is one of the drugs that are used in ophthalmology give analgesic effect if you put it as an ompment after treatment or after surgery.

_you need to know that brufen is used for dysmenorrhea (popular used in women )….WHY??
Because you might prescribe ibuprofen to her , and she used to take brufen for dysmenorrhea (or dolaraz which is the same as brufen)  so she will take 2 drugs contain brufen… so the level of brufen will increase in the blood of the lady (high dose of brufen) and the liver & kidney will be destroyed.

-so you have to be careful with what to give to the patient ,and you have to know the OTC drugs they take.

-All agents (ketaprofen ,ibuprofen…) have the same effect but have different potency.
Means:
Ketaprofen= brufen
40 mg = 200 mg
in activity…. [ potency]

Flurobrufen = brufen
200 mg = 800mg
All these drugs are present on the book (table on the book)…..just ll 2manh 2l 3lmeh =)
oxaprozin …58 hour half-life (once daily) !!!!


NOTE:
If the patient have allergic from aspirin  you will consider that he have also allergy from brufen , naproxen , diclofenac and voltaren ….so you do not give these agents to him and you give “acetaminophen”
-all have the same allergic reaction cross reaction in patient (ALL agents EXCEPT acetaminophen)
-you can use…codeine

*BRUFEN IN DENTISTRY:
- pain relive from TMJ and toothache.
-dosing:
*NORMAL pain 200 mg roughly =pain relief effect.
MAX. prescription of aspirin,acetaminophen1gram(1000mg).
Here we have “potency”….so brufen is better than acetaminophen & better than aspirin(high activity)

*more SEVER dental pain  we increase the dose .
(in normal pain we stay on LOW dose =200mg).

SO in SVER pain HIGH dose ……such as the pain following oral surgery ,the analgesic effect of 400 mg of ibuprofen is superior to 1000 mg of aspirin Or acetaminophen at least equal to 600 mg of acetaminophen + 60 mg of codeine (like we said  increase the efficacy).

So in pregnant or children instead of given brufen you give (the Dr. then said you will not give to a pregnant lady this , when we`ll talk about codeine we’ll know more) 600 mg of acetaminophen + 60 mg of codeine……[the acetaminophen reach the level of brufen in efficacy ‘in high dose’].

*AGAIN…on the level of pain
- if the pain is normal  (200 – 400) mg.
-if the level of pain is little more than normal  (400 -800) mg.

**Then we’ll compare brufen to :
1) Aspirin … because aspirin is the oldest drug present , so it`s the prototype.
2) Acetaminophen … because it is the MOST used .
- So.. Brufen is BETTER than acetaminophen & aspirin (when you take 200 or 400 milligram)
- in acetaminophen and codeine  brufen will not be better than them (almost equal ).
- Extra panadol & modern extra  they don`t contain high dose ,they contain 12.5 of codeine.
-SO…panadol extra is weaker than brufen
- Brufen (400 -800 mg) is STRONGER than acetaminophen with codine (imp.)


Note:
-General effective prescription for brufen following a dental surgery 400 mg every (4-6 hours) as needed for pain …. & the maximum dose should not exceed 2400 mg which mean  6 tablets of 400 mg (imp.)
-Don`t give the patient more than 2400 mg except in sever pain ( TMJ pain)so high dose but normally don`t exceed 2400 (because of the risk\ benefit).
-3200 mg of sever pain( 800 mg tablet 4 times a day) this is the max. dose ….more is not allowed.
-not contraindicated in children ( you can give it to them but with changing the dose)…ex.there is brufen syrup daily dosing for children depend on (based on):
1.age
2.body weight.

RVESION:
BRUFEN..
• very famous use in dentistry (we have to understand every thing about it…imp)
• Prescription..
-start from 200- 800 depend on the pain.
-max. dose 3200mg (if the pain is sever like in mandibular pain)….
but the usual dose that we should not exceed it…generally speaking if the pain is moderate  you give 2400 .
- mandibular pain 800 mg.
- normal pain1200 mg(400 mg 3 times a day) .

**Possible side effects:
--dry mouth (occasionally xerostomia ….related to dentistry) how?? Nobody knows …maybe because of prostaglandin) ,,,,otherwise  short time use less than 1 week.

*MOST common side effects for ibuprofen :
1)abdominal pain  because patient will have ulceration( change in homeostasis of stomach ).
2)Nausea
3)Increase bleeding time.
NOTE:
• Incidents of these side effects are lower compared to aspirin.
• We always compare with aspirin .


NAPROXEN:
• NSAIDs group.
• Related to dentistry.
• Long duration of action … MEANS twice daily ,,activity us for (8-12 hours)it is easy to use (give naproxen to the patient instead of ibuprofen every 4-6 hours).
• Dosage for dental purposes:
General effective prescription of naproxen sodium following dental surgery is 450 -550 every (8-12 hours) as needed for pain here the activity of the drug is better than ibuprofen on the dosage level (called compliance) because the patient always forget to take the drug, but in dental pain he will never forget it because of the pain (not like the hypertension  which is a silent killer ..The patient dose not take the drug because he feel better) but in dental pain that will not happen because of the toothache.
MEANS…if he take ibuprofen 6 hours …after 6 hours the pain start again like if you have headache & u took ibuprofen, the pain will start again after 6 hours.
SO…compliance of the patient is not a problem in pain (analgesia  he is in pain so he have to take the drug) [not silent killer].
• There is a MAX. Daily dose  1350 , 3 doses of 440mg on the first day of therapy and 1100 mg on the following days…why?? Because building up of the drug will take place (accumulation)
• if you give the patient 1350 mg daily he will reach to the toxic dose.
• NOT recommended for children under 14because it is toxic to children (imp.) …..(Remember  ibuprofen you can give it to children but u have to change the dose depending on age & weight )
• The activity (half-life)is from 8-12 hours depend on the patient ..every patient is different….depend on: what he ate ,how much is absorbed , eliminate ,diaries….so there is always a range for the half-life because of variation between patients like in obese patients need more, children needs more……& there will be no problems because the limit which is 1350 mg on the 1st day will not be exceeded then no more than 1100mg.

ENDOMETHASONE
*the MOST potent NSAIDs.
* least used NSAIDs.

REVISION:
• Aspirin  the most drug used before…BUT now its usage decreases & it is only used for arthritis & heart problems.
• Acetaminophen Most drug that is in use now.
• Ibuprofen most drug used in dentistry.
• Naproxen very nice because it is given twice a day but you should not give it to children.
• Endomethasone  most potent NSAIDs & least used…..

*Endomethasone can be use in:
-gout in old patients… because they take diuretic which induce gout.
* dentistry doesn’t use it …why?? Because it has a GI compliant (like ibuprofen &aspirin) &makes CNS effect ,confusion ,sever depression …
So…SIDE EFFECTS:
1) CNS effect.
2) Makes hematological reaction (neutropenia)


Contraindications:
1) nursing mothers.
2) Psychiatric patients.
3) Renal disease
4) Patients with epilepsy .
*** it is a very strong & POTENT drug





DECLOPHENAC

*used in dentistry but naproxen & profen are BETTER.
* if you have Stiffness in your neck you take myogesic or voltaren (gel)…..any pain linked with muscles strains or stiff we give declophenac Na+ .
*Declophenac is also used in short term of acute skeletal muscle injury , tendonitis .& dysmonorrhea.

WHY we use declophenac in muscle pain more than other drugs??? The answer will be next lecture 2n $Allah.



~GoOd LucK~

DONE BY: KARAM YASIR ELIAS
DATE OF LECT.:1.11.2010