pharma # 18 -ATHEER AL-KHARABSHEH

Lec.18 26-10-2010

We have finished 2 subjects :
- Introduction to pharmacology
- Autonomic nervous system
**In autonomic nervous system there are drugs A and B but in CNS drugs
more toward *A* than *b* bcoz analgesics (مهدأ) &anesthetic (مخدر)& hypnotic منوم) ):drugs affect on CNS.
Another drugs:
Anxiolytic : anti stress drugs
**Most used drugs by dentist (analgesics &anesthetic& Anxiolytic&antibiotic
Non steroidal anti-inflammatory drugs:
_ group of analgesic drugs
_one of the imp. drug in dentistry to treat pain( which bring patient to dentist) we will explain in this sheet
Pain
Whatever the patient tells you (which is different between people according how they receipt pain) like(راسي بوجعني ,رجلي ,سني .....)
But patient cannot describe it exactly bcoz it is psychological more than physical ( ex: فيه واحد بيقدر يتحمل وجع الاسنان اكثر من غيره
It bring patients to dentist so we have to understand everything about it to relive it(no one visit us if does not have pain they concern about function not healthy.
-sometimes you do not give anesthesia from the beginning until the patient tell you “there is pain “.
-About fair of pain : can keep patient from going to dentist at appropriate time. (s.times we cannot dial with teeth until the patient take antibiotics & analgesics ….
-Ibuprofen most prescribed analgesic drug for dental pain but not all the time right choice bcoz our life update .
-Dental treatment are often done on inflamed ,hypersensitive tissues of patient .
-Pain is result from release mediators (PG(α,E2 ,f ,ILs…etc), bradykinin, histamine ,serotonin) most imp. Are PG its sensitive to pain
-PGs are released in damaged tissue toward Nerve pain messaging(sensitization for pain)
If there is injure in the leg swelling response PG release pain

Inflammation
Protective mechanism (good ,bad thing )
--Good; type of our immune response
1- (tonsillitis –overtaking around bacteria in tonsils )
2-(Bronchitis –patient enter bad thing toward bronchia & inflammation against these thing)
--Bad (hypersensitive patient ;any thing can trigger inflammation like hay fever (حساسية الربيع ) rhinitis (20%from Jordanians suffer from it) most of them do not know just coughing ..etc)
Back to some terms
1-Analegesics
2-Anti inflammatory
3-Anti pyretic
**linked together: they mediated by the same thing –PG response in our body produce 3 thing pain, fever, inflammation
#Pain(messaging toward nerve then to brain then pain in any organ )
#Inflammation (edema - increase vasodilatation increase permeability increase entrance of interstitial fluid toward
Inflamed area inflammation)
#fever(link with PGE2 go to fever center in brain in hypothalamus increase set point like ثيرموستات في السيارةتحافظ على حرارة السيارة if pathogen enter stimulate PGE2 increase body temperature above 37.5
-The drugs that deactivate PG (fever, pain ,inflammation) that mean work as 1.2.3 + anti biotic &these drug are NSAIDs
-It is suitable for dentistry :treat inflammation +pain+ fever at the same time . because of that using Ibuprofen or aspirin (NSAIDs)is better than paracthemol or acetaminophen that has less activity on inflammation)
Note : pain +inflammation at the same place around teeth so solve 2 problems by NSAIDs
-NSAIDs are from the oldest drugs especially aspirin (1830-1831) **in handout 1829** but morphine (1821)من شجرة الخشخاش
- analgesic Drugs used to relive pain derived from Greek an-,”without “and –algia”pain” 1st drugs were used
act on peripheral & CNS it 2 types :
1- opioids( morphine, herowen ,codaine , phntanel, mpreline)
2- NSAIDs
- Arthritis الروماتيزم (swelling &pain in legs ) the main application of NSAIDs in clinic (medicine)
About anti biotic effect :
We see it every day especially in children like diclogesic (suppositories)
If child >1year (diclogesic)
If child<1 year (adol)
To reduce body temperature by acting on hypothalamus that may explain in sym. & parasym like aspirin it reduce temperature but not below normal set point ( normal person does not affect by aspirin 37.5 before &after taking aspirin)
4- Addiction
Happen when there is dependence &tolerance more related to opioids
Strong relation between opioids &addiction dependent on substances like alcohol &drugs to point stopping is very difficult and cause severe physical and mental reactions. (when we study opioids we will talk too much about it

NSAIDs
1st group : v.easy
Widely use therapeutic agents (every one took NSAIDs in different form like Ibuprofen or diclogesic gel on the skin ,aspirin ,piroxicam ……etc
There are problems about these drugs (2003-2010) controversially issue about usage of NSAIDs (long term) &different opinions about that.

- inhibition of COX that inhibit transduction of PG & thrombaxins(A2)or general
- Back to physiology PG activity & production
- Production :from phospholipids in the cell membrane (from arachidonic acids there is long cascade contain COX1,COX2,COX3(rare) {COX: CYCLOOXYGENASE }
- ALL drug s NSAIDs inhibit cox that mean inhibit of PG ,THROMBAXINE
- PG mediator in inflammation
- Thrombaxine ; has role of inflammation , platelet gathering factor when inhibit it anti platelet activity
- COX
- Cox1:wide spread constitutive enzyme &imp. In tissue homeostasis
- Cox2 : induced in inflammatory cell by inflammatory mediator (the target of anti inflammatory drugs )
- Cox3: does not have wide replication boz it is isoform of cox1 >
- We have to know the difference between them
- why aspirin cause irritation in the stomach ?
- answer: bcoz it work on cox1 (wide spread, constitutive enzyme &imp. In tissue homeostasis) that keep stomach walls by mucous secretion which prevent acids reach stomach tissue (when we give anti inflammatory drug block cox1 inhibition of mucous secretion and tissue open to acid (1.5pH) like you give him HCL (v.acidic)
--to resolve this problem :when we give this drug ask patient if he has
(peptic ulcer) or tell him if there is any pain in your stomach tell me or give him drug decrease stomach acidity like omeprazole decrease( H+, inflammatory injure )
-we concern about cox2 inhibitor selectively to prevent adverse effect .most of drugs act on cox1&cox2 except cox 2 inhibitor drug :vaiox ,selebrix (trade name) & generic name lethoxin that inhibit cox2 without cox1
-VIOX : after2002(use it instead of Ibuprofen, diclofenac. patient who take it do not suffer from peptic ulcer but there is sudden death (patient with heart problem more susceptible to heart attack sudden death) after that no more using of this drug )
- when new drugs are discovered we have to do toxicity test (on #of patients (randomly) and wait for side effects to know if this drug safe or not in normal person (without heart problem or hypertension ….etc) but in reality some companies do this test & do not wait(no trial time &reports) many problems appear after that especially with dentists, doctors and nurses they do not have reports so they should write side effects &send to company (clinical pharmacology).
-in some drugs this state written on it “this is drug has been approve in normal patient> what about not normal, that why the test is very imp. Is this drug is suitable or not.
-About الدوائية الثقافة it is v. imp bcoz many drugs have limits like Viagra with patient have heart problems & take nitrates .more problems
-Back to aspirin & GI disturbances & it is the most drug that used &we know a lot about it .
-Aspirin hypersensitivity : 15% of patients suffer from it (it has wide applications)
-Hypersensitivity is normal case (although you do not see it in yourself ) due to mast cell Histamine itching ,respiratory stress ,difficulty in speakingبدل السين شين
-some NSAIDs are superior to aspirin& it cause less gastric irritation & /or take less frequently .,less side effects
-aspirin{ (ASA)acetyl salicylic acid} is unique in ability to acetylates COX irreversibly (give it acetyl group & inhibition it) and continue until the body produce new COX &it is enough to inactivate thrombaxine A2(only aspirin do that) if patient suffer from chest pain & he has history of angina pectoris ,MI)
We give him aspirin not Ibuprofen (Ibuprofen cannot acetylate COX irreversibly)
-other NSAIDs are reversible inhibitor of COX
- aspirin is rapidly break down in body to produce salicylate ( not v.imp)
-Like other NSAIDAs anti inflammatory, antipyretic and analgesic effects.
-contraindicated in children bcoz hypersensitivity toxicity anaphylactic shock (15m or 10mg) may cause death ABOUT elder patients intolerance & -most prescribed Anti palate aggregation drug (baby aspirin)
-aspirin as anti inflammatory : the primary clinical application of this action is in treatment of musculoskeletal disorders : rheumatic arthritis(as we explain before about PG) although it inhibit inflammation in arthritis it does not arrest the progression of disease nor induce remission(cure:شفاء
-Aspirin is treatment) for symptoms bcoz it is auto immune disease
-Aspirin still 1st line therapy for rheumatic arthritis(it may not true ,it old info. Since 2003 but aspirin still used)
- it used as Pain relieve in mild to moderate pain
(mild :headache from stress , didn’t eat)
Moderate : reason for pain like while playing football –injured or problem in leg (spindle التواء)
Sever : chronic problem open heart (very painful) /cancer like in bone
-we don`t use aspirin as analgesic bcoz it weak not like Ibuprofen less potent (we give high dose)as we say act in CNS & OUT OF IT we reduction PG in(low) mild to moderate like headache ,arthritis.
- as antipyretic :we give it to febrileيرتجف patient due to fever bcoz it acts peripherally & cause vasodilatation excessive sweating more than Ibuprofen& diclofenac &other drugs heat dissipation (loss of heat)by conduction,radiation,evaporation of sweat (when you run ATP body temperature so we want keep set point in thermostat
-aspirin is one of the most effective drugs in heat dissipation.
-When aspirin acts as :( we will talk about ratio of dosage){{1tablet=325mg}}
1-anti pyretic: low dose (2 tablets/6hours)
2-anti inflammatory: high dose (3-4tablets/6h0urs)
3-analgesic: low dose (2tablets/6hours)
4- Anti platelet aggregation (81mg very low dose) we give him prophylactic toward heart problems (baby aspirin)
Aspirin dosage different with different patient, situation &different condition

ATHEER AL-KHARABSHEH

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Gd luck in ur exams