ANTI-INFLAMMATORY DRUGS IN DENTISTRY.
INTRODUCTION
Anti-inflammatories are often prescribed in odontostomatology for certain clinical pictures associated with adequate antibiotic therapy.
However, it must be recognized that they are consumed quite frequently and are trivialized by self-medication, hence the need to prefer well-conducted medication to anarchic self-medication.
Currently in dentistry, anti-inflammatory drugs (NSAIDs) are mainly used as analgesics.
Inflammation: REMINDER
1. The inflammatory reaction is a physiological (defensive) reactive process of the organism triggered by an attack from a pathogenic agent: infectious, traumatic, immune or other.
2. This process is very complex, schematically it takes place in 3 phases: vascular, cellular and healing
1- Vasculo-sanguineous phase = initial phase includes vasodilation of the vessels responsible for active congestion. The plasma fluid passes into the interstitial environment, this is the inflammatory edema
This phase is responsible for the 4 cardinal signs of inflammation : redness, pain, heat and swelling.
Similarly, many anti-inflammatory and pro-inflammatory chemical mediators are released or synthesized: prostaglandins, interleukin 1 and 6.
2- cellular or late phase : involves immune cells: polymorphonuclear cells, macrophages and monocytes.
3- healing phase which begins at the end of the vasculo-exudative phase with the formation of a fleshy bud.
In severe cases, inflammation can, in addition to these local phenomena, have systemic repercussions involving a deterioration in the general condition and fever.
This inflammatory reaction ends with the restitution of pre-existing tissues.
Definition of anti-inflammatories
Anti-inflammatories (AI) are chemical substances whose objective is to stop or reduce the inflammatory phenomenon when it is of significant magnitude; therefore they are used as symptomatic treatment aimed at reducing the functional signs of inflammation and especially pain.
AIs are classified into 3 (4) groups according to their chemical structure
*non-steroidal AI NSAIDs
* steroidal or glucocorticoid AIs
* enzymes
* coxibs
They act at different levels of the inflammatory process.
1- NON-STEROIDAL ANTI-INFLAMMATORY DRUGS: NSAIDs
They are fast-acting symptomatic drugs; they are characterized by the absence of a steroid chemical structure, thus differentiating themselves from glucocorticoids, although belonging to several chemically distinct families. NSAIDs form a homogeneous therapeutic class characterized by common therapeutic properties, a common mechanism of action, common adverse effects and drug interactions.
In dentistry, NSAIDs are mainly of interest in the symptomatic management of acute painful phenomena of inflammatory origin.
1-1 NSAIDs: PHARMACOLOGY : NSAIDs are characterized by:
- An anti-inflammatory effect : which varies depending on the type of inflammation;
- during acute inflammation: NSAIDs counteract the cardinal signs of inflammation (1st phase of inflammation): symptomatic treatment with curative effect.
- during chronic inflammatory processes: their action is purely symptomatic and not curative.
- An analgesic effect : NSAIDs are good analgesics for moderate intensity pain ( nociceptive pain ).
- An antiplatelet effect : all NSAIDs inhibit platelet aggregation to varying degrees.
- An antipyretic effect : (Aspirin and Ibuprofen) they lower fever without causing hypothermia.
1-2 MECHANISM OF ACTION
The most commonly accepted mechanism of action is the inhibition of cyclooxygenases COX1 and COX2, resulting in a blockade of the synthesis of prostaglandins and thromboxane A2 from arachidonic acid.
Membrane phospholipids
phospholipase A2
Arachidonic acid
COX1+COX2
NSAID inhibition
– Prostaglandins – Leukotriene
– Thromboxane
1-3-NSAIDs: Classification : several groups:
1- Pyrazoles and derivatives: the products in this group are the oldest but due to their serious adverse effects, they are prescribed less and less (Phenylbutazone).
2 – Indole derivatives (indomethacin, etc.) and oxicams (piroxicam, etc.): reserved for severe rheumatological conditions.
3- Propionic (Ibuprofen, Naproxen…), phenylacetic acid (Diclofenac) and fenamates (niflumic acid).
4- Acetylsalicylic acid and derivatives (Aspirin, Aspégic®, catalgine®) for an analgesic effect.
- INDOLICS: reserved for rheumatic pain.
Indomethacin: powerful anti-inflammatory effect
Special features: anti-inflammatory and analgesic at the same dose.
Side effects: – high blood pressure
– vision problems
– insomnia
– severe headache.
1-3-2 PROPIONICS: significant analgesic effect and anti-inflammatory action at high doses
a) IBUPROFEN : generally reserved for adults but there are pediatric forms.
– Suppositories 500 mg (1 suppository 3/day)
– 400 mg tablets (1 tablet 3 to 4 times a day during meals)
– Mode of action: competitive inhibition of cyclooxygenase.
It is the NSAID with the best efficacy-toxicity balance.
Ibuprofen (generics) has an analgesic action exceeding that of paracetamol and very similar to weak opioids.
ANTI-INFLAMMATORY DRUGS IN DENTISTRY.
EXAMPLE :
400 mg of Ibuprofen have
- analgesic efficacy greater than 1000 mg of Paracetamol
- comparable to the combination Paracetamol + Codeine (600 to 1000mg /60mg).
b) KETOPROFENE : Profenid® tablets and suppositories at 100 mg; widely prescribed in rheumatology
The pain of desmodontitis that is resistant to conventional analgesics justifies its prescription.
| Speciality | Dosage form | Dosage |
| algifen 20 mg Antalfen | Oral suspension | Children from 3 months to 12 years: 20 – 30 mg/Kg /day 3 to 4 doses (6-8 hour interval) |
| Upfen 200 mg | Effervescent tablets (10-20cp) | Adults and children over 15 years: 200 to 400 mg per dose (repeatable every 4 to 6 hours) |
| Gelufen Nuroflash Nurofen 200Brufen | Capsules 200mg (20 to 30 gel) Tablets 200mg (12 to 20 tabs) | Same upfen |
Main forms: Ibuprofen (max dose = 1,200mg/24h).
1-2-3 Phenylacetic Acid:
a) DICLOFENAC:
-Adult: Tablets 25-50 mg (100 to 150) mg/day
Suppositories 25-100 mg (1 sup / day)
– Child: ° 25mg tablets
° Suppo. 25mg
– Diclofenac LP 75 mg (24h)
– Diclofenac sodium (voltaren) 25 mg or 50 mg tablet and 100 mg suppository: maximum dose/day = 150 mg in 3 doses
– Diclofenac potassium: rapid K+ action (same).
1-2-4 The Fenamates:
- Niflumic acid (Nifluril) : weaker anti-inflammatory and analgesic activity than other NSAIDs.
Galenic forms: *capsules 250 mg (2 to 3 capsules/day)
*250 mg suppositories; 700 mg (1 suppository morning and evening)
* 3% ointment
-Mode of action: competitive inhibition of cyclooxygenase.
– Side effects:
* Allergic reaction.
* Gastrointestinal disorders.
* Nutritional disorders
1-2-5 Acetylsalicylic acid and derivatives (little interest in odonto-stomatology)
Aspirin: (bag) 100 – 250 -500 mg -1g
°Adult: 0.5 to 2g/day
°Child: 50 mg/kg/day
-Aspirin is contraindicated in cases of viral infection (flu for example), in children from 6 months to 15 years old because of REYE syndrome.
– is contraindicated in pregnant women.
Aspégic: (bag) 250-500-1000mg
°Adult: 2 to 3 g/day (2 to 3 doses)
°Child: 1 to 4 sachets of 250 mg/day
1-3 – INDICACTIONS :
NSAIDs should not be used alone in the treatment of inflammation where the infectious process is the origin.
They are likely to reduce the means of defense against infection leading to the extension of the microbial process if this is not controlled by vigorous antibiotic therapy and by the suppression of the oral-dental etiology.
In Odontostomatology: NSAIDs are prescribed
- Used mainly as painkillers.
- etiological treatment of certain conditions (trismus)
- Treatment of infectious and postoperative edema.
- During desmodontitis or periapical inflammations following root canal treatments
An appropriate antibiotic prescription will be associated.
– In inflammatory or traumatic syndromes of the temporomandibular joint, NSAIDs may be of some benefit.
1-4-NSAIDs and spread of infection :
This role is not clearly established; however, some retrospective epidemiological studies studying the risk factors associated with diffuse and/or widespread cervicofacial cellulitis report a positive correlation between the use of NSAIDs, particularly for analgesic purposes, and the severity of the infection.
Due to their anti-inflammatory action (reduction of edema, reduction of chemotaxis of neutrophil NP, disruption of the normal healing process, etc.), NSAIDs indirectly promote bacterial proliferation.
Despite the lack of established scientific evidence, it is strongly advised against prescribing a 1-
ANTI-INFLAMMATORY DRUGS IN DENTISTRY.
1-5 – Side effects
– Digestive disorders: nausea, vomiting, gastralgia, gastroduodenal ulcer, perforation and obvious hemorrhages (anemia)
-Allergic accidents: pruritus, skin rash, Quincke’s edema (Lyell or Stevens-Johnson syndrome = rare)
-Respiratory problems: bronchospasms, asthma attacks, etc.
-Neurological disorders: headaches, dizziness, tinnitus, asthenia
-rarely liver damage, kidney damage (renal failure, oliguria) and hematological disorders (anemia, neutropenia)
-Spread of microbial infections.INS in case of serious or uncontrolled infection.
1-6- Drug interactions
It is not recommended:
To combine 02 NSAIDs: co-prescription of an NSAID with another NSAID (increase in gastric toxicity).
Association with an anticoagulant or an antiplatelet agent: increased risk of bleeding
With a drug with a low therapeutic index: digoxin, lithium, metothrexate: increase in plasma level and risk of reaching the toxic threshold.
1-7 NSAIDs and Pregnancy (especially 2nd trimester )
Prostaglandins participate in the normal course of pregnancy, their reduction can induce at the beginning of pregnancy an alteration of the implantation of the fertilized egg.
NSAIDs do not have any significant malformative potential.
Prostaglandin inhibition is responsible for the non-closure of the ductus arteriosus, causing right heart failure with pulmonary hypertension in the newborn.
Decreased glomerular filtration rate leading to renal failure
Increased risk of intracranial hemorrhage
Inhibition of uterine contractions, prolongation of labor and increased risk of hemorrhage at the time of delivery if prescribed at the end of pregnancy.
1-8 NSAIDs: Contraindications
Directly related to adverse effects:
- Known allergy to aspirin or other NSAIDs
- History of gastroduodenal ulcer (even cured!, 06 months)
- History of aspirin-related asthma attack
- Severe hepatocellular insufficiency and renal insufficiency
- Severe heart failure
- Patients on anticoagulants or antiplatelet drugs
- Hemostasis disorders
- Pregnancy beyond the 5th or 6th month even with occasional use or breastfeeding.
ANTI-INFLAMMATORY DRUGS IN DENTISTRY.
| Chemical class | DCI | Pharmaceutical specialty | Presentation | Dosages |
| Salicylates | Acetylsalicylic acid and soluble salts | Aspirin Aspégic | Cp 500Cp 1000Bag 500 / 1000mg | 500 to 1 gr/day 1 to 3 doses Up to 6 gr/day |
| Arylcarboxylics | Diclofenac Ibuprofen | Diclofenac Voltaren | Cp 25-50Supp100mg | 75-150mg/day2-3 doses with meals1 suppository in the evening |
| Selective COX 2 inhibitors | celecoxib | Celebrex | Gel 100-200mg | 200mg/day Max dose 400mg/day (2p) |
| Fenamates | Ac Niflumic | Nifluril | Gel 250mgSup 700mg(adult)Sup 400 child | 3g/dayMax dose=6g in 3 doses1 suppo x2/day |
2-ANTI-INFLAMMATORY STEROIDS GLUCOCORTICOIDS (AIS)
2-1- DEFINITION
Corticosteroids are molecules that the body synthesizes such as cortisol or hydrocortisone to regulate numerous physiological immune and metabolic mechanisms.
Synthetic compounds used in therapy: glucocorticoids at higher doses have anti-inflammatory properties.
These steroids or steroids analogous to the precursors of cortisone, naturally secreted by the adrenal glands, have numerous pharmacological properties, many of which are the cause of undesirable effects .
In dentistry, glucocorticoids represent a major and essential class in therapy.
Due to their nature very close to cortisone, these glucocorticoids have the capacity to significantly inhibit:
-all phases of the inflammatory reaction
-a very important part of the immune system
2-2 -PHARMACOLOGY
Synthetic glucocorticoids are derivatives of cortisol (cortisone) having:
– better anti-inflammatory activity
– cause little or no sodium retention
** the main AIS administered orally:
– Prednisone (cortancyl)
– Prednisolone (solupred and solumedrol)
– Betamethasone (celestene)
– Dexamethasone (decadron)
Oral corticosteroids have a biological half-life of 12 to 54 hours, much longer than the plasma half-life.
This characteristic will modulate the distribution of doses: a single daily dose is sufficient : administered in a single dose in the morning in order to reproduce the physiological circadian rhythm of cortisol.
2-3- MECHANISM OF ACTION
The anti-inflammatory activity of corticosteroids is the result of a cascade of reactions starting inside the cell and leading to the limitation of inflammatory phenomena.
* Binding to intracellular receptors.
*Inhibition of phospho-lipase A2
Membrane phospholipids
Corticosteroids———- inhibition of phospholipaseA2
Arachidonic acid
-prostaglandin – Leukotriene
-thromboxane
Their pharmacological effect is identical to that of the natural hormone. They act with all major physiological systems (like cortisol).
1/ action on metabolism:
*Glucocorticoids are hyperglycemic : they facilitate the synthesis of glucose from amino acids (neoglucogenesis) and muscle and bone proteins. They reduce the consumption of glucose by peripheral tissues.
*increase protein catabolism, thus promoting muscle wasting and opposing osteogenesis.
*mobilize fats and redistribute them in a particular way with accumulation in the facial and upper dorsal region.
Have a discreet but real mineralocorticoid action:
- promote water retention, sodium and potassium leakage
- increase urinary elimination of calcium and phosphorus
- reduce the digestive absorption of calcium responsible for a calcium deficit.
2/ action on the endocrine system:
Glucocorticoids inhibit their own synthesis (phenomenon of negative feedback on the hypothalamic-pituitary axis = putting the adrenals to rest by a hypothalamic-pituitary braking mechanism .
3/ anti-inflammatory action:
*glucocorticoids reduce the clinical and biological symptoms of inflammation (edema, redness, heat, pain) by inhibiting all phases of inflammation.
Act on the initial and late phase of inflammation: they inhibit the synthesis of prostaglandins and leukotrienes preventing the formation of granulation tissue fibroblasts and reduce collagen formation.
4/ immunosuppressive action:
* They decrease the number of circulating lymphocytes, the synthesis of cytokines by T lymphocytes and the activation of B lymphocytes.
*they intervene in allergic manifestations by reducing sensitivity to histamine and slowing its release by mast cells and basophils.
2-4- CLASSIFICATION OF CORTICOIDS:
Natural hormone (cortisol or cortisone) used mainly in renal therapy. Synthetic compounds (derivatives of prednisone and prednisolone): superior anti-inflammatory action
- Main AIS used in dentistry (oral)
*Prednisone and Prednisolone: intermediate duration of action
*Betamethasone and Dexamethasone: long duration of action.
| ½ plasma life: min | ½ biological life h (duration of action) | Anti-inflammatory activity | Mineralocorticoid activity | Equivalence of mg doses | |
| Cortisol | 90 | 8-12 | 1 | 1 | 20 |
| Cortisone | 30 | 8-12 | 0.8 | 0.8 | 25 |
| Prednisone | 60 | 12-36 | 4 | 0.8 | 5 |
| Prednisolone | 200 | 12-36 | 4 | 0.8 | 5 |
| methylprednisone | 210 | 12-36 | 5 | 0 | 4 |
| Betamethasone | 270 | 36-54 | 25 | 0 | 0.75 |
| Dexamethasone | 270 | 36-54 | 25 | 0 | 0.75 |
2-5- INDICATIONS
03 main indications in dentistry:
1- control of post-operative inflammation ( anti-edematous)
2- preventive treatment of allergic reactions
3- treatment of auto- or dys-immune diseases of the oral mucosa.
2-6- CONTRAINDICATIONS:
There is no absolute contraindication to corticosteroid therapy for life-saving purposes . However, there are some contraindications:
- All progressive infectious conditions
- Some developing viruses: shingles, chickenpox, hepatitis, herpes.
- Psychotic states not controlled by treatment.
- Live vaccines
- Hypersensitivity to any of the constituents.
ANTI-INFLAMMATORY DRUGS IN DENTISTRY.
2-7- DRUG INTERACTIONS
* associations not recommended :
– live or attenuated vaccines (risk of fatal generalized vaccine disease unlikely with corticosteroid therapy for less than 2 weeks)
-sultopride: increased risk of ventricular rhythm disorders.
* precautions for use :
– gastrointestinal topicals, antacids, charcoal: decrease in digestive absorption of glucocorticoids.
-hypoglycemic sulfonamides, insulin, metformin: increases blood sugar
-rifampicin: decreases plasma concentration and effects of AIS
-oral anticoagulants: increases risk of bleeding
-Carbamazepine: decreases plasma concentration and effects of AIS.
-Other anticonvulsants: decrease plasma concentration and AIS effects
However, in case of necessity, AIS may be prescribed under certain conditions:
- Diabetes: glycemic control; readjustment of insulin doses or oral antidiabetics and strict carbohydrate restriction
- HTA: well balanced: no problem
- Peptic ulcer: combine anti-ulcer gastric protection.
- Pregnancy: short-term corticosteroid therapy does not cause fetotoxicity or malformation regardless of the age of gestation.
- Osteoporosis in the elderly: even long-term treatment is permitted
2-8- Adverse effects
Are to be feared at high doses or during prolonged treatment over several months (long-term treatment). Are very unlikely during relatively short corticosteroid therapy.
The only effect that appears from the start of high-dose attack treatment (prednisone > 10 mg) is the significant inhibition of the immune system, hence the absolute necessity of implementing systematic ATBpie.
Other side effects during prolonged treatment:
– hydroelectric disorders: hypokalemia, hypertension, etc.
– endocrine and metabolic disorders, stunted growth in children, decreased glucose tolerance, menstrual irregularities, etc.
-digestive, skeletal, cutaneous, neuropsychiatric disorders…
2-9-Prescription methods : corticosteroids must absolutely be prescribed in decreasing doses without abrupt discontinuation. However, in dentistry, corticosteroids are used in “flash” or short-term, allowing their prescription not to exceed 05 days. (This duration is considered sufficient to limit acute inflammation following oral surgery procedures) This short duration allows the anti-inflammatory effect of the product to be obtained without the side effects inherent in long-term corticosteroid therapy.
| DCI | Specialty | Dose /day | Administrative rhythm | Duration of the trt |
| Prednisolone | Hydrocortancyl 5mg tab dry Prednisone ® Gé 20 mg tab Solupred 20 mg tab Efferv 20mg tab orodispersible 5mg tab efferv 5mg tab orodis | Adult: 0.35 to 1.2 mg/kg/day Child: 5 to 15 mg/day | 1 time in the morning | Post-operative indication function: 03 days. |
| Prednisone | Cortancyl 1 mg tab 20mg tab dry 5 mg tab Prednisone ® Gé 200mg tab dry 5 mg tab dry | idem | idem | idem |
3- ENZYMES
- indications and contraindications of NSAIDs and AIS.
- modest anti-inflammatory activity.
- use as anti-edematous drugs locally or orally.
- inactivate certain specific inflammation proteins.
- are proposed in the treatment of post-traumatic or post-surgical edema .
- The main contraindication is hypersensitivity to one of the components.
- are mainly prescribed for adults and at a lower dosage for children over 6 years old.
- It is best not to use them during pregnancy
- Alpha chymotrypsin, lyso 6; maxilase
Little used in stomatology.
ANTI-INFLAMMATORY DRUGS IN DENTISTRY.
4- COXIBS
These are new anti-inflammatories, which will only inhibit COX2, responsible for inflammation. These are Celebrex in 100 or 200 mg capsules.
It is a selective COX2 inhibitor (no effect on stomach-protective prostaglandins). They have reduced the risk of ulcers and digestive hemorrhage by 50%.
Very little or not prescribed in dentistry.
Used in the management of flare-ups of rheumatic conditions (osteoarthritis and rheumatoid arthritis)
Vioxx withdrawn from the market: studies have shown a doubling of the relative risk of cardiovascular accidents. These products always arouse a lot of controversy.
Conclusion
NSAIDs and corticosteroids represent two therapeutic families of great interest in dental and stomatological practice.
The assessment of the interest of these anti-inflammatories must take into account the benefit provided by their anti-edematous and/or analgesic action as well as the risks inherent in their prescription.
ANTI-INFLAMMATORY DRUGS IN DENTISTRY.
Cracked teeth can be healed with modern techniques.
Gum disease can be prevented with proper brushing.
Dental implants integrate with the bone for a long-lasting solution.
Yellowed teeth can be brightened with professional whitening.
Dental X-rays reveal problems that are invisible to the naked eye.
Sensitive teeth benefit from specific toothpastes.
A diet low in sugar protects against cavities.