NSAIDS /certified fixed orthodontic courses by Indian dental academy

INDIAN DENTAL ACADEMY
Leader in continuing dental education
www.indiandentalacademy.com


USE OF STEROIDAL & NONSTEROIDAL ANTI-INFLAMMATORY
DRUGS IN ORAL AND MAXILLOFACIAL
SURGERY PATIENTS
MODERATOR: Dr.Preetham Shetty
PRESENTER: Dr.Tanveer.Ahmed

CONTENTS
1.
2.
3.
4.
5.
6.
7.
8.
9.

INTRODUCTION
IMPORTANCE OF INFLAMMATION
DEFINITION
MEDIATORS OF INFLAMMATORY
PROCESS
CLASSIFICATION OF NSAIDS
INDIVIDUAL DRUGS
SELECTIVE COX-2 INHIBITORS
CONCLUSION
REFRENCES

• IMPORTANCE OF INFLAMMATION
• DEFINITION OF INFLAMMATION
As per Ebert & Grant “Inflammation is a
process that begins following sub lethal
injury to tissue and ends with permanent
destruction of tissue or with complete
healing”.

FUNDAMENTAL EVENTS IN
INFLAMMATION
1. Increased permeability of the micro
vasculature.
2. Accumulation and activation of
Leucocytes.


MEDIATORS OF
INFLAMMATORY PROCESS
• MAJOR GROUPS
 TISSUE
 Lymphocyte products

 Macrophage products
 Mast Cell products

•

MAJOR MEDIATORS

Interferon γ
Interleukins
Skin reactive factor
TNF-α
PAF

Histamine
Cytokines
Prostaglandin D2

 Eosinophil Products

• PLASMA
 Kinin System
 Complement System
 Clotting System

• Lysosomal Enzymes
• Major Basic proteins
• Leukotrienes
Bradykinin
C3 fragments
C5 fragments
Fibrinopeptides
Fibrin Degradation
products


HOW NSAIDS WORKS
• Interfering with cycloxygenase pathway
• Process begins with AA-a dietary 20 carbon poly
unsaturated fatty acid obtained from animal fat
• AA is liberated from membrane phospholipids by the
action of phospholipase A2.
• Free AA is metabolically transformed through either
cycloxygenase or lipoxygenase pathway
• When AA is enzymatically oxidized by cycloxygenase it
forms unstable intermediates(PGG2 and PGH2) leading to
prostanoid synthesis
• By the action of lipoxygenase,AA forms leukotrienes
• This process is referred to as arachidonic acid cascade

ARACHIDONIC ACID

Lipooxygenase

Leukotrienes

Bronchospasm
Inflammation

COX-1

Prostaglandin

Gastric
protection
uterine
contraction,
renal function

Tissue damage

COX-2

Throboxanes

prostaglandins

Platelet
Aggregation


Pain inflammation, renal
function

Cox-1 And Cox-2
• Cox-1(constitutive)
“-House keeping” function
- For blood clotting
- For kidney function
- For stomach protection
• Cox-2 (induced) contributes:
- Pain
- Heat
- Swelling

CLASSIFICATION OF NSAIDS
A. ANALGESIC AND ANTI – INFLAMMATORY
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.

Salicylates : Aspirin, Salicylamide, Diflunisal.
Pyrazolone : Phenylbutazone, Oxyphenbutazone.
Indole Derivatives : Indomethacin,Sulindac.
Propionic acid derivatives : Ibuprofen,Naproxen,
Ketoprofen, Fenoprofen.
Anthranilic Acid derivative : Mephenamic acid.
Aryl – acetic acid derivative : Diclofenac,Tolmetin.
Oxicam derivative : Piroxicam, Tenoxicam, Meloxicam.
Pyrrolo – Pyrrole derivative : Ketorolac.
Sulfonanilide derivative : Nimesulide.
Alkanones : Nabumetone.

B. ANALGESIC BUT POOR ANTIINFLAMMATORY
1. Para- aminophenol derivative : Paracetamol
(Acetaminophen).
2. Pyrazolone derivative : Metamizol (Dipyrone)
propiphenazone.
3. Benzoxazocine derivative : Nefopam.


SALICYLATES
 ASPIRIN
ACTIONS:- 1
i. Analgesic, Anti- pyretic and Anti-inflammatory.
ii. Weaker analgesic than morphine type drugs.
iii. Analgesic action is mainly due to obtunding of
peripheral pain receptors and prevention of PG
mediated sensitization of nerve endings.
iv. It resets the hypothalamic thermostat and rapidly
reduces fever by promoting heat loss but does not
decrease heat production.

2. Aspirin and released Salicylic acid irritates
gastric mucosa – causes epigastric distress,
nausea, vomiting.
3. It interferes with platelet aggregation and
bleeding time is prolonged to nearly twice the
normal.
- Absorbed from stomach and small intestine.
- Slowly enters brain and freely crosses placenta.


Effects of NSAIDS on upper GIT


Contraindications to the use of
Aspirin and other salicylates:
• Disease state
1 Ulcer
2 Asthama

3 Diabetes

Possible adverse effect
Internal Bleeding,possible
hemorrhage
Asthmatic attack
resembling allergic
reaction.
low doses may cause
hyperglycemia .
high doses may cause
hypoglycemia.

Adverse effects:
1. Analgesic dose – nausea, vomiting, epigastric
distress and increased blood loss in stools.
2. Hypersensitivity and Idiosyncrasy.
3. Inflammatory doses- produce syndrome called ‘
Salicylism’ .
4. Acute Salicylate poisoning more common in
children causes vomiting, dehydration ,
electrolyte imbalance, delirium,
hallucinations,convulsions, and death.

USES
1. Analgesic- for headache, backache, myalgia,
joint pain, neuralgias,etc.low dose .3 to .6 gm
sixth hourly.
2. Antipyretic- effective in fever of any origin.
3. Acute rheumatic fever- It is the first drug to be
used in all cases.
4. Rheumatoid arthritis- It is the first drug to be
tried.Produces relief of pain, swelling, and
morning stiffness.
5. Other conditions: Osteoarthritis, post myocardial
infarction and post stroke patients.

Precautions:
• Should be stopped a week before elective
surgery.
• Should be avoided during pregnancy,
lactation.
• Should be avoided in chronic liver diseases
and in patients with bleeding tendencies.


Pyrazolones:
• Phenylbutazones:
1. Inhibits Cox and is more potent Anti
inflammatory.
2. Analgesic and anti-pyretic effect ois poor and
slower in onset.
3. Causes definite retention of Na and water by
direct action on renal tubules-edema,which
occurs after 1-2weeks of use.
4. Completely absorbed orally and completely
metabolised in liver.

Adverse effects;
More toxic than Aspirin
• Nausea,vomitting,epigastric distress, and
epigastric ulceration are common.
• edema is a major limitation for use for more than
1-2 weeks.
• Hypersensitivity reactions like rashes,serum
sickness and stomatitis.
• Bone marrow depression, agranulocytosis and
Steven-Johnsons syndrome are more serious.

Indole derivatives:
• Indomethacin:
• Water insoluble , and soluble in common organic slovents.
• Actions:
Analgesic and potent anti-inflamatory and anti pyretic
action.
inhibits PG synthesis as well as phospho- diesterase thus
increasing cyclic AMP intracellularly.
Also interferes with migration of leukocytes to inflammatory
cells
Absorbed orally reaching peak plasma levels in one and half
hours.

Clinical use:
•
•
•
•
•

Rheumatoid Arthritis and associated disorders.
Ankylosing spondylitis.
Gout.
Neurovascular headache.
Malignancy associated fever refractory to other
anti-pyretic.
• Most commonly used drug for closure for closure
of PDA.

Propionic Acid Derivatives:
Ibuprofen:
• Actions similar to Aspirin but are better
tolerated orally although they may produce
gastric irritation and ulceration.
• Highly bound to plasma protiens- 90 –99%
• Metabolised in liver.


Interactions/Contraindications
1 should be avoided with anti-coagulants as
they inhibit platelet funtions
2 Not to be prescribed during pregnancy and
peptic ulcer patients.
3 Contra indicated in indivisuals with nasal
polyps, angioedema and bronchospasmic
activity to aspirin.

Anthranilic Acid derivative:
Mefenamic acid
• Actions: weaker analgesic than aspirin.
• Inhibits PG synthesis.
• Exerts peripheral as well as central
analgesic activity.


Clinical use:
• Dull aching pain.
• Indicated primarily as an analgesic in
muscle,joint and soft tissue pain-where
strong anti-inflammatory action is not
needed.


Adverse effects
• Nausea,vomitting,epigastric distress, and
epigastric ulceration are common.
• Dizziness,headache,skin rashes,heamolytic
anemia and blood dyscrasias.


ArylAcetic acid derivatives:
Diclofenac,Tolmetin
• Actions:
• Newer analgesics and antipyretic and antiinflammatory drug.
• Inhibits PG synthesis and short lasting antiplatelet
action.
• Concentration in synovial fluid is three times more
than in plasma.
• Well absorbed orally.
• Plasma t1/2-2hrs

Clinical use:
• Osteoarthritis,Rheumatoid
arthritis,ankylosing spondylitis,bursitis.
• Post traumatic and post-op inflammatory
conditions-affords quick relief of pain and
wound edema.


Oxicam derivatives
piroxicam
• Actions:
• lowers PG concentrations in synovial fluid.
• Produces ratio of T-helper to T-supressor
lymphocytes.
• Inhibits platelet aggregation thus prolongs
bleeding time.
• Half life-28-45hrs.

Pyrolo-pyrrole derivatives
ketorolac:
• Actions;
• Highly potent member of a new class of analgesic
compound.
• Has both anti-inflammatory and anlgesic property but is
more systemic analgesic then anti-inflammatory.
• More potent than indomethacin andphenylbutazone.
• Inhibits PG synthesis and is believed to relieve pain by
peripheral mechanism.
• In post-op pain it has equal efficacy of morphine.
• Excreted in urine-90% unchanged.


Uses:
• Frequently used in post op and acute
musculo-skeletal pain
• May also be used for renal colic, migraine
and pain due to bone metastasis.
• Should not be given in patients on anticoagulants.


Sulfonanilide derivatives:
nimesulide:
• Selective for Cox-2.
• Can be given for asthamatics.
• Newer NSAID and is a relatively weaker
inhibitor of PG synthesis.
• Completely absorbed orally and is excreted
in urine.


Uses:
• Primarily in short lasting painful
inflammatory conditions like sport
injuries,sinusitis,other ENT disorders,dental
surgeries,bursitis,low back ache and post op
pain.
• Nimesulide is safe (Hindustan Times-13th
Jan 2003)

ParaAminoPhenol derivatives
paracetamol(acetaminophen)
• Action:
• Central analgesic action is similar to Aspirin but
negligible anti-inflammatory action.
• Good and promptly acting anti-pyretic.
• Doest not affect platelet function.
• No effect on CVS,and rare gastric irritation.
• Well absorbed orally,uniformly distributed in
body and excreted rapidly in urine.
• Plasma t1/2- 2-3hrs.

Adverse effects:
• In isolated anti-pyretic doses , it is safe and
well tolerated.
• Nausea and rashes occur rarely.
• Analgesic nephopathy occurs after years of
heavy ingestion of the drug.
• Acute paracetamol can occur specially in
small children who have low hepatic
glucoronide conjugating ability.

Acute Paracetamol poisoning
• Occurs if a large dose of more than 150mg/kg is
taken.
• Fatality is common with more than 250mg/kg.
• Early manifestations are nausea,vommiting,
abdominal pain and liver tenderness with no
impairment of conciousness.
• After 12-18hrs centri-lobular hepatic necrosis
occurs.
• Hypoglycemia may progress to coma.]
• Jaundice occurs after 2 days.

Treatment:
• If patient is brought early, vomiting should
be induced or gastric lavage done.
• Activated charcoal is given orally or
through tube to prevent further absorption.
• Specific:
N-Acetyl Cysteine 150mg/kg should be
infused iv over 15mins followed by the
same dose iv over the next 20hrs.

SELECTIVE COX2 INHIBITORS
• First generation
- Celecoxib and rofecoxib
• Second generation
- Valdecoxib


CELECOXIB
• First selective cox2 inhibitor to be approved by
FDA
• Launched in 1999
• Exerts potent anti inflammatory analgesic and
anti-pyretic action with low ulcerogenic potential
• Time action and peak analgesic effort is approx.
half than that of ibuprofen 600mg.


ADVERSE EFFECTS
• Mild diarrhoea
• Abdominal pain
• Dyspepsia
DOSAGE
100-200mg BD


• Celecoxib is effective for cancer prevention in

people with familial adenomatous polyposis
• Celecoxib is the only drug that is approved
by USA-FDA for the treatment of familial
adenomatous polyposis


• Rofecoxib-selective cox2 inhibitor
• Reported to be more selective cox2 inhibitor than
celecoxib using in-vitro assays
• Greater analgesic effect than celecoxib
• 800 times more selective for cox2 than cox1
• Half life 17 hr
DOSAGE

• 50 mg OD


• VALDECOXIB
• Has quicker action than rofecoxib
• Administration of valdecoxib resulted in better
pain relief and lower pain intensity as compared to
rofecoxib
• DOSAGE
• 20mg BD


DRUGS IN THE PIPELINE
• PARECOXIB
- An injectable product of valdecoxib used for
managing severe acute pain including post op pain
-Parecoxib 40mg and 80 mg is effective and safe
for treating post op pain
ETORICOXIB
- Currently being reviewed by FDA
- Highly selective for cox2

REFERENCES
• Essentials of medical pharmacology fourth edition
K.D.TRIPATHI
• Principles of medical pharmacology fifth edition
KALANT
• Pharmacology-fourth edition
DALE,RANG AND RITTER
• Basic and clinical pharmacology
BERTRAN AND KATZUNG
• Dental therapeutic update october 2002

THANK YOU


NSAIDS /certified fixed orthodontic courses by Indian dental academy

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