Nsaid Tanveer-Final (NXPowerLite) / orthodontic courses by Indian dental academy

INDIAN DENTAL ACADEMY

Leader in continuing dental education www.indiandentalacademy.com

www.indiandentalacademy.com

USE OF STEROIDAL & NON-STEROIDAL ANTI-INFLAMMATORY

DRUGS IN ORAL AND MAXILLOFACIAL SURGERY PATIENTS

MODERATOR: Dr.Preetham ShettyPRESENTER: Dr.Tanveer.Ahmed


CONTENTS1. INTRODUCTION2. IMPORTANCE OF INFLAMMATION3. DEFINITION4. MEDIATORS OF INFLAMMATORY

PROCESS5. CLASSIFICATION OF NSAIDS6. INDIVIDUAL DRUGS7. SELECTIVE COX-2 INHIBITORS8. CONCLUSION9. 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 InterleukinsSkin reactive factor

TNF-PAF

HistamineCytokinesProstaglandin D2


Eosinophil Products

• PLASMA Kinin System Complement System

Clotting System

• Lysosomal Enzymes• Major Basic proteins• Leukotrienes

Bradykinin C3 fragments

C5 fragmentsFibrinopeptidesFibrin 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 COX-1 COX-2

Prostaglandin Throboxanes

Gastric protection

uterine contraction,

renal function

Platelet Aggregation

Leukotrienes

BronchospasmInflammation

prostaglandins

Pain inflammation, renal function

Tissue damage


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 NSAIDSA. ANALGESIC AND ANTI – INFLAMMATORY 1. Salicylates : Aspirin, Salicylamide, Diflunisal.2. Pyrazolone : Phenylbutazone, Oxyphenbutazone.3. Indole Derivatives : Indomethacin,Sulindac.4. Propionic acid derivatives : Ibuprofen,Naproxen, Ketoprofen, Fenoprofen.5. Anthranilic Acid derivative : Mephenamic acid.6. Aryl – acetic acid derivative : Diclofenac,Tolmetin.7. Oxicam derivative : Piroxicam, Tenoxicam, Meloxicam.8. Pyrrolo – Pyrrole derivative : Ketorolac.9. Sulfonanilide derivative : Nimesulide.10. Alkanones : Nabumetone. www.indiandentalacademy.com

B. ANALGESIC BUT POOR ANTI-INFLAMMATORY

1. Para- aminophenol derivative : Paracetamol (Acetaminophen).

2. Pyrazolone derivative : Metamizol (Dipyrone) propiphenazone.

3. Benzoxazocine derivative : Nefopam.


SALICYLATES ASPIRIN ACTIONS:- 1i. 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 Possible adverse effect1 Ulcer Internal Bleeding,possible hemorrhage2 Asthama Asthmatic attack resembling allergic reaction.3 Diabetes 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.


USES1. 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

cellsAbsorbed 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 anti-

inflammatory 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 derivativespiroxicam

• 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 derivativesketorolac:

• 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 anti-coagulants.


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 derivativesparacetamol(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 DOSAGE100-200mg 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


Nsaid Tanveer-Final (NXPowerLite) / orthodontic courses by Indian dental academy

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