9th

PAIN MANAGEMENT IN DENTISTRY

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Pain is defined as an unpleasant sensation that can be either acute or chronic and that is a consequence of complex neurochemical processes in the peripheral and central nervous system (CNS).

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Analgesics are the drugs (natural or synthetic origin) which relieve pain by acting on CNS or peripheral pain mechanism without causing loss of consciousness.
Analgesics can be divided into two main groups:
Opioid/narcotic/morphine like analgesics.
Nonopioid/nonnarcotic/aspirin like analgesics.

Pharmacological Action-NSAIDs

All NSAIDs act by inhibiting synthesis of prostaglandins
Chemical mediators that are released in allergic & inflammatory processes
Arachidonic acid (AA) present in phospholipids of cell membrane is released by action of phospholipase A2 under various stimuli.
Then AA is oxygenated by cyclooxygenase or lipooxygenase


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Cyclooxygenase Pathway

Arachidonic acid is metabolized by cyclooxygenase COX into prostaglandins

COX exists in two isoforms:

- COX-1
- COX-2

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NSAIDS

NSAIDs are group of agents that differ in their antipyretic, analgesic & anti-inflammatory activities
All NSAIDs act by inhibiting synthesis of prostaglandins
They act by inhibiting cyclooxygenase enzymes, leading to decreased prostaglandine synthesis with both beneficial & unwanted effects

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NSAIDS

NSAIDs are categorized according to their COX specificity:
Non-selective inhibitors (COX-1 & -2 inhibitors)
Selective inhibitors (COX-2 inhibitors)


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Therapeutic uses of NSAIDs

Inflammation is a normal, protective response to tissue injury caused by physical trauma, chemicals & microbiological agents
Rheumatoid Arthritis
T-lymphocytes: Stimulate B-cell to attack the antigen
• Analgesia:
• - Effective for pain of mild to moderate intensity including headache, migraine, musculoskeletal, postoperative pain, osteo- & inflammatory arthritis
• - Unlike opioids, they do not cause dependence

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Therapeutic uses of NSAIDs-2

Antipyretic:
Fever is caused by elevated levels of PGE2
PGE2 signals to the hypothalamus to increase the body's thermal set point.
Antiplatelets function:
- Aspirin is indicated for treatment & prevention myocardial infarction (MI), transient ischemic attacks (TIA) & embolic strokes
- Thromboxane (TXA2) enhances platelets aggregation
- Low doses of aspirin inhibits production TXA2


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Patency of ductus arteriosus:

- PGs maintain patency
- Indonmetacin given to new-born child results in closure of ductus arteriosus
Primary dysmenorrhea : PGs cause uterine hypercontractility & pain.
PG are released during menstruation, due to the destruction of the endometrial cells, and the resultant release of their contents.

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Therapeutic uses of NSAIDs-3

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Adverse effects:

Renal effects:

CAUTION IS NEEDED!
Renal failure in elderly, those with pre-existing renal disease or those with diuretic sufficient to reduce intravascular volume
Salt and fluid retention
Hypertension


Adverse effects-2
• PG is Gastroprotective: by inhibiting acid secretion, promoting secretion of mucous
• Inhibition of PG synthesis, removes this protection
• Risk factors for the development of peptic ulcer disease include
• Advanced age
• History of previous ulcer
• Concomitant use of corticosteriod or anticoagulants
• Higher dosage of NSAID
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NSAIDs Drugs

Propionic acid derivatives:
Ibuprofen, naproxen, ketoprofen
Inhibit COX (non-selectively) & thus inhibit synthesis of PG.
All possess anti-inflammatory (reduce inflammation), analgesic (reduce pain) & antipyretic (reduce fever) activities.
Chronic treatment of RA & osteoarthritis
Most common adverse effects: GI dyspepsia to bleeding

Ibuprofen has fewer side effects than other non-selective NSAIDs

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Acetic acid derivatives
Indomethacin (Indocin), sulindac & etodolac
They are not used to lower fever
Toxicity of indomethacin limits its use to treat acute gout arthritis
Indomethacin side-effects: headache, dizziness & GI disturbances
useful in treatment of RA,OA

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Acetic acid derivatives

Sulindac is a prodrug. Its active metabolite is, like diclofenac, an acetic acid derivative

Sulindac is useful in treatment of RA,OA

Less adverse effects than Indomethacin & other NSAIDs
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Mefenamic Acid (Ponstan)

Used for pain and inflammation in RA and OA; postoperative pain; mild to moderate pain; dysmenorrhoea and menorrhagia.
Dose
ADULT over 18 years, 500 mg 3 times daily
CHILD 12–18 years, acute pain including dysmenorrhoea,
menorrhagia, 500 mg 3 times daily.
Has minor anti-inflammatory properties.
It has occasionally been associated with diarrhea and haemolytic anaemia which require discontinuation of treatment.
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Oxicam derivatives
Piroxicam, meloxicam (Mobic), Tenoxicam
Are used to treat RA, OA, AS (ankylosing spondylitis)
They have long half-life (50hrs), once daily
Piroxicam has more GI side-effects than most other NSAIDs
Meloxicam selective COX-2 inhibitor
At high dose, Meloxicam is nonselective, inhibiting both COX-1 & COX-2

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Diclofenac

Voltaren, Diclogesic
Is approved for long-term use in treatment of RA, OA, AS
It is more potent than indomethacin or naproxen
Diclofenac accumulates in synovial fluids

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Selective COX-2 inhibitors

Celecoxib ,rofecoxib, ..
COX-2 inhibitors shows a lower risk for development of peptic ulcer & GI bleeding
Have no effects on platelets
They are indicated for:
- Patients who require chronic use of NSAIDs & are at high risk for NSAIDs-induced ulcer
COX-2 inhibitors should be avoided in patients with chronic renal insufficiency, severe heart disease & hepatic failure
Its half-life eleven hrs, is taken once daily


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Acetaminophen (Paracetamol)

It inhibits prostaglandine synthesis in CNS, this explains its antipyretic & analgesic properties
Unlike NSAIDs, acetaminophen has little or no anti-inflammatory activity
Has less effect on cyclooxygenase in peripheral tissues, which accounts for its weak anti-inflammatory activity
Has no effects on platelets or increase blood clotting time
Half-life 2hrs
Oral dose: 0.5-1g every 4-6 hrs, maximum daily dose 4g
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Therapeutic uses

• 1. It is effective in mild to moderate pain e.g. headache, dysmenorrhoea
• 2. Is a substitute for analgesic & antipyretic effects of aspirin (its analgesic efficacy is equal to that of aspirin)
• 3. Children with viral infections or chickenpox
• 4. In patients with gout who are taking probenecid

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Aspirin (Acetylsalicylic acid)

Mechanism of action:
- Irreversibly inhibits COX by acylating active site of enzyme, so preventing formation of thromboxane, prostacyline & other prostaglandins


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Therapeutic uses of Aspirin

• Antipyretic & analgesic:
• - PGE2 sensitizes nerve endings to chemical mediators released by inflammation
• - Aspirin decreases PGE2, thus repress sensation of pain
• - Are used in treatment of gout, rheumatic fever & RA
• - Headache, arthralgia & myalgia
• - Dose 300-900 mg every 4-6 hrs

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Therapeutic uses of Aspirin

2. Cardiovascular effects:
Salicylates are used to inhibit platelets aggregation
Low dose of aspirin 75 mg daily are used to prophylactically to decrease incidence of transient ischemic attacks & stroke
A single dose of 300 mg is given as immediate treatment of MI
3. Aspirin facilitates closure of patent ductus arteriosus (PGE2 is responsible for keeping ductus open)

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