Top 200: NSAIDs & Anti-inflammatory

• Treats inflammation
• Treats mild to moderate pain
• Treats fever
• May affect platelets

Non-steroidal Anti-inflammatory drugs

• Decrease inflammation
• Decrease pain
• Treat fever
• Most NSAIDs inhibit Cox-1 and Cox-2 enzymes

Cyclooxygenase (COX) is an enzyme that catalyzes the conversion of free essential fatty acids to prostaglandins (mediators of inflammatory reactions)

There are different types of prostaglandins (good and bad)

Inhibition of COX can provide relief from symptoms of inflammation and pain

Cox 1, 2 and 3

Enzymes act in the same fashion

Selective inhibition changes side effects

• Produced normally in various body tissues:

–Gastric mucosa

–Kidney

–Platelets

•Speeds up the production of prostaglandins

• –Promotes the production of the natural mucus
• lining that protects the inner stomach

–Preserves the integrity of the GI mucosa

•Platelet aggregation is mediated by COX-1

•Not produced normally in most tissue

•Production increased in the presence of inflammation and tissue injury

•Leads to prostaglandin synthesis involved in pain and inflammation (different from COX-1)

•Inhibition of COX-2 leads to beneficial effects

The main COX inhibitors are the non-steroidal anti-inflammatory drugs (NSAIDs).

-Ibuprofen

-Naproxen

• These are NOT selective (they inhibit all types of
• COX)

• Main adverse effects:
• -peptic ulceration
• -dyspepsian

• “Dual-insult" of NSAIDs:
• 1) direct irritation of the gastric mucosa (many NSAIDs are acids)
• 2) inhibition of prostaglandin synthesis by COX-1

• Prostaglandins (ie Cox-1) have a protective role in the gastrointestinal tract, preventing acid-insult to the mucosa.
• Inhibiting Cox-1 has been shown to increase GI side effects (decrease GI protective enzyme)
• Inhibiting Cox-1 can cause renal insufficiency and hyperkalemia

Recall that NSAIDs reduce inflammation and thus reduce pain.

• NSAIDs are commonly used to treat:
• -Arthritis
• -Back pain
• -Heavy periods
• -Sprains/Strains
• -Migraine

All NSAIDS exert anti-inflammatory effects

All NSAIDS exert analgesic effects

All NSAIDS exert antipyretic effects (reduce fever)

All NSAIDS exert gastric side effects (Selective COX-2 has a lesser effect than COX-1)

All NSAIDS can cause renal toxicity

Adult maximum dose is 3.2 grams/day

Pediatric Dosing

-Approved for use in children 6 months of age and older

-Temp <102.5: 5mg/kg/DOSE

-Temp >102.5: 10mg/kg/DOSE

-Dosed every 6-8 hours

Max dose: 40mg/kg/DAY

- Normal body temperature is maintained at a relatively constant level

- The thermoregulatory center in the hypothalamus receives information about body temperature from thermosensitive neurons located in the CNS and skin

- Fever often is a sign that the body is mounting an immune response to infection or immunization

• - Fever does not necessarily indicate the presence of bacterial infection (viral infection also can cause
• fever)

- Fever is the most common symptom of disease in children

- ~20% to 30% of calls from parents to pediatricians are about fever

- Fever is the most frequent reason for office visits by children under 2 years of age

- 1 out of 5 ER visits for children is related to fever

• Temperature levels triggering physiologic and behavioral mechanisms to return the temperature back to normal:
• -Sweating
• -Vasodilation
• -Increased peripheral blood flow
• -Hyperventilation

- Whether and when fever should be treated is a controversy among health care professionals

- Fever usually poses little danger to the patient

- Fever may have beneficial effects

- Antipyretic therapy is indicated mainly to aid in patient discomfort and parent anxiety

-"mild fever" = 100°F-102°F

- “high fever“ =103-105°F

• - “very high fever” = >106°F This is when serious
• complications can occur. This is RARE!

- The American Academy of Pediatrics recommends that parents and caregivers call the pediatrician immediately if their child has a fever and:

• Is 2 months of age or younger with a rectal temperature of ≥100.2°F (37.9°C)

• Looks very ill, is unusually drowsy, or is very fussy

• • Has additional symptoms such as a stiff neck, severe headache, severe sore throat, severe ear pain, an unexplained rash, or repeated vomiting
• or diarrhea

• Has a condition that suppresses immune responses such as sickle-cell disease or cancer, or is taking steroids

• Has had a seizure

-What do you ask the mother?

-Provide feedback (You said your daughter was 7 months old?)

-Daughter’s weight

-How long has she had the fever (>3 days= see Dr.)

-Taking any other meds?

-Allergies?

-How high is the fever?

-Type of ibuprofen

-Physician referral if fever doesn’t come down

-Convert 16 pounds to kg

16 lbs X kg/ 2.2 lbs =7.27 kg

-Calculate dosage (temp)

- Recall the pediatric guidelines: (Temp<102.5 = 5mg/kg/dose)

7.27 kg X 5 mg/kg = 36mg/dose

-Bottle reads 100mg/teaspoonful

• 1 teaspoonful = 5 ml, therefore...
• 36 mg X 5 ml /100 mg = 1.8 ml

Adult max dose 1200-1650mg/day

Children < 16 years old should not take aspirin because there is an association with Reye's syndrome.

-COX-2 inhibitors are newly developed drugs for inflammation that selectively block the COX-2 enzyme.

-Blocking this enzyme impedes the production of the chemical messengers (prostaglandins) that cause the pain and swelling of arthritis inflammation

-Not clinically more effective than other NSAIDS

-Some medications have been voluntarily withdrawn from the market due to increased risk of cardiovascular disorders (Bextra®, Vioxx®)

Mechanism of Action:

• Inhibits prostaglandin synthesis by decreasing the
• activity of the enzyme, cyclooxygenase-2 (COX-2), which results in decreased formation of prostaglandin precursors.

Celecoxib does not inhibit cyclooxygenase-1 (COX-1) at therapeutic concentrations.

A very weak COX-1 and COX-2 inhibitor.

Children <12 years:

10-15 mg/kg/dose every 4 hours as needed

do not exceed 5 doses (2.6 g) in 24 hours

Adults:

325-650 mg every 4 hours

1000 mg 3-4 times/day

do not exceed 4 grams/day

-Ibuprofen

-Acetaminophen

-Aspirin

-Celebrex

-Mobic

-Lodine

-Relafen

-Cataflam

-Voltaren

-Naprosyn