Top 200: NSAIDs & Anti-inflammatory
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What are the indications of anti-inflammatory medications?
- Treats inflammation
- Treats mild to moderate pain
- Treats fever
- May affect platelets
What does NSAID stand for?
Non-steroidal Anti-inflammatory drugs
What are the indications of NSAIDS?
- Decrease inflammation
- Decrease pain
- Treat fever
- Most NSAIDs inhibit Cox-1 and Cox-2 enzymes
What is Cox?
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
COX-1: The Good COX
• Produced normally in various body tissues:
•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
is mediated by COX-1
COX-2: The Bad COX
•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
What drug class serves as the main COX inhibitors? Are they selective?
The main COX inhibitors are the non-steroidal anti-inflammatory drugs (NSAIDs)
- These are NOT selective (they inhibit all types of
What are the main adverse effects of NSAIDs?
- Main adverse effects:
- -peptic ulceration
What is meant by the "dual insult" of NSAIDs?
- “Dual-insult" of NSAIDs:
- 1) direct irritation of the gastric mucosa (many NSAIDs are acids)
- 2) inhibition of prostaglandin synthesis by COX-1
What are some of the functions of Prostaglandins (Cox-1), and what are the consequences of inhibiting 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
What conditions are NSAIDs commonly used to treat?
Recall that NSAIDs reduce inflammation and thus reduce pain.
- NSAIDs are commonly used to treat:
- -Back pain
- -Heavy periods
What do ALL NSAIDs have in common?
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
What is the maximum adult dose of Motrin/Advil (Ibuprofen)?
Adult maximum dose is 3.2 grams/day
What is the pediatric dosing of Motrin/Advil (Ibuprofen)?
-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 in Children
- 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
What are the body's physiologic responses to return temperature back to normal from a feverish state?
- Temperature levels triggering physiologic and behavioral mechanisms to return the temperature back to normal:
- -Increased peripheral blood flow
How should one treat a fever?
- 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!
American Academy of Pediatrics recommendations for when to call the pediatrician about children with fever (American Academy of Pediatrics, 2002)
- 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
Case Study: "My daughter is 7 months old and has been crying a lot lately. I think she is
teething. She has a fever and I want to give her some Motrin. The bottle doesn’t say how much to give her? What do you recommend?"
-What do you ask the mother?
-Provide feedback (You said your daughter was 7 months old?)
-How long has she had the fever (>3 days= see Dr.)
-Taking any other meds?
-How high is the fever?
-Type of ibuprofen
-Physician referral if fever doesn’t come down
Calculations Example of Ibuprofen dosing: “My daughter weighs 16 pounds and her temperature is 102." How do you calculate the dose?
-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
What is the max adult dose for Naprosyn (Naproxen)?
Adult max dose 1200-1650mg/day
What are the age guidelines regarding Aspirin?
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®)
What is the COX-2 Mechanism of Action?
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.
What kind of inhibitor is Tylenol?
A very weak COX-1 and COX-2 inhibitor.
What is the dosing for Tylenol?
Children <12 years:
10-15 mg/kg/dose every 4 hours as needed
do not exceed 5 doses (2.6 g) in 24 hours
325-650 mg every 4 hours
1000 mg 3-4 times/day
do not exceed 4 grams/day
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