Download Over The Counter Medications (OTCs) NSAIDs

Pharmacology for the Athletic Trainer
Over The Counter Medications (OTCs)
NSAIDs
David S. Knitter, MD, FCCP
February 7, 2000
In 1997, the Nonprescription Drug Manufacturers Association
(NDMA) published the report of a study conducted by Kline
& Co. and subtitled "Economic Benefits of Self-Medication."
“The economic analysis resulted in an estimate that OTC availability for
the categories studied resulted in savings to the consumer of $20.6 billion
annually when compared with the costs of treating the ailments using
physicians and prescription medications. The researchers estimated that
nearly two-thirds of the calculated savings could be traced to Rx-to-OTC
switched products.”
Time Limits on OTC Use
Because nonprescription products may be
used without any medical advice, making
patients aware of time limits can be critical in
ensuring their safety.
Time Limits on OTC Use
•
Sustained use of nonprescription products could mask a
serious underlying condition that should be diagnosed.
•
If there is no noticeable response by that time, the risk of an
adverse reaction outweighs any possible benefit to further
use.
•
Prevent patients from using them as alternatives to healthier
interventions
•
The problem should have resolved if the product was used
properly and the patient actually had the problem for which
the product was indicated.
•
Some products may result in addiction if overused
Time Limits for OTC Usage
Medication Category
Diarrhea
Eye Drops
Steroid Creams
Constipation
Hemorrhoid
Gingival analgesics
Sore throat products
Headache
Sleep Aids
Antifungal Creams
Nicoteine Replacement
Diet Aids
Rogaine
Limit on Use
48 hours
3 days
7 days
7 days
7 days
7 days
7 days
10 days
14 days
14 days
12 weeks
3 months
4 - 12 months
No Time Limits of OTC Use
•
the condition they treat is not easily
confused with any other;
•
the condition requires lifelong therapy;
•
the medications used to treat the condition
are fairly safe;
•
the medication prevents a problem.
Examples
•
fluorides for dental care,
•
antihistamines for motion sickness or
allergic rhinitis,
•
simethicone for intestinal gas,
•
sunscreens to prevent sunburn,
•
acne medications
Rise In OTC Sales
Category
1996 ($ in
millions)
2001 ($ in
millions)
Analgesics
935.1
1,262.6
% average
annual growth
rate
7.5
Antifungal
(vaginal)
233.0
253.7
14.7
Smoking
cessation
53.0
410.0
51.0
Product
Percent of sales dollars of top
21 OTC products
Advil
9.0%
Aleve
4.0
Motrin IB
3.0
NSAID Classes
Acetylated Salicylic
acid
Non-Acetylated
Salicylic acid
Acetic acid
derivatives
Aspirin
Difunisal
Choline salicylate
Choline-magnesium
trisalicylate
Sodium salicylate
Salsalate
Magnesium salicylate
Indomethacin
Sulindac
Toletin
Etodolac
Diclofenac
Propionic Acids
Fenamic acids
Enolic acids
Fenoprofen
Flurbiprofen
Ibuprofen
Ketoprofen
Naproxen
Oxaprozin
Meclofenamate
Piroxicam
Phenylbutazone
Current OTC NSAIDs
• Aspirin
• 325mg not to exceed 4 grams in 24 hours
• Ibuprofen
• 200mg not to exceed 1200 mg in 24 hours
– Advil
– Nuprin
– Mortin AB
• Naprosyn
• 200mg not to exceed 600mg in 24 hours
– Aleve
• Ketoprofen
• 12.5mg not to exceed 75mg in 24 hours
– Orudis KT
Prostaglandin (PG) Synthesis
•
Prostaglandins have been implicated in
pathogenesis of inflammation and fever
•
Aspirin-like drugs inhibit the biosynthesis and
release of PGs
•
Inhibition of the synthesizing enzyme (cyclooxygenase) is fairly well correlated with antiinflammatory action

Inhibition of COX2 (inducible) may be responsible for
therapeutic effects of NSAIDs

Inhibition of COX1 (constituitive) may be responsible
for many adverse effects of NSAIDs
Prostaglandin (PG) Synthesis
Pain
•
Direct administration of PGs causes local pain
evidence suggests that PGs (PGE2?)sensitizes pain
receptors to bradykinin, a local mediator of pain
released during inflammation
•
Aspirin is less effective against sharp pain (direct
stimulation of nerve endings - no PGs, opioids more
effective) than against the dull, throbbing pain of
inflammation (involves PGs)
Prostaglandin (PG) Synthesis
Fever
•
Infection bacterial endotoxins cause release of
endogenous pyrogens from neutrophils
•
Tissue damage or inflammation interleukin 1 released
by macrophages (principal role is to activate
lymphocytes) affects hypothalamus
•
Aspirin-like drugs work by increasing heat loss
(vasodilatation of peripheral blood vessels) not by
reducing heat production
Prostaglandin (PG) Synthesis
Inflammation
•
Signs of inflammation - erythema, edema, tenderness
and pain
•
Damage to microvasculature - leakage of blood
components
•
Infiltration of leukocytes
•
Release of chemical mediators including PGs
•
Aspirin-like drugs relieve symptoms not pathology
Possible Future Switches of NSAIDS
•
Diclofenac potassium and sodium
•
Diflunisal
•
Etodolac
•
Naproxen sodium (controlled-release)
•
Piroxicam
•
Sulindac
•
Tolmetin
Adverse Effects
• Gastrointestinal Effects
 nausea and vomiting stimulation of CTZ in medulla
 gastric bleeding 3-8 ml/day blood loss with 4-5 g aspirin/day vs 0.6 ml in
untreated subjects
• Blood Clotting
 aspirin irreversibly inhibits platelet synthesis of thromboxane A2 (TXA2)
which is required for aggregation
 other NSAIDs - reversible effect on clotting
 non-acetylated salicylates - no effect on clotting
 terminate chronic use of aspirin 1 week prior to elective surgery (most
other NSAIDs 24-48 hr)
Adverse Effects
• Salicylism
 characterized by tinnitus (may be related to increased labyrinthine
pressure or effect on cochlear hair cells, pehaps secondary to
vasoconstriction of auditory microvasculature), headache, nausea and
vomiting, dizziness and dimness of vision
• Aspirin Hypersensitivity or ”Aspirin Intolerance"
 1/4 million in USA
 symptoms include rhinitis, profuse watery secretions, bronchial asthma,
bronchconstriction, hypotension, vasomotor collapse, coma
 non-acetylated salicylates may be used cautiously
Adverse Effects
• Reye's syndrome
 rare but often fatal consequence of infection with
varicella and various other viruses
 salicylates are contraindicated in children and
adolescents with chicken pox or influenza
Acetaminophen
•
Little or no anti-inflammatory activity
•
Mechanism of action is unknown

Very weak inhibitor of cyclo-oxygenase

Greater effect in the CNS ??
•
Minimal gastrointestinal irritation
•
No effect on bleeding time
Acetaminophen Toxicity
•
Hepatic necrosis (acute - 10-15 g; >25 g usually fatal)
•
Increased incidence of hepatotoxicity in the presence of
ethanol and/or fasting (with as little as 4 g/day)
•
Ethanol induces hepatic MFO metabolism (pathway 3)
shifting reaction toward toxic metabolite (limited
glutathione available)
Renal Tubular Necrosis
•
Increased risk with lifetime intake
•
Associated greater than 1000 tablets of acetaminophen
•
Associated greater than 5000 tablets of NSAIDs
•
? effect of aspirin