NSAIDs

Nonsteroidal
Antiinfl
ammatory Drugs
Dr Mehran Rezvani pain

fellowship anesthesiologist &
acupuncturist
Nonsteroidal anti-infl ammatory drugs

(NSAIDs) are a diverse group of
chemically unrelated compounds that
are classifi ed together based on their
therapeutic property of possessing an
anti-infl ammatory action

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MECHANISM OF
ACTION

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Tissue injury occurs

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Mediator
s
Pain
Inflammation

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Summary

acupuncturist
Dr Mehran Rezvani pain fellowship

anesthesiologist & acupuncturist
Figure43-1 Arachidonic acid pathway.

NSAIDs
Large and chemically diverse group of drugs
with the following properties:

Analgesic
Anti-inflammatory
Antipyretic
Antirheumatic

Review
When to use NSAIDs?

When NOT to use NSAIDs?

NSAIDs: Indications
Analgesia (mild to moderate)
Antigout effects
Anti-inflammatory effects
Antipyretic effects
Relief of vascular headaches
Platelet inhibition (ASA)
Various bone, joint, and muscle pain
Osteoarthritis
Rheumatoid arthritis
Dysmenorrhea
NSAIDS: Mechanism of
action
Inflammation: response to tissue injury and infection
Cardinal signs of inflammation
Chemical Mediators
Prostaglandins
Vasodilation, relaxation of smooth muscles, increased capillary permeability
& sensitization of nerve cells to pain
Cyclooxygenase (COX)
COX-1 & COX-2
Enzyme responsible for conversion of arachidonic acid into prostaglandins
-Leukotrienes
NSAIDs: Mechanism of
Action
Analgesiatreatment of headaches, mild to
moderate pain, and inflammation

Antipyretic: reduce fever
Inhibit prostaglandin E2 within the area of
the brain that controls temperature
Salicylates also have antiplatelet activity

Inhibit platelet aggregation

NSAIDs
Mechanism of action
inhibits cyclo-oxygenase (prostaglandin
synthase) that is responsible for conversion of

arachidonic acid to cyclic endoperoxides
2 isoforms of enzyme
- COX-1 constitutive, present in platelets,
stomach and kidney

- COX-2 inducible by cytokines &
endotoxins at
sites of inflammation e.g., joints

NSAIDs
Main actions
1.) Analgesic -effective against mild to moderate pain, do
not cause dependence
2.) Anti-inflammatory
3.) Anti-pyretic
4.)Anti-platelet- prevent thromboxane production,
derived from prostaglandins and cause platelet
aggregation
Others
5.) Useful in treatment of dysmenorrhea, associated
with increased prostaglandin synthesis and increased
uterine contractility
6.) Used to close
the patent
arteriosus
Dr Mehran
Rezvani pain ductus
fellowship




NSAIDs: Salicylates
salicylates (aspirin)
More potent effect on platelet aggregation
and thermal regulatory centre in the brain

Analgesic
Antipyretic
Anti-inflammatory
Antithrombotic effect: used in the
treatment of MI and other thromboembolic

disorders
Aspirin (acetyl salicylate)

Actions
Analgesic - central and peripheral action
Antipyretic - act in hypothalamus to lower the
set point of temperature control elevated by
fever,
anti-inflammatory - inhibition of peripheral
prostaglandin synthesis
respiratory stimulation - direct action on
respiratory centre, indirectly by CO2
production

Reduced platelet adhesion- irreversible
inhibition of COX by acetylation, prolongs

bleeding time, useful in arterial disease
Note: low doses are adequate for this
purpose since the platelet has no
biosynthetic capacity and can not
regenerate the enzyme


OVERDOSAGE
Ingestion of > 10 g can cause
moderate/severe poisoning in an adult
Clinical features - salicylism
tremor, tinnitus, hyperventilation, nausea,
vomiting, sweating
Management- mainly supportive

NSAIDs: Acetic Acid

diclofenac sodium, Voltaren
Indomethacin, indocin
Sulindac, Clinoril
tolmetin

NSAIDs: Propionic Acids

Flurbiprofen, Ansaid
Ibuprofen, (Advil, Motrin)
Ketoprofen(Orudis)
Naproxen(Aleve, Anaprox, Naprosyn)

NSAIDs: Other Agents

Oxicams
Meloxicam, Mobic
piroxicam
Fenamic acids
mefenamic acid
Nonacidic compounds
nabumetone

NSAIDs
Non selective Vs selective COX2 inhibitors
risk of cardiovascular adverse events with
COX 2 inhibitors
Rofecoxib was withdrawn from the market
Higher BP, incidence of myocardial infarction,
stroke
Mechanism _ ? Unopposed effect of
cox 1
action
- ? Block protective effect of COX2 on
ishaemic myocardium or atherogenesis
NSAIDs: Other Agents

COX-2 inhibitors
Celebrex
Vioxx (removed in 2004)


NSAIDs
Classifications
Mild to moderate anti-inflammatory action
- propionic acid derivatives ibuprofen, naproxen
- fenamic acids mefanamic acid
Marked anti-inflammatory action
- salicylic acids aspirin

- pyrazolone derivatives azapropazone,
phenylbutazone
- acetic acid derivatives diclofenac, indomethacin
- oxicam derivatives piroxicam
Selective COX2 inhibitors celecoxib, rofecoxib



Nursing Implications
(contd)
Salicylates are NOT to be given to children
under age 12 because of the risk of Reyes

syndrome
Because these agents generally cause GI
distress, they are often better tolerated if
taken with food, milk, or an antacid to
avoid irritation
Explain to clients that therapeutic effects
may not be seen for 3 to 4 weeks
Common Adverse
Effects of NSAIDS

Common Adverse
Effects
Platelet Dysfunction
Gastritis and peptic ulceration with
bleeding (inhibition of PG + other effects)

Acute Renal Failure in susceptible
Sodium+ water retention and edema
Analgesic nephropathy
Prolongation of gestation and inhibition
of labor.
Hypersenstivity (not immunologic but
due to PG inhibition)
The Salicylates Aspirin

Effect on Respiration: triphasic
1. Low doses: uncoupling
phosphorylation CO2
stimulates respiration.
2. Direct stimulation of respiratory
center Hyperventilation resp.
alkalosis renal compensation
3. Depression of respiratory center and
cardiovascular center BP,
respiratory acidosis, no
compensation
acidosis
Dr Mehran Rezvani+
pain metabolic
fellowship
also
Aspirin
GI system
1. Dose dependent hepatitis

2. Reyes syndrome
Metabolic
1. Uncoupling of Oxid. Phosphorylation
2. Hyperglycemia and depletion of
muscle and hepatic glycogen

Other NSAIDs
Phenylbutazone : Aplastic anemia.
Indomethacin: CNS most common:
halucinations, depression, seizures

Acetaminophen: differes in effects
Main toxicity: hepatitis due to toxic
intermediate which depletes glutathione.
Treat with N-acetylcysteine.


Attempts to
Decrease
Toxicity of
NSAIDs
Nitroaspirins

Selective COX-II
Inhibitors
Anti-inflammatory with less
adverse effects, especially GI

events.
Potential toxicities: kidney and
platelets - ? increased risk of
thrombotic events
Role in Cancer prevention
Role in Alzheimers disease
VIGOR - Confirmed Thrombotic

Cardiovascular Events
Patients with Events (Rates per 100 Patient-Years)
Rofecoxib
N=4047
Naproxen
N=4029
Confirmed
CV events
45 (1.7)
19 (0.7)
0.42
(0.25, 0.72)
Cardiac
events
28 (1.0)
10 (0.4)
0.36
(0.17, 0.74)
Cerebrovascular
events
11 (0.4)
8 (0.3)
0.73
(0.29, 1.80)
Peripheral
vascular events
6 (0.2)
1 (0.04)
0.17
(0.00, 1.37)
Event Category

Relative Risk
(95% CI)
Source: Data on file, MSD
NSAIDs: Antigout Agents

Gout: condition that results from
inappropriate uric acid metabolism

Underexcretion of uric acid
Overproduction of uric acid
Uric acid crystals are deposited in tissues and
joints, resulting in pain

NSAIDs: Antigout Agents (contd)

allopurinol
Used to reduce production of uric acid
colchicine
Reduces inflammatory response to the deposits
of urate crystals
probenecid, sulfinpyrazone
Increase excretion of uric acid in the urine

Use of Aspirin in Unstable Angina

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NSAIDs

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Nonsteroidal

Dr Mehran Rezvani pain

Nonsteroidal anti-infl ammatory drugs

Dr Mehran Rezvani pain

Dr Mehran Rezvani pain

Tissue injury occurs

Dr Mehran Rezvani pain

Dr Mehran Rezvani pain

Dr Mehran Rezvani pain

Dr Mehran Rezvani pain

Dr Mehran Rezvani pain

Dr Mehran Rezvani pain fellowship

Figure43-1 Arachidonic acid pathway.

with the following properties:

Dr Mehran Rezvani pain fellowship

When to use NSAIDs?

Dr Mehran Rezvani pain fellowship

moderate pain, and inflammation

the brain that controls temperature

Salicylates also have antiplatelet activity

Dr Mehran Rezvani pain fellowship

synthase) that is responsible for conversion of

stomach and kidney

sites of inflammation e.g., joints

Dr Mehran Rezvani pain fellowship

Dr Mehran Rezvani pain fellowship

Dr Mehran Rezvani pain fellowship

Dr Mehran Rezvani pain fellowship

Dr Mehran Rezvani pain fellowship

and thermal regulatory centre in the brain

Antithrombotic effect: used in the

treatment of MI and other thromboembolic

Aspirin (acetyl salicylate)

Aspirin (acetyl salicylate)

inhibition of COX by acetylation, prolongs

Dr Mehran Rezvani pain fellowship

Aspirin (acetyl salicylate)

Dr Mehran Rezvani pain fellowship

NSAIDs: Acetic Acid

Dr Mehran Rezvani pain fellowship

NSAIDs: Propionic Acids

Dr Mehran Rezvani pain fellowship

NSAIDs: Other Agents

Dr Mehran Rezvani pain fellowship

NSAIDs: Other Agents

Vioxx (removed in 2004)

Dr Mehran Rezvani pain fellowship

Dr Mehran Rezvani pain fellowship

- salicylic acids aspirin

Selective COX2 inhibitors celecoxib, rofecoxib

Dr Mehran Rezvani pain fellowship

Dr Mehran Rezvani pain fellowship

under age 12 because of the risk of Reyes

Dr Mehran Rezvani pain fellowship

bleeding (inhibition of PG + other effects)

The Salicylates Aspirin

1. Dose dependent hepatitis

muscle and hepatic glycogen

Dr Mehran Rezvani pain fellowship

halucinations, depression, seizures

Dr Mehran Rezvani pain fellowship

Dr Mehran Rezvani pain fellowship

Dr Mehran Rezvani pain fellowship

adverse effects, especially GI