Antiinflammatory Agents

INFLAMMATION
• A response to tissue injury and infection
• A protective mechanism
• Fluid, elements of blood, leukocytes (WBCs),
and chemical mediators accumulate at the
injured tissue or infection site.
 CARDINAL SIGNS OF INFLAMMATION
• REDNESS
• SWELLING (EDEMA)
• HEAT
• PAIN
• LOSS OF FUNCTION
• PROSTAGLANDINS
• CYCLOOXYGENASE (COX)

• Causes inflammation and pain at a tissue

injury site
• Antiinflammatory agents also relieve pain
(analgesic),
– Reduce elevated body temperature (antipyretic)
– Inhibit platelet aggregation (anticoagulant)

• ASPIRIN is the oldest antiinflammatory drug

Nonsteroidal Antiinflammatory Drugs
(NSAIDs)
• NSAIDs are aspirin and aspirin-like drugs that
inhibit the enzyme COX, which is needed for
the biosynthesis of prostaglandins.
• Prostaglandin inhibitors
• Mild headaches and mildly elevated temp
• ASPIRIN
• IBUPROFEN (Advil, Motrin)
 7 groups of NSAIDs
1. Salicylates
2. Para-chlorobenzoic Acid
3. Phenylacetic acid derivatives
4. Propionic acid derivatives
5. Fenamates
6. Oxicams
7. Selective COX-2 inhibitors
 SALICYLATES
• ASPIRIN
• Acetylsalicylic acid (ASA)
• A prostaglandin inhibitor that decreases the
inflammatory process
• Also an antiplatelet drug (for cardiac or
cerebrovascular disorders)
• Common side effect: GASTRIC DISTRESS
• Take with food!
EC – ENTERIC COATED ASPIRINS
- doesn’t disintegrate in the stomach

DO NOT CHEW OR CRUSH TABLET!

 SALICYLATES
• DO NOT GIVE ASPIRIN TO CHILDREN WITH FLU
SYMPTOMS (viral infection)!
• May cause the potentially fatal REYE
SYNDROME (swelling in the liver and brain)
 SALICYLATES
• Hypersensitivity to ASPIRIN:
• Tinnitus (ringing in the ears)
• Vertigo
• Bronchospasm (esp in asthma pts)
 PARA-CHLOROBENZOIC ACID
• Used for rheumatoid arthritis, gouty arthritis,
osteoarthritis
• Very irritating to the stomach, should be taken
with food
• Indomethacin (Indocin)
• Sulindac (Clinoril)
• Tolmetin (Tolectin)
 Phenylacetic acid derivatives
• Similar effects as aspirin, but it has minimal to
no antipyretic effects.
• RA, osteoarthritis, ankylosing spondylitis
• Diclofenac Na (Voltaren, Voren)
• Ketorolac (Toradol) – first injectable NSAID
– short-term mgmt of pain
– For postsurgical pain
 PROPIONIC ACID DERIVATIVES
• Aspirin-like but have stronger effects and
create less GI irritation
• GI upset occurs, but not as severe as aspirin
and indomethacin
• Ibuprofen (Advil, Motrin, Alaxan, Dolan)
• Naproxen (Naprosyn, Flanax, Skelan, Penles)
 FENAMATES
• Used for acute and chronic arthritic conditions
• GI irritation
• CI: patients with Hx of peptic ulcer

• MEFENAMIC ACID (Ponstan, Dolfenal)

• Meclofenamate sodium monohydrate
(Meclomen)
 OXICAMS
• Long-term arthritic conditions, such as RA,
osteoarthritis.
• Can also cause GI problems, but incidence is
lower than other NSAIDs.
• Piroxicam (Feldene, Feldene Flash)
 st
General SE & AR for 1 Gen NSAIDs
• GASTRIC IRRITATION
• Na and water retention
 nd
2 GEN:
Selective COX-2 Inhibitors
• Protects the stomach lining
• Less GI upset
• Celecoxib (Celebrex)
• Parecoxib (Dynastat)
CORTICOSTEROIDS
 CORTICOSTEROIDS
• Prednisone
• Prednisolone
• Dexamethasone
 DISEASE-MODIFYING
ANTIRHEUMATIC DRUGS (DMARDS)
 DMARDS
• When NSAIDs do not control
immune-mediated arthritic disease
sufficiently, although more toxic, can be
prescribed to alter the disease process
1. Immunosuppressive agents
2. Immunomodulators
3. Antimalarials
 Immunosuppressive Agents
• Used to treat refractory RA (arthritis that does
not respond to antiinflammatory drugs)
• Azathioprine (Imuran)
• Cyclophosphamide (Cytoxan)
• Methotrexate (Mexate)
• Primarily used to suppress cancer growth and
proliferation
 Immunomodulators
• Treat to moderate to severe RA by disrupting the
inflammatory process and delaying disease
progression.
• Anakinra (Kineret) – administered subcutaneously
• Etanercept (Enbrel) - SQ
• Infliximab (Remicade) - IV
• Adalimumab (Humira) - SQ
• Leflunomide (Arava) - oral
 ANTIGOUT DRUGS

GOUT is an inflammatory condition

that attacks joints, tendons, and
other tissues.
Gouty arthritis
 Gouty arthritis
• The most common site of acute gouty
inflammation is at the joint of the big toe
• Increase in urates (uric acid salts) and an
accumulation of uric acid (hyperuricemia) or
an ineffective clearance of uric acid by the
kidneys
• Gout may appear as bumps or tophi, in the
subcutaneous tissue of earlobes, elbows,
hands, and the base of the large toe.
 Gouty Arthritis
• Increase fluid intake while taking antigout
drugs to promote uric acid excretion
• Causes:
• Foods high in purine (organ meats, sardines,
salmon, gravy, herring, liver, meat soups)
• Alcohol (esp beer)
 COLCHICINE
• Effective for acute gout attacks
• Not effective in decreasing inflammation
occurring in other inflammatory disorders
• Causes GI irritation (taken with food)
• Stop giving if diarrhea occurs
 Uric Acid Inhibitor
• Allopurinol (Zyloprim) – inhibits uric acid
biosynthesis, lowers serum uric acid
• Used as prophylactic to prevent gout
• Increase fluids when taking this drug
 Uricosurics
• Increase the rate of uric acid excretion
• Effective in chronic gout
• Probenecid (Benemid)
• May be taken with Colchicine
NONOPIOID and OPIOID
ANALGESICS
 NONOPIOID ANALGESICS
• Less potent than opioid analgesics
• For mild to moderate pain
• ASPIRIN
• ACETAMINOPHEN
• IBUPROFEN
• NAPROXEN
 Acetaminophen
• A nonopioid drug
• Not an NSAID
• Does not have the antiinflammatory
properties of aspirin
• Tylenol
• Midol
• Vicodin
• Percocet
 Acetaminophen
• Hepatotoxic – n/v, abd pain, diarrhea,
elevated liver enzymes
• Nephrotoxic - oliguria

• ANTIDOTE: ACETYLCYSTEINE
 OPIOID ANALGESICS
• Moderate to severe pain
• Obtained from the sap of seed pods of the
opium poppy plant
• MORPHINE SULFATE – a potent opioid analgesic
 Morphine SO4
• Effective against acute pain from acute
myocardial infarction (AMI), cancer, and
dyspnea from pulmonary edema
• May be used as preoperative medication
• A/R: RESPIRATORY DEPRESSION!
• Orthostatic hypotension, urinary retention,
constipation, miosis
• ANTIDOTE: ?
 Morphine SO4
• Monitor VS before and after, esp RR
• RR <10 cpm/min = respiratory distress
• Check for pupil changes (miosis)
• Have Naloxone (Narcan) available
 OPIOID ANALGESICS
• Meperidine (Demerol) – less adverse reactions
• Hydromorphone (Dilaudid) – 6x more potent
than morphine (faster onset and shorter
duration)
• Withdrawal symptoms:
• Irritability, diaphoresis , restlessness, muscle
twitching, ↑hr, ↑ bp
 OPIOID ANALGESICS
• Codeine
• Hydrocodone
• Oxycodone (Oxycontin)
• Oxycodone + acetaminophen (Percocet)
• Fentanyl
• Methadone
 Contraindications
• Patients with head injury
• Opioids decrease RR → CO2
accumulation/retention → vasodilation
(cerebral vessels) → increased ICP
• Hypotension, shock
 OPIOID AGONIST-ANTAGONISTS
• Medications in which an opioid antagonist
(Naloxone) is added to an opioid agonist.
• To decrease opioid abuse
• Pentazocine (Talwin)
• Nalbuphine (Nubain)
 OPIOID ANTAGONISTS
• Naloxone (Narcan)
• Naltrexone (Revia)
• Reverse respiratory and CNS depression
 HEADACHES: MIGRAINE AND
CLUSTER
MIGRAINE - are caused by inflammation and
dilation of the blood vessels in the cranium.
Causes n/v
Etiology: unkown
2 types:
Classic Migraines - associated with an AURA that
occurs minutes to 1 hour before onset
Common Migraines - not associated with an
AURA
 Cluster Headaches
Characterized by a severe unilateral
nonthrobbing pain usually located around the
eye.
Occurs in a series of cluster attacks - one or
more attacks every day for several weeks.
Not associated with an AURA.
Do not cause n/v
 TREATMENT
1. Beta Adrenergic blockers
a. Propranolol (inderal)
b. Atenolol (Tenormin)
2. Anticonvulsants
a. Valproic Acid (Depakote)
b. Gabapentin (Neurontin)
c. Tricyclic antidepressants such as amitriptyline
(Elavil) and Imipramine (Tofranil)
3. Analgesics
4. Opioid Analgesics
5. Ergot Alkaloids
 TREATMENT
6. Selective serotonin receptor agonists -
“Triptans”
Sumatriptan (Imitrex)
7. NSAIDS
a. Aspirin - may be used in combination with
caffeine
b. Acetaminophen
c. Ibuprofen
d. naproxen (Aleve)
END