Transcript Anti-inflammatory, Antirheumatoid and Related Agents

Antiinflammatory
Agents
and Nonsteroidal
Antiinflammatory
Drugs (NSAIDs)
Groups of anti-inflammatory agents and
mechanism of action:
1) nonsteroidal anti-inflammatory drugs - NSAI
2) glucocorticosteroids (GCS)
+
Phospholipids
glucocorticosteroids
Phospholipase
LK
А2
Arachidonic
acid
NSAID
Cyclooxygenases
(COG-1, COG-2, COG-3)
Cyclic
endoperoxydases
Prostaglandins
Inflammation
Pain
Fever
Thromboxan
Vasoconstriction
Increasing of
platelets aggregation
-
- depressing effect
+
- stimulating effect
NSAIDs
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Large and chemically diverse group of drugs
with the following properties:
Analgesic
 Antiinflammatory
 Antipyretic
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NSAIDs: Mechanism of Action
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Activation of the arachidonic acid
pathway causes:
pain
headache
fever
inflammation
Arachidonic Acid
Pathway
NSAIDs: Mechanism of Action
Analgesia—treatment of headaches and pain
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Block the undesirable effects of prostaglandins, which
cause headaches
NSAIDs: Mechanism of Action
Antipyretic: reduce fever
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Inhibit prostaglandin E2 within the area of the brain
that controls temperature
NSAIDs: Mechanism of Action
Relief of inflammation
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Inhibit the leukotriene pathway, the prostaglandin
pathway, or both
NSAIDs
Six structurally related groups:
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Acetic acids
Carboxylic acids
Propionic acids
Enolic acids
Fenamic acids
Nonacidic compounds
NSAIDs: Acetic Acid
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diclofenac sodium (Voltaren)
diclofenac potassium (Cataflam)
etodolac (Lodine)
indomethacin (Indocin)
sulindac (Clinoril)
tolmetin (Tolectin)
NSAIDs: Carboxylic Acids
Acetylated
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aspirin (ASA)
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choline magnesium salicylate (Trilisate)
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diflunisal (Dolobid)
Nonacetylated
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salicylamide
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salsalate (Disalcid)
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sodium salicylate
NSAIDs: Propionic Acids
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fenoprofen (Nalfon)
flurbiprofen (Ansaid)
ibuprofen (Motrin, others)
ketoprofen (Orudis)
ketorolac (Toradol)
naproxen (Naprosyn)
oxaprozin (Daypro)
NSAIDs: Other Agents
Enolic acids
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phenylbutazone (Butazolidin)
piroxicam (Feldene)
Fenamic acids
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meclofenamic acid (Meclomen)
mefenamic acid (Ponstel)
Nonacidic compounds
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nabumetone (Relafen)
NSAIDs: Other Agents
COX-2 Inhibitors
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celecoxib (Celebrex)
rofecoxib (Vioxx)
Acetylsalicylic acid
Aspirin С
Aspirin
Butadion
Indometacin (methyndol)
Ibuprofen (brufen)
Piroxicam
Sodium diclofenac
Voltaren
NSAIDs: Drug Effects
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Analgesic (mild to moderate)
Antigout
Antiinflammatory
Antipyretic
Relief of vascular headaches
Platelet inhibition (ASA)
NSAIDs: Therapeutic Uses
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Relief of mild to moderate pain
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Acute gout
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Various bone, joint, and muscle pain
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Osteoarthritis
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Rheumatoid arthritis
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Juvenile rheumatoid arthritis
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Dysmenorrhea
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Fever
NSAIDs: Specific Agents
salicylates (aspirin)
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More potent effect on platelet aggregation and thermal
regulatory center in the brain
 analgesic
 antipyretic
 antiinflammatory
Antithrombotic effect: used in the treatment of MI
and other thromboembolic disorders
NSAIDs: Specific Agents
phenylbutazone (Butazolidin)
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Greater effects on uric acid production and excretion,
in addition to antiinflammatory effects
More commonly used for treatment of gout
NSAIDs: Side Effects
Gastrointestinal
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dyspepsia, heartburn, epigastric distress, nausea
**GI bleeding
**mucosal lesions (erosions or ulcerations)
Misoprostol (Cytotec) can be used to reduce these
dangerous effects.
NSAIDs: Side Effects
Renal
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reductions in creatinine clearance
acute tubular necrosis with renal failure
NSAIDs: Side Effects
Cardiovascular
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noncardiogenic pulmonary edema
NSAIDs: Salicylate Toxicity
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Adults: tinnitus and hearing loss
Children: hyperventilation and CNS effects
Effects arise when serum levels exceed
300g/mL.
Metabolic acidosis and respiratory alkalosis may
be present.
NSAIDs: Nursing Implications
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Before beginning therapy, assess for
conditions that may be contraindications to
therapy, especially:
GI lesions or peptic ulcer disease
 Bleeding disorders
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Assess also for conditions that require
cautious use.
Perform lab studies as indicated (cardiac,
renal, liver studies, CDC, platelet count).
NSAIDs: Nursing Implications
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Perform a medication history to assess for
potential drug interactions.
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Several serious drug interactions exist:
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alcohol
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heparin
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phenytoin
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oral anticoagulants
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steroids
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sulfonamides
NSAIDs: Nursing Implications
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Salicylates are NOT to be given to children
under age 12 because of the risk of Reye’s
syndrome.
Because these agents generally cause GI distress,
they are often better tolerated if taken with
food, milk or an antacid to avoid GI irritation.
Explain to patients that therapeutic effects may
not be seen for 3 to 4 weeks.
NSAIDs: Nursing Implications
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Educate patients about the various side effects
of NSAIDs, and to notify their physician if
these effects become severe
or if bleeding or GI pain occur.
Patients should watch closely for the occurrence
of any unusual bleeding,
such as in the stool.
Enteric-coated tablets should not be
crushed or chewed.
NSAIDs: Nursing Implications
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Monitor for therapeutic effects, which vary
according to the condition being treated:
decrease in swelling, pain, stiffness,
and tenderness of a joint or muscle area
GLUCOCORTICOIDS
• Reduce inflammation and immune responses
• In clinical practice since 1948
• $10,000,000,000./year market size in US
Steroid Hormones: Derived from Cholesterol
Lipid Soluble: Able
to cross plasma
membrane by
passive diffusion
PHYSIOLOGICAL EFFECTS OF
GLUCOCORTICOIDS
 Regulation of carbohydrate, protein
and lipid metabolism
 Maintenance of fluid and electrolyte
balance
Preservation of normal function of the
cardiovascular system, the immune
system, the kidney, skeletal muscle, the
endocrine system and the nervous system
Preservation of organismal homeostasis
GR
GR
Effects of Glucocorticoids on Components
of Inflammatory/Immune Responses
CELL TYPE
FACTOR
COMMENTS
Macrophages
Monocytes
Prostaglandins,
Leukotrienes
Inhibition of COX-2,
Phospholipase A2
IL-1, IL-6. TNF
Inhib. Transcript., Release
Endothelial Cells
ICAM-1. ELAM-1
IL-1, Prostagl., Leuko.
Inhib. Transcript., Release
As above
Basophils
Histamine, Leukotriene
Inhib. IgE Release
Lymphocytes
IL-1, IL-2, IL-3, etc
As above
The anti-inflammatory and
immunosuppressive actions of
glucocorticoids play an important role in
preventing potential damaging effects of an
unopposed inflammatory response and can
be exploited therapeutically
Glucocorticoids: Side Effects
The beneficial effects of systemic
glucocorticoids to limit inflammation is
counter-balanced by its many adverse side
effects
The broad anti-inflammatory actions of
glucocorticoids are due primarily to
transcriptional repression of many proinflammatory genes in multiple cell types by
the glucocorticoid receptor.
From Glass and Rosenfeld
Relative Potencies of Glucocorticoids
Compound
Anti-Inflammatory
Na+ -Retaining
Duration
Potency
Potency
of Action
Cortisol
1
1
S
Cortisone
0.8
0.8
S
Prednisolone
4
0.8
I
Triamcinolone
5
0
I
Betamethasone
25
0
L
Dexamethasone
25
0
L
S, short (i.e., 8–12 hour biological half-life); I, intermediate
(i.e., 12–36 hour biological half-life); L, long (i.e., 36–72
hour biological half-life)
IMPORTANT CONCEPT 7: Structural
modifications of the natural glucocorticoid
cortisol generate hormones with enhanced
half-life and more potent and efficacious
glucocorticoid activity
Antiseptics and Disinfectants
Antiseptics and Disinfectants
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Most desirable quality is the ability to destroy
microorganisms
They have 2 uses: disinfect instruments and treat
infections in oral cavity and on body surfaces
2 different agents may have to be used to
achieve adequate cleaning
Actions of Antiseptics and
Disinfectants
Agent
Action
antiseptic
inhibits growth of microorganisms
disinfectant
chemical applied to objects
fungicide
destroys fungi
germicide
destroys bacteria
preservative
prevents decomposition
sanitizer
reduces the number of bacteria
sporicide
destroys spores
Drug List
Antiseptics and
Disinfectants
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alcohol, isopropyl
hexachlorophene (pHisoHex)
povidone-iodine (Betadine)
sodium hypochlorite (Clorox)
hexachlorophene (pHisoHex)
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Surgical scrub and bacteriostatic skin cleanser
Especially effective against gram-positive
bacteria
Do not leave on skin for an extended period of
time
Drug List
Antiseptics and
Disinfectants
Heavy Metal Compounds
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silver nitrate
zinc oxide (Desitin Creamy)
Drug List
Antiseptics and
Disinfectants
Orals
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benzocaine (Hurricaine, Orabase-B)
carbamide peroxide (Gly-Oxide Oral)
cevimeline (Evoxac)
chlorhexidine gluconate (Hibiclens)
clove oil (Eugenol)
Drug List
Antiseptics and
Disinfectants
Others
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benzalkonium chloride (Zephiran)
hydrogen peroxide
phenytoin (Dilantin)
What characteristics make an ideal antiseptic?
Answer: can inhibit all forms of microorganisms,
nontoxic, does not induce sensitization, can
penetrate tissues and body fluids, water soluble,
noncorrosive, inexpensive