Anti-Inflammatory Drugs

ANTI-INFLAMMATORY

* Common to all of us
Barrier Defense
skin
Cellular Defenses
SLE (autoimmune) hyperactive
immune system
The inflammatory response
The immune response

* Prostaglandin causes pain

Anti-Inflammatory Drugs
* Corticosteroids suppress immune system

Anti-
Inflammatory

Block or alter
chemical
reactions
associated with
the
inflammatory
response to stop
one or more of
the signs and
symptoms of
inflammation
(rubor, dolor,
calor, tumor,

1. NSAIDS
 Anti-Inflammatory Drugs
Non-Steroidal Anti-Inflammatory
Drugs
Are aspirin and aspirin-like drugs that
inhibit the synthesis of prostaglandin
Large & chemically diverse group of
drugs with varying degrees of the
following properties:
Analgesic
Anti-Inflammatory
Antipyretic
e.g. acetaminophen (paracetamol)
*Alaxan combination of ibuprofen
+ paracetamol
* stuffy nose, flu ibuprofen
Mechanism of Action:
Activation of the arachidonic acid
pathway causes:
Headache
o Analgesia : treatment of
headaches & pain
- Block the undesirable
effects of prostaglandins,
which cause headache
Fever
o Antipyretic: reduce fever
- Inhibit prostaglandin E2
within the area of the
brain that controls
temperature
Inflammation
o Relief of Inflammation
- Inhibit the leukotriene
pathway, the
prostaglandin pathway or
both
Six Structurally related groups
1) Acetic acids
2) Carboxylic acids
3) Propionic acids
4) Enolic acids
5) Fenamic acids
6) Nonacidic compounds
A. NSAIDS: CARBOXYLIC ACIDS
(SALICYLATES)
Acetylated
Aspirin (ASA)
Choline Magnesium Salicylate
(Trilisate)
Nonacetylated
Salicylamide Balsalazide
Salsalate Olsalazine
(Disalcid) Mesalamine
Sodium
Salicylate
SALICYLATES
Block the inflammatory response
Antipyretic (fever blocking)
Analgesic (pain blocking)
More potent effect on platelet
aggregation and thermal regulatory
center in the brain
Antithrombotic effect: used in the
prevention of stroke, TIA (Transient
ischemic Effect) and other
thromboembolic disorders
Reduce risk of death and MI in patients
with hx of MI and Angina
Watch out for: SALICYLISM
Toxic effects of drug
Patient will verbalize theres ringing in
the ears = tinnitus (pp 341)
Normal therapeutic range: 15-30
mg/dL
> 30 mg/dL = Mild toxicity
>50 mg/dL = Severe toxicity
* observe for signs of bleeding
* stop drug for 7-14 days before tooth
extraction or surgery
* dont give salicylates to pediatric
patient
* Reyes syndrome = if salicylates given
to ptx wth chicken pox and flu-like
symptoms
* when you hear salicylates, remember: it
causes bleeding and Reyes syndrome
* Antithrombotic- means it prevents blood
clot therefore causing the ptx to bleed
NSAIDS
COX1
COX2
GI bleeding
Pain
PA (Platelet
Inflammation
Aggregation)
Fever
 Anti-Inflammatory Drugs
Adverse Effects (Salicylates)
GI Irritation
N/V, epigastric discomfort C. NSAIDS: PROPIONIC ACIDS
Bleeding fenoprofen (Nalfon)
Salicylism flurbiprofen (Ansaid)
Dizziness, ringing in the ears, ibuprofen (Advil, Motrin)
difficulty hearing, nausea, short t 1/2 , highly CHON bound
vomiting, diarrhea, mental ketoprofen (Orudis)
confusion, lassitude naproxen (Naprisyn)
Salicylate Toxicity (see page 340- oxaprozin (Dapro)
341)
- Respiratory alkalosis, D. NSAIDS: OTHER AGENTS
hyperpnea, tachypnea, Enolic Acids/Oxicams
hemorrhage, excitement, phenylbutazone (Butazolidin)
convulsions, tetany, piroxicam (Feldene)
metabolic acidosis, fever, long t 1/2 ; taken once daily
Fenamates Acids
coma, cardiovascular,
meclofenamic acid (Meclomen)
renal and respiratory
mefenamic acid (Ponstan)
collapse
diflunisal (Dolobid)
Nonacidic Compounds
Half-life of aspirin nabumetone (Relafen)
t = 2-3 hours (low dose)
Excretion = 50 % COX INHIBITORS
COX-1 is present in all tissues and seem
Caution Use Salicylate to be involved In many body functions
Renal Disorder including clotting, protecting the stomach
Asthmatic patients lining and maintaining sodium and H2O
Viral Illness balance in the kidney
Reyes Syndrome COX-2
Vomiting, drowsiness, COX-2 Inhibitors
disorientation, irritability, valdecoxib (Bextra)
Severe ICP celecoxib (Celebrex)
May cause seizures, coma, etoricoxib (Arcoxia)
abnormal accumulations of fat in rofecoxib (vioxx)
the liver, child may stop breathing
B. NSAIDS: ACETIC ACID Adverse effects:
diclofenac sodium (Voltaren) GI Bleeding
indomethacin (Indocin) HA, Dizziness
Can promote closure of premature Fatigue
infants PDA Bone marrow depression
ketorolac (Toradol) Rash and mouth sores
1st injectable Interactions:
etodolac (Lodine) Loop diuretics (COX 1 responsible
tolmetin (Tolectin) for sodium and H2O imbalance)
tulindac (Clinoril) For HPN, edema ptx
*page 342 Beta blockers
Lithium ibuprofen (for manic
patients)
ACETAMINOPHEN (Tylenol)
 Anti-Inflammatory Drugs
Acts directly on the thermoregulatory
cells in the hypothalamus to cause
sweating and vasodilation
Mechanism of action related to the
analgesic effects of acetaminophen has
not been identified
No effect on inflammation and platelet
function
Extensively metabolized in the liver
*Prolonged use
toxicity leading to hepatotoxicity
*Antidote: acetylcysteine
*Don't give to patients with liver problem
* Max dose: 4g/day
* page 355
Adverse Effects:
Headache
Hemolytic anemia
Skin rash & fever
Hepatotoxicity
Interactions:
- Decreases effect with oral contraceptive,
anticholinergics, cholestyramine, charcoal
- Increase effect with caffeine, diflunisal
2. CORTICOSTEROIDS (pp. 344)
*last choice in treating patients in pain
* can cause immunosuppression (if
prolonged use)
* mimics diurnal rhythm (sleep and wake
pattern)
ANATOMY
Adrenal Glands
Adrenal Medulla
inner layer of adrenal gland;
sympathetic ganglia, releases
norepinephrine and epinephrine into
circulation in response to sympathetic
stimulation
Adrenal Cortex
outer layer of adrenal gland;
produces glucocorticoids and
mineralocorticoids in response to
ACTH stimulation, also responds to
sympathetic stimulation
- hypertensive ( b/c of Na and H2O
retention)
- increased blood sugar
(hyperglycemia)
* When stressed, we eat too much
Diurnal Rhythm
Secretion of CRH, ACTH, and cortisol
are high in the morning in day-
oriented people those who have a
regular cycle of wakefulness during
the day and sleep during the night. In
such individuals, the peak levels of
cortisol usually come between 6 and
8 am. The levels then fall off slowly
(w/ periodic spurts) and reach a low
in the late evening, with the lowest
levels around midnight
*4-6 pm -> irritable, want to rest and sleep
*midnight ->low cortisol
GLUCOCORTICOIDS
Enter target cells and bind to
cytoplasmic receptors, initiating
many complex reaction that are
responsible for anti-inflammatory
and immunosuppressive effects
Indicated for the short term
treatment of many inflammatory
disorders, to relieve discomfort and
to give the body a chance to heal
from effects of inflammation
Blocks the action of arachidonic
acid thus decreasing
prostaglandins and leukotrienes
Manifestations of viral
infection
- runny nose
- frequent throat
Rebound congestion
- topical/ inhalants use, nawawala
ang initial congestion but pag
bumalik, mas malala
GLUCOCORTICOIDS: COMMON DRUGS
Dexamethason Psoriasis, breathing
e (Decadron) disorders
Betamethasone Promotes fetal lung
(Celestone) maturity
Hydrocortisone Severe allergic rxns,
(Solu-cortef) breathing problems
Methylprednisol Asthma, bronchitis
 Anti-Inflammatory Drugs
one (Solu- therapy in primary and secondary
problems
medrol) adrenal insufficiency
Prednisone Lupus *Tx of salt-wasting
(Orasone SLE adrenogenital syndrome
fludocortisone (Flurinef)
Adverse effects: * taper dose (avoid severe side
Gastric irritation/ Peptic ulcer effects)
development ADVERSE SIDE EFFECTS
*N/C: with meals Increased fluid
fluid retention CHF
volume seen
congestive heart failure Arrhythmias
with Na and
*if you give = cause edema Weakness
H2O retention hypokalemia
CNS stimulation headache
increased appetite, weight gain edema, hpn
* Na & H2O retention
- hypertensive, 2lbs/wk = edema Nursing Consideration on Corticosteroid
fragile skin, loss of hair
therapy
hyperglycemia, hypokalemia,
monitor fluid and electrolyte balance
hypocalcemia administer with meals
weakness, muscle atrophy administer in the morning
Cataracts, Glaucoma limit Na intake
Amenorrhea * b/c Na & H2O retention
Increased sensibility to infections - do not discontinue abruptly
* Immunosuppression * taper the dosage
* N/C: Increase immune response *Corticosteroid is given to rheumatoid,
of ptx by increasing fluid intake, bed rest arthritis, if Di Na nagwo-work or walang
Development of cancers effect NSAIDS
Adverse effects on children
risk for growth retardation associated Gouty arthritis
with suppression of the hypothalamic- - lumalaki joints and accumulation of
pituitary system fluid...??
Interactions *po 343 antigout
o Erythromycin & Ketoconazole
-> Increased toxicity 3. DISEASE MODIFYING ANTI-ARTHRITIS
o ASA (aspirin) and Phenytoin DRUGS (DMARDS)
-> decreases effect of Gold Compounds
Glucocorticoid Chrysotherapy
* there is hypertensive, hypercalcemia, tx with gold compounds
hyperglycemia, hirsutism, moon faces?, absorbed by macrophages thus
buffalo hump inhibits phagocytosis
* moon faces - namamaga/namamanas ang tx of rheumatoid arthritis
mukha Common Drugs
Auranofin (Ridawra)
MINERALOCORTICOIDS - oral agent (long term)
Increased sodium reabsorption in - inhibits phagocytosis
the renal tubules and increased Aurothioglucose (Solgenal?)
potassium and hydrogen - injected (early tx)
excretion , leading to retention Gold Na Thiomalate?
indicated in combination with a (Aurolate)
glucocorticoid, for replacement Adverse Effects
 Anti-Inflammatory Drugs
GI mucosal irritation
Stomatitis, gingivitis, colitis
Gold Bronchitis & Pneumonitis
Dermatitis
DMARDs
DRUGS USES
Genetically engineered
TNF receptor
Given per SC for active
rheumatoid arthritis
etanercept
Can cause CNS damage
(Enbrel)
and severe
myelosuppression and
cancer development
leflunomide Inhibits dihydroorotate
(Arava) dehydrogenase
Hepatotoxic
penicilamine Lowers IgM rheumatoid
( factor
Takes 2-3 months
before a response is
noted
sodium Injected to the joints to
hyaluronate
ADVERSE EFFECTS: DMARDs
Local irritation risk for infection
at injection sites Rashes
Pain at injection Fatal
sites hepatotoxicity
Other Anti-Arthritis Drugs
IMMUNOSUPPRESIVE DRUGS
Primarily suppresses cancer
growth and proliferation might
be used to suppress the
inflammatory process when
other treatment fails
Used to treat refractory
rheumatoid arthritis
Ex: Azathioprine (Imuran)
Cyclophosphamide
(Cytoxan)
Methotrexate (Mexate)
ANTIMALARIAL AGENTS
Unknown mechanism of action
in suppressing rheumatoid
arthritis
Used to treat rheumatoid
arthritis when other methods of
treatment fails
Effect may take-12 weeks
Usually used in combination
with NSAIDs in ptx with arthritis
is not under control
ANTI-GOUT DRUGS
Gout metabolic disease of
unknown cause; inflammatory
condition that attacks the joints
and other tissues; characterized by
defect in purine metabolism;
Hperuricemia hallmarks of gout
TREATMENT GOALS:
1) End acute gouty attack ASAP
2) Prevent recurrence of acute gouty
arthritis
3) Prevent formation of uric acid stone in
kidney
4) Decrease or prevent disease
complications that result from Na+ urate
deposit into joints and kidneys
NON-PHARMACOLOGIC MANAGEMENT
Increase fluid intake
Urine should be alkalinized
Using NaHCO3;
Avoid foods rich in purine
Use acetaminophen instead of aspirin
*give with milk and food, increase water
PHARMACOLOGIC MANAGEMENT
Colchicine
For acute gouty arthritis
the motility of leukocytes,
phagocytosis
Constrict blood vessels and affect
central vasomotor stimulation
Inhibits migration on WBC to inflamed
joints thus inhibiting uric acid
deposition
Side effects; N/V, blood dyscracias
 Anti-Inflammatory Drugs
Nursing responsibilities: Uric acid stone
1) Administer with food if given per formation Headache
orem Bleeding and GI Pain
2) Cautiously used to elderly and hypoglycemia- N/V
those with cardiac, renal or gastric ulfinepyrazone
diseases
3) Avoid alcoholic beverages URIC ACID INHIBITORS
4) If given per IV
Allopurinol Improves
Avoid extravasation
Incompatible with D5 solution (Zyloprim) solubility of uric
5) With narrow margin of safety decreases acid
6) Inc. fluid intake and monitor I&O production of uric
7) Monitor blood level acid by inhibiting
xanthine oxidase
DRUG INTERACTION
risk of rash
formation
URICOSURICS AMOXICILLIN OR effect of
Anti-gout drugs AMPICILLIN Coumadin and
Reduces reabsorption of uric acid oral
Inhibits excretion of weak organic hyperglycemias
acids such as penicillin and some ACE INHIBITIORS hypersensitivity
cephalosporin risk of bone
COMMON DRUGS CYCLOPHOSPHAMIDE marrow
PROBENECID Prevents supression
reabsorption of
uric acid
SULFINPYRA Antigout effect
ZONE Anticoagulant OTHER ANTI-GOUT AGENTS ADVERSE
(can cause effect RXNS
synergistic Has a synergistic Rash, pruritis, fever
effect on effect on Bone marrow depression, hepatotoxicity
diabetes OHA N/V with abdominal pain, diarrhea,
patients) dizziness

URICOSURICS DRUG INTERACTON NURSING CARE

renal excretion of 1) Increase fluid intake
Ketoprofen 2) Monitor renal function
ketoprofen
Antineoplastic 3) Give with milk or food
uric acid nephropathy 4) Alkalinize urine (NaHCO3 and K citrate)
agents
5) Begin therapy when acute attack
renal excretion of subsides
Aspirin
aspirin 6) Limit intake of purine rich foods
Heparin Prolonged effect 7) Avoid alcohol
toxic effects of 8) Avoid activities that require mental
Nitrofurantoin alertness
nitrofurantoin
9) Remember that it prevents gout but not
relieve gout episodes
ADVERSE EFFECT: URICOSURICS