CHAPTER 16:

ANTI – INFLAMMATORY, ANTI-ARTHRITIS, AND RELATED AGENTS

Reporter: GABIANA, KHYSS CLAUDETH C.

The inflammatory response, which is important for protecting the body from injury and invasion,
produces many of the signs and symptoms associated with disease, including fever, aches and
pains, and lethargy. Anti-inflammatory drug block various chemicals associated with
inflammatory reaction. Chronic or excessive activity by the inflammatory response can lead to
release of lysosomal enzyme and tissue destruction. Anti-inflammatory drugs also may have
antipyretic (fever blocking) and analgesic (pain blocking) activities.

Corticosteroids are used systemically to block the inflammatory and immune systems. Blocking
these important protective processes may produce many adverse effects, including decreased
resistance to infection and neoplasms.

Anti-histamine is used to block the release of histamine in the initiation of the inflammatory
response. Many of the immune modulating agents are used to block or decreased the effects of
inflammation in chronic disorders such as rheumatoid arthritis and Crohn’s disease.

Salicylates are popular anti-inflammatory agents not only because of their ability to block the
inflammatory response, but also because of their antipyretic (fever blocking) and analgesic
(pain blocking) properties. They are generally available without prescriptionand are relatively
nontoxic when used as directed. Salicylates block prostaglandin activity, which decreases the
response and relieves the signs and symptoms of inflammation. Salicylates can also cause GI
irritation, eight cranial nerve stimulation and salicylism – ringing in the ears, acidosis, nausea,
vomiting, diarrhea and mental confusion and lassitude.
Therapeutic Action

The desired and beneficial actions of salicylates are as follows:

  It inhibits synthesis of prostaglandin, an inflammatory reaction mediator.
 Antipyretic effect is through blocking of prostaglandin mediator of pyrogens
(chemicals released by active white blood cells that cause increase in body
temperature) at the thermoregulatory center of the hypothalamus.
 Aspirin at low levels can affect reduce platelet aggregation by inhibiting synthesis of
thromboxane A2, a potent vasoconstrictor that normally increases platelet
aggregation and blood clot formation. On the other hand, at higher levels, it inhibits
the synthesis of prostacyclin, a vasodilator that inhibits platelet aggregation.

Indications

Salicylates are indicated for the following medical conditions:

 Treatment of mild to moderate pain, fever, numerous inflammatory conditions

(e.g., rheumatoid arthritis and osteoarthritis).
 Mesalamine and balsalazide are indicated for ulcerative colitis and other
inflammatory bowel conditions in adults.
 Sodium thiosalicylate is used in treatment of arthritis and muscular pain.

Here are some important aspects to remember for indication of anti-inflammatory agents, anti-
arthritis, and NSAIDs in different age groups:

Children

 Ensure correct dose because this population is more susceptible to GI and CNS side
effects of drugs. Most of these drugs are available over the counter so primary
caregivers should be instructed to read the label to find out the dose that they are
supposed to give.
 Aspirin and choline magnesium trisalicylate are the salicylates recommended for
children. However, they are contraindicated when risks for Reye Syndrome is present.
 Acetaminophen is the most used anti-inflammatory drug for children. Overdose can
cause severe hepatotoxicity.
  In general, several NSAIDs are approved for use in children,
i.e. ibuprofen, naproxen, tolmetin, meloxicam, and indomethacin for some cases.

Adults

 Caution about the presence of these drugs in many OTC products.

 Instruct adults to report OTC drug use to their health care provider when they are
receiving any other prescription drug to avoid possible drug-drug interactions and the
masking of signs and symptoms of disease.

Cultural consideration: African Americans have a documented decreased sensitivity to the

analgesic property of anti-inflammatory agents. They also have increased risk of developing GI
adverse effects to these drugs. Educate these patients about signs and symptoms of
GI bleeding and monitor them closely.

Pregnant women

 As for pregnant and nursing women, use is only justified when benefits clearly
outweigh the risks.

Older adults

 Dose adjustment is needed as this age group is also more susceptible to GI and CNS
drug side effects.
 Naproxen, ketorolac, and ketoprofen come with geriatric warnings because of
reports of increased toxicity so these drugs should be avoided if possible.
 Gold salts, a treatment for arthritis is particularly toxic for geriatric patients. It can
cause renal, GI, and liver problems.

Pharmacokinetics

Here are the characteristic interactions of salicylates and the body in terms of absorption,

distribution, metabolism, and excretion:

Route Onset Peak Duration

Oral 5-30 min 0.25-2 h 3-6 h

Rectal 1-2 h 4-5 h 6-8 h

T1/2: 15 min-12 h
Metabolism: liver
Excretion: urine

Contraindications and Cautions

The following are contraindications and cautions for the use of salicylates:

 Allergy to salicylates, NSAIDS, tartrazine (dye with cross-sensitivity with aspirin). Prevent
risk of allergic reaction.
 Bleeding abnormalities. Changes in platelet aggregation.
 Impaired renal function. Drug is excreted through urine.
 Chickenpox or influenza. Risk of Reye Syndrome in children and teenagers.
 Surgery or other invasive procedures within one week. Risk of increased bleeding.
 Pregnancy and lactation. Potential adverse effects on the neonate or mother.

Adverse Effects

Improper use of salicylates may result to these adverse effects:

 GI: nausea, dyspepsia, heartburn, epigastric discomfort

 Hema: blood loss, bleeding abnormalities
 WARNING Salicylism can occur with high levels of aspirin characterized by dizziness,
ringing in the ears, difficulty hearing, nausea, vomiting, diarrhea, mental confusion,
and lassitude.
 WARNING Acute salicylate toxicity occurs at doses of 20-25 g in adults or 4 g in
children. Signs include hyperpnea, tachypnea, hemorrhage, excitement, confusion,
 pulmonary edema, convulsions, tetany, metabolic acidosis, fever, coma, and
cardiovascular (CV), renal, and respiratory collapse.

Interactions

The following are drug-drug interactions involved in the use of salicylates:

 Anticoagulants: increased risk of bleeding

 NSAIDs: increased serum levels of NSAID
 Activated charcoal: decreased absorption of salicylates
 Antacids: decreased effects of the salicylates
 Carbonic anhydrase inhibitor: increased risk for salicylism

Nursing Considerations

Here are important nursing considerations when administering anti-inflammatory agents:

Nursing Assessment

These are the important things the nurse should include in conducting assessment, history taking,
and examination:

 Assess for contraindications or cautions (e.g., history of allergy to salicylate and

tartrazine, renal disease, bleeding disorders, pregnancy and lactation, etc.) to avoid
adverse effects.
 Establish baseline physical assessment to monitor for any potential adverse effects.
 Assess for presence of skin lesions to monitor for dermatological effects.
 Monitor temperature to evaluate drug’s effectiveness in lowering temperature.
 Evaluate CNS status to assess CNS effects of the drug.
 Monitor pulse, blood pressure, and perfusion to assess for bleeding effects or
cardiovascular effects of the drug.
 Evaluate respirations and adventitious sounds to detect hypersensitivity reactions.
  Perform a liver evaluation and monitor bowel sounds to detect hypersensitivity
reactions, bleeding, and GI effects of the drug.
 Monitor laboratory tests for CBC, liver and renal functions tests, urinalysis, stool guaiac,
and clotting times to detect bleeding or other adverse effects of the drug and
changes in function that could interfere with drug metabolism and excretion.

Nursing Diagnoses

Here are some of the nursing diagnoses that can be formulated in the use of this drug for
therapy:

 Acute pain related to CNS and GI effects

 Risk for ineffective breathing pattern related to toxic effects
 Risk for disturbed sensory perception: auditory, kinesthetic related to toxic effects

Implementation with Rationale

These are vital nursing interventions done in patients who are taking anti-inflammatory agents:

 Administer drug with food to alleviate GI effects.

 Check all drugs being taken for possible salicylate ingredients to avoid toxic levels.
 Monitor for severe reactions to avoid problems and provide emergency procedure
(e.g., gastric lavage, induction of vomiting, etc.)
 Arrange for supportive care and comfort measures (e.g., rest, environmental control)
to decrease body temperature or to alleviate inflammation.
 Ensure patient is well hydrated during therapy to decrease risk of toxicity.
 Provide patient education about drug effects and warning signs to increase
knowledge about drug therapy and to increase compliance with drug.

Evaluation

Here are aspects of care that should be evaluated to determine effectiveness of drug therapy:
  Monitor patient response to therapy (improvement in condition being treated, relief
of signs and symptoms of inflammation).
 Monitor for adverse effects (e.g., GI upset, CNS changes, bleeding).
 Evaluate patient understanding on drug therapy by asking patient to name the drug,
its indication, and adverse effects to watch for.
 Monitor patient compliance to drug therapy.

NSAIDs -- or nonsteroidal anti-inflammatory drugs -- are among the most common pain relief
medicines in the world. Every day more than 30 million Americans use them to soothe headaches,
sprains, arthritis symptoms, and other daily discomforts, according to the American
Gastroenterological Association. And as if that wasn't enough, in addition to dulling pain NSAIDs also
lower fever and reduce swelling. Examples of the most common NSAIDs include: aspirin salsalate
(Amigesic), diflunisal (Dolobid), ibuprofen (Motrin), ketoprofen (Orudis), nabumetone (Relafen),
piroxicam (Feldene), naproxen (Aleve, Naprosyn,) diclofenac (Voltaren), indomethacin
(Indocin), sulindac (Clinoril), tolmetin (Tolectin), etodolac (Lodine), ketorolac (Toradol), oxaprozin
(Daypro), celecoxib (Celebrex).

NSAIDs blocks prostaglandin synthesis at cyclooxygenase – 1 (COX-1) and COX 2 sites. This
blocks inflammation but also blocks protection of the stomach lining, as well as the kidney’s
regulation of water.
Therapeutic Action

The desired and beneficial action of NSAIDs is:

 Inhibition of prostaglandin synthesis thereby exerting its anti-inflammatory, analgesic,

and antipyretic effects.
 It blocks two enzymes, namely cyclooxygenase (COX) 1 and 2 present in all tissues
and seems to be involved in many body functions, like blood clotting, stomach lining,
and sodium-water balance in the kidney. COX-1 turns arachidonic acid into
prostaglandins as needed. COX-2 is active at sites of trauma or injury when more
prostaglandins are needed. Therefore, NSAIDs block inflammation before all of the
signs and symptoms can develop.
 Acetaminophen, a related agent, acts directly on the thermoregulatory cells in
the hypothalamus to cause sweating and vasodilation causing release of heat. The
mechanism related to analgesic effects has not been identified.

Indications
NSAIDs are indicated for the following medical conditions:

 Relief of signs and symptoms of rheumatoid arthritis and osteoarthritis

 Relief of mild to moderate pain
 Treatment of primary dysmenorrhea
 Fever reduction
  Acetaminophen, a related agent, is used to treat moderate to mild pain and fever in
children and often used in place of the NSAIDs or salicylates. It is found in many
combination products and can cause severe liver toxicity that can lead to death
when taken in high doses.
 Acetaminophen is also used in treatment of influenza, for prophylaxis of children
receiving diphtheria-pertussis-tetanus (DPT) immunizations, and for relief of
musculoskeletal pain associated with arthritis.

Pharmacokinetics

Here are the characteristic interactions of NSAIDs and the body in terms of absorption,
distribution, metabolism, and excretion:

Route Onset Peak Duration

Oral 30 min 1-2 h 4-6 h

IV Start of infusion Minutes 4-6 h

T1/2: -1.8 – 2.5 hrs.

Metabolism: liver
Excretion: urine

Contraindications and cautions for the use of NSAIDs include:

 Allergy to NSAIDs or salicylate. Prevent adverse effects.

 Allergy to sulfonamides. Contraindication with celecoxib.
 CV dysfunction or hypertension. Varying effects of prostaglandins
 Peptic ulcer or known GI bleeding. Potential to exacerbate GI bleeding.
 Pregnancy or lactation. Potential adverse effects on the neonate or mother.
 Renal or hepatic dysfunction. Can alter metabolism and excretion of the drug.
 Any other known allergies. Indicate increased sensitivity.

Adverse Effects
 Use of NSAIDs may result to these adverse effects:

 CNS: headache, dizziness, somnolence, fatigue

 CV: hypertension
 GI: nausea, dyspepsia, GI pain, constipation, diarrhea, flatulence
 Hema: bleeding, platelet inhibition, bone marrow depression

Interactions

The following are drug-drug interactions involved in the use of NSAIDs:

 Loop diuretics: decreased diuretic effect

 Beta-blockers: decreased antihypertensive effect
 Ibuprofen: potential for lithium toxicity
 Oral anticoagulants: increased bleeding with acetaminophen
 Chronic ethanol ingestion: risk of toxicity with acetaminophen

Nursing Considerations

o Assessment (history and physical exam)

o Nursing diagnosis
o Implementation
o Evaluation
Difference between COX1 and COX2
Different types of prostanoids can be easily synthesized in the body by using an enzyme named
as cylcooxygenase (COX). These prostanoids including
prostaglandins, prostacyclin and thromboxane are important biological mediators that play
crucial role in the development of pain and inflammation in the body. So it is possible to get
relief from pain and inflammation by inhibiting the COX enzyme.

There are three different types of COX enzymes such as COX1, COX2 and COX3. They are similar
in different aspects and have some differences too. The difference between COX1 and COX2 is
outlined below.

Difference in Name:
COX-1 is also called as constitutive enzyme because it is produced by a cell under all types of
physiological conditions. The amount at which constitutive enzymes are produced remain
constant without regard of substrate concentration and physiological demand. On the other
hand COX-2 is an inducible enzyme as it is produced under certain specific conditions like
inflammation.
Difference in Locations:
COX-1 is commonly found in the kidney, stomach and platelets whereas COX-2 is located in
macrophages, leukocytes and fibroblasts.

Difference in Functions:
COX-1 play important role in housekeeping such as it protects gastric mucosa, regulate gastric
acid and maintain normal functions of the kidney by stimulating prostaglainds. COX-2 is
involved in the synthesis of prostaglandins that causes pain and inflammation in the body.

Difference in Production:
The stimulation of COX-1 enzyme is done on a continuous basis by the body but COX-2 enzyme
didn’t present at normal condition and produced only at the time of need. The stimulation of
COX-2 enzymes is dependent upon cytokines.

Difference in Usefulness:
COX-1 enzymes are protective in nature and therefore are useful for the body. So there is no
need to inhibit them but COX-2 enzymes play an important role in inflammation and pyrexia. So
it is desirous to inhibit COX-2 enzymes.

Difference in Inhibition:
There are different types of drugs that are used to inhibit COX-2 enzyme including Celecoxib.
Non-steroidal anti-inflammatory drugs inhibit both COX-1 and COX-2 enzymes.

Note:
According to some studies COX-2 enzyme has also role in angiogenesis.

Acetaminophen belongs to a class of drugs called analgesics (pain relievers) and antipyretics
(fever reducers). The exact mechanism of action of acetaminophen is not known. It may reduce
the production of prostaglandins in the brain. Prostaglandins are chemicals that cause
inflammation and swelling. Acetaminophen relieves pain by elevating the pain threshold, that is,
by requiring a greater amount of pain to develop before a person feels it. It
reduces fever through its action on the heat-regulating center of the brain. Specifically, it tells
the center to lower the body's temperature when the temperature is elevated. The FDA
approved acetaminophen in 1951. Acetaminophen can cause liver failure. It is found in many
OTC products, teaching patient to avoid toxic doses of acetaminophen would help.
 Action/indications

 Acts directly on the thermoregulatory cells of the hypothalamus

 Mechanism of action related to analgesic effects is not certain
 Used to treat pain and fever
 Treatment of pain and fever associated with a variety of conditions, including influenza
 Prophylaxis of children receiving diphtheria–pertussis–tetanus (DPT) immunizations
 Relief of musculoskeletal pain associated with arthritis

Pharmacokinetics

 Absorbed from the GI tract

 Peaks in ½ to 2 hours
 Metabolized in the liver
 Excreted in the urine
 T½ is about 2 hours

Contraindications

 Known allergy
 Use with caution in pregnancy and lactation

Adverse reactions

 Headache, hemolytic anemia, renal dysfunction, skin rash, fever, and hepatotoxicity
 Drug-to-drug interactions
 Oral anticoagulants increase bleeding

Rheumatoid arthritis (RA) happens when your body's defenses – your immune system – targets your
joint linings. RA affects joints on both sides of the body, such as both hands, both wrists, or both
knees. This symmetry helps to set it apart from other types of arthritis. It can also affect the skin, eyes,
lungs, heart, blood, or nerves.

Anti-arthritis Drugs

o Etanercept (Enbrel)
o Leflunomide (Arava)
o Penicillamine (Depen)
o Hyaluronidase derivative (Synvisc)
o Sodium hyaluronate (Hyalgan)
o Anakinra (Kineret)

Gold Compounds

Gold salts prevent macrophage phagocytosis, lysosomal release, and tissue damage because
the gold salts are taken up by phagocytes, which then are not able to function in a normal way.
Gold salts are deposited in the tissue and cause an assortment of inflammatory reactions,
including stomatitis, glossitis, gingivitis, pharyngitis, laryngitis, colitis, diarrhea, and other
gastrointestinal inflammation; gold bronchitis and interstitial pneumonitis; bone marrow
 depression; vaginitis and nephritic syndrome; dermatitis, pruritus, and exfoliative dermatitis; and
allergic reactions ranging from flushing, fainting, and dizziness to anaphylactic shock. The gold
salts cause many systematic inflammatory reactions. Other anti-arthritis drugs are associated
with local injection site irritation and increased susceptibility to infection, leflunomide is
associated with severe hepatic toxicity.

Action
Absorbed by macrophages, which results in inhibition of phagocytosis

Indication
Tissue destruction is decreased

Pharmacokinetics
 Absorption varies based on the site of administration
 Widely distributed throughout the body

Contraindications
 Known allergy
 Diabetes, CHF, and renal or hepatic impairment

Adverse reactions
Stomatitis, glossitis, gingivitis, bone marrow depression, and dermatitis

Drug-to-drug interactions
Penicillamine, antimalarials, cytotoxic drugs, and immunosuppressive agents

Drugs used to alter the inflammatory process involved in arthritis are called disease modifying
anti-rheumatic drugs (DMARDs) and can also be associated with serious to potential fatal
infections. If used early in the disease, they can prevent or slow down the damage caused to
the joints. The DMARDs can cause local irritation at the injection site to liver impairment and a
variety of CNS problems, including demyelinating disorders. DMARDs alter the course of the
inflammatory process and treats arthritis by aggressively affecting the process of inflammation.

Conventional DMARDs

This group of drugs is slow-acting and can take several weeks to work, so it's important to keep
taking them even if they don't seem to have any effect at first.

Methotrexate — Methotrexate was originally used as a chemotherapy treatment for cancer.

When used in much lower doses for rheumatoid arthritis and other rheumatic diseases,
methotrexate works to reduce inflammation and to decrease joint damage. It is usually taken
once per week as a pill, liquid, or injection. Methotrexate may be combined with other DMARDs
or with a biologic agent if methotrexate alone does not adequately control a patient's disease.
(See 'Biologic agents' below.)

Common side effects include upset stomach and a sore mouth. Methotrexate can interfere with
the bone marrow's production of blood cells. Low blood cell counts can cause fever, infections,
swollen lymph nodes, and easy bruisability and bleeding. Liver or lung damage can occur, even
with low doses, and therefore requires monitoring. People using methotrexate are strongly
discouraged from drinking alcoholic beverages because of the increased risk of liver damage
with this combination. Patients should not become pregnant while taking methotrexate.

Monitoring reduces the risk of long-term damage from methotrexate. Testing is performed prior
to starting treatment to determine if there has been exposure to certain infections. A chest x-ray
is also recommended before beginning treatment, and regular blood testing is recommended.
While taking methotrexate, all patients should take folic acid 1 mg daily or folinic acid 5 mg
weekly to reduce the risk of certain side effects, such as upset stomach, sore mouth, low blood
cell counts, and abnormal liver function.

Sulfasalazine — Sulfasalazine is used in the treatment of rheumatoid arthritis and of arthritis

associated with ankylosing spondylitis and inflammatory bowel disease (ulcerative colitis and
Crohn disease). It is not clear how sulfasalazine works. It may be combined with other DMARDs if
a person does not respond adequately to one medication. It is taken as a pill two to four times
per day, and it is usually started at a low dose and is increased slowly to minimize side effects.

Side effects of sulfasalazine include changes in blood counts, nausea or vomiting, sensitivity to
sunlight, skin rash, and headaches. People who are allergic to sulfonamide medications, such as
sulfamethoxazole-trimethoprim (sample brand names: Bactrim, Septra), may have a cross-
reaction to sulfasalazine and should therefore not take it. Periodic blood tests are
recommended to monitor the blood count on a regular basis.

Sulfasalazine is a yellow-orange color; patients who take it may notice that their urine, tears, and
sweat develop an orange tinge, which can stain clothing and contact lenses. Patients should
drink plenty of fluids while taking sulfasalazine and should avoid taking it on an empty stomach
or with antacids.

Hydroxychloroquine — Hydroxychloroquine, originally developed as a treatment for malaria,

was later found to improve symptoms of arthritis. It can be used early in the course of
rheumatoid arthritis and is often used in combination with other DMARDs. It is also very frequently
used for treatment of systemic lupus erythematosus. It can be combined with steroid
medications to reduce the amount of steroid needed. It is usually taken in pill form once or twice
per day.

Taking a high dose of hydroxychloroquine for prolonged periods of time may increase the risk of
damage to the retina of the eye, although high doses are not usually required for treatment of
rheumatoid conditions or lupus. An eye examination by an ophthalmologist is recommended
before starting treatment and periodically thereafter. It is common to have an eye check-up
done once each year.

Leflunomide — Leflunomide inhibits production of inflammatory cells to reduce inflammation. It is

often used alone but may be used in combination with methotrexate for people who have not
responded adequately to methotrexate alone or together with a biologic agent. It is taken by
mouth once daily.

Side effects include rash, temporary hair loss, liver damage, nausea, diarrhea, weight loss, and
abdominal pain. Testing for prior exposure to hepatitis and regular blood testing while on
therapy are needed to monitor for liver damage and other toxicities. Patients should not
become pregnant while taking leflunomide or while it is still detectable in the body.

Azathioprine — Azathioprine has been used in the treatment of cancer, rheumatoid arthritis,
lupus, and a variety of other inflammatory illnesses since the 1950s. It has also been used in organ
transplantation to prevent rejection of the transplanted organ. Azathioprine is generally reserved
for patients who have not responded to other treatments.

The most common side effects of azathioprine include nausea, vomiting, decreased appetite,
liver function abnormalities, low white blood cell counts, and infection. It is usually taken by
mouth once to four times daily. Blood testing is recommended during treatment with
azathioprine.

Cyclosporine — Cyclosporine was originally developed to prevent rejection after organ

transplantation. It works in patients with rheumatoid arthritis to inhibit T lymphocytes, a cell that
contributes to the inflammation associated with rheumatoid arthritis. There is concern about the
long-term safety of cyclosporine and its association with kidney disease and high blood pressure,
so it is generally reserved for patients who have not responded to other treatments. It is usually
taken by mouth in pill or liquid form twice per day; an injectable form is also available. It is
occasionally used to treat kidney disease due to lupus.
Side effects include high blood pressure, swelling, kidney damage, increased hair growth,
nausea, diarrhea, and heartburn. Patients should have blood pressure and kidney function
monitoring on a regular basis.

BIOLOGIC AGENTS

Another class of medications used in persons with rheumatoid arthritis and related inflammatory
rheumatic conditions is biologic agents, sometimes called biologic DMARDs (in contrast to the
conventional or traditional nonbiologic DMARDs discussed in this topic review), including
etanercept, adalimumab, infliximab, certolizumab pegol, and golimumab, which are all part of
a class of drugs called tumor necrosis factor (TNF) inhibitors, and a variety of other agents with
different targets, including anakinra, abatacept, rituximab, and tocilizumab. Another group of
DMARDs, called kinase inhibitors, includes tofacitinib. A biologic DMARD or a kinase inhibitor is
often combined with methotrexate or other DMARDs to improve efficacy.

Contraindications
The choice of first agent or combination of agents should be based on a risk/benefit analysis for
individual patients. In general these medicines should not be prescribed during pregnancy or
breast-feeding unless advised by a specialist.

Drug Contraindications
Severe liver disease, severe kidney disease
Bone marrow aplasia, history of blood
disorders
Exfoliative dermatitis
Gold - sodium aurothiomalate
Necrotising enterocolitis
Porphyria
SLE
Pulmonary fibrosis

Moderate-to-severe kidney disease

Penicillamine
SLE

Sulfasalazine Salicylate hypersensitivity

Chloroquine and
Pre-existing retinopathy
hydroxychloroquine

Hepatic impairment
Methotrexate Active infection
Immunodeficiency syndromes

Azathioprine Hypersensitivity to azathioprine

 Renal impairment
Uncontrolled hypertension
Ciclosporin
Uncontrolled infections
Malignancy

Severe immunodeficiency
Serious infection
Leflunomide
Liver dysfunction
Severe hypoproteinaemia

Infliximab Severe infections

Etanercept Active infection

Complications and reasons to discontinue drugs

Although some have greater tendency than others, all DMARDs have a potential to cause
myelosuppression. Many also cause renal or liver toxicity, skin rash, or gastrointestinal
disturbance.[6]

Patients should be warned to report any warning symptoms or signs as detailed below:

Symptoms of myelosuppression

 Sore throat
 Fever and other signs of infection
 Unexpected bleeding or bruising
 Purpura and rashes
 Mouth ulcers
 Cough or breathlessness

Many anti-inflammatory drugs are available OTC, and care must be taken to prevent abuse or
overuse of these drugs.

REFERENCES:

https://nurseslabs.com/salicylates/

http://intranet.tdmu.edu.ua/data/kafedra/internal/magistr/classes_stud/English/First%20year/Clinical
%20Pharmacology/02_Clin_Pharm_drugs%20_%20CNS.htm

http://www.nursingbuddy.com/2011/03/10/anti-inflammatory-agents/

https://nurseslabs.com/nonsteroidal-anti-inflammatory-drugs-nsaids-related-agents/
http://medimoon.com/2013/05/difference-between-cox1-and-cox2/

https://www.medicinenet.com/acetaminophen/article.htm#what_are_the_side_effects_of_acetaminop
hen

https://www.webmd.com/rheumatoid-arthritis/rheumatoid-arthritis-medications#1

https://www.uptodate.com/contents/disease-modifying-antirheumatic-drugs-dmards-beyond-the-
basics

https://www.arthritisresearchuk.org/arthritis-information/drugs/dmards.aspx

https://patient.info/doctor/disease-modifying-antirheumatic-drugs-dmards-pro#nav-4

Karch, A. (Focus on Nursing Pharmacology) 6th ed.