Chapter 25 Drugs Treating Rheumatoid ​Arthritis and Gout

Gout

A disease of altered purine metabolism resulting in hyper uremia. However, hyperuricemia alone does not always result in gout

Maximizing Therapeutic Effects of Allopurinol

-Administer allopurinol in conjunction with colchicine. ​ -Assist the patient to develop meal plans that limit uric acid production.​

Maximizing Therapeutic Effects of Methotrexate

-Administer medication as ordered.​ -Drink plenty of water to prevent nephrotoxicity.​

Maximizing Therapeutic Effects of Colchicine

-Administer with a full glass of water at evenly spaced intervals throughout the day.​ -Adherence to diet and alcohol restrictions decreases hyperuricemia.​

Patient and Family Education of Colchicine

-Discuss importance of dietary restrictions.​ -Discuss side effects of therapy.​

Tumor Necrosis Factor Inhibitors

-Enbrel was produced by recombinant DNA technology. ​ -In the past, TNF inhibitors were used in patients who did not respond to MTX. ​ -Combination therapy with TNF inhibitors and MTX has exceptional results and is now considered the "gold standard" of RA treatment.​ Prototype drug: etanercept (Enbrel) ​

Pharamacodynamics of Methotrexate

-Exerts immunosuppressive effects by inhibiting the replication and function of T lymphocytes that stimulate the production of cytokines​ -Influence Folate depletion which leads to inhibition of purine synthesis and results in the arrest of DNA, RNA, and protein synthesis ​

Minimizing Adverse Effects of Allopurinol

-Fluid intake should range between 2.5 and 3 L/day​ -Titrate drug based on uric acid levels.​

Minimizing Adverse Effects of Methotrexate

-Folic acid may decrease the potential for adverse effects ​ -Can cause photosensitivity​

Patient and Family Education of Methotrexate

-Instruct patient how to administer medication properly.​ -Teach adverse effects to report to the physician.​

Ongoing Assessment and Evaluation of Colchicine

-Monitor for hematopoietic and renal toxicity, joint involvement, deformity, and range of motion.​ -Therapy is considered effective if the patient reports decreased frequency of acute gout attacks and remains free of adverse effects.​

Ongoing Assessment and Evaluation of Methotrexate

-Monitor patients for signs of blood dyscrasias, suppressed bone marrow function, pulmonary changes, and hepatic or renal dysfunction.​ -Effective treatment should show improved symptoms.​

Minimizing Adverse Effects of Colchicine

-Monitor pre-existing medical conditions.​ -Start medications at the first sign of an attack.​

Patient and Family Eucation for Allopurinol

-Take medication as prescribed.​ -Teach adverse effects and when to notify provider.​ -Teach importance of fluid intake.​

Monoclonal Antibody

A cell that is produced with the ability to recognize and bind to a specific antigen

Pannus

A destructive granular tissue that extends into synovial space damaging the articular cartilage

Pharmacodynamics of Allopurinol

Decreases the production of uric acid by inhibiting the action of xanthine oxidase​

Disease-Modifying Antirheumatic Drugs (DMARDs)

Delay joint destruction and should be initiated within 3 months of diagnosis of rheumatoid arthritis

Disease-Modifying Antirheumatic Drugs

Disease-modifying antirheumatic drugs (DMARDs) are used in conjunction with salicylates and NSAIDs, or as monotherapy​ They are so named because they are capable of arresting the progression of RA and can Induce remission in some patients. ​ The therapeutic class of DMARDs is a combination of several different pharmacologic classes of drugs. ​ Prototype drug: methotrexate (Rheumatrex)

Tumor Necrosis Factor Inhibitors

Etanercept adalimumab infliximab anakinra rituximab

Ankylosis

Extreme stiffness or joint fusion

Colchicine is considered first-line drug therapy for acute gout

False

Pharmacotherapeutics of Methotrexate

Folate antimetabolite used in treating various malignancies and rheumatoid arthritis

What is the advantage of using DMARDs within 3 months of diagnosis of RA

Joint destruction begins in the early stages of the disease, even before some patients have physical symptoms. Using DMARDs within 3 months of diagnosis halts the progression of the damage and ultimately can decrease the extent of damage

Adverse Effects of Methotrexate

Rash, headache, nausea and vomiting, diarrhea, stomatitis, alopecia, suppression of bone marrow

Antigout Drugs

Resolve symptoms in two different ways: Colchicine opposes leukocyte phagocytosis, which inhibits further urate deposits, whereas uricosuric agents reduce hyperuricemia

Uricosuric Drugs

balance urate concentration. Because they have no anti-inflammatory or analgesic activity, they are not useful in treating acute gout attacks.

Antigout Drugs (Chronic)

Allopurinol probenecid sulfinpyrazone

A contraindication for taking allopurinol is​

Hypersensitivity

Diagnosis and Outcomes of Colchicine

***Acute Pain related to drug-induced abdominal cramps or paralytic ileus ​ Desired outcome: The patient will contact the prescriber if abdominal pain occurs. ​ Risk for Injury related to drug-induced renal toxicity or possible extravasation of IV colchicine ​ Desired outcome: The patient administering colchicine at home will contact the prescriber if urinary changes occur. The hospitalized patient will remain free of extravasation of IV Colchicine Risk for Deficient Fluid Volume related to drug-induced nausea, vomiting, and diarrhea​ Desired outcome: The patient will contact the prescriber if GI symptoms occur.​ Ineffective Protection related to possible blood dyscrasias​ Desired outcome: The patient will contact the prescriber if sore throat, easy bruising, or lethargy occurs.​

Antigout Drugs

Antigout drugs are used to treat acute cases of gout and to prevent gout. ​ Antigout drug therapy focuses on either decreasing the inflammatory response caused by hyperuricemia or reducing hyperuricemia itself. ​ First-line drugs for acute gout are NSAIDS​ Second-line drugs are colchicine and glucocorticosteroids. ​ Prototype drug: colchicine​

Which of the following is the underlying cause of rheumatoid arthritis

Autoimmune

Pharmacokinetics of Colchicine

Administered: Oral or IV. Metabolism: liver. Excreted: feces​

Pharmacokinetics of Allopurinol

Administered: oral or IV. Metabolism: liver​

Pharmacokinetics of Methotrexate

Administered: orally or parenterally. Metabolized in the liver, excreted in the kidneys​

Pharmacological Classes of DMARDs

Alkylating agents, tumor necrosis factor (TNF) inhibitors, monoclonal antibodies, Interleukin antagonist, and immune response modifiers

Prototype Drug for Treating Chronic Gout

Allopurinol (Zyloprim, Lopurin)

Contraindications and Precautions of Colchicine

Cardiac disease, hepatic disease, and renal disease

Prototype Drug for Antigout

Colchicine

Compare colchicine and allopurinol

Colchicine decreases the inflammatory process induced by gout, therefore, it is used in acute gout. Allopurinol increases the excretion of uric acid. It is used as a prophylactic medication

Diagnosis and Outcomes of Methotrexate

Comfort Impaired: Nausea related to drug therapy​ Desired outcome: The patient will eat small, frequent meals when nauseated to maintain nutritional balance.​ Risk for Infection related to potential depression of bone marrow function and blood dyscrasias​ Desired outcome: The patient will recognize signs of depressed bone marrow function and blood dyscrasias and contact the health care provider immediately for intervention if any appear.​ ​Imbalanced nutrition: Less than body requirements related to potential nausea, stomatitis, and gingivitis​ Desired outcome: The patient will maintain nutritional balance throughout therapy.​ Risk for Injury related to drug accumulation caused by hepatic or renal dysfunction​ Desired outcome: The patient will remain injury free throughout therapy.​

Gout

Gout is a disease of purine metabolism. ​ Gout occurs when the hyperuricemia forms monosodium urate crystals, which precipitate into the synovial fluid and initiate an inflammatory response.​ Hyperuricemia is clearly a risk factor for the development of gout.​ The onset of an acute gout attack is rapid ​ The diagnosis of gout is made by analysis of synovial fluids.​

Core Patient Variables of Methotrexate

Health status​ Assess for comorbid conditions.​ Routine monitoring CBC, liver profile, serum albumin, serum creatinine every 4-8 weeks ​ Life span and gender​ Give with caution to the young and elderly.​ Pregnancy Category X ​ Lifestyle, diet, and habits​ Evaluate for alcohol or elicit drug use.​ Malnourished may be more immunosuppressed​ Caffeine decreases effectiveness ​ Environment​ Routinely given at home​

Core Patient Variables of Colchicine

Health status​ Assess for conditions that are contraindicated in therapy.​ Life span and gender​ Pregnancy category C​ Alcohol can cause an overproduction and underexcertion of uric acid ​ Lifestyle, diet, and habits​ Evaluate patient's diet.​ Environment​ Usually self-administered at home​ 3-4 times daily ​

Core Patient Variables of Allopurinol

Health status​ Assess medical history.​ Life span and gender​ Pregnancy category C​ Lifestyle, diet, and habits​ Administer after meals.

Contraindications and Precautions of Allopurinol

Hypersensitivity​

Contraindications and Precautions of Methotrexate

Immunosuppression, blood dyscrasia, pregnancy, and lactation​

Diagnosis and Outcomes of Allopurinol

Increased Risk for Injury related to allopurinol-induced renal toxicity​ Desired outcome: The patient will contact the prescriber if any urinary changes occur.​ Deficient Fluid Volume related to nausea and vomiting​ Desired outcome: The patient will contact the prescriber if nausea and vomiting persist.​ Ineffective Protection related to drug-induced blood dyscrasias​ Desired outcome: The patient will contact the prescriber if sore throat, easy bruising, or lethargy occurs.​

Pharmacodynamics of Colchicine

Inhibits the activity of leukocytes by decreasing their migration into the affected area​

Arthritic Inflammatory Diseases

Initially treated with salicylates and NSAIDS

Drug Interactions of Allopurinol

Interacts with many drugs

Pharmacotherapeutics of Allopurinol

Management of chronic gout, recurrent calcium renal stones, and hyperuricemia​

Drug Interactions of Methotrexate

Many drug interactions

Prototype Antirheumatic Drugs

Methotrexate (Rheumatrex)

Adverse Effects of Colchicine

Nausea, vomiting, diarrhea, abdominal pain, and paralytic ileus (up to 80%)​

Nitritoid Crisis

Potential reaction pf aurothioglucose with symptoms such as flushing, feeling of warmth, light headedness, and hypotension

Adverse Effects of Allopurinol

Pruritus, maculopapular rash, nausea and vomiting, elevated LFTs, and acute gout symptoms​

Rheumatoid Arthritis​

RA is a systemic Inflammatory disease. ​ The effects are not limited to joint destruction.​ RA affects all age groups.​ RA is thought to be an autoimmune.​ The primary characteristic of RA is symmetric polyarticular inflammation. RA can cause inflammation of glands, the linings of the heart, the lungs, and the vascular system. ​ The clinical course of RA is highly variable ​ RA has a substantial effect on quality of life because of the associated pain, fatigue, and depression, and the increased risk of heart disease. ​ ​

Drug Interactions of Colchicine

Radiation therapy, drugs that depress bone marrow function and cyanocobalamin​ Interacts with cyanocobalamin (vit b 12) ​ Cyclosporine, erythromycin, and NSAIDS

What contraindication and potential adverse effect is common to all TNF inhibitors

TNF inhibitors should not be given to any patient with an active infection, and they should be given very cautiously to an immunocompromised patient.The potential adverse effect common to all these drugs is an increased risk of serious infections. These drugs alter the immune and inflammatory responses. Thus, the patient may acquire a life threatening infection

Methotrexate

The DMARD of choice for most rheumatologist. Its efficacy is enhanced when given in combination with TNF inhibitors

Why are so many different classes of medications under the umbrella term DMARD

The autoimmune and inflammatory processes of the body have many substances that continue the cycle. Multiple classes of drugs may be used because they have different mechanisms of action that can affect the immune response, the inflammatory response, or both responses at different sites of the cycle or affect different substances within the cycle

Why are biologic drugs such as etanercept, abatacept, and anakinra not given as combination therapy

The biologic drugs have been the same type of serious adverse effects. Severe infection and malignancy. When given concurrently they do not increase the efficacy of treatment but substantial increase the risk for serious adverse effects

What is the major disadvantage of using DMARDs

The frequency of potentially serious adverse effects, such as depressed bone marrow function, hepatotoxicity, and renal toxicity. Another disadvantage is that most of the common DMARDs have a long period before results of the therapy can be noticed by the patient

Chrysotherapy

The use of gold salts to treat early active cases of both adult and juvenile types of RA that have not responded to salicylates and NSAIDS

Ongoing Assessment and Evaluation for Allopurinol

Therapy is considered effective when the patient reports reduced pain and inflammation and remains free of adverse effects.​

What advantage do DMARDs have over salicylates, NSAIDS, and acetaminophen

These drugs control only symptoms of the disease but DMARDs have an advantage of actually halting the progression of inflammatory diseases and the potential damage they may cause

Pharmacotherapeutics of Colchicine

Treating acute gout and as presurgical prophylaxis to prevent gout

What is TNF

Tumor Necrosis Factor is a cytokine produced by macrophages and activated T cells, which play a roll in RA by mediating cytokines that cause inflammation and joint destruction

Drugs for Treating Chronic Gout

Uricosuric drugs balance urate concentration. ​ Because they have no anti-inflammatory or analgesic activity, they are not useful in treating acute gout attacks. ​ In fact, when first initiated, they can exacerbate an acute attack of gout. ​ Prototype drug: allopurinol (Zyloprim, Lopurin)

Disease-Modifying Antihemumatic Drug (DMARD)

Used in conjunction with salicylates and NSAIDS, or as monotherapy when salicylates and NSAIDS are ineffective or not tolerated. They are known to stop regression and inhibit remission of RA

Antigout Drugs

Used to treat acute cases of gout and to prevent gout

Methotrexate is a pregnancy category ____ drug

X

Antigout Drugs (Acute)

colchicine glucocorticoid steriods

DMARDs

have a common goal of reducing the progression of rheumatoid arthritis but have different mechanisms of action to achieve that goal

TNF Inhibitors and other biological DMARDs

may induce serious infections or malignancies

Disease Modifying Antirheumatic Drugs (DMARDs)

methotrexate cyclophosphamide cyclosporine gold salts -auranofin -aurothioglucose -gold sodium thiomalate glucocorticoid steroids hydroxychloroquine leflunomide D-penicillamine sulfacalazine