Problem 1/2/3 Methotrexate, Ibuprofen and MTX combo, Monotherapy DMARD Treatment Flashcards
How would you define Rheumatoid Arthritis?
Autoimmune disease that affects bilateral joints (any joint can be affected). Better with activity and worse with rest, joint stiffness in the morning, inflammation of systemic organs may occur, less prevalent that osteoarthritis.
Swollen, inflamed synovial membrane, cartilage wears away and reduced joint space.
Explain the pathophysiology of RA and possible risk factors?
Chronic, inflammatory, autoimmune disorder. The synovial membranes that line the synovial joint become inflamed and there is no other underlying cause (e.g. viral arthritis, polyarticular gout and thyroid disease).
CD4 T and B cells are involved in RA pathophysiology. The B cells produce rheumatoid factor (RF). RF is an autoantibody to IgG that triggers autoimmune reactions. Many other cell types and cytokines are also involved in mediating a series of autoimmune events.
Risk factors: genes
Researchers have shown that people with a specific genetic marker called the HLA shared epitope have a fivefold greater chance of developing rheumatoid arthritis than do people without the marker.
hormones, environmental factors, bacteria and viruses, smoking and air pollution
Explore the common signs and symptoms of RA and how it is diagnosed?
Signs of RA: Rheumatoid factor present in the blood, positive test result in the metacarpophalangeal (MCP) squeeze test
Pericarditis and lungs affected
Symptoms: Pain, heat and redness in affected joints
Stiffness in the morning and after inactivity of more than 30 minutes
Fever and sweating, poor appetite, weight loss and fatigue
Both: cannot make a fist or flex fingers, redness and swelling around the joints, joint deformity.
Why is methotrexate prescribed for Mrs Li
NICE guidelines; initiating treatment, first line is a DMARD including MTX:
In people with newly diagnosed active RA, offer a combination of DMARDs (including methotrexate and at least one other DMARD, plus short-term glucocorticoids) as first-line treatment as soon as possible, ideally within 3 months of the onset of persistent symptoms. [2009]
Consider offering short-term treatment with glucocorticoids (oral, intramuscular or intra-articular) to rapidly improve symptoms in people with newly diagnosed RA if they are not already receiving glucocorticoids as part of DMARD combination therapy. [2009]
Discuss the appropriateness of the methotrexate dosage regimen?
Moderate to severe RA: 7.5mg ONCE weekly is a normal starting dose (can be adjusted accordingly to response, maximum 20mg per week).
However, according to NICE guidelines a second DMARD should be added to control symptoms as soon as possible. Glucocorticoids also used for short-term therapy to bring autoimmune reactions under control.
Explain why Mrs Li has been prescribed folic acid?
It is generally agreed that folic acid supplementation reduces the toxicity of methotrexate without significantly affecting efficacy; although there seems to be a consensus of opinion that folic acid supplementation should be avoided on the day of methotrexate in case it adversely affects absorption. Folic acid supplementation should be continued for the duration of methotrexate therapy because adverse effects can occur at any time.
MOA: inhibition of folic acid reductase, leading to inhibition of DNA synthesis and inhibition of cellular replication. The mechanism involved in its activity against rheumatoid arthritis is not known.
Describe how you would counsel Mrs Li on her new medication, reason for being given treatment booklet and for regular monitoring? Give consideration to potential barriers in patient understanding and how this might be resolved
Key counselling points: Methotrexate (what it is and what its for) Dose Time to work (3 months) Monitoring Treatment booklet Side effects OTC NSAIDs Multivitamins containing folic acid levels Signposting
Explain the safety measures in place that would prevent once daily dosing of methotrexate
Patient safety alert: safe prescribing checklist, (outlines the risk and benefits), avoiding the use of “as directed” on prescriptions. Repeat prescriptions are kept separate for prescriber review, awareness of side effects.
Dosage record booklet, counselling from doctor, pharmacist and at clinic. Supply kept to a minimum.
The patient is carefully advised of the dose and frequency. Only one strength of 2.5mg is prescribed and dispensed. The presricption and dispensing label much should dose and frequency clearly. Patient warned immediately to report onset of any feature of blood disorders, sore throat, bruising, mouth ulcers, liver toxicity, nausea vomiting abdo discomfort, dark urine or any respiratory effects such as sob.
Explain your understanding of a “never event”
Outlined to CCGs, Care and Foundation Trusts, Medical Directors.
Events or experiences that are used to Implement policy within organisations providing NHS funded care to make sure it is never repeated
Mis-selection of a potassium solution that is the incorrect concentration / infusion bag for the patient is an example of a never event.
Overdose of methotrexate for a non-cancer patient is also a never event; “When a patient receives methotrexate ,via any route, for non-cancer treatment which
results in more than the intended weekly dose being taken, despite the care setting
having an electronic prescribing and administration system , or in primary care an
electronic prescribing and dispensing system, in place”
Comment on whether it is appropriate for the GP to initiate this prescription?
Patient should be referred to a specialist for the prescription of methotrexate for RA - needs diagnosing
Mrs Li’s drug history consisted of taking regular ibuprofen for her pain. Discuss the potential problems with using NSAIDs in patients on methotrexate?
Increased methotrexate toxicity, sometimes life-threatening, has been seen in a few patients also taking NSAIDs, whereas other patients have taken an NSAID and methotrexate uneventfully. The pharmacokinetics of methotrexate can also be changed by some NSAIDs, aspirin or other salicylates. The development of toxicity may be dose related: the risk appears to be lowest in those taking low-dose methotrexate for psoriasis or rheumatoid arthritis who have normal renal function.
Clearance of methotrexate reduced by ibuprofen (compared in studies with paracetamol). A patient given ibuprofen and methotrexate would need prolonged folinic acid rescue dose due to clearance of methotrexate being reduced by two-thirds.
Increased the risk of patients experiencing induced methotrexate nephrotoxicity.
There are several indications where abrupt stopping of DMARDs is necessary. Considering MOA, explore the rationale for with-holding methotrexate during acute infection
Be aware that major toxicity with DMARDs can occur during intercurrent illness, particularly if there is impairment of renal function or sepsis.
Contraindicated in severe chronic or actue infections
This is due to its immunosuppressive activity; The immunosuppressive effect of methotrexate should be taken into account when immune responses of patients are important or essential. Special attention should be paid in cases of inactive chronic infections (e.g. herpes zoster, tuberculosis, hepatitis B or C) because of their potential activation.
• Extreme caution is required in the presence of acute infection. If infection occurs or becomes a threat during methotrexate use, it should be stopped.
What are the options available for control of disease?
DMARDs, glucocorticoids, biological DMARDs
Pain should be managed using paracetamol or codeine. Oral NSAIDs should not be used but may be prescribed with a PPI (or topical NSAIDs).
