Corticosteroids are mostly glucocorticoids used as anti-inflammatory drugs. They are cortisol analogs.
In severe progressive RA prednisone can give some benefits. Because of the seriousness of side effects corticosteroids are considered to be the drugs of last choices.
They are used in,
1.Acute flare-ups of the disease
2.As adjuncts with other slow-acting drugs
3.In elderly patients as alternatives for more toxic second-line drugs
4.In patients who cannot tolerate or who are allergic to NSAIDs.
5.In patients with a systemic attack of RA.
Administration and Dosage
Oral prednisone is 5 to 10mg may be enough to some patients
Because of the serious adverse effects dosage should be limited to possible low with care.
If pain is localized to one or few inflamed joints an intraarticular injection may be beneficial.
Side Effects
1. Immunosuppression leads to delay in wound healing
2.G.I.Bleeding
3.Myopathy
4.Cataracts
5.Hyperglycemia
6.Hypertension
7.Osteoporosis
Topical Treatments
Topical treatments are safer but less systemic. They are counter irritants and rubefacients.
Capsaicin which is a pungent hot ingredient of pepper can be used as a rubefacient to relieve RA.
Capsaicin is blocking the substance-P which transmits the pain impulses from the periphery to the brain through sensory nerves.
Capsaicin can be applied three or four times a day to get good relief.
It is available in the market by the brand Zostrix
Counter Irritants
1.Allyl isothiocyanate
2.Methylsalicylate
3.Menthol
All the above drugs produce mild counter inflammations and thereby relieve the RA pain.
They should be applied to the skin followed by gentle massages.
The mechanism of its anti-rheumatic action is due to its ability to alter the immune response of the body. Penicillamine used to treat refractory rheumatoid arthritis. Its use is now very limited with more modern medication with fewer side effects.
Chemically penicillamine is a breakdown product of penicillin.
It delays the onset of joint erosions in RA.
Absorption
Penicillamine should be given in an empty stomach as food may interfere with its potency and block its absorption. As penicillamine is a chelating agent it may chelate all polyvalent ions present in the food such as calcium, magnesium, copper, iron, and zinc. These chelates are not absorbed by the intestine.
Dosage
The initial dosage is 125 - 250 mg once daily. Then the dosage is doubled after 3 months. After the next 3 months again the dose is doubled to a maximum of 750 mg daily until to get a required therapeutic effect. Very rarely the daily dosage can be maximized to 1000 to 1500mg under strict supervision. The basic dosing moto for this drug is to go low-go slow.
Side Effects
1.Reversible side effects such as rash, fever, blood urine, proteinuria, dysgeusia(distortion of the taste sense) and aphthous ulcers(mouth ulcers)
2.Vascular complications like leukopenia, thrombocytopenia and aplastic anemia
3. Systemic Lupus Erythematosus, Good Pasteur's Syndrome, and pemphigus have occurred. All these are autoimmune diseases in which the body's own immune system wrongly attacks its own skin, kidneys, and lungs.
6.Azathioprine
It is an autoimmune suppressor. It is a purine analog. It is used as a last attempt if other agents are not responded (refractory RA)
The dosage is 50 to 100 mg twice daily (1mg/kg). After 6 to 8 weeks the dose can be increased by ever 4 weeks by 0.5mg/kg.to a maximum of 2.5mg/kg.daily.
The dosage should be reduced in patients with renal dysfunctions.
Side Effects
1.Gastrointestinal effects such as nausea, vomiting, stomach pain,
2.Liver damage
3.Bone marrow suppression
4.Lymphoma
7.Cyclophosphamide
Similar to other immunosuppressive agents this antineoplastic agent can also be used in the treatment of refractory RA. But the use is limited because of its severe toxicity when compared with other immunosuppressive agents.
The initial dose is 1.5 to 3 mg/kg of the body weight.
Side Effects
1.Bone marrow depression
2.hemorrhagic cystitis
3.steriliy
4.Alopecia
5.Bladder cancer.
Other similar drugs are chlorambucil, cyclosporine. These are also immunosuppressive agents used in neoplastic treatments with a high toxic profile. Used to treat refractory RA.
Minocycline an antibiotic that can affect the Mycoplasma organism, the organism which causes RA.
Unlike drugs like aspirin and NSAIDs which are considered as fast-acting and first-line drugs these drugs are said to be slow-acting anti-rheumatic drugs(SAARD) or disease-modifying anti-rheumatic drugs (DMARDs).
When a patient suffers from sustained disabilities with RA only an anti-inflammatory course is not sufficient. The course of the disease should be modified to ease the disability. This is possible with second-line drugs like hydroxychloroquine, methotrexate, gold compounds, penicillamine, and sulfasalazine. These drugs are used as an adjuvant along with the anti-inflammatory treatments.
These drugs are acting by delaying or modifying the development of the disease. Therapeutic effects may take several months. Careful monitoring of the patients must be necessary because of the serious side effects.
In general these drugs are used along with anti-inflammatory drugs. But some doctors may initiate with these drugs alone and interchange them if they found one drug is ineffective. The ineffective drug should be discontinued before changing to other drugs.Initiating a second-line drug is possible if the patient is not tolerating anti-inflammatory drugs and their prolonged may result in some possible side effects. Yet these drugs too show potential side effects.
1.Hydroxychloroquine
The dosage is started with 200mg twice daily (400mg/day) or 6.5mg/kg whichever is less. It is possible as per the condition the daily dose can be reduced to 200mg once daily.
The patients should be taking care of the following side effects:-
1. Nausea and epigastric pain is possible but not seriously
2. Rare effects on eyes, skin, CNS, and bonemarrow are possible on the recommended dosage
3. Hydroxychloroquine causes retinal damage and hence visual checkup is recommended every 3 to 6 months by an eye specialist.
It is highly advisable to discontinue the medicine if the first sign of the retinal damage is notified.
4. Corneal damages can be reversible but the retinopathy is irreversible.
2.Methotrexate
As methotrexate acts faster than other second-line drugs some physicians are considering it as a first-line drug yet it is somehow slower than anti-inflammatory drugs.
Methotrexate is a folic acid antagonist and is used in many neoplastic disease treatments.
The initial weekly doses are 5 to 10 mg. This can be divided as twice-daily doses but is not safer and much beneficial.
The dosage can be slowly increased to 15 to 20 mg every 3 to 6 weeks.
Intramuscular dosage also available if the oral route is ineffective or may produce gastric trouble.I.M.dosage is once per month.
The following precautions must be taken:-
Aspirin may increase the toxicity of methotrexate by delaying its excretion. Hence aspirin should not be used with it.
Adverse Effects
1. Gastric effects like nausea, anorexia, stomach cramps, and ulcers)
2.Bone marrow suppressions
3.Liver damage
4. Hypersensitivity reactions lead to pneumonitis
5. Rarely pneumonia and chickenpox may precipitate as the drug is immunosuppressive.
6.Monitor RBC, WBC, and platelet counts.
3.Gold Compounds
Gold compounds are proved as very effective second-line drugs in relieving RA by delay progressions of joint erosions.
a)Gold Sodiumthiomalate i.m.injection
b)Aurothioglucose i.m.injection
A test dose of 10mg is given followed by 25mg of the initial weekly dose for two weeks.
After that the dose can be increased to 50mg per week for 20 weeks can be given.
Once there is an expected effect occur the treatment should be continued with the same 50 mg dosage with 2 weeks intervals followed by every three weeks and then to reach every month for 3 to 6 months.
The treatments should continue as a monthly therapy. Abrupt discontinue of the treatment may result in a relapse of RA which may not respond again to gold therapy.
Side Effects
1.Proteinuria
2.Blood dyscrasias
3.Rashes
4.Leucopenia
5.Thrombocytopenia
6.Aplastic anemia
7.Anaphylaxis
8.Angioneurotic edema
9.Glossitis
10.Interstitial pneumonitis
11. Gold Sodium thiomalate because of its water solubility can produce vasodilation, hypotension, and syncope. These effects do not occur with aurothioglucose which is fat-soluble.
c)Auranofin(Oral)
This drug is orally active, less effective, and less toxic.
The initial dose is 3 mg twice a day or 6 mg once a day for six months.
If no effect the dose can be increased to 3 mg three times daily or 9 mg once daily.
Still there is no effect reached auranofin should be discontinued.
Side Effects
1.Diarrhea, stomach pain usually reversible
2. Rash and stomatitis also reversible
3. Proteinuria also reversible
4.Rarely bone marrow suppression and renal toxicity.
4.Sulphasalazine
Sulphasalazine is a sulphonamide derivative used as an anti-RA drug widely in many countries.
It is a very effective drug
It slows the progression of joint damage
It can be given orally.
The dose is 0.5mg twice daily.
The dose is slowly increased by 0.5mg every week up to 2 to 3 gram /day in divided doses.
The brain is the head of the department our body and is the IT head call center of our body.
Ever functions of our body are at the sole discrete decision of our brain empire.
The Central Nervous System which is branched into numerous networks spread throughout the body. Even the Autonomic Nervous System and the Somatic(skeletal muscle) Nervous System which serves as Peripheral Nervous networks too are in some way connected with the Brain Kingdom.
If the brain dies everything will stop and our eternal life starts.
Generally it is very difficult to diagnose RA at the early stages as it is mostly asymptomatic in the beginning.
RA diagnoses are based on their symptoms and laboratory findings as follows.
Diagnoses
1. Joint symptoms such as swelling, abnormal fluid collections in articular cavities, synovial thickening, and edema with pain on motion, indicates the presence of RA.
2. Subcutaneous nodules mostly occur in the sites exposed to external pressure such as elbow, shoulder, and wrist but also in other organs indicates the presence of RA. These nodules are rubbery, round, and firm masses can be identified with fingers.
3. A deeper diagnosis by X-radiation can indicate the presence of asymptomatic early RA by the presence of mild painless soft tissue swellings.
4. A blood test can show the presence of RA factors, heterogeneous antibodies present in most RA patients.
5.ESR test may be high which indicates the presence of early RA.
6. The presence of normochromic, normocytic anemia may indicate the presence of RA.
Treatments
The treatments involve two methodological approaches such as Mechanical and Pharmacological.
Mechanical Methods
The patient should be trained with proper balanced daily exercises and rests as follows:-
1. In the beginning start with how to keep the joints in rest.
2. Start the exercise by step by step movements of the joints without straining them to strengthen the muscles.
3.when return to sleep train how to keep the joints by aligning them by the use of specially designed lightweight splints.
4. Complete immobilization should be avoided.
5. When the above methods fail a mild surgery to improve the functions and movements of hands and knees are advised.
Pharmacological Methods
Analgesics and anti-inflammatory drugs such as aspirin and NSAIDs are beneficial. Paracetamol has not been used as it is not having any anti-inflammatory effects.
Anti-inflammatory drugs at their therapeutic dosage are riskier and the risk factors override the required therapeutic response.
Aspirin
We have already dealt with this drug in detail in another post (9-12-2015) in the same blog under the heading "Paracetamol, Aspirin and other NSAIDs".Please download it.
A piece of additional information is aspirin is the first-line drug to treat rheumatism. Aspirin is used in higher dosage to treat inflammation and it is more economical. But its risk factor overrides its benefits.
Mechanism
Aspirin is acting similar to other NSAIDs but to a lesser extent it is preventing the synthesis and release of prostaglandin.
Dose
4 to 6 gms daily
For side effects please refer to the post "Paracetamol, Aspirin, and Other NSAIDs" in this blog.
Other NSAIDs:-
They are ibuprofen, naproxen, sulindac, and piroxicam. Please refer to the following table.
Actions are similar to aspirin by inhibiting cyclooxygenase 1 and 2 and thereby inhibiting the synthesis and release of prostaglandin.
NSAIDs have the advantage over aspirin by producing the required effects in a much lower dosage than aspirin but are more expensive.
Special Precautions
1. They should be avoided in asthmatic patients as they can elevate bronchospasm. Aspirin is suitable for them.
2. Unlike aspirin NSAIDs reversibly affect the platelet function, hence safer than aspirin but still should be cautious in using them to those who have gastric bleeding.
Misoprostol is used to treat gastric hemorrhages caused by NSAIDs.(Misoprostol dosage:100 to 200 mcg four times daily along with NSAIDs treatment)
3.NSAIDs decrease the renal blood flow and renal failure may ensue in patients who already suffer from less renal flow due to CHF and Diuretic therapy. Sulindac is safer.
4.Liver failure
5.CNS effects such as drowsiness, dizziness, anxiety, tinnitus, and confusion, that disappear on continuous use. Headache is more common with indomethacin
6.Blood dyscrasias(Rare)
7. Naproxen and ibuprofen are safer than other NSAIDs in producing GI effects
Nabumetone causes lesser gastric irritation
Meclofenamate and Mefenamic acid may cause severe diarrhea
Piroxicam which has a longer duration of action may cause higher gastric bleeding. It should be avoided in elderly patients.
Indomethacin can cause more serious CNS effects than other NSAIDs.
Nonacetylated salicylates such as salsalate, choline salicylate are safer than aspirin in aspirin-sensitive patients as they do not have respiratory effects similar to aspirin.
Rheumatoid arthritis is an inflammatory chronic and systemic disease most apparently involved in the synovial joints. The inflammation can spread over extra-articular tendons and organ structures.
Criteria
There are many criteria as follows:-
1.Morning Stiffness
Morning stiffness in any part of our body might have been experienced by somebody else especially at the knees or the feet. This may last for at least one hour.
2.Joints Swelling
At least three joints must have been experiencing swelling with fluid. The possible areas are the wrist, elbow, knee, ankle, and phalangeal (Hand and Feet Fingers) joints.
3.At least One Joint Area
At least one joint area in the hand such as the wrist, metacarpophalangeal(MCP), or proximal interphalangeal(PIP)
4.Symmetric
Simultaneous experience of arthritis in the bone joints at both sides of the body.
5.Subcutaneous Nodules(Rheumatoid nodules)
These nodules must be observed over bony prominences, extensor surfaces, or in juxta-articular regions by a physician.
6.Abnormal Presence Of Serum Rheumatoid Factor
It should be observed by a physician by any methodology
7.Radiological Changes
Bony erosions or decalcifications must be present in the hand or wrist x-ray.
Rheumatoid Arthritis (RA) is more common in women than men with a ratio of 3:1 respectively.
Occurrence
In general, the occurrence is rare (1 to 3%) in early ages, and medial at 30 to 40 years and more common at above 40 years.
Etiological Factors
Although it is still not knowing the exact reasons yet the following might have been observed as the etiological factors.
1. A specific leukocyte antigen is often involving some inflammatory reaction if the individual is exposed to certain environment.75% whites have this antigen while 30% from the rest of the population is suffering from RA.
2. Some infectious diseases may also be as factors to precipitate RA.
Symptoms
1.Synovial swellings with inflammation, with fluid collection and edema. If left untreated the RA becomes chronic and the synovium becomes thick and boggy.
2. The thickened synovium grow inward across the cartilage results in cartilage degradation, loss of adjacent bone, and erosions.
The news is very pleasant and induces hopes to the life expectancy of old aged people.
As the age increase the bones get weakened and more brittle.
Osteoporosis is more common in old aged people and is a hurdle to make a surgery to repair a broken hip in that age.
But now the news said regional anesthesia, better pain management, and implanting uncemented surgical parts make the procedure less risky.
There are two methods of hip repairs.1. Total hip replacement in which the whole hip bones and the ball are replaced.2.Hemiarthroplasty in which only the ball is replaced.
The first one is more complicated than the second one and holds more life expectancy.
Both can be possible at an old age but the most preferable one is hemiarthroplasty.
