The treatment of rheumatism is quite a lot of drugs, but basically can be grouped into four categories:
1, non-steroidal anti-inflammatory drugs: this class of drugs is also commonly known as anti-inflammatory and painkillers, mainly for the treatment of rheumatic pain, such as rheumatoid arthritis, seronegative spondyloarthropathy, osteoarthritis, gout.
2.Steroidal anti-inflammatory drugs: often called hormones, mainly used in the treatment of systemic lupus erythematosus, systemic sclerosis, myositis, dermatomyositis, dry syndrome, leukoarthrosis, vasculitis.
3.Alterative drugs: also known as slow-acting drugs, this class of drugs is mainly used to control the development of the disease.
4.Anti-tumor necrosis factor TNF-a inhibitor, this kind of drugs have fast onset of action and strong targeting.
Non-steroidal anti-inflammatory drugs (NSAIDs).
1.Role
(1) anti-rheumatic effects: widely used in the symptomatic treatment of rheumatic diseases, such as gouty arthritis, acute rheumatic fever, Wright’s syndrome, rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, psoriatic arthritis, juvenile idiopathic arthritis and many other acute and chronic arthritis, as well as a variety of soft tissue pain, tenderness, morning stiffness, swelling, effusion and other inflammatory manifestations, but can not cure inflammation, can not prevent tissue damage, joint destruction and incapacity.
(2) Analgesic effect: clinically, NSAID can be used as the first-stage treatment drug in the three-step treatment of cancer pain, and can also be used for analgesia after minor surgery such as tooth extraction and anal surgery, as well as the treatment of pain such as dysmenorrhea and migraine.
(3) Antipyretic effect: NSAID produces an antipyretic effect by inhibiting the synthesis of prostaglandins to normalize the body temperature regulation point, therefore, non-steroidal anti-inflammatory drugs can bring down excessive body temperature with little effect on normal body temperature.
(4) Anti-platelet aggregation effect: clinical use of small doses of aspirin for patients with cardiovascular diseases at risk of arterial thrombosis can reduce the incidence of stroke and myocardial infarction and mortality
(5) Inhibitory effect on malignant tumors: Early epidemiological studies showed that patients taking NSAID for a long time had a significantly reduced incidence of rectal/colon cancer. In animal experiments, NSAIDs such as meloxicam and sulforaphane can inhibit the growth of tumor cells.
2.Adverse reactions and countermeasures
(1) Gastrointestinal side effects. Gastrointestinal adverse reactions are the first of all kinds of side effects. The clinical manifestations of the effects on the upper gastrointestinal tract are nausea, vomiting, epigastric discomfort, fullness, belching, loss of appetite and other indigestive symptoms in the milder cases, and acute gastric mucosal lesions, induced and aggravated gastric and duodenal ulcers, resulting in bleeding and perforation in the heavier cases.
(2) nephrotoxicity. the main clinical manifestations of renal adverse reactions caused by NSAID are proteinuria, tubular urine, red and white blood cell urine and other abnormalities in urinalysis, but also edema, dizziness, hypertension and other symptoms, and in severe cases can cause acute interstitial nephritis, even renal papillary necrosis, acute renal insufficiency.
(3) Allergic reactions. Drug allergy is mainly due to reactive changes that occur when patients have been exposed to drugs that play an antigenic or allergic role, and these reactions are not related to the dose of drugs used. The main clinical manifestations are photosensitivity, skin pruritus, various forms of rash such as erythema, papules, urticaria or angioneurotic edema, and in severe cases, Stevens-Johnson syndrome, exfoliative dermatitis and anaphylaxis. Those with vasomotor rhinitis, nasal polyps and bronchial asthma triad are prone to induce acute bronchial asthma after taking NSAID.
(4) Central nervous reactions: The main clinical manifestations of central nervous reactions to NSAID are headache, dizziness, tinnitus, reduced vision and hearing, drowsiness, confusion, confusion, etc. Occasionally, convulsions and aseptic meningitis can be seen.
(5) Hematologic side effects: Long-term application of NSAIDs can also result in a decrease in red blood cells, white blood cells, and platelets, which are recovered after timely detection and discontinuation of the drug. Some NSAIDs can cause aplastic anemia, granulocyte deficiency and platelet deficiency. Although rare, once they occur they are serious and should be discontinued immediately.
(6) Liver damage Most drugs are metabolized by the liver and can cause liver damage. It generally manifests as elevated transaminases, mild jaundice, poor appetite and reduced food intake.
Glucocorticoids
1.Role
(1) Anti-inflammatory effect of glucocorticoids. Glucocorticoids have inhibitory effects on inflammation (immune factors, mechanical factors, chemical factors and infectious irritants) caused by a variety of mechanisms. Their anti-inflammatory effects are manifested in the inhibition of immunomodulatory proteins and immunomodulatory cells, including: reduction of inflammatory exudation; reduction of the production and efficacy of inflammatory regulatory factors; reduction of the aggregation of inflammatory cells to the site of inflammation and inhibition of inflammatory cell activation. In conclusion, glucocorticoids suppress cellular immunity more than humoral immunity. They are widely used in the treatment of rheumatic diseases such as systemic lupus erythematosus, dry syndrome, dermatomyositis, vasculitis, scleroderma, mixed connective tissue disease and rheumatoid arthritis.
(2) Non-immunomodulatory effects of glucocorticoid drugs. They have effects that are not directly related to immunomodulation. For example, their effects on metabolism are of clinical importance. Although they are not directly related to immunomodulatory activity, they may cause adverse effects in patients. For example, they cause insulin resistance and decrease glucose tolerance. It can also be an alteration of blood lipid concentration, which generally tends to develop atherosclerosis.
2.Adverse reactions of glucocorticoids
(1) Increase the susceptibility to infection. The immunosuppressive effects of glucocorticoids can produce adverse effects, such as increased risk of infection by bacteria, viruses, fungi, and protozoa. In fact, the results are mixed and difficult to evaluate. Because most patients with diseases requiring corticosteroids may themselves be susceptible to infections.
(2) Osteoporosis. Glucocorticoids reduce intestinal calcium absorption, increase renal calcium loss, secondary hyperparathyroidism, inhibit osteoblast function, inhibit growth factors, increase bone resorption, and decrease sex hormone concentrations, all of which contribute to osteoporosis. The risk of fracture in patients using glucocorticoids is 11-15%, and the level of risk is influenced by the dose of glucocorticoids and their disease itself. Vitamin D and intranasally administered calcitonin have the potential to alleviate glucocorticoid-induced osteoporosis.
(3) Osteonecrosis. The risk of osteonecrosis is higher in patients with SLE and relatively low in patients with rheumatoid arthritis, but the risk is further increased by the use of glucocorticoids. Osteonecrosis most often involves the hip, followed by the knee and shoulder joints, and is usually bilateral and simultaneous. The risk of osteonecrosis induced by glucocorticoids is related to the dose and duration of its use and to the disease itself. Low doses of prednisone generally do not induce osteonecrosis.
(4) Myopathy. Glucocorticoids can induce myopathy, especially at high doses for prolonged periods of time. Myopathy is characterized by progressive muscle weakness, which can even affect walking in severe cases. Myopathy should be found as soon as possible to reduce the dose and gradually stop the drug.
(5) Peptic ulcer: Glucocorticoids may induce or aggravate peptic ulcer. Especially when glucocorticoids are combined with non-steroidal anti-inflammatory drugs, it further increases the risk of peptic ulcer and gastrointestinal bleeding.
(6) Hypertension. Its occurrence is related to endogenous overproduction and exogenous overgiving of glucocorticoids. Because dexamethasone has no salt corticosteroid-like effects and prednisone has only weak salt corticosteroid-like effects, the mechanism of its induced hypertension cannot be briefly stated to be caused by salt corticosteroid-like effects of water and sodium retention. Absorption in argues that the altered vascular response to pressor is more important. Low doses of prednisone have only a small effect on blood pressure and are not an important cause of hypertension.
(7) Fat metabolism. The use of moderate to high doses of glucocorticoids often leads to weight gain, which may be associated with increased appetite and metabolic changes. High doses can lead to redistribution of fat, causing typical Cushing’s syndrome symptoms such as full-moon face, centripetal obesity, and buffalo back. It generally does not occur at low doses.
(8) Suppression of hypothalamic-pituitary-adrenal axis. Abrupt interruption of glucocorticoid therapy may cause acute adrenal insufficiency, which may lead to circulatory collapse or even risk of death if appropriate control measures are not taken.
(9) Neuropsychiatric. Glucocorticoids may cause many psychiatric symptoms, mainly mood changes, emotional instability, euphoria, insomnia, depression, psychosis, etc. Most patients with psychiatric adverse reactions appear in the first five days of treatment.
Methotrexate (MTX)
1.Application
It is widely used clinically in the treatment of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, systemic lupus erythematosus, vasculitis and systemic sclerosis.
2.Side effects and toxicity
(1) Intestinal reactions. The most common, it is the main cause of dose reduction or even discontinuation. The main symptoms include loss of appetite, nausea, vomiting, diarrhea, abdominal pain, dyspepsia and weight loss, etc. Most of the symptoms are relatively mild and appear mostly a short time after the administration of the drug. Reducing the dose, or using parenteral route of administration, or supplementation also count, can reduce the symptoms. And with the use of time extension, the patient can gradually tolerate.
(2) Hepatotoxicity. The incidence is very low. In order to reduce the toxic effects of MTX on the liver, weekly but not daily use of MTX is recommended.
(3) Lung injury. acute and chronic lung toxicity due to MTX is common in RA. Dyspnea is the earliest symptom, followed by cough, fever, headache and malaise. Clinical symptoms may precede the appearance of radiographic lesion signs in the chest. The incidence of pneumonia is approximately 2.1-5.5%, with most completely cured and a small percentage of patients left with permanent lung damage. Before MTX treatment, the patient should be informed of the lung condition and reminded to pay sufficient attention to the pulmonary symptoms during the application of MTX and to consult the doctor in time for early diagnosis and early treatment.
(4) Hematological abnormalities. Toxic manifestations are leukopenia, thrombocytopenia, megaloblastic anemia and complete blood cytopenia, the incidence is less than 5%.
Cyclophosphamide (CTX)
1.Application
Cyclophosphamide can be used to treat various rheumatic diseases, including systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, systemic sclerosis, polyarteritis nodosa and systemic arteritis.
2.Adverse reactions
(1) Myelosuppression: leukopenia, thrombocytopenia, anemia and complete blood cytopenia caused by CTX have been reported. The highest incidence is leukopenia, and its appearance is related to the dose of the drug, usually in 3-7 days of drug use. Leukocytes are generally lowest 8-12 days after shock treatment, with a decrease in both B and T lymphocytes.
(2) Urinary and reproductive system toxicity. It has been reported abroad that cyclophosphamide application can cause hemorrhagic cystitis, while in China, the incidence of such cases is low, and more water can be drunk during treatment to dilute the concentration of the drug in the bladder. The drug can inhibit ovarian function and destroy follicles in the ovaries, affecting fertility. Therefore, it should be used with caution in young patients with fertility requirements, and if it must be used, it should not be used too often to avoid loss of reproductive function.
(3) Digestive system. First of all, when cyclophosphamide treatment, it can produce more serious gastrointestinal reactions, such as nausea, vomiting, etc. At this time, metoclopramide (gastric reversion), domperidone (morpholine) and other gastrodynamic drugs can be used.
(4) Infection. Infections are often associated with low white blood cells and combined glucocorticoid therapy. Severe infections are rare and include pneumonia, infectious arthritis and sepsis.
(5) Tumors, increased incidence of tumors, lymphoma, leukemia, skin and bladder tumors are higher than the normal population, is the main reason for the increased mortality of immunosuppressive drugs.
Antimalarial drugs
At present, chloroquine and hydroxychloroquine are more commonly used in clinical practice.
1.Application
Widely used in systemic lupus erythematosus, rheumatoid arthritis, discoid lupus erythematosus, and connective tissue diseases such as dry syndrome, psoriasis and dermatomyositis.
2.Side effects and toxicity
(1) Gastrointestinal reactions. Anorexia, heartburn, nausea, vomiting and weight loss are mostly seen in the early stage of drug use. Abdominal distension, diarrhea or abdominal discomfort is not uncommon, and gastrointestinal bleeding is not seen. Occasionally, liver function damage was seen.
(2) Skin and hair damage. Mossy, urticaria-like, measles-like and maculopapular rashes were mostly seen. Pigment changes such as gray hypopigmentation or blue-black hyperpigmentation of the skin or hair are seen, most often in patients with long treatment dates or high doses. Hair loss is rarely seen.
(3) Neurological symptoms. Occasional headache, dizziness, insomnia, and nervousness are not severe and may recover.
(4) Ocular lesions. There are three manifestations: impaired eye adjustment reflexes, corneal deposition, and retinopathy.
Salazosulfapyridine
1.Application
Widely used in rheumatoid arthritis, spondyloarthropathy, ulcerative colitis, Crohn’s disease, etc.
2.Side effects and toxicity
(1) Digestive system reaction. Nausea, vomiting, anorexia, dyspepsia and abdominal pain are the most common side effects, and 2/3 of patients interrupt treatment because of them. Transient, asymptomatic mild transaminase increases are occasionally seen and do not affect continued treatment. Severe hepatotoxic or allergic reactions are less common, often occurring within 2-3 weeks of drug administration and manifesting as fever, rash, lymphadenopathy, hepatomegaly, increased liver enzyme profile, and hyperbilirubinemia.
(2) Respiratory system. Respiratory complications include subacute fibrous alveolitis, bronchitis, laryngitis with bronchial asthma and a complication that clinically and radiologically resembles eosinophilic pneumonia. The latter two complications appear within 2-5 months of drug administration, with dyspnea, cough, fever and weight loss as the main signs and symptoms.
(3) Male infertility. Decreased sperm count and abnormal sperm motility and morphology are usually seen within two months of drug administration. The incidence may be high, but it is mostly reversible and fertility is restored after a few weeks of drug discontinuation.
Leflunomide
1. Application
Currently, the autoimmune diseases for which Leflunomide has been applied include rheumatoid arthritis, systemic lupus erythematosus, lupus nephritis, dry syndrome, ankylosing spondylitis, psoriasis, scleroderma, polymyositis, Behçet’s disease, Wegener’s granulomatosis, and idiopathic thrombocytopenic dictionary.
2.Adverse reactions
The main adverse reactions of leflunomide are: diarrhea, pruritus, rash, transient transaminase elevation and white blood cell drop, reversible alopecia, etc.. They are generally mild and moderate, and serious adverse reactions are rare.
Biological agents
The biologic agents that are widely used in clinical practice are TNF-α receptor antagonists, which are highly effective in the treatment of rheumatoid arthritis and spondyloarthropathies. The improvement of the disease is very rapid during the treatment. The side effects observed in clinical practice are mainly infections, including bacterial, viral and tuberculosis infections.