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Active ingredients
Methylprednisolone
Release form
Pills
Composition
Active ingredient: Methylprednisolone (Methylprednisolone) Active ingredient concentration (mg): 4
Pharmacological effect
Synthetic GCS. It has anti-inflammatory, antiallergic, immunosuppressive effects, increases the sensitivity of β-adrenoreceptors to endogenous catecholamines. It interacts with specific cytoplasmic receptors (GCS receptors exist in all tissues, especially many in the liver) with the formation of a complex that induces the formation of proteins (including enzymes that regulate vital processes in cells). The effect of methylprednisolone on protein metabolism: reduces the amount of globulins in the plasma, increases the synthesis of albumin liver and kidney (with an increase in the ratio of albumin / globulin), reduces the synthesis and increases the protein catabolism in muscle tissue. abdomen), leads to the development of hypercholesterolemia. The effect of methylprednisolone on carbohydrate metabolism: increases the absorption of carbohydrates from the gastrointestinal tract, increases the activity of glucose-6-phosphatase (increases glucose uptake from the liver to the blood), increases the activity of phosphoenolpyruvate carboxylase and the synthesis of aminotransferases (activates gluconeogenesis), contributes to the development of hyperglycaemia. reduces bone mineralization. The anti-inflammatory effect is associated with the inhibition of release of inflammatory mediators by eosinophils and mast cells by inducing anija lipokortinov and decrease the number of mast cells that produce hyaluronic acid with a decrease capillary permeability, stabilization of cell membranes (particularly lysosomal) and organelle membranes. It acts on all stages of the inflammatory process: inhibits prostaglandin synthesis at the level of arachidonic acid (lipocortin inhibits phospholipase A2, inhibits arachidonic acid liberation and inhibits the biosynthesis of endopereas, leukotrienes, including inflammatory processes, allergies), synthesis of proinflammatory cytokines. hinterleukin 1, tumor necrosis factor alpha), increases the resistance of the cell membrane to the action of various damaging factors. The immunodepressive effect is caused by the involution of lymphoid tissue, the suppression of lymphocyte proliferation (especially T-lymphocytes), the suppression of B-cell migration and T-and B-lymphocyte interaction , inhibition of the release of cytokines (interleukin-1, 2, gamma-interferon) from lymphocytes and macrophages and a decrease in the formation of antibodies. The anti-allergic effect develops as a result of a decrease in Effects and secretion of allergy mediators, inhibition of release from sensitized mast cells and histamine basophils and other biologically active substances, reducing the number of circulating basophils, T and B lymphocytes, mast cells, suppressing the development of lymphoid and connective tissue, reducing the sensitivity of effector cells to allergy mediators , inhibition of antibody production, changes in the immune response of the body. In obstructive respiratory diseases, the effect is mainly due to inhibition of inflammation Yelnia processes, prevention or reduction of severity of mucosal edema, reduction of eosinophil infiltration bronchial epithelium submucosal layer and deposition in the bronchial mucosa of circulating immune complexes and erozirovaniya inhibition and mucosal desquamation. Increases the sensitivity of β-adrenoreceptors of the bronchi of small and medium caliber to endogenous catecholamines and exogenous sympathomimetics, reduces the viscosity of mucus by reducing its production. Suppresses the synthesis and secretion of ACTH and secondary synthesis of endogenous GCS. Inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar formation tissue.
Pharmacokinetics
Absorption and distributionWhen ingestion is rapidly absorbed, the absorption is more than 70%. Exposed to first pass through the liver. The time to reach Cmax in the blood plasma after oral administration is 1.5 hours. Binding to plasma proteins (only to albumin) is 62% regardless of the dose administered. Metabolism Metabolized mainly in the liver. Metabolites (11-keto and 20-hydroxy compounds) do not possess glucocorticoid activity and are excreted mainly by the kidneys.Within 24 hours, about 85% of the administered dose is found in the urine, and about 10% in the feces. It penetrates the BBB and placental barrier. Metabolites are found in breast milk. Excretion of T1 / 2 from blood plasma when administered orally is approximately 3.3 hours. Due to the intracellular activity, a marked difference between T1 / 2methylprednisolone from blood plasma and T1 / 2 from the body as a whole (approximately 12-36 hours) is detected. Pharmacotherapeutic action is maintained even when the concentration of the drug in the blood is not determined.
Indications
Systemic diseases of connective tissue (SLE, scleroderma, periarteritis nodosa, dermatomyositis, rheumatoid arthritis); acute and chronic inflammatory diseases of the joints - gouty and psoriatic arthritis, osteoarthritis (incl. post-traumatic), polyarthritis (including senile), scleroculocytic periarthritis, ankylosing spondylarthritis (Bechtreev disease), juvenile arthritis, Stilla syndrome in adults bursitis, nonspecific tendosynovitis, synovitis and epicondylitis; acute rheumatism, rheumatic carditis, small chorea; bronchial asthma, asthmatic status; acute and chronic allergic diseases (including allergic reactions to drugs and food products, serum sickness, urticaria, allergic rhinitis, angioedema, medicinal rash, pollinosis); skin diseases - pemphigus, psoriasis, eczema, atopic dermatitis (common neurodermatitis), contract dermatitis (with damage to a large surface of the skin), toxidermia, seborrheic dermatitis, exfoliative dermatitis, toxic epidermal necrolysis (Lyell’s syndrome), bulla herpetitis, acute epidermal necrolysis, toxic epidermal necrolysis, epithelial necrolysis, epidermal necrolysis, leukopathy, septicemia, exfoliative dermatitis, toxic epidermal necrolysis ; swelling of the brain (including on the background of a brain tumor or associated with surgery, radiation therapy or head injury) after prior parenteral administration of GCS; allergic diseases of the eye - allergic forms of conjunctivitis; inflammatory diseases of the eye - sympathetic ophthalmia, severe sluggish anterior and posterior uveitis, optic neuritis; primary or secondary adrenal insufficiency (including state after adrenal gland removal); congenital adrenal hyperplasia; diseases of the kidney autoimmune genesis (includingacute glomerulonephritis); nephrotic syndrome; subacute thyroiditis; diseases of the blood and hematopoietic system - agranulocytosis, panmielopathy, autoimmune hemolytic anemia, lymphoid and myeloid leukemia, lymphogranulomatosis, thrombocytopenic purpura, secondary thrombocytopenia in adults, erythroblastopenia (erythrocytic anemia, anemia, anemia, anemia interstitial lung diseases - acute alveolitis, pulmonary fibrosis, stage II-III sarcoidosis; tuberculous meningitis, pulmonary tuberculosis, aspiration pneumonia (in combination with specific chemotherapy); berylliosis, Leffler syndrome (not amenable to other therapy); lung cancer (in combination with cytostatics); multiple sclerosis; ulcerative colitis, Crohn's disease, local enteritis; hepatitis; hypoglycemic states; prevention of graft rejection after organ transplantation; hypercalcemia against oncological diseases, nausea and vomiting during cytostatic therapy; myeloma
Contraindications
For short-term use for vital reasons, the only Contraindications is hypersensitivity to methylprednisolone or the components of the drug. In children during the growth period, GCS should be used only according to absolute indications and with careful observation of a physician. The drug should be prescribed with caution in the following diseases and conditions: gastrointestinal diseases - gastric ulcer and duodenal ulcer, esophagitis, gastritis, acute or latent peptic ulcer, a newly created intestinal anastomosis, UC with the threat of perforation or abscess formation, diverticulitis; parasitic and infectious diseases of a viral, fungal or bacterial nature (currently or recently transferred, including recent contact with a patient) - herpes simplex, herpes zoster (viremic phase), chicken pox, measles, amebiasis, strongyloidiasis, systemic mycosis; active and latent tuberculosis (use for severe infectious diseases is permissible only against the background of specific therapy); pre- and post-vaccination period (8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination, immunodeficiency states (including AIDS or HIV infection); diseases of the cardiovascular system (includingrecent myocardial infarction - in patients with acute and subacute myocardial infarction, the focus of necrosis may spread, slowing the formation of scar tissue and, consequently, cardiac muscle rupture), severe chronic heart failure, arterial hypertension, hyperlipidemia; endocrine diseases - diabetes mellitus (incl. impaired carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Itsenko-Ksinga disease, obesity (III-IV degree); severe chronic renal and / or hepatic failure, nephroluritis; hypoalbuminemia and conditions predisposing to its occurrence; systemic osteoporosis, myasthenia gravis, acute psychosis, poliomyelitis (with the exception of the form of bulbar encephalitis), open-and closed-angle glaucoma; pregnancy.
Precautionary measures
Prolonged use of the drug Metypred can lead to the appearance of posterior subcapsular cataracts and nuclear cataracts (especially in children), exophthalmos or glaucoma with possible damage to the optic nerve and provoke the addition of a secondary ocular fungal or viral infection. With the use of the drug Metypred, an increase in blood pressure, fluid retention and salt in the body, loss of potassium, hypokalemic alkalosis is noted. These effects are less pronounced with the use of synthetic derivatives, with the exception of cases of their use in large doses. It may be necessary to limit the need for salt and sodium-containing products. Metypred therapy may mask the symptoms of peptic ulcers and in this case perforation or bleeding may develop without significant pain. Metypred side effects of the cardiovascular system, such as dyslipidemia, an increase in blood pressure may provoke new reactions in predisposed patients in case of using high doses of the drug Metypred and prolonged treatment. In this regard, the drug Metypred should be used with caution in patients with risk factors for cardiovascular diseases. Requires regular monitoring of heart function. The use of low doses of the drug Metypred every other day may reduce the severity of these side effects. Patients taking the drug Metypred should be cautiously prescribed acetylsalicylic acid and NSAIDs analgesics.
Use during pregnancy and lactation
In a number of animal studies with the introduction of methylprednisolone in high doses, fetal deformities were detected.Corresponding studies of the effect on human reproductive function have not been conducted. Since it is impossible to exclude the possible harm of methylprednisolone, taking the drug during pregnancy and in women planning a pregnancy is indicated only if the expected therapeutic effect on the mother exceeds the risk of negative effects on the fetus. Methylprednisolone should be prescribed during pregnancy only if absolutely necessary. Methylprednisolone penetrates the placental barrier. An increase in the number of infants with intrauterine growth retardation, born to mothers who received methylprednisolone, was also observed, and there were cases of cataracts in the newborn. The effect of methylprednisolone on the course and outcome of labor is unknown. Newborns born to mothers who received methylprednisolone during pregnancy should be carefully examined to identify possible symptoms of adrenal insufficiency. Because methylprednisolone passes into breast milk, breastfeeding should be stopped if lactation is necessary.
Dosage and administration
Inside, during or immediately after a meal, washed down with a small amount of liquid. The entire daily dose of the drug is recommended to take a single or double daily dose - every other day, taking into account the circadian rhythm of endogenous GCS secretion in the range from 6 to 8 am. A high daily dose can be divided into 2–4 doses, with a large dose taken in the morning. The initial dose of the drug can be from 4 to 48 mg of methylprednisolone per day, depending on the nature of the disease. For less serious diseases, it is usually sufficient to use lower doses, although individual patients may require higher doses. High doses may be required for such diseases and conditions as multiple sclerosis (200 mg / day), brain edema (200–1000 mg / day) and organ transplantation (up to 7 mg / kg / day). If after a sufficient period of time a satisfactory clinical effect is not obtained, the drug should be discontinued and a different type of therapy prescribed to the patient. For children, the doctor determines the dose based on the weight or surface of the body. When adrenal insufficiency - inside 0.18 mg / kg or 3.33 mg / m2 per day in 3 doses, with other indications - 0.42–1.67 mg / kg or 12.5–50 mg / m2 per day in 3 doses. With long-term use of the drug, the daily dose should be reduced gradually. Long-term therapy should not be stopped suddenly!
Side effects
From endocrine system: reduction of glucose tolerance, steroid diabetes, manifestation of latent diabetes mellitus, adrenal suppression, Cushing's (moon face, obesity, pituitary type, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, muscle weakness, striae) syndrome, delayed sexual development in children. On the part of the digestive system: nausea, vomiting, pancreatitis, steroid gastric ulcer and duodenal ulcer, erosive esophagitis, gastrointestinal bleeding, perforation of the gastrointestinal tract, anorexia, impaired digestion, flatulence, hiccups; rarely, increased activity of hepatic transaminases and alkaline phosphatase. Since the cardiovascular system: arrhythmias, bradycardia (up to cardiac arrest); in predisposed patients, the development or increase in the severity of heart failure, ECG changes characteristic of hypokalemia, increased blood pressure, hypercoagulation, thrombosis; in patients with acute and subacute myocardial infarction, necrosis can spread, slowing the formation of scar tissue, which can lead to rupture of the heart muscle. CNS and peripheral nervous system: delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness, anxiety, insomnia, dizziness, vertigo, pseudo-tumor of the cerebellum, headache, convulsions. On the part of the senses: posterior subcapsular cataract, increased intraocular pressure with possible damage to the optic nerve, a tendency to develop secondary bacterial, fungal or viral infections of the eye, trophic changes of the cornea, exophthalmos, sudden loss of vision (with parenteral administration in the head, neck, nasal shells, scalp possible deposition of crystals of the drug in the vessels of the eye). On the part of the metabolism: increased excretion of calcium, hypocalcemia, increased body weight, a negative nitrogen balance (increased protein breakdown), increased sweating; due to mineralocorticoid activity - fluid and sodium retention (peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).On the part of the musculoskeletal system: slower growth and ossification processes in children (premature closure of the epiphyseal growth zones), osteoporosis (very rarely - pathological bone fractures, aseptic necrosis of the head of the humerus and femur), muscle tendon rupture, steroid myopathy, muscle mass reduction (atrophy). Dermatological reactions: delayed wound healing, petechiae, ecchymosis, thinning of the skin, hyper- or hypopigmentation, steroid acne, stretch marks, tendency to the development of pyoderma and candidiasis. Allergic reactions: skin rash, itching, anaphylactic shock, local allergic reactions. Local reactions with parenteral administration: burning, numbness, pain, tingling at the injection site, infection of the injection site; rarely - necrosis of surrounding tissues, scar formation at the injection site, atrophy of the skin and subcutaneous tissue when i / m administration (especially in the deltoid muscle). Others: the development or exacerbation of infections (jointly used immunosuppressants and vaccination contribute to the occurrence of this side effect), leukocyturia, withdrawal syndrome, flushing to the head.
Overdose
Acute toxicity with methylprednisolone is unlikely. After chronic overdose, due to possible insufficiency of adrenal function, the dose of the drug should be gradually reduced. In the case of a single oral overdose, treatment should be supportive; you can conduct a gastric lavage and assign activated carbon. There are no specific antidotes for methylprednisolone. Methylprednisolone is derived from dialysis.
Interaction with other drugs
Methylprednisolone is a substrate for the cytochrome P450 enzyme; metabolized mainly by the CYP3A4 enzyme. The CYP3A4 enzyme is a key enzyme of the CYP subfamily. The greatest amount is found in the liver. It catalyzes 6-beta-hydroxylation of steroids and is an important first phase of the metabolic process for both endogenous and synthetic corticosteroids. Many substances substrates of CYP3A4 are known, some of them (including other medicinal substances) are able to influence GCS metabolism by inducing or inhibiting the CYP3A4 enzyme. CYP3A4 isoenzyme inhibitors: drugs inhibiting CYP3A4 activity reduce the hepatic clearance and increase the concentration of drugs in the blood, acting as substrates of the isoenzyme CYP3A4 (methylprednisolone).If the patient is already receiving a CYP3A4 inhibitor, the dose of Metypred should be adjusted in such a way as to prevent overdose. This group includes erythromycin, clarithromycin, troleandomycin, ketoconazole, itraconazole, isoniazid, diltiazem, aprepitant, fevers, inhibitors, inhibitors, inhibitors, suppressants, inhibitors, inhibitors, inhibitors, inhibitors, inhibitors, inhibitors, inhibitors, inhibitors, inhibitors, inhibitors, inhibitors, inhibitors, inhibitors, inhibitors, inhibitors, inhibitors, inhibitors, inhibitors, inhibitors, inhibitors, inhibitors, inhibitors, overdose. ), cyclosporine and ethinyl estradiol, norethisterone, histamine H2 receptor blockers (cimetidine). CYP3A4 inhibitor is also grapefruit juice. CYP3A4 isoenzyme inducers: medicinal substances that induce CYP3A4 activity increase hepatic clearance and thereby lower blood concentrations of medicinal substances that act as substrates of CYP3A4 isoenzyme. Concomitant therapy with CYP3A4 inducers requires an increase in the dose of the drug Metypred to achieve the desired result from treatment. The drugs in this group include: rifampicin, carbamazepine, phenobarbital, phenytoin. CYP3A4 isoenzyme substrates If the patient already receives any CYP3A4 substrates, this can inhibit or induce the hepatic clearance of methylprednisolone. In this case, a dose adjustment of the drug Metypred is required. There is a possibility that side effects characteristic of both drugs may occur more often when they are taken together. Simultaneous intake of methylprednisolone and tacrolimus can reduce the concentration of tacrolimus in the body. Simultaneous intake of cyclosporine and methylprednisolone inhibits their joint metabolism, which can increase plasma concentrations of either one of these substances, or both. As a consequence, the undesirable effects of these drugs that occur during monotherapy may be more pronounced when they are combined. There are cases of seizures that occur with simultaneous treatment with cyclosporine and methylprednisolone.
special instructions
Since the complications of drug therapy Metypred depend on the size of the dose and the duration of treatment, in each case, based on the analysis of the risk / benefit ratio, they decide on the need for such treatment, and also determine the duration of treatment and the frequency of administration. dose of the drug Metypred.When the effect is achieved, the dose should be gradually reduced to maintenance or discontinued treatment. Due to the risk of arrhythmia, use of the drug Metypred in high doses should be carried out in a hospital with the necessary equipment (electrocardiograph, defibrillator). With long-term treatment, the patient should be regularly examined (chest X-ray, plasma glucose concentration is and 2 hours after a meal, urinalysis, blood pressure, body weight control, it is desirable to conduct radiological or endoscopic examination with a history of gastrointestinal ulcer disease) It should be carefully monitor the growth and development of children who are on long-term therapy with Metypred. Growth retardation may be observed in children receiving long-term daily, divided into several doses, therapy. Daily use of methylprednisolone for a long time in children is possible only by absolute indications. Using the drug every other day may reduce the risk of developing this side effect or will avoid it altogether. Children who receive long-term therapy with Metypred are at increased risk of developing intracranial hypertension. Metypred should also be prescribed with great caution to patients with confirmed or suspected parasitic infections, such as strongyloidosis. Immunosuppression caused by methylprednisolone in such patients leads to strong hyperinfestation and dissemination of the process with a widespread migration of larvae, often with the development of severe enterocolitis and gram-negative septicemia with a possible lethal outcome. For example, chickenpox and measles can have a more severe course, even death in unimmunized children or in adults receiving Metypred. Patients who may be exposed to stress during therapy with Metypred show an increase in the dose of the drug before, during and after stressful situation. On the background of drug therapy Metypred, susceptibility to infections may increase, some infections may occur in a worn out form, in addition, new infections may develop. In addition, the body’s ability to localize the infection process is reduced.The development of infections caused by various pathogenic organisms, such as viruses, bacteria, fungi, protozoa or helminths, which are localized in various systems of the human body, may be associated with the use of the drug Metypred, both as monotherapy and in combination with other immunosuppressants on cellular immunity, humoral immunity or on neutrophil function. These infections can be mild, however, in some cases it may be severe and even fatal. Moreover, the higher doses of the drug are used, the higher the likelihood of infectious complications. Patients receiving treatment with Metypred in doses that have an immunosuppressive effect are contraindicated in the introduction of live or live attenuated vaccines, but killed or inactivated vaccines can be administered, but the response to the introduction of such vaccines may be reduced or even absent. According to appropriate indications, patients receiving treatment with Metypred in doses that do not have immunosuppressive action can be immunized. Use of Metypred with active tuberculosis should be limited to cases of fulminant and disseminated tuberculosis, when Metypred is used to treat a disease in combination with an appropriate anti-tuberculosis chemotherapy. Metypred is prescribed to patients with latent tuberculosis or with positive tuberculin tests, then The treatment should be carried out under strict medical supervision, since it is possible to reactivate the disease. During long-term drug therapy, such patients should receive appropriate prophylactic treatment. It is reported that Kaposi's sarcoma was observed in patients who received therapy with Metypred. With the abolition of the drug, clinical remission may occur. With the use of the drug Metypred in therapeutic doses for a long period, suppression of the hypothalamic-pituitary-adrenal system (secondary insufficiency of the adrenal cortex) may develop. The degree and duration of adrenal insufficiency are individual for each patient and depend on the dose, frequency of use, time of treatment and duration of therapy. The effect of this effect can be reduced by using the drug every other day or gradually reducing the dose.This type of relative insufficiency of the adrenal cortex can last for several months after the end of treatment, therefore, in any stressful situations during this period, Metypred should be reappointed. Since the secretion of mineralocorticosteroids may be disrupted, the concomitant administration of electrolytes and / or mineralocorticosteroids is necessary. Acute adrenal insufficiency leading to a lethal outcome may develop, with abrupt withdrawal of Metypred. Withdrawal, apparently not related to adrenal insufficiency, may also occur due to the abrupt withdrawal of the drug Metypred. This syndrome includes symptoms such as anorexia, nausea, vomiting, lethargy, headache, fever, pain in the joints, peeling of the skin, myalgia, weight loss and a decrease in blood pressure. It is assumed that these effects occur due to a sharp fluctuation of plasma methylprednisolone concentration, and not due to a decrease in plasma plasma concentration of methylprednisolone. Patients with hypothyroidism or liver cirrhosis increase the effect of the drug Metypred. in blood plasma, worsening of current diabetes mellitus. Patients receiving long-term drug therapy Metypred may be predisposed to the development of diabetes. On the background of drug therapy Metypred, various mental disorders can develop: from euphoria, insomnia, mood instability, personality changes and severe depression to acute mental manifestations. In addition, already existing emotional instability or tendencies to psychotic reactions may increase. Potentially severe mental disorders may occur when using the drug Metypred. Symptoms usually appear within a few days or weeks after starting therapy. Most reactions disappear either after a dose reduction or after drug withdrawal. Despite this, specific treatment may be required. Patients and / or their relatives should be warned that in the event of a change in the patient’s psychological status (especially with the development of a depressive state and suicidal attempts), it is necessary to apply formedical care. Patients or their relatives should also be warned about the possibility of the development of mental disorders during or immediately after reducing the dose of the drug or completely discontinuing it. Allergic reactions are possible. Due to the fact that patients receiving GCS rarely observed such phenomena as skin irritation and anaphylactic or pseudo-anaphylactic reactions, necessary measures should be taken before prescribing GCS, especially if there is a history of allergic reactions to drugs in the patient's history. Due to the existing risk of corneal perforation, GCS should be prescribed for the treatment of eye infections caused by the herpes simplex virus (ophthalmic herpes) with caution. High doses of GCS can cause acute pancreatitis. High-GCS therapy can cause acute myopathy; at the same time, patients with impaired neuromuscular transmission (for example, myasthenia gravis), as well as patients receiving concomitant therapy with cholinolytics, for example, neuromuscular blockers, are most susceptible to the disease. This kind of myopathy is generalized; it can affect the muscles of the eyes or the respiratory system, and even lead to paralysis of all limbs. In addition, the level of creatine kinase may increase. In such cases, clinical recovery can take weeks and even years. Osteoporosis is a frequently occurring (but rarely detectable) complication of long-term therapy with high doses of GCS. GCS is carefully prescribed for long-term therapy in elderly patients because of the increased risk of osteoporosis and fluid retention the body that potentially causes an increase in blood pressure. Simultaneous treatment with methylprednisolone and fluoroquinolones increases the risk of tendon rupture, especially in elderly patients. High doses GCS can cause pancreatitis in detey.Vysokie methylprednisolone dose should not be used during brain damage caused by trauma golovy.T.k. Methylprednisolone may enhance the clinical manifestations of Cushing's syndrome; use of methylprednisolone in patients with Itsenko-Cushing disease should be avoided. Patients receiving systemic corticosteroids should be closely monitored,and recent myocardial infarction. Patients with a history or currently have thrombosis or thromboembolic complications must be carefully monitored. Caution should be exercised on the ability to drive motor vehicles and control mechanisms. persons driving vehicles or engaging in activities requiring increased concentration and psychomotics orny reactions.