Symptomatic treatment of multiple sclerosis

This article briefly discusses the most frequent symptoms of multiple sclerosis and their pharmacological treatment. In patients with multiple sclerosis against a background of fever of any origin, pseudo-exacerbations may occur, which are explained by reversible temperature-dependent changes in the conductivity of demyelinated axons. Methylprednisolone should not be prescribed for an untreated infection, as it may be the cause of the increase in symptoms. At the advanced stage of the disease, many patients take a combination of several agents to relieve symptoms. It is important to remember that the likelihood of side effects (eg, cognitive dysfunction in the use of anticholinergic drugs) increases with the simultaneous use of several drugs, for example, the means for normalizing urination, GABA-ergic antispastic agents, anticonvulsants and tricyclic antidepressants for the treatment of pain and depression. Often it is difficult to decide whether new symptoms are caused, such as fatigue or muscle weakness, the effect of drugs or the disease itself.

Patients with multiple sclerosis may need general medical care, but they may need special devices that compensate for their motor defect (for example, a special table for gynecological examination). However, with multiple sclerosis, there are rarely any procedures or medications needed for other diseases contraindicated. They are also not contraindicated in general or regional anesthesia, pregnancy, childbirth or immunization. Careful studies have not shown an adverse effect of influenza vaccination on the frequency of exacerbations or the rate of progression of the disease.

[1], [2], [3], [4], [5], [6], [7], [8], [9]

Spasticity

Spasticity arises as a result of the defeat of the central motor neurons and the elimination of their inhibitory effect on the segmental apparatus of the spinal cord, through which the reflex arcs are closed. It is usually caused by damage to the descending pyramid tracts. The defeat of pyramidal tracts is the most frequent cause of motor disorders in multiple sclerosis. It is manifested by the weakness of the limbs, increased muscle tone, muscle spasms in the upper and especially in the lower extremities. With moderate spasticity, movements in the joints are difficult. Most often, extensor spasms are observed, accompanied by a contraction of the quadriceps femoris and extension of the tibia. Flexible spasms with flexion in the knee joint are usually of a painful nature and are especially difficult to treat. With a gross violation of movements in the limbs, contractures in the joints can develop. Spasticity may worsen with fever, urinary infection, and in some cases in the treatment of INFBET.

Baclofen. Baclofen is an analogue of gamma-aminobutyric acid (GABA), which is the main inhibitory neurotransmitter in the spinal cord and brain. Baclofen inhibits both monosynaptic and polysynaptic spinal reflexes, and may also have some effect on supraspinal structures. His dose mainly limits the depressing effect on the central nervous system, which may manifest drowsiness or confusion. The dose of the drug is limited by other side effects, for example, constipation and urinary retention. After oral administration, the concentration of the drug in the blood reaches a peak after 2-3 hours, the half-elimination period is 2.5-4 hours. 70-80% of the drug is excreted unchanged in the urine. Treatment begins with a dose of 5-10 mg at night, and then it is gradually increased, switching to a 3-4-fold reception. In some cases, the effective dose is 100-120 mg or more. In severe cases, when maximum doses administered inside do not bring sufficient effect, it is possible for intrathecal (endolumbic) administration of baclofen using an implanted pump to control the rate of drug delivery.

Other agonists are GABA. Diazepam or clonazepam can be used to enhance the effect of baclofen, especially to reduce nocturnal muscle spasms, although they have a more pronounced depressant effect on the central nervous system than baclofen. Clonazepam has the longest action (up to 12 hours) and can be used in a dose of 0.5-1.0 mg 1-2 times a day. Diazepam is prescribed in a dose of 2 and 10 mg to 3 times a day.

Tizanidine. Tizanidine is an alpha2-adrenergic receptor agonist, acting mainly on polysynaptic (but not monosynaptic) spinal reflexes. After oral administration, the concentration of the drug in the serum reaches a peak after 1.5 hours, and the half-elimination period is 2.5 hours. When administered, the bioavailability is 40% (due to the metabolism of the first passage through the liver). Although the antihypertensive activity of tizanidine is 10-15 times lower than that of clonipine, it may appear after taking 8 mg of the drug. In view of the possible hepatotoxic effect, it is recommended to investigate the level of aminotransferases 1, 3, 6 months after the start of the drug and then at a certain periodicity. Tizanidine should be used with caution in elderly people and patients with impaired renal function due to decreased clearance of the drug. Treatment begins with 4 mg, in the subsequent dose is increased to 24 mg / day.

Other drugs used to treat spasticity. Dantrolene is indicated in patients with sharply expressed spasticity with ineffectiveness of other agents. The possibility of severe liver damage and other side effects limits its use in multiple sclerosis. Paroxysmal spasms of the upper and lower extremities may be weakened by the effect of anticonvulsants, including carbamazepine, phenytoin, or valproic acid. These drugs can be effective in case of paroxysmal symptoms of a different kind, including pain (for example, trigeminal neuralgia), myoclonia or dysphonia. For the treatment of spasticity in multiple sclerosis resort to local intramuscular administration of botulinum toxin.

Dysfunction of the pelvic organs

Violation of urination is one of the most common symptoms in multiple sclerosis. Sometimes a marked violation of urination is noted in cases where the remaining manifestations of the disease are mild. Hyperreflective urinary bladder is characterized by a decrease in functional capacity due to disinhibited detrusor cuts. In this case, cholinolytic agents that relax the muscle of the bladder, such as oxybutynin, tolteradine or tricyclic antidepressants, such as imipramine or amitriptyline, are effective. Oxibutinin hydrochloride is prescribed in a dose of 5-10 mg 2-4 times a day, tolteradine - in a dose of 1-2 mg 2 times a day, tricyclic antidepressants are first used in a dose of 25-50 mg per night, then it is gradually increased to obtain the desired effect .

Hyoscyamine sulfate is an alkaloid of belladonna with cholinolytic activity. It is prescribed in a dose of 0.125 mg every 4 hours. Hyoscyamine is also released in a sustained release dosage form, which is prescribed at 0.375 mg 2 times a day.

An alternative to anticholinergics or an addition to them can be vasopressin, which also helps with rapid urination. It is used in the form of nasal spray, which is prescribed once a day - in the evening or in the morning. Propanthelin bromide or dicyclomine hydrochloride is also used.

Violation of the emptying of the bladder can result from weak detrusor cuts or because detrusor cuts occur against the background of a closed external sphincter (detrusor detrusor and external sphincter). With detrusor weakness, intermittent catheterization is most effective, preventing the accumulation of a large volume of residual urine, but cholinergic drugs, for example, betanechol, may be useful. Antagonists of alpha2-adrenergic receptors (eg, terazosin and phenoxybenzamine), relaxing sphincter, can be used to treat dissonance. It is also possible to use clonidine, which is an alpha 2-adrenoreceptor agonist.

Disruption of bowel function may be manifested by constipation, diarrhea, or urinary incontinence. Drugs with holinoliticheskim action, used to treat spasticity, disorders of urination or depression, can strengthen the already existing tendency to constipation. With constipation, a diet with a high content of dietary fiber is recommended, as well as the use of laxatives.

[10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21]

Fatigability

Physiological mechanisms of increased fatigue in multiple sclerosis are not well understood. In some cases, fatigue is probably associated with a large expenditure of energy to overcome spasticity with daily activity. However, fatigue with multiple sclerosis can be pronounced and may even be a leading symptom in patients with minimal motor defect and even without any motor defect. In patients with multiple sclerosis with a decline in strength, depression should be excluded. To treat pathological fatigue in multiple sclerosis, two drugs are most often used: amantadine, an indirect agonist of dopamine receptors, and pemolin, an amphetamine-like drug. Amantadine, given in a dose of 100 mg 2 times a day, is usually well tolerated, but has only a moderate effect on fatigue. Occasionally, it causes a reticular liver on the skin. Pemolin is prescribed in a dose of 18,75-37,5 mg once a day. Due to the possibility of tachyphylaxis with regard to the anti-asthenic effect of pemoline, it is recommended to take breaks in taking the drug for 1-2 days a week.

[22], [23], [24], [25], [26], [27], [28], [29], [30], [31]

Pain

Pain sometimes occurs in patients with spinal cord injury. Usually it has the same localization as sensitivity disorders and is described by patients as burning, resembling paresthesia or, conversely, as deep. To reduce pain apply tricyclic antidepressants and anticonvulsants, including drugs with GABA-yergicheskim action - gabapentin, diazepam or clonazepam. Baclofen can also be useful in these cases.