Pulse therapy with methylprednisolone or prednisolone

Pulse therapy (PT), or pulse therapy, means the administration of large doses of drugs, most commonly hormonal, in an intermittent way to enhance therapeutic effects and reduce side effects.

For the first time, pulse therapy was used to successfully prevent rejection of a kidney transplant. Subsequently, pulsatile doses of corticosteroids were used to treat other diseases, such as lupus nephritis, rheumatoid arthritis and gangrenous pyoderma.

Usually PT is used for treatment only in emergency situations, therefore it is not the preferred method of exposure.Methylprednisolone was the very first drug used in PT at a dose of 1 g per dose over a variable number of days.

Video Corticosteroids (pulse therapy), immunoglobulins intravenously, plasmapheresis with multiple sclerosis

History of pulse therapy

The definition of "pulse-therapy" was first used by Pasricha and Ramji in 1984. [1 - Kaul R, Sanjay CJ. Review on pulse therapy: A novel approach in the treatment of pemphigus vulgaris. J Pulsar therapy means the administration of large (supra-pharmacological) doses of hormonal drugs in a discontinuous way to achieve therapeutic effects and reduce side effects. The first use of pulse therapy with the use of corticosteroids is attributed to Kountz and Cohn, who used it to prevent the rejection of the kidney transplant in 1973. [2 - Panat SR, Aggarwal A, Joshi A. Pulse therapy: A boon or bane. J Dent Sci Oral Rehabil 2012; 3: 1-3]

Description of pulse therapy

Pulse therapy is a discontinuous intravenous infusion of high doses of the drug, which may be equivalent to 250 mg of prednisolone per day for one or several days.

Drug groups, most commonly used in the process of pulse therapy:

• Corticosteroids
• Immunosuppressive means
• Antifungal drugs
• Antibiotics.

Initially, the duration of infusion of hormonal drugs was 10-20 minutes. However, it is known that rapid infusions are associated with a higher risk of hemodynamic disorders. To date, the corticosteroid drug is dissolved in 150-200 ml of 5% dextrose and administered intravenously slowly for 2-3 hours.

Advantages of using corticosteroids as a pulse therapy:

1. It allows to achieve an immediate, deep anti-inflammatory effect, while the toxicity observed with traditional high-dose oral therapy is rather low.
2. A faster clinical recovery is determined when symptoms disappear than with oral therapy, with clinical improvement occurring approximately 3 weeks after one course of treatment.
3. There is a prolonged suppressive effect on the hypothalamic-pituitary system.

The goal of pulse therapy is to achieve faster and stronger efficacy and reduce the need for long-term use of steroids.The paradox here is that the introduction of high doses of steroids is used to achieve the effect of reducing steroids. The greatest experience of pulse therapy in patients with pemphigus has been reported. Pasricha described hormone-sparing effects and prolonged remission, lasting up to 9 years [3 - Sinha A, Bagga A. Pulse steroid therapy. Indian J Pediatr 2008; 75: 1057-66]

Mechanism of action of pulse therapy

Glucocorticoids have a variety of immunosuppressive, anti-inflammatory and anti-allergic effects. They mediate their actions with the help of genomic and non-genomic methods of influence. Buttgereit et al. Identified three "modules" of the glucocorticoid effect on cells resulting from various concentrations:

1. Low concentrations mediate effects through genomic messages.
2. Mean concentrations bind to receptors on the cell membrane, which activate the transfer of transverse membrane signals for genomic and non-genomic intracellular messages.
3. At very high concentrations, steroids dissolve in the cell membrane, which leads to greater stability of the cell membrane and a decrease in the function of the non-genomic cells.

In general, effects of corticosteroid impulses seem to include a decrease in the regulation of immune cell activity and the production of pro-inflammatory cytokines. This effect is qualitatively similar to that observed with antitumor necrosis-alpha therapy

Indications for pulse therapy

It is usually used for such diseases as:

• Rheumatoid arthritis
• Juvenile rheumatoid arthritis
• Systemic lupus erythematosus
• Poliomyositis
• Severe form of vasculitis
• Steroid-resistant nephritic syndrome
• Half-month glomerulonephritis
• Acute rejection of allograft
• Pemphigus (pemphigus)
• Bullous dermatitis herpetiformis.

It is rarely used in such pathologies as:

• Psoriatic arthritis
• Ankylosing spondylitis
• Kawasaki disease
• Lupus nephritis
• Heavy Stevens Johnson Syndrome
• Severe myasthenia gravis
• Severe Ulcerative Colitis
• Exfoliative dermatitis.

Contraindications to pulse therapy

• Systemic infections, fungal sepsis, uncontrolled hypertension and hypersensitivity to a steroid drug
• Absolutely contraindicated in pregnant, lactating and unmarried patients
• Therapy is also contraindicated in patients with a known hypersensitivity to a steroid drug.

Side effects

The most significant and serious consequences for children are:

• Elevated blood pressure in already hypertensive children during and after infusion
• Attacks, especially with systemic lupus erythematosus, which can be associated with a fast flow of electrolytes
• Anaphylactic shock after another infusion, usually associated with methylprednisolone succinate methyl ester.

Pulse therapy with methylprednisolone

Methylprednisolone is an intermediate potent anti-inflammatory drug with a low tendency to induce sodium and water retention compared to hydrocortisone. Its biological half-life is 12-36 hours, its effectiveness is 1.25 times compared with prednisolone.

Dosage

Methylprednisolone is administered at a dose of 20-30 mg / kg (500-1000 mg) per administration and, if necessary, the dose is adjusted to a maximum of 1 g / kg.

Video Hormonal medications - Dr. Komarovsky's school