Treatment of myasthenia gravis

Drug therapy has to be tailored to individual patients and includes anticholinesterase drugs, anti-inflammatory corticosteroids and immunosuppressant drugs. 

Anticholinesterase drugs work by inhibiting the enzyme that normally destroys acetylcholine after it has stimulated its receptors at the neuromuscular junction. This leads to increased amounts of acetylcholine available to interact with remaining receptors and so improves the ability of muscles to contract. An example of an anticholinesterase drug is 

Side effects of these drugs include excessive salivation, muscle twitching and abdominal pain, nausea and diarrhoea. 

Anti-inflammatory corticosteroids, for example prednisolone, can be used to suppress the antibody formation in myasthenia gravis. They should be used together with anticholinesterase drugs and once an improvement is seen the dose should be decreased. 

Long-term use of corticosteroids leads to serious side effects, including suppression of the pituitary-adrenal axis, immunosuppression, muscle wasting, osteoporosis and impaired wound healing (see page 119 and Table 7.1). 

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The anainoacridines, tacrine (19) and its 1-hydroxy metaboUte, velnacrine (20), are reversible inhibitors of AChE. Tacrine was synthesi2ed in the 1940s and has been used clinically for the treatment of myasthenia gravis and tardive dyskinesia (115). Placebo-controUed studies have indicated modest efficacy of tacrine to treat AD dementia (122,123) and in 1993 the dmg was recommended for approval by the PDA under the trade name Cognex. Tacrine (19) has been shown to interact with sites other than AChE, such as potassium channels (124) and muscarinic receptors. However, these interactions are comparatively weak and are not thought to contribute to the biological activity of the dmg at therapeutic levels (115). 

D.F.P. was administered intramuscularly in small doses to ten patients for periods varying from 2 weeks to 2 years. It was concluded that D.F.P. was not a very suitable drug for the routine treatment of myasthenia gravis, since it did not relieve signs and symptoms as effectively and consistently as neostigmine. 

Because anticholinesterase agents also inhibit plasma pseudo-ChE, they will potentiate the effects of succinylcholine by inhibiting its breakdown. This is important, for example, when succinylcholine is to be employed in patients who have previously received cholinesterase inhibitors for the treatment of myasthenia gravis or glaucoma. 

Neostigmine is a drug of choice in the treatment of myasthenia gravis, a chronic disease characterized by muscular weakness and rapid fatiguability of the skeletal muscles due to impaired neuromuscular transmission. The defect may be presynaptic or postsynaptic. 

Apart from neostigmine, pyridostigmine and ambenonium are the other standard drugs used in the treatment of myasthenia gravis. 

Edrophonium Alcohol, binds briefly to active site of acetylcholinesterase (AChE) and prevents access of acetylcholine (ACh) Amplifies all actions of ACh increases parasympathetic activity and somatic neuromuscular transmission Diagnosis and acute treatment of myasthenia gravis Parenteral quaternary amine does not enter CNS Toxicity Parasympathomimetic excess Interactions Additive with parasympathomimetics... 

Uses treatment of myasthenia gravis (has fewer side effects -salivation, Gl disturbances, bradycardia- than neostigmine) antidote to nondepolarizing blockade caused by muscle relaxants during surgery. 

Ephedrine, given im/iv/sc, is indicated for the treatment of acute hypotensive states, treatment of Adams-Stokes syndrome with complete heart block, stimulation of the central nervous system (CNS) to combat narcolepsy and depressive states, treatment of acute bronchospasm, treatment of enuresis, and treatment of myasthenia gravis. When given in nasal form, ephedrine is used in the treatment of nasal congestion, promotion of nasal or sinus drainage, or relief of eustachian tube congestion. 

Which ONE of the following drugs would be useful in the long-term treatment of myasthenia gravis ... 

Contrary to the need for periphery-selective drugs that avoid the brain for the treatment of myasthenia gravis, AD treatment demands carbamates which easily penetrate the blood-brain barrier. Moreover, since any activity in the periphery will cause undesirable side effects , it is preferable to develop and use a CNS-selective drug. Since physostigmine had already been shown to be of value in AD patients, it is only natural that the new carbamates were modeled on its structure. 

The pharmacologic treatment of myasthenia gravis is based on increasing the amount of available acetylcholine by use of oral cholinesterase inhibitors such as neostigmine or pyridostigmine. Pyridostigmine bromide (Mestinon) is used most often and effectively relieves myasthenic symptoms in small muscles innervated by cranial nerves, particularly those involved in ptosis. 

The methylsulfate salt is used posloperativcly as a urinary stimulant and in (he diagnosis and treatment of myasthenia gravis. 

Following skin contact with large amounts of liquid, the dermal effects may be delayed up to 30 min. Long-term exposure to an OP, diisopropyl phos-phorofluoridate, used in the treatment of myasthenia gravis, caused side effects including nightmares, confusion, and hallucinations. 

Pyridostigmine is a carbamate that is used in the treatment of myasthenia gravis, a neuromuscular disease. It can also be used as a method of protection against nerve agent poisoning. Carbamates can occupy the catalytic site of acetylcholinesterase (AchE), which temporarily prevents phosphorylation. 

Indications Post-operative urinary retention. Post operative ileus and intestinal atony. Adjunct in the treatment of Myasthenia gravis. 

Physostigmine has limited medicinal use since it has serious side-effects, and as a result it has only been used in the treatment of glaucoma. However, simpler analogues have been made and have been used in the treatment of myasthenia gravis and as an antidote to curare. These analogues retain the important features mentioned above. Miotine (Fig. 11.51) still has the necessary carbamate, aromatic, and tertiary... 

The therapeutic use is (like pilocarpine) to decrease the intraocular pressure in the eye in glaucoma. Furthermore, intestinal peristalsis is stimulated and physostigmine is used to remove intestinal atonia after operations. The effect of physostigmine on striated muscles is also important. As an acetylcholine inhibitor physostigmine (and synthetic analogues) is used in the treatment of myasthenia gravis and as an antidote in the case of overdosage of tubocurarine used as a muscle relaxant in complete anaesthesia. 

Ambenonium, a cholinesterase inhibitor (5 to 25 mg p.o. t.i.d.), is indicated in the symptomatic treatment of myasthenia gravis. Ambenonium results in accumulation of acetylcholine-stimulating cholinergic receptors at the myoneural junction (see Figure 12). 

Edrophonium is an anticholinesterase muscle stimulant that facihtates myoneural junction impulse transmission by inhibiting acetylcholine destmction by cholinesterase. It is indicated in differential diagnosis of myasthenia gravis as an adjunct in evaluating treatment of myasthenia gravis in evaluation of aner-gency treatment of myasthenic aises in reversal of neuromuscular blockade by curare gallamine or tubo-curarine and in treatment of respiratory depression caused by curare overdose. 

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