Neurogenerative Disorders And Muscle Spasms And Spasticity

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Parkinson's Disease

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Degenerative disease-Loss of dopamine-containing neurons in substantia nigra. Characterized by onset of tremor, muscle rigidity, and dificulty in initiating movement. Usually occurs in elderly patients- but impurities in street drugs can cause this disease in young addicts as well.
In unaffected persons, acetylcholine and dopamine in caudate are balanced, but as dopamine cells are lost, acetylchonline effects tend to dominate therefore you can either increase dopamine efects or decrease acetylchonline effects.

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Benztropine

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Muscarinic antagonists decrease the effects of excess acetylcholine. .
Side-effects Anti-SPLUDD effects. Postural hypotension, numbness, and tachycardia.
Adverse Reactions: Confusion, glaucoma attack
Overdose: More severe then side effects.
drug interactions: Enhances sedation effects o ETOH and CNS depressants

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Ways to increase Dopamine Effects

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Increase synthesis: L-DOPA, carbidopa
Increase Release: Amantadine
Directly stimulate dopamine receptors Pergolide (dopamine agonsit), ropinirole (used in restless legg syndrome)
Decrease Degradation: MAO-B Inhibitor (Selegyline (Deprenyl), COMT Inhibitor: Tolcapone

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L-DOPA

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Crosses blood brain barrier and is convereted to dopamine in remaining cells in substantia nigra.
Side Effects: Choreiform movements, dificulty in urination, mood change, psychosis, aggressiveness, dysrhythmias, hypotension, nausea and vomiting "on/off" phenomena
Drug interactions: MAOI, antipsychotics, vitamin B6 (Pyridoxal)

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Carbidopa and L-DOPA

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Increases the amount of L-Dopa that gets into the CNS.
Allows lower L-dopa doses, and usually reduces the incidence and severity of side effects and drug interactions.

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Myasthenia Gravis

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Autoimmune disease-body produces antibodies against nicotinic receptors on muscle cells that respond to acetylcholine to cause paralysis of the muscles.
Progressive and incurable
Symptoms are muscle weakness, that is worst for repetitive tasks. Diagnosis: short-term improvement seen with the short-acting anticholinesterase edrophonium
Treatment: Thymectomy, plasmapheresis (to remove antibodies), corticosteroids (to inhibit immune response). Primary treatment is anticholinesterases. Rationale: By blocking breakdown of acetylcholine more is available to activate the remaining muscle nicotinic receptors.

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Myasthenia Gravis Treatment drugs

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Edrophonium
Side effects: SPLUDD effects,
Treatment of side effects: Atropine or other anti-muscarinics.
Contraindicated: Asthma or pregnancy

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Alzheimer's Disease:

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Incurable progressive mental impairment in elderly: characterized by plaques and tangles in brain posthumous diagnosis. Symptoms: Memory Loss, loss of logical thinking, disorientation leading to wandering behavior. Theories: Loss of cholinergic neurons in the brain. Genetic abnormality, autoimmune disease, abnormality in protein processing-amyloid.

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Rivastigmine

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Indication Alzheimer's Centrally acting anticholinesterase.
Common adverse effects: N/V, anorexia. Use caution with asthma, COPD, can cause bradycardia, incontinence. Interacts with other cholinergic drugs. Give on an empty stomach to maximize absorption, but if severe GI upset occurs, can be taken with food.

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Riluzole for ALS

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Amytrophic Lateral Sclerosis (ALS)
Progressive loss of motor neurons leading to death by suffocation. Riluzole delays the need for tracheostomy, and decreases glutamate effects in the CNS. Monitor liver function, as Riluzole can damage the liver.

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Glatiramer for Multiple Sclerosis

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Patients mount an autoimmune attack on the myelin that insulates their nerves. Glatiramer is a synthetic similar to basic myelin protein that acts as an immune modulator. Side effects: Hives, rash, chest pain, and breathing difficulties. Contraindicated:Allergy to mannitol, use caution in immunocompromised patients.

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Muscle Spasm and Spasticity

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Spasms are sudden involuntary muscle contractions while spasticity involves muscles that are continually contracted.

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Cyclobenzaprine

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Acts in the CNS to block muscle spasms. Causes sedation: Warn patients about driving and operating dangerous machines. Sudden withdrawal can cause anxiety, hallucinations, seizures, psychosis. Can interact with CNS depressants or alcohol. Anticholinergic side effects: Dry mouth and skin, difficulty urinating or defecating, anti-SPLUDD effects. Avoid for glaucoma patients.

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Centrally-Acting Spasmolytics: Baclofen

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Used to treat intractable hiccups, types of neuropathic pain, multiple sclerosis, general spasticity
Do not use to treat spasticity after stroke, cerebral palsy or Parkinson's or Huntington's Disease. Acts like transmitter GABA in CNS. Sudden withdrawal causes seiqures, agitaion, hallucination, psychoses. Causes sedation and interacts with CNS depressants

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Peripheral Spasmolytics: Dantrolene

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Used for malignant hypothermia, cerebral palsy, spinal cord injury and MS. Decreases contractions by blocking calcium release within muscles. Causes muscle weakness, not used for cerebral palsy cases where spasticity provides support to patients. Major adverse effect: Extended use can cause fatal hepatitis in women >35 taking estrogen. Can cause liver damage: watch for yellow skin and eyes, nausea, vomiting, loss of appetite. Use with lever function tests.