CNS DRUGS.docx

[CNS DRUGS] PARKINSON DISEASE -degeneration of the neurons that supply the dopamine to the striatum **tremor at rest**, rigidity, postural instability, and **bradykinesia**. proper function of striatum requires balance between acetylcholine and dopamine. Drug therapy can help maintain functional...

[CNS DRUGS] PARKINSON DISEASE -degeneration of the neurons that supply the dopamine to the striatum **tremor at rest**, rigidity, postural instability, and **bradykinesia**. proper function of striatum requires balance between acetylcholine and dopamine. Drug therapy can help maintain functional mobility and quality of life. Initial tx for mild symptoms selegiline or rasagiline Long-term use higher risk for developing dyskinesias. "off" periods occur when the dopamine levels drop to reduce, combining dopamine with COMT inhibitors or MAO-B inhibitors will help Levodopa/Carbidopa: avoid high protein diet - Levodopa - Gradual loss or "wearing off" develops near end of dosing interval can minimize by shortening the dosing interval, giving a drug that prolongs levodopa's half-life (COMT inhibitors), or giving a direct acting dopamine agonist - MOA: increasing dopamine synthesis in the striatum. Activity of decarboxylase is enhanced by vitamin B6 (pyridoxine) - AE: n/v, dysrhythmias (B1 activation), postural hypotension increase intake of salt and water, psychosis, visual hallucinations, vivid dreams, paranoia, CNS effects - Dyskinesia can be managed in three ways: 1) reduce the dosage of levodopa, 2) add amantadine, or 3) surgery and electrical stimulation - Teach: darkens sweat and urine, activated malignant melanoma yearly skin assessment! - Interactions: - Antipsychotics, chlorpromazine, and haloperidol decrease levodopa effects - HTN crisis if administered with MAO inhibitor - w/anti-cholinergic contribute to dyskinesias and enhance responses to levodopa DOPAMINE AGONISTS 1^st^ line drugs for Tx of PD. Cause DIRECT activation of dopamine receptors. Less effective than levodopa, not dependent on enzymatic conversion to be active, do not compete w/ dietary proteins, lower incidence of response failure and less likely to cause dyskinesias. +-----------------------------------+-----------------------------------+ | Nonergot Derivatives | | +===================================+===================================+ | Pramipexole | \- used alone in early stages and | | | w/levodopa in advancing | | | | | | \- maximal benefits take several | | | weeks | | | | | | \- AE: nausea, dizziness, daytime | | | somnolence, insomnia, | | | constipation,wk, and | | | hallucinations | | | | | | \- AE w/levodopa: orthostatic | | | hypotension, dyskinesias, inc in | | | hallucinations. Rare: gambling, | | | compulsive/self-rewarding | | | behavior | +-----------------------------------+-----------------------------------+ | Ropinirole- selective for D2/3 | Same as above | | | | | | \- do not use in pregnancy | +-----------------------------------+-----------------------------------+ | Rotigotine | AE: skin reactions at site of | | | app, hyperhidrosis or excessive | | | perspiration | +-----------------------------------+-----------------------------------+ | Apomorphine- no typical opioid | \- acute tx of hypo-mobility | | effects | during of periods | | | | | | \- not for routine Parkinson's | | | management | +-----------------------------------+-----------------------------------+ | Ergot Derivatives | | | | | | These drugs are poorly tolerated | | | so limited use. | | +-----------------------------------+-----------------------------------+ | Bromocriptine | \- can be used alone or | | | w/levodopa | | | | | | \- w/levodopa can prolong | | | therapeutic responses and reduce | | | motor fluctuations, allows the | | | dosage of levodopa to be reduced, | | | and dyskinesias from levodopa may | | | be reduced | | | | | | \- AE: nausea, psychological, | | | retroperitoneal fibrosis, | | | pulmonary infiltrates, | | | Raynaud-like phenomenon, | | | erythromelalgia, and valvular | | | heart disease | +-----------------------------------+-----------------------------------+ | Cabergoline | \- off label, not FDA approved | | | | | | AE: valve regurgitation, HF, | | | pulmonary and cardiac fibrosis | | | | | | \- | +-----------------------------------+-----------------------------------+ COMT INHIBITORS **Inhibit the metabolism of levodopa in the periphery**. No direct therapeutic effects of their own. +-----------------------------------+-----------------------------------+ | Entacapone- selective | \- use w/levodopa | | irreversible | | | | \- inhibits the metabolism of | | | levodopa in the intestines and | | | peripheral tissues prolongs | | | levodopa available to the brain | | | | | | \- AE: dyskinesias, orthostatic | | | hypotension, nausea, | | | hallucinations, sleep disturb, | | | impulse control disorders | | | | | | \- s/e: n/v/d, constipation, and | | | yellow/orange urine | | | | | | Interactions: increased levels of | | | drug metabolized by the COMT | | | levodopa, methyldopa, dobutamine, | | | and isoproterenol | +===================================+===================================+ | Tolcapone | \- used only w/levodopa | | | | | | \- BBW: liver failure death | | | | | | \- tx should be limited to 3 | | | weeks and especially if | | | beneficial response is absent | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | Selegiline- selective | \- benefits decline w/in 12-24 mo | | irreversible | | | | \- BBW: antidepressants increased | | | risk of suicidal thoughts in | | | pediatric and young adults | | | monitor during first 1-2 months | | | of therapy or during dose | | | adjustments | +===================================+===================================+ | Rasagiline | AE: insomnia, orthostatic | | | hypotension, buccal mucosa | | | irritation, and HTN crisis | | | | | | \- increases risk for malignant | | | melanoma | +-----------------------------------+-----------------------------------+ | Amantadine | \- responses diminish 3-6 mo | | | | | | \- AE: confusion, anxiety, | | | blurred vision, retention, | | | drymouth. Can cause Liivedo | | | reticularis (mottled | | | discoloration) | +-----------------------------------+-----------------------------------+