Chapter 23

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  Kee: Pharmacology, 8th Edition Chapter 23: Drugs for Neurologic Disorders: Parkinsonism and l!heimer s DiseaseDo#nloada$le Key Points ã Parkinsonism is a chronic neurologic disorder that affects the extrapyramidal motor tract, which controls posture, balance, and locomotion. Its three major features include rigidity,  bradykinesia (slow movement), and tremors. ã l!heimer s disease is a chronic, progressive, neurodegenerative condition with marked cognitive dysfunction. ã It is theori!ed l!heimer s disease results from neuritic pla#ues, degeneration of the cholinergic neurons, and deficiency in acetylcholine. ã $here are different types of parkinsonism. Pseudoparkinsonism fre#uently occurs as an adverse reaction to antipsychotic drugs, especially the phenothia!ines. In addition,  parkinsonism symptoms could result from poisons, arteriosclerosis, and %ilson s disease. ã &ymptoms of parkinsonism can be lessened through the use of nonpharmacologic measures such as patient teaching, exercise, nutrition, and group support. ã Parkinsonism is caused by an imbalance of the neurotransmitters dopamine (') and acetylcholine (h). It is marked by degeneration of neurons of the extrapyramidal motor tract. $he reason for the degeneration of neurons is unknown. 'rugs used to treat  parkinsonism reduce the symptoms or replace the dopamine deficit. $hese drugs fall into five categories (*) anticholinergics, (+) dopamine replacements, () dopamine agonists, (-) /01 inhibitors, and (2) /$ inhibitors. ã nticholinergic drugs reduce the rigidity and some of the tremors characteristic of  parkinsonism but have minimal effect on bradykinesia. $he anticholinergics are  parasympatholytics that inhibit the release of acetylcholine. ã $he first dopaminergic drug was levodopa3 the en!yme dopa decarboxylase converts levodopa to dopamine in the brain. 'opa decarboxylase is also found in the peripheral nervous system and allows 445 of levodopa to be converted to dopamine before it reaches the brain. ã 1ecause of the side effects of levodopa and the fact that so much levodopa is metaboli!ed before reaching the brain, an alternative drug, carbidopa, was developed to inhibit the en!yme dopa decarboxylase. 1y inhibiting the en!yme in the peripheral nervous system, more levodopa reaches the brain. ã &ide effects of carbidopa0levodopa may include nausea, vomiting, dystonic movement (involuntary abnormal movement), and psychotic behavior. ã /ther dopaminergics called dopamine agonists stimulate the dopamine receptors. ã mantadine hydrochloride acts on dopamine receptors. It may be taken alone or in combination with carbidopa0levodopa or an anticholinergic drug. ã 1romocriptine mesylate acts directly on dopamine receptors in the 6&, cardiovascular system, and 7I tract. Patients who do not tolerate carbidopa0levodopa are fre#uently given bromocriptine. ã $he en!yme monoamine oxidase01 (/01) causes catabolism of dopamine. &elegiline opyright 8 +9*2, +9*+, +994, +99:, +99, +999, *44;, *44 by &aunders, an imprint of <lsevier Inc.  'ownloadable =ey Points+0+inhibits /01, thus prolonging the action of levodopa. It decreases >on0off? fluctuations. ã @arge doses of selegiline may inhibit /0, an en!yme that promotes metabolism of tyramine in the 7I tract. If they are not metaboli!ed by /0, ingestion of foods high in tyramine can cause a hypertensive crisis. ã $he en!yme catechol0/0methyltransferase (/$) inactivates dopamine. %hen taken with a levodopa preparation, /$ inhibitors increase the amount of levodopa concentration in the brain. ã $olcapone was the first /$ inhibitor taken with levodopa for advanced parkinsonism.$his drug can affect liver cell function3 therefore, serum liver en!ymes should be closely monitored3 entacapone does not affect liver function. ã $he common side effects of anticholinergics include dry mouth and dry secretions, urinary retention, constipation, blurred vision, and an increase in heart rate. ental effects such as restlessness and confusion may occur in the older adult. ã $he side effects of carbidopa0levodopa are numerous. 7I disturbances are common  because dopamine stimulates the chemoreceptor trigger !one ($A) in the medulla, which stimulates the vomiting center. $aking the drug with food can decrease nausea and vomiting, but food slows the absorption rate. ã mantadine has few side effects, but they can intensify when the drug is combined with other antiparkinson drugs. ã &ide effects from bromocriptine are more common than from amantadine. If  bromocriptine is taken with carbidopa0levodopa, usually the drug dosages are reduced, and side effects and drug intolerance decrease. ã Pramipexole (irapex) and ropinirole (Be#uip) can cause nausea, di!!iness, somnolence,weakness, and constipation. ã %ith entacapone, the urine can be dark yellow to orange3 with tolcapone, the urine can be bright yellow. 1oth tolcapone and entacapone can intensify the adverse reactions of levodopa. ã nticholinergics are contraindicated for persons with glaucoma. Persons with severe cardiac, renal, or psychiatric health problems should avoid levodopa drugs. Patients with chronic obstructive lung diseases can have dry, thick mucous secretions caused by large doses of anticholinergic drugs. ã l!heimer s disease is an incurable dementia illness characteri!ed by chronic,  progressive neurodegenerative conditions with marked cognitive dysfunction. ã <tiology of l!heimer s is unknown. Cactors thought to influence the occurrence of l!heimer s are genetic predisposition, virus, infection, or inflammation that attacks  brain cells, as well as nutritional, environmental, and immunologic. ã &ymptoms of l!heimer s disease include memory loss, confusion, inability to communicate, aggressive behavior, depression, and psychoses. ã $here is no known cure for l!heimer s disease. C'0approved medications to treat l!heimer s disease symptoms include acetylcholinesterase (h<) inhibitors. h< inhibitors increase cognitive function for patients with mild to moderate l!heimer s disease. opyright 8 +9*2, +9*+, +994, +99:, +99, +999, *44;, *44 by &aunders, an imprint of <lsevier Inc.  'ownloadable =ey Points+0 ã Bivastigmine (<xelon), an h< inhibitor, is prescribed to improve cognitive function for patients with mild to moderate l!heimer s disease. $his drug increases the amount of h at the cholinergic synapses. Bivastigmine tends to slow the disease process. opyright 8 +9*2, +9*+, +994, +99:, +99, +999, *44;, *44 by &aunders, an imprint of <lsevier Inc.
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