Pharmacologic Therapy PDF

10/24/23, 3:20 PM Realizeit for Student Pharmacologic Therapy Antiparkinsonian medications act by increasing striatal dopaminergic activity; reducing the excessive influence of excitatory cholinergic neurons on the extrapyramidal tract, thereby restoring a balance between dopaminergic and choliner...

10/24/23, 3:20 PM Realizeit for Student Pharmacologic Therapy Antiparkinsonian medications act by increasing striatal dopaminergic activity; reducing the excessive influence of excitatory cholinergic neurons on the extrapyramidal tract, thereby restoring a balance between dopaminergic and cholinergic activities; or acting on neurotransmitter pathways other than the dopaminergic pathway. Levodopa is the most effective agent and the mainstay of treatment. Levodopa is converted to dopamine in the basal ganglia, producing symptom relief. Carbidopa is often added to levodopa to avoid metabolism of levodopa before it can reach the brain. The beneficial effects of levodopa therapy are most pronounced in the first year or two of treatment. Benefits begin to wane and adverse effects become more severe over time (Hickey & Strayer, 2020). Within 5 to 10 years, most patients develop a response to the medication characterized by dyskinesia including facial grimacing, rhythmic jerking movements of the hands, head bobbing, chewing and smacking movements, and involuntary movements of the trunk and extremities. The patient may experience an on–off syndrome in which sudden periods of near immobility (“off effect”) are followed by a sudden return of effectiveness of the medication (“on effect”). Changing the drug dosing regimen or switching to other drugs may be helpful in minimizing the on–off syndrome. Other potential adverse effects include nausea, vomiting, appetite loss, decreased BP, dystonia, dyskinesia, and confusion (Comerford & Durkin, 2020). To minimize adverse effects of levodopa over time, current practice includes delaying use of levodopa-containing drugs as long as possible, with the use of other drugs for symptom control in the interim. Table 65-1 provides a summary of select medications used in PD. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2… 1/39 10/24/23, 3:20 PM Realizeit for Student https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2… 2/39 10/24/23, 3:20 PM Realizeit for Student Overview of Parkinson's Disease QSEN Alert: Evidence-Based Practice As stated above, the development of dementia in patients with Parkinson's disease is not uncommon. Memantine is an N-methyl-d-aspartate antagonist that is used to slow the progression of moderate to severe Alzheimer's disease. The goal of the study was to determine if memantine resulted in improved patient-reported outcomes and health-related quality of life in Parkinson's patients who experienced dementia. At the end of the 22-week study, memantine improved individually set goals and lessened the burden on caregivers compared to the participants who were administered a placebo. Drug Therapy Drugs used in Parkinson’s disease include dopamine receptor agonists , which help correct the neurotransmitter imbalance by increasing levels of dopamine, and catechol-O-methyltransferase (COMT) inhibitors , which inhibit the metabolism of levodopa in the periphery. See Table 48.1 . (The older belladonna alkaloids and the newer centrally acting anticholinergic agents inhibit the actions of acetylcholine in the brain). Dopamine Receptor Agonists Levodopa (l-dopa), the original prototype dopamine receptor antagonist, was developed in the 1960s. It is routinely administered with the drug carbidopa; therefore, the combination medication is discussed as the prototype. Levodopa–carbidopa (Sinemet, Duopa, Rytary) is well established as the most effective drug for the symptomatic treatment of idiopathic Parkinson’s disease. (Carbidopa is used only in conjunction with levodopa.) The combination is particularly effective for the management of akinetic symptoms. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2… 3/39 10/24/23, 3:20 PM Realizeit for Student Pharmacokinetics In peripheral tissues (e.g., gastrointestinal [GI] tract, liver), levodopa is metabolized extensively by the enzyme aromatic amino acid decarboxylase (AADC) and to a lesser extent by COMT. Because most levodopa is metabolized in peripheral tissues, large doses are required to obtain therapeutic levels of dopamine in the brain. These large amounts increase adverse drug effects. To reduce levodopa dosage and decrease adverse effects, carbidopa, an AADC inhibitor, is given to decrease the peripheral metabolism of levodopa. The combination of levodopa and carbidopa greatly increases the amount of available levodopa, so that levodopa dosage can be reduced by approximately 70%. When carbidopa inhibits the decarboxylase pathway of levodopa metabolism, the COMT pathway becomes more important (see COMT Inhibitors for a discussion of entacapone and tolcapone). Levodopa is well absorbed from the small intestine after oral administration, reaches peak serum levels within 30 to 90 minutes, and has a short serum half-life (1–3 hours). Absorption is decreased by delayed gastric emptying, hyperacidity of gastric secretions, and competition with amino acids (from digestion of protein foods) for sites of absorption in the small intestine. Pyridoxine (vitamin B6) promotes the breakdown of levodopa, reducing its effectiveness. Levodopa is metabolized to 30 or more metabolites, some of which are pharmacologically active and probably contribute to drug toxicity; the metabolites are excreted primarily in the urine, usually within 24 hours. Action Dopaminergic drugs increase the amount of dopamine in the brain by various mechanisms (Fig. 48.1). If levodopa is administered alone, large doses must be taken to produce therapeutic effects. Carbidopa combined with levodopa prevents the decarboxylation of the levodopa, which makes levodopa more available for transportation to the brain. Levodopa is the metabolic precursor of dopamine, and after levodopa crosses the blood–brain barrier, it converts to dopamine in the brain. This is thought to be the mechanism whereby the drug relieves symptoms of Parkinson’s disease. Carbidopa does not cross the blood–brain barrier and does not affect levodopa metabolism. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2… 4/39 10/24/23, 3:20 PM Realizeit for Student Figure 48-1 Mechanisms by which dopaminergic drugs increase dopamine in the brain. AADC, amino acid decarboxylase; COMT, catechol-O-methyltransferase; MAO-B, monoamine oxidase B. Use Levodopa–carbidopa is a treatment of idiopathic Parkinson’s disease, postencephalitic and arteriosclerotic parkinsonism, and parkinsonism related to carbon dioxide and manganese intoxication. Prescribers may also order levodopa to reduce the symptoms of restless legs syndrome (RLS). People with RLS, also known as Ekbom’s syndrome, experience paresthesias of the muscles, particularly in the calf and thighs, creating the urge to move. Movement relieves the paresthesia, which returns when the person is at rest or trying to sleep. The disorder may result in insomnia, mental distress, and, in some cases, suicide. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2… 5/39 10/24/23, 3:20 PM Realizeit for Student Levodopa and carbidopa are usually given together in a fixed-dose formulation called Sinemet. Table 48.2 gives the doses of this combination and other dopamine receptor agonists used to treat Parkinson’s disease. Table 48-2 DRUGS AT A GLANCE: Dopamine Receptor Agonists https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2… 6/39 10/24/23, 3:20 PM Realizeit for Student https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2… 7/39 10/24/23, 3:20 PM Realizeit for Student Use in Children Safety and effectiveness for use in children have not been established for most antiparkinson drugs. Parkinsonism is a degenerative disorder of adults, and antiparkinson drugs are most likely to be used in children for other purposes, such as the stimulation of growth hormone in children with Down's syndrome. Use in Older Adults It may be necessary to reduce dosages of levodopa–carbidopa because of an age-related decrease in peripheral AADC, the enzyme that carbidopa inhibits. The risk of hallucinations is increased in older patients who take dopamine agonist drugs. Use in Patients With Renal Impairment Caution is necessary with the use of levodopa–carbidopa in patients with renal failure. Dosage adjustments are required. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2… 8/39 10/24/23, 3:20 PM Realizeit for Student Use in Patients With Hepatic Impairment With levodopa, cautious use in patients with hepatic impairment is warranted, and dosage reduction may be necessary. Reduced dosages are indicated with severe hepatic impairment. It is important to monitor liver transaminase enzymes frequently to assess for liver impairment. At the earliest sign of hepatotoxicity, drug withdrawal is essential, and there should be no reinstatement. Use in Patients With Critical Illness Caution is necessary with the use of levodopa in patients with severe neurologic, cardiac, or hepatic injuries. Dosage adjustment to the lowest level required for therapeutic effects is essential. Use in Patients Receiving Home Care The home care nurse can help patients and caregivers understand that the purpose of drug therapy is to control symptoms and that noticeable improvement may not occur for several weeks. Also, the nurse can encourage patients to consult physical therapists, speech therapists, and dietitians to help maintain their ability to perform activities of daily living. In addition, teaching about preventing or managing adverse drug effects may be necessary. Caregivers may need to be informed that most activities (e.g., eating, dressing) take longer and require considerable effort by patients with parkinsonism. Adverse Effects Because of the adverse effects and recurrence of parkinsonism symptoms after a few years of levodopa therapy, levodopa is usually reserved for patients with significant symptoms and functional disabilities. The most common CNS adverse effects are headache and anxiety. Older patients may experience problems such as hallucinations, dementia, and drowsiness. The most severe adverse effect is depression with suicidal tendencies. Cardiovascular adverse effects include ectopic beats, tachycardia, anginal pain, palpitations, hypotension, vasoconstriction, dyspnea, bradycardia, and a widened QRS. The medication can cause orthostatic hypotension. This effect is common during the first few weeks but usually subsides. Concurrent administration of nonselective monoamine oxidase (MAO) inhibitors (used in the treatment of depression) and levodopa can result in extreme elevations in blood pressure or hypertensive crisis . (MAO exists in two types, MAO-A and MAO-B, both of which are found in the CNS and peripheral tissues.) In addition, some patients report anorexia, bruxism, and nausea and vomiting. Other less common adverse effects are piloerection, azotemia, and gangrene with prolonged use. Dermatologic effects such as hypersensitivity, anaphylaxis, and urticaria occur less frequently. Contraindications https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%2… 9/39 10/24/23, 3:20 PM Realizeit for Student Contraindications to the use of levodopa–carbidopa include a known hypersensitivity to the drug. The drug can dilate pupils and raise intraocular pressure; thus, narrow-angle glaucoma is also a contraindication. Levodopa may activate malignant melanoma; people with suspicious skin lesions or a history of melanoma should not take it. To avoid the severe hypertension that may occur with concurrent use of some MAO inhibitors and levodopa, it is essential that MAO inhibitors be discontinued 14 days prior to beginning levodopa therapy. In addition, use of levodopa warrants caution in patients with severe cardiovascular, pulmonary, renal, hepatic, or endocrine disorders; depression; and peptic ulcer disease. Nursing Implications Preventing Interactions The administration of levodopa–carbidopa with an MAO inhibitor can precipitate a hypertensive crisis. Postural hypotension occurs with the administration of tricyclic antidepressants and levodopa– carbidopa. Methyldopa combined with levodopa increases CNS effects. Dysrhythmic effects are increased when combined with halogenated general anesthetics. Several drugs interact with levodopa– carbidopa, increasing or decreasing its effects ( Box 48.1 ). A high-protein meal increases the effects of levodopa–carbidopa, and kava decreases the effects of the drug. BOX 48.1 Drug Interactions: Levodopa–Carbidopa Drugs That Increase the Effects of Levodopa–Carbidopa Monoamine oxidase inhibitors Increase the risk of hypertensive crisis Drugs That Decrease the Effect of Levodopa–Carbidopa Anticholinergics Increase anticholinergic effects by delaying gastric emptying Pyridoxine (vitamin B6) Stimulates decarboxylase, the enzyme that converts levodopa to dopamine, causing metabolism in the peripheral tissues and decreasing medication distribution to the central nervous system Phenytoin, papaverine, tricyclic antidepressants, and benzodiazepines Decrease drug efficacy Administering the Medication The nurse ensures that: Levodopa–carbidopa is administered with or just after food or following a meal to reduce nausea and vomiting. Sinemet CR is not crushed. Levodopa is not given with iron preparations or multivitamin– mineral preparations that contain iron. Levodopa–carbidopa is not administered with a high-protein diet. Adequate hydration is also necessary. In addition, the nurse should ensure a temperature-controlled environment; this prevents hyperpyrexia. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 10/39 10/24/23, 3:20 PM Realizeit for Student QSEN Alert: Patient-Centered Care When administering levodopa, carbidopa, and other medications for Parkinson’s disease, it is important that medications be given to the patient on time. Timing of medication administration is critical for optimal therapeutic effect. Assessing for Therapeutic Effects With levodopa and other dopaminergic agents, the nurse observes for improvement in mobility, balance, posture, gait, speech, handwriting, and self-care ability. Elimination of drooling and seborrhea may occur. Mood elevation may result. After 2 to 5 years, the medication may lose its overall effectiveness, and the dosage may need to be increased. The nurse needs to be aware of symptoms such as ataxic gait, tremors of the hands and fingers, drooling, and masklike facial expressions. Assessing for Adverse Effects The nurse assesses for anorexia, nausea, and vomiting. These symptoms usually disappear after a few months of levodopa–carbidopa therapy. As previously stated, giving the drug with food minimizes these effects. The nurse also assesses the patient’s blood pressure in the sitting and standing positions to identify signs of orthostatic hypotension. This effect, too, commonly dissipates a few weeks after beginning therapy. Levodopa and its metabolites stimulate beta-adrenergic receptors in the heart. Patients with preexisting coronary artery disease may take propranolol (Inderal) to counteract cardiac dysrhythmia effects. It is necessary to assess the patient for dyskinesia. The involuntary movements of the tongue, mouth, and face are common adverse effects. Decreasing the dose of the medication decreases dyskinesia. Patient Teaching Box 48.2 identifies patient teaching guidelines for levodopa–carbidopa. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 11/39 10/24/23, 3:20 PM Realizeit for Student BOX 48.2 Patient Teaching Guidelines for Levodopa–Carbidopa Take the medication as prescribed. Do not crush the sustained-release preparation. Do not take multivitamin preparations containing pyridoxine. Understand that there are adverse effects of medication such as drowsiness, dizziness, and orthostatic hypotension. Change positions slowly to prevent drop in blood pressure. Avoid alcohol. Take the medication with food to prevent nausea and vomiting. Do not take the medication with a high-protein meal. Report fainting, light-headedness, irregular heart rate, uncontrolled facial movements, urinary retention, nausea, and vomiting to the prescriber. Notify the prescriber of any increase in symptoms such as static gait, altered mobility, and “pill rolling.” Other Drugs in the Class Amantadine hydrochloride is an antiparkinson and antiviral agent (see Chap. 23). It increases the dopamine release in the nigrostriatal pathway of patients with Parkinson’s disease. It is absorbed in the GI tract with an onset of action of 36 to 48 hours, a peak of action of 1.5 to 8 hours, and a half-life of 10 to 25 hours. It crosses the placenta and enters the breast milk. It is excreted unchanged in the urine. The most common adverse effects of amantadine are dizziness, light-headedness, and insomnia. The nurse instructs the patient to report swelling of the fingers or ankles, difficulty walking, urinary retention, tremors, slurred speech, or thoughts of suicide to the health care provider. It is important not to discontinue this drug abruptly. Apomorphine hydrochloride (Apokyn) is an antiparkinson agent administered for “ off time ,” or “off” episodes, of Parkinson’s disease—to assist in diminishing the symptoms of hypomobility. “Off time” is the period when the medication is not adequately controlling the patient’s symptoms. Patients who suffer from “off time” episodes have advanced Parkinson’s disease. Administration is subcutaneous. Doses are incremental, generally ranging from 20 to 40 mg. The most common dosage is 30 mg, or 0.3 mL, and the maximum dosage is 60 mg. The patient’s blood pressure must be monitored for hypertensive crisis during the administration. When apomorphine is administered to patients with a known cardiac history, periodic electrocardiogram results should be monitored as well as serum electrolytes. Bromocriptine mesylate (Parlodel, Cycloset) is an ergot derivative that directly stimulates dopamine receptors in the brain. It is used in the treatment of idiopathic Parkinson’s disease, with levodopa– carbidopa, to prolong effectiveness and to allow reduced dosage of levodopa. Administration to patients with a history of myocardial infarction with residual dysrhythmia requires caution. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 12/39 10/24/23, 3:20 PM Realizeit for Student Inbrija is an orally inhaled levodopa inhalation powder and a dopamine precursor. In December 2018, the U.S. Food and Drug Administration (FDA) approved Inbrija for the intermittent treatment of OFF episodes in patients with Parkinson’s disease, already treated with carbidopa/levodopa. OFF episodes in Parkinsonism are noted when levodopa’s effect wears off before the next dose. Inbrija must be used concurrently with carbidopa/levodopa. OFF episodes occur in Parkinson’s disease because the GI system may become delayed in the absorption of levodopa, and levels will be altered. The advantage of Inbrija is the systemic pulmonary route, which enables its effect to control parkinsonism to be more consistent than that of levodopa. Clinical trials revealed a 10-minute onset of action with an 84-mg dose of Inbrija and improvement in motor function within 30 minutes. The drug comes in a capsule form, to be administered only through the Inbrija inhaler, which comes with the medication. Each capsule dose is 42 mg; the inhaler holds one capsule at a time. Once the capsule has been placed in the haler, replace the mouthpiece, breath out, close lips around the inhaler, and take a deep, comfortable breath and you will hear the capsule spin inside the inhaler. Remove the inhaler, and take a deep breath and hold it for 5 seconds. Remove and discard the capsule. Repeat with a second capsule. Capsules should never be swallowed. The approved daily dose is 84 mg up to five times daily as needed for OFF period symptoms in Parkinson’s disease. The maximum daily dose is 420 mg. Adverse reactions include cough, low blood pressure, chest discomfort, headache, hallucinations, nausea/vomiting, decreased red blood cell count, and sputum discoloration. Concerns related to adverse effects include hallucinations, thinking/behavioral changes, CNS depression, dyskinesias, and neuroleptic malignant syndrome. Oral administration of levodopa crosses the placenta and is present in the breast milk. The manufacturer of Inbrija advises caution to patients when considering breastfeeding and the risk of infant exposure. Pramipexole (Mirapex, Mirapex ER) and ropinirole (Requip, Requip XL) stimulate dopamine receptors in the brain. The U.S. FDA has approved their use in both early and late stages of Parkinson’s disease. In early stages, one of these drugs can be used alone to improve motor performance, improve ability to participate in usual activities of daily living, and delay levodopa therapy. In advanced stages, one of these drugs can be used with levodopa and perhaps other antiparkinson drugs to provide more consistent relief of symptoms between doses of levodopa and allow reduced dosage of levodopa. These drugs, which are not ergot derivatives, may not cause some adverse effects associated with bromocriptine (e.g., pulmonary and peritoneal fibrosis, constriction of coronary arteries). Pramipexole is rapidly absorbed with oral administration. Peak serum levels are reached in 1 to 3 hours after a dose and steady-state concentrations in about 2 days. The drug is less than 20% bound to plasma proteins and has an elimination half-life of 8 to 12 hours. Most of the drug is excreted unchanged in the urine; only 10% is metabolized. As a result, renal failure may cause higher-than-usual plasma levels and possible toxicity. However, hepatic disease is unlikely to alter drug effects. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 13/39 10/24/23, 3:20 PM Realizeit for Student Rasagiline (Azilect) is an irreversible MAO inhibitor. It is indicated for initial treatment for idiopathic parkinsonism and as an adjunct therapy with levodopa to reduce “off time” when movements are poorly controlled. Because it has not been determined to be selective for MAO-B in humans, care must be taken to avoid tyramine-containing foods as well as sympathomimetic medications to prevent hypertensive crisis. In addition, rasagiline has the potential to increase serotonin neurotransmission. When given with other drugs that enhance stimulation of serotonergic receptors (e.g., antidepressants, St. John’s wort, dextromethorphan, and meperidine), serotonin syndrome, a potential fatal CNS toxicity reaction characterized by hyperpyrexia and death, can occur. Rasagiline should be discontinued at least 14 days before beginning treatment with most antidepressants or other MAO inhibitors. Fluoxetine should be discontinued at least 5 weeks before initiating rasagiline, due to its long half-life. Rasagiline is well absorbed orally, metabolized in the liver, and excreted primarily by the kidney. It is contraindicated with foods containing tyramine or sympathomimetic amine–containing medications (e.g., nonprescription cold preparations and anesthetics) because of the risk of hypertensive crisis and with antidepressants (e.g., tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, mirtazapine), meperidine, and dextromethorphan because of the potential for inducing serotonin syndrome. Ropinirole (Requip, Requip XL) is also well absorbed with oral administration. It reaches peak serum levels in 1 to 2 hours and steady-state concentrations within 2 days. It is 40% bound to plasma proteins and has an elimination half-life of 6 hours. It is metabolized by the cytochrome P450 enzymes in the liver to inactive metabolites, which are excreted through the kidneys. Less than 10% of ropinirole is excreted unchanged in the urine. Thus, hepatic failure may decrease metabolism, allow drug accumulation, and increase adverse effects. Renal failure does not appear to alter drug effects. Rotigotine (Neupro) is an antiparkinson agent that is a dopamine agonist. It is a transdermal patch in which the mechanism of action is unknown. When starting the medication, the patient should be aware that decreases in blood pressure can place the patient at risk for falls. Instruct to cautiously change positions due to orthostatic hypotension. Safinamide (Xadago) is a monoamine type B inhibitor that blocks the catabolism of dopamine, to increase the dopamine level and dopaminergic activity in the brain. It is administered as an adjunctive therapy with levodopa to increase motor function. It is important to monitor blood pressure with the administration of safinamide. Selegiline (Emsam, Zelapar) inhibits the metabolism of dopamine by MAO, which exists in two types (as previously stated). These types are differentiated by their relative specificities for individual catecholamines. MAO-A acts more specifically on tyramine, norepinephrine, epinephrine, and serotonin. This enzyme is the main subtype in GI mucosa and in the liver and is responsible for metabolizing dietary tyramine. If MAO-A is inhibited in the intestine, tyramine in various foods is absorbed systemically rather than deactivated. As a result, there is excessive stimulation of the sympathetic nervous system, and https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 14/39 10/24/23, 3:20 PM Realizeit for Student severe hypertension and stroke can occur. This is sometimes called the “cheese reaction” because aged cheeses are high in tyramine. This life-threatening reaction can also occur with some medications (e.g., sympathomimetics) that are normally metabolized by MAO. MAO-B metabolizes dopamine; in the brain, most MAO activity is due to type B. At oral dosages of 10 mg/day or less, selegiline inhibits MAO-B selectively and is unlikely to cause severe hypertension and stroke. However, at dosages greater than 10 mg/day, selectivity is lost and metabolism of both MAO-A and MAO-B is inhibited. Dosages greater than 10 mg/day should be avoided in patients with Parkinson’s disease. Selegiline inhibition of MAO-B is irreversible, and drug effects persist until more MAO is synthesized in the brain, which may take several months. In early Parkinson’s disease, selegiline may be effective as monotherapy (level A). In advanced disease, prescribers order the drug to enhance the effects of levodopa. Its addition aids symptom control and allows the dosage of levodopa–carbidopa to be reduced. Once proposed to have neuroprotective properties, authorities now believe that there is insufficient evidence to recommend the use of selegiline to confer neuroprotection in patients with Parkinson’s disease (level U). Catechol-O-Methyltransferase Inhibitors Tolcapone (Tasmar) is the prototype COMT inhibitor. COMT plays a role in brain metabolism of dopamine and metabolizes approximately 10% of peripheral levodopa. By inhibiting COMT, tolcapone increases levels of dopamine in the brain and relieves symptoms more effectively and consistently. Pharmacokinetics Tolcapone is absorbed rapidly and is highly protein bound. It is metabolized in the liver and possesses a 2- to 3-hour half-life. It crosses the placenta and enters the breast milk. It is excreted in the feces and urine. Action The main mechanism of action of tolcapone seems to be inhibiting the metabolism of levodopa in the bloodstream, thus increasing the plasma concentration and duration of action of the drug. It may also inhibit COMT in the brain and prolong the activity of dopamine at the synapse. Use https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 15/39 10/24/23, 3:20 PM Realizeit for Student Tolcapone is useful for the treatment of signs and symptoms of idiopathic Parkinson's disease. Administration is only in conjunction with levodopa–carbidopa, and a reduction in levodopa dosage is required. If a patient does not show a clinical benefit within 3 weeks of starting treatment, discontinuation of tolcapone is necessary. Use in Older Adults When administering tolcapone to geriatric patients, it is important to reduce the dosage and adjust it slowly to prevent adverse effects. Use in Patients With Renal Impairment Caution is warranted in administration of tolcapone to patients with renal impairment because it is excreted in the urine. Use in Patients With Hepatic Impairment If liver values are greater than two times the upper limit of normal, discontinuation of tolcapone is necessary. Patients with moderate to severe hepatic impairment should not take tolcapone at doses exceeding 100 mg three times per day. The FDA has issued a BLACK BOX WARNING stating that patients who take tolcapone risk potentially fatal acute fulminant liver failure. It is important to monitor liver function tests before therapy begins and every 2 weeks thereafter. Adverse Effects Tolcapone produces adverse effects in several major body systems, including the CNS, cardiovascular system, dermatologic system, GI system, and respiratory system. The most severe adverse effect is fulminant liver failure, which may be fatal. CNS adverse effects include disorientation, confusion, hallucinations, and psychosis. Dry mouth, dizziness, and orthostatic hypotension may also occur. Contraindications Contraindications to tolcapone include a hypersensitivity to the drug. Other contraindications are liver disease, nontraumatic rhabdomyolysis, hyperpyrexia, and confusion. Caution is warranted with hypertension, hypotension, and renal impairment. Nursing Implications Preventing Interactions It is essential that tolcapone and other COMT medications not be administered with MAO inhibitors due to the risk of hypertensive crisis. Administering the Medication It is necessary to administer tolcapone in conjunction with levodopa–carbidopa and to monitor the patient's response to the medication. The addition of the drug may require a decrease in the levodopa dosage. Abrupt withdrawal of tolcapone can lead to serious complications. Tapering over 2 weeks is https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 16/39 10/24/23, 3:20 PM Realizeit for Student necessary to prevent adverse effects. Assessing for Therapeutic Effects The decrease or absence of symptoms of Parkinson's disease such as improved gait and mobility, diminished tremors, and rigidity is indicative of tolcapone's therapeutic effectiveness. Assessing for Adverse Effects The nurse assesses for disorientation and confusion, light-headedness, and orthostatic hypotension. It is necessary to take blood pressure lying down, sitting, and standing up. Frequent monitoring of liver enzymes is essential. Patient Teaching Box 48.3 presents patient teaching guidelines for tolcapone. BOX 48.3 Patient Teaching Guidelines for Tolcapone Take the medication exactly as prescribed. Do not stop the medication abruptly; taper it over 2 weeks. Take the medication in conjunction with levodopa–carbidopa. Use barrier contraceptives while using this medication. Do not breast-feed while taking the medication. Use caution when operating machinery due to central nervous system (CNS) depression. Use hard candy to decrease dry mouth. Have liver function tests as scheduled. Avoid concurrent use of alcohol or other CNS depressants. Other Drugs in the Class Entacapone (Comtan) is well tolerated and safer than tolcapone, and thus, prescribers more commonly order entacapone. This COMT inhibitor is well absorbed after oral administration and reaches a peak plasma level in 1 hour. It is highly protein bound (98%), has a half-life of about 2.5 hours, and is metabolized in the liver to an inactive metabolite. The dosage must be reduced by 50% in the presence of impaired liver function. The parent drug and metabolite are 90% excreted through the biliary tract and feces, and 10% of excretion occurs in the urine. Adverse effects include confusion, dizziness, drowsiness, hallucinations, nausea, and vomiting, which can be reduced by lowering the dose of either levodopa or entacapone. Although clinical trials report few instances of liver enzyme elevation or hemoglobin decreases, it is recommended that liver enzymes and red blood cell counts be measured periodically. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 17/39 10/24/23, 3:20 PM Realizeit for Student Catechol-O-Methyltransferase Inhibitor and Decarboxylase Inhibitor/Dopamine Precursor One antiparkinson drug is a combination of levodopa, carbidopa, and entacapone (Stalevo). Administration of Stalevo allows for greater convenience and improved Parkinson symptom management. Use of the drug combination provides the patient with the convenience of one medication. Pharmacokinetics The combination drug Stalevo has the same pharmacokinetics as those of levodopa–carbidopa and entacapone. Action Levodopa is the metabolic precursor of dopamine. Depleted in Parkinson's disease, levodopa is circulated in the plasma and crosses the blood–brain barrier, where it is converted to dopamine by the striatal enzymes. Carbidopa inhibits the peripheral plasma breakdown of levodopa by inhibiting decarboxylation, thus increasing levodopa. Entacapone is a reversible and selective inhibitor of COMT. It alters the pharmacokinetics of levodopa, allowing for more sustained levodopa serum levels and increased concentrations for absorption across the blood–brain barrier. Use Stalevo is used for the treatment of idiopathic Parkinson's disease. Use in Patients With Renal Impairment It is necessary to administer Stalevo with caution in patients with severe renal impairment. Dosage reduction to prevent further renal insufficiency may be warranted. Use in Patients With Hepatic Impairment Cautious administration of Stalevo is also necessary in patients with hepatic impairment because the medication is metabolized in the liver. Adverse Effects Stalevo may affect the GI, dermatologic, respiratory, and cardiovascular systems. GI adverse effects include diarrhea as well as nausea, vomiting, bruxism, dry mouth, and excess salivation. The development of diarrhea is indicative of drug-induced colitis, and it is necessary to discontinue Stalevo if diarrhea occurs. Somnolence has been reported in which patients fall asleep without warning. This adverse effect is linked to entacapone. Also, the risk of melanoma may increase. If dyskinesia occurs, it may be necessary to reduce the dose. As with other antiparkinson medications, hypotension is a risk, along with heart attack, stroke, and cardiovascular death. Also, there is an increased risk of cardiovascular events in patients who received Stalevo versus those who received Sinemet. However, https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 18/39 10/24/23, 3:20 PM Realizeit for Student studies show that the risk of cardiovascular events is not statistically significant, but research is continuing. In addition, postmarketing studies report that impulsivity and compulsive behaviors may occur. Contraindications Contraindications to the use of Stalevo include a known sensitivity to the levodopa, carbidopa, or entacapone. The concurrent use of MAO inhibitors, or use within 14 days, is also a contraindication. Levodopa may trigger melanoma; therefore, patients with a history of melanoma should not receive Stalevo. Also, it is important to note that ergot-derived dopamine agonists administered with Stalevo have been associated with fibrotic complications such as pleural effusion, pleural thickening, and pulmonary infiltrates. Nursing Implications Preventing Interactions The administration of catecholamines such as epinephrine, dopamine, and methyldopa enhances the action of entacapone, one of the components of Stalevo. Administering the Medication Patients whose medication regimen is being changed to Stalevo should be administered levodopa and the adjunctive entacapone. The levodopa dose should be adjusted prior to the conversion to Stalevo therapy. The dose should be individualized based on the therapeutic response. The presence of dyskinesia necessitates a dosage adjustment. The dose may be adjusted by changing the strength or adjusting the dosing intervals. Fractionated doses are not recommended, and only one tablet should be administered at each dosing interval. The maximum daily dose is eight 50-, 75-, 100-, 125-, and 150-mg tablets and only six 200-mg tablets. (Patients who take more than 600 mg/day of levodopa should not switch directly to Stalevo.) Patients should swallow the tablets whole—not crushed, broken, or chewed. Stalevo can be administered without regard to meals. To prevent fluctuation in levodopa absorption, it is necessary to distribute protein intake throughout the day. People should take iron, iron supplements, and multivitamins that contain minerals separately from Stalevo. Assessing for Therapeutic Effects The decrease or absence of Parkinson's symptoms such as muscle rigidity, excessive salivation, “pill rolling,” and tremors is indicative of Stalevo's therapeutic effectiveness. Assessing for Adverse Effects The nurse assesses the patient’s cardiovascular status, including heart rate and blood pressure, to determine alterations in cardiovascular symptoms. It is also necessary to assess for chest pain, confusion, and weakness of extremities related to cerebrovascular accident or myocardial infarction. In https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 19/39 10/24/23, 3:20 PM Realizeit for Student addition, the nurse assesses the patient’s skin for unusual skin lesions and checks the patient’s fecal elimination for drug-induced colitis. It is important to teach the family to report any statements that indicate suicidal ideations. The nurse assesses for abnormal compulsive urges. Patient Teaching Patient education for Stalevo is the same as the patient education for the drug’s individual components: levodopa, carbidopa, and entacapone. With entacapone, the nurse instructs the patient to report hallucinations and diarrhea. It is also necessary to tell the patient that his or her urine may become brownish orange. This is a normal reaction to the medication and is not harmful. In addition, the nurse tells the patient to protect against falls due to orthostatic hypotension; patients can stand up slowly. Overview of Anticholinergic Drugs Anticholinergic drugs inhibit the actions of acetylcholine in the brain and affect the parasympathetic nervous system. Most anticholinergic drugs interact with muscarinic cholinergic receptors in the brain, secretory glands, heart, and smooth muscle and are sometimes called antimuscarinic drugs . When given at high doses, a few anticholinergic drugs are also able to block nicotinic receptors in autonomic ganglia and skeletal muscles. Glycopyrrolate (Robinul) is an example of such a medication. This drug class includes belladonna alkaloids and their derivatives, such as atropine, and many synthetic substitutes. Most anticholinergic medications are either tertiary amines or quaternary amines ( Table 48.5 ). Tertiary amines are uncharged lipid-soluble molecules. Atropine and scopolamine are tertiary amines and therefore are able to cross cell membranes readily. They are well absorbed from the GI tract and conjunctiva, and they cross the blood–brain barrier. Tertiary amines are excreted in the urine. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 20/39 10/24/23, 3:20 PM Realizeit for Student https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 21/39 10/24/23, 3:20 PM Realizeit for Student Quaternary amines carry a positive charge and are lipid insoluble. Some belladonna derivatives and synthetic anticholinergics are quaternary amines. Consequently, they do not readily cross cell membranes. They are poorly absorbed from the GI tract and do not cross the blood–brain barrier. Quaternary amines are excreted largely in the feces. Clinical Use https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 22/39 10/24/23, 3:20 PM Realizeit for Student The widespread effects of anticholinergic drugs limit their clinical usefulness. Consequently, several synthetic drugs have been developed in an effort to increase the selectivity of action on particular body tissues, especially to retain the antispasmodic and antisecretory effects of atropine while eliminating its adverse effects. This effort has been less than successful—all the synthetic drugs produce atropine-like adverse effects when doses are sufficient. Some synthetic drugs are used for antispasmodic effects in GI disorders and overactive urinary bladder. Another group of synthetic drugs includes centrally active anticholinergics used in the treatment of Parkinson’s disease; these drugs balance the relative cholinergic dominance that causes the movement disorders associated with parkinsonism. Specific body systems and conditions in which anticholinergic medications are administered are listed in Table 48.6 . Drug Therapy Anticholinergic drugs act by occupying receptor sites on target organs innervated by the parasympathetic nervous system, thereby leaving fewer receptor sites free to respond to acetylcholine (Fig. 48.2 ). Parasympathetic response is absent or decreased, depending on the number of receptors https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 23/39 10/24/23, 3:20 PM Realizeit for Student blocked by anticholinergic drugs and the underlying degree of parasympathetic activity. Because cholinergic muscarinic receptors are widely distributed in the body, anticholinergic drugs produce effects in a variety of locations, including the CNS, heart, smooth muscle, glands, and the eye. Figure 48.2. Mechanism of action of anticholinergic drugs. Anticholinergic (antimuscarinic) drugs prevent acetylcholine from interacting with muscarinic receptors on target effector organs, thus blocking or decreasing a parasympathetic response in these organs. Specific effects on body tissues and organs include the following: CNS stimulation followed by depression, which may result in coma and death. This is most likely to occur with large doses of anticholinergic drugs that cross the blood–brain barrier (atropine, scopolamine, and antiparkinson agents). https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 24/39 10/24/23, 3:20 PM Realizeit for Student Decreased cardiovascular response to parasympathetic (vagal) stimulation that slows heart rate. Atropine is the anticholinergic drug most often used for its cardiovascular effects. According to the advanced cardiac life support (ACLS) protocol, atropine is the drug of choice to treat symptomatic sinus bradycardia. Low doses (less than 0.5 mg) may produce a slight and temporary decrease in heart rate; however, moderate to large doses (0.5–1 mg) increase heart rate by blocking parasympathetic vagal stimulation. Although the increase in heart rate may be therapeutic in bradycardia, it can be an adverse effect in patients with other types of heart disease because atropine increases the myocardial oxygen demand. Atropine usually has little or no effect on blood pressure. Large doses cause facial flushing because of dilation of blood vessels in the neck. Bronchodilation and decreased respiratory tract secretions. Anticholinergics block the action of acetylcholine in bronchial smooth muscle when given by inhalation. This action reduces intracellular guanosine monophosphate (GMP), a bronchoconstrictive substance. When anticholinergic drugs are given systemically, respiratory secretions decrease and may become viscous, resulting in mucous plugging of small respiratory passages. Administering the medications by inhalation decreases this effect while preserving the beneficial bronchodilation effect. Antispasmodic effects in the GI tract due to decreased muscle tone and motility. The drugs have little inhibitory effect on gastric acid secretion with usual doses and insignificant effects on pancreatic and intestinal secretions. Mydriasis and cycloplegia in the eye. Normally, anticholinergics do not change intraocular pressure, but with narrow-angle glaucoma, they may increase intraocular pressure and precipitate an episode of acute glaucoma. When the pupil is fully dilated, photophobia may be uncomfortable, and reflexes to light and accommodation may disappear. Miscellaneous effects. These include decreased secretions from salivary and sweat glands; relaxation of ureters, urinary bladder, and the detrusor muscle; and relaxation of smooth muscle in the gallbladder and bile ducts. Table 48.7 lists the various anticholinergic medications. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 25/39 10/24/23, 3:20 PM Realizeit for Student Belladonna Alkaloid and Derivatives Atropine sulfate, the prototype of the anticholinergic drugs, is a naturally occurring belladonna alkaloid that can be extracted from the belladonna plant or prepared synthetically. It is usually prepared as atropine sulfate, a salt that is very soluble in water. Atropine sulfate is also classified as a muscarinic antagonist. Pharmacokinetics https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 26/39 10/24/23, 3:20 PM Realizeit for Student Atropine is well absorbed after all forms of administration. The peak effect occurs in 0.7 to 4 minutes with intravenous (IV) preparations, 30 minutes with intramuscular (IM) preparations, 1 to 2 hours with subcutaneous preparations, and 1.5 to 4 hours with inhalation preparation. The pharmacologic effects last for about 4 hours, except for ocular effects, which last for up to 2 weeks in normal eyes. The drug is absorbed systemically when applied locally to mucous membranes. Atropine crosses the blood–brain barrier and enters the CNS, where large doses produce stimulant effects and toxic doses produce depressant effects. It is metabolized in the liver and rapidly excreted in the urine. Atropine crosses the placenta and enters the breast milk. Action Atropine competitively blocks the effects of acetylcholine at muscarinic cholinergic receptors that mediate the effects of parasympathetic postganglionic impulses. It also prevents the action of acetylcholine in the CNS. Atropine depresses the salivary and bronchial secretions, dilates the bronchi, and increases cardiac output. Large doses can decrease motility of the GI and GU tracts. In addition, it relaxes the pupil of the eye and prevents the accommodation for near vision. Use In the past, atropine was used to control the symptoms of Parkinson’s disease—to relieve tremors and decrease rigidity. The development of the centrally acting anticholinergic agents has replaced the use of atropine for Parkinson’s disease. Impaired renal or hepatic function is a contraindication to the use of atropine. The most common use of atropine is the restoration of cardiac rate and arterial pressure during anesthesia when vagal stimulation produced by intra-abdominal traction causes a decrease in pulse rate, lessening the degree of atrioventricular block when increased vagal tone is a factor. Atropine also relieves bradycardia and syncope due to hyperactive carotid sinus reflex. It also serves as an antidote for cardiac collapse with an overdose of parasympathomimetic drugs also known as cholinergic agents and cholinesterase inhibitors such as physostigmine. Also, practitioners administer atropine in the preanesthesia stage to reduce respiratory tract secretions. In addition, atropine is an antidote for mushroom poisoning (Amanita muscaria). Symptoms of muscarinic poisoning include salivation, lacrimation, visual disturbances, bronchospasm, diarrhea, bradycardia, and hypotension. Atropine prevents the poison from interacting with muscarinic receptors, thus reversing the toxic effects. Muscarinic poisoning can also occur from cholinergic agonist drugs, cholinesterase inhibitor drugs, and insecticides that contain organophosphates. Use in Children https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 27/39 10/24/23, 3:20 PM Realizeit for Student Systemic anticholinergics, including atropine, have essentially the same indications in children of all ages as in adults. Anticholinergic drugs cause the same adverse effects in children as in adults. However, the effects may be more severe in children, who are especially sensitive to these drugs. Facial flushing is common, and skin rashes may occur. In addition, the administration of atropine sulfate to children can cause hyperpyrexia or atropine fever. Use in Older Adults It is necessary to administer atropine cautiously in the geriatric population. In older adults, CNS reactions are more likely to occur. Use in Patients With Critical Illness When atropine is administered for cardiovascular symptoms, it is necessary to monitor the patient's cardiac status with an electrocardiogram. Adverse Effects Atropine sulfate may adversely affect several body systems. Cardiovascular adverse effects include bradycardia (low doses) and tachycardia (high doses). CNS adverse effects include blurred vision, mydriasis, cycloplegia, photophobia, and increased intraocular pressure. In the geriatric population, nervousness, weakness, confusion, and excitement are common. The most severe GI adverse effect is paralytic ileus. Genitourinary effects are urinary hesitancy and retention. The patient may also complain of decreased sweating, which leads to heat prostration. Overdose of atropine or other anticholinergic drugs produces the usual pharmacologic effect such as decreased secretions, increased heart rate, relaxation of the bronchial smooth muscle, and decreased GI and genitourinary tone in severe and exaggerated forms. The anticholinergic overdose syndrome is characterized by hyperthermia; hot, dry, flushed skin; dry mouth; mydriasis; delirium; tachycardia; paralytic ileus; and urinary retention. Myoclonic movements and choreoathetosis may be evident. Seizures, coma, and respiratory arrest may also occur. Treatment involves the use of activated charcoal to absorb the ingested drug. Hemodialysis, hemoperfusion, peritoneal dialysis, and repeated doses of charcoal are not effective. Physostigmine salicylate (Antilirium), an acetylcholinesterase inhibitor, is a specific antidote for overdose of anticholinergics. It is usually given intravenously at a slow rate of 1 mg/min because rapid administration may cause bradycardia, hypersalivation (with subsequent respiratory distress), and seizures. The IM/IV adult dose is 0.5 to 2 mg, IM or IV, and may be repeated every 10 to 30 minutes until a response is achieved. Additional doses may be required for life-threatening anticholinergic effects. For infants, children, and adolescents, give IM or IV at an initial dose of 0.02 mg/kg, with a maximum dose of 2 mg. The drug should be administered IV no faster than 0.5 mg/min to prevent bradycardia, respiratory distress, and seizures. The pediatric dose is warranted only for life-threatening cases. For infants, children, and adolescents, give IM or IV at an initial dose of 0.02 mg/kg, with a maximum dose of 2 mg. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 28/39 10/24/23, 3:20 PM Realizeit for Student Administer IV no faster than 0.5 mg/min to prevent bradycardia, respiratory distress, and seizures. Repeated doses may be given every 5 to 10 minutes if life-threatening dysrhythmias, convulsions, or coma occurs with anticholinergic overdose. However, the benefit of repeat dosing must be balanced against the risk of physostigmine overdose. Excessive administration of physostigmine can precipitate a cholinergic crisis, leading to seizures and dysrhythmias. Atropine is the antidote for physostigmine overdose. Diazepam or a similar drug may be given for excessive CNS stimulation (e.g., delirium, excitement) that accompanies anticholinergic toxicity. Ice bags, cooling blankets, and tepid sponge baths may help reduce fever. Artificial ventilation and cardiopulmonary resuscitative measures are used if excessive depression of the CNS causes coma and respiratory failure. Infants, children, and the elderly are especially susceptible to the toxic effects of anticholinergic drugs. Contraindications Contraindications to the use of atropine include a known hypersensitivity to anticholinergic agents. Other contraindications include glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, bronchial asthma, and bladder neck obstruction, as well as hepatic or renal disease. Nursing Implications Preventing Interactions Drugs that increase the anticholinergic effects of atropine include amantadine, antihistamines, tricyclic antidepressants, quinidine, disopyramide, and procainamide. Some herbs also increase the effectiveness of atropine ( Box 48.4 ). BOX 48.4 Herb and Dietary Interactions: Atropine Sulfate Herbs and Foods That Increase the Effects of Atropine Sulfate Aloe Cascara Senna Administering the Medication Prior to administering atropine, the nurse assesses for hypersensitivity to anticholinergic agents, glaucoma, stenosing peptic ulcer, paralytic ileus, bronchial asthma, bladder neck obstruction, and cardiac dysrhythmias. The patient should be well hydrated, and the environment should be cool to protect from hyperpyrexia. If the patient has a history of urinary retention, the patient should void before administration of the drug. https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 29/39 10/24/23, 3:20 PM Realizeit for Student Assessing for Therapeutic Effects The nurse assesses the heart rate if atropine is administered for bradycardia. In preoperative patients, the nurse assesses for diminished secretions, particularly when the drug is administered for head and neck surgery. Patients with Parkinson's disease or Parkinson-like syndromes require assessment for decreased spasticity and tremors. Assessing for Adverse Effects The nurse assesses for the following conditions, which may indicate a severe anticholinergic reaction: Changes in rate, quality, and rhythm of the heart that indicates ventricular tachycardia. Urinary retention. Bowel sounds for signs of paralytic ileus. Photophobia, mydriasis, blurred vision, and increased intraocular pressure. Dry mouth. Increased temperature. Elderly people and children are prone to hyperpyrexia due to suppression of perspiration and heat loss. . Patient Teaching Box 48.5 identifies patient teaching guidelines for atropine sulfate. BOX 48.5 Patient Teaching Guidelines for Atropine Sulfate Avoid excessive high temperatures. Drink water frequently. Rinse the mouth frequently. Maintain good dental hygiene. Use hard candy to decrease dry mouth. Void before taking the medication. Visit the ophthalmologist regularly. Notify your prescriber if fluid intake is greater or less than urine output. Notify your prescriber if you develop a fever. Notify your prescriber if weakness becomes severe. Avoid the use of machinery if visual acuity or alertness is impaired. Other Drugs in the Class Homatropine hydrobromide is a semisynthetic derivative of atropine used as eye drops to produce mydriasis and cycloplegia. Compared with atropine, homatropine may be preferable, because its ocular effects do not last as long. Ipratropium (Atrovent HFA) is an anticholinergic drug chemically related to atropine. When given as a nasal spray, it is useful in treating rhinorrhea due to allergy or the common cold. When given in inhaled or aerosol form to patients with chronic obstructive pulmonary disease (COPD), it is beneficial as a https://herzing.realizeithome.com/RealizeitApp/Student.aspx?Token=0Dn26kXyU%2f6F5gOCz4%2f2IUFUzXhwrkmByRPKGm7XOkO3V8uhfXYXOmPZGy%… 30/39 10/24/23, 3:20 PM Realizeit for Student bronchodilator. Using the respiratory route instead of the systemic route to administer anticholinergic drugs results in less thickening of respiratory secretions and therefore a reduced incidence of mucusplugged airways. Scopolamine has similar uses, adverse effects, and peripheral effects when compared with atropine but is different with regard to its central effects. When scopolamine is given parenterally, it depresses the CNS and causes amnesia, drowsiness, euphoria, relaxation, and sleep. Effects of the drug appear more quickly and disappear more readily than those of atropine. Scopolamine also is used in motion sickness. It is available as oral tablets and as a transdermal adhesive disk that is placed behind the ear. The disk (Transderm-V) protects against motion sickness for 72 hours. Tiotropium bromide (Spiriva HandiHaler, Spiriva Respimat) is administered for COPD; Spiriva HandiHaler is a dry powder in capsule form intended for oral inhalation with the HandiHaler inhalation device. Spiriva Respimat is a spray in which the Spiriva Respimat cartridge is inserted in the Spiriva Respimat inhaler. This long-acting, antimuscarinic, anticholinergic, quaternary ammonium compound inhibits M3 receptors in smooth muscle, resulting in bronchodilation. Tiotropium is indicated for daily maintenance treatment of bronchospasm associated with COPD. It is not indicated for acute episodes of bronchospasm (i.e., rescue therapy). Tiotropium is eliminated via the renal system, and patients with moderate to severe renal dysfunction should be carefully monitored for drug toxicity. No dosage adjustments are required for older patients or patients with hepatic impairment or mild renal impairment. Centrally Acting Anticholinergics Older anticholinergic drugs such as atropine are rarely used to treat Parkinson’s disease because of their undesirable peripheral effects (e.g., dry mouth, blurred vision, photophobia, constipat