THE SITUATION
A.J., a 75-year-old man with an unremarkable medical history, is seen in the clinic for evaluation of memory loss and confusion. Three years ago, his wife began to notice memory gaps and confusion when A.J. was driving around town. He would get lost only a few blocks from home. The problem has gotten steadily worse. He was diagnosed with Alzheimer’s disease after neurological tests and medical evaluation ruled out other causes for his problem. He did not want to take any drugs, but when he heard the diagnosis he became quite frightened and agreed to try medication. His wife states that she is somewhat concerned about giving him medication because he has sometimes had trouble swallowing and chokes on his food. She excitedly tells A.J.
that once he starts the medication, his memory will return and things will be normal again. A.J. is placed on rivastigmine.
Critical Thinking
What could be responsible for A.J.’s symptoms?
What modifications can be made to the prescription to ensure patient safety if A.J.
is having trouble swallowing?
What important information about the disease and the effectiveness of drug therapy needs to be discussed with A.J. and his wife? Will things return to normal?
What potential adverse effects can be anticipated with rivastigmine, and how
might these effects complicate the situation for this patient and his wife?
DISCUSSION
Alzheimer’s disease is a chronic, progressive disease that involves the loss of neurons in the cortex of the brain that are responsible for making connections between different memories. A.J. has had the problem for at least 3 years, and his loss of memory and confusion have gotten worse over that period of time. Unfortunately, there is nothing available at this time that can stop the loss of neurons or restore the function that has already been lost.
One of the problems that occur with Alzheimer’s disease is difficulty swallowing.
Swallowing is a complex CNS reflex that requires coordination of impulses, and with this disease the ability to swallow in a coordinated manner is often lost. This can lead to aspiration and pneumonia, which are often the underlying causes of death with Alzheimer’s disease. Since A.J. already has some difficulty swallowing, it would be important to look into the forms in which rivastigmine is provided. In this case the drug is available in capsule form and as an oral solution. The oral solution might be suggested because it could be much easier to swallow. As the disease progresses the drug is available as a transdermal system, which would eliminate the need to swallow the drug. The status of A.J.’s swallowing should be evaluated before starting therapy and periodically as time goes on to determine how safe the dosage form of the drug is for his particular situation.
A.J. and his wife should receive information on Alzheimer’s disease and its progression. The drugs available at this time do not reverse the memory loss and they do not cure the disease. A.J.’s wife may be encouraged to monitor A.J.’s behavior, ability to perform activities of daily living, and other significant markers of importance to them. The drug should slow the progression of the disease, and it might be helpful to monitor progress to see if the drug is being effective. She might also want to become involved in an Alzheimer’s support group or organization, which could provide valuable support, educational materials, and access to community resources. This is an overwhelming diagnosis, and it might be necessary to approach these individuals over several visits to give them both time to adjust. It is important to always include a family member and provide information in writing for later reference when providing teaching to a patient with Alzheimer’s disease.
Many of the adverse effects associated with the indirect-acting cholinergic agonists are a result of the parasympathetic stimulation caused by these drugs and may complicate A.J.’s care as his disease progresses. GI effects can include increased salivation, which may further add to his difficulty swallowing; nausea and vomiting, which could make it difficult to maintain nutrition; and cramps, diarrhea, and involuntary defecation related to the increase in GI secretions and activity, which could make toileting difficult and add to Mrs. J.’s home care burden. Cardiovascular effects can include bradycardia, heart block, and hypotension, which could lead to
dizziness and weakness and further complicate safety issues. Urinary tract effects can include a sense of urgency related to stimulation of the bladder muscles and sphincter relaxation, which could lead to incontinence as the patient becomes less responsive to normal reflexes. Miosis and blurred vision, headaches, dizziness, and drowsiness can occur, further complicating safety issues. The benefits of slowing the progression of the disease often need to be weighed against all of the potential adverse effects that can complicate care and safety.
Nursing Care Guide for A.J.: Indirect-Acting Cholinergic Agonists
Assessment: History and Examination
Assess for contraindications or cautions: Known allergies to any of components of this drug, arrhythmias, coronary artery disease, hypotension, urogenital or GI obstruction, peptic ulcer, recent GI or GU surgery, and regular use of NSAIDs, cholinergic drugs, or theophylline.
Focus the physical exam on the following:
CNS: Orientation, affect, reflexes, memory response, ability to carry out simple commands, vision
CV: Blood pressure, pulse, peripheral perfusion, electrocardiography GI: Abdominal exam
GU: Urinary output, bladder tone
Respiratory: Respirations, adventitious sounds Skin: Color, temperature, texture
Nursing Diagnoses
Decreased cardiac output related to CV effects Impaired urinary elimination related to GU effects Risk for injury related to CNS effects
Risk for diarrhea
Deficient knowledge regarding drug therapy
Planning
The patient will receive the best therapeutic effect from the drug therapy.
The patient will have limited adverse effects to the drug therapy.
The patient will have an understanding of the drug therapy, adverse effects to anticipate, and measures to relieve discomfort and improve safety.
Implementation
Ensure safe and appropriate administration of the drug; monitor the ability to swallow and the appropriateness of dosage form.
Provide comfort and safety measures (e.g., physical assistance, raising side rails on the bed); temperature control; pain relief; small, frequent meals.
Monitor cardiac status and urine output throughout drug therapy.
Provide support and reassurance to deal with side effects, discomfort, and GI effects.
Provide patient and family teaching regarding drug name, dosage, side effects, precautions, and warning signs of serious adverse effects to report.
Evaluation
Evaluate drug effects: Slowing of progression of dementia.
Monitor for adverse effects: CV effects—bradycardia, heart block, hypotension;
urinary problems; GI effects; respiratory problems.
Monitor for drug–drug interactions.
Evaluate the effectiveness of patient and teaching program and comfort and safety measures.
Patient/Family Teaching for A.J.
The drug that was ordered for you is called rivastigmine. It is called a cholinergic agonist or a parasympathetic drug because it mimics the effects of the parasympathetic nervous system. Cholinergic drugs get this name because they act at certain nerve–nerve and nerve–muscle junctions in the body that are called cholinergic sites. They use a chemical called acetylcholine to carry out their functions. The nerves in your brain that are affected by Alzheimer’s disease use acetylcholine to help you to remember things and make connections between memories. This drug will not reverse the losses of memory, but may slow the loss.
Some of the following adverse effects may occur.
Nausea, vomiting, diarrhea: It is wise to be near bathroom facilities after taking your drug. If these symptoms become too severe, consult with your health care provider.
Flushing, sweating: Staying in a cool environment and wearing lightweight clothing may help.
Increased salivation: This may increase your difficulty in swallowing.
Urgency to void: Maintaining access to a bathroom may relieve some of this discomfort.
Headache: Aspirin or another headache medication (if not contraindicated in your particular case) will help to alleviate this pain.
Changes in vision, dizziness: These might lead to falls or more confusion.
Report any of the following to your health care provider: very slow pulse, light- headedness, fainting, excessive salivation, abdominal cramping or pain, weakness or confusion, blurring of vision, further signs of dementia.
Tell any doctor, nurse, or other health care provider involved in your care that you are taking this drug.
KEY POINTS
Myasthenia gravis is an autoimmune disease characterized by antibodies to ACh receptors. This results in a loss of ACh receptors and eventual loss of response at the neuromuscular junction.
Acetylcholinesterase inhibitors are used to treat myasthenia gravis because they allow the accumulation of ACh in the synaptic cleft, prolonging stimulation of any ACh sites that remain.
Alzheimer’s disease is a progressive dementia characterized by a loss of ACh- producing neurons and ACh receptor sites in the neurocortex.
Acetylcholinesterase inhibitors that cross the blood–brain barrier are used to manage Alzheimer’s disease by increasing ACh levels in the brain and slowing the progression of the disease.
SUMMARY
Cholinergic drugs are chemicals that act at the same site as the neurotransmitter ACh, stimulating the parasympathetic nerves, some nerves in the brain, and the neuromuscular junction.
Direct-acting cholinergic drugs react with the ACh receptor sites to cause cholinergic stimulation.
Use of direct-acting cholinergic drugs is limited by the systemic effects of the drug. One drug is used to induce miosis and to treat glaucoma; one agent is available to treat neurogenic bladder and bladder atony postoperatively or postpartum, and another agent is available to increase GI secretions and relieve the dry mouth of Sjögren’s syndrome.
All indirect-acting cholinergic drugs are acetylcholinesterase inhibitors. They block acetylcholinesterase to prevent it from breaking down ACh in the synaptic cleft.
Cholinergic stimulation by acetylcholinesterase inhibitors is due to an accumulation of the ACh released from the nerve ending.
Myasthenia gravis is an autoimmune disease characterized by antibodies to the ACh receptors. This results in a loss of ACh receptors and eventual loss of response at the neuromuscular junction.
Acetylcholinesterase inhibitors are used to treat myasthenia gravis because they allow the accumulation of ACh in the synaptic cleft, prolonging stimulation of any ACh sites that remain.
Alzheimer’s disease is a progressive dementia characterized by a loss of ACh- producing neurons and ACh receptor sites in the neurocortex.
Acetylcholinesterase inhibitors that cross the blood–brain barrier are used to manage Alzheimer’s disease by increasing ACh levels in the brain and slowing the progression of the disease.
Side effects associated with the use of these drugs are related to stimulation of the parasympathetic nervous system (bradycardia, hypotension, increased GI secretions and activity, increased bladder tone, relaxation of GI and GU sphincters, bronchoconstriction, pupil constriction) and may limit the usefulness of some of these drugs.
Answers to the questions in this chapter can be found in Answers to Check Your Understanding
Questions on .
MULTIPLE CHOICE
Select the best answer to the following.
1. Indirect-acting cholinergic agents
a. react with acetylcholine receptor sites on the membranes of effector cells.
b. react chemically with acetylcholinesterase to increase acetylcholine concentrations.
c. are used to increase bladder tone and urinary excretion.
d. should be given with food to slow absorption.
2. A patient is to receive pilocarpine. The nurse understands that this drug would be most likely used to treat which of the following?
a. Myasthenia gravis b. Neurogenic bladder
c. Sjögren’s disease dry mouth d. Alzheimer’s disease
3. Myasthenia gravis is treated with indirect-acting cholinergic agents that a. lead to accumulation of acetylcholine in the synaptic cleft.
b. block the GI effects of the disease, allowing for absorption.
c. directly stimulate the remaining acetylcholine receptors.
d. can be given only by injection because of problems associated with swallowing.
4. A patient with myasthenia gravis is no longer able to swallow. Which of the following would the nurse expect the physician to order?
a. Rivastigmine b. Memantine c. Pyridostigmine d. Edrophonium
5. Alzheimer’s disease is marked by a progressive loss of memory and is associated with a. degeneration of dopamine-producing cells in the basal ganglia.
b. loss of acetylcholine-producing neurons and their target neurons in the CNS.
c. loss of acetylcholine receptor sites in the parasympathetic nervous system.
d. increased levels of acetylcholinesterase in the CNS.
6. The nurse would expect to administer donepezil to a patient with Alzheimer’s disease who
a. cannot remember family members’ names.
b. is mildly inhibited and can still follow medical dosing regimens.
c. is able to carry on normal activities of daily living.
d. has memory problems and would benefit from once-a-day dosing.
7. Adverse effects associated with the use of cholinergic drugs include a. constipation and insomnia.
b. diarrhea and urinary urgency.
c. tachycardia and hypertension.
d. dry mouth and tachycardia.
8. Nerve gas is an irreversible acetylcholinesterase inhibitor that can cause muscle paralysis and death. An antidote to such an agent is
a. atropine.
b. propranolol.
c. pralidoxime.
d. neostigmine.
Multiple Response
Select all that apply.
1. A nurse is explaining myasthenia gravis to a family. Which of the following points would be included in the explanation?
a. It is thought to be an autoimmune disease.
b. It is associated with destruction of acetylcholine receptor sites.
c. It is best treated with potent antibiotics.
d. It is a chronic and progressive muscular disease.
e. It is caused by demyelination of the nerve fiber.
f. Once diagnosed, it has a 5-year survival rate.
2. A nurse would question an order for a cholinergic drug if the patient was also taking which of the following?
a. Theophylline b. NSAIDs c. Cephalosporin d. Atropine e. Propranolol f. Memantine
BIBLIOGRAPHY AND REFERENCES
Andrews, M., & Boyle, J. (2011). Transcultural concepts in nursing care (6th ed.). Philadelphia, PA: Lippincott Williams & Wilkins.
Brunton, L., Chabner, B., & Knollman, B. (2011). Goodman and Gilman’s the pharmacological basis of therapeutics (12th ed.). New York: McGraw-Hill.
Facts and Comparisons. (2015). Drug facts and comparisons. St. Louis, MO: Author.
Iqbal, K., & Grundke-Iqbal, I. (2004). Inhibition of neurofibrillary degeneration: A promising approach to Alzheimer’s disease and other tautopathies. Current Drug Targets, 5(6), 495–501.
Kaminski, H. (2011). Myasthenia gravis and related disorders. New York: Springer Publishing.
Karch, A. M. (2014). Lippincott’s nursing drug guide. Philadelphia, PA: Lippincott Williams & Wilkins.
Medical Letter. (2015). The medical letter on drugs and therapeutics. New Rochelle, NY: Author.
Naylor, M. D., Stephen, C., Bowles, K. H., et al. (2005). Cognitively impaired older adults: From hospital to home.
American Journal of Nursing, 105, 52–61.
Porth, C. M. (2013). Pathophysiology: Concepts of altered health states (9th ed.). Philadelphia, PA: Lippincott Williams
& Wilkins.
Reisberg, B., Doody, R., Stöffler, A., et al. (2003). Memantine in moderate-to-severe Alzheimer’s disease. New England Journal of Medicine, 348, 1333–1341.
Anticholinergic Agents 33
Learning Objectives
Upon completion of this chapter, you will be able to:
1. Define anticholinergic agents.
2. Describe the therapeutic actions, indications, pharmacokinetics, contraindications and cautions, most common adverse reactions, and important drug–drug interactions of anticholinergic agents.
3. Discuss the use of anticholinergic agents across the lifespan.
4. Compare and contrast the prototype drug atropine with other anticholinergic agents.
5. Outline the nursing considerations, including important teaching points, for patients receiving anticholinergic agents.
Glossary of Key Terms
anticholinergic: drug that opposes the effects of acetylcholine at acetylcholine receptor sites
belladonna: a plant that contains atropine as an alkaloid; used to dilate the pupils as a fashion statement in the past; used in herbal medicine much as atropine is used today
cycloplegia: inability of the lens in the eye to accommodate to near vision, causing blurring and inability to see near objects
mydriasis: relaxation of the muscles around the pupil, leading to pupil dilation parasympatholytic: lysing or preventing parasympathetic effects
Drugs that are used to block the effects of acetylcholine are called anticholinergic drugs.
Because this action lyses, or blocks, the effects of the parasympathetic nervous system, they are also called parasympatholytic agents. This class of drugs was once very widely used to decrease gastrointestinal (GI) activity and secretions in the treatment of ulcers and to decrease other parasympathetic activities to allow the sympathetic system to become more dominant. Today, more specific and less systemically toxic drugs are available for many of the conditions that would benefit from these effects. Therefore, this class of drugs is less commonly used. Atropine is the only widely used anticholinergic drug. Box 33.1 discusses the use of anticholinergics across the lifespan.
BOX 33.1
Drug Therapy Across the Lifespan
Anticholinergic Agents/Parasympatholytics Children
The anticholinergic agents are often used in children. Children are often more sensitive to the adverse effects of the drugs, including constipation, urinary retention, heat intolerance, and confusion. If a child is given one of these drugs the child should be closely watched and monitored for adverse effects, and appropriate supportive measures should be instituted. Dicyclomine is not recommended for use in children.
Adults
Adults need to be made aware of the potential for adverse effects associated with the use of these drugs. They should be encouraged to void before taking the medication if urinary retention or hesitancy is a problem. They should be encouraged to drink plenty of fluids and to avoid hot temperatures because heat intolerance can occur and it will be important to maintain hydration should this happen. Safety precautions may be needed if blurred vision and dizziness occur. The patient should be urged not to drive or perform tasks that require concentration and coordination.
These drugs should not be used during pregnancy because they cross the placenta and could cause adverse effects on the fetus. If the benefit to the mother clearly outweighs the potential risk to the fetus, they should be used with caution. Nursing mothers should find another method of feeding the baby if an anticholinergic drug is needed because of the potential for serious adverse effects on the baby.
Older Adults
Older adults are more likely to experience the adverse effects associated with these drugs; dose should be reduced, and the patient should be monitored very closely.
Because older patients are more susceptible to heat intolerance owing to decreased body fluid and decreased sweating, extreme caution should be used when an anticholinergic drug is given. The patient should be urged to drink plenty of fluids and to avoid extremes of temperature on exertion in warm temperatures. The older adult is more likely to experience confusion, hallucinations, and psychotic syndromes when taking an anticholinergic drug. Safety precautions may be needed if CNS effects are severe. Older adults may also have renal impairment, making them more likely to have problems excreting these drugs. Further reduction in dose may be
needed in the older patient who also has renal dysfunction.
Anticholinergics/Parasympatholytics
Anticholinergic agents include aclidinium (Tudorza Pressair), atropine (generic), darifenacin (Enablex), dicyclomine (generic), fesoterodine (Toviaz), flavoxate (generic), glycopyrrolate (Robinul), hyoscyamine (Symax and others), ipratropium (Atrovent), meclizine (Bonine), methscopolamine (Pamine), propantheline (generic), scopolamine (Transderm Scop), solifenacin (VESIcare), tiotropium (Spiriva), toliterodine (Detrol), and trospium (Sanctura) (see Table 33.1).
Table 33.1 Drugs in Focus: Anticholinergic Agents/Parasympatholytics
COPD, chronic obstructive pulmonary disease; GI, gastrointestinal.
Therapeutic Actions and Indications
The anticholinergic drugs competitively block the acetylcholine receptors at the muscarinic cholinergic receptor sites that are responsible for mediating the effects of parasympathetic postganglionic impulses (Figure 33.1). Some are more specific to particular receptors in the respiratory, genitourinary (GU), or GI tracts, making them preferred for treating specific conditions, and others more generally depress the parasympathetic system. When the parasympathetic system is blocked the effects of the sympathetic system are more prominently seen. These drugs can be used to decrease secretions before anesthesia, to treat parkinsonism (by blocking the stimulating effects of acetylcholine), to restore cardiac rate and blood pressure after vagal stimulation during surgery, to relieve bradycardia caused by a hyperactive carotid sinus reflex, to relieve pylorospasm and hyperactive bowel, to prevent the signs and symptoms of motion sickness and vomiting, to relax biliary and ureteral colic, to relax bladder detrusor muscles and tighten sphincters, to help to control crying or laughing episodes in patients with brain injuries, to relax uterine hypertonicity, to help in the management of peptic ulcer, to control rhinorrhea associated with hay fever, as an antidote for cholinergic drugs and for poisoning by certain mushrooms, and as an ophthalmic agent to cause mydriasis or cycloplegia in acute inflammatory conditions (Table 33.1). Anticholinergic drugs also are thought to block the effects of acetylcholine in the central nervous system (CNS), which may account for their effectiveness in treating motion sickness and preventing nausea and vomiting.