10.4 Alzheimer’s Drugs

Donepezil

Donepezil, a centrally acting reversible cholinesterase inhibitor, is used primarily for treatment of mild to severe forms of AD. Centrally acting agents readily cross the blood–brain barrier. Donepezil increases ACh in the brain by preventing its breakdown. Drug absorption is unaffected by food. Peak effects occur in 3–8 hours. Metabolism occurs in the liver, resulting in the production of several pharmacologically active metabolites. Excretion is through the kidneys. An important pharmacokinetic note is that donepezil is highly protein bound (96%); therefore, it has a prolonged half-life of 70 hours. This means that it takes an estimated 15 days for the drug to reach steady state.

Galantamine

Galantamine is only used in those with mild to moderate AD. The drug is prepared by extraction from daffodil bulbs. Like donepezil, this drug is a reversible inhibitor of AChE. GI effects are greater than with donepezil but less than with oral rivastigmine (see the next section). Adverse effects are the same as for donepezil with the addition of potential life-threatening skin reactions, such as Stevens–Johnson syndrome. Clients and caregivers should stop the drug and report any signs of a skin rash to their health care provider. As with the other AChE inhibitors, benefits of the drug are modest and short-term. The drug is available in IR and ER tablets as well as an oral solution. Its half-life is 7 hours.

Rivastigmine

Rivastigmine is FDA-approved for those with mild to severe AD because it enhances cholinergic function. The manner in which it does so is not fully known. It is believed to increase the ACh concentration by reversible inhibition of its hydrolysis by cholinesterase. Additionally, rivastigmine is used in the management of mild to moderate dementia due to Parkinson’s disease. The drug is available in capsules, oral solution, and a transdermal patch. Peripheral cholinergic effects, such as nausea, vomiting, diarrhea, and anorexia, occur more frequently with this drug. Blood levels are lower when using the transdermal route; therefore, the intensity of adverse effects is decreased. The liver does not metabolize this agent, so there are no significant drug–drug interactions.

Table 10.5 lists common AChE inhibitors and typical routes and dosing for adult clients.

Adverse Effects and Contraindications

Many of the adverse effects caused by AChE inhibitors relate to the stimulation of the PSNS. GI effects are the most common, including nausea, vomiting, diarrhea, abdominal pain, increased salivation, and anorexia. These drugs can cause cardiac-suppressive effects, which can result in symptomatic bradycardia, heart block, and even cardiac arrest. They stimulate the contraction of the bladder muscle and relax the internal sphincter, which causes a sense of urinary urgency for the client. CNS cholinergic effects include miosis, blurred far vision, and difficulty seeing in dim light. Other CNS effects of headaches, dizziness, drowsiness, and possible seizures can also occur. AChE inhibitor drugs can also impair breathing in those with pulmonary disorders, such as asthma and chronic obstructive pulmonary disease (COPD), due to bronchoconstriction and increased bronchial secretions. Frequent monitoring of the breathing pattern is required. Clients with cardiac conduction disorders should be monitored carefully due to the suppressive effects on cardiac impulses.

Contraindications include peptic ulcer disease because these drugs increase the secretion of hydrochloric acid in the stomach, which can worsen the ulcer and potentially cause perforation and/or bleeding. Because of the stimulatory effect on the bladder and bowel, anyone with a bladder or bowel obstruction (mechanical or neurologic) should avoid taking these drugs to reduce the risk of rupture.

Any drugs with anticholinergic effects—such as first-generation histamine-1 receptor antagonists (H1RAs), conventional antipsychotics, and tricyclic antidepressants (TCAs)—should not be used concurrently because they will reduce or block therapeutic effects of cholinergic agonists. Other parasympathomimetics can cause a synergistic effect if used concurrently. Frequent intake of nonsteroidal anti-inflammatory drugs (NSAIDs) or glucocorticoids (steroids) can increase the risk of peptic ulcer disease. Clients taking drugs such as beta blockers (propranolol/metoprolol) or digoxin should be especially careful of significant bradycardia because they both cause negative chronotropic effects.

Table 10.6 is a drug prototype table for AChE inhibitors featuring donepezil. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.

Memantine

Memantine (Namenda, Namenda XR) is indicated for clients with moderate to severe dementia of the Alzheimer’s type. This drug has been shown to exhibit neuroprotective action (slows the neurotoxicity). Memantine is an antagonist of the NMDA receptor subtype of the glutamate receptor. The drug blocks the influx of calcium when extracellular glutamate is low but permits calcium influx when extracellular glutamate is high. When the glutamate level is low, memantine can occupy the NMDA receptor channel. During this time, the level of intracellular calcium can normalize because no further calcium entry is permitted. During an action potential, a burst of glutamate is released, displacing memantine. This causes a short period of calcium influx. Because intracellular calcium is low, normal signaling of memory and learning can occur. When glutamate moves away from the receptor, memantine reblocks the channel, which stops further calcium entry.

Memantine ER has a terminal half-life of 60–80 hours; therefore, it can be prescribed once a day. In contrast, the immediate-release form is administered at 10 mg twice daily. A target dose of 5 mg twice daily is recommended in clients with severe renal impairment. This drug is predominately excreted unchanged in the urine. The drug is available in capsule form and administered orally. Any condition or drug that raises urinary pH to 8 or more can reduce drug elimination by 80% (see drug interactions and caution in Table 10.7), which will result in the accumulation of memantine within the plasma and increase the risk of adverse effects. If a client takes too much memantine, acidifying the urine with K-Phos Neutral or ascorbic acid, for example, will help promote elimination of the drug.

Table 10.7 is a drug prototype table for NMDA receptor antagonists featuring memantine ER. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.

Nursing Implications

The nurse should do the following for clients receiving medications for AD:

• Emphasize that treatment is not a cure and will not reverse signs or symptoms and usually will only produce modest benefits.
• Obtain baseline data, such as orientation, mood/affect, and ability to carry out activities of daily living.
• Assess client’s presence of bowel sounds, urine output, muscle strength, and mental status.
• Assess blood pressure, heart rate, electrocardiogram, respiratory status, and changes in urine and bowel elimination.
• Evaluate the client’s ability to swallow with ease and speech pattern.
• Administer antiemetics to reduce nausea and vomiting.
• Monitor client’s therapeutic response to the drug, such as improved memory and mood stabilization.
• Monitor renal and liver function periodically because this can alter the metabolism and elimination of the drugs.
• Ensure that caregivers are provided additional resources to help cope with the disease of their loved one.
• Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.