The Pharmacist’s Role in the Management of Alzheimer’s Disease

Yvette C. Terrie , BSPharm, RPh

Pathophysiology

Although the exact etiology of AD still is unknown, research suggests that it can be attributed to both inherited and environmental factors. The 3 standard neuropathologic features of AD include amyloid plaques; neurofibrillary tangles; and a third factor, which has been described only in the last 3 decades—synaptic and neuronal cell death that involves a progressive or gradual loss of connections between neurons.^6,8,9 As the death of the neurons progresses and spreads through the brain, brain atrophy occurs in the affected areas.⁹ Whereas researchers have known about these features of AD for several years, they are still learning more about them and their roles in the development and progression of AD. The progression of AD often is unpredictable, and the severity varies from patient to patient.

There are 2 distinct forms of AD: (1) familial and (2) sporadic.¹⁰ Familial AD is considered very rare and typically occurs before the age of 60. It also is referred to as early-onset AD. Less than 5% of the cases are early-onset, and this form is believed to be caused by gene mutations on chromosomes 1, 14, and 21.^10,11

As for sporadic AD, genes may not be the direct cause of the disease but may influence the risk of developing it. Sporadic AD also is referred to as lateonset AD, because many cases occur in individuals after the age of 60, with the vast majority in their 70s and 80s.^10,11 There are, however, exceptions to thegeneral observations regarding age at onset.

The apolipoprotein E (apo E) gene, which is found on chromosome 19, is the best studied susceptibility gene in sporadic AD.¹⁰ The apo E gene is responsible for the manufacturing of a protein that moves cholesterol and other fats throughout the body.¹⁰ It is postulated that this protein may be involved in the structure and function of the fatty membrane that surrounds a brain cell.¹⁰ The apo E gene occurs in many forms or alleles. The 3 forms that occur most frequently are apo E-II, apo E-III, and apo EIV.^10-12 Furthermore, the apo E-IV gene may increase an individual’s chance of developing late-onset AD. It is estimated that between 35% and 50% of individuals with AD carry some form of the apo E-IV gene.¹⁰

Risk Factors

Current research indicates that AD may be triggered by several factors, including age, genetics, serious head injuries, and inflammation of the brain, as well as environmental factors. Age is the most well-documented risk factor. Other possible risk factors include the following^13-15:

• Down’s syndrome
• Head injury
• Diabetes mellitus
• Hypertension
• Hypercholesterolemia
• Hyperglycemia
• Family history
• Sedentary lifestyle
• Diets high in saturated fat

Signs and Symptoms

Recognizing the warning signs associated with the development of AD is crucial in order to initiate early intervention, as well as to differentiate AD from other forms of dementia. In many cases, an individual’s symptoms may progress gradually over time and may not be obvious initially. Patients may exhibit cognitive or intellectual symptoms, such as acalculia (inability to perform simple mathematical calculations), aphasia (inability to communicate effectively), apraxia (inability to perform daily activities such as brushing teeth or combing hair), amnesia, and agnosia (loss of the ability to interpret sensory stimuli) as the disease progresses. Behavioral signs and symptoms—such as depression, apathy, and anxiety—typically are present in the early stages, and delusions, hallucinations, and psychosis are prevalent during the latter stages.^16,17 In the advanced stages, individuals also may present with extrapyramidal symptoms, such as gait disturbance, myoclonus, tremor, and urinary incontinence.¹⁶

Potential Warning Signs

Some warning signs of AD are as follows¹⁶:

• Memory loss that may affect job performance
• Difficulty in performing routine, familiar tasks
• Difficulty or problems with speech
• Decrease in judgment skills
• Difficulty with abstract thinking
• Disorientation as to time and place
• Difficulty in finding objects or misplacing items
• Changes in mood, personality, or behavior, such as agitation, aggression, and hallucinations
• Loss of initiative or motivation
• Impaired memory or thinking
• Impaired visual or spatial skills

Stages

Because AD progresses in severity over time, the disease generally is characterized by the following stages: mild, moderate, and severe. During the mild stage, the individual may start to experience some memory loss, which may be insignificant enough that others may not notice a problem. Short-term memory usually is affected first.

As the disease progresses from mild to moderate, the signs may become more noticeable to family and friends, because the patient may exhibit difficulty in self-care and in accomplishing everyday tasks. At this stage, some behavioral changes often are noted, such as frustration, anger, and anxiety. Usually at this stage, the need for caregiver assistance may become essential for the safety of the individual.

In the severe stage of AD, individuals typically are characterized as being solely dependent on the caregiver. Some patients in this stage may experience loss of bladder and bowel control and episodes of aggression. Table 1 lists, for each stage of AD, behavioral and cognitive changes as well as how the disease may affect the individual’s daily routine.

The Role of the Pharmacist

In almost every area of pharmacy practice, pharmacists are very likely to encounter a patient with AD and/or a caregiver. Therefore, it is imperative for pharmacists to keep abreast of new developments in research and pharmacologic therapies regarding the disease.

Pharmacists can be a vital resource for both patients and their caregivers, thereby improving quality of life. A comprehensive understanding of the etiology, pathophysiology, and stages of AD, as well as pharmacologic therapy, is imperative to provide effective care to the patient.

Pharmacists can assist patients with AD through monitoring drug regimens for potential drug interactions as well as possible contraindications. More importantly, pharmacists always should try to demonstrate empathy toward patients with AD and their caregivers, keeping them informed about new developments in the fight against this condition and suggesting resources of information for them.

Caring for a patient with AD involves more than drug treatment. Caregivers should be encouraged to join a local support group and to take care of themselves and seek assistance when warranted.

During counseling, pharmacists can provide patients and their caregivers with various suggestions for techniques that may aid in the management of AD, such as the use of memory aids or schedules. Examples of memory aids include a list of daily routines, important telephone numbers in case of an emergency, and instructions on how to perform various tasks. In addition, pharmacists can make recommendations for creating a safe environment and establishing an exercise routine, if appropriate.⁴⁴

PRESENT CONTINUOUS/ELECTRICITY

 

El “Present Continuous” (Presente Continuo) lo utilizamos cuando queremos hablar de acciones que están ocurriendo “ahora” o, en un tiempo cercano a “ahora” o, que no han terminado.
Por ejemplo: Estoy comiendo (I’m eating) o, estoy leyendo un libro (I’m reading a book). En este último caso, te refieres a una acción inacabada, no a que estás leyendo el libro en el momento en que hablas.

Estructura: Sujeto + “to be” en presente + el verbo principal acabado en “ing”.

Ejemplo 1: I am (I’m) working . Yo estoy trabajando.

Ejemplo 2: She is (She’s)studying . Ella está estudiando.

Ejemplo 3. It is (It’s) working . Está funcionando.

Ejemplo 4: They are (They’re) looking . Ellos/Ellas están mirando.

Problemas que presenta el Present Continuous: En teoría es un tiempo muy sencillo de dominar. No obstante, dado que a veces en español utilizamos el “Presente” para hablar de algo que ocurre en el momento en que hablamos, en inglés cometemos el error de utilizar el “Presente” cuando deberíamos utilizar el “Present Continuous”.

Por ejemplo, decimos: “She comes” , cuando deberíamos decir: “She’s coming” . (Ella viene). Es verdad que en inglés hay algunos verbos que no se conjugan en “Present Continuous”, por ejemplo, “want”  (querer), pero son pocos.

Recuerda: Para hablar de algo que está ocurriendo en el mismo momento en el que hablas, debes utilizar en inglés el “Present Continuous”, no el tiempo “Simple Present Tense” Por ejemplo: “It’s raining now.”  (Ahora llueve). No:”It rains now.”

¿Cómo se pregunta con el “Present Continuous”?

Estructura preguntas: Verbo + sujeto + verbo principal terminado en “ing”+?

Ejemplo: Is she working?  ¿Está ella trabajando

¿Cómo se niega con el “Present Continuous?

Estructura negación: Sujeto + verbo “to be” en presente + not + verbo principal terminado en “ing”.

Ejemplo: She is not (isn´t)working . Ella no está trabajando.
Repaso de las estructuras:

Positivo	Sujeto+ Verbo”to be” en presente+VP terminado en “ing”. You are (You’re)working.
Negativo	Sujeto + Verbo “to be”en presente +not+VP terminado en“ing”. You are not (aren’t) working.
Pregunta	Verbo “to be” en presente+ Sujeto+ VP terminado en “ing”+?Are you working?

FORM[am/is/are + present participle]

Examples:

• You are watching TV.
• Are you watching TV?
• You are not watching TV.  

USE 1 Now

 Use the Present Continuous with Normal Verbs to express the idea that something is happening now, at this very moment. It can also be used to show that something is not happening now.

Examples:

• You are learning English now.
• You are not swimming now.
• Are you sleeping?
• I am sitting.
• I am not standing.
• Is he sitting or standing?
• They are reading their books.
• They are not watching television.
• What are you doing?
• Why aren’t you doing your homework?

USE 2 Longer Actions in Progress Now

 

In English, “now” can mean: this second, today, this month, this year, this century, and so on. Sometimes, we use the Present Continuous to say that we are in the process of doing a longer action which is in progress; however, we might not be doing it at this exact second.

Examples: (All of these sentences can be said while eating dinner in a restaurant.)

• I am studying to become a doctor.
• I am not studying to become a dentist.
• I am reading the book Tom Sawyer.
• I am not reading any books right now.
• Are you working on any special projects at work?
• Aren’t you teaching at the university now?

USE 3 Near Future

 

Sometimes, speakers use the Present Continuous to indicate that something will or will not happen in the near future.

Examples:

• I am meeting some friends after work.
• I am not going to the party tonight.
• Is he visiting his parents next weekend?
• Isn’t he coming with us tonight?

USE 4 Repetition and Irritation with “Always”

The Present Continuous with words such as “always” or “constantly” expresses the idea that something irritating or shocking often happens. Notice that the meaning is like Simple Present, but with negative emotion. Remember to put the words “always” or “constantly” between “be” and “verb+ing.”

Examples:

• She is always coming to class late.
• He is constantly talking. I wish he would shut up.
• I don’t like them because they are always complaining.

REMEMBER Non-Continuous Verbs/ Mixed Verbs

It is important to remember that Non-Continuous Verbs cannot be used in any continuous tenses. Also, certain non-continuous meanings for Mixed Verbs cannot be used in continuous tenses. Instead of using Present Continuous with these verbs, you must use Simple Present.

Examples:

• She is loving this chocolate ice cream. Not Correct
• She loves this chocolate ice cream. Correct

ADVERB PLACEMENT

The examples below show the placement for grammar adverbs such as: always, only, never, ever, still, just, etc.

Examples:

• You are still watching TV.
• Are you still watching TV?

ACTIVE / PASSIVE

Examples:

• Right now, Tom is writing the letter. Active
• Right now, the letter is being written by Tom. PassiveACTIVITY

ACTIVITY

Simple Present / Present Continuous

Using the words in parentheses, complete the text below with the appropriate tenses,

1. Every Monday, Sally (drive)_________ her kids to football practice.

2. Usually, I (work) ______as a secretary at ABT, but this summer I (study)______ French at a language school in Paris. That is why I am in Paris.

3. Shhhhh! Be quiet! John (sleep)________ .

4. Don’t forget to take your umbrella. It (rain)________ .

5. I hate living in Seattle because it (rain, always)_________ .

6. I’m sorry I can’t hear what you (say)______ because everybody (talk)______ so loudly.

7. Justin (write, currently)_____________ a book about his adventures in Tibet. I hope he can find a good publisher when he is finished.

8. Jim: Do you want to come over for dinner tonight?
Denise: Oh, I’m sorry, I can’t. I (go)_______ to a movie tonight with some friends.

9. The business cards (be, normally )________ printed by a company in New York. Their prices (be) ______inexpensive, yet the quality of their work is quite good.

10. This delicious chocolate (be)_________ made by a small chocolatier in Zurich, Switzerland.

PHARMACY

Are We Speaking the Same Language?

Michael J. Gaunt, PharmD

Dr. Gaunt is a medication safety analyst and the editor of ISMP Medication Safety Alert! Community/Ambulatory Care Edition.

The Problem

Many people, even health care professionals, have trouble functioning well as patients—whether limited by knowledge, emotional or clinical state, socioeconomic factors, cultural background, or language differences. The television show ER portrayed this problem in an episode in which a Spanish-speaking woman misunderstood the directions for taking isoniazid (INH). The prescription label stated to take the medication “once” daily. In the Spanish language, however, “once” means “eleven.” In the show, the patient died from taking such an excessive dose.

A similar, real-life problem occurred when a Spanish-speaking mother applied oxiconazole 1% cream (Oxistat) to her baby’s inflamed rash up to 11 times each day. The mother was simply following prescription label directions that stated, half in English and half in Spanish, “Aplicarse once cada dia til rash is clear.” The problem is that “once” means “eleven” in Spanish. Fortunately, this was a topical medication, and while the inflammation got worse, no permanent harm resulted. Had this been an oral medication, however, the outcome could have been much more serious.

When a pediatric patient with seizures was discharged from the hospital, the physician wrote the following prescription: “phenytoin suspension 30 mg/5 mL, take 5.8 cc three times a day.” Since the patient and his family spoke only Spanish, the nurse gave the patient’s mother the written prescription and an oral syringe marked with tape at the 5.8 mL mark. Because phenytoin suspension is no longer commercially available in the 30 mg/5 mL concentration, however, the pharmacy where the mother took the prescription filled it with phenytoin 125 mg/5 mL. The prescription was labeled correctly and stated that the patient was to be given 1.3 mL 3 times a day. The pharmacist, who did not speak Spanish, could not counsel the patient’s mother. As a result, the mother used the syringe the nurse had given her, and she administered 145 mg 3 times a day instead of 34.8 mg 3 times a day. A few days later, the patient was readmitted to the hospital intensive care unit nearly comatose with phenytoin toxicity. The child recovered and was discharged.

In another example, a physician prescribed “Amoxicillin 200 mg/5 mL” with instructions to administer 5 mL tid to a 3-year-old child. The pharmacy carried only a 250 mg/5 mL strength, so the pharmacist changed the directions to “Take 4 cc (4/5 teaspoonful) by mouth 3 times a day.” The child’s father misunderstood the directions, as English was his second language. He did not know what “cc” meant, but upon seeing “4/5 teaspoonful,” he thought he should give his child 4.5 teaspoons of the medication. After 5 doses, he brought his child to the emergency department with severe diarrhea. The use of 2 abbreviations—“cc” and a slash mark (/)—contributed to the error. The child’s father did not interpret either abbreviation as intended. Inadequate patient counseling also played a role. Although he had been given a 10 mL measuring device for oral solutions marked in mL and teaspoons, specific directions for measuring each dose were not reviewed with the father when he picked up the prescription.

Safe Practice Recommendations

Patient counseling is always important, especially if a pharmacist must use a different concentration of a drug than originally prescribed because the directions that the physician initially provided to the patient differed from the actual directions on the prescription label. If the patient—or the family, in the case of a pediatric patient—does not speak English, however, it is a difficult situation. If you have a lot of patients who speak another language, consider having patient information brochures already translated into that language. While oral and written instructions are definitely preferred, for those patients who speak other languages written brochures may be the only way to provide counseling.

ELECTRIC CIRCUITS

electr-images1

You might have been wondering how electrons can continuously flow in a uniform direction through wires without the benefit of these hypothetical electron Sources and Destinations. In order for the Source-and-Destination scheme to work, both would have to have an infinite capacity for electrons in order to sustain a continuous flow! Using the marble-and-tube analogy, the marble source and marble destination buckets would have to be infinitely large to contain enough marble capacity for a “flow” of marbles to be sustained.

The answer to this paradox is found in the concept of a circuit: a never-ending looped pathway for electrons. If we take a wire, or many wires joined end-to-end, and loop it around so that it forms a continuous pathway, we have the means to support a uniform flow of electrons without having to resort to infinite Sources and Destinations:

each electron advancing clockwise in this circuit pushes on the one in front of it, which pushes on the one in front of it, and so on, and so on, just like a hula-hoop filled with marbles. Now, we have the capability of supporting a continuous flow of electrons indefinitely without the need for infinite electron supplies and dumps. All we need to maintain this flow is a continuous means of motivation for those electrons, which we’ll address in the next section of this chapter.

It must be realized that continuity is just as important in a circuit as it is in a straight piece of wire. Just as in the example with the straight piece of wire between the electron Source and Destination, any break in this circuit will prevent electrons from flowing through it:

An important principle to realize here is that it doesn’t matter where the break occurs. Any discontinuity in the circuit will prevent electron flow throughout the entire circuit. Unless there is a continuous, unbroken loop of conductive material for electrons to flow through, a sustained flow simply cannot be maintained.

 

·         REVIEW:

·         A circuit is an unbroken loop of conductive material that allows electrons to flow through continuously without beginning or end.

·         If a circuit is “broken,” that means it’s conductive elements no longer form a complete path, and continuous electron flow cannot occur in it.

·         The location of a break in a circuit is irrelevant to its inability to sustain continuous electron flow. Any break, anywhere in a circuit prevents electron flow throughout the circuit.

Voltage and current in a practical circuit

Because it takes energy to force electrons to flow against the opposition of a resistance, there will be voltage manifested (or “dropped”) between any points in a circuit with resistance between them. It is important to note that although the amount of current (the quantity of electrons moving past a given point every second) is uniform in a simple circuit, the amount of voltage (potential energy per unit charge) between different sets of points in a single circuit may vary considerably:

Take this circuit as an example. If we label four points in this circuit with the numbers 1, 2, 3, and 4, we will find that the amount of current conducted through the wire between points 1 and 2 is exactly the same as the amount of current conducted through the lamp (between points 2 and 3). This same quantity of current passes through the wire between points 3 and 4, and through the battery (between points 1 and 4).

However, we will find the voltage appearing between any two of these points to be directly proportional to the resistance within the conductive path between those two points, given that the amount of current along any part of the circuit’s path is the same (which, for this simple circuit, it is). In a normal lamp circuit, the resistance of a lamp will be much greater than the resistance of the connecting wires, so we should expect to see a substantial amount of voltage between points 2 and 3, with very little between points 1 and 2, or between 3 and 4. The voltage between points 1 and 4, of course, will be the full amount of “force” offered by the battery, which will be only slightly greater than the voltage across the lamp (between points 2 and 3).

This, again, is analogous to the water reservoir system:

 

Between points 2 and 3, where the falling water is releasing energy at the water-wheel, there is a difference of pressure between the two points, reflecting the opposition to the flow of water through the water-wheel. From point 1 to point 2, or from point 3 to point 4, where water is flowing freely through reservoirs with little opposition, there is little or no difference of pressure (no potential energy). However, the rate of water flow in this continuous system is the same everywhere (assuming the water levels in both pond and reservoir are unchanging): through the pump, through the water-wheel, and through all the pipes. So it is with simple electric circuits: the rate of electron flow is the same at every point in the circuit, although voltages may differ between different sets of points.