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Drug Information: A Guide for Pharmacists, 6e

Chapter 2: Formulating an E ective Response: A Structured Approach

Amy Heck Sheehan; Joseph K. Jordan

Learning Objectives
A er completing this chapter, the reader will be able to

Develop strategies to overcome the impediments that prevent health care professionals from providing
e ective responses and recommendations.

Outline the steps that are necessary to identify the actual drug information needs of the requestor.

List and describe the four critical factors that should be considered and systematically addressed when
formulating a response.

Define analysis and synthesis, and describe their application in the process of formulating responses and
recommendations.

List the elements and characteristics of e ective responses to medication-related queries.

Key Concepts
1 Rational pharmacotherapy can be promoted by ensuring that drug information is correctly interpreted
and appropriately applied.

2 The absence of su icient background information and pertinent patient data can greatly impair the
process of information synthesis and the ability to formulate e ective responses.

3 Critical information that defines the problem and elucidates the context of the question is not readily
volunteered, but must be expertly elicited.

4 Providing responses and o ering recommendations without knowledge of pertinent patient information,
the context of the request, or how the information will be applied can be potentially harmful.

5 Formulating the response requires the use of a structured, organized approach whereby critical factors
are systematically considered and thoughtfully evaluated.

6 Approaching a question haphazardly, or prematurely fixating on isolated details, can misdirect even the
most skilled clinician.7.

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7 Responses to drug information queries o en must be synthesized by integrating data from diverse
sources through the use of logic and deductive reasoning.

Introduction
Health care professionals are asked to provide responses to a variety of drug information questions every
day. Although the type of requestor, query, and setting can vary, the process of formulating responses
remains consistent. This chapter introduces an organized, structured approach for formulating e ective
responses and recommendations to drug information questions.

As the medical literature expands, access to drug information resources by health care professionals and
the public continues to grow. Yet many professionals and consumers lack the necessary skills to use this
information e ectively. 1 Rational pharmacotherapy can be promoted by ensuring that drug information is
correctly interpreted and appropriately applied. This presents an opportunity and a challenge for
pharmacists who are true drug therapy experts and play a broader role in patient care.

Regardless of specialty or practice site, health care professionals with the responsibility for overseeing the
safe and rational use of medications must strive to develop expertise in applied pharmacotherapy. Whether
working in a community setting, nursing home, outpatient clinic, hospital, or in any other practice site,
pharmacists and other health care professionals can apply their skills and knowledge for the optimal care
of patients. Pharmacists should not be relegated to the role of information dispenser or gatekeeper, but
they should instead extend their knowledge of drugs and therapeutics to the clinical management of
individual patients or the care of large populations.

Steps for Answering a Question

ACCEPTING RESPONSIBILITY AND ELIMINATING BARRIERS

Health care professionals should recognize that their responsibility extends beyond simply providing an
answer to a question. Rather, it is to assist in resolving therapeutic dilemmas or managing patients’
medication regimens for their entire therapeutic outcome. Knowledge of pharmacotherapy alone does not
ensure success. Moreover, isolated information is not su icient for formulating responses to questions or
ensuring proper patient management. In fact, it is uncommon to find comprehensive answers in the
literature that completely and e ectively address specific situations or circumstances that clinicians
encounter in their daily practices. Responses and recommendations must o en be thoughtfully
synthesized using information and knowledge gathered from a number of diverse sources. To e ectively
manage the care of patients and resolve complex situations, added skills and competence in problem
solving and direct patient care are also necessary.

In order to provide meaningful responses and e ective recommendations to drug information questions,
real or perceived impediments must first be overcome. One such impediment is the false perception that
many drug information questions do not pertain to specific patients. Another is the perception that the
seemingly casual interactions with requestors and the lack of formal, written consultation somehow
preclude the need for in-depth analysis and extensive involvement in patient management.
Oversimplification of these interactions with requestors and failure to identify the context of the question

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or recognize its significance can jeopardize the clinical management of patients. 2 The absence of su icient
background information and pertinent patient data can greatly impair the process of information synthesis
and the ability to formulate e ective responses.

IDENTIFYING THE GENUINE AND PRECISE NEED

Evolution of the Systematic Approach

Historically, the approach to answering drug information queries has centered on the use of a systematic
method first described by Watanabe and Conner and subsequently modified by others.1,2 This simple
approach relied on the collection of basic information to document and categorize the request and to
subsequently develop an organized strategy for formulating cogent responses. Although this structure
remains theoretically useful from a training standpoint, if strictly applied without proper context and
guidance, it has the potential to artificially fragment the process and disrupt the natural exchange of
information. A documentation form (see Appendix 2-1) may be useful to guide the process of data
collection and ensure that all relevant information is considered. More recently, the Pharmacists’ Patient
Care Process (PPCP) has been used as a model by colleges and schools of pharmacy to provide students
with a systematic, patient-centered approach to improving medication outcomes.3 This approach is similar
to Watanabe's method and includes collection of all necessary information in order to understand the
clinical status of the patient; followed by analysis of data, development and implementation of an
evidence-based plan, and appropriate follow-up.

Eliminating Potential Barriers

Ultimately, the success of providing an e ective response will depend largely on maintaining the flow of
information with minimal distractions and unnecessary or ill-timed questions. The goal should be to
remove obstacles, such as those provided by lack of background or situational information, when
communicating with clinicians so as to reveal the actual informational needs. This is particularly relevant in
clinical settings where most queries are not purely academic or general in nature. In fact, it is rational to
assume that queries from health care providers will invariably involve specific patients and unique clinical
circumstances. For example, a physician who asks about the association of liver toxicity with atorvastatin is
probably not asking this question whimsically or out of curiosity. The physician most likely is caring for a
patient who has developed signs or symptoms of hepatic impairment possibly associated with the use of
this medication. Although other reasonable scenarios, albeit less likely, could have prompted this question,
it would be most prudent nonetheless to consider the possibility of a patient-specific drug-induced liver
injury.

Eliciting Critical Information

Even questions that are not related to patient care (refer to Case Study 2-1 as an example) must be viewed
in their proper context. Requestors of information are typically vague in verbalizing their needs and
generally provide adequate information only when specifically asked and/or thoughtfully prompted.
Although these requestors may seem confident about their perceived needs, they may be less certain a er
further probing. Requestors, regardless of background, are o en uncertain about the nature and extent of
information that should be disclosed in order to derive the most optimal assistance. 3 Critical information
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that defines the problem and elucidates the context of the question is not readily volunteered, but must be
expertly elicited. This can be accomplished through the use of e ective questioning strategies (asking
logical questions in a logical sequence) and other means of information gathering that are essential for
formulating informed responses. Failure of the requestor to disclose critical information or clarify the
question does not obviate the need for such information or relieve the pharmacist of the duty to collect it.
Although it is easy to assign blame to the requestor for failing to disclose all of the necessary information, it
is ultimately the responsibility of the provider of the response to obtain this information completely and
e iciently.

Case Study 2–1

INITIAL QUESTION

What is the molecular weight of fosamprenavir calcium?

POTENTIAL RESPONSE IN THE ABSENCE OF RELEVANT BACKGROUND INFORMATION

Fosamprenavir is an oral antiretroviral agent that is indicated for the treatment of human
immunodeficiency virus (HIV-1) infection in combination with other antiretroviral agents.5,6 The molecular
weight of fosamprenavir is 623.7 g/mol.6

PERTINENT BACKGROUND INFORMATION

The requestor is a basic scientist who is conducting an in vitro experiment to evaluate the pharmacologic
e ects of fosamprenavir. She would like to know the molecular weight of fosamprenavir so that she can
perform appropriate calculations specified for this experiment.

PERTINENT PATIENT FACTORS

N/A

PERTINENT DISEASE FACTORS

N/A

PERTINENT MEDICATION FACTORS

Fosamprenavir is a prodrug that is converted in vivo to the pharmacologically active form, amprenavir.5,6
Fosamprenavir is available for prescription use in the United States as 700-mg oral tablets and 50 mg/mL
oral suspension. Amprenavir has been discontinued and is no longer commercially available in the United
States.

ANALYSIS AND SYNTHESIS

Considering that fosamprenavir is a prodrug that must be converted to a pharmacologically active

compound in vivo, and given that this researcher wishes to conduct an in vitro study, the researcher should
use the active form of the drug in the experiment. Therefore, they should have requested the molecular
weight of amprenavir.

RESPONSE AND RECOMMENDATIONS

Fosamprenavir is an oral antiretroviral agent indicated for the treatment of human immunodeficiency virus
(HIV-1) infection in combination with other antiretroviral agents.5,6 Because fosamprenavir is a prodrug

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that requires conversion to the active form, the requestor was advised to consider using amprenavir in the
experiment. The molecular weight of amprenavir is 505.6 g/mol, and is available for purchase from several
chemical vendors.7

CASE MESSAGE

This example illustrates the importance of collecting pertinent background information, even for seemingly
uncomplicated questions. Failure to understand exactly how the information that is provided will be used
could result in an inaccurate or misleading response. In this case, providing the molecular weight without
alerting the requestor that in vitro fosamprenavir is pharmacologically inactive would have resulted in
wasted time and money, and the results of the experiment would likely have been invalid.

Good communication skills (both listening and questioning) are essential for gathering relevant
information, discerning the real question, and identifying the genuine needs of the requestor. 4 Providing
responses and o ering recommendations without knowledge of pertinent patient information, the context
of the request, or how the information will be applied can be potentially harmful. For assistance in
identifying some of the questions that should be posed, please refer to Appendix 2-2. Even well-equipped
drug information centers with trained sta are not immune to this problem. A study of the quality of
pharmacotherapy consultations provided by drug information centers in the United States found that the
centers generally failed to obtain pertinent patient data, thereby risking incorrect responses and
inappropriate recommendations.4

Verifying the Context of Question

Some health care professionals may be quick to attempt to answer questions without adequately
understanding the context or unique circumstances from which they evolved. They focus exclusively on the
answer and ignore or fail to obtain key information needed to establish the framework of the question. In
essence, this can result in a correct response being provided to address an incorrect question. For example,
in a question about the dose of an antibiotic, an incorrect response can be formulated and inappropriate
recommendations made if one fails to consider such factors as the patient's age, sex, condition being
treated, end-organ function, weight and body composition, concomitant diseases (e.g., cystic fibrosis),
possible drug interactions, site of infection, spectrum of activity of the antimicrobial, resistance patterns, or
other factors such as pregnancy or dialysis.

Before attempting to formulate responses, one must consider several important questions to ensure that
they understand the context of the query and the scope of the issue or problem (see Table 2-1). Without
this information, there is a risk of providing general responses that do not address the needs of the
requestor. More concerning, however, is that the information provided can be misinterpreted or
misapplied. This not only compromises one's credibility, but also can jeopardize patient care. Pharmacists
must recognize the value and potential benefits of their contributions as members of the health care team.
Lack of confidence in communicating with requestors can be a limiting factor. Because a telephone call
from another health care provider or even a face-to-face interaction may not be perceived as a formal
request for a consult, the significance of such apparently informal daily interactions can easily be
overlooked. Interactions with physicians and other health care providers present valuable opportunities for
direct involvement in patient care. The lesson o en missed is that there is a fine line between a simple,
seemingly general drug information question and a meaningful pharmacotherapy consult. Knowing the
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context of the question, obtaining the pertinent patient data and background information, and
understanding the true needs of the requestor o en can be the di erence.

Case Study 2–2

INITIAL QUESTION

Can you tell me the recommended dose of azithromycin for gastroparesis?

POTENTIAL RESPONSE IN THE ABSENCE OF RELEVANT BACKGROUND INFORMATION

Azithromycin is structurally similar to erythromycin, a macrolide that has been used historically for short-
term management of gastroparesis. While erythromycin is noted to reduce symptoms from delayed gastric
emptying in either the IV or oral formulation, current guidelines from the American Gastroenterology
Association do not address the role of azithromycin.8 A search of tertiary and secondary sources did note a
few reports of using IV or oral formulations of azithromycin at doses of 250 to 500 mg daily.9-13

PERTINENT BACKGROUND INFORMATION

The requestor is an internal medicine physician who is managing a patient with diabetic gastroparesis. A
nurse recently informed the internal medicine team of a nationwide erythromycin shortage. The physician
would like to know if azithromycin is an alternative to erythromycin, and if so what the appropriate dose
would be for this specific patient.

PERTINENT PATIENT FACTORS

CD is a 53-year-old female. She is presenting today to the o ice with a reported history of abdominal pain,
persistent nausea, occasional vomiting, decreased appetite, and flatulence for the past 2 months. Currently
the patient is receiving as-needed metoclopramide 10 mg PO 10 minutes a er meals.

Past Medical History

Type 2 diabetes mellitus × 13 years

Peripheral neuropathy × 5 years

Diabetic gastroparesis × 2 years

Hypertension × 8 years

Social History

Negative for ethanol

Negative for tobacco or illicit drugs

Current Medications and Supplements

Insulin Glargine 15 units subcutaneously at bedtime

Insulin Lispro 5 units subcutaneously 15 minutes before each meal

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Lisinopril 10 mg PO daily

Hydrochlorothiazide 50 mg daily

Metoclopramide 10 mg PO 10 minutes a er meals PRN

Atorvastatin 40 mg PO QPM

Acetaminophen 1,000 mg PO Q6H PRN pain

Centrum Women daily multivitamin

Fish oil supplement

Allergies and Intolerances

Morphine

Laboratory Results

T 98°F, BP 151/84 mmHg, P 91 BPM, RR 18/min, O2 sat 93%

SCr 1.3 mg/dL, BUN 22 mmol/dL

WBC 5.4 × 109 per liter

Glucose 88 mg/dL, A1C 9.4% (3 months ago)

LDL 126 mg/dL, HDL 44 mg/dL, TG 155 mg/dL

PERTINENT DISEASE FACTORS

Gastroparesis is characterized by delayed gastric emptying and is most commonly associated with diabetes
mellitus. The incidence increases with the duration of diabetes and the presence of complications such as
retinopathy, neuropathy, or nephropathy. Common symptoms of this condition include nausea, vomiting,
abdominal pain, and fullness. Treatment of gastroparesis generally involves modifications to diet and
pharmacotherapy with prokinetics, antiemetics, and non-opiate analgesics.8

PERTINENT MEDICATION AND SUPPLEMENT FACTORS

Erythromycin is a macrolide antibiotic with known prokinetic e ects resulting from stimulation of motilin
receptors in the gut. Azithromycin is also a macrolide antibiotic but is more commonly used for infection-
related conditions as opposed to gastrointestinal motility. As compared with erythromycin, azithromycin
has less drug interactions and a longer half-life. While large trials comparing erythromycin and
azithromycin for the treatment of gastroparesis were not located, there are some smaller trials comparing
manometry results with both agents.10-12 The administration of IV azithromycin 250 mg infused over 30
minutes was found to have a greater e ect in the postprandial period than a dose of IV erythromycin 250
mg infused over 20 minutes.10,11 Due to the long half-life of the agent, the authors argue that the product
can be given once daily compared with the four times daily regimen of erythromycin. In addition, at higher
doses of 500 mg of IV azithromycin infused over 30 minutes, a greater e ect on manometry readings was
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noted.12 A case report describing the e ectiveness of azithromycin in an elderly woman with diabetic
gastroparesis notes successful resolution of symptoms a er a 3-day regimen of 500 mg IV azithromycin
followed by a 14-day regimen of 500 mg PO azithromycin.13

ANALYSIS AND SYNTHESIS

As CD is already on the first-line agent for gastroparesis (i.e., metoclopramide) and is still symptomatic,
erythromycin would be an option to improve gastric emptying and symptoms from delayed gastric
emptying. However, CD is not optimally taking the metoclopramide since she is taking it a er meals instead
of the recommended before meals. This should be pointed out since this may be contributing to
symptoms. Since erythromycin is unavailable at the present time, azithromycin is an additional option
based on similar e ects seen in manometry studies.

RESPONSE AND RECOMMENDATIONS

Metoclopramide is a first-line agent for treatment of diabetic gastroparesis at a dose of 10 mg up to four

times daily before meals and at bedtime.8 Taking the medication a er meals, instead of the recommended
30 minutes before meals, will decrease the e icacy of the prokinetic agent. Before making additional
changes to CD's regimen, it is worth adjusting the metoclopramide dosing.

CASE MESSAGE

This question highlights the importance of skillful problem solving. As always, collecting appropriate
background information and patient data is critical. Analyzing this information before synthesizing a logical
response is paramount for e ective patient management. In this case, failure to recognize that the patient
was inappropriately taking metoclopramide could lead to potentially unnecessary addition of therapy for
her diabetic gastroparesis.

TABLE 2–1.

QUESTIONS TO CONSIDER BEFORE FORMULATING A RESPONSE

Is the requestor's name, profession, and a iliation known?

Does the question pertain to a specific patient?
Is there a clear understanding of the question or problem?
Is the correct question being asked?
Why is the question being asked? Why now?
Are the requestor's expectations understood?
Has pertinent patient history and background information been obtained?
What are the unique circumstances that generated the query?
What information is actually needed?
When is the information needed and in what format (e.g., verbal, written)?
How will the information provided be used or applied?
How has the problem or situation been managed to date?
Are there alternative explanations or management options that should be explored?
How can the requestor be contacted (e.g., pager, e-mail, cellphone)?

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In the absence of information that provides the proper context, a question about the half-life of a
medication appears rather simple. However, if the question was posed for the purpose of assisting the
requestor in determining a su icient washout period for a crossover study, one would be remiss if factors,
other than the half-life of the parent compound, were not considered. Proper determination of a washout
period also would mandate consideration of other factors such as the activity and half-lives of known
metabolites; the presence of potentially interacting medications; the e ects of age, illness, or end-organ
function; the persistence of pharmacodynamic e ects of the medication beyond its detection in the plasma
(e.g., omeprazole); and the e ect of administration route on the apparent half-life (e.g., transdermally
administered fentanyl).

The case studies in this chapter emphasize the importance of looking beyond the initial question and
recognizing that the requestor's needs o en go well beyond a superficial answer to the primary question.
Pharmacists should always anticipate additional questions or concerns, including those that are not
directly asked or addressed by the requestor. These questions nonetheless must be considered if a clinical
situation is to be managed optimally. In Case Study 2-3, as an example, a question is posed about
antibiotics as a possible cause of tooth discoloration. Although the requestor may neglect to provide
clarifying information or pose insightful questions that further inform the case, additional related issues
and complementary questions should nonetheless be considered, as these will likely be critical in
determining the ultimate success of the response (see Table 2-2). Failure to address such questions will
undoubtedly result in either an incorrect or inadequate response.

Case Study 2–3

INITIAL QUESTION

Do any of the following antibiotics cause teeth discoloration—amoxicillin, nitrofurantoin, and

sulfamethoxazole-trimethoprim?

POTENTIAL RESPONSE IN THE ABSENCE OF RELEVANT BACKGROUND INFORMATION

An extensive search of tertiary and secondary literature sources noted that tooth discoloration has been
seen rarely with amoxicillin.14 However, with dental hygiene practices such as brushing or professional
cleaning, this discoloration may be reversible. No documentation was found of tooth discoloration with
nitrofurantoin or sulfamethoxazole-trimethoprim.

PERTINENT BACKGROUND INFORMATION

The requestor is a urology nurse practitioner who is caring for a patient with vesicoureteral reflux. The
patient had been receiving ½ teaspoon of sulfamethoxazole-trimethoprim for about 8 months when his
parent noticed darkening of his two teeth. The clinician would like to use an antibiotic prophylaxis for
vesicoureteral reflux, but wants to make sure that tooth discoloration is unlikely with choice.

PERTINENT PATIENT FACTORS

AB is a 10-month-old male with vesicoureteral reflux.

Past Medical History

N/A

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Social History

N/A

Current Medications and Supplements

Trimethoprim/sulfamethoxazole (40–200 mg/5 mL) 2.5 mL daily × 8 months [stopped]

Patient is currently breastfed

Liquid multivitamin supplement (Poly-Vi-Sol® with iron) 0.5 mL by mouth once daily

Allergies and Intolerances

N/A

PERTINENT DISEASE FACTORS

Vesicoureteral reflux (VUR) involves the retrograde passage of urine from the bladder into the upper urinary
tract. Patients with VUR who develop bladder infection are at increased risk for febrile urinary tract
infections (UTI) compared with patients without VUR. The management of VUR involves preventing
recurring febrile UTIs, preventing renal injury from potential kidney infections (e.g., acute pyelonephritis),
and minimizing morbidity of treatment.15-17 Antibiotic prophylaxis has been given for several decades
under the idea that sterilizing the urine will lead to less kidney infections and in turn, less kidney scarring.
Children younger than 1 year of age are recommended to receive antibiotic prophylaxis since they are more
likely to su er morbidity with acute kidney infections than older children.17

Tooth discoloration is described as either extrinsic (i.e., outer surface) or intrinsic (i.e., within enamel).
Extrinsic discoloration can be seen with tea, co ee, tobacco, and some medications such as mouth rinses
and iron salts. In contrast to intrinsic stains, extrinsic stains can usually be removed with tooth brushing or
dental scaling and polishing.14

PERTINENT MEDICATION AND SUPPLEMENT FACTORS

Reports of tooth discoloration with amoxicillin, but not trimethoprim-sulfamethoxazole or nitrofurantoin,

were found in the primary and tertiary literature. A review of the patient's current medication and
supplements reveals an iron-containing multivitamin. Iron-containing products have more reports of tooth
discoloration than amoxicillin.14

Trimethoprim-sulfamethoxazole and nitrofurantoin have traditionally been used for VUR prophylaxis at
one-half to one-fourth of the usual therapeutic doses for treating acute infections. Amoxicillin is not
traditionally used secondary to concerns of increased likelihood of resistant organisms.15-17

ANALYSIS AND SYNTHESIS

As AB is less than 1 year of age and has a history of febrile UTI, it is recommended to receive antibiotic
prophylaxis. Trimethoprim-sulfamethoxazole and nitrofurantoin are the most common antibiotics
recommended. While AB has been on trimethoprim-sulfamethoxazole for 8 months, there is no record of
having received dental cleaning during this time. Amoxicillin and nitrofurantoin are other options for VUR
prophylaxis although amoxicillin has reports of tooth discoloration. A more likely causative factor is the
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liquid multivitamin containing iron. Iron supplements are usually not needed in children who are breastfed
or who get iron-fortified infant formula. Since AB is still being breastfed, there is likely not a need for the
iron supplement.

RESPONSE AND RECOMMENDATIONS

A review of AB's current medications reveals one agent, a liquid multivitamin containing iron, which has
been reported to cause extrinsic tooth discoloration. This discoloration is usually reversible with tooth
brushing and polishing.14 Trimethoprim-sulfamethoxazole has not previously been reported to cause tooth
discoloration but it cannot be ruled out as a possible cause. The practitioner was advised to consult a
dentist for cleaning of the extrinsic discoloration and to discuss discontinuing the iron-containing
multivitamin supplement with the parents. If the staining returns a er discontinuation of the iron
supplement, then transition to nitrofurantoin could be considered.

CASE MESSAGE

This question highlights the importance of skillful problem solving. As always, collecting appropriate
background information and patient data is critical. Analyzing this information before synthesizing a logical
response is paramount for e ective patient management. In this case, failure to recognize that the patient
was receiving a liquid multivitamin with iron could have led to possible suboptimal antibiotic prophylactic
therapy for VUR.

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TABLE 2–2.

IMPORTANT QUESTIONS NOT POSED BY THE REQUESTOR

Initial query posed by requestor: Do any of the following antibiotics cause tooth discoloration?—amoxicillin,
nitrofurantoin, and sulfamethoxazole-trimethoprim?
What is the incidence of antibiotic-induced tooth discoloration?
Are specific antibiotic agents (i.e., amoxicillin, nitrofurantoin, or sulfamethoxazole-trimethoprim) more
likely to cause tooth discoloration than others?
Are there any known predisposing factors?
Is the pathogenesis of this adverse e ect understood?
How does the tooth discoloration typically present?
Are there any characteristic subjective or objective findings?
Does tooth discoloration caused by antibiotics di er from that caused by other medications, or other
etiologies?
Is the tooth discoloration dose related?
How severe can it become?
Is antibiotic tooth discoloration reversible?
How is antibiotic-induced tooth discoloration usually managed?
Are there other antibiotics available that can be used in place of the patient's current agents?
Are there alternative explanations for the tooth discoloration in this patient (including other medications,
medication combinations, or underlying medical conditions)?
What complications, if any, can be expected?

To expertly address requests for drug information, pharmacists also must depend on their patient care
skills, problem-solving skills, insight, and professional judgment. Computer databases and other
specialized information sources can assist in identifying critical data, but overreliance on such resources
without careful attention to pertinent background information and patient data can mislead even the most
experienced clinician.

Formulating the Response

BUILDING A DATABASE AND ASSESSING CRITICAL FACTORS

Formulating a response comprises a series of steps that must be performed completely, objectively, and in
a logical sequence. The steps in the process include assembling and organizing a database of the patient
information, gathering information about relevant disease states, collecting medication information,
obtaining pertinent background information, and identifying other relevant factors and unique or special
circumstances. 5 Formulating the response requires the use of a structured, organized approach whereby
critical factors are systematically considered and thoughtfully evaluated. Table 2-3 outlines in detail the
specific types of information that may need to be considered for each factor depending on the nature of the
query. A more thorough list of possible background questions is found in Appendix 2-2. It should be noted
that only some of this information might be pertinent for a given query or case scenario.
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TABLE 2–3.

FACTORS TO BE CONSIDERED WHEN FORMULATING A RESPONSE

Patient Factors

Demographics (e.g., name, age, height, weight, gender, race/ethnic group, and setting)
Primary diagnosis and medical problem list
Allergies/intolerances
End-organ function, immune function, nutritional status
Chief complaint
History of present illness
Past medical history (including surgeries, radiation exposure, immunizations, psychiatric illnesses, and so
forth)
Family history and genetic makeup
Social history (e.g., alcohol intake, smoking, substance abuse, exposure to environmental or occupational
toxins, employment, income, education, religion, travel, diet, physical activity, stress, risky behavior, and
compliance with treatment regimen)
Review of body systems
Medications (prescribed, nonprescription, and complementary/alternative)
Physical examination
Laboratory tests
Diagnostic studies or procedures

Disease Factors

Definition
Epidemiology (including incidence and prevalence)
Etiology
Pathophysiology (for infectious diseases consider site of infection, organism susceptibility, resistance
patterns, and so forth)

Clinical findings (signs and symptoms, laboratory tests, diagnostic studies)a

Diagnosis
Treatment (medical, surgical, radiation, biologic and gene therapies, other)
Prevention and control
Risk factors
Complications
Prognosis

Medication Factors

Name of medication or substance (proprietary, nonproprietary, other)

Status and availability (investigational, nonprescription, prescription, orphan, foreign,
complementary/alternative)

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Physicochemical properties
Pharmacology and pharmacodynamics
Pharmacokinetics (liberation, absorption, distribution, metabolism, and elimination)
Pharmacogenomics
Indications (Food and Drug Administration [FDA] approved and unlabeled)
Uses (diagnosis, prevention, replacement, or treatment)
Adverse e ects
Allergy
Cross-allergenicity or cross-reactivity
Contraindications and precautions
E ects of age, organ system function, disease, pregnancy, extracorporeal circulation, or other conditions or
environments
Mutagenicity and carcinogenicity
E ect on fertility, pregnancy, and lactation
Acute or chronic toxicity
Drug interactions (drug–drug or drug–food)
Laboratory test interference (analytical or physiologic e ects)
Administration (routes, methods)
Dosage and schedule
Dosage forms, formulations, preservatives, excipients, product appearance, delivery systems
Monitoring parameters (therapeutic or toxic)
Product preparation (procedures, methods)
Compatibility and stability

Pertinent Background Information, Special Circumstances, and Other Factors

Setting
Context
Sequence and time frame of events
Rationale for the question
Event(s) prompting the question
Unusual or special circumstances (including medical errors)
Acuity and time constraints
Scope of question
Desired detail or depth of response
Limitations of available information or resources
Completeness, su iciency, and quality of the information
Applicability and generalizability of the information

aFactors such as disease or symptom onset, duration, frequency, and severity must always be carefully assessed.

For patient-related questions, development of a patient-specific database is one of the first steps in
preparing a response. This requires the collection of pertinent information from the patient, caregivers,

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health care providers, medical chart, and other patient records. A comprehensive medication history also is
essential. This database would invariably include information that overlaps with the medical and nursing
databases. Because physicians, nurses, patients, and others o en lack a clear understanding of the type of
information needed for e ective pharmacotherapy consultations, pharmacists must be able to identify and
e iciently extract pivotal patient information from diverse sources.

Case Study 2–4

INITIAL QUESTION

What is the maximum dose of rizatriptan?

POTENTIAL RESPONSE IN THE ABSENCE OF RELEVANT BACKGROUND INFORMATION

Rizatriptan is an oral selective serotonin 5-HT1B/1D receptor agonist indicated for the acute treatment of

migraine headache.18 The recommended dose for acute migraine is 5 to 10 mg. If the migraine resumes or
symptoms have not subsided within 2 hours, a second dose may be administered. The maximum daily
dose is 30 mg in a 24-hour time period.18

PERTINENT BACKGROUND INFORMATION

The requestor is a medical resident who is caring for a patient with migraine headaches. The patient has
experienced an increased intensity and frequency of migraines over the last several months. She reports
that she has experienced two to three migraines per week over the last month. The patient uses 5 mg of
rizatriptan for treatment of acute migraine attacks. This has worked in the past. However, recently she has
required a second dose for complete resolution of symptoms. The medical resident would like to know if
higher doses of rizatriptan have been studied. He is planning to increase the patient's dose of rizatriptan to
provide more rapid relief to the patient.

PERTINENT PATIENT FACTORS

EF is a 27-year-old woman who has su ered from migraine headaches for the last 7 years. She presents
today complaining of increased frequency and intensity of migraine headaches over the last month. The
migraines are now a ecting her job performance as a teacher, and she has recently missed several days of
work.

Past Medical History

Recurrent migraine headaches

Depression

Social History

EF is a kindergarten teacher and lives with her husband

EF denies alcohol and tobacco use

Current Medications

Rizatriptan 5 mg orally for acute migraine

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Bupropion 150 mg twice daily

Loratadine 10 mg daily

Allergies/Intolerances

NSAIDs (anaphylaxis)

PERTINENT DISEASE FACTORS

Migraine is characterized by episodic attacks of severe headaches that are associated with throbbing pain,
nausea, vomiting, and photophobia, with or without aura.19 If not treated, the duration of a migraine
headache can range from 4 hours to several days. Recommended treatments for the management of acute
migraine include acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), selective serotonin 5-
HT1B/1D receptor agonists, anti-emetics, and dihydroergotamine.20 For patients who experience greater
than six migraines per month or have very severe symptoms that are not relieved by acute treatment, use
of preventive treatments are recommended.21 First-line preventive treatments with established e icacy
include antiepileptic drugs (e.g., valproate, topiramate) and beta-adrenergic blocking agents (e.g.,
metoprolol, propranolol).22

PERTINENT MEDICATION FACTORS

The recommended dose of rizatriptan for treatment of migraine in adults is 5 to 10 mg. If the migraine
resumes or symptoms have not subsided within 2 hours, a second dose may be administered. The
maximum daily dose is 30 mg in a 24-hour time period.18 A dose of 10 mg may provide greater e icacy over
a dose of 5 mg. However, adverse events of selective serotonin 5-HT1B/1D receptor agonists have been
shown to be dose-related. In clinical trials, patients who received 40 mg of rizatriptan reported dizziness
and somnolence.18

ANALYSIS AND SYNTHESIS

Although increasing EF's dose of rizatriptan to 10 mg may provide greater e icacy for acute migraine relief,
doses above this level are associated with a higher incidence of adverse e ects. Review of EF's migraine
history reveals that she is a candidate for preventive treatment. Addition of a preventive treatment will
likely have a greater clinical impact than increasing the rizatriptan dose by reducing the frequency of
migraine headaches that she has been experiencing.

RESPONSE AND RECOMMENDATIONS

The practitioner was advised that the maximum dose of rizatriptan during a 24-hour period is 30 mg.
Although it may be reasonable to increase EF's dose for acute migraine relief to 10 mg, EF should also be
started on a preventive treatment, such as valproate, to minimize the frequency of migraine headaches
that she has been experiencing.

CASE MESSAGE

This example demonstrates the importance of understanding the proper context of the query. In this case,
the pharmacist must collect critical background information to determine the actual drug information
needed. Had the pharmacist failed to collect pertinent patient information, the physician may have

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increased the dose of the medication a er being told that the maximum dose is of 30 mg in a 24-hour time
period. Given this patient's migraine history, it would be more important to also consider the addition of a
preventive treatment in order to minimize the total number of migraine attacks. Moreover, larger doses of
this medication are associated with a higher incidence of adverse e ects.

Once these data are collected and carefully assembled, they must be critically analyzed and evaluated in
the proper context before final responses and recommendations are synthesized. Background reading on
topics related to the query (e.g., diseases, medications, laboratory tests) is o en essential. This process
also o en involves careful evaluation of the literature (see Chapters 4 and 5). To e ectively perform the
steps outlined previously, one must begin with a broad perspective (i.e., observing the big picture) to avoid
losing sight of important information. 6 Approaching a question haphazardly, or prematurely fixating on
isolated details, can misdirect even the most skilled clinician.

ANALYSIS AND SYNTHESIS

Analysis and synthesis of information are among the most critical steps in formulating responses and
recommendations. Together, they assist in forming opinions, arriving at judgments, and ultimately drawing
conclusions. Analysis is the critical assessment of the nature, merit, and significance of individual
elements, ideas, or factors. Functionally, it involves separating the information into its isolated parts so that
each can be critically assessed. Analysis requires thoughtful review and evaluation of the quality and
overall weight of available evidence. Although this process requires consideration of all relevant positive
findings, pertinent negative findings should not be overlooked.

Once the information has been carefully analyzed, synthesis can begin. Synthesis is the careful, systematic,
and orderly process of combining or blending varied and diverse elements, ideas, or factors into a coherent
response. 7 Responses to drug information queries o en must be synthesized by integrating data from
diverse sources through the use of logic and deductive reasoning. This process relies not only on the type
and quality of the data gathered, but also on how the data are organized, viewed, and evaluated. Synthesis,
as it relates to pharmacotherapy, involves the careful integration of critical information about the patient,
disease, and medication along with pertinent background information to arrive at a judgment or
conclusion. Synthesis can give existing information new meaning and, in e ect, create new knowledge. The
use of analysis and synthesis to formulate a response is similar to assembling a jigsaw puzzle. If the pieces
are identified and then grouped, organized, and assembled correctly, the image will be comprehensible.
However, if too many of the pieces are missing—as may be the case if patient information or if supporting
evidence is incomplete or absent—or are not arranged logically (e.g., when information is not evaluated,
interpreted, or applied correctly), formulating a cogent response may prove di icult or altogether
impossible.

RESPONSES AND RECOMMENDATIONS

An e ective response obviously must adequately address and answer the question. Other characteristics of
e ective responses and recommendations are outlined in Table 2-4. The response to a question must
include a restatement of the request and clear identification of the problems, issues, and circumstances.
The response should begin with an introduction to the topic and systematically present the specific
findings. Pertinent background information and patient data should be succinctly addressed. Conclusions

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and recommendations are also included in the response along with pertinent reference citations from the
literature. In formulating responses, one should disclose the available information that is most relevant to
the question and present all reasonable options and alternatives along with an explanation and evaluation
of each. Specific recommendations must be scientifically sound, clearly justified, and well documented. A
carefully written record of the response must be maintained for follow-up and legal reasons. The records
may be confidentially maintained in a patient's chart or in the provider's secure files.

TABLE 2–4.

DESIRED CHARACTERISTICS OF A RESPONSE

Timely
Current
Accurate
Complete
Concise
Supported by the best available evidence
Well-referenced
Clear and logical
Objective and balanced
Free of bias or flaws
Applicable and appropriate for specific circumstances
Answers important related questions
Addresses specific management of patients or situations

FOLLOW-UP

When recommendations are made, follow-up always should be provided in a timely manner. Follow-up is
required for assessment of outcomes and, when necessary, to reevaluate the recommendations and make
appropriate modifications; it is also a hallmark of a true professional and demonstrates a commitment to
patient care. Furthermore, follow-up allows the provider of the information to know if their
recommendations were accepted and implemented. Finally, follow-up also allows the provider to receive
valuable feedback from other clinicians and to learn from the overall experience.

Conclusion
Formulating e ective responses and recommendations requires the use of a structured, organized
approach whereby critical factors are systematically considered and thoughtfully evaluated. The steps in
this process include organizing relevant patient information, gathering information about the disease
states and a ected body systems, collecting medication information, obtaining pertinent background
information, and identifying other relevant factors that can potentially influence outcomes. Once these
data are collected and carefully assembled, they must be critically analyzed and evaluated in the proper

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context. Responses and recommendations are synthesized by integrating information from diverse sources
through the use of logic and deductive reasoning.

References

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