الفهرس 
Introduction
Effect of a drug interactionOnly 14 pages are availabe for public view
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Abstract
A drug-drug interaction may be defined as the pharmacologic or clinical response
to the administration of a DDI combination different from that anticipated from the known
effects of the two agents when given alone. Also, an interaction is said to occur when the
effects of one drug are changed by the presence of another drug, food, drink or by some
environmental or chemical agent.
The interaction may be potentiation or antagonism of one drug by another, or
occasionally some other effect. The clinical result of a DDI may manifest as antagonism
(i.e. 1 + 1 < 2), synergism (i.e. 1 + 1 > 2), or idiosyncratic (i.e. a response unexpected from
the known effects of either agent). When evaluating any potential drug interaction, a
primary concern is the clinical relevance or significance of the interaction (significance
rating, onset, severity and documentation) then, mechanism of drug interaction which may
be pharmacodynamic; affect the processes by which drugs are absorbed, distributed,
metabolized and excreted, or pharmacokinetic in which the effects of one drug are changed
by the presence of another drug at its site of action.
In order to avoid DDIs, physicians should be able to detect and recognize the drug
interaction related signs and symptoms, choose a drug with higher therapeutic index,
monitoring drugs with narrow therapeutic index and to optimize the number of drugs per
prescription. In order to monitor the undesirable effects of an interaction, it may be
necessary to change one of the drug pairs to a non-interacting agent ”substitution”, alter the
dose of the interacting drug when therapy by the precipitant drug is initiated or
discontinued ”dose adjustment”, separation of doses of interacting agents ”spacing of
dosing times”, in addition to ”close monitoring” of the therapy, so that drug combinations
do not have to be avoided.
Objectives of the study:
To describe the epidemiological characteristics of patients in the CCUs in
Alexandria main university hospital, to determine the prevalence of DDIs among
medications prescribed to the patients and to classify DDIs according to their severity.
Materials and methods:
A cross sectional study was carried on 750 patients admitted to the CCUs (namely
1st and 3rd CCUs) of Alexandria Main University Hospital (all ages and both sexes) whose
medical prescriptions contain 4 or more drugs, excluding the topical drugs (ointments,
creams, ear drops, eye drops). The sample was calculated using Epi info 6 program taking
into consideration the prevalence of DDI to be 8.4%, (8) with a level of significance 5% and
level of precision 2%.
The data collection tools and methods included:
• Interview with the patients (if conscious) or one of their relatives (during the
official times for the visit) using a pre-designed interview questionnaire was used
for the collection of socio demographic data as: age, sex, marital status, education
and occupation as well as social habitual risk factors as smoking cigarettes and
shisha.
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• Record review of CCUs on admission, during the hospital stay for completion and
on discharge. The data collected included the present medical history (diagnosis)
with the observation of any kidney or liver abnormalities, comorbid conditions,
chronically (long-term) used medications, any present hospital acquired infection
and its type, Acute Physiology And Chronic Health Evaluation score (APACHE II
score), length of stay in CCU, Lab abnormalities and 24 hour prescriptions which
included number of drugs per prescription, dosage form, doses and dose regimen
with the observation of the number of prescribing physicians during the patient’s
stay in the CCU.
The list of drugs for each prescription was analyzed using Drug interaction checker
software ”Drug Interaction Facts” (iFacts-AZ) published by ”Facts and Comparisons”,
stockley’s drug interaction, British national formulary and other free online drug
interaction checkers. Drug Interaction Facts classifies the severity of an interaction into
three categories: major, moderate, and minor. It classifies the degree of documentation into
five categories: established, probable, suspected, possible, and unlikely, while the onset of
interaction into rapid and delayed; it also assigns a significance of 1-5 to each interaction,
based on a combination of these two categorizations.
Data were coded and entered to computer using the Statistical Package for Social
Sciences (SPSS version 16.0 software) for tabulation and analysis. Descriptive statistics
using frequency distribution tables and graphs were used.
Results:
As regards the epidemiological characteristics of patients in the CCUs, namely 1st
and 3rd critical care units, the age ranged from 9 months to 99 years with a mean of 44.46
years. More than one third (34%) of the critically ill patients were in the age group from 40
years to less than 60 years. The percentage of males was slightly larger than females
(54.80% and 45.20% respectively). More than two thirds (69.62%) of the studied sample
were married, those who were illiterate constituted more than one third (34.17%) of the
studied sample and more than one third of the studied sample (33.53%) was housewives.
About two thirds (59.39%) of the patients were nonsmokers, while about 41% were
smokers and the mean duration of smoking was 21.84±13.09 years. Nearly 61% were
heavy smokers and the majority of patients weren’t shisha smokers.
The mean length of stay in the CCU was 9.02±12.70 days ranging from 1-125 days.
As regards the lab abnormalities, two thirds of patients (68%) had lab abnormalities.
Among them, nearly 44% had both kidney and liver abnormalities, while 32.35% had only
kidney dysfunction and 24.31% had liver dysfunction. Concerning the principle conditions
for admission of patients to the CCUs less than half (44.53%) of the patients were admitted
due to cardiovascular diseases while about one fifth (19.60%) were admitted for
respiratory reasons. About 62% of patients had co-morbid conditions, of which less than
half of patients (46.46%) had cardiovascular diseases and about one fourth (26.25%) of
patients had endocrinological and metabolic diseases. Also more than half (53.47%) of the
patients used medications.
The prevalence of DDIs among patients admitted to CCUs was 53.07%. The
number of DDIs ranged from 1-12 drug interactions with a mean value of 2.98±1.91
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interactions. The majority of patients (67.34%) had 1-3 interactions among their
medications. The most frequent interactions resulted from the co-administration of
Clopidogrel with Aspirin (47.99%). About 34% of DDIs had a significance number 4.0,
the majority (71.91%) was found to have delayed onset, about 60% were found to have a
moderate severity and 38.2% of the interactions had a possible documentation.
The logistic regression model revealed that only two variables were significantly
affecting the development of DDIs. The first was the age of the patient. DDIs are 1.02
times more likely to develop among patients in the older age groups than among patients in
the younger age groups (OR=1.023). The second variable was the number of prescribed
drugs.
It was concluded that critically ill patients are at risk of potential drug interactions.
So, to avoid DDIs and improve the treatment of hospitalized patients in the CCUs
continued education, computer system for prescriptions, pharmacotherapy monitoring of
patients and the pharmacist participation in the multidisciplinary team are essential.
Conclusion:
The study demonstrated a high prevalence of potential DDIs in the ICUs (53.07%)
due to the complexity of pharmacotherapy. Positive associations were observed between
the occurrence of DDIs and the patient’s age and number of prescribed drugs, which
suggests that DDIs are a significant clinical problem in which potential harm to patients
could be avoided.
Recommendation:
The most important recommendations of this study are:
• Emphasize the role of clinical pharmacists as an inpatient services.
• Establishing a method for reporting any identified medication related problems
and the optimal strategy for solving the identified problems.
• Efforts must be directed towards improving communication between the
different healthcare providers in the ICUs.
• It is important that medical students should be taught about drug interactions,
their mechanisms and effects, how to obtain information about them, and how
to avoid them.