CHAPTER # 01

RATIONAL USE OF DRUGS

Contents
Rational use of drugs
Approaches to rationale use of drugs
Rationale prescribing
Irrational use of drugs
Factors responsible for irrational use of drugs
How to avoid irrational use of drugs
Sampling of drug use
Study design
Sampling methods
Iftikhar Ahmad
Session: 09-14
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CHAPTER # 01 RATIONAL USE OF DRUGS
Rational use of drugs:
According to W.H.O , rational use of drugs requires that patient receives medication, appropriate
to their clinical needs, in the doses that meet their own individual requirements, for adequate
period of time and to the lowest cost of them and their community.
Approaches to achieve rational use of drugs:
Rational use of drugs can be achieved by going through following steps.
i. Patient problem.
ii. Diagnosis
iii. Therapeutic goals
iv. Select the treatment
v. Start the medication
vi. Result of therapy
vii. Conclusion of therapy
i. Patient problem:
The clinician should try to find explanation to the patient problem. Two factors may
prove helpful in this case:
- History of illness.
- Patient history of medication.
ii. Diagnosis:
It can be made by:
- Past medical history
- Past medication history
- Present complaints
An accurate diagnosis is pre-requisite for rational use of drug. If patient is not diagnosed
properly, the use of drugs becomes irrational.
iii. Therapeutic goals:
Primarily, the therapeutic goals should include;
- Relieving of symptoms
- Prevention of disease
- Combination of both
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iv. Select the treatment:
Selection of treatment has two phases:
Phase-I:
In phase-I, it is determined that either any simple option is available i.e there is no need
of the drug. Anyhow, if drug use is necessary, suitable group of drug is selected.
Phase-II :
In this phase, the drug is evaluated on the basis of:
- Efficacy
- Safety
- Ease of administration
- Easy availability
- Cost effectiveness
- Storage condition
v. Start the treatment:
Inform the patient about the beneficial and side effects of the drug.
Instruct the patient how to deal with the side effects.
Patient should be given a date for the next visit so that result can be concluded.
vi. Result of therapy:
It should be assessed that if the problem has solved, therapy is rational and if, response
has not been shown, the therapy is irrational.
vii. Conclusion:
Determine;
If therapeutic objective has been achieved or not.
Has the drug use solved the patient problem?
RATIONAL PRESCRIBING
Definition
The right dose of the right drug for the right diagnosis to the right patient at right time and via
right route is called rational prescribing.
It is a balancing act that is composed of four major components.
i. Maximizing effectiveness.
ii. Minimizing risks.
iii. Minimizing costs.
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iv. Respecting the patient choice.
Criteria for Rational Prescribing
i. Appropriate diagnosis
ii. Appropriate medication
iii. Appropriate patient
iv. Appropriate dose and dosage regimen
v. Appropriate route of administration
vi. Appropriate duration
vii. Appropriate information
viii. Appropriate monitoring plant
ix. Appropriate program for patient education
i. Appropriate diagnosis
Appropriate diagnosis is based upon clinical picture and laboratory tests. Clinical picture
plays important role when lab facilities are not available, especially in remote areas.
For example, pneumonia in children can be diagnosed by counting the respiratory rate
and dwelling of chest in the absence of lab facilities.
Similarly a 35 years old woman suffering from pain in joints, stiffness, inflammation,
worsening early in the morning should be considered as patient of rheumatoid arthritis.
The diagnosis should be shared with the patient. It will save time, money and labor work.
Pathophysiological implications of diagnosis:
If pathophysiology of the patient is well understood, the prescriber is in a better position
to prescribe more rationally. E.g in rheumatoid arthritis, there is increase level of
inflammatory mediators. So the sound knowledge of all these mediators is very necessary
for prescriber in order to make proper diagnosis and rational prescription.
Selection of therapeutic objectives:
Therapeutic objectives are of two types:
(1). Short term therapeutic objectives
(2). Long term therapeutic objectives
Short term therapeutic goals include:
- Relief of pain
- Reduction of inflammation by decreasing level of mediators.
Long term therapeutic goals include:
- Prevention of disease
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- Prevent recurrences
- Prevent complications
ii. Appropriate medications:
The prescriber should know that either drug is needed or not.
The decision to prescribe medication depends upon medical rational. For example,
Diarrhea, may be viral (due to Rota virus) which needs no treatment or bacterial which
requires appropriate medication
Selection of drug of choice:
It is based upon following criteria:
- Efficacy,
- Suitability,
- Cost consideration
- Easy availability.
For selection of drug of choice, make list of all available options and then select the
group on the basis of above mentioned criteria.
The selection of group of choice is based upon host factors such as age, other diseases or
other therapy the patient is already taking.
Examples:
Penicillin sensitive patient should be given other antibiotics.
Aspirin is contraindicated for less than 12 years of age.
Ciprofloxacin is contraindicated in pregnancy and children.
iii. Appropriate patient
It should be ensured that:
- No contraindication exists.
- Likelihood of ADRs is minimal.
It is better to avoid drug during pregnancy and lactation.
Drug use in pregnancy is done by weighing the risk-benefit ratio of mother or fetus.
iv. Appropriate dose and dosage regimen
Appropriate dose should be prescribed for all categories of patients. It is necessary
because the dosage adjustment is required for pediatric and geriatric patients due to their
low metabolizing capacity of vital organs.
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Dosage regimen is determined by the pharmacokinetic of drug but patient history and
concomitted diseases such as renal and hepatic insufficiency should also be considered
before prescription.
Similarly for drugs accumulated in the kidney and metabolized in the liver, dose is also
adjusted e.g. penicillin.
v. Appropriate route of administration
If oral route is possible, avoid parentral route because parentral route is;
- Expensive
- Increased risk of ADRs chances
- Against rational criteria
vi. Appropriate duration
In certain disease, the prescriber fix the duration. But in some cases duration is not fixed
such as severe illness and chronic diseases.
For example, in case of cholera tetracyclies should be used for 3-days only. If it is used
for 5-7 days, it is irrational.
vii. Appropriate information
Patient should be provided with relevant, accurate and clear information about his/her
own condition and medication.
viii. Appropriate monitoring plan
Monitoring plan is of two types:
a. Active monitoring plan:
It is done by the physician with the help of lab investigation and physical
examination.
b. Passive monitoring plan;
It is done by the patient him/herself by telling the symptoms.
Advantage: it tells the patient not to stop medication before specified time.
On this basis disease can be categorized into two categories.
Disease that need little and limited therapy:
In this patient should be told not to stop the medication before the therapy course is over.
Disease that need prolong and indefinite therapy:
In this the patient should be told that if he/she feels any other symptoms or ADRs, he/she
should contact the prescriber.e.g rheumatoid arthritis.
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ix. Appropriate program for patient education
The physician and other health care members should be prepared to repeat, extend and
reinforce patient education program to make the drug use more rational.
Greater the potency of a drug, greater would be the need for patient education.
Irrational drug use
The ultimate medical criteria for drug use is to prevent, cure or relieve the diseases on the basis
of scientific documentation but unfortunately in real world prescribing pattern does not always
confer to these standards and as a result there is irrational drug use.
Key points responsible for irrational drug use
i. Selection of Drug
ii. Patient characteristics
iii. Lack of patient education and compliance
iv. Incorrect prescribing
v. Inappropriate prescribing
vi. Overprescribing
vii. Multiple prescribing
viii. Inappropriate administration
ix. Use of expensive drugs
i. Selection of drug
Find whether the drug is selected on the basis of efficacy, safety, cost and availability.
e.g.
Use of antimotility agents in acute diarrhea have doubtful and unproven efficacy. For
such case attapulgite is the ist drug of choice.
ii. Patient characteristics
Presence of factors such as hepatic or renal impairment may need:
Change in drug.
Change in dosage and duration.
Change in dosage form.
For Example;
Metronidazole normal dose is 900-1200 mg/day.
In case of hepatic insufficiency, the dose is to be reduced up to 300 mg/day.
iii. Lack of Patient education and compliance
Patient should be informed about the drug effects, side effects, warning and precautions.
Lack of these information, result in patient non-compliance leading to the irrational drug
use.
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iv. Incorrect Prescribing
It occurs when proper diagnosis has not been made, so the drugs prescribed will not be
the true drugs i.e wrong drug is prescribed due to wrong diagnosis or lack of knowledge.
Wrong diagnosis example: Use of tetracycline in childhood diarrhea when they can be
treated with O.R.S.
Lack of knowledge example: Substitution of ciprofloxacin with erythromycin.
(Note: Always start with narrow spectrum antibiotics)
v. Inappropriate prescribing:
In certain cases, the drug prescribed is not the drug of choice.e.g in endocarditis
aminoglycoside and penicillin groups are drugs of choice. If ceftriaxone is prescribed, it
is irrational. Similarly prescription of antibiotics for viral respiratory infection would be
irrational.
vi. Overprescribing
It includes;
a. Polypharmacy.
b. Combination of two or more drugs.
c. When the drug in the prescription is not needed.
d. Excessive dose.
e. Unnecessary long time treatment.
vii. Multiple prescribing
It means prescription contains large number of drugs although few drugs can produce
beneficial effects
.
viii. Inappropriate administration
It means the selection of parentral route when the oral route is feasible and vice versa.
E.g selection of Ampicillin-G injection is inappropriate administration for a stable
patient, so select ampicillin capsules.
ix. Use of expensive drugs
Use of expensive drugs is irrational such as prescription of 3
rd
generation cephalosporins
is irrational when the spectrum is covered by ist and 2
nd
generation cephalosporins.
The use of expensive medicines in Pakistan is due to promotional activities of
pharmaceutical firms.
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Factors Responsible For Irrational Drug Use
Following factors may be considered responsible for irrational drug use.
i. Patient related factors.
ii. Prescriber related factors.
iii. Work-place related factors.
iv. Drug related factors.
i. Patient related Factors
These include:
a. Drug information
b. Misleading believing about therapy
c. Patient demand and expectation
d. OTC
e. Self treatment
f. Taking drugs more than instructed.
g. Selecting inappropriate route of administration
ii. Prescriber related Factors
These include:
a. Lack of education and training.
b. Misleading belief about drug efficacy.
c. Lack of objective drug information.
iii. Work place related factors
These include:
a. Heavy patient load.
b. Lack of lab facilities.
c. Lack of staff.
iv. Drug supply related
a. Drug shortage
b. Unreliable supplies
c. Expired drug supplies
i. PATIENT RELATED FACTORS
a. Drug information
Proper majority have no knowledge about drugs .e.g. expired medication may be
taken.
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b. Misleading belief about therapy
Even educated people may have certain misbelieves about certain antibiotics
related to gastric upsets and so, and/or taking any medicine with milk, not
specified.
c. Patient demand and expectation
Usually if the patient has trust in prescriber, he/she demands and expects therapy
from the prescriber which would benefit him/her and thus, the patient shows
compliance. It is much important, usually in psychiatric cases.
d. OTC
A patient taking certain OTC may not get benefited, and so, when he/she visits
physician, the physician may prescribe the same generic the patient is already
taking, thus leading to irrationality.
e. Self treatment
Sometime a patient may start self treatment, which is irrational e.g. using
Vibramycin cap and Ansid tab for tooth ache as self treatment.
f. Taking drug more than instructed
It means to take high dose intentionally to get healthier quickly. It may be life
threatening if the drug is potent.
g. Inappropriate route of administration
It may be very hazardous to administer parentral by the patient him/her self. So
skillful personnels are required.
ii. PRESCRIBER RELATED FACTORS
a. Lack of education and training
Lack of education and training on prescriber part is also one of the cause of
irrational drug use. For example, Tab erythromycin 250 mg t.i.d for adult is
irrational.
b. Misleading belief about drug efficacy
For example, there is a general concept that citalopram enhances the suicidal
tendency where as escitalopram decreases the suicidal tendency, but it is a pseudo
concept and has no justification.
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c. Lack of object drug information
It is very important in case of potent drugs. for example, warfarin has 99%
protein binding. If phenylbutazone is given simultaneously, it displaces 1%
warfarin, leading to life threatening consequences.
iii. WORK-PLACE RELATED FACTORS
a. Heavy patient load
If the number of patient is large, then the clinician may not give proper
consultation time to the patient which ultimately will result in irrational drug use.
b. Lack of lab facilities
In remote areas, usually lab facilities are not available. Thus proper diagnosis may
not be made by the clinician and there is a chance of irrational prescription.
Anyhow, if lab facilities are available and the physician does not ask for lab test,
it is irrational.
c. Lack of consultation time:
If there is lack of consultation staff, there will be lack of consultation time for
patient and will lead to irrational.
iv. DRUG SUPPLY RELATED FACTORS
a. Drug shortage
Drug shortage may leads to drug substitute by the dispenser which is irrational
without the permission of physician.
b. Unreliable supplies:
Unreliable drug supply at the retail pharmacy is also one of the major factors
contributing to irrational drug use.
c. Expired drug supplies:
Dispensing of expired drugs also leads to irrational use of drugs. So it is the
responsibility of retail pharmacist to check the expiry date before filling a
prescription. The general rule First in, First out should be followed to minimize
this factor.
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PROBLEMS OF IRRATIONAL DRUG USE
1. Reduction in quality of drug leading to increase in diseases and high death rates
2. Wastage of resources leading to reduced availability of vital drugs and increased costs.
E.g Prescribing parentral product when oral route is feasible such as prescribing
augmentin injection instead of tablets.
3. Increased risk of unwanted effects such as adverse reactions
4. Development of drug resistance because basic diagnostic tests are not performed before
prescription. e.g. prescribing 3
rd
generation cephalosporins without performing culture
sensitivity test.
5. Irrational drug use leaves negative psychological impact on the patient about therapy as
well as prescriber.
HOW TO AVOID IRRATIONAL DRUG USE
Irrational drug use can be prevented by having thorough knowledge of:
i. Generic name and cost of therapy
ii. Pharmacokinetics and pharmacodynamics
iii. Effectiveness of therapy in the condition being treated and its advantage over the other
drugs.
iv. ADRs, precautions, contra indications, drug interactions and dosage regimen.
v. Toxicology of drug and its treatment.
INDICATORS OF DRUG USE
WHO provided following indicators of drug use may be implemented.
1. Prescribing indicators
2. Patient care related indicators
3. Facility indicators
1. Prescribing indicators
The prescribing indicators include:
i. Average number of drugs per encounter.
ii. % age of drugs prescribed by generic names.
iii. % age of antibiotics prescribed
iv. % age of injection prescribed
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i. Average no of drugs per encounter
If the prescription contains more drugs, there are more chances of drugs interactions. In
order to minimize that risk, the average number of drugs per encounter should be
minimum, making the prescription more rational.
ii. % age of drugs prescribed by generic names
Usually, there is promotional stress on the physician from pharmaceutical companies to
prescribe their brands. To avoid this, WHO indicates that prescription should contain
drugs by their generic names.
iii. % age of antibiotics prescribed
Before prescribing antibiotics, culture sensitivity test should be performed and the
therapy should be started with narrow spectrum antibiotics.
iv. % age of injection prescribed
Cost effectiveness is necessary which depends upon the route of administration.
Prescription of injectable would be rational only if oral route is not feasible, otherwise it
would be irrational.
2. PATIENT CARE RELATED INDICATORS
i. Average consultation time
If the physician does not give proper consultation time, he/she may not be able to make
proper diagnosis and thus there is a chance of irrational prescription. So due consultation
time is of extreme importance.
ii. Average dispensing time
Dispensing is the responsibility of pharmacist. Less dispensing time may be due to either
lack of knowledge or increase workload, leading to irrational use of drugs.
Thus, it is the responsibility of pharmacist to give proper dispensing time to the patient,
preferably using patient mother language and asking for the feedback to confirm that
patient has understood what he/she has been told.
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SAMPLING OF DRUG USE
Definition:
Sampling is a process by which we study a small part of a population to make judgments about
that population.
Whenever we want to learn about health in the community or practices in the health system, we
need to draw samples since it would be impractical to collect data on every person or event. In
drug use surveys we need to draw samples to select facilities to survey, prescriptions to study, or
patients to observe.
So, to get a representative sample we would need to ensure that all facilities or patients can be
included in the survey.
Sampling involves the selection of a number of study units from a defined study
population.
A study unit may be a person, a health facility, a prescription, or another such unit.
The study population, sometimes called the reference population, is the collection of the entire
population of all possible study units. Again, this population may be people, health facilities,
prescriptions or other such units.
A representative sample has all the important characteristics of the
population from which it is drawn.
Objectives:
i. To establish efficacy of the drug.
ii. To study risk aspects of the drug including both long term and short term side effects.
iii. To study risk benefit ratio of drug prescribing.
iv. To study the socio-economic aspects of the drug.
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STUDY DESIGN
There are two types of approaches/study design for sampling of drug use, which are:
1. Experimental study
2. Non-experimental study
1. Experimental studies
These are also called Randomized Controlled clinical trials.
In this design, the researcher controls assignment of study by random allocation of participant to
the treatment.
This design is particularly used for detection of ADRs. E.g association of clofibrate( lipid
lowering agent) and cholecystitis.
2. Non-experimental studies:
These are of two types :
i. Cohort study
ii. Case control study
i. Cohort study:
Cohort studies are conducted to determine the agent under investigation (drug or risk
factor) for an outcome (effect or disease) . In this case, the individuals are divided into
two groups . i.e exposed group which has exposure to the risk factor/drug and unexposed
group which has no exposure to the risk factor and then the variable of interest (
outcome/disease) is observed.
For example, does exposure to smoking ( agent under investigation) associate with lung
cancer ( outcome ). Such a study would recruit a group of smokers and a group of non-
smokers (the unexposed group) and follow them for a set period of time and note
differences in the incidence of lung cancer between the groups at the end of this time.
ii. Case control study:
A study that compares patients who have a disease or outcome of interest (cases) with
patients who do not have the disease or outcome (controls), and looks back
retrospectively to compare how frequently the exposure to a risk factor is present in each
group to determine the relationship between the risk factor and the disease.
The goal is to retrospectively determine the exposure to the risk factor of interest from
each of the two groups of individuals: cases and controls. These studies are designed to
estimate odds.
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Case control studies are also known as "retrospective studies" and "case-referent studies
SAMPLE SIZE
The appropriate sample size depends on:
Expected variation of the data:The more variation the larger sample required.
The expected rate of the variable: For example, a smaller sample will be required to
obtain the same degree of accuracy if the rate of antibiotic prescribing is 50% than if the
rate is 15%.
The degree of accuracy required: The larger the sample, the less the uncertainty.
The appropriate sample size is usually a compromise between what is STATISTICALLY
DESIRABLE and what is FEASIBLE.
In general, a minimum sample size is 30
SAMPLING METHODS
There are two broad types of sampling methods. These are:
Non -- probability sampling
Probability sampling
The method of sampling depends whether there is a sampling frame available.
If a sampling frame exists, or if it can be created, probability sampling is used.
If sampling frame is not available, probability samplings cannot be used.
A sampling frame is a list of all of the available units in the study population. If a complete
listing is available, the sampling frame is identical to the study population.
It is always better to use probability sampling,because;
- Probability sampling is more effective than than non probability methods.
- The results of non probability sampling methods are not valid because there is
supposition.
However, in some situations, non -probability sampling is the only possible method.
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A. NON -PROBABILITY SAMPLING METHODS
If a sampling frame is not available or it cannot be created, a non-probability sampling method
will need to be used.
There are two common methods.
These are :
- Convenience sampling
- Quota sampling.
1. Convenience Sampling is a method which refers to sampling by obtaining units or
people who are most conveniently available, at the time of data collection. Convenience
samples are least reliable but normally the cheapest and easiest to conduct.
2. Quota sampling is a method by which different categories of sample units are included
to ensure that the sample contains units from all these categories. For example, a quota
sample of patients from a health center that might included 10 patients with Acute
Respiratory Infection, 10 with diarrhea, and 10 with malaria.
Non-probability sampling is not necessarily representative of the reference population.
However, we often need to use these methods ;
- when we have inadequate record sample frames
- or when a time constraint exists.
-
B. PROBABILITY SAMPLING METHODS
If a sampling frame (a list of the population units) exists then probability sampling may be used.
Whenever possible, use probability sampling to obtain results which are not less biased. There
are a number of different methods.
Probability sampling involves RANDOM selection procedures to
ensure that each sample unit is chosen on the basis of CHANCE.
1. Simple Random Sampling
This is the simplest form of simple probability sampling. A lottery is an example of a random
sample. The simple random sampling procedure is as follows:
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a) Make a numbered list of all units in the reference population from which you will select the
sample (for example, a list all the health centers in the country)
b) Decide on the size of the sample (for the WHO Drug Use Indicators method this would be a
minimum of 20 facilities).
c) Choose the facilities to include by a lottery method. (For example the numbers of all the
facilities can be placed in a box and drawn, a random number table can be used, or random
numbers can be generated using a spreadsheet or calculator.
2. Systematic Sampling
In systematic sampling, samples are randomly selected from a list of entire population at a
regular interval.
To calculate the sampling interval, divide the size of the list by the desired sample size.
For example, if we want to select 20 health centers from a list of 46 in our sampling frame, our
sampling interval would be 46/20 = 2.3.
It means all the 46 have 2.3 times chance of selection in the list.
3. Stratified Sampling
The population is broken down into particular groups sharing common factors and participants
are selected randomly from these groups in the appropriate proportions.
For example, this would might be the case in a study which included urban and rural facilities,
facilities with or without doctors, male or female patients.
When stratified sampling is used, the sample frame (the list of the overall population) is divided
into two or more groups. These different strata (groups) may then be sampled either randomly or
systematically.
The WHO manual recommends the use of stratified systematic sampling methods for selecting
facilities. For example, the sampling frame might include the following list of facilities.
Fascility
number
1 2 3 4 5 6 7 8 9 10
Type Urban Rural Rural rural Urban Rural Urban Urban Rural Rural
This could then be grouped and sorted into 2 strata as follows:
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Fascility
number
1 5 7 8
Type Urban Urban Urban Urban
and a sample would be selected separately from both the urban list and the rural list.
4. Clustor Sampling
In a clustor sample, a group of sample units is selected together, rather than each unit being
selected separately.
The recommended EPI WHO sampling procedure of selecting 30 groups of 7 children is a
common cluster sampling method.
Advantages
- Easy to use.
- Simpler to organize.
Disadvantage
The samples selected may be less representative especially when the number of clusters selected
is low.
5. Multistage Sampling
When the two or more sampling methods are combined, then t is called multistage sampling. For
example, we might wish to select 32 health facilities in 56 districts of Pakistan, each of which
contains a number of health facilities. From the 56 districts, 16 districts would first be selected.
In each district two health facilities would then be randomly selected. This would be two stage
random sampling.
By :
Iftikhar Ahmad (E)
Session 2009-14
Fascility
number
2 3 4 6 9 10
Type Rural Rural Rural Rural Rural Rural