Basic Principal of Rational

Pharmacotherapy

Mustofa
Laboratorium Farmakologi & Terapi
Fakultas Kedokteran-Kesehatan Masyarakat dan Keperawatan
UGM Yogyakarta

Locally Rooted, Globally Respected www.ugm.ac.id

 Case :
A 1 week old, 4 kg infant develops neonatal septicaemia
and meningitis. A broad spectrum antibiotic that
penetrate the CSF is desired. Chloramphenicol (100
mg/kg/day) is chosen since it meets both criteria. After 4
days, baby develops listlessness, refusal to suckle,
abdominal distention, and regular and rapid respiration.
This syndrome progresses to periods of cynanocis,
flaccidity, hypothermia, and the baby develops an ashen
gray color. The antibiotic is stopped, and the infant
recovers. What happened?

Locally Rooted, Globally Respected www.ugm.ac.id

 Rational therapeutics
Priscribing drug in manner that maximizes clinical
effect (maximizing efficacy and minimazing
toxicity), functional status, and overall patient
satisfaction, at the lowest possible total cost.

Rational therapeutics try to individualize the

therapeutic plan to match the need of a particular
patient based on scientific principles of medicine
and pharmacology.

Locally Rooted, Globally Respected www.ugm.ac.id

 WHO conference of experts Nairobi 1985
The rational use of drugs requires that patients receive
medications appropriate to their clinical needs, in doses
that meet their own individual requirements for an
adequate period of time, and at the lowest cost to them
and their community.
• correct drug
• appropriate indication
• appropriate drug considering efficacy, safety, suitability for
the patient, and cost
• appropriate dosage, administration, duration
• no contraindications
• correct dispensing, including appropriate information for
patients
• patient adherence to treatment
Locally Rooted, Globally Respected www.ugm.ac.id
 Philosophy of Pharmacotherapy
• Pharmacotherapy involves a great deal more than
matching the name of the drug to the name of
disease;
• It requires knowledge, judgment, skill and wisdom,
but above all a sense of responsibility;
• A book can provide knowledge and can contribute
to the formation of judgment, but it can do little to
impact skill and wisdom, which are the products of
experience and innate and acquired capacities.

Locally Rooted, Globally Respected www.ugm.ac.id

Process of Rational Pharmacotherapy

Process of Rational Result of

Patient Presentation
Therapeutics Intervention

Presenting 1. Making Dx 2. Understanding Functional Outcome

symptoms pathophysiology • relief of symptoms
Clinical
Clinical outcomes Patient
Patient
features • efficacy satisfactions
expectations
of illness 3. Reviewing menu • toxicity
of Rx options • morbidity
Potential • mortality Costs
consequences • direct
4. Selecting • indirect
optimal drug/
dose for patient

6. Making alliance 5. Choosing

with patient, endpoints
following to follow
endpoints

Locally Rooted, Globally Respected www.ugm.ac.id

 6 Key Steps When Practicing of Pharmacotherapy

1. Making diagnosis with reasonable certainty,

2. Understanding pathophysiology of the disease and the
opportunities for the interventions,
3. Understanding the pharmacology of the drugs that could be
used to treat the disease,
4. Selecting the drug and dose that are likely to be optimal for
the specific patients,
5. Selecting appropriate endpoints of efficacy and toxicity to
follow,
6. Developing a therapeutic alliance with the patients, and
maintaining it.

Locally Rooted, Globally Respected www.ugm.ac.id

 Factors in implementation
of rational pharmacotherapy

Intrinsic
Information Prior
Knowledge
Scientific
Habits
Information

Influence Social &

of Drug Industry Cultural Factors

Societal
Workload & Economic &
Staffing Prescribing Legal Factors

Workplace
Infrastructure Authority &
Relationships Supervision
With Peers

Workgroup

Locally Rooted, Globally Respected www.ugm.ac.id

Need for rational drug therapy
• Drug explosion : increase in the number of drug available has
complicated the choice of appropriate drug for particular
indication,
• Effort to prevent the development of resistance : irrational drugs
use may lead premature demise of highly efficacious & life saving
new antimicrobial drug due to resistance.
• Growing awareness: the information about drug development,
it’s use & adverse effects travel with amazing speed through
various media,
• Increased cost of treatment : increase in drug cost increases
economic burden on the public and government. It can be reduce
by rational drug use,
• Consumer Protection Act (CPA): Extension of CPA in medical
profession may restrict the irrational drugs use.

Locally Rooted, Globally Respected www.ugm.ac.id

 Philosophy of Pharmacotherapy
• Pharmacotherapy involves a great deal more than
matching the name of the drug to the name of
disease;
• It requires knowledge, judgment, skill and wisdom,
but above all a sense of responsibility;
• A book can provide knowledge and can contribute
to the formation of judgment, but it can do little to
impact skill and wisdom, which are the products of
experience and innate and acquired capacities.

Locally Rooted, Globally Respected www.ugm.ac.id

Need for rational drug therapy
• Drug explosion : increase in the number of drug available has
complicated the choice of appropriate drug for particular
indication,
• Effort to prevent the development of resistance : irrational drugs
use may lead premature demise of highly efficacious & life saving
new antimicrobial drug due to resistance.
• Growing awareness: the information about drug development,
it’s use & adverse effects travel with amazing speed through
various media,
• Increased cost of treatment : increase in drug cost increases
economic burden on the public and government. It can be reduce
by rational drug use,
• Consumer protection Act (CPA): Extension of CPA in medical
profession may restrict the irrational drugs use.

Locally Rooted, Globally Respected www.ugm.ac.id

 Case :
A 68 year old women with metastatic breast cancer was
admitted to the hospital for radiation therapy of painful
bone metastases. She was given large dose of
meperidine, up to 100 mg every 2 hours, to control her
pain. Due to unrecognized prerenal azotemia and
hypercalcemia, she developed progressive renal failure,
and her creatinine increased from 1.4 mg/dL on
admission to 4.2 mg/dL 4 days after. On her 5th hospital
day, she had severe myoclonic jerking movements of her
extremities. By the next day, she had severe and
refractory grand mal seizures.

Locally Rooted, Globally Respected www.ugm.ac.id

 Problems with Irrational Pharmacotherapy

Locally Rooted, Globally Respected www.ugm.ac.id

Problems with Irrational Pharmacotherapy
Diagnosis
1. Complex diseases or health problems:
A patient has many symptoms, but is embarrassed to talk about the
main one, so the situation does not get addressed
2. Lack of appropriate training skills by prescribers to give
proper diagnosis:
Prescriber does not do a physical exam and prescribes drugs based
solely on oral information provided by the patient
3. Overworked prescribers:
Health facility has only one prescriber, and an average of 300
patients per day to consult
4. Lack of basic diagnostic equipment and tests
No microscope or reagents to examine blood & urine
No x-ray machine to test a patient suspected of having tuberculosis
Locally Rooted, Globally Respected www.ugm.ac.id
Prescribing
1. Using expensive drugs when equivalent ones are available
The antibiotic cefalexin is more expensive than co-trimoxazole in treating simple
infections.
Ampicillin injection is prescribed when the patient could take ampicillin tablets,
which are cheaper, easy to take, and involve lower risk of side effects

2. Selecting the wrong drug for the patient’s illness

An antidiarrhoeal drug is prescribed when the patient is dehydrated with simple
diarrhoea and only ORS is needed.
3. Prescribing several drugs when fewer drugs would provide the
same effect
Sulfadoxine/pyrimethamine and paracetamol are prescribed when the patient has fever,
but not malaria

4. Prescribing drugs when the disease is self limiting and the

patient would get better without taking any drugs
Ampicillin is prescribed when the patient has a simple cold, without sore throat, cough or
fever.

Locally Rooted, Globally Respected www.ugm.ac.id

 Dispensing
1. Wrong interpretation of the prescription:
Ampicillin is prescribed, but amoxicillin is dispensed.
2. Wrong quantity dispensed
Artemether/Lumefantrine is prescribed to be taken four tablets
two times daily for three days (should be a total of 24 tablets),
but the patient only receives 16 tablets, which is sufficient for
only 2 days
3. Labelling incorrect or inadequate
Sulphadoxine/pyrimethamine (white tablet) is dispensed, but
the name of the drug is not written on the container label,
meaning that the drug will be unidentifiable once the patient
leaves the pharmacy

Locally Rooted, Globally Respected www.ugm.ac.id

 4. Incorrect/insufficient dispensing information:
Paracetamol 250mg is prescribed for a child, but only
paracetamol 500mg is available in the pharmacy. The
higher dosage pill is given to the child’s mother without
telling her to divide the tablet before giving it to the child

5. Unsanitary practices:
20 tablets of paracetamol 500mg were being counted,
when some tablets fell to the floor. These were picked up
and dispensed to be given to the patient anyway

Locally Rooted, Globally Respected www.ugm.ac.id

 Packaging
1. Poor quality of packaging material
Packaging material must protect the drug against the sun and
humidity in order to ensure the integrity and quality of the dosage
form required by the patient

2. Inadequate container size when repackaging the product

The size of the packaging material must conform to the quantity of
medication dispensed. In the case of oral drugs, too large a container
could cause break-up of the items packed within

3. Inadequate labelling and identification of the drug

After the patient leaves the health centre and arrives home, it is very
easy to forget instructions given by the prescriber and dispenser.

Locally Rooted, Globally Respected www.ugm.ac.id

 Poor Compliance
Compliance is the degree to which the patient
carries out the physician’s instructions on how to
take the prescribed drug and treatment.
Many studies about outpatient compliance carried
out in developing countries indicate that only about
50% of patients follow the instructions given by the
physician

Locally Rooted, Globally Respected www.ugm.ac.id

 Causes of poor compliance include:
1. Improper labelling
Neither the name of the patient, nor the name of the drug is
on the container labels when dispensed. If two or more drugs
are dispensed together, the patent does not know which
drug he/she is taking
2. Inadequate instructions:
The instructions on dosage frequency must be written on the
drug label, or the patient could forget how to take it when
he/she arrives home and becomes involved in other activities
3. Treatment /instructions that do not consider the socio-
economic and cultural aspects of the patient
In cases where the patient does not know how to read,
proper instructions would include graphic symbols of how to
take the drug.

Locally Rooted, Globally Respected www.ugm.ac.id

 Explanations Poor Compliance :
• Lack of knowledge
• Influenced by others
• Negative attitudes
• Own experience
• Own perceptions
• Difficult/complicated regimen
• Extremes of age and need for assistance

Locally Rooted, Globally Respected www.ugm.ac.id

 Consequences in Irrational Therapy
1. Public health and economic consequences
• Adverse possibility lethal effects, e.g. due to antibiotic misuse
or inappropriate use of drugs in self medications
• Limited efficacy, e.g. in the case of under-therapeutic dosage
of antibiotic, tuberculosis or leprosy drugs
• Antibiotic resistance, due to widespread overuse of
antibiotics as well as their use in under-therapeutic dosage
• Drug dependence, e.g. due to daily use of pain killers and of
tranquilizers
• Risk of infection due to improper use of injections: abscesses,
polio, hepatitis and HIV/AIDS

Locally Rooted, Globally Respected www.ugm.ac.id

 2. Adverse drug events
• 4-6 th leading cause of death in the USA
• Estimated costs from drug-related morbidity &
mortality 30 million-130 billion US$ in the USA
• 4-6% of hospitalisations in the USA & Australia
• Commonest, costliest events include bleeding,
cardiac arrhythmia, confusion, diarrhoea, fever,
hypotension, itching, vomiting, rash, renal failure

Locally Rooted, Globally Respected www.ugm.ac.id

 3. Antimicrobial resistance
• Malaria
• choroquine resistance in 81/92 countries
• Tuberculosis
• 2 - 40 % primary multi-drug resistance
• Gonorrhoea
• 5 - 98 % penicillin resistance in N. gonorrhoeae
• Pneumonia and bacterial meningitis
• 12 - 55 % penicillin resistance in S. pneumoniae
• Diarrhoea: shigellosis
• 10-90+ % amp, 5-95% TMP/SMZ resistance

Locally Rooted, Globally Respected www.ugm.ac.id

 4. Economic consequences
• Inappropriate drug use or irrational therapy
have also a impact on household and national
health budgets,
• Example :
✓ the use of expensive brand-name product
while cheaper generic drug are available,
✓ combinations preparation,
✓ multi-drug prescribing

Locally Rooted, Globally Respected www.ugm.ac.id

 Strategies to improve use of drugs
Educational:
✓ Inform or persuade
– Health providers
– Consumers
Managerial:
✓ Guide clinical practice
– Information systems/STGs
– Drug supply / lab capacity

Use of
Medicines

Economic: Regulatory:
✓ Offer incentives ✓ Restrict choices
– Institutions – Market or practice controls
– Providers and patients – Enforcement

Locally Rooted, Globally Respected www.ugm.ac.id

Interventions targeted at prescribers
1. Educational materials
• Standard treatment guidelines or clinical guidelines
• Bulletins/newsletters
• Flow charts/diagnostic cards
• Simple forms of printed informations
2. Approaches to introduce educational materials
• Face to face education
• Seminar or workshop
• Focus group discussion/participatory training approach
• Peer review and feedback
• In-service training/supervision
• Involving the target group in developing of training materials
• Drug informations centers

Locally Rooted, Globally Respected www.ugm.ac.id

 3. Managerial Strategies
• Essential drug list
• Kit system distribution
• Pre-printed order form
• Stock control
• Course-of-therapy packaging
• Effective package labelling
4. Financial interventions
• Drugs are sold at a slightly higher price to create a fund for
improving PHC services
• Making people pay for drugs could reduce overconsumption
• Improve drug supply and cost-sharing
5. Regulatory strategies
• Banning unsafe drugs
• Limiting the import of drugs on the market

Locally Rooted, Globally Respected www.ugm.ac.id

 2. Interventions targeted at consumers/patients
1. Educational materials
• Patient education
• Public education
2. Managerial strategies
• Course of therapy packaging
• Blister packs facilitated patient adherence to
leprosy treatment
• The use of antimalarial drug packaging resulted in
a significant improvement in patient compliance
3. Financial interventions
• Community revolving drug funds

Locally Rooted, Globally Respected www.ugm.ac.id

 Terima kasih

Locally Rooted, Globally Respected www.ugm.ac.id