RATIONAL DRUG USE

Dr Bassi PU MBBS, MSc, FMCP

Consultant Physician/Clinical Pharmacologists

University of Abuja

MBBS Lecture Series

​

Objectives

• Define rational use of medicines and identify the magnitude of the problem

​

• Understand the reasons underlying irrational use

​

• Discuss strategies and interventions to promote rational use of medicines

​

• Some questions to ponder

Definition

• 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.�WHO conference of experts Nairobi 1985
• Oxford English Dictionary defines “rational” as that which is based on reason, which is sensible, same, or moderate.
• The definition implies that rational use of drugs, especially rational prescribing, should meet certain criteria as in next slide

​

‘Criteria’ for Using Medicines

• Rational drug therapy may be used interchangeably with the concept of prescribing .
• Appropriate indication
• Affordable cost
• Appropriate dispensing,administration, dosage and duration
• Appropriate patient
• Appropriate patient information
• Appropriate drug considering efficacy, safety, suitability for the patient

​

Criteria’ for Using Medicines

• Appropriate indication: The decision to prescribe drug(s) is entirely based on medical rationale and the drug therapy is an effective and safe treatment.
• Appropriate drug: The selection of drugs is based on efficacy, safety, suitability, and cost considerations.
• Appropriate patient: No contraindications exist, the likelihood of adverse reactions is minimal and the drug is acceptable to the patient.
• Appropriate patient information: Relevant, accurate, important, and clear information is given to patients regarding their conditions and the medication(s) that are prescribed.
• Appropriate evaluation: The anticipated and unexpected effects of medications are appropriately monitored and interpreted

Irrational use of medicines

Irrational use of medicines is a major problem worldwide

• More than half of all medicines are prescribed, dispensed or sold inappropriately
• Half of all patients fail to take them correctly
• Overuse, underuse or misuse of medicines results in wastage of scarce resources,
• Health hazards

(WHO,2014)

​

Factors Underlying Irrational Use of Drugs

Big question is who is responsible for allowing irrational drug therapy and irrational prescriptions?

• The major forces affecting use of drug can be categorized as those deriving from
• patients,
• prescribers,
• the workplace,
• the supply system including industry influences,
• regulation,
• drug information and misinformation, and
• combinations of these factors

Factors Underlying Irrational Use of Drugs�

Prescriber Factor

• Lack of education and inadequate training: One of the important determinants of irrational drug prescribing is lack of updated drug information.

• Extravagant prescribing: Some doctors prescribe the drug with notion that effectiveness of drug is directly proportional to the cost of drug.
• A low priced drug will provide comparable efficacy and safety.
• This is not always genuine.
• Drug company Promotion:On the basis of promotional activities by companies, doctors prefer to prescribe brand name drugs even when cheaper alternatives are available, for example, use of a third generation, broad-spectrum antimicrobial when a first-line, narrow spectrum, agent is indicated.

Factors Underlying Irrational Use of Drugs

Irrational prescribing: Under, over, incorrect, or multiple prescribing are assorted facets of irrational prescribing. Irrational prescribing may be manifested by the following examples:

a. Prescribing of medicines when no medicine therapy is indicated, for example, antibiotics for viral upper respiratory infections.

b. The use of correct medicines with incorrect administration, dosages, and duration, for example, use of IV metronidazole when suppositories or oral formulations would be appropriate.

c. The use of the wrong medicine for a specific condition requiring medication therapy, for example, antibacterial in childhood diarrhea instead of oral rehydration salts

Factors Underlying Irrational Use of Drugs

d. The use of medicines with doubtful/unproven efficacy, for example, use of antimotility agents in acute diarrhea.

e. Failure of dosage adjustments for coexisting medical, genetics, environmental, or other factors.

f. Failure to provide available, safe, effective, and affordable medications.

g. Two or more medications are used when fewer would achieve same effect.

h. Prescribing unnecessary fixed-dose combinations (one ingredient not needed for the patient).

i. Polypharmacy: Using many medicines concomitantly is known as polypharmacy. Prescribing drug for several related conditions or every symptom of disease even when treatment for primary condition could improve or cure the secondary issues.

Unjustified polypharmacy can increase the incidence of ADRs, drug interaction, and cost of treatment.[

Factors Underlying Irrational Use of Drugs

Dispensing:

• Incorrect interpretation of the prescription

• Retrieval of wrong ingredients

• Inaccurate counting, compounding, or pouring

• Inadequate labeling

• Unsanitary procedures

• Packaging:

– Poor-quality packaging materials

– Odd package size, which may require repackaging

– Unappealing package

​

Factors Underlying Irrational Use of Drugs

Busy doctor

• Many times due to excess patient load, physicians are not able to provide appropriate counseling about the disease or drugs to the patients.

​

Prescribing by non-allopathic doctors

• Sometimes allopathic drugs are prescribed by practitioners of traditional system of medicine (Ayurveda, Unani, Homeopathy, and Siddha practitioners) who are not well aware about efficacy and safety of allopathic drugs.

Factors Underlying Irrational Use of Drugs

Patient adherence:

Belief of a pill for every ill: Sometimes patient’s approach doctor for minor illness expecting that there exists a pill for every illness.

They create a high presumption for a prescription in every consultation

Misleading beliefs: Some cultural practices and environmental beliefs, fear of becoming drug dependent, lack of appropriate health literacy, and ignorance toward health lead to non-compliance which in turn causes irrational therapy.

1. Patient demands/expectations - Sometimes under pressure of

patients or their relatives doctors may have to prescribe the

drugs or dosage forms which may not be necessary for the

patient. •

Factors Underlying Irrational Use of Drugs

For example insisting to give injections in place of oral

dosage form Inadequate verbal instructions

2. Self-medication -Taking the drug without doctor’s prescription, not having adequate knowledge of drugs, and drugs dispensed by pharmacists without prescription of doctor are important determinants of irrational use of drug

Factors Underlying Irrational Use of Drugs

• WORKPLACE
• Heavy patient load: Because of increased workload, doctor becomes too busy to imply his
• or her knowledge and discretion in selection of the drug.
• Lack of diagnostic facilities: On account of poor diagnostic facilities, proper examination of patient
• suffers which may lead to wrong diagnosis. Uncertain diagnosis induces mistaken choice of drug.
• Insufficient staff: Inadequate human resources at each level of health-care system leads
• to poor pharmaceutical care

common Pattern of Irrational Drug Use

• The use of drugs when no drug therapy is indicated, e.g. antibiotics for viral upper respiratory infections. 
• The use of the wrong drug for a specific condition requiring drug therapy, e.g. tetracycline in childhood diarrhea requiring ORS. 
• The use of drugs with doubtful or unproven efficacy, e.g. the use of ant motility agents in acute diarrhea

Snapshots in Low and Middle Income Countries

common Pattern of Irrational Drug Use

• Failure to provide available, safe and effective drugs, e.g. failure to vaccinate for measles or tetanus, or failure to prescribe ORS for acute diarrhea. 
• The use of correct drugs with incorrect administration, dosage and duration, e.g. using intravenous route where oral or suppository routes would be appropriate. 
• The use of unnecessarily expensive drugs, e.g. the use of a third generation, broad-spectrum antimicrobial when a first line, narrow spectrum agent is indicated.  Antibiotics misuse

Data from EMP Pharmaceuticals Database

Overuse and misuse of antimicrobials contributes to antimicrobial resistance

• Malaria: choroquine resistance in 81/92 countries
• Tuberculosis: 0-17 % primary multi-drug resistance
• HIV/AIDS: 0-25 % primary resistance to at least one anti-retroviral
• Gonorrhoea :5-98 % penicillin resistance in N. gonorrhoeae
• Pneumonia and bacterial meningitis : 0-70 % penicillin resistance in S. pneumoniae
• Diarrhoea: shigellosis:10-90% ampicillin resistance, 5-95% cotrimoxazole resistance
• Hospital infections:0-70% S. Aureus resistance to all penicillins & cephalosporins

Source: WHO country data 2000-3

Hazards of Irrational Drug Use

• Ineffective & unsafe treatment
• Exacerbation or prolongation of illness.
• Distress & harm to patient Increase the cost of treatment
• Increased morbidity and mortality
• Adverse drug reactions
• Loss of patient confidence in health system.

​

obstacle to Rational of of Medicine

• Lack of objective information & of continuing education & training in pharmacology. 
• Lack of well organized drug regulatory authority & supply of drugs. 
• Presence of large number of drugs in the market & the lucrative methods of promotion of drugs employed by pharmaceutical industries. 
• The prevalent belief that “every ill has a pill.”

​

Changing a Drug Use Problem:�An Overview of the Process

Many Factors Influence Use of Medicines

Strategies to Improve Use of Drugs

Educational Strategies�Goal: to inform or persuade

• Training for Providers
• Undergraduate education
• Continuing in-service medical education (seminars, workshops)
• Face-to-face persuasive outreach e.g. academic detailing
• Clinical supervision or consultation
• Printed Materials
• Clinical literature and newsletters
• Formularies or therapeutics manuals
• Persuasive print materials
• Media-Based Approaches
• Posters
• Audio tapes, plays
• Radio, television

Training for prescribers�The Guide to Good Prescribing

• WHO has produced a Guide for Good Prescribing - a problem-based method
• Developed by Groningen University in collaboration with 15 WHO offices and professionals from 30 countries
• Field tested in 7 sites
• Suitable for medical students, post grads, and nurses
• widely translated and available on the WHO medicines website

Managerial strategies �Goal: to structure or guide decisions

• Changes in selection, procurement, distribution to ensure availability of essential drugs
• Essential Drug Lists, morbidity-based quantification, kit systems

​

• Strategies aimed at prescribers
• targeted face-to-face supervision with audit, peer group monitoring, structured order forms, evidence-based standard treatment guidelines

​

• Dispensing strategies
• course of treatment packaging, labelling, generic substitution

Economic strategies:�Goal: to offer incentives to providers an consumers

• Avoid perverse financial incentives
• prescribers’ salaries from drug sales
• insurance policies that reimburse non-essential drugs or incorrect doses
• flat prescription fees that encourage polypharmacy by charging the same amount irrespective of number of drug items or quantity of each item
• (reverse – Quebec, dispensing fee is given even if pharmacist does not dispense for good reason)
• Reimburse without treatment guidelines (ceftriaxone as an OPD medicine)

Regulatory strategies�Goal: to restrict or limit decisions

• Drug registration
• Banning unsafe drugs - but beware unexpected results
• substitution of a second inappropriate drug after banning a first inappropriate or unsafe drug
• Regulating the use of different drugs to different levels of the health sector e.g.
• licensing prescribers and drug outlets
• scheduling drugs into prescription-only & over-the-counter
• Regulating pharmaceutical promotional activities

​

Only work if the regulations are enforced

Source: WHO Policy Perspectives no.5

Reminder: 10 national strategies to promote RUM�need political support, investment and staff

1. Evidence-based standard treatment guidelines

2. Essential Medicines Lists based on treatments of choice

3. Drug & Therapeutic Committees in hospitals

4. Problem-based pharmacotherapy teaching in universities

5. Continuing medical education as a licensure requirement

6. Independent drug information e.g bulletins, formularies

7. Supervision, audit and feedback

8. Public education about medicines

9. Avoidance of perverse financial incentives

10. Appropriate and enforced drug regulation

Why does irrational use continue?

Very few low and middle income countries regularly monitor drug use and implement effective nation-wide interventions - because…

• they have insufficient funds or personnel?
• they lack of awareness about the funds wasted through irrational use?
• there is insufficient knowledge of concerning the cost-effectiveness of interventions?
• they do not bear the cost of irrational use? (OOP?)

Essential drug concept

Essential Medicine(Drug) Concept

“Those drugs that satisfy the priority of healthcare needs of the population” – World Health Organization

They are selected with due regard to public health relevance, evidence on efficacy and safety, and comparative cost-effectiveness.

​

Essential Medicine(Drug) Concept

Essential Medicine Should be available within the context of functioning health systems:

• Should available at all times
• In adequate amounts
• In the adequate dosage forms
• With assured quality, and
• With adequate information
• At an affordable price to individual and community

​

Essential Medicine(Drug) Concept

Essential Medicine Includes

Drug name

Dosage forms

Dosage strength

Indications ??

Includes single formulations

Fixed drugs are included only if its efficacy is proven to be higher

Anti-Tubercular Agents

Anti-Malarial Agents

Drugs listed as Main List and Complementary List

Importance for developing countries

• Development of treatment guidelines and national formularies
• Comprehensive national drug formulary
• Strategies to drug procurement and supply
• Drug financing and Drug donations
• Research priorities for drug use
• Drugs needed for specific disease

Guidelines for establishing a national programme for essential drugs

• National drug regulatory authority should be established

� National drug and therapeutic committee (NDTC) should be established

� Committee includes people from

• Medical
• Clinical Pharmacology
• Pharmacy
• Public health fields
• Also from other appropriate health care fields

• Generic names should be used for all drugs

� Concise, accurate and comprehensive drug information should be prepared

� Stability and bioavailability should be assured

� Efficient administration of supply, storage and distribution of drugs

� Management of stocks and eliminate waste

Essential Medicine(Drug) Concept

• National Drug Formulary and Essential Medicines List
• Review Committee by Decree Number 48 of 1989,
• 7th Edition Nigeria Essential Medicines List;lauched 2020
• The Sixth edition was produced in 2016 and an addendum was incorporated into this edition in March 2018 when the need arose in respect of some emerging health conditions in the country

Criteria for the selection�of essential drugs

• Pattern of prevalent disease and treatment facilities

� Level of training and experience of the personnel

� Financial resources available in the country

� Genetic, demographic and environmental factors

� Evidence based and not suituation based

� Selected drugs should have adequate data on their efficacy and safety

​

• Performance of drugs in general has been proved in a variety of medical setting

� Available in adequate quantities and in the dosage forms that is recommended by NDTC

� Assured quality, stability and bioavailability

� Two or more drugs having same quality, stability and bioavailability, choice on the basis of efficacy, safety, quality, price and availability

• Cost , an issue; unit cost of drug alone should not be
• considered. Cost of total treatment, cost/benefit ratio
• should also be considered
• � Comparative pharmacokinetic properties of drugs in
• the same therapeutic category
• � Local facilities to manufacture and storage also be
• considered
• � Should contain only single drug, combination
• advantage over single drug in therapeutic effect, safety
• and patient compliance

Selection of Pharmaceutical dosage forms

• General utility and wide availability of the dosage forms

� Tablets have wide acceptability and also cost effective

� Stability of dosage form under ambient climate conditions

� Established local preference

� Bioavailability and pharmacokinetics of dosage forms

� Selection of convenient dosage forms for selected population Eg: Paediatric dosages, SR/CR dosage inclusion require adequate documentation

� Selection of specified salt form for a particular drug

Example: Chloramphenicol Palmitate, Amlodipine Besylate,Erythromycin estolate

Quality Assurance and WHO certification scheme

• � Should confirm with required standards of good Manufacturing practice (GMP) and quality control
• � Bioavailability of drugs
• � Should confine International Pharmacopoeia and its standards

Nomenclature

� Each pharmaceutical substance by a globally acceptable generic name is importance

� International nonproprietory (INN) names becomes an important arm of essential drug list and is almost globally accepted

� INN periodically published by WHO for new addition of pharmaceutical products

Tasks after the formation of�Essential drug list

• Updating the essential drug list

� Essential drug list for primary health care centres

� Specialist control of drug use

� Research and development

� Drug information and education activities

� Making a list of reserve microbials

� Post registration drug studies

Updating the essential drug list-Continuous process�WHO guiding principles�

� Must accomodate local situations to meet health needs of majority of population

� Extent to which country establish EDL

� Guiding essential drug list by WHO is a contribution to solve problems

� Need to include additional drugs for rare disease. Eg: TB drugs in India

� Exclusion does not mean rejection

� Public health issue, epidemiological changes, new drugs availability, progress in pharmacological and pharmaceutical knowledge.

Essential drug list for primary�health care centres

� Existing system of medicine

� National health infrastructure

� Pattern of endemic diseases

� Supplies

Specialist control of drug use

​

� Adequate specialist skills and complemaentary resources needed before the introduction of new drugs. Examples of situation requiring specialist control of drug use

� Use of reserve antibiotics for multiresistant bacteria

� Adequate regimen for TB and leprosy

� Use of antineoplastic, immunosupressive agent, antiretrovial agent

Research and development�

� Pharmaceutical aspects

• Development of drug procurement, drug quality, processing, packaging and distribution

� Clinical and epidemiological aspect

• To assess efficacy, safety, genetic and ethnic difference

� Educational aspects

• Development of training programme

Drug information and education activities

​

� Develop formulary and drug information sheet on all drugs in EDL

� Continual education programme on all aspects of medical care, disease pattern, selection of antimicrobials , diagnostic and other therapeutic guidelines

Making a list of reserve microbials

� Amoxicillin plus clavulianic acid

� Ceftriaxone

� Ceftazidine

� Vancomycin etc…

Post registration drug studies�

� Some drugs fail to produce benefit. Reasons are

• Clinical trial does not Iinclude groups like children, pregnant women, old people
• Genetic and environment factors differs from population to population
• Unexpected use of drugs, data on overdose not available
• Poor manufacturing practice

� Post registration drug studies help to estimate future demands, quantify drug inventory, evaluate drug use

Conclusions

• Irrational use of medicines is a very serious global public health problem.
• Much is known about how to improve rational use of medicines but much more needs to be done
• policy implementation at the national level
• implementation and evaluation of more interventions, particularly managerial, economic and regulatory interventions
• Rational use of medicines could be greatly improved if a fraction of the resources spent on medicines were spent on improving use.
• (WAIT!)

Some issues to think about

• There are textbook cases of Technical Success in RUM�Tools to identify the problem, design an intervention to measure the effect, feedback and adjust BUT
• What is more important than Technical Excellence?
• What maybe the proportion spent for medicines from the health budget if RUM is implemented?
• What role does Universal Health Coverage play in the success of RUM?
• Can single interventions help in RUM in low and middle income countries?
• Can single interventions help in high income countries?

Some issues to think about

• Can we achieve RUM in a health sector dominated by the private sector?
• Is quality of medicines an important issue in RUM? (Does it differ between LMICs and HICs?)
• Is Information Technology important in promoting RUM?�Can it accelerate progress or be the "fix" for irrational use?
• What is the most important lessons that we can learn from high income countries in RUM ?
• Would Universal Health Coverage be the driver for RUM?
• What would be stronger for RUM? Health? Cost to Health care systems?

Thank You

?

References

• Katzung BG, Masters S, Trevor A. Basic and Clinical Pharmacology 12/E. McGraw Hill Professional ; 2012
• Rang & Dales Pharmacology, 6th Edition.  Lippincott Pharmacology, 5th Edition.
• Methling, K; Reszka P; Lalk M; Vrana O; Scheuch E; Siegmund W; Terhaag B; Bednarski PJ (2008). "Investigation of the in Vitro Metabolism of the Analgesic Flupirtine". 37: 479–493.
• Klotz U (2009). "Ziconotide—a novel neuron-specific calcium channel blocker for the intrathecal treatment of severe chronic pain—a short review". Int J Clin Pharmacol Ther 44(10): 478–83.

​