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DRUGS FOR DEVELOPING

COUNTRIES - THE VIEWS OF A

PRACTISING DOCTOR IN THE TROPICS

K. K. ADJEPON-YAMOAH

Department 0/Pharmacology,

University ofGhana Medical School,

Accra, Ghana

Introduction

Most of the countries in the tropics may be referred to as developing countries arid

have certain features in common. Orthodox scientific medicine is relatively young

and these countries lack sufficient skilIed manpower. Medical technology is underdeveloped and consequently they import most of their drugs from the advanced

countries. The objectives of the drug exporting companies are not necessarily in the

best interest ofthe importing countries.

This paper highlights some of the problems encountered in the tropical world in

relation to drugs , and the examples quoted come mainly from Ghana.

Sources of drugs

There are three main sources of drugs in the tropical countries. Most importantly,

drugs are imported as fmished products. In Ghana 80 to 90% of drugs used in

orthodox medicine are imported (Botchway, 1980, unpublished observations).

Secondly, drugs may be imported as serni-fmished raw materials. They are then

formulated into tablets, capsules, syrups, and so on. Thirdly, a large section of the

population use herbai or traditional medicines.

This paper concentrates mainly on imported fmished products and on locally

manufactured drugs from imported raw materials.

Drugs found in countries like Nigeria and Ghana have been imported from a

variety of countries. Ghana for instance obtains its drug supplies from almost all the

Western countries, Israel , many of the Eastern European countries and China. In

1978 there were three hundred and twenty official drug importers in Ghana

alone. Each importing firm had its own favourite country and company.

The number of different proprietary drugs is necessarily large and there are many

brand name drugs containing the same pharmacological agent. Thus arecent survey

on the Ghanaian market revealed 15 different brands of ampicillin from different

sources.

DRUGS FOR DEVELOPING COUNTRIES 537

The assumption by the unsuspecting doctor in the tropics is that these different

brands, containing apparently the same pharmacological agent, are equivalent in

chemical and biological properties when equivalent doses are given.

The major questions to be answered in relation to drugs are: a) quality, b) cfficacy,

c) safety and d) quantities to satisfy national needs.

Quality

The great diversity of the sources and types of proprietary drugs available in many

tropical countries necessarily means th at there are likely to be wide differ ences in the

chemical and biological properties ofimported drugs belonging to the same pharmacological c1ass. However, because of limited manpower and resources there are few

studies locally.

Chemical studies indicate that a number of the drugs circulating in the tropical

world are ofvery poor quality indeed (Binka, 1973; Ayim, 1977). Some ofthe drugs

arrive in these countries poorly packaged and already damaged at the port of entry.

Counter/eil drugs

A disturbing feature wh ich has been noticed on a number of occasions is that inert

substances are packed into, for example, capsules, and sold to the developing world

as specific drugs. These could be termed 'counterfeit' drugs.

During a pharmacy c1ass experiment in Ghana in 1972, a random sampie of

procaine penicillin in a government hospital was found to contain no antibacterial

activity. It was subsequently shown to contain an inert sub stance (Buadu, 1980,

personal communication). During a period when calamine lotion was in short supply

in Ghana, a large consignment of supposed 'calarnine' powder was shipped to the

country in 1976. The colour was pink on arrival and chemical analysis revealed no

calamine in the powder. In another study a sampie of imported fortified procaine

penicillin was found to contain one part procaine penicillin and five parts penicillin

G, the official requirement is the reverse ratio (Ayim, 1977).

Substandard drugs

Apart from 'counterfeit' drugs, the quality of the actual drugs may be very poor in

that the amount ofactive ingredients are more or less than the stated official values.

A systematic analysis was conducted in the Ghana Government Regional Medical

Stores between July and December, 1972. Penicillins, streptomycin, tetracyclines,

chloramphenicol, antimalarials and analgesic antipyretics were studied. The results

indicated that a large number ofsubstandard drugs were circulating in the hospitals

(Table I). Thus, 50% ofpenicillin sampies, 34.6% oftetracycline sampies and 41.9%

Table 1 Drugs analysed duringa quality control programme. From Binka (1973), with

permission.

Drug

A. Antibiotics

i. Pencill ins

ii. Streptomycin

iii. Tetracyclines

iv. Chloramphenicol

B. Analgesie - antipyretics

C. Antimalarials

Total number0/

samples

24

68

26

I1

17

25

Samplesfo und

unacceptable (%j

50.0

11.8

34.6

18.2

41.9

12.0

538 K. K. ADJEPON-YAMOA H

of analgesic antipyreti cs were considered unacceptable. Penicillin co ntent ofsome of

the preparations was as low as 22.38% and streptornycin conte nt in one sa mp ie

studied was as low as 4.19% of the stated content. One sa m pie of chloram p henicol

powder for injection was found caked. What was even more disturbing was the fact

th at the sam p ie of substa nda rd streptomycin mentioned and most of th e drugs

studie d had not reached th eir stat ed expiry dates (Bink a , 1973 ). Chlora m phenicol

recently im ported from an Eastern Eu ropean country was found to conta in 58%

ac tivi ty (Buadu , 1980 , personal communicat ion).

Obser vation s ha ve indicated that th e co m me nts on subs ta ndard imported drugs

a pply to some ofthe locall y manufactured drugs. The main ca uses a re poor quality,

imported raw material s, poor formul at ion s and del iber at e ch eat ing. Thus, a capsule

on th e market in Ghana conta ined 30% of the sta ted ac tivity . lt was subseq uently

shown th at the supplier ofthe ac tive ingredient had adulte ra ted the drug with sugar

and duped the bu yer with a see m ingly authentic Certiftcate ofAnalysis. A pparently

suc h pr act ices are common on the European continent (Ayim , 1977). Caps ules of

cephalex in (250 mg) manufactu red in Ghana, contained impurities including tox ic

N-n-dimethyl aniline (Ohene-M anu, 1976, personal communication) .

Drugs and the environme nt

The stability and hence the qual ity and biological properties of drugs are adversely

afTected by many factors. The rate of degradation of some drugs is increased by

conditions of high temperatu re, high humidity and high intens ity of light. These

envi ronme ntal condit ion s pr evail in man y tropical countries. Degrad at ion of th e

active drugs results in a decrease in poten cy, and the degrad at ory product s ma y be

toxic, for exam ple, tetracycline. The tro pica l conditions , therefore, ac ce lera te th e

rate of degradation ofdrugs.

Whilst ca re is tak en by so me ph armaceutical compan ies in pr esenting exp orted

drugs in suc h a way as to minim ise deterioration in th e tropical env iro nme nt, not

eno ugh is in vested in th is area by some com pa nies.

T abl ets, for exampl e cod eine co m pound, freq uen tly cha nge co lour. Hygroscopic

tablets and ca psules often so ften. Obser vat ion s indicate that poor packaging,

ina ppropri ate co ntai ners and faulty formulati on s ma y be major contributing factors.

For exa mple, diphenoxylat e hydrochl oride plus atro pine sulpha te tabl ets (Lomotil,

Searl e) packed singly in sea led ai r-tig ht a lumi ni um foil stay ' fresh' much longer than

when man y tablets are pack ed in glass co nta iners.

Apart from th e accelerated ph ysical and che m ica l degrad at ion of drugs, poor

sto rage facil ities, under the tr opical co ndi tions, render some of the drugs readily

contaminat ed by mi cro-org anism s. Thus, Boakye-Yiad orn & Buadu (1974) found

that 30% of 50 random sa mpIes of stoc k solutions of drugs for oral and topical

applications conta ined over 100,000 organism s mI-I. E. coli, Pseudom onas

aeruginosa and salmonellae wer e am ong the organisms ide ntified (Table 2 & 3). Such

contaminat ion s are therapeutically undesirable and dangerous. In another study,

Boakye-Yiadorn & Fukuo (1975) found a low degree ofbacterial contamination in

eye drops, nasal and ear drops, but, a high degree of bacteri al contamination in

Table 2 Total viable bacterial count in 50 randorn sarnples ofs tock solutions of drugs for oral

or topical application. Frorn Boakye-Y iadorn & Buadu (1974), with perrnission.

Viable bacterial count mt" % Nu mber of samples

Less than 10,000

Between 10,000 to 100,000

More than 100,000

44

26

30

DR UGS FOR DEVELOPI NG CO UNTRIES 539

mouth was h samp ies, du sting powder sa m pies and aqueous crea ms was ob served and

thi s was att ributed to high bacterial conta m ina tion ofthe raw materi al s used in their

pr eparations. The pre sen ce of sta phy lococci, Pseudom onas aeroge nase, Salmo nella

and E. eoli were also confi rrned. U mbilica l cord po wder has been inc ri mi na ted in

some cases of neonata l tet anus.

Table3 Path ogen count in rand om samplesofs toc k solutions. From Boakye-Yiadom &

Buadu (1 974), with permission .

Type ofbaeteria % Number ofsamples

Presu mpti ve coag ulase positive 18

Staphylococcus aureus

Coagulase negat ive 32

Siaphylococcus aureus

Escherichia eoli 10

Pseudomonas aeruginosa 34

Salmonellae 16

Ana erobes 28

Therapeutic usefulness and toxicity ofimported drugs

Undoubtedl y many of th e drugs imported ha ve been of grea t th er apeu tic value but

there is con sid erable room for improvement. There ha ve been man y insta nces of

failure of therapy in th e tropics. Wh ilst so me of the insta nces noted may be du e to

bacterial drug resistance , man y a re att ributa ble to poor qu al ity drugs, as have been

referred to abov e. T reatment of a case of infection with a 'counte rfeit' drug or

degraded drug is dangerous and has ca used th erapeutic disasters.

There are a large number of proprietary drugs whic h are of doubtful or unproven

therapeutic va lue circulating in th e tropics. Many of th ese are from th e European

continent. These drugs are unfortunately very popular and seil weil and are so called

drugs of ' vit ality' , th at is, bloo d ' to n ics', vita min com plexes, so ca lled neu ro-tropic

drugs a nd ana lgesics.

A no the r disturbing fact or is the rat e at which drug co mbinations of an undesirable

nature are read ily found in th ese co untries. Examples of th ese incIude br and drugs

lik e Ergertine (amido pyri ne + phenylbutazone) and Rh eumopyrine (phen ylbutazon e

+ amin ophen azon e). The rati on al e be hind comb in ing drugs whic h are highl y to xic

and bel on g to the sa me chemical cIass is best known to th e manufact ur ers. Phenylbutazone and other antirheumatic drugs acc ounted for 40 % of all deaths du e to

marrow depression (Table 4) following the use of drugs in Denmark bet ween 1968

and 1973 (Danish National Health Ser vices Report, 1974). Wh y are some exporti ng

firrn s pu shing such drugs in large quantities to the tropical world? lt is di sheartening

to note th at such drugs are very expensive and ha ve gained so much popularity that

th ey are readil y bought in the streets and markets, and are tr eated like tonics in the

developing countries.

Restrieted or banned drugs

When drugs and other ehernieals are either found or suspected to be toxic, some

exporting co mpanies shi p them to the developing countries. For exa m ple, ben zen e

hydrochloride ha s been show n to be carcinogenic in rodents and its registration ha s

been voluntarily withdrawn by the manufacturing firm in the country of origin. The

compound is found in large qu antities in G hana and is in th e form ofa lice-killer drug

(Donnar's lice-killer), and th is drug has caused fataliti es.

540 K. K. ADJEPON-YAMOAH

Table 4 Deaths caused by bone marrow depression following the use of drugs. Modified from

Danish National Health Services Board Report (1974).

Drug groups Number ofdeaths

Anti-infective 8

Antirheumatic 16

Cytotoxic 6

Ncurolcptic 3

Antithyroid 2

rn~ 5

Tm~

Phenacetin is now restricted in some industrialised countries, for exarnple, Britain,

because of its nephrotoxicity, yet the compound is still being shipped in large

quantities to the tropical world .

Arsenic is hardly used in the developed world as a drug , but it is found here as

Stovarsol in the form ofvaginal pessaries or tablets. There is a lot ofbeliefin this drug

in Ghana and Ivory Coast and it is mixed with all kinds of herbai preparations.

Aplastic anaemia, agranulocytosis and chronic arsenic poisoning have been noticed

by the author, in three patients in Accra following the use ofStovarsol.

Genetic and ethnic factors

The therapeutic usefulness and the toxicity of some of the drugs circulating in the

tropics may be greatly modified by genetic factors . There is the need for a closer study

in this field, so that the appropriate drugs are imported into each country. For

example, the incidence ofglucose-6-phosphate dehydrogenase deficiency is very high

in African and Mediterranean countries. In Ghana this is estimated to be 23% in the

male population (Owusu, 1972b). People with this deficiency may develop

haemolytic anaemia following the use of drugs such as sulphonarnides, primaquine,

nitrofurantoin and co-trimoxazole. Unpublished observations suggest that West

African hypertensive patients respond weil to reserpine and related drugs without the

associated reported high incidence of depression. Evidence is also accumulating that

there may be ethnic differences in the metabolism of other drugs such as diphenylhydantoin (Andoh, Idle, Sloan, Smith & Woolhouse, 1980), and phenylbutazone

behaves paradoxically in African diabetics (Owusu, 1972a).

Drugs, health and poIitics

The inflation rate in many tropical countries is alarmingly high, reaching over 60%

in some cases. This factor and the determination of the leaders in many tropical

countries to provide better health care has meant that the health bill is very high and

is rising alarmingly. Thus, Ghana spends between 8-10% of her budget on health.

Between 30-50% of the health fund in these countries is spent on drugs. In 1969,

Nigeria spent 32 million and in 1979, 120 million naira on drug importation alone

(Sofowora , 1979).

The question is, are the relatively large sums of money spent on drugs being

effectively utilised in the importation or manufacture ofthe right types ofdrugs in the

right quantities? The answer is probably in the negative. The reason for this view is

that shortage of essential drugs , such as vaccines, chlorarnphenicol, anthelmintics

and antimalarials, in the hospitals and clinics is a regular feature in many tropical

countries including oil-rich Nigeria. In the face ofthese shortages, the shops, market

piaces and streets are usually full of an array of what may be termed non-essential,

but economically fast moving drugs, such as different types of analgesic agents, drugs

ofvitalitv', for example, vitamins and 'aphrodisiacs', and so on .

DRUGS FOR DEVELOPING COUNTRIES 541

There appears to be very little relationship between the drugs that are available

and the real health needs ofthe developing world. Several factors have contributed to

this state ofaffairs. Some ofthese are discussed below.

Political andfinancial considerations

There are powerful political and business interests in both the exporting and

importing countries. The prime objective is profit-rnaking. So strong are these forces

that therapeutic considerations become secondary in the choice of drugs for export

and import.

A variety of methods are employed to perpetuate this confusion in the drug scene.

These include the use of powerful advertisement techniques which are sometimes

misleading , and direct or indirect bribery or politicians, doctors, Ministry of Health

personneI, Bank and Ministry ofTrade officials who are connected with approval of

funds and policies for drug importation or manufacture. Ministry of Health

personnel may favour pol itical favourites in the allocation of licences for drug

importation or manufacture, where award of licences are prerequisites to drug

importation.

In some instances, donor countries wishing to win influence in a particular country

dump drugs of dubious quality as gifts. Some ofthese drugs have expired at the time

of arrival in the receiving countries.

Non-registration 01drugs for export

With the exception ofvery few countries like Japan and New Zealand, which requ ire

that no drug should be exempted from certification or registration procedures, many

countries exempt all or some of the drugs meant for export from registration. The

laxity of the laws in the exporting countries actively encourages and contributes to

the manufacture ofpoor quality drugs for export to the Tropical World.

Absence 01effective drug s control agencies

Many tropical countries have poorly organised drug control agencies. Where such

bodies exist, the laws governing drugs are often outmoded and need drastic revision .

Thus, Ghana has only now formed a committee to prepare a draft for the establishment ofa Drugs, Poisons and Cosmetics Commission.

Laws governing the types and quality of drugs may be formulated in the tropical

world , but there are considerable difficulties in the enforcement ofthese laws. Some

of these include the shortage of qualified experts, such as, inspecting pharmacists or

chemists. Nigeria has a pharmacist to population ratio of 1:90,602 (Adenika, 1979).

Corruption and political interference in the horne countries may playa role. Another

major difficulty is the absence of good quality controllaboratories.

Paar planning

The distribution of funds, facilities and manpower for health care in man y tropical

countries is inversely related to the distribution ofthe population.

Emphasis has been placed on the provision of expensive institutional care which in

these countries covers mainly the urban population. Thus, only about 30% of the

population enjo y all the health facilities. Disease distribution in the rural areas is

very different from that in the urban areas . Diseases of infestation and infection

constitute numerically the major problems in the rural areas whereas degenerative,

chronic and metabolie diseases assurne great importance in the urban areas.

It is now generally realised that there should be emphasis on primary health care

542 K. K. ADJEPON-YAMOAH

which seeks to provide basic health amenities to the rural population. The primary

health care concept covers promotive, preventive and basic curative services at

health posts, health centres and satellite clinics .

Drugs which are found in these countries are mainly in the urban areas and thus

there is a tendency for drug importers to satisfy the requirements of the urban

population.

There is therefore little relationship between drugs that are available in these

countries and drugs that are required to maintain the health of the majority of the

population.

Suggested solutions

Given the present conditions of limited fmances, shortage of manpower and the

inappropriate importation ofmany substandard drugs, the tropical countries need to

formulate policies aimed at the provision of the minimum number of essential good

quality drugs for their health services .

a) As a first step, it is suggested that central governmental agencies should replace the

many business houses involved in the importation ofeither fmished drug products or

bulk pharmaceuticals. A drug importation committee which will give expert advice

to such a central procurement agency should also be formed .

b) The sources of drug procurement should be limited to companies with reputable

records. The types of drugs to be imported should be based on local knowledge of

morbidity and mortality patterns, population statistics and local environmental and

genetic factors. Emphasis should be placed on drugs for primary health care .

c) Drug control agencies should be modernised or established where they do not exist

and they should be made etTective. This will involve the training of more personnel

needed for the enforcement of drug regulations. There must be a willingness on the

part ofthe various governments to make such regulatory bodies etTective.

d) Quality control laboratories should be established or strengthened. All drugs

entering the country should be analysed for quality and stability under the tropical

conditions. As an initial measure, it will be necessary for the countries in identifiable

geographical areas to collaborate for the establishment of regional centres, since

many countries may not have the needed funds and person neI.

e) These countries should also cooperate with each other on the exchange of

information on drugs . They mayaiso seek the assistance of the World Health

Organization.

f) Facilities for drug distribution and storage need urgent attention, as drugs

deteriorate quickly and microbes multiply readily in the tropical environment.

g) Local manufacture of good quality drugs could help to cut down the cost of drugs.

There should be a gradual shift from the importation of fmished products to the

importation of good quality bulk pharmaceuticals for the local manufacture ofdrugs.

Here again, regional cooperation will be of great advantage. Such a shift will

eventually decrease the local prices of drugs.

h) lt is estimated that about 70% of the rural population resort to traditional

medicine and indeed many people have a lot of confidence in indigenous drugs .

There is also some evidence for the usefulness ofsome ofthese local rcmedies. There

are many problems related to the preparation, evaluation, stability and dosage of

traditional drugs . Ghana, for example, has made a beginning by the establishment of

a Centre for the Scientific Research into Plant Mcdicine. More attention should be

focussed on local remedies.

i) Lastly, there are major obligations on the developed world . The developed

countries can greatly assist the tropical world in the transfer of technology and the

exchange ofmanpower. Most irnportantly, the developed countries should pass laws

which will prohibit the export of drugs which have not met their local registration

requirements,

DRUGS FOR DEVELOPING COUNTRIES

Conclusions

543

Many drugs of poor quality and of doubtful therapeutic value are circulating in the

poor countries. Some ofthese drugs are inappropriate and may even be toxic.

It is a moral obligation on the part of politicians, medical scientists and

pharmaceutical companies in the importing and exporting countries to stop this

practise.

Acknowledgements

I thank the organisers of the World Conference on Clinical Pharmacology &

Therapeutics for inviting me and for sponsoring my trip, I am also grateful for the

Pharmaceutical Division of Ghana Industrial Holding Corporation for partially

sponsoring me .

I thank Mr A. Opoku for typing this manuscript.

References

Adenika, F. B. (1979). Problems of drugs usagecontrol in Nigeria. Nig . J. Pharm., 10, 132-137.

Andoh, B., Idle, J. R., Sioan, T. P., Smith, R. L. & WooIhouse, N. (1980). Inter-ethnic and interphenotype differences among Ghanaians and Caucasians in the metabolie hydroxylation

ofphenytoin. Brit. J. clin. Pharmac., 9, 282~283

Ayim, I. S. K. (1977). Drug manufacture and quality control. Ghana Pharm. J., 5,8-9.

Binka, J. Y. (1973). Quality evaluation of some drugs in the Ghana market. Ghana Pharm. J.,

1,77-81.

Boakye-Yiadom, K. & Buadu, C. Y. (1974). Evaluation of the microbial contaminationof

pharmaceuticals in Government hospital dispensaries in Ghana. Ghana Pharm. J., 2,

12-13.

Boakye-Yiadom, K. & Fukuo, Y. D. (1975). Evaluation of the microbial contamination of

pharmaceuticals in Government hospital dispensaries in Ghana. Ghana Pharm. J., 3,

57-59.

Danish National Health Services Board Report (1974). In Adverse Reactions on Drugs. Report

No. 19,482-431.

Owusu, S. K. (l972a). Paradoxical behaviour ofphenylbutazone in African diabetics. Lancet, 1,

440.

Owusu, S. K. & Opare-Mante, A. (1972b). Electrophoretic characterisation of Glucose-6-

phosphate dehydrogenase in Ghana. Lancet , 2,44.

Sofowora, A. (1979). Drugs from indigenous plants. Nig. J. Pharm., 10, (3) 115-124.

DRUGS FOR DEVELOPING

COUNTRIES:

VIEWOFTHE

PHARMACEUTICAL

INDUSTRY

W.B.ABRAMS

Me rck Sharp & Dohme Resea rch Laberatortes .

W('st Point,

Pennsylvania 19486,

USA

Two hundred yea rs aga a developing country in the western hemisphere

successfully fought a war to rid itself from colonial rule . The situation has some

parallels to the struggles of today's developing countries. While the leaders wrestled

with military, political , and economic issues, the greatest threat to the people was

disease (Abrams. 1976), The American Colonists suffered terribly from epidemics of

smallpox, yellow fever , dysentery, influenza, and measles. Five Colonial soldiers died

of disease for every on e killed by the British (Allen . 1970), A soldier had a 98%

chance of walking off a baulefield alive , but the odds on his leaving a hospital alive

were only three in four (Allen . 1970), In coping with these problerns, the American

government seemed to lack sufftcient understanding and funds to provide the needed

faciliti es, supplies, and organization. At thi s point, however, the paralleis end, For

one thing, there were no effective remedies for these devastating infectious diseases at

the time of the American revolution: there are today . For another, the American

Colonies had an adequate economic base to avoid widespread malnutrition, which

kills by itself and adds to the morbidity and mortality of disease . Finally, a health

care infrastructure was part ofthe de velopment ofthe United States from the beginning. Thus, as tools bec ame available from its universities and industries and from

Europe, the country was able to substantia lly reduce or eliminate from its shores the

diseases listed above and later malaria, cholera, hookworm, pneumonia , tuberculosis, poliomyelitis, whooping cough, diphtheria, and others (Abrams, 1976), lt is

also evident th at money had to be avail able through economic development to get the

new drugs, vaccines and public health measures to the people.

The world is still developing, but the site ofthe struggle has shifted to the emerging

countries situated largel y in the tropical and subtro p ica l regions of the earth. This

location introduces unique parasitic diseases to cope with in addition to those faced

by the developed countries over the past 200 years. The concern ofthe United States

Government for the development of pharmaceuticals to fight these diseases was

DR UGS FOR DEVELOPI NG COUNTRIES: INDUSTRI A L V IEW 545

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