Pharmacoprudence

If you are looking for a single word to describe the varied job functions of the clinical pharmacist, that word is "pharmacoprudence".

 We, members of the Apothecary fraternity, have inherited a very fortunate heritage; a word to describe any field of particular study or endeavour, old or new, of a natural origin or acquired, may be formed by simply prefixing the root morpheme " pharmaco-" (obtained from the Greek pharmakon, for drug) to a tail word with a suggestive character. Hence we have in our lexicon words such as pharmacology, pharmacognosy, pharmacokinetics, pharmacodynamics, pharmacopoeia, pharmacopaedia, pharmacotherapy, pharmacogenomics, pharmacoepidemiology, pharmacovigilance, et cetera; words which are each pregnant with ideas which otherwise could only have been expressed sufficiently through elaborate usage of common vocabulary.

 The word "pharmacoprudence" first appeared in the year 2012 in an article published as an Idea Paper in the online journal INNOVATIONS in Pharmacy. In that seminal paper the word "pharmacoprudence" was originally suggested as the terminological equivalent of the word "jurisprudence" and was conceived to carry parallel connotations.

 Jurisprudence, as used in common notion, means the study of the nature and administration of law. On the same level pharmacoprudence may be explained simply as the study of the components and administration of healthcare. In that seminal paper the term "pharmacoprudence" was defined as 'the science and practice of the rational, efficient, efficacious and economical utilization of therapeutic agents'. It embodies such interrelated concepts, specialized learning and activities as clinical pharmacology, pharmacotherapeutics, pharmacoeconomics, pharmaceutical compounding, complementary and alternative therapy, rational drug utilization, medical records management, medication use reviews, pharmacovigilance, pharmacoepidemiology, pharmaco-medical information systems management, medical sociology, et cetera.

 In parallel with the lawyer who is the advocate of a client in the administration of law, the clinical pharmacist is the advocate of the patient in particular, and the whole healthcare system in general, to safeguard against abuse and misuse in the process of delivery of healthcare services. Like the former the services of the latter should have to be solicited for by a client, when pharmacoprudence is practised in a private office, but where the clinical pharmacist is an employee of a healthcare institution the performance of the role of pharmacoprudence becomes a professional obligation. Again, like the lawyer, the clinical pharmacist should have to specialize and confine his/her practice to a few, selected medical and/or pharmaceutical specialties to ensure concentrated learning and activity.

 Indeed so much similarities may be found upon detailed analysis of the job functions of both the lawyer and the clinical pharmacist that the juxtaposition of the terms jurisprudence and pharmacoprudence is more than apt. Furthermore, the term "pharmacoprudence" is more excellent in beauty in comparison with the phrase "clinical pharmacy", in the sense that the former circumvents a very serious ambiguity that inheres in the usage of the latter; the fact that the phrase "clinical pharmacy" naturally restricts this field of practice to only practitioners within conventional healthcare institutions, to the exclusion of community pharmacists and pharmacists who may perform same job functions in private business offices. In contrast, the term pharmacoprudence captures all these practice settings.

 Therefore I commend the term "pharmacoprudence" to you as preferred to the traditional phrase "clinical pharmacy", for your usage both in your lay and technical discussions, so that you avoid unnecessary ambiguity and carry your communications forcefully.


 References:
Adjei M. Clinical Pharmacy: A Theoretical Framework for Practice. Innov Pharm. 2012; 3(3): Article 83. http://pubs.lib.umn.edu/innovations/vol3/iss3/2.

Ibuprofen Sodium: A case for pharmaceutical compounding

2-(4-Isobutylphenyl)propionic acid, known in common pharmaceutical parlance as Ibuprofen, was invented in 1968 by the two English chemists John Stuart Nicholson and Stewart Sanders Adams. It was a member of a homologous series of p-substituted phenylalkanoic acid derivatives which they synthesized, tested and confirmed to possess the pharmacologic triad of anti-inflammatory, analgesic and antipyretic effects. They have been driven in their search, per their own claims, by motives to find therapeutically useful alternatives having all the abovementioned medicinal effects and supplemented with the following advantages over Aspirin which was then the mainstay for treating rheumatic diseases, namely;

               1. Are less toxic

               2. Have higher therapeutic ratio

               3. Are more stable in the presence of water and water vapour

               4.Are more soluble in water


 The collective clinical experience with Ibuprofen up to the current time vindicates the inventors so far as higher therapeutic ratio is concerned, given that the safe daily adult dose of Ibuprofen is in the range of 600mg—3200mg (Martindale 36, 2009; pp. 64—66), but the other three purported advantages are not beyond reasonable doubts. Notwithstanding the foregoing observation, however, Ibuprofen has attained sufficient popularity with clinicians globally, and in the Ghanaian healthcare sector currently, it is the main alternative drug to Paracetamol in their category for children.

 Building on the concluding remarks of the above paragraph, it is obvious that paediatric preparations of Ibuprofen are essential pharmaceutical commodity in our local health sector. But I am not oblivious of the many different brands of Ibuprofen Suspension sitting on the shelfs of our pharmacies; when it is paediatric Ibuprofen formulation that you want in Ghana, invariably, you are served Ibuprofen Suspension. I intend to pose a puzzle here, a query that none other but a pharmacist is qualified to answer by reason of his/her chosen profession: What (at all) does it take to prepare something in the nature of Ibuprofen Oral Solution?. Think about a homogeneous liquid of Ibuprofen Oral Solution and contrast its pharmaceutical properties with those of a heterogeneous Ibuprofen Suspension. The merits of the former preparation over the latter are indisputable, including; aesthetic elegance, user-friendliness, ease of measuring dose, and accuracy of measured dose.

 That said, one should ask just what are the odds against the preparation of an Ibuprofen Oral Solution?. To the extent that my studies have revealed, it is none other hurdle than the poor solubility of Ibuprofen in water. The physicochemical characteristics of Ibuprofen are; colourless, crystalline stable solid, m.p. 75—77°C, relatively insoluble in water (Merck Index 14; p. 4886). In our conventional terminology “relatively insoluble” translates into the reality that 1000mL or more of water is required to completely dissolve just 100mg of Ibuprofen, with implication that it is practically not feasible to prepare an Ibuprofen Oral Solution at a strength of 100mg per 5mL. Hence the general tendency for the pharmaceutical industry to go the easier way; Ibuprofen Suspension 100mg/5mL.

 Pharmacy is both an art and a science, and the highly-coveted practice of the apothecaries predated the rise of the pharmaceutical industry. Amidst the rapid growth of the latter we are not to relinquish and forsake the traditional roles of our forebears the apothecaries, nor are we to succumb to pressures and be pushed out of our traditional domain. Expansion of our professional territories is desirable, but we should ever be awake to the fact that the pharmaceutical industry is our competitor, not ally. There is an Akan proverb which goes like; “A mighty warrior is worthy of his name only on the battlefront”. As pharmacists we give much meaning to our profession when we are able to bring science and art to bear to masterfully solve puzzles such as the one under consideration here. Within a spirit of competition with the pharmaceutical industry, we should aim to summon our expertise on the microscale to formulate products having added advantages for our clients.

 Now let us revert to the Ibuprofen puzzle. The compound is actually a weak acid and, as such, theoretically should be able to dissolve in an aqueous solution of a weak alkali. The dissolution of Ibuprofen powder in aqueous solution of sodium bicarbonate (NaHCO3) will convert it to Ibuprofen Sodium, which is very soluble in water, with the production of water and carbon dioxide bubbles as byproducts. Compare below the structures of Ibuprofen and Diclofenac on one hand, and Ibuprofen Sodium and Diclofenac Sodium on the other hand. It is noteworthy to state that it is Diclofenac Sodium as a soluble salt, and not the Diclofenac base, that is the form predominantly used in the formulation of almost all the Diclofenac preparations on the market. So, is it that no one has thought about Ibuprofen Sodium then?

 By stoichiometric analysis I arrived at the following formula for preparation of Ibuprofen Solution of concentration 100mg per 5mL;

                     Ibuprofen ———————— 20.00g

                     Sodium bicarbonate ———-- 8.15g

                     Purified Water to ————— 1000mL


 Method: Form alkaline solution by dissolving the sodium bicarbonate in about 2-5th (400mL) of the total volume; add the Ibuprofen powder and stir gently to completely dissolve; add sufficient amount of Purified Water to make up to total volume.

This basic formula can be adapted by including the appropriate excipients to prepare on the microscale Ibuprofen Oral Solution 100mg/5mL either by using raw Ibuprofen powder or equivalent number of preformulated Ibuprofen tablets. In the latter case, crush the Ibuprofen tablets in a mortar and comminute to produce a fine powder. Stir powdered tablet in the alkaline solution as above to extract Ibuprofen Sodium. Filter through a standard filter paper and then incorporate filtrate into the formulation.

 To conclude, I wish to affirm that pharmaceutical compounding is still a relevant role of the practising pharmacist as it was in the days of the apothecaries. Many are the pharmaceutical needs which the pharmaceutical industry has currently not filled, nor will ever be able to satisfy. We live in an era when the popular ideology is to customize or individualize healthcare interventions, that is, most of the clients we deal with will require special or unique pharmaceutical products and services. Do we as pharmacists throw up our hands in the air and look on helplessly when the pharmaceutical preparations our clients need are not available in the marketplace?. I advocate that inasmuch as we seek to expand our professional boundaries to include much of the clinical dimension we also do not forget the origins of our profession, but jealously preserve the art of the apothecaries. We need to orient our mindset to see the pharmaceutical industry as a real threat to our noble profession, not yielding to the former as helpless consumers, but formidably competing with the established industry as jealous and rightful custodians of the art and science of pharmacy. This we can do on the microscale. Every standard pharmacy, community or institutional, should necessarily be equipped with well-kept facility for purposes of pharmaceutical compounding. Let us rise above the retail-only pharmacies.

Decision making in clinical practice

In one hospital setting a doctor calls the Pharmacy Unit on the phone, and when the pharmacist’s assistant picks up he furiously passes on this message: “Tell your pharmacist never to change my prescriptions, okay”. The pharmacist upon taking delivery of this display of overt interprofessional animosity decided to query the disturbed doctor. The case in reference was a known hypertensive patient who presented with upper respiratory tract infection (URTI) on the previous visit, for whom this doctor had prescribed a full-dose regimen of an ephedrine-containing cough mixture to be taken at home over a period of seven(7) days. The pharmacist apparently got alarmed to the adrenergic effects of ephedrine and the possibility for the said formulation further raising this patient’s blood pressure(BP) and his intervention was substitution with a generic formulation having both expectorant and antitussive effects. In this hospital the pharmacy staff are deprived of patients’ medical folders at the point of service delivery, so that this pharmacist did not have information on the patient’s BP as well as the presenting symptoms at the time and so his action was based on pure theoretical judgment.

In the dialogue that ensued between the pharmacist and doctor the former explained the theoretical reasoning behind his action, whilst the latter on his part intimated that the former should have conferred with him on that point prior to any such action. And the doctor quickly added a remark to the effect that, in all cases, the final authority for therapeutic decision-making resides with a doctor and that a pharmacist is duty-bound to dispense any prescription regardless of his/her opinion on it. The pharmacist could simply not accept this assertion, of course not in this era of the clinical pharmacy movement when the hospital pharmacist is fervently seeking to establish the concept that therapeutic decision-making is not the prerogative of the medical profession, but a shared responsibility among the healthcare team.

The twist which occurred on the doctor’s side of the dialogue is the most fascinating. Admittedly, the pharmacist committed an ethical error in not consulting with the doctor on his opinion on the choice of cough mixture and about his intended action prior to it, by which means he could have effected a perpetual positive change in the doctor’s practice in first pass. Notwithstanding, for the doctor to appropriate to himself alone the final authority for therapeutic decision-making is a fallacy which requires remediation. The prevailing idea within the medical profession that a doctor’s thoughts are superior to those of all other healthcare professionals is yet another consequence of the rather outmoded concept of the healthcare team, the hierarchy model, wherein the doctor is placed at the top of therapeutic decision-making. It is against some of these fallacies and old-fashion models that pharmacists today should deal with if the clinical pharmacy movement will make further inroads.

Economic utility of a "green pharmacy" culture

The most sophisticated chemical factory in the world would not match the synthetic power of the lowliest herb. So many different chemical compounds are being synthesized in the same one plant at any one moment than is possible in any chemical factory in the world. In order to synthesize a very simple chemical molecule artificially it would require so much space and money to construct the chemical factory for this purpose. In contrast this analysis of space and money are of insignificance when it concerns a single plant. Yet the chemical substances which are being produced in even the lowliest of herbs are so much complex in structure that it is inconceivable for human efforts to duplicate them in a manmade chemical factory. Humanity already possesses in the plant kingdom the most sophisticated and efficient chemical factories ever possible.

 Plants are useful in themselves in that they are involved in maintenance of the natural cycles of Earth. This means that if mankind did not obtain anything more plants would still be considered as beneficial to humans. In addition to their own usefulness, however, the chemical substances that are produced by plants are also useful to mankind in many varying applications, including their uses as raw materials, nutrients and drugs. For reasons which are not immediately identifiable plants that have medicinal application are all referred to in common terminology as “herbs”. The practice of using plant resources in the treatment and prevention of diseases is therefore termed herbal medicine, and the concept of employing naturally-derived chemical compounds as mainstay in therapeutics and prophylaxis we may now term “green pharmacy”. Indeed, herbs are no meagre sources of drugs for human usage. The full diversity of all known drugs and even more are obtainable from the plant kingdom. One would find in medical history that drugs research began with plants and even in current medical practice several drugs are still being used which were first isolated from herbs. Many of what has been called “miracle drugs” continue to be found from herbs. These are natural chemical substances which are effective for treatment of the many serious, or if you like dangerous, diseases for which the existing synthetic drugs are ineffective. It is therefore very unfortunate that herbs are being ignored and maligned in orthodox medical practice.

In this and the following three short paragraphs the reader is here being led to recognize what has been called the economic utility of herbs. These are four reasons why the government and citizenry of a developing nation such as Ghana should depend on herbs for drug resources. The first point concerns ease of access to herbs. Among the plant resources within any geographical area one would find several useful herbs. It is already known that remarkable overlapping exists in the range of chemical substances plants synthesize, so that when taken together the herbs in any one geographical location are not unique but similar to the herbs in another geographical area. The implication of this statement is that the population of any country could confidently depend on indigenous plants to obtain all their herbal resources. It is a common misconception that superior herbs are those found in only specific foreign lands. The countries of the world are placed on the same platform on the basis of access to herbal medicines. There is no difference between a developed nation and a developing one as every country has its own natural supply of indigenous herbal drugs. If a developing country depended on its indigenous supply of herbs for treatment of diseases it would not have to import synthetic drugs from foreign countries. One of the elements which developed nations employ to maintain their economic dominance over developing countries is the chemical industry. It is inconceivable how a developing country like Ghana could catch up with, for example, the United States in the production of drugs and other synthetic chemical substances. Developing countries would ever have to import synthetic drugs at high cost from the already advanced countries to meet the drug needs of their populations. This dependency syndrome would be curtailed if such a developing country reverts to its indigenous herbs for drug needs. This situation would afford such a country a considerable measure of economic freedom and greater possibility of fulfilling the medical needs of its population.

 The second point is the low cost of herbal drugs in comparison with synthetic drugs. Despite the fact that herbs would require initial processing in some cases to make them usable, all things considered, it is far more expensive to produce synthetic drugs than herbal drugs. The design and construction of a chemical factory cost so much investment capital. On the contrary an herb may be usable in the raw state and if processing is required at all such procedures are so simple as to require only a few basic equipment. Any healthcare system which heavily depends on herbs for drug resources would operate on a smaller budget than one which is based on synthetic drugs. When a government has successfully reduced its healthcare expenditure using this approach it would have much surplus funds to invest in other sectors of the economy.

 The third point is that the herbal drug industry is protective of the environment whilst the synthetic drug industry promotes environmental degradation. The chemical industry is known to be responsible for producing most of the environmental pollutants that are threatening the ozone layer, oceans, land and forests. The herbal drug industry on the other hand has plant cultivation as its basis. Such observance of “green culture” as in the farming of herbs engenders such secondary benefits as replenishment of oxygen supply in the atmosphere, protection of ozone layer, cooling of environmental temperature, and maintenance of natural cycles of Earth. As populations revert to herbs for drug resources they would have solved the problem of global warming to a large extent.

 The last, but not least, point is that the herbal drug industry has the potential to provide employment for the greater number of the population than is possible by the synthetic drug industry. In the chemical factory the fact is that much of the manufacturing processes are being performed by automated machineries. On the contrary the cultivation of raw herbal drugs is a very labour-intensive enterprise which would require so many peasant farmers each working in small scale to produce sufficient quantities to meet the demands of the population. Thus cultivation of herbs alone would provide employment for a large number of citizens of the country. Between the farmer and the patient who consumes the herbal drug the herbal drug industry would enable the practice of several other professions. Such intervening professions would include the pharmacist who would prepare the raw herb into a usable product; the medical doctor who would prescribe the herbal drug in treatment of diseases; and the nurse who would administer the drug to the patient at the hospital ward. Two other professions are the agronomist who would be occupied with the breeding of superior species of herbs; and the clinical pharmacologist who would research into the medical applications of herbal drugs. By a thorough comparison one would find that herbal drugs have greater economic utility than synthetic drugs and that by using them developing nations would not only satisfy their drug needs but would also actualize economic emancipation.

Essential Medicine Sheabutter

Sheabutter, Butyrum Medicinalis (q. vide, Paracelsus Transactions 2018;2:1-18 https://archive.org/details/Par.Trans.2118/mode/2up ), is now officially recognized as a medicinal substance in Ghana. It is currently listed in the Ghana Essential Medicines List (Ministry of Health/Ghana National Drugs Programme, 2017) in page 23 among miscellaneous medicinal substances for treatment of dermatological diseases.

 Advocates of the “green pharmacy” movement are delighted and hail the entire Ghana national formulary committee for this bold policy initiative.

 The listing of Sheabutter in the group of miscellaneous dermatological products simply means that further studies are required to clarify its medicinal properties, and this is where collaborative effort is needed. The Ghanaian pharmacist owes a duty to the nation to lead by developing methods for extraction of the pure substance and formulation of Sheabutter into dosage forms conforming to the pharmaceutical standards of modern times. Academics can intervene with scientific studies to further characterise the chemical and physical properties of this product as well as participate in multidisciplinary teams for conducting clinical trials on it, and medical doctors are to contribute by trying Sheabutter and formulations based on it on their patients for therapeutic uses.

 Sheabutter is eaten as cooking fat in traditional cuisines. There is in addition to this numerous anecdotal reports about its medicinal usefulness, including the following;

•  Relieves pain and prevents blister formation when applied to scalded skin. 

•  Cures acneiform lesions. 

•  Relieves pain and consolidates boils. 

•  Effective as massage aid for treating musculoskeletal pain. 

•  Relieves pain and inflammation arising from insect stings. 

•  Relieves pains and swelling caused by physical injuries. 

•  Effective for keeping the skin soft and supple. 

•  Effective for treating allergic nasal conditions. 

 The story of Sheabutter will be the story of how a developing nation could employ its indigenous natural resources to its economic advantage. A country such as Ghana is strong enough to compete on the global arena only if it depends heavily on its own indigenous resources and human capacity. In listing Sheabutter as an essential medicine the Ghana national formulary committee has demonstrated good leadership. Now duty beckons to all well-meaning Ghanaians, especially the technical and health professional class, to join the front to push this national agenda forward.

Useful tip on nebulisation technique

There is a very good reason why whenever a prescription is written for "Salbutamol 5mg by nebulisation" the healthcare staff should select two(2) vials of the Salbutamol nebules 2.5mg/2.5mL strength, in preference to one(1) vial of the Salbutamol nebules 5mg/2.5mL strength.

Obviously in each case you get the nominal dose of Salbutamol 5mg prescribed, but a mechanical factor limiting the performance of nebuliser machines leads to different results. All available nebulisers suffer the limitation called "dead volume"; which is a fixed volume of solution which is left in the medication cup of the nebuliser after each procedure. This fixed volume of liquid medication cannot be picked up and aerosolised by the machine and is left behind.

This gives a margin of error to the actual dose of the drug that is discharged to the patient.

Nebuliser brands differ in the extent of the "dead volume", but let's assume a figure of 0.5mL in order to demonstrate its significance.

When a prescription for "Salbutamol 5mg by nebulisation" is written and two(2) vials of Salbutamol nebules 2.5mg/2.5mL is filled into the nebuliser, if you adjust for a dead volume of 0.5mL you get 4.5mg of the drug discharged to the patient. If the same procedure is performed by filling one(1) vial of Salbutamol nebules 5mg/2.5mL into the machine you obtain only 4mg of Salbutamol discharged to the patient.

The 0.5mg variation between the two procedures makes a lot of difference in inhalation therapy. Remember that usual prescribed dose for Salbutamol inhaler for an adult is only 0.2mg (200micrograms), meaning that 0.5mg (500micrograms) cannot be ignored.