An appeal for scientific criticism in pharmacy practice

A much revered wise-saying in Akan goes like this; “Dua kontonkyitonkyi na ɛma yɛhunu dwumfoɔ”. An English rendition of which will be, “a crooked piece of wood reveals the skillful carver”. This adage gives us a test for artful craftsmanship, pointing to the fact that it takes so much learned or innate skill to make meaning out of a seemingly useless situation. In the context of professional practices it illumines us to understand that skill is what sets apart the professional from a lay person.

In our modern world, many thanks to information communication technology(IT), both pharmacists and the lay public now have an almost free access to a large breadth of information on drugs, specifically, and healthcare in general. But much as breadth in perspective is seen effortlessly, so much skill and labour are required to discover depth. The capacity to process and make meaning of the same information presented to both the pharmacist and the lay person is what sets the one apart from the other. And this skill is most relevant in situations when there are obvious contradictions or unfilled gaps with the pieces of information presented. It is requisite for a pharmacist, a sine qua non, in order for him or her to excel in the chosen profession, to possess the skill to expertly sift the available pieces of information on drugs and take an informed position. There will be no difference if a pharmacist also absorbs any information presented hook, line and sinker just as the lay person. In the events when there are unfilled gaps with the available information, a recourse to an educated guess will be necessary. A pharmacist who proceeds along this line of thought is guided by the merits of scientific criticism in his or her practice.

A recent report tells of a pharmacist who declined to dispense diazepam to a client, having been requested of the latter for that drug by name to relieve an episode of insomnia, and recommended the intake of chamomile tea instead. Was scientific criticism involved in the decision-making process here? That depends on what this pharmacist would give for a reason. It is a scientific argument if the pharmacist’s reason is that diazepam is a controlled substance, a prescription-only drug (POM), and therefore the client required a valid prescription to access it (The Legal Argument). It is a scientific argument if the pharmacist is just being mindful that the habit of taking a drug to induce sleep could lead that client to a state of drug dependency or addiction (The Addiction Argument). It is again a scientific argument if the pharmacist’s recommendation was a matter of preference for natural therapies and a personal disposition to promote any therapy of natural origin above synthetic drugs (The Orientation Argument).

In this case, however, an argument made within pharmacology (The Pharmacology Argument) will not stand the test of scientific criticism. Why, because whereas a large body of knowledge has been documented in literature in favour of diazepam, currently there is an information gap as far as the herb chamomile is concerned. The pharmacist most likely knows, or at least can easily access, so much information on the pharmacology of diazepam, including its chemical identity, mechanism of action, duration of activity, known and predictable drug interactions, risk of tolerance and its addiction potential, safe dosing regimens, and much more. This wealth of information on diazepam has, rather unexpectedly, bred a common phobia against it within the healthcare community. On the other hand, the literature is currently not as much rich with these pieces of information towards chamomile. It is fine if this dearth of information on the pharmacology and toxicology of chamomile is appreciated and not misinterpreted to mean a better safety profile of this herb compared to diazepam. To wit, our pharmacist will not be right in this instance if his or her recommendation to that client was on the basis of an idea that chamomile tea is a safer option.

To elaborate on the pharmacology argument, how else could chamomile effect sedative properties if it does not contain active principles (secondary metabolites) which also interfere with the activities of one or more neurotransmitters in the CNS? Assuming even that the active principle(s) in chamomile does not exert action on the GABA-ergic neuronal pathways diazepam is known to be involved with, it is very reasonable to say that that active compound and diazepam are both molecular entities and for that matter the classical laws of drug-receptor interaction hold all the same. The only difference here being that whereas the active principle(s) in chamomile is naturally derived, and perhaps not yet isolated, diazepam is a purely synthetic drug. It is only when we were to have a detailed pharmacological profile of chamomile can we scientifically compare this natural therapy with diazepam along the lines of pharmacology.

It makes so much difference how we defend our positions and choices in the practice of pharmacy. If doing a scientific criticism means taking a position opposed to the orthodox viewpoint on the matter do it for being the noblest course of action. This holds true so long as some pieces of evidence, either documented or experiential, can be adduced in defence of the position espoused.

A coalition of pharmacists against professional drug peddling?

In the community where my retail pharmacy is located a colleague pharmacist is sponsoring the OTCMS shops around to fiercely compete with me. What is his modus operandi? He moves about with his van from his own business territory, and entering my territory hops from one OTCMS shop to another, to supply them with not only Class C medicines but also the Class A and B groups according to the requirements of those shops.

 

He calls this activity a smart business move enabling him to extend the boundaries of his business territory, I call it professional drug peddling and everything but ingenious. For the benefit of this discussion let's explain "professional drug peddling" as the practice of a licensed wholesale or retail pharmacy carrying bulk  stocks of medicines from the registered premises on an itinerant journey and selling these stocks in portions to other pharmaceutical facilities en route, usually covering long distances and many days in trekking.

Direct end-to-end delivery of stocks from a wholesale premises to a retail or dispensing facility is excluded from the scope of this definition.

 

Our usage of the qualification of "professional" is not intended to imply quality of performance but, rather, the fact that such activities are done by the direct instructions or under the supervision of pharmacists.

 

Professional drug peddling, which is both an illegality in Ghana and an affront to sound ethical principles of pharmacy practice, is gradually establishing itself as a normal practice in this country and I am not the only victim of its consequences. A full analysis of the ripple effects of professional drug peddling in this country will require a broad-based enquiry beyond the strengths of this rather short discussion, but we do not have to develop an academic thesis for anyone to comprehend that professional drug peddling is the direct cause how OTCMS shops can access Class A and B medicines. When a wholesale pharmacy sends out a trekking mission to the field with a part of its stocks, it must of necessity make sales on the field and not waste fuel. Faced with a dilemma between survival and ethics, the choice naturally would go in the way of the former option. Ethics will always be slaughtered on the alters of survival instincts.

 

By law a pharmacy is a fixed premises, never a movable structure. The laws in Ghana give practical significance to this assertion by providing for the registration of pharmacies or other premises for the dispensing of medicines separately from the licensure of the practitioners who work in these premises. Itinerant vans of licensed wholesale pharmacies in effect move the premises of those wholesale/retail pharmacies in part from the recognized location to other territories. This practice contravenes existing regulations of pharmaceutical practice, perhaps only giving an exception for direct end-to-end delivery of stocks from a wholesale premises to a retail/dispensing facility in response to a concluded transaction for being of a different business model. So to reiterate, professional drug peddling is unlawful in Ghana, at least as of the present time, and hence any pharmacy or a pharmacist who perpetrates it commits an illegality.

 

From the point of view of ethics pardon me to ask if we as pharmacists are ever mindful of the effects our deeds and misdeeds, actions and inactions, have on our profession and colleague pharmacists at large. In the present scenario, professional drug peddling adversely affects the standards of pharmacy practice and nurtures an unfavourable environment which makes it extremely difficult for other pharmacies to thrive, with pharmacies in the small districts and rural areas hit the hardest.

 

When once in a discussion with a senior officer of the Pharmacy Council around this subject matter I asked why the regulator has not been successful in curtailing this phenomenon, his answer pierced me to the core. He in turn asked me of what cadre of professionals the supervising practitioners of wholesale pharmacies are which do send out vans on trekking. At the end of the discussion I couldn't help but agree with him that our predicament is one of in-fighting. Just a handful, in relative terms, of pharmacists are by this means fighting against the larger body of pharmacists and also making the work of the regulator more difficult. He was quite point-blank, that many of the challenges Pharmacy Council is grappling with were caused by one pharmacist or the other, only for the bigger fold to turn back with criticisms that the Council is not doing much for our profession.

 

So, how about resorting to the approach of self-regulation in an attempt to exterminate the fledgling phenomenon of professional drug peddling in this country?  A prompt action is necessary before this phenomenon gets fixed in the minds of current and future generations of Ghanaian pharmacists as both acceptable and lawful.

In the considered opinion of this writer, no other instrumentality could be superior to self-discipline at controlling misdemeanour.

 

In our context "self" refers to the PSGH and the entire body of pharmacists. This is a call to reactivate the erstwhile committee of the PSGH charged with self-regulation of members of the professional body, as well as the pharmaceutical environment, to deliver on its mandate.

 

As a second step the writer recommends the formation of a coalition of pharmacists to volunteer information and field evidence to support the work of the aforesaid committee. These volunteers scattered across the length and breadth of this country, keeping watchful eyes for professional drug peddlers from their community pharmacies as sentry posts, could report with the timely information and evidence to facilitate the work of that committee and the Pharmacy Council.

 

Possibly, such an advocacy group of pharmacists will be a game-changer for pharmacy practice in our dear country.

On the maximum doses for IV/IM Artesunate and IM Artemether

PROBLEM STATEMENT:

•Both national and international treatment guidelines for malaria currently recommend a dosage of 2.4mg/Kg BW artesunate per dose by both IV and IM routes in adults and older children, and 3mg/Kg BW per dose in children with body weights below 20Kg. Three doses are initially administered over 24hrs at fixed times of 0hr, 12hr and 24hr, with repeat doses given at 24hr intervals if necessary.

 

•Recommended dosage for IM artemether is 3.2mg/Kg BW as a bolus dose, with repeat doses of 1.6mg/Kg BW at intervals of 24hrs apart if necessary.

 

•The guidelines are however silent on the maximum allowable doses for both of these drugs given by the parenteral routes, resulting in a lack of consensus among healthcare practitioners on this particular matter.

 

•This represents a classic example of situations in medical practice when the carefully considered opinions of individual practitioners are brought to bear in decision-making.

 

 

INDIRECT EVIDENCE:

•The current WHO Guidelines for malaria (published on 14 March 2023) makes the following explicit recommendations on the dosages of ACT antimalarial therapy by the oral route. Interest here is on the artemisinin-derivative components of the medications.

 

•Oral artemether/lumefantrine

Up to a maximum of 80mg artemether BID (160mg daily).

 

•Oral artesunate/amodiaquine

Up to a maximum of 200mg artesunate daily as a single dose.

 

•Oral artesunate/mefloquine

Up to a maximum of 200mg artesunate daily as a single dose.

 

•Oral artesunate/sulfadoxine-pyrimethamine

Up to a maximum of 200mg artesunate daily as a single dose.

 

•Oral dihydroartemisinin/piperaquine

Up to a maximum of 200mg dihydroartemisinin daily as a single dose.

 

 

 

PHARMACOKINETIC PRINCIPLES:

•Every drug exerts its actions within a therapeutic window, bounded by both a minimum effective concentration [minimum dose, Cmin.] and a maximum effective concentration [maximum dose,  Cmax.].

 

•Increasing the dose of a drug above its Cmax threshold increases the incidence and severity of toxic effects associated with the drug, usually without producing any incremental benefits in the positive therapeutic effects of the same drug.

 

•Moreover, the associated increments in the cost of higher doses are not offset by any further benefits in treatment outcomes, raising concerns about economics of healthcare and wastage of resources.

 

•By reason of barriers to drug absorption from the GI tract such as solubility and first-pass metabolism, bioavailability of drugs after oral administration are almost always lower than levels achieved after administration by any of the parenteral routes.

 

•Deductive arguments from the foregoing principles are that, firstly, there should be a maximum allowable dose for both artesunate and artemether when administered by the parenteral routes (only perhaps  this matter has not attracted the attention of researchers yet), and secondly, both drugs when given by any parenteral route should demonstrate at least equal potency at doses specified in current guidelines as maximum daily oral dose for each drug.

 

 

QUESTIONS:

1. What are the maximum doses of IV/IM artesunate and IM artemether in absolute terms?

 

The opinion of the author is as follows;

 

•IV/IM Artesunate, max. 200mg per dose

 

•IM Artemether, max. 160mg per dose

 

 

2. When is it appropriate to initiate oral ACT after initial parenteral treatment?

 

On the basis of dosage frequency recommended by current guidelines for parenteral artesunate or artemether, it is very reasonable to recommend that oral ACT medications be initiated anytime around 24hrs after the last parenteral dose.

 

3. How safe is a switch to IV artesunate after an initial IM artemether?

 

The PubChem monograph on Artemether depicts that after IM administration artemether is detectable in plasma in appreciable amounts by 1hr, and peak concentrations are established between 2-4hrs.

In situations when clinicians are considering that giving IV artesunate after an initial IM artemether is an emergency in order to achieve rapid clearance of heavy parasitaemia, the decision should depend mainly on elapsing time interval post IM artemether. Whereas giving IV artesunate within 1hr of IM artemether administration may be safe, the opinion of the author is that the estimated dose of artesunate should be reduced by a margin as a precaution to avoid occurrence of adverse effects. Administration of IV artesunate well after 1hr of IM artemether injection may not be necessary.

OpenDTC_FAQs

The OpenDTC Collaboration

 

FREQUENTLY ASKED QUESTIONS

 

1. Why is exchange of practical information important in the healthcare process?

 

The young healthcare practitioner would realize soon after induction that theoretical knowledge does not always apply directly on the field of practice and that some level of processing of theoretical information is necessary against a background of preexisting experience. The formation of The OpenDTC Collaboration was motivated by the philosophy that excellence in medical practice depends less (around only 40 per cent) on theoretical knowledge and very much (around 60 per cent) on practical experience gathered on the field of practice. Considering the immensity of practical information as an important resource in the healthcare process and bearing in mind the fact that an individual healthcare practitioner will at all times be limited in scope of experience already attained, there was identified the necessity of having in place a system or mechanism by which practical information could be exchanged between practitioners across all practice environments.

 

 

2. Who can join The OpenDTC Collaboration?

 

The OpenDTC Collaboration is an interdisciplinary platform for networking healthcare practitioners from various professional backgrounds and the full spectrum of clinical practice settings. The other important prerequisite for membership is that the practitioner should be duly registered and in good standing with the designated professional regulatory authority.

 

 

3. How do I apply for membership?

 

Membership is granted after completing the designated form for registration of the practitioner's personal and professional data with the Secretariat. Kindly consult the Secretariat for further assistance.

 

 

4. How much do I pay for membership?

 

Both the initial registration and membership of The OpenDTC Collaboration are free of charge at all times.

 

 

5. What is the difference between a member and subscriber?

 

The designation of Subscriber is applied only for the purpose of discussions on the official Channel of The OpenDTC Collaboration on the Telegram app. All members automatically become subscribers to the Channel after registration.

 

 

6. Why do I have to subscribe to the Channel?

 

The official Channel of The OpenDTC Collaboration on the Telegram app is the sole medium for exchange of practical information among members of the Collaboration. Messages posted on the Channel are case studies or reviews from individual members after going through and passing a process of peer-review.

The Channel is linked to an external group discussion page on the same platform to enable members to comment on and discuss messages posted.

 

 

7. What are case studies or case reviews?

 

A case study is defined as the active study or attentive monitoring of an individual patient, a cohort of patients, an intervention, a procedure, or a medical technology on the field of practice in an attempt to answer yet unresolved questions or find new practical information. The case study must of necessity be a firsthand experience on the field of practice and either confirm an existing knowledge or expand the frontiers of practical information available for the healthcare process.

On the contrary, a case review differs from case study in being retrospective in approach.

 

 

8. What is the attribution policy for case studies published?

 

Case studies or reviews that are published on the official Channel after successful peer-review ordinarily are appended with the names, professional titles and affiliations of authors who contributed them. However, a member also has the option to have case studies or reviews published anonymously on the Channel.

 

 

9. What happens during peer-review of case studies or reviews?

 

The Secretariat has in place an editorial committee made up of eleven (11) members for each particular health profession or specialty of medical practice for the purpose of peer-review and approval of case study reports before publication. After receiving the script for a case study or review report, this is forwarded to members of the appropriate editorial committee to review the content and assess the practical relevance of that material on the basis of predetermined criteria. All case study reports will either be rejected or accepted for publication on the recommendations of the editorial committees.

 

 

10. Can I serve on an editorial committee?

 

Definitely. Kindly verify with the Secretariat for vacancy on the editorial committee for your profession.

 

 

11. How does The OpenDTC Collaboration contribute to continuous professional development of healthcare practitioners?

 

The reality is that the individual healthcare practitioner will never get the opportunity of exposure to all practice environments throughout a lifetime, but still a wealth of practical experience gathered on the front of diverse practice settings is an aid to professional excellence. It is therefore imperative that the healthcare practitioner depends on the experiences of colleagues, from which wealth of information he or she can draw when faced with similar situations. The Channel provides a mechanism for unifying practical experience across the full spectrum of the healthcare sector by means of the published peer-reviewed case studies and reviews.

The OpenDTC Collaboration is accredited by various professional regulatory authorities as a provider of continuous professional education (CPD/CME/CPE) to healthcare practitioners. Every member of The OpenDTC Collaboration is awarded with two (2) credit points annually for membership. Kindly consult the Secretariat to verify CPD accreditation status for your profession.

An individual practitioner additionally will be awarded with credit points for publishing case studies or reviews on the Channel, as explained in the following section.

 

 

12. What CPD credit point award scheme is applied?

 

Beside the award of two (2) CPD credit points annually for membership of The OpenDTC Collaboration, a member also obtains additional CPD credit points for case studies or reviews successfully peer-reviewed and published on the Channel. Two (2) CPD credit points are awarded to an author for presenting a total of five(5) case studies or reviews through the peer-review process. The tally of count of published contributions from the same author may extend over one calendar year but once an award has been issued the same case studies do not qualify for re-award. However, an already published case study or review may be republished multiple times.

 

 

13. What is the meaning behind the name OpenDTC?

 

OpenDTC is an acronym for Open Drugs and Therapeutics Committee, a DTC unlimited by geographical boundaries and practice settings. Globally the DTC is an organ of healthcare institutions responsible for clinical governance and quality assurance of the healthcare process, and is usually constituted with representatives from the various health professions.

The OpenDTC Collaboration has a nationwide scope of activity.

 

 

14. How can I contact the Secretariat?

 

Send an email message through fleshandbrain@live.com, or call +233242162382, +233206120649.

Phosphorus

The term “phosphorus” was originally used to describe any physical substance which after some exposure to light would glow when put in darkness. Now, “Phosphorus” is the name given to the chemical element with atomic number 15, symbol P, and atomic weight of 30.97. Historical accounts have it that a certain Hennig Brand first prepared Phosphorus in the year 1669 by the process of destructive distillation of urine.

The focus of this essay is to briefly discuss the medical importance of this element.

 

The natural distribution of Phosphorus

Phosphorus does not occur in nature as the pure elemental substance, but combined with oxygen as the phosphate ion (PO₄^3-) it is widely distributed throughout the lithosphere, hydrosphere and biosphere of our planet Earth. This is to say that as the phosphate ion Phosphorus is universally distributed throughout the earth crust and its mineral resources, the oceans and waterbodies, and all the living organisms of this planet. As a monument to the great importance of Phosphorus to the life courses on Earth nature intervened with the phosphorus cycle, a complex network of geological processes which are constantly in operation to recycle the phosphate ion through these three spheres of life on our planet.

In the lithosphere Phosphorus occurs as deposits of calcium phosphate minerals, otherwise known as phosphate rocks. These mineral deposits are predominantly insoluble in water and hence immobile. The natural process of weathering breaks down these rocks to very fine particles in the passage of time, upon which rainwater subsequently acts, dissolves, releases and carries the phosphate ion in the running stream. This latter process is termed leaching. The fate of the phosphate ion formed depends much on its destination. It may be absorbed with groundwater and utilized as an essential nutrient by plants, and also by lower living species that can utilize phosphate ion as a source of Phosphorus. Humans and animals cannot utilize the phosphate ion directly but otherwise obtain their supply of Phosphorus by consuming plants mainly. This describes a bird’s-eye view of the movement of Phosphorus from the lithosphere to the biosphere. The death and consequent decomposition of living organisms represents a reverse process which returns phosphate ions from the biosphere to the lithosphere.

The phosphate ion carried in running water may end up in the waterbodies, and there combine with mostly calcium ions, but also with aluminum and iron to some extent, and then precipitate as insoluble mineral species.

The following discussion of how Phosphorus occurs in humans typically reflects the occurrence of this element in all of the biosphere.

 

The occurrence of Phosphorus in humans

I open this section with the following quotation from Mellor’s Treatises: “Phosphorus was on the earth in gaseous, liquid, or solid form before the dawn of life, and since then, all animal and vegetable creations have combined with the physical forces always at work in inanimate nature to distribute and redistribute the phosphorus, to divide it up, and carry it from place to place. If the biography of atoms could be written, the chapters on phosphorus would be the most interesting and the most varied. --- WBM Davidson, 1893”.

Human life depends on Phosphorus for its existence and it is inconceivable if any other chemical element could match it in importance in this regard. Phosphorus occupies the core of both the tissues (structure) of humans and the metabolic processes (function) that occur therein, as exemplified by the discussions below.

BONE. The bones impart shape to the human body, make movement possible, and provide protective housing for marrow which is the organ within which blood is made. Bone tissue is made up of a network of collagen protein fibres, strengthened with a derivative compound of Phosphorus known as hydroxylapatite. In terms of bulk this hydroxylapatite constitutes more than half the mass of the hard bone tissue, and imparts mechanical strength to the bone. The hydroxylapatite of bone is a variant of the compound calcium phosphate Ca₃(PO₄)₂ wherein Phosphorus is combined with calcium and oxygen, this basic material is hydrated with water molecules, and there is trace amounts of other ions such as magnesium, fluoride, chloride and carbonate. It is not known why nature chose Phosphorus above every other element as the core of this important bone tissue, and what substitution of Phosphorus with any other element means for the structural integrity of bone tissue, but what has been said already is the natural state of affairs. It is what it is, and it can be said again that Phosphorus is an essential element for the formation of bone tissue.

TEETH. Human teeth is a bony structure and what has been said above about the importance of Phosphorus to the structural makeup of bones holds true to a very large extent. Phosphorus is also at the core of the structure and strength of human tooth enamel.

CELL MEMBRANE. The main building blocks of the cell membrane of every living cell are phospholipids, four kinds of which are known to occur naturally in humans namely phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol. In a typical cell membrane these chemical substances are arranged in a mosaic pattern of double layer encasing the cellular subunits to form a separate entity, an arrangement which makes the cell membrane fluid in structure and also imparts on the cell adaptive characteristics to survive in the aquatic environment prevalent within human tissues. All four of these phospholipids are in chemical nature compounds of Phosphorus, in which this essential element as the phosphate intermediate is chemically combined with a glycerol backbone, fatty acid side chains and either of choline, ethanolamine, serine or inositol. Again, why the natural order settled for Phosphorus above every other element in the making of this critical cellular substructure cannot be told with certainty but the phospholipids present yet another testimony of how essential our chemical element is to life.

NERVOUS TISSUE. Regular phospholipids and a type of it known as sphingomyelins form the basic fabric of the nervous tissues of humans, of which the proportion of sphingomyelins in both the central and the peripheral nervous system is currently thought to supersede all other tissues of the body. The element Phosphorus is again deeply embedded in the structures of both of these chemical substances.

DNA. The storage molecule for genetic information in cells, deoxyribonucleic acid (DNA), will be in the form of a very long ladder if it could be straightened out. The rungs on this ladder will be pairings of the purine bases with pyrimidines, namely adenine with thymine and guanine with cytosine, in loose chemical bonding that could be likened to two human beings with an arm each joined palm-to-palm over a large gulley whilst the other arm of each person is wrapped tightly round a firmly fixed stake on either side of this gulley. The ease of breaking this chemical union is just as simple as each person letting go of the arm of the other person. The rail on either side of this ladder which serves as backbone for the purine and pyrimidine bases is made up of a small sugar molecule known as deoxyribose and the element Phosphorus, as its phosphate derivative. Deoxyribose is strongly joined with phosphate (a derivative of Phosphorus) in covalent bonding in an alternating arrangement to form the backbone of the DNA molecule on both sides. Thus is the critical role of the element Phosphorus in the genetic material of cells.

RNA. Ribonucleic acids (RNAs) are usually copied out of definite segments along the DNA strands and encode the genetic information for the synthesis of specific functional and structural proteins within cells. One key difference between DNA and RNA is that the latter is a single strand, very much like what is formed after cutting a ladder apart along its long axis. Moreover the RNA molecule is much shorter in length compared to DNA. Otherwise, phosphate (a derivative of the element Phosphorus) is covalently bonded to ribose (a derivative of deoxyribose in DNA) in alternating arrangement, with one kind of purine base or pyrimidine bonded directly to each ribose unit depending on the gene(s) encoded. Thus, RNAs are again another form in which the element Phosphorus occurs in humans.

ATP. Biochemists colloquially refer to adenosine triphosphate (ATP) as the “energy currency” within living organisms. The myriad of daily life activities which every human being is involved with, and all the metabolic processes occurring in humans, are all possible because of ATP. Just as money ATP is simply exchanged between the biological systems and metabolic processes; ATP is recycled by being consumed in anabolic (synthetic) metabolic processes and regenerated through catabolic (breakdown) processes. Structurally, the ATP molecule is made up of adenine, ribose and three molecules of phosphate (a derivative of the element Phosphorus) in such an arrangement that the first two components are bonded in one arm whilst the phosphate fragments are bonded one to another as in a chain in a separate arm of the ribose unit. Cleavage of the phosphate bonds of ATP releases energy, and their formation is a mechanism for entrapment and storage of chemical energy in biological systems. We again see our element Phosphorus in ATP molecules.

PHOSPHORYLATION. Almost all enzymes, B-complex vitamins and most other functional proteins in the body are activated through a process known as phosphorylation. These biological components are otherwise inactive and as such useless to the body; by means of the mechanism of phosphorylation these vital principles are kicked to action. The process of phosphorylation simply is the bonding of a phosphate (a derivative of the element Phosphorus) group to the inactive principle, which instantaneously imparts activity to the component involved. The source of phosphate for the purpose of phosphorylation is varied but is mostly obtained from ATP. Our interest here in this vital process of life is the involvement of the element Phosphorus, which is presented as its derivative phosphate.

 

Significance of Phosphorus in human disease

The reader should appreciate by now that very scientific and rational considerations underlie the attempt of this author to relate the element Phosphorus to human disease. The supply of Phosphorus to a human being is dynamic, this element predominantly obtained as organic phosphate compounds in the diet. Depending on the richness of diet in terms of these phosphate compounds, however, the supply of Phosphorus to the human consumer could be more or less inadequate. Insufficient consumption of phosphate derivatives as nutrients in diet over a long period of time will lead to Phosphorus (or phosphate) deficiency, with deleterious consequences on multiple organ systems of the human body.

The fact that Phosphorus exits in the human body in a dynamic equilibrium and what that means as a contributory factor to human disease has evaded popular attention. In pursuance of an orientation to such an idea the following quotation is made verbatim from Mellor’s Treatises: “The waste of muscular and nervous tissue involves a decomposition of the phosphorus compounds. The products of decomposition are carried by the blood to the kidneys, and there excreted with the urine chiefly as sodium ammonium phosphate. There seems to be a relation between the amount of phosphorus compounds discharged from the system, and the activity of the brain, and this led to the inference that phosphorus is a metabolic product of the activity of the brain, and that phosphate foods are needed for brain workers. The idea has crystallized in the well-worn phrase ‘ohne Phosphor kein Gedanke’, without phosphorus no thought. A normal adult excretes the equivalent of 3 to 4g of phosphoric acid per diem. Part of this is derived from the food, and part from muscular waste”.

The physiological state during which the levels of Phosphorus in the human body is consistently lower than what is needed to support metabolism is referred to as hypophosphataemia. According to a factsheet recently published by the National Institutes of Health (NIH, USA) the effects of hypophosphataemia on health can include anorexia, anaemia, proximal muscle weakness, skeletal diseases (bone pain, rickets, osteomalacia), increased infection risks, paraesthesias, ataxia, and confusion. In the opinion of this author hypophosphataemia results to degeneration and failure of multiple organ systems of the human body, and is a major underlying cause for ailments including asthenia, muscular weakness, chronic fatigue syndrome, neuropathy, and osteoporosis.

 

Supplementation of Phosphorus

The author affirms that medical treatments for the ailments namely asthenia, chronic fatigue syndrome, peripheral neuropathies, and osteoporosis should always be supported with supplementation of Phosphorus. However, the Phosphorus in its pure elemental form is extremely poisonous and cannot be taken. Calcium phosphate may be safely used for this purpose, from which after digestion Phosphorus is absorbed as phosphoric acid into the bloodstream for further processing. Although calcium phosphate falls short of the ideal as a source of Phosphorus by reason of its high content of calcium ions, with evidence emerging to increasingly implicate calcium ion in the causation of some cardiovascular diseases.

The soluble alkali metal salts of phosphate should also be avoided as a source of Phosphorus. Among this group are sodium triphosphate, sodium hydrogen phosphate, sodium dihydrogen phosphate, and their potassium counterparts. These salts are not safe for internal consumption as they are associated with much greater risk for precipitating insoluble stones in body tissues and the kidneys.

The ideal form of Phosphorus for supplementation is phosphoric acid (H₃PO₄). The latter is water-soluble and readily absorbed from the intestines into the bloodstream. Once absorbed phosphoric acid is fed directly into the body’s metabolic processes wherein the phosphate ion is required. The big note of caution here is that by phosphoric acid is meant a finished pharmaceutical preparation including phosphoric acid as a major active ingredient. The phosphoric acid of commerce is a very pure and strong acid which can easily destroy the tissues of the body. The layman should have nothing to do with this form of phosphoric acid, and at best, should never keep stock of it at home. Reference is here made to phosphoric acid which has been professionally diluted by a pharmacist or prepared ready to consume as a finished pharmaceutical product. These forms are usually given with specific instructions for further dilution so that the consumer is guided to safely administer them.

 

References:

·        JW Mellor (1947). A comprehensive treatise on inorganic and theoretical chemistry, vol. 8, pp 732, 737. Longman, Green and Co.

·        NIH (USA). Phosphorus – Fact Sheet for health professionals. Online resource accessed at https://ods.od.nih.gov/factsheets/Phosphorus-HealthProfessional/#en1. Date: Friday, 25 August 2023.

Contra-Darwinian evolution, or devolution theory

It is not known yet whether Darwin himself or any of the classical theorists recognized and ever discussed the opposite process by which living organisms lose both form and function in the passage of time. The orthodox doctrine of biological evolution projects a progressive course, in the sense that organisms develop finer forms and functions to survive within hostile environments around them as time passes. The changing environment makes it imperative for living organisms to develop adaptive characteristics in order to survive, and organisms that are unable to adapt to a changing environment in accordance with this natural law are exterminated from existence. An inherent presumption in the classical theory of biological evolution is that living organisms progressively become better in both form and function in respect to the external environment within which they live.

The opposite process whereby living organisms lose form and function, that which in this piece is described as contra-Darwinian evolution or devolution theory, perhaps, has evaded general attention. At least this latter process is not as so much discussed as classical evolutionary theory. However, it will be a mistake of immense proportion to assume that extinction of biological species consequent in Darwinian evolution always occur spontaneously through catastrophic causes. Although natural catastrophes are not excluded from the possible mechanisms of natural selection, of greater importance is the subtle process of devolution (deterioration) through which living organisms are stripped of vital characteristics which deprive them of the capacity to survive within their environments. The devolution of living organisms, which by reason of its occurrence at the cellular level is imperceptible to the observer, mostly accounts for the periodic changes in form and function that affect all living organisms.

Therefore, not only do biological species evolve in the passage of time. They also devolve. The opposite biological processes of evolution and devolution are in constant parity, and together regulate form and function in the biosphere. Both processes are ever occurring at the subcellular and cellular levels in opposite directions, in response to ever changing environmental conditions, and culminate in periodic changes in the structure and functions of biological species.

The devolution theory has practical significance a sketch of which is discussed in the following sections.

 

Origin of unicellular species

Unicellular species are relics of multicellular organisms and emerge in the process of devolution of higher living organisms. Each individual cell of multicellular organisms are self-sustaining to some extent and can survive for a limited period independently of other cells in the tissues in which they co-occur. In the cellular economy of multicellular tissues each cell is constantly exposed to threats from both the extracellular and external environments, albeit in various degrees, which makes them susceptible to devolution. The cells that are impinged the hardest tend to lose some of their original functions and structure. If during this process the essential structures which enable the affected cell to attach to other cells to participate in the cellular economy are lost, that cell is sloughed from within the tissue. This does not mean instant cell death. Subsequently the sloughed cell can continue to live independently for a time, the length of which time depends on the prevailing environmental conditions. Apart from unicellular species emerging from this endogenous route from living higher organisms, the decay of dead multicellular organisms is another important mechanism which adds to the pool of unicellular species.

The fate of cells after detachment from source tissues may be any of the following; firstly, instant cell death can occur. Secondly, other intervening conditions within the environment drive further the process of devolution. The cell continues to lose essential organelles and vital structures and in the process changes to completely new cellular species. In the terminal stage the unicellular species that finally emerge will be very dissimilar to cells of the source tissue. Or thirdly, the process of devolution halts and, if the surrounding environment is favourable for it, the entrant species begins to replicate more of its kind. The gist of this discussion is that unicellular species emerge from multicellular organisms through the process of devolution and not in the reverse direction as is posited in classical evolutionary theory.

 

Medical significance

The theory of biological devolution may be applied in the fields of medical microbiology, oncology and rheumatology. The search for effective treatment options for the medical conditions which occur in these three fields should be pursued bearing in mind their pathological convergence in the devolution of the human body and physiology. In medical microbiology recognition to endogenous infection states is necessary, apart from the already known fact that infectious agents may also intrude the human body from the external environment. Thus, an infectious agent may devolve internally from normal cells of the human body and not always have to invade from outside the body. The common feature in both cases is that the infectious agent has reserved ability to attach to normal cells of the body.

Oncological and rheumatic lesions similarly arise from normal cells in the process of devolution of the human body, with degeneration in rheumatic diseases advanced to such an extent that cellular debris produced during devolution contribute substantially to disease development. The deductive proposition in this discussion is that any therapeutic option which works for medical conditions in one of these fields may equally be effective for conditions occurring in the other two fields.

Glucosamine: a drug or toxin?, Part I

 

As a basic principle in pharmacotherapy a drug should have a favourable cost-benefit ratio to justify its usage in medical practice. This means that the cost to the patient for using the drug should be overridden by benefits derived. Cost is not determined by the nominal value of the drug product only, but includes missed opportunities as a result of using scarce financial resources to purchase the drug, as well as the harms potentially sustained from the usage of the drug.

Glucosamine is currently widely prescribed for the treatment of arthritis. There is however no pharmacological basis to support its application in therapeutics, and proof of its efficacy is lacking in the available pharmaco-medical literature.

The commonly projected claim that glucosamine stimulates the regeneration of worn-out cartilaginous tissues in the joints is dubious and not supported by any known scientific evidence. Rather, what has been demonstrated is that glucosamine is embedded in the structure of polymers which form the essential substance of cartilaginous tissues, it occurring together with several other molecular entities.

But between the discovery of glucosamine in cartilage and its current usage as a drug in treatment of arthritis there are still many unanswered scientific questions. A few of these questions are the following: Knowing that glucosamine is a metabolite of glucose how sure are we about the origin of the former in cartilage tissues? Is glucosamine converted from glucose and subsequently embedded in cartilage, or that already embedded glucose in cartilage is modified to glucosamine to strengthen the tissue? Also, like mucus, is it not likely that cartilage itself is an excretory product that is deposited on the bony surfaces at the joints, and that glucosamine is an unwanted metabolite in the human body that through evolutionary adaptation some mechanism has evolved to trap this molecule in cartilage? Until these possibilities have been investigated and excluded we cannot say for certain that glucosamine is a useful metabolite to the human body, much less to talk of loading the body with it from an exogenous source in an attempt to treat some disease condition.

The lack of efficacy of glucosamine as an analgesic has already been established, and there is currently no evidence for the claim that this substance stimulates the regeneration of cartilage. This unfavourable analysis is compounded by evidence accumulating to show that glucosamine is potentially toxic to the body.

Glucosamine has been known for decades to cause insulin resistance in healthy humans and to cause a deterioration of diabetic cases. On-going research and a lot of already published scientific papers have dealt with this matter, only that the topic has evaded general attention. Maybe it is because glucosamine was not used widely in the past as now. And therefore with lots and lots of people taking this substance now the subject matter merits a second look.

 

The first inkling of probable toxicity of glucosamine will arise after juxtaposing the structure of glucosamine against that of streptozotocin.

 

                                                                                                  GLUCOSAMINE

                                                                                                  STREPTOZOTOCIN

 

Streptozotocin was first isolated from cultures of the microorganism Streptomyces achromogenes. In addition to the fermentation pathway the compound is currently also synthesized through two other mechanisms, both using glucosamine as a precursor molecule; either by synthesis from tetra-O-acetylglucosamine hydrochloride, or by reaction of glucosamine with N-nitrosomethylcarbamylazide or N-methylisocyanate.

Streptozotocin is used in biomedical research to induce diabetes mellitus in healthy mammals. A single intravenous injection of 50 – 200mg/Kg/BW of streptozotocin causes destruction of pancreatic β-cells resulting in classic diabetes mellitus in mammals including dogs, rodents and monkeys.

The extent to which the methylnitrosocarbamoyl substituent at position C2 of streptozotocin contributes to its diabetogenic properties is uncertain, but emerging evidence points to the fact that glucosamine itself induces insulin resistance and impairs glucose uptake by skeletal muscles. Therefore a possible mechanism to account for the effect of streptozotocin is that there is first a cleavage by hydrolysis of the amide bond at position C2 forming free glucosamine molecules after administration. Considering the fact that the dosage level of streptozotocin stated above is more than twice the molar equivalent of the usually recommended adult daily dose for glucosamine, that toxic dose could result in a toxic response in the acute phase.

But what if the said substituent is solely responsible for the diabetogenic action of streptozotocin? Can we not reasonably anticipate the risk of that substituent getting bonded to glucosamine in vivo by some yet unknown mechanism after administration?

Time may prove glucosamine an actual toxin and deficient of any real pharmacological effect. For the present, however, we can only safely conclude that the usage of glucosamine is attended with considerable hazards, and for a substance which has not yet been proven to be effective, the prudent course of action is to avoid it.

 

REFERENCE:

Baron AD, Zhu J-S, Zhu J-H, Weldon H, Maianu L, and Garvey T. Glucosamine induces insulin resistance in vivo by affecting GLUT4 translocation in skeletal muscle: Implications for glucose toxicity. J. Clin. Invest. 1995; 96: 2792 – 2801.