Doses and measures

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In the pharmacist’s work, it is crucial to establish doses: the doses of ingredients in preparations and the doses of medicinals to administer to patients. Both are included in ancient pharmaceutical recipe books, but the physician’s authority for doses to be administered became progressively more exclusive, as the professional profiles of physicians and pharmacists became more and more defined in order to avoid overlapping responsibilities. An example in the 1750 Antidotarium Bononiense: the closing contains a reminder of the maximum levels for dangerous medicinals and the College of Physicians, which issued the regulatory text, urges the Pharmacist, "monitus volumus Pharmacopoeos", to not exceed the amount indicated in the recipe without the opinion of the physician who wrote it, "Medici auctoris consilium" (p. 467).
To define the doses to administer, one can refer to the sort of medieval quiz-style manual for becoming a pharmacist, which is the Compendium aromatariorum by Saladino d'Ascoli. In the Third part, the examinee is questioned about what a dose is and, technically, the response is that a dose is the minimum necessary and effective quantity of a medicinal: "Dosis est limitata mensura, vel quantitatis simplicis, vel compositae medicinae, quae de se apta nata est facere sufficientem operationem, et non diminutam, neque superfluam" (pt. 2, c. 256r).

How to determine the doses?
The Library of Pharmaceutical and Pharmacological Sciences of the University of Padova has an anthology of brief practice- and scope-based treatises on the medicinal doses, published in Padua in 1556. In the collected works, diseases had been for a long time considered the result of an imbalance of the humours that regulate the body, that is blood, phlegm, yellow bile and black bile, and to the related qualities of hot, cold, dry and wet.

The anthology begins with the Dosandi methodus by Matteo Corti (1475-1542 ca). A professor at Padua from 1524, as commentator on Anathomia by Mondino de Liuzzi, he then became papal archiater, eventually of Cosimo de Medici. The work is dedicated to apprentices ("ad tyrunculos"). He describes the doses for the preparation of syrups, focusing on the amount of water to be mixed, and on solutive medicines, i.e. purgatives of the excess of the humours. He always compared the authoritative sources with the practical.

An examination of the theme can be found in the following treatise by Benedetto Vittori (1481-1561), professor of logic and philosophy, theology and medicine at the universities of Padova and Bologna. With regards to doses, the author does not define fixed quantities, but he appeals to practical sense and prudence in the prescription and preparation of medicinals. There is a distinction between solutive and digestive (syrups) medicines and local applications (ointments and poultices). In the doses of solutive medicines, the patient’s age must be carefully considered. To manage the density, attention is paid to the quantities of sugar or honey for syrups, of wax for the ointments and oils for the poultices in the doses. Moreover, if the illness is also related to the imbalance of a quality (hot, cold, dry, wet), the medicine will act in compensation with ingredients of an opposite quality, but even here, there is an appeal for caution.

The importance of the skill and judgment of the physician in defining the doses is also highlighted by Guillaume Rondolet (1507-1566), an anatomist in Montpelier, who in 1565 wrote a general treatise on pharmacy, Dispensatorium seu pharmacopolarum officina (digital copy). De materia medicinali & compositione medicamentorum is a small, practical manual, as stated in the title ("brevis methodus"). It begins with a description of the medical conduct during a visit of a patient in order to facilitate an accurate diagnosis. The imbalance of the humours is central to the disease. To balance them, expulsion through extensive use of enemas, leeches, bloodletting, emetics and purgatives is favoured. Rondolet provides a list of herbs indicated for different diseases and examples of recipes, with the doses, the technique for preparation and administration.

Bartolomeo da Montagnana (1380-1452 ca), professor of practical medicine in Padua from 1422, is known for his Consilia addressed to the most noble and illustrious clientele of the Venetian provinces as well as the Roman Curia and the German aristocracy, edited by students who returned home after their studies in Padua. The author is also known for his treatise on the Euganean thermal baths. The treatise, De compositione et dosi medicamentorum "blatantly copies in the second part – even at time literally – the very brief Tractatus de dosi medicinae... by Mondino de Liuzzi" (entry of the Dizionario biografico degli italiani, vol. 75, 2011). Here the dose is calibrated on the degree of the quality of the simples, which are used: each medicinal plant has its own quality (hot, cold, dry, wet) of a more or less high degree. As an example, chamomile is hot and dry in the first degree (the highest), so it is very effective and requires a minimum dose. Additionally, the dose will be greater if the part of the body to be treated is larger: for example, agaric cures phlegm and will be in a minimum dose if it must only act on the stomach, maximum if it is for the entire body. There follows a list of simples and the doses prescribed for the preparations.
The theory of degrees dates back to De medicinarum compositarum gradibus by Al-Kindi (Abū Yūsuf Yaʿqūb ibn Isḥāq al-Kindī 801-873) (Hasse p. 337), that the Library of Pharmaceutical and Pharmacological Sciences of the University of Padova has in the 1623 Venetian anthology. The Arab philosopher presented a table with the combination of simples in compounds based on the degree of their quality.

The ancient recipes pose at least two crucial problems of interpretation: the correspondence of the ancient name of the ingredients with that in use and the equivalence of weights, a complex undertaking in the absence of conventions. "Almost all major Cities have their weights and measures", Donzelli reported in the late seventeenth century (p. 15).

We are always helped by Saladino d'Ascoli. The Third part dedicated to doses includes the ancient units of weight measures: the principle ones in order of size are the scrupolo, the dramma, the oncia and the libbra. The reference to calculate the scrupolo is a wheat grain. One can imagine the great variances that come from this choice, depending on the size and weight of the chosen grain. Saladino recommended that, left in doubt, the pharmacist choose an average grain and to create its equivalent in metal, lead, tin or other for use: "Nota etiam, quod grana tritici sunt secundum diversas provincias maiora, vel minora, seu crassa, vel minuta. Medici autem, et aromatarii pro faciendis ponderibus debent eligere mediocra, et ex illis facere pondera de plumbo, aut de stanno, vel alio metallo" (pt. 2, c. 256r). To add to the confusion, the grain used as the basic unit could be of wheat or barley: Saladino suggested using wheat unless otherwise indicated. In addition, the equivalence varied according to the place: if the scrupolo is always equal to 20 grano, the dramma is equal to 3 scrupolo, the oncia is equal to 9 dramma for the Salerno School, to 8 for the "Paduani Doctores" and to 10 for the "Neapolitani" (ibid). In addition to those five main units, Saladino also included many others: the Exagium or Solidum, that is a dramma and a half, the Sextarium or Cotyla, two and a half libbra, the Obolus, half a scrupolo, the Kist, one and a half libbra, the Hemina, one libbra and three once, and so on. Totally arbitrary measures include the Manipulus, a handful, defined as what can be held in the hand "quantum potest manu capi" (pt. 2, c. 256v) and the Puglillus, a pinch, the amount held in a closed fist, "quantum potest cum pugillo stricto capi" (ibid). At the end of the chapter, Saladino offers a poem, as a practical mnemonic technique for the aspiring pharmacist who must navigate the chaos of ancient weights.

The nomenclature used for weights were the most varied. In the same 1623 Venetian anthology that published the text by Saladino d'Ascoli, there is another brief treatise Apulei De ponderibus, et mensuris, et signis cuiuscunque ponderis, in which the weight measures in an increasing order of size have completely different names or, if homonyms, they don’t correspond: Calculus, Siliqua (4 Calculi), Obolus (3 Siliquae), Dramma or Chema or Olca or Denarius, Solidus, etc. In 1667, Donzelli listed around fifty terms and the libbra is different for the Merchant of Constantinople, the Milanese, the Parisian, those of Lyon, and of Spain and that of the Goldsmiths. The author mentions some units of measure specific to pharmacy, such as drops: "la sua quantità eccovela elegantemente difinita da un Moderno Letterato.... cioè quanto una calda lacrima da gl'occhi tramandata" (its dosage has been elegantly defined by a modern scholar… and corresponds to a warm tear, shedding from the eye) (p. 15). For the same libbra, twenty years later, Passera added to the variants listed by Donzelli, those of Bergamo, Brescia, Venice and Genoa. The author wrote: "depending on the country, there is much variety. But there must be an agreement in Medicine in weights and measures, as in stable, permanent and universal, since otherwise, there would be many, innumerable errors" (col. 83-85). Passera addressed the issue of liquid measurements and compared "l'Oglio" (oil), wine and honey with their equivalents in libbra.

A work from 1617 tried to stem the confusion caused by the variety of the measures of weight: the Disputatio de officinae pharmaceuticae veris, & legitimis antiquorum ponderibus by Alberto Quattrocchi, a Venetian physician. The author emphasised that it was indispensable to address the issue if one wanted to correctly, "modo recte" (p. 5), prepare, administer and implement, "componi, exhiberi, & applicari" (ibid), the ancient medicines of Galen, Eginea, Avicenna and Mesue. Correctly defining the quantities is important in the civilised world to avoid fraud in the trade, for the mathematician and all the more for the physician, so that he may prepare the medications in order to get the most benefit for man’s health, "ita Medici fini esse debet, rectè medicamenta parare, ijsque ad sanitatem hominis, maximo, quo fieri potest, beneficio uti" (p. 7). Not only are the measures defined, but also the measuring instruments, for which Quattrocchi recommended the acquisition of precision scales.
In the work, the measures have been limited to the common ones: libbra, oncia, dramma, scrupolo, obolo, siliqua and grano (pound, ounce, dram, scrupulum, obolus, carat and wheat grain). The equivalences in use by 24 authors of antidotaries were compared, starting from Niccolò di Salerno and Saladino, up to the antidotaries of Rome, Florence, Nuremberg, the recent ones by Wecker and Sylvius aka Jacques Dubois (1478-1555), and the ancient authority of Aegina. Quattrocchi also mentions other authors in the 24 case studies. The work offers an ingenious tool for comparison: a gnomonic wheel chart that can be turned to show in the window of the chart the equivalences of the weight measurements used by the author, chosen from among 24 included in a radial pattern on the circle below. In the example of Saladino, already cited, turning the wheel, the scrupolo is equal to 20 grano and the Drachma (dram) to 3 scrupolo. The differences are not only among the authors, but also among the cities, and that is why Quattrocchi also proposed a chart of correspondence of the libbra in around forty cities, from Padua to Ravenna, from Rome to Udine, from Bergamo to Sicily, including foreign cities like Marseilles and Barcelona. In conclusion, he proposed a standard table of equivalences (p. 21). Another table shows the equivalences between the Romans, Arabs and Greeks.
Quattrocchi also illustrated a test organised by the Mint of Venice, in the presence of the College of Physicians and two Herbalists to verify the correspondence of wheat grains with the Venetian silver oncia kept there. Quattrocchi did not fail to address the issue of the roles of the physician and the pharmacist in defining the doses: the first has the responsibility of defining them, in the composition of the ingredients of the medicinals, "essentiam, et quidditatem materiae medicae compositum ingredientis" (p. 51), as well as in the effective dose to be administered, "speculatio, quae dosim medicamenti exhibendi determinat, in sola Medici peritia consistit" (ibid); the pharmacist’s responsibility is to comply with these instructions: "in arte compositionis à praeceptis medicis Pharmacopaei diligentiae, curae, et fidei commissa est" (ibid).