Pharmacology

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Pharmacology2017-07-07T23:31:14+00:00

Pharmacology

pharmacology image from New Medical Terms

Pharmacy of the Middle Agest

As long as humans have been on the planet, they’ve needed to treat illness. Medicinal plants–e.g., ephedra (Ephedra sinica) and opium (Papaver somniferum), have been found in archeological digs from 60,000 years ago long predating recorded history. It is possible that these botanical remedies were used in the same way as they are today by herbalists, for pain–opium or for their stimulant and decongestant properties–ephedra. One can easily get lost in the rich history of pharmacology. Here, one can cite:  

• Ebers and Edwin Smith papyri of ancient Egypt (1600 BC),

• Sushruta Samhita—an Indian ayurvedic treatise (400 BC),

• Shennong Bencao Jing—a 40-volume pharmacopoeia of the Han dynasty (100 AD),

• Pharmacies of the Golden Age of Islam (Baghdad, 900 AD)

• Apothecaries of pre-renaissance Europe (Florence, circa 1300s, see top image).

Considering the sheer volume of work produced by the ancients, very few of their therapeutics have been incorporated in any form into current compendia, and none in their original forms. 

Early rumblings of the modern era of therapeutic medicine came from physiologists–e.g., Françoise Magendie, who proved that strychnine-induced convulsions arose in the spinal cord; Friedrich Wohler, whose synthesis of urea from inorganic substances torpedoed the naive vital force theory*; and Claude Bernard, whose work with the arrow poison curare, disrupted the stimulation of muscle by nerve impulses at the neuromuscular junction. They were followed by Oswald Schmiedeberg (1838-1921), a German physician who became professor at the University of Strasbourg,  and is widely acknowledged as the father of modern pharmacology.

*The vital force theory, proposed by Swedish chemist JJ Berzelius in 1815, held that organic (carbon-containing) chemicals could only be produced by living organisms (plants and animals). One can easily see that if this posit were true, then synthesis of any organic compound would require a complex search of all biotica to find an organism capable of producing the reaction of interest. There are multiple spellings of Strasbourg… it is located in France, thus the French spelling is the most appropriate. 

Schmiedeberg’s work focused on correlating chemical structures with their therapeutic effect. His Grundriß der Arzneimittellehre, 1883 – Fundamentals of Pharmacology, was the crown jewel of his 200 publications and explained in part the pre-eminence of the German pharmaceutical industry in the early 20th century… he’d trained most of the pharmacology professors of the era. In 1890, one of his disciples, JJ Abel, became the first chair of pharmacology in the US, at the University of Michigan, where  acetylcholine, epinephrine, histamine, and pure insulin were first isolated. Schmiedeberg would hardly recognize the industry born of his loins now, a century after his death. 

Pharmacology & drug development Image from New Medical Terms

Candidate agents and timeframe for drug development

The early 20th century saw the development of therapeutics on all fronts. Alexander Fleming’s 1928 discovery of penicillin closed the brief chapter on Salvarsan, a commercial arsenical that was the first effective antibacterial for managing syphilis, and was followed by countless antibiotics. Corticosteroids, which are used for chronic inflammatory diseases–e.g., rheumatoid arthritis and dermopathies were first extracted from animal adrenocortical tissue in the 1930s and synthesized in the 1950s. The first effective agents for treating cancer were developed at Yale (nitrogen mustard, Goodman and Gilman, 1946) and Harvard (methotrexate, Farber, 1948). 

The latter half of the 20th century saw the development of NSAIDs–e.g., ibuprofen, and others, which have antipyretic, anti-inflammatory and analgesic effects; the approval of lithium for managing bipolar disorder and benzedrine for behavioral disorders; monoclonal antibodies for managing transplant rejection, inflammatory arthropathies, dermopathies, metastatic cancer and other conditions; and recombinant proteins and peptides–e.g., recombinant erythropoietin, recombinant factor VIIa (for hemophilia A/B), and recombinant insulin. 

The number of therapeutic agents in the pipeline in the 21st century is staggering; this is a requisite of the process (see bottom image). Of 5,000 to 10,000 “new molecular entities” first analyzed by a drug company, a mere handful reach phase 1 clinical trials and perhaps one of them will get FDA approval for marketing. The full process takes 11 to 15 years and costs $200 million dollars. Small wonder that drug companies fight tooth and nail to keep their intellectual property rights alive as long as possible, despite indignant  howls against corporate greed by the lay public

References

https://www.takingcharge.csh.umn.edu/explore-healing-practices/botanical-medicine/how-long-have-humans-used-botanicals

http://carrington.edu/blog/student-tips/education/historical-overview-of-pharmacology/

https://en.wikipedia.org/wiki/History_of_pharmacy

https://en.wikipedia.org/wiki/Oswald_Schmiedeberg

https://www.ncbi.nlm.nih.gov/pubmed/22018177

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622599/