Safer medicines in children and adults: video discussions from the international 2016 EACPT Focus Meeting in Opatija

From the EACPT Focus Meeting on How to Assess Medicines, Opatija, 6-9 October 2016. 

In these videos, Donald Singer discusses with speaker Suzana Mimica Matanovic evaluation of drugs in the pediatric population with an update on the impact of recent initiatives from the European Medicines Agency and discusses with Janne Backman from Helsinki how to identify and minimise risk of drug-drug interactions.

 

Discussants

- Suzana Matanovic: Assistant Professor of Clinical Pharmacology, School of Medicine, University of Osijek, Croatia and PCO alternate delegate at the European Medicines Agency

- Janne Tapio Backman: Professor in Clinical Pharmacology and Individual Medicine, University of Helsinki, Finland

- Professor Donald Singer: member of the Executive Committee of the European Association for Clinical Pharmacology and Therapeutics and EACPT delegate on the European Medicines Agency Health Professionals Working Party. 

Here is a summary of the key points from Professor Backman's  talk at the EACPT Focus Meeting in Opatija: 

Drug-drug interactions can either markedly reduce or enhance the therapeutic or adverse effects of drugs by causing alterations in the pharmacokinetics or pharmacodynamics of drugs. If such interactions are not understood or accounted for in patient care, they can have harmful, even hazardous clinical consequences. 

Drug-drug interactions have been a major cause of drug withdrawals from the market. Regulatory agencies, including the European Medicines Agency (EMA) have therefore published guidance documents that are designed for the industry to guide their DDI studies during drug development. In particular, detailed scientific recommendations can be given concerning pharmacokinetic interactions, because such interactions can be mediated via mechanistic changes in absorption, distribution, metabolism and excretion of drugs. 

Specific approaches are suggested concerning cytochrome P450 enzymes (CYPs), non-CYP enzymes and membrane transporters. In addition, current guidance also recommends use of modelling approaches, such as physiologically based pharmacokinetic (PBPK) models to design and extend the interpretation of preclinical and clinical drug-drug interaction studies. For designing clinical drug-drug interactions studies, detailed preclinical in vitro and early clinical pharmacokinetic information is necessary. 

Despite detailed guidelines, there are many challenges in characterization of the interaction potential of a drug, both as a perpetrator and as a victim of the interaction. Such challenges arise from complex interaction mechanisms, eg, simultaneous involvement of transporters and drug metabolizing enzymes, autoinhibition and autoinduction of metabolism, time-dependent inhibition and involvement of major drug metabolites. 

Understanding the challenges and pitfalls of drug-drug interaction studies is thus necessary in interpretation of the results of studies. In this lecture, basic methods of clinical drug-drug interaction studies will be reviewed, with examples of potential pitfalls and basic principles of interpretation.

The next EACPT biennial congress will be held in Prague Congress from 24th - 27th June 2017. The programme will provide an international scientific and educational forum for discussion of clinical pharmacology and therapeutics, including personalised pharmacotherapy. See more on our website. 

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Incubation - an ancient Egyptian sleep cure for medical ills

The British Museum is hosting until 27 November an outstanding exhibition on underwater

From the Ebers papyrus: US NLM/NIH

archaeology from sunken ancient cities on the Nile Delta (the lost cities of Thonis-Heracleion and Canopus).
The exhibition highlighted trade, cultural and religious exchange among old Mediterranean civilizations and in particular interchange between ancient Greece and ancient Egypt.  Examples  were featured of a major Hellenised Egyptian deities.
A fascinating element of the exhibition was discussion of a Temple for Incubation as a way to cure ills, the granite building long submerged in soft sands, its disappearance accelerated with the sands became liquid due to seismic activity. It is intriguing to note the siting of an important temple for incubation on the Nile delta, as the name for ancient Egypt was Kemet (‘km.t’) after black earth of the Nile Delta.
The aim of sleeping the night in the temple was to allow incubi - bad dreams - to carry away toxic humours as causes of illness and so heal the sufferers - in return for generous donations.
This practice reflected widespread tradition linking dreams to temples, and the release of dreams as a way to cure disease: the ancient culture of visits to oracular shrines (oracles) where a god could be consulted through an inspired priest – the most famous perhaps the Oracle at Delphi in Western mainland Greece. A common further method to consult a god was incubation: the inquirer would sleep in the temple holy place and be rewarded with an answer in a dream. This would then be interpreted by the priest with an often ambiguous answer.
Cures might also be delivered through a dream: for example at the oracle to Amphiaraus at Oropus in Attica, the temple to the god of medicine Asclepius at Epidaurus, the oracle of Dionysus at Amphicleia, and the oracle of Trophonius in Levadhia.
Ancient Egyptian medicine is considered to date at least to the 27th century B.C.E. to the time when the Old Kingdom physician and architect Imhotep was the Vizier of Djoser. Imhotep was later deified. A key belief was that disease could be caused by an angry god or an evil spirit. However the Egyptians of the time were pragmatic in formulated effective treatments.

Sources for ancient Egyptian scientific medical practices include the Papyrus on surgical trauma bought by Edwin Smith in 1862 and dating to ~1600 B.C.E and credited to the much earlier Imhotep; and the Papyrus dating to 1500 B.C bought by Georg Ebers in 1873 at Luxor. The latter papyrus includes more than 700 remedies and spells to be used to ward off disease-causing spirits.The ancient texts also describe dreams and how to interpret them.
Priests played a key role in prescription of how to live as a way to avoid disease.  There were healing sanctuaries affiliated to temples where physician-priests could prescribe for the healthy and treat patients.
Purification included special diets, ritualized bathing and removal of all body hair. The patient could also be required to maintain a specific diet including what were considered to be unclear fish and animals. Perhaps via or influencing Hippocratic sources, diet might include involving fava beans (now recognized now as a precipitate for anaemia in people deficient in the enzyme glucose-6-phosphate dehydrogenase, a genetic disorder common in the Eastern Mediterranean and in Sub-Saharan Africa).

More on sleep and the interpretation of dreams in Ancient Egypt. 
British Museum. The dream book.