Facing the rapidly spreading novel coronavirus disease (COVID-19), evidence to inform decision-making at both the clinical and policy-making level is highly needed. Based on the results of a study by Petrilli et al, we have developed a calculator using patient data at admission to predict the risk of critical illness (intensive care unit admission, use of mechanical ventilation, discharge to hospice, or death). 
We report a retrospective validation of the risk calculator on 145 consecutive patients admitted with COVID-19 to a single hospital in Israel. Of the 18 patients with critical illness, 17 were correctly identified by the model(sensitivity: 94.4%, 95% CI, 72.7% to 99.9%; specificity: 81.9%, 95% CI, 74.1% to 88.2%). Of the 127 patients with non-critical illness, 104 were correctly identified. This, despite considerable differences between the original and validation study populations. 
Our results show that data from published knowledge can be used to provide reliable, patient level, automated risk assessment, potentially reducing the cognitive burden on physicians and helping policy makers better prepare for future needs.

https://pharmrev.aspetjournals.org/content/pharmrev/48/4/567.full.pdf

International Union of Pharmacology. XII. Classification of opioid receptors

The Methylation Effect in Medicinal Chemistry Eliezer J. Barreiro,* Arthur E. K€ummerle, and Carlos A. M. Fraga Laborat orio de Avaliac-~ao e Síntese de Subst̂ancias Bioativas (LASSBio), Faculdade de Farm acia, Universidade Federal do Rio de Janeiro, CCS, Cidade Universit aria, CP 68.006, 21941-902 Rio de Janeiro, RJ, Brazil Programa de P os-Graduac-~ao em Farmacologia e Química Medicinal, Instituto de Cîencias Biom edicas, Universidade Federal do Rio de Janeiro, Cidade Universit aria, Ilha do Fund~ao, Rio de Janeiro, RJ, Brazil Programa de P os-Graduac-~ao em Química, Instituto de Química, Universidade Federal do Rio de Janeiro, Cidade Universit aria, Ilha do Fund~ao, Rio de Janeiro, RJ, Brazil

The methylation effect in medicinal chemistry.

Opiates are among the oldest medications available to manage a number of medical problems. Although pain is the current focus, early use initially focused upon the treatment of dysentery. Opium contains high concentrations of both morphine and codeine, along with thebaine, which is used in the synthesis of a number of semisynthetic opioid analgesics. Thus, it is not surprising that new agents were initially based upon the morphine scaffold. The concept of multiple opioid receptors was first suggested almost 50 years ago (Martin, 1967), opening the possibility of new classes of drugs, but the morphine-like agents have remained the mainstay in the medical management of pain. Termed mu, our understanding of these morphine-like agents and their receptors has undergone an evolution in thinking over the past 35 years. Early pharmacological studies identified three major classes of receptors, helped by the discovery of endogenous opioid peptides and receptor subtypes—primarily through the synthesis of novel agents. These chemical biologic approaches were then eclipsed by the molecular biology revolution, which now reveals a complexity of the morphine-like agents and their receptors that had not been previously appreciated.

Mu Opioids and Their Receptors: Evolution of a Concept

The characteristics of the interaction between dihydromorphine (DHM) and a synaptic plasma membrane (SPM) fraction from rat brain cerebral cortex have been studied. DHM at 10+9 M concentration is bound in a reversible process which is partly specific. The specific binding is inhibited by the sulphydryl reagents, N-ethylmaleimide and p-chloromercuribenzoic acid. The binding is strongly inhibited by 10−8 M levorphanol but significantly less inhibited by its optical antipode, dextrorphan, which is much less analgetic. At 10−8 M concentration, nalorphine and naloxone were strongly inhibitory while heroin at 10−8 M and codeine at 10−7 M were nearly inactive. A mixture of 10−5 M acetylcholine and 2.5 × 10−5 M eserine caused a moderate inhibition while dopamine, noradrenaline, serotonin, histamine and propranolol were classified as inactive (i. e. caused less than 25 % inhibition at 10−5 M). The observed binding characteristics of the SPM fraction are compatible with those which might be expected for the actual narcotic receptor. Analogous SPM preparations from subcortical parts of the cerebrum and from the brain stem also showed stereospecific binding of narcotics.

Characteristics of the "receptor" for narcotic analgesics in synaptic plasma membrane fraction from rat brain.

A Review of the Use of Fentanyl Analgesia in the Management of Acute Pain in Adults

Summary
1The evidence is presented for the probability of the activity exhibited by analgesics and their antagonists being due to their association with a specific receptor surface.
2The configurations of those isomers exhibiting nearly all the activity of certain racemic mixtures are identical, and related to that of D-(–)-alanine; the stereochemical requirements of analgesics are considered.
3Active analgesics are shown to have structures which enable them to present similar surfaces to allow of their association with a proposed “analgesic receptor surface,” the essential features of which are described.
4A number of essential structures are outlined as prerequisites for compounds designed as analgesics.

A H Beckett

Papers

Synthetic analgesics: stereochemical considerations.