JUSTICE HAS BEEN SERVED

JUSTICE HAS BEEN SERVED 

Granny: No printer, just fax!

In Which Dr. Baffled Tortures His Residents

I was rounding in the nursery with 2 interns today.  There are 7 babies in the nursery.  One of them had a large, hyper-pigmented nevus on his right calf.  All of the other babies have completely normal exams.  When I asked them if any of the babies had any findings on exam they said no.  I told them that one baby had a clear abnormality on the exam and they should go back in and re-examine all the babies and find it.  They examined babies and reported non-existent findings for an hour with no progress.  I then told them which baby had the findings and they then stared at that baby for 20 minutes before they found it.  The whole incident was painful to watch.

Whats the moral or the story?  A physician’s history and physical exam skills are among the most important aspects of medicine.  Without them, you’re just wandering around the diaspora throwing spaghetti at the wall and hoping something sticks.

The hardest battle you will ever have to fight is between who you are now and who you want to be.

Anonymous (via wnq-anonymous)

Some of my favourite printables! Firstly,apologies for the awful photos,it’s a rainy day and by the time I got home it was getting dark but I just had to post them.

Daily Agenda from @euphoricstudying I really,really like this printable. It’s clean and big,no messing about. However,I liked the grid background on the original which didn’t show up very well on my printed version? This may have just been an issue with the printer(although the grid showed up on another printable so maybe not). All in all this is such a useful printable! I’m likely to use it at the weekends/for particularly busy days and it does everything I need,and well!

To-Do List and Homework Planner from @meddiestudies This is such a cute little to do list!!!! It has just enough spaces so as not to be too overwhelming,I like to use it alongside the daily agenda for specific homework tasks as opposed to general appointments and reminders/scheduling. A really lovely little page!!

Weekly Planner from @arystudies I love love love this planner. It’s everything I could hope for in a weekly planner;simple,grid background, black and white so I can add my own colour schemes weekly! I love the fact Saturday and Sunday have smaller boxes since my weekdays are busier than my weekends what with school. I would definitely recommend trying this planner out,it even has a lovely little water tracker!

Yearly Planner from @emmastudies This is a lovely calendar,I went for the purple colour but there are a few to choose from to match everyone’s tastes. It’s a lovely and simple lay out with plenty of space in each box and some really lovely lettering for the months!

Quantitative Structure-Activity Relationship (QSARs) - Drug Development

QSAR modelling predicts the biological activity of a compound based off its physical properties. They are used to avoid synthesising and testing every possible version of a molecule to find the optimum for bioactivity. A small number of structurally similar molecules are synthesised and tested, and these results are used to mathematically predict other similar molecules on a computer.

Hydrophobicity 

This dictates the ease at which a molecule will pass through a cell membrane. Too hydrophobic and the molecule will be drawn to lipids and its bioactivity will be reduced, too hydrophilic and the molecule will be too polar to pass through the phospholipid bilayer and will not carry out its desired activity (will be excreted in urine)

LogP - a measure of the whole molecule’s hydrophobicity 

High logP = more hydrophobic

Low logP = more hydrophillic (polar)

Optimum for bioavailibility = 2-4.5

A regression equation can be formed with c=concentration for max activity

1/c = K1 logP + k2

If linear, values for other similar structures can be taken off the line. If parabolic = logP^2, indicating that after a max concentration bioavalibility will not increase as the drug becomes too hydrophobic and moves into fats.

Substituent hydrophobicity constant,  π

Measures the hydrophobicity of individual substituents in a compound.

π = logPX - logPH

X= partition coefficient for substituted compound 

H= partition coefficient for unsubstituted compound (Hydrogen (so if H was in place of the substituent of interest))

Compares how hydrophobic a substituent is compared to hydrogen

π = +ve –> X= more hydrophobic than hydrogen

π = -ve –> X= less hydrophobic than hydrogen

Note: can be used to calculate logP by adding substituents, rather than having to synthesise and test the molecule (clogP = calculated logP)

Electronics

Pharmacokinetics (administration, distribution, metabolism and excretion) rarely depends on hydrophobicity alone. The polarity of a compound dictates its passage through the patient and its binding at point of activity.

Hammett substituent constant, σ

The starting point  is a chemical equilibrium for which both the substituent constant and the reaction constant are arbitrarily set to 1: the ionization of benzoic acid (R and R’ both H) in water at 25 °C.

Provides K0.

RCO2H <–> RCO2- + H+

uses the dissociation constant

kH = [RCO2-][H+] / [RCO2H]

If X is electron withdrawing, it will stabilise RCO2- and shift the equilibrium to the right. kX will increase

eg NO2, CN, Cl –> +ve  σ

If X is electron donating, it will destabilise the RCO2- anion and shift equilibrium to the left, with a drop in kX.

eg alkyls, ethyls, methyls = -ve  σ

σ = logkX - logkH

Steric properties 

Taft steric parameter, Es = rate of hydrolysis of XCH2CO2Me under acidic conditions

Es = logkX - logKH

If X is physically small, the rate of hydrolysis (time taken to reach tetrahedral intermediate) will be fast.

Here, the size of R affects the rate of reaction by blocking nucleophilic attack by water.

           H             1.24 +ve value: little steric resistance to hydrolysis          Me             0.00 the reference substituent in the Taft equation          t-Bu          -2.78 -ve value: large resistance to hydrolysis

Small X = large Es, large X = small Es

Accuracy of calculation decreases as the bulk and length of the chain increases.

Hansch equations put several of the parameters together to compare overall bioavailibility of different compounds.

Craig plots

Plots 2 constants

functional groups with similar activity will be in the same quadrant

the optimum quadrant, eg +ve σ and -ve π, will contain all the substituents worth investigating