ICU Materials Part 1

ICU Materials part 1

After 4 years of volunteering in the ICU of the local hospital for respiratory diseases I’ve finally started to really understand a lot of the diagnostic procedures and the meaning of their results.

So I’ve decided to share with you some of the materials I use to study the ICU Stuff:

ABG interpretation

https://abg.ninja/abg - The site gives you a results from ABG analysis and you have to make a reading of them, then it show you if you are correct or wrong and gives you a full description why. On this site there some other very nice medical quzzes as well - Glasgow coma scale, Cranial Nerves, Basic ECG etc.

Lung function tests

http://www.ums.ac.uk/umj080/080(2)084.pdf

http://www.ics.gencat.cat/3clics/guies/184/img/–americanfamilyphysician.pdf In these PDFs the basic aproach to spirometry is described, everything you need to know when you stumble across spirometry results.

Coagulation tests

http://thrombosiscanada.ca/wp-content/uploads/2013/08/Bloody_Easy_Coag_2013.pdf

http://www.pathology.vcu.edu/clinical/coag/Lab%20Hemostasis.pdf Very consise and well writen guidelines for coagulation tests interpretations.

Chest radiology

https://lane.stanford.edu/portals/cvicu/HCP_Respiratory-Pulmoanry_Tab_2/Chest_X-rays.pdf

http://www.southsudanmedicaljournal.com/assets/files/Journals/vol_1_iss_2_may_08/how%20to%20read%20a%20cxr.pdf Basic guidelines for reading a Chest X-ray

Echography - Ultrasound Imaging

http://www.sah.org.au/assets/files/PDFs/For%20Doctors/2011-crit-care-us-heart.pdf

http://www.cardioegypt.com/cardioeg/ACSCA2014-Presentations/002001.pdf

http://www.annalsofintensivecare.com/content/pdf/2110-5820-4-1.pdf

http://www.cardiovascularultrasound.com/content/pdf/1476-7120-12-25.pdf

http://www.ccforum.com/content/pdf/cc5668.pdf Very simple and easy to understand presentations for the newbies(like me) in Ultrasound imaging. To be continued…

Please like or reblog if you use! xx

ICU Materials part 1

After 4 years of volunteering in the ICU of the local hospital for respiratory diseases I’ve finally started to really understand a lot of the diagnostic procedures and the meaning of their results.

So I’ve decided to share with you some of the materials I use to study the ICU Stuff:

ABG interpretation

https://abg.ninja/abg - The site gives you a results from ABG analysis and you have to make a reading of them, then it show you if you are correct or wrong and gives you a full description why. On this site there some other very nice medical quzzes as well - Glasgow coma scale, Cranial Nerves, Basic ECG etc.

Lung function tests

http://www.ums.ac.uk/umj080/080(2)084.pdf

http://www.ics.gencat.cat/3clics/guies/184/img/–americanfamilyphysician.pdf In these PDFs the basic aproach to spirometry is described, everything you need to know when you stumble across spirometry results.

Coagulation tests

http://thrombosiscanada.ca/wp-content/uploads/2013/08/Bloody_Easy_Coag_2013.pdf

http://www.pathology.vcu.edu/clinical/coag/Lab%20Hemostasis.pdf Very consise and well writen guidelines for coagulation tests interpretations.

Chest radiology

https://lane.stanford.edu/portals/cvicu/HCP_Respiratory-Pulmoanry_Tab_2/Chest_X-rays.pdf

http://www.southsudanmedicaljournal.com/assets/files/Journals/vol_1_iss_2_may_08/how%20to%20read%20a%20cxr.pdf Basic guidelines for reading a Chest X-ray

Echography - Ultrasound Imaging

http://www.sah.org.au/assets/files/PDFs/For%20Doctors/2011-crit-care-us-heart.pdf

http://www.cardioegypt.com/cardioeg/ACSCA2014-Presentations/002001.pdf

http://www.annalsofintensivecare.com/content/pdf/2110-5820-4-1.pdf

http://www.cardiovascularultrasound.com/content/pdf/1476-7120-12-25.pdf

http://www.ccforum.com/content/pdf/cc5668.pdf Very simple and easy to understand presentations for the newbies(like me) in Ultrasound imaging. To be continued…

Effort won’t betray you

my korean friend when I asked her how she motivates herself for lessons that last until 11 pm each day -studybdy (via misehry)

If someone has an 'enhanced metabolism' that processes drugs faster, is it easier or harder for them to overdose? Wouldn't they uptake more of a drug quicker, therefor making it more dangerous? I see this a lot with Captain America and Spider-man and such, where the dose of various medicines will be raised and I'm not sure that makes sense?

…oooooh you sure have opened a can of pharmacokinetic worms here….

Simply put, whether the drug never reaches therapeutic blood levels, or exceeds them, depends on 1) how the character’s metabolism works, and 2) what kind of drug they ingested (skip to the bolded part at the end of the post to get the tl;dr).

When you take a drug, the following happens (this process is sometimes denoted as “ADME” or “LADME”:

The drug must separate from the vehicle that brought it into the body (for example, a pill must disintegrate in the stomach, releasing the drug, or an IM or IV drug must separate from its solution): Liberation

The drug must be absorbed into the bloodstream (for a pill this would mean getting absorbed through the lining of the stomach or intestine, for IM injections this means getting absorbed by blood vessels running through the muscle where the drug is): Absorption

The drug must be deposited from the bloodstream into a location where it can be used: Distribution

The drug must be metabolized (broken down or changed by a biologic process, creating different chemicals called metabolites): Metabolism

The drug metabolites must be excreted from the body: Elimination

The first end of this process is largely driven by regular old chemistry. A pill has to dissolve to release the drug, and assuming that these characters have similar stomach/small intestine environments, this is not going to be different for them.

Absorption is mostly driven by a concentration gradient (substances like to be at the same concentration across membranes, so if there’s more drug in the small intestine than there is in the blood around the small intestine, the drug gets absorbed into the blood as the concentrations try to equalize), so this too is probably not going to be all that different. Even distribution is (mostly) driven by that concentration gradient, so, again, this process wouldn’t necessarily be any different from that of a normal human.

Now, the latter half of this process is a lot more dependent on a person’s specific physiology. When we talk about metabolism, we’re talking about how the body changes ingested chemicals into something excrete-able. For many drugs, this change involves enzymes in the liver.

About 6 different liver enzymes are responsible for the metabolism of about 90% of drugs. Each different enzyme is responsible for the breakdown of a different group of drugs.

Some people have genetic mutations that cause more or less of an enzyme to be produced. People who make more of an enzyme metabolize that group of drugs faster, while people who make less of them metabolize those drugs more slowly.

Through certain genetic tests, real life people can be designated one of the following for any given group of drugs:

Ultrarapid Metabolizers have the genetic wiring to produce way, way more copies of an enzyme than the typical person, and metabolize the corresponding drugs very, very quickly

Extentive Metabolizers produce more copies of the enzyme than most people

Intermediate Metabolizers produce an average number of copies

Poor Metabolizers produce significantly fewer copies than average, leaving them unable to metabolize the drugs normally

Now, remember how I said it also has to do with what kind of drug it is? There are two different kinds of drugs I’m talking about: Active Drugs and Prodrugs. Active drugs are able to be used by the body as-is. Prodrugs only have an effect once they’ve been metabolized by the body into a different substance.

Say someone is an ultrarapid metabolizer of an active drug. They take the drug, it gets absorbed and distributed like normal, but they rapidly metabolize it into inactive substances and excrete it. This person would either get no effect from a typical dose, or only a very slight one, because the drug is never allowed to build up to effective levels in their blood before getting metabolized.

But say that same person is a poor metabolizer of a different active drug. They take the drug, it gets absorbed, but they only very slowly are able to metabolize and excrete it. The drug ends up building up in their blood and staying there longer, possibly causing an overdose of the drug at a typical dose.

The situation would be reversed if the drugs were prodrugs instead. An ultrarapid metabolizer of a prodrug ends up metabolizing too much of the active substance too quickly, possibly causing overdose, while a poor metabolizer of a prodrug maybe never metabolize enough to get effective concentrations of the end substance (check out this post on the prodrug codeine).

Finally, applying this real-life precedent to Captain America, or Flash, or Spider-Man canon evidence, you would have to assume that due to their respective super powers, they all produce a metric sh*tton of liver enzymes capable of metabolizing drugs super fast and hella effective kidneys for excreting them. Typical doses of active drugs would barely work on them, while prodrugs might have a short, but incredibly strong effect on them.

R E F E R E N C E S

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