Another structure quiz answers

Here are the answers to another structure quiz

1, Chloroform – note the simple hydrocarbon structure in common with many of the volatile anaesthetic agents, including the next two below

Chloroform

2. Isoflurane

iso-structure

3. Enflurane – note that isoflurane and enflurane are structural isomers of each other. They have the same atoms, rearranged in a different order. What differences due the change in arrangement of the atoms make to the properties of these two drugs?

medchem1ic_Enflurane_full_498_229__0_native

4. Codeine – the methylated form of the drug below. Demethylation by CYP2D6 results in conversion to morphine

1200px-Codein_-_Codeine.svg

5. Morphine – naturally occurring phenanthrene

1200px-Morphin_-_Morphine.svg

6. Tramadol – can you find the structural similarity to codeine, which results in the two drugs being metabolised at the same enzyme?

150px-(1S,2S)-Tramadol_gespiegelt.svg

7. Naloxone – did anyone get this one. Interestingly all conventional mu receptor antagonists are structural analogues of morphine, with a bulky substitution the N17 position.

naloxone.jpg.pagespeed.ce.Q70R1-33LY-2

8. Tubocurarine – purely of historic interest. Did some of you pick the class of drug based on the quaternary ammonium and the isoquinoline  structure?Tubocurarine.svg

9. Glycopyrrolate – another drug working a the ACh receptor. Look for similarities in structure with the drug above. How does glycopyrrolate differ from atropine structurally? What difference does this make in clinical practice?

g-386

10. Neostigmine – what features help it associate with the AChE? Can you find the carbamyl ester?

g-590

Relationship between blood pressure & cerebral blood volume

Last Wednesday I posted a question on Primary LO of the Day “How can you manipulate BP to minimise cerebral blood volume?”

As I mentioned, most registrars initially jump to the incorrect conclusion..

Here are the graphs and equations you should have used to work out you answer, but I’ll leave the final conclusion to you…

 

Firstly a graph relating cerebral blood flow to MAP

AUKimage-template

Cerebral blood flow is usually relatively constant between a MAP of 50 – 150mmHg, assuming intact auto regulation and normotension.

Next, which equation relates Flow to Pressure. Think back to Ohm’s Law V=IR and you will be able to derive the equation

Q=△P/R  

Q=Flow, △P = pressure change R= resistance

If flow remains constant if face of a changing pressure, then resistance must also be changing.

In this context we are looking a cerebrovascular resistance. Cerebrovascular resistance controls the diameter of the vessels and hence the volume of blood contained within the cerebral circulation.

Which way will resistance change in each of the high and low MAP situations?

Now you can determine the calibre of the vessels at each end of the flat portion of the curve and determine a MAP to minimise cerebral blood volume.

Remember this only applies with intact autoregulation. If you do the sums for the steep parts of the curve, you will come up with quite different conclusions – give it a go…

Some answers

Here are the answers to the Primary LO of the Day post from March 8

Excuse the hand drawn graphs – my computer graphics skills are limited ( read almost non existent)

1.answer 1

2. Note the potency of the full agonist is reduced but the efficacy remains unchanged 

3.Note the ED50 for both drugs is identical, but the efficacy of the partial agonist is lower

4.Note the efficacy of the partial agonist is 0.5 but the ED50 is closer to the origin reflecting its higher potency compared with the full agonist

5. Graph three could represent the agonist in the presence of an irreversible antagonist, where the efficacy is lowered but the potency of the agonist is unchanged