Vitamin K is High Yield for the USMLE Step 1

• Vit. K is needed for the γ-carboxylation of clotting factors 2, 7, 9 and 10
• This gives them a Ca binding site
• This explains why the vit. K dependent factors are the same factors that are dependent on calcium
• Deficiency:

o Primary problem is an inability to γ-carboxylate factors 2, 7, 9 and 10

• therefore, factors ARE made but can NOT be activated by Ca
• Involves several factors, including factor 7 which:
• has the shortest t½ of all the clotting factors
• therefore, factor 7 is the first factor unable to be activated
• Since factor 7 is specific to the extrinsic pathway the extrinsic pathway is affected first
• Since the prothrombin time (PT) is a measure of the extrinsic pathway, it is the value expected to be elevated first
• Leads to ↑↑PT (AND eventually ↑PTT) – therefore, PT is most sensitive since its ↑’d 1^st
• Bleeding time, a measure of platelet function, is normal since platelets are not affected
• Deficiency can be seen in the following patients:
• Newborns born at home
• Breast milk has low levels of vit K
• All babies in the US are given vit. K shots @ birth in the hospital to prevent hemorrhagic disease of the newborn
• Pts on broad spectrum antibiotics
• Bacteria in colon synthesize much of our vit. K
• Pts w/ steatorrhea
• Loss of fat in the stools also leads to a loss of the fat soluble vitamins, including vit. K
• Vitamin E toxicity
• Inhibits vitamin K dependent carboxylation of clotting factors
• Treatment
• Vitamin K Injection
• If bleeding is serious then give fresh frozen plasma

Myocardial Infarctions Are HY for the USMLE

The formula for a Myocardial Infarction essentially is

Oxygen demand > (greater than) Oxygen supply

Myocardial tissue must therefore switch from aerobic to anerobic metabolism which generates only 2 ATP.

***AT REST THE HEART IS EXTRACTING ALMOST ALL OF THE O2 FROM ITS BLOOD SUPPLY***

therefore, for oxygen supply to increase, more blood must be pumped to the heart tissue (MOA of nitrates for ischemic chest pain). If supply cannot meet demand, the heart tissue may infarct.

Hacking Myocardial Infarctions on the EKG
The leads these changes are seen are listed in my drawing (see below)

• Peaked or Inverted T Waves - often earliest sign of ischemia
  
• ST segment
• Elevation
• Differential diagnosis: Prinzmetal's Angina
  
• a vasospasm of the smooth muscle of the artery
• Si/Sx: chest pain at rest
• cardiac enzymes = negative (differing it from an MI)
• Depressed in stable angina and subendocardial MI
  
• Deep Q waves
  
• These do not go away after the MI. Ever.
  
• therefore, deep Q waves indicats the patient may have suffered an MI

Pharmacology Formulas are High Yield

For this I would point you to pg. 209 of First Aid 2007, there you would find all the formulas you will need.

If I was to ask you this,
"An extremely old medication used by African witch doctors for curing one's "voodoo" is being studied in NIH labs for a possible benificial effect in the treatment of beningin prostatic hyperplasia. The drug is initially studied on 2 rats with enlarged prostates (poor fellows), Rat A and Rat B.

I now, as the question writer proceed to write of bunch of BS and you'll want to read through this and tag it as such real fast on exam day

Rat A and B were born from the same mothers and both have lived in the same cage and blah blah blah and (end BS)

It is calculated that Rat A has a clearance time of 60 seconds where as rat B has a clearance time of one minute and 50 seconds.

Now I ask you this:

1) Given the same dose of the African drug, which of the following must be different.

2) If the 2 rats are found to have the same rate of elimination, which of the following explains the difference in clearance.

Answers to be posted after I receive at least one comment on this post.

Glucagon for Beta Blocker Overdose

Here's a great board question that I don't know if its ever been asked, but can you think why you would want to give glucagon for a beta blocker overdose? Hint: It’s all about cAMP

• Beta blockers at toxic doses would dangerously ↓ HR.
• The heart has β1 receptors which act through a G_s to raise intracellular cAMP
• Glucagon, via its own receptor can ↑ cAMP independently of the blocked β1 receptor
• Also note, that this is an example of physiologic antagonism
• Giving a β1 agonist to overcome the β-block would be an example of competitive antagonism

Can you say, "Gunner Level?"

2nd Messangers

bangledoc writes:

Thanks miky.It will hep greatly every one taking step 1.
could u write more about other 2nd messenger with application (as cGMP).As this are highly asked in exam.
Thanks again

I agree, 2nd messengers are very HY and therefore should be in any blog called HY for the USMLE


Lets start with this:

For the USMLE Step 1, it is more important to understand how each different 2nd messenger system works individually then to memorize if alpha 1 is a cAMP or cGMP or Gs or Gi. It happens to be cAMP and Gs.

I overlooked this point and placed greater emphasis on which receptor goes with which 2nd messenger system. The basic mnemonics in First Aid should suffice for the exam but there is a little more I would add, and since it is so late it will have to wait for tomorrow. (It involves the regulatory subunits of protein kinase A)

I also have a drawing to help you remember Gq, though I admit its corney!

cGMP is High Yield

• Know that the drugs acting via cGMP are
• Nitrates (Nitroglycerin, isosorbide dinitrate)
• Increases production of cGMP
• Activation (denitration) to NO occurs within the smooth muscle cells enwrapped around vascular endothelium.
• NO activates guanylyl cyclase → ↑cGMP → dephosphorylates myosin light chain kinase → smooth muscle relaxation
• Note, tolerance develops rapidly
• Addressed by telling pt to take a break from the particular drug or Rx w/ a different anginal drug
• Occupation exposure → Monday Disease
• Nitroprusside
• Rx: Hypertensive emergencies
• Same mechanism as nitrates
• AE: Cyanide toxicity (rx: sodium thiosulfate)
• Sildenafil
• Decreased breakdown of cGMP
• Inhibits 5’-phosphodiesterase
• The enzyme that breaksdown cGMP
• Do not give a pt on a nitrate sildenafil (will synergistically cause their diastolic BP to fall through the floor!)
• Instead give Alprostadil
• If you accidentally did combine the 2 above what drug would you want to give?
• α-1 agonist
• Hydralazine
• dilates arterioles more than veins= reduces afterload; AE: SLE like syndrome
• Know that ANP (Atrial Natriuretic Peptide) acts by activating guanylyl cyclase