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Parasympathetic Physiology and Anticholinergic Pharmacology

ProfJameson Pharmacology, Physiology 2 Comments

Anticholinergic drugs and the many, many more drugs with anticholinergic side effects are ubiquitous in medical practice. The presentation below will describe parasympathetic physiology as well as anticholinergic pharmacology.

Use the pause and play buttons to move through the flash animations below or download the powerpoint for free at the bottom of this page.

Parasympathetic Drive
Parasympathetic Drive
parasympathetic-drive ppt.ppt

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Sympathetic Nervous System Physiology

ProfJameson Physiology 5 Comments

Understanding the sympathetic nervous system is critical to understanding the pharmacology of a myriad of drugs. This power point will refresh your feeble memories and make it all clear. The key is to understand all the effects as a system designed for survival.

Use the pause and play buttons to move through the flash animations below or download the powerpoint for free –>

Sympathetic Nervous System Physiology
Sympathetic Nervous System Physiology
sympathetic-drive[1].pdf

620.9 KiB
869 Downloads
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Estimating Renal Function

ProfJameson and ProfSmith Physiology Leave a comment  

For Research Purposes

The Gold Standard for GFR is iodine 125 labeled iothalamate clearance

equation for calculating actual creatinine clearance
The Gold Standard for Creatinine Clearance is :

For Clinical Purposes

Evaluating and Monitoring Renal Function

  • The state of the art equation for estimating GFR (eGFR) is the CKD-EPI equation.
  • This equation is an update to the MDRD equation that fixes the overestimate at higher GFRs
  • The CKD-EPI gives an estimated GFR (eGFR) normalized to 1.73 m2

Rationale:

  • GFR vs Creatinine Clearance
  • For an assessment of renal function, you want to estimate GFR
  • Creatinine clearance approximates GFR, but it is not exact because creatinine is secreted in the renal tubule as well as filtered at the glomerulus. Therefore creatinine clearance overestimates GFR. The over estimate due to secretion of creatinine becomes more significant as GFR decreases.

Adjusting Drug Doses

For the reasons given above, the CKDepi should be the best equation for adjusting dosages for renally cleared drugs.   HOWEVER…..

cockcroft and gault equation

So this is probably what you should still use.   Yes, with all it’s shortcomings.

Frequently Asked Questions:

What about correcting Cockcroft and Gault (normalizing it to a 72kg person)?

Don’t bother. If you want a normalized measure, use the CKD-EPI

What about rounding up the creatinine to 0.8?

  • For the CKD-EPI you don’t need to even think about it, they have included modified calculations for low SCr.
  • For the Cockroft and Gault:
    1. Rounding to 0.8 probably makes sense IF it is a frail person that probably has less lean mass and therefore produces less creatinine
    2. Data to support this was derived prior to standardization of laboratory creatinine values.
    3. Manufacturers never report doing this when developing dosage adjustment recommendations.
    4. Generally…. don’t do it.

So what is the most accurate estimate of Creatinine Clearance?

For people with Creatinine clearances greater than 30ml/min , Cockcroft and Gault gives the best estimate of actual creatine clearance. But often that is not what you want to know.

The problem is that drug clearance correlates better with GFR than with Creatinine Clearance. Creatinine clearance is generally higher than GFR because creatinine is secreted by the renal tubule in ADDITION to being filtered.

Which weight should I use for Cockcroft and Gault?

  • The data comes from non-obese healthy people
  • Creatinine comes from lean mass
  • Therefore a reasonable approach would be to use Ideal body weight (IBW) plus 40% of weight in excess of IBW. Use weight= IBW + 0.40(Total Body Weight – IBW)
  • IBW= 50kg plus inches over 5 feet for men and 45kg plus inches over 5 ft for men.

Bottom LIne: How do we adjust drug doses for renal impairment?

  1. Check the package insert for the method that was used in developing the dosage adjustment recommendations.
  2. If no method is stated, use the original C&G equation.
  3. If the patient has a low serum creatinine use the CKD-EPI equation and denormalize it. (multiply the creatinine clearance calculated by the patients body surface area / 1.73 m2


Ace Inhibitors and the Kidney

ProfJameson Pharmacology, Physiology 2 Comments

We have prepared a powerpoint to demonstrate how ACE inhibitors can be either beneficial or harmful to the kidney, depending on the patients physiology:

Click to download ACE INHIBITORS AND THE KIDNEY