BT_PO 1.54 Pharmacology of beta receptor blocking agents

jan 2006 156

I asked about these drugs in the recent in exams and was fascinated (read horrified and astounded) that only one person had a plausible explanation as to how these little chaps cause hypotension…..

These drugs are actually mentioned in 5 LOs BT_PO 1.54 and BT_PO 1.57-1.60

We see a lot of patients on these drugs, partly because they have been shown to confer a survival advantage in people with heart failure, so it is probably a good idea to know a bit about them…

BT_PO 1.54 Describe the pharmacology of commonly used alpha and beta receptor blocking agents, their clinical use, adverse effects and use in the perioperative period

 

Metoprolol is metabolised by the CPY2D6, and hence prone to large inter individual variation in response   TRUE/FALSE

Beta1 selective blockers produce a significant reduction in blood pressure when given to normotensive individuals     TRUE/FALSE

Hypotension with beta blockers is mediated by the dilation of vessels in skeletal smooth muscle   TRUE/FALSE

Beta blockers cause a reduction in the release of renin TRUE/FALSE

Some beta blockers have an alpha agonist effect TRUE/FALSE

Patient of the week

Recently I was anaesthetising an adult with a congenital syndrome. I was quite worried about the airway—but in the end it wasn’t that which caught me out. She had no congenital heart disease, but had a pericardial effusion drained a few years previously. I was quite sparing with the induction agents as I wanted to maintain spontaneous respiration, but nonetheless…

About 5 minutes after induction, I noticed the blood pressure was 54/28.

BT_SQ 1.6

T/F At low levels of blood pressure, the NIBP tends to give spuriously low values.

T/F The most accurate component of the NIBP is the mean.

At the same time, her saturation dropped to 88, even though she was breathing 100% oxygen. The pleth had a good volume and looked normal.

BT_SQ 1.6BT_PO 1.29

T/F The fall in SpO2 was most likely to be artifactual.

I gave three doses of 1mg metaraminol, but, although the saturation improved, the blood pressure remained in the low 70s. Heart rate was in the 40s. Worried that I might see another fall in saturation I decided to run a noradrenaline infusion.

BT_PO 1.52

In such a situation, the most appropriate vasoactive agent would be:

a) Ephedrine

b) Metaraminol

c) Adrenaline

d) Noradrenaline

e) Isoprenaline

After a 20µg bolus dose of noradrenaline, the heart rate dropped to 28.

T/F The most likely cause of the fall in heart rate is alpha 1 receptor agonism in the SA node.

I found out, after the (otherwise uneventful) operation, that she normally has quite a low blood pressure. A good reminder that, when having trouble with anaesthesia, one should first look to the proximal end of the needle.

BT_PO 1.52 and 1.53 Adrenergic agonists

You may have spotted a couple of these little creatures whilst undertaking yesterday’s quiz.

These drugs lend themselves very well to a discussion of structure activity relationships, as there a large number of ways the basic catecholamine structure has been altered, to produce a range of drugs with different pharmacokinetic and pharmacodynamic properties

BT_PO 1.53 describe the pharmacology of adrenergic agonists

Here is one true statement to get you oriented:

Phenylethylamine can be considered the parent drug on which all sympathomimetics are based.

Here is the molecule with the carbons numbered

Phenylethylamine_numbered.svg

 

Maximal  ⍺ and B potency is conferred by OH substitutions on the 3′ and 4′ positions of the benzene ring T/F

Sympathomimetics can be chiral around either the ⍺ or B carbon T/F

A very large substitution on the terminal amine promotes B1 selectivity T/F

A methyl substitution at the ⍺ carbon prevents metabolism by monoamine oxidase and prolongs duration of action T/F

Absence of hydroxyl groups on the benzene ring improves oral bioavailability by preventing metabolism by COMT T/F

BT_PO 1.60 : Digoxin

Describe the pharmacology of drugs used to manage acute or chronic cardiac failure, including: sympathomimetics, phosphodiesterase inhibitors, digoxin, diuretics, ACE inhibitors, nitrates and beta blockers

 

A guest post from an ex PEX chair :

Agatha Christie knew a lot about poisoning, probably as a result of working with a pathologist.  (https://bookshop.theguardian.com/catalog/product/view/id/323440/).  After reading this book, you would have to be brave to go into an English garden.
   
One of her garden poisons was foxglove, which made me think of digoxin.   As did the recent death of Miles Vaughan Williams, who classified anti arrhythmics.   So often we see digoxin toxicity in clinical practice.     An old drug, but one that continues to be used, and is loved by examiners because it allows for candidates to demonstrate  an understanding of many different facets of pharmacology.    

TRUE/FALSE  Digoxin is highly protein bound, hence the introduction of another highly protein bound drug is likely to precipitate toxicity

TRUE/FALSE  Digoxin is primarily excreted renally, and frequently patients who are prescribed digoxin may have borderline or impaired renal function which may precipitate toxicity

TRUE/FALSE  Overdosage of digoxin may be treated using Digibind (R)  which is an example of an immunoglobulin which binds to digoxin to cease its therapeutic effect

TRUE/FALSE  Hypokalaemia is frequently seen in digoxin toxicity, reflecting digoxin’s inhibition of the Na/Ca pump

TRUE/FALSE  The bioavailability of digoxin is reasonably high (approx 70%) allowing for oral loading doses to be only slightly slower in reaching therapeutic effects compared with intravenous loading doses