Known as "beta blockers" - Introduction

Dr Angelo Pieris. Teaching Fellow in Clinical Pharmacology and Therapeutics. Barts & The London Medical School.

Updated by Dr Hew Torrance, July 2013.

Key+Topics+%0D%0ASympathetic+autonomic+nervous+system++%0D%0AHypertension+%0D%0AArrhythmia+%0D%0AHeart+failure+%0D%0ATremor%2C+anxiety%2C+%26amp%3B+symptomatic+hyperthyroidism+%0D%0A1st+pass+metabolism+%0D%0ABroncho-constriction+in+asthma+%0D%0APeripheral+vascular+disease++%0D%0ASympathetic+response+to+hypoglycaemia+%0D%0AMyocardial+infarction
Key Topics Sympathetic autonomic nervous system Hypertension Arrhythmia Heart failure Tremor, anxiety, & symptomatic hyperthyroidism 1st pass metabolism Broncho-constriction in asthma Peripheral vascular disease Sympathetic response to hypoglycaemia Myocardial infarction

The sympathetic nervous system affects all organs in order for the body to maintain optimal organ perfusion and prioritise certain sensory and motor functions in various circumstances. This is classically termed the fight or flight enabling response.

Question

Here is a starter..

What is the effect on cardiac muscle and bronchial wall smooth muscle of sympathetic stimulation?

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Known as "beta blockers" - Pharmacology
Sir+James+Black.+The+lead+doctor+behind+the+development+of+propranalol%2C+the+first+beta+blocker+in+the+1960s.+%0D%0A+%0D%0AHe+was+awarded+the+1988+Nobel+prize+for+medicine+based+on+his+advancement+of+the+principles+by+which+cardiovascular+disease+could+be+treated+and+his+approach+to+drug+development.
Sir James Black. The lead doctor behind the development of propranalol, the first beta blocker in the 1960s. He was awarded the 1988 Nobel prize for medicine based on his advancement of the principles by which cardiovascular disease could be treated and his approach to drug development.
Question

When will there be increased sympathetic nervous system stimulation of the heart?

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Sympathetic nervous stimulation of the heart increases heart rate and contractility. This happens after the release of neurotransmitters noradrenaline and adrenalin. These act on the mainly beta 1 type of adrenergic nerve receptors in the heart, including those of the sino-atrial (SA) node, the primary pacemaker.

Adrenaline from the adrenal glands is secreted into the bloodstream and thus has a systemic effect. Noradrenaline is released from the nerve terminals and has a local effect.

Why are we dealing with terms like "beta 1" not just "adrenoceptor" antagonists?

The adrenoceptors vary a little. This variability has been targeted by pharmacologists. For example the lungs display more beta 2 receptors than the heart which has more beta 1 receptors. This has led to the development of medicines that are designed to work on specific receptors (adrenoceptors). The idea is to avoid unwanted adverse effects. Salbutamol for example is a beta 2 agonist. But it still affects the heart and causes a tachycardia. In reality there is overlap with "selective" adrenergic medication.

So avoid beta blockers in people with asthma and those little blue inhalers?

Yes.

1.+Can+you+identify+what+the+correct+sequence+of+events+when+the+man+starts+running%3F+%0D%0A+%0D%0A+%0D%0AStriated+cardiac+muscle+fibres+as+shown+under+electron+microscopy+are+depicted+in+the+top+right+hand+corner.+These+have+lots+of+mitochondria+for+energy+production+and+depend+on+aerobic+metabolism.
1. Can you identify what the correct sequence of events when the man starts running? Striated cardiac muscle fibres as shown under electron microscopy are depicted in the top right hand corner. These have lots of mitochondria for energy production and depend on aerobic metabolism.

Why might the above scenario cause a problem if the man had ischaemic heart disease?

If the beta adrenoceptors are blocked by a drug how will this help the patient to avoid angina pain? (Imagine a patient who is walking, not running!)

Pharmacology

  • Beta blockers are well absorbed orally, but intravenous preparations also exist (e.g. labetalol) for extraordinary situations.
  • There is a very large 1st pass metabolism effect. This means that the (oral) drug is absorbed from the gastrointestinal tract and carried via the portal circulatuion to the liver, where a very large proportion is metabolised into inactive metabolites.
  • Drugs can be eliminated by means of liver metabolism (This tends to result in a shorter drug duraction of action) or urinary excretion. The latter is possible if the drug is hydrophillic.
  • Propranalol and metoprolol are are relatively short acting. (The more lipid soluble ones, occasionally associated with bad dreams as they cross to the brain more easily)
  • Bisoprolol and atenolol are longer acting. They can be given once daily. They are more hydrophillic enabling renal excretion.
  • Question

    A sixty year old woman who normally takes metoprolol 50mg twice daily undergoes drainage of a peri-anal abscess under general anaesthetic. She has been nil-by mouth for eighteen hours as her operation kept being pushed back due to other emergencies taking priority. Unfortunately she goes into fast AF in recovery. The anaesthetist decides to give her a dose of metoprolol by intravenous injection.

    Based on the information above (And the BNF) what intravenous dose might be given of the same beta-blocker?

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    Known as "beta blockers" - Indications

    In which of the conditions mentioned below are beta blockers recognized as a treatment option?

  • Hypertension
  • Arrhythmia
  • Heart failure
  • Tremor, anxiety, & symptomatic hyperthyroidism
  • Cardiogenic shock
  • Following myocardial infarction
  • Broncho-constriction in asthma
  • Peripheral vascular disease
  • Hypertension

    Are ACE-Inhibitors and calcium channel blockers not used to treat hypertension instead of beta blockers?

    All these drugs are used to treat high blood pressure. The evidence suggests that white and Asian people under 55 are often benefit from ACE-Inhibitors most, whilst black and over 55 year olds are often given calcium channel blockers first.

    Why the ethnic divide?

    Black people often have low-renin hypertension, so gain less benefit from ACE-inhibitors.

    Heart Failure

    Why use beta blockers in heart failure? Should these people not be on infusions of noradrenaline instead??

    Beta blockers are strongly indicated in stable heart failure and are associated with decreased mortality. For the reasons stated on the previous page. Another reason for this is that patients with heart failure are at high risk of death from developing sudden cardiac arrhythmias. Beta blockers reduce the incidence of such arrhythmias.

    The key principle to bear in mind is that they are NOT given to patients in a de-compensated state, i.e. patients who have suddenly developed symptoms such as pulmonary oedema, who may have difficulty maintaining a satisfactory blood pressure for adequate organ perfusion.

    So how should they be used in treating heart failure?

    They are started at a very low dose, the patient may initially feel worse. Functional benefit may not be apparent for weeks. The drugs slow the progression of disease and reduce deaths from arrythmias.

    Atrial fibrillation.

    Is that when the atria go wobbly?

    Well the AV node is no longer the pacemaker, there is disorganised contraction. The atria dilate.

    It can be new onset or recurrrent, symptomatic or asymptomatic, caused by a variety of disease or idiopathic.

    So what use are beta blockers?

    They are useful if the patient is symptomatic. They can slow the ventricular rate. In patients that have paroxysmal AF they can keep the patient in sinus rythmn.

    Here+is+an+ECG+that+you+could+be+presented+with+as+an+F1+on+the+ward.+%0D%0A1.+Can+you+see+regular+p+waves+before+the+QRS+complex%3F+%0D%0A2.+What+is+the+ventricular+rate%3F++%0D%0A3.+Is+the+rate+regular%3F
    Here is an ECG that you could be presented with as an F1 on the ward. 1. Can you see regular p waves before the QRS complex? 2. What is the ventricular rate? 3. Is the rate regular?
    Question

    In the treatment of atrial fibrillation which is most accurate?

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    Question

    A patient on the acute medical unit is diagnosed with an acute coronary syndrome. The consultant sees him on admission and decides to start a beta blocker.

    What evidence is that based on?

    A 15% reduction in mortality in the first week following myocardial infarction (MI) was reported by the ISIS1 study.

    When is a beta blocker contra-indicated in MI patients?

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    Known as "beta blockers" - Adverse Effects

    Potentially dangerous adverse effects :

  • Bronchospasm in asthmatics.
  • Bradycardia with heart block.
  • Falls secondary to hypotension or heartblock.
  • Impaired gluconeogenesis in people with diabetes.
  • The most common side effect that patients can not tolerate is fatigue or lethargy.
  • Erectile dysfunction (Patients are often shy to say, so ask if this is an issue)
  • Cold peripheries
  • Vivid (unplesant) dreams
  • Impairment of normal mental function/state including depression.
  • Question

    Case. The next three questions fit together.

    Mr Bashir is a 72 year old who was admitted with chest pain 24 hours ago. He has a past medical history of angina. His medications are aspirin, bisoprolol, simvastatin, and isosorbide mononitrate.

    You are the F1 on call. You are asked to review him because the nurse has found his blood pressure to be 109/60 and his pulse to be 55.

    What do you do first?

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    Question

    Mr Bashir is sitting in a chair drinking a cup of tea, smiles and greets you as he sees you approaching.

    You ask him how he is doing.

    What might issues you specifically want to explore with the patient in this short consultation?

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    Question

    Mr Bashir tells you that he is looking forward to being able to go home now that he is feeling pain free and is able to gently move around without any symptoms. He is willing to endure percutaneous angioplasty if he is advised to do so.

    You discuss your findings with the nurse and agree a plan which is:

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    Question

    Rita Ryvita is a well sixty four year old with essential hypertension. She has no hypertension related organ damage. Her GP starts bisoprolol 2.5mg once daily and follows the patient up a month later. On her return visit the patient reports no adverse symptoms. The GP checks her blood pressure, which is found to be 149/85 and then increases the bisoprolol to 5 mg.

    What follow up blood tests for drug monitoring the does Rita require?

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