Beta blockers (as a class)





PD

MOA

Competitive antagonism of beta receptors

Classification

Antagonists with varying receptor selectivity

  • Beta1 selelctive (i.e. cardioselective)
    • Atenolol
    • Esmolol
    • Metoprolol
  • Non-selective beta blockers
    • Labetalol
    • Propranolol
    • Sotalol

Others:

  • Partial agonists

    • i.e. some intrinsic sympathomimetic activity
    • Less likely to produce bradycardia
    • e.g.
      • Pindolol
      • Timolol

  • Some have membrane-stablising activities

    • Probably no clinical significance due to high dosage required
    • e.g.
      • Labetalol
      • Metoprolol
      • Propranolol
      • Timolol

Actions

CVS

Main CVS effects include:

  • Negative inotropic and chronotropic effects
  • Antiarrhythmic effects
  • Improves cardiac oxygen supply / demand balance

Negative inotropic and chronotropic effects

Due to:

  • Reduced SA automaticity
  • Prolonged AV node conduction time

Hypotension possible, due to:

  • Negative inotropic and chronotropic effects
  • Inhibition of renin release (due to beta1 blockade at JGA)

May precipitate cardiac failure

Anti-arrhythmic effects

  • Class II anti-arrhythmic drugs
  • Used to treat arrhythmias associated with high catecholamine levels

Improves cardiac oxygen supply / demand balance

  • Despite increased coronary vascular resistance (due to beta2 blockade)

Mild vasoconstriction

  • Due to beta2 blockade
  • Leads to poor peripheral circulation and cold hands
  • Also affects coronary vessels

Resp

  • Bronchospasm
    • Due to beta2 blockade
    • Less common with cardioselective agents

CNS

Includes:

  • Depression
  • Hallucination
  • Nightmares
  • Paranoia
  • Sedation

NB:

  • More likely with lipid soluble drugs
    • e.g. metoprolol, propranolol

Electrolyte

  • Can increase serum potassium level

Metabolic

BSL

  • Blunt BSL response to exercise and hypoglycaemia
    • Should not be used with oral hypoglycaemia
  • May mask symptoms of hypoglycaemia
  • May INcrease resting BSL in diabetics
  • Higher risk of developing diabetes later on
    (see EBM section)

Lipid profile

  • Increased triglyceride
  • Decreased HDL

NB:

  • Beta2 normally stimulate
    • Hepatic glycogen breakdown
    • Pancreatic release of glucagon

Others

  • Eyes

    • Decreased intraocular pressure
    • Decreased production of aqueous humour

  • GIT

    • Dry mouth
    • GI disturbances

  • Sexual dysfunction

  • Could cause muscle weakness in myasthenia gravis

PK

If low lipid solubility:

  • Poorly absorbed orally
  • Little hepatic metabolism
  • Mostly excreted unchanged in urine

If high lipid solubility:

  • Well absorbed orally
  • Extensively metabolised in liver
  • Shorter T1/2
  • Higher incidence of CNS symptoms

Clinical

Indication

  • Hypertension
  • Angina
  • Peri-MI
  • Hyperthyroidism
    • esp propanolol
  • Hypertrophic obstructive cardiomyopathy
  • Glaucoma
  • Phaeochromocytoma
    • But ONLY AFTER alpha blockade has been started

NB:

If used in untreated phaeochromocytoma (high vasoconstriction) → Risk of dramatically reduced cardiac output

Contraindication

  • Bradycardia
  • Heart block (of any type)
    • Some beta blockers are not contraindicated in Type 1 heart block
  • Cardiac failure
  • Obstructive airway disease
    • esp Asthma
  • Sick sinus syndrome

Caution

Abrupt withdrawal

Can precipitate angina or MI

Concomitant Rx with Ca2+ channel blockers

Can cause excessive SA and AV node depression → Bradycardia, heart block, or even asystole

EBM

Anglo-Scandinavian Cardiac Outcomes Trial - Blood Pressure Lowering Arm in 2007

Patient more likely to develop diabetes when hypertension is treated with combination of diuretics and beta blocker

Treatment for hypertension

[Reference: Wikipedia]

  • Not first line agent for HTN anymore
  • Betablocker is now a fourth line agent
    ... after thiazide, ACE inhibitors, and Ca2+ channel blockers

First line agents for HTN

  • US, WHO, Cochrane 2009:

    • First line: Low dose thiazide-based diuretics

  • UK

    • Over 55 yo: Calcium channel blocker
    • Young: ACE inhibitors