Beta blockers are competitive inhibitors at beta adrenergic receptors and counter the effects of catecholamines such as epinephrine and nor-epinephrine. This action leads to decrease sympathetic effects mainly on cardiovascular system. This is why beta blockers are useful in treatment of cardiovascular diseases i.e. hypertension, heart failure, cardiac arrhythmias. Some beta blockers are also used in other clinical conditions such as migraine prophylaxis and glaucoma.
TYPES OF BETA BLOCKERS
Beta blockers can be classified according to α or β receptor selectivity or both. Beta blockers can also be divided in generations which is following nowadays.
| Generation | Selectivity | Generic name | Brand name |
|
1st generation |
Non-selective, acts on β1 and β2 receptors |
Propanolol | Inderal, Hemageol, InnoPran XL |
| Sotalol | Betapace | ||
| Pindolol | Visken | ||
| Nadolol | Corgard | ||
| Timolol | Blocadren, Timoptic (ophthalmic) | ||
|
2nd generation |
Selective β1, also called cardio selective |
Atenolol | Tenormin |
| Acebutalol | Sectral | ||
| Bisoprolol | Zebeta | ||
| Esmolol | Brevibloc | ||
| Metoprolol | Lopressor, Toprol | ||
|
3rd generation |
Non-selective, both α and β blockers with additional vasodilation activity | Carvedilol | CoregS |
| Labetalol | Normodyne, Trandate | ||
| Selective β1, blocker with additional vasodilation activity | Nebivolol | Bystolic | |
| Betaxolol | Kerlone |
MECHANISM OF ACTION
Adrenoceptors and its presence in the body
Adrenoceptors are broadly classified in three types, alpha, beta and dopamine receptors.
Alpha and beta receptors are divided on the basis of potencies towards endogenous catecholamines such as alpha receptors have potencies epinephrine > norepinephrine > isoproterenol while beta blockers has vice versa isoproterenol > norepinephrine > epinephrine. Dopamine receptors is selective for dopamine produce in the body.
DISTRIBUTION OF ALPHA AND BETA RECEPTORS SUBTYPES IN THE BODY
| Type | Tissue | Action |
| α1 | Most vascular smooth muscles, papillary dilator muscles, prostate and heart | Contraction, pupillary dilation, increase force of contraction of heart |
| α2 | Postsynaptic CNS adrenoceptor, platelets, adrenergic and cholinergic nerve terminals, smooth vascular muscles, fat cells | Platelets aggregation, contraction, inhibition of lipolysis and neuro-transmitter release |
| β1 | Predominantly in heart | Increase force and rate of contraction |
| β2 | Respiratory, urinary and smooth muscles, skeletal muscles, liver | Smooth muscles dilation, potassium uptake from skeletal muscles, activates glycogenolysis. |
| β3 | Fat cells | Activates lipolysis |
Pharmacodynamics of Beta blockers:
The major effects of beta blockers is the beta receptor blockage. However beta blockers also possess partial agonist activity and local anesthetic action which differ among the beta blockers.
Effects on cardiovascular system
When beta blockers inhibits beta receptors, it decreases blood pressure in patient with hypertensions. However, the exact mechanism is unknown. It might be due to the effects on heart and blood vessels, suppression of the renin-angiotensin system and effects in the central nervous system. Beta blockers have negative inotropic and chronotropic effects which make it useful drugs for patients with angina chronic heart failure. In the vascular system it cause beta mediated vasodilation. These mechanisms cause decrease in cardiac output.
Effects on the Eye
Many beta blockers are used in the treatment of glaucoma because it reduces the intraocular pressure and decreases the aqueous humor production.
Effects on the Metabolic and Endocrine effects:
Beta receptor blockers specially propranolol inhibit lipolysis by the inhibition of sympathetic nervous system. The chronic use of beta blockers has been seen to increase plasma concentration of VLDL and HDL and has no effect on LDL. Thus, overall HDL/LDL balance decline that may increase the risk of coronary artery disease.
Effects other than beta receptor blockage (Intrinsic sympathomimetic activity)
Some beta blockers also have intrinsic sympathomimetic activity. In this process, the beta blockers not only block beta receptors but also weakly stimulate both β1 and β2 receptors which leads to diminishing effects on cardiac output and cardiac rate.
Furthermore, some beta blockers also possess local anesthetic action which is also called membrane stabilizing. This action is due to the blockage of sodium channels.
ACTION WITH RESPECT TO GENERATION BETA BLOCKERS
1st generation, Non-selective beta blockers acts on both β1 and β2 receptors decrease heart rate, delayed conduction through AV node, reduced contractility thus, finally decrease cardiac output and oxygen demand by heart muscles. This class include propranolol, timolol, pindolol, sotalol.
2nd generation is cardioselective and inhibits β1 receptors and reduce blood pressure. This class includes atenolol, acebutalol, esmolol, metoprolol
3rd generation is both selective and non-selective. Selective third generation include nebivolol and betxolol. These drugs not only blocks β1 receptors but also cause vasodilation. Nebivolol cause vasodilation by Nitric oxide from endothelial cell and betxolol cause vasodilation by blocking calcium channel blockage. Non selective third generation includes carvedilol and labetalol. Both drugs not only blocks β1 receptors but also cause peripheral vasodilation by blocking α1 receptors.
PHARMACOKINETICS
Most of the drugs in beta blockers are well-absorbed in after oral administration. Generally peak concentration of these drugs occur 1-3 hours after orally taken the drug. Only propranolol undergoes extensive hepatic metabolism among these beta blockers that’s why have low bioavailability i.e. 30% while other drugs have 50-90% bioavailability. Beta blockers have low lipid solubility except carvedilol, propranolol and penbutolol which have high lipid solubility and that’s the reason these drugs can cross blood brain-barrier. Most beta blockers have half-life in the range of 3-10 hours except esmolol which is rapidly hydrolyzed and has 10 minutes half-life. Propranolol and metoprolol are extensively metabolized by liver. Other drugs are less completely metabolized and nadolol is excreted unchanged in the urine and has the longest half-life among beta blockers available. The half-life of nadolol can be prolonged in renal disease and propranolol in live disease.
INDICATIONS
- Hypertension
- Ischemic heart disease
- Cardiac arrhythmias
- Heart failure
- Following Myocardial infarction
- Dissecting aneurysm (Esmolol)
- Glaucoma
- Migraine prophylaxis
- Hyperthyroidism
- Tremors (propranolol and metoprolol)
CONTRAINDICATIONS
- Hypersensitivity
- Renal failure (Atenolol)
- Decompensated heart failure
- Peripheral vascular disease
- Raynaud’s phenomenon
- Asthma
- COPD
- Bronchoconstriction
- Bradyarrythmia
SIDE EFFECTS & ADVERSE EFFECTS
- Insomnia
- Intolerance include fatigue, cold extremities, erectile dysfunction
- Asthma or COPD (with non-selective beta blockers)
- Hypoglycemia (insulin dependent diabetic patient)
- Heart block
- Metabolic disturbance
- Others include
- Rash
- Blurred vision
- Weakness
- Muscle cramps
- Headache
- Nausea vomiting
- Confusion
- Pheochromocytoma
DRUG INTERACTION
- Antacids and antidiarrhoeals may cause modest reduction in the absorption of atenolol, propranolol, sotalol and probably slight increase in the absorption of metoprolol. But all these effects are clinically not significant.
- Most NSAIDs can increase blood pressure when given with beta blockers including piroxicam, Indometacin, ibuprofen, naproxen. Celecoxib reduce the metabolism of metoprolol.
- Barbiturates effected the plasma level and action of beta blockers that are metabolized by liver e.g. alprenolol, timolol, metoprolol
- The use of concurrent use of beta blockers and dihydropyridine type calcium channel blockers appeared to be safe and useful clinically e.g. felodipine, isradipine, lacidipine, nicardipine, nimodipine. Although Nifedipine and nifoldipine may cause severe hypotension and heart failure when given with beta blockers.
- Diltiazem may enhance the antihypertensive effects of beta blockers and clinically significant when given concurrently but close monitoring is necessary.
- Verapamil may enhance the antihypertensive effects of beta blockers and clinically significant when given concurrently but close monitoring is necessary.
- Bupropion may cause bradycardia and severe hypotension when given with beta blockers.
- Dextropropoxyphene may increase the bioavailability of metoprolol when given concurrently, but it is not seen with propranolol.
- The concurrent use of ergot derivatives and beta blockers in the management of migraine may cause severe peripheral vasoconstriction and hypertension.
- Fish oil may enhance the hypotensive effects of beta blockers.
- The concurrent use of flecainide and beta blockers may cause additive cardiac depressant effects. But when flecainide given with sotalol and timolol, it may cause bradycardia and severe AV block.
- Grape juice markedly reduce the bioavailability of celiprolol and talinolol while orange juice reduce the bioavailability of celiprolol and atenolol.
- Food may increase, decrease or no change to the beta blockers but it has no clinically significance.
- Cimetidine may cause bradycardia, irregular heart beat and hypotension when given with atenolol, metoprolol and labetalol respectively.
- Nizatidine may cause bradycardiac effects when given with atenolol
- Haloperidol may cause increase risk of QT interval prolongation when given with sotalol
- Erythromycin IV and sotalol concurrent use must be avoided because of increased risk of QT interval prolongation due to the additive effects.
- Sulfasalazine markedly reduce the absorption of talinolol.
- Intraocular acetylcholine may cause when given with metoprolol.
- Tobacco smoking may reduce the beneficial effects of beta blockers i.e. heart rate and blood pressure.
- The concurrent use of sotalol and quinolone should be avoided due to increased risk of QT interval prolongation.
- Rifampicin may increase the clearance of beta blockers when given concurrently
- Sotalol and quinidine may cause increase QT interval prolongation when given concurrently, thus increase the risk of torsade de pointes arrhythmia.
- Propafenone may increase the plasma level (two to five fold) of propranolol and metoprolol which can increase toxicity.
- The use of potassium depleting drugs with sotalol may cause torsade de pointes arrhythmia unless potassium level is maintained in the body
- Concurrent use of chlorpromazine with propranolol and thioridazine with pindolol may increase the plasma level of all drugs. Both drugs can cause hypotension. Concurrent use of sotalol with phenothiazine that prolonged the QT interval must be avoided.
- Beta blockers may cause anaphylactic reactions of penicillin when given concurrently.
NURSING INTERVENTIONS
- Inquire patient’s complete health history including allergies, diabetes or any respiratory diseases
- Monitor blood pressure and pulse prior administration of medicine. If blood pressure and pulse is not in normal range inform the health practitioner.
- Observe daily intake an output of fluid. Check body weight.
- If patient is on parenteral drug then check blood pressure and pulse frequently.
- Patient with respiratory disease specially with asthma or COPD should be closely monitored for sign and symptoms.
- Observe lab determining electrolytes, BUN, creatinine levels.
- In diabetic patient observe hypoglycemic effects
PATIENT EDUCATION
- Counsel the right dose and time of medicine.
- If patient is taking metoprolol then counsel patient to take with meal or after meal.
- Don’t break, crush or dissolve sustained release medicine.
- Counsel them the possible side effects of medicine.
- If blood pressure or pulse is too low then immediate contact to the doctors
- Change position slowly to avoid orthostatic hypotension
- Ask doctor prior to take any multivitamins or any supplements
- Report immediately to the doctor if feeling chest pain, SOB, faintness with exercise or during work activities.