BETA ADRENERGIC BLOCKERS
Drugs included in this category are having more significant medical value as most of these drugs are used as life-saving medicines in the treatments and prevention of various cardiovascular diseases.
Beta-adrenergic receptors are situated at the synapses of the postganglionic nervous system similar to alpha receptors. Unlike alpha receptors, they are mostly scattered in the cardiovascular and pulmonary systems.
Sub Classifications:-
All the beta-blockers are competitive antagonists. However, they can be sub-grouped according to three major properties.
1.The selectivity of receptor blockade
2.Possession of intrinsic sympathomimetic activities
3. Capacity to block alpha receptors.
A.Beta-1 Selective Blockers:-
1.Atenolol (Tenormin, Aten)
2.Esmolol
3.Acebutolol
4.Metoprolol (Lopressor)
In general in beta-blockers, the drug by name starting with 'A' or' M is mostly cardioselective
The drugs in this category are grouped as beta-1 selective but they have minor or negligible effects on beta-2 receptors at normal or therapeutic dosage. At toxic or high dosage they have a marked blockade effect on beta -2 receptors.
Beta-2 receptors are more scattered in the pulmonary(Lungs) system and hence beta-2 blockade may result in bronchial congestion and give unwanted results to the asthmatic patients. Also, beta-2 blockade may result in hypoglycemia. Hence care should be taken when calculating a therapeutic dosage of the beta-1 cardioselective blocker.
Therapeutical Indications
1.For Atenolol-Hypertension, Myocardial Infarction
2. For Esmolol-As esmolol's action is quick but with a very short duration (10 mins) it is used for emergency situations like thyroid storm. It should be given intravenous route(I.V.)
3.For Acebutol- Hypertension.
Metoprolol- Hypertension,Angina,Myocardial infarction.
B.Non-Selective Beta-Blockers:-
In this category propranolol is the best example.
Pharmacological Effects:-
1.Decreased cardiac output and blood pressure
2.Reduction of the sinus rate and conduction through the atria
3.Peripheral vasoconstrictions
4.Bronchoconstrictions
5.Hypoglycemia due to decreased glycogenolysis at liver
6.Counter effects by decreased glucagon secretions at the pancreas
6.Increased VLDL and decreased HDL.
Kinetics of Propranolol:-
Propranolol is well absorbed orally, but only one-fourth of the absorbed drug reaches the systemic circulation as most of them are metabolized by the liver as the first-pass metabolism.
Clinical Uses:-
1.Hypertension
2.Angina
3.Tachycardia
4.Arrhythmia
5.Thyroid storm
6.Acute panic syndrome
7.Migraine
8.Tremors
The other examples in this nonselective beta-blockade are Timolol and Nadolol. These drugs are having a long half-life. Their duration of action is at least 20 hours.
Therapeutics:-
Timolol and nadolol are mostly used in eye preparations in glaucoma. Because of their long duration, they reduce the aqueous humor production in the eyes by the cilia muscle (beta-2 blockade) very well.
Side effects of nonselective beta-blockers:-
1.Bradycardia
2.Bronchoconstrictions
3. Confuse the tachycardia effects of hypoglycemia and hence these drugs make difficult to monitor diabetics
4.Tiredness
5.Depression
6.Gynecomastia decreased libido and sexual dysfunction
C.Beta-Blockers with Partial Sympathomimetic Activities.
These drugs by nature are adrenergic partial agonists of beta receptors. This partial agonist does not produce full agonism effects instead it will cause a receptor blockade with partial agonism. These drugs because of this partial blockade will not produce some of the side effects that are caused by full agonists or antagonists.
They will not cause bronchoconstriction at a normal dosage.
Acebutolol and Pindolol:-
These two are known examples of this classification.
They are non-selective.
Clinical use:-
Treatment of hypertension in asthmatic patients and those who are prone to get bradycardia
Also, they have the advantage of not interfere with lipid and glucose metabolism.
D.Beta-blockers with Alpha Blocking Effects:-
These drugs are having a beta-blocking effect with selective alpha-blocking effects.
1.Labetalol:-
The mechanism is a nonselective beta-blockade with a selective alpha blockade. The alpha-blocking effects results in peripheral vasodilation rather than vasoconstriction as with other beta-blockers.
Clinical Use:-
Hypertension with atrial fibrillation.
Side effects:-
Orthostatic hypotension
Dizziness
2.Carvedilol:-
A nonselective beta-blocker with the selective alpha-1 blockade.
Uses:-
1.Hypertension
2.Chronic Congestive Heart Failure (CHF) as they improve diastolic dysfunctions by improving diastolic filling time. The advantage is they reduce sympathetic activity while correcting the BP.
Contraindications:-
While using beta-blockers in patients to treat CHF care should be taken as they may worsen the condition if the patient is not otherwise hemodynamically stable means the patient should not have any blood circulation problems.
E.Indirect Adrenergic Blockers:-
These drugs do not directly block the adrenergic receptors but they may cause interference with the availability of noradrenaline the prototype sympathetic stimulant at the receptors.
1.Guanethidine:-
This drug enters the peripheral adrenergic nerves by a reuptake mechanism (maybe due to the stimulation of presynaptic alpha-2 receptors) and bind to storage vesicles and block the release of norepinephrine from the store.
Uses:-
Hypertension
Side effects:-
1.Orthostatic Hypotension
2.Sexual dysfunction.
2.Reserpine:-
It is an alkaloid of the plant Rauwolfia serpentina.
Unlike guanethidine reserpine block the transport of norepinephrine from its place of synthesis that is cytoplasm to its storage and thereby causes unavailability of the stimulant at the receptor. Like guanethidine, it may also stimulate the presynaptic alpha-2 receptor in order to have an entry into the nerve cell by a reuptake mechanism.
Uses:-
Hypertension (Very rare)
