Abstract
The road to modern day β-blockers has by no means been unhindered. The creation of humble propranolol in the 1960’s has lead to current life saving therapeutics, regardless of the opposition encountered throughout the journey. The discovery of various β-blockers original compounds may have followed similar paths, but it is the physiological consequences of the drugs that set them apart. Beta-adrenoceptors bind endogenous neurotransmitters such as adrenaline and noradrenaline. It is the ability to block this reaction that gives the antagonists their name. By blocking this binding, responses of the sympathetic nervous system are inhibited, resulting in decreases in heart rate, cardiac inotrope and conduction velocity. The ability of …show more content…
For example, in the case of heart failure, the SNS increases vasoconstriction in peripheral vasculature and cardiac stroke volume in order to preserve perfusion pressure (Triposkiadis et al 2009). Unfortunately in the long term this support leads to increased morbidity and mortality. β-blockers can work to wholly or partially inhibit theses reactions. Originally β-blockers were not selective of adrenoceptors until the 1970’s when cardio selective drugs were developed. These days technology has allowed for the development of medicines, which are not only selective, but maintain vasodilatory behaviour via blocking of alpha-adrenoceptors in vasculature (Klabunde, 2013). Much is now known about the distribution of the various adrenoceptors, for example, β2-adrenoceptors are in greater number in the atria of the heart than the ventricles, but if the myocardium becomes stressed through large influxes of adrenaline, they may be conscripted to increase both heart rate and force of contraction (Brodde et al 1992). A knowledge base of adrenoceptors and corresponding antagonists has grown steadily over the past 50 years through countless studies and clinical …show more content…
β-blockers were however indicated for some cases of hyperthyroidism (Levy et al 1970). The first generation beta-blockers such as propranolol, nadolol, timolol and pindolol were non-selective, so resulted in blockage of β2-receptors in smooth muscle within the bronchi. This became an issue when constriction of bronchi in asthmatic patients proved hazardous (Golan, 2008). Furthermore, blocking all β-receptors could conceal hypoglycaemic symptoms in cases of diabetes (Golan, 2008). On these grounds more selective medications became a necessity. By 1970, although classification of varying β-receptors was yet to be announced, practolol was known to selectively target β-adrenoceptors in the heart, but not occupy receptors in the bronchi or peripheral vasculature (Whelton et al 1970). Lipid solubility was suggested as the mechanism for this action at the time and practolol was found to be an effective therapeutic for arrhythmias, particularly for asthma sufferers (Whelton et al 1970). Unfortunately 27 patients (Table 1) suffered Oculomucocutaneous syndrome as a consequence of its use (Wright, 1975). Systemic lupus erythrematosis syndrome was also linked to the drug, which was removed from clinical use in the UK in 1975 (Raftery and Denman, 1973; Cobert,
The road to modern day β-blockers has by no means been unhindered. The creation of humble propranolol in the 1960’s has lead to current life saving therapeutics, regardless of the opposition encountered throughout the journey. The discovery of various β-blockers original compounds may have followed similar paths, but it is the physiological consequences of the drugs that set them apart. Beta-adrenoceptors bind endogenous neurotransmitters such as adrenaline and noradrenaline. It is the ability to block this reaction that gives the antagonists their name. By blocking this binding, responses of the sympathetic nervous system are inhibited, resulting in decreases in heart rate, cardiac inotrope and conduction velocity. The ability of …show more content…
For example, in the case of heart failure, the SNS increases vasoconstriction in peripheral vasculature and cardiac stroke volume in order to preserve perfusion pressure (Triposkiadis et al 2009). Unfortunately in the long term this support leads to increased morbidity and mortality. β-blockers can work to wholly or partially inhibit theses reactions. Originally β-blockers were not selective of adrenoceptors until the 1970’s when cardio selective drugs were developed. These days technology has allowed for the development of medicines, which are not only selective, but maintain vasodilatory behaviour via blocking of alpha-adrenoceptors in vasculature (Klabunde, 2013). Much is now known about the distribution of the various adrenoceptors, for example, β2-adrenoceptors are in greater number in the atria of the heart than the ventricles, but if the myocardium becomes stressed through large influxes of adrenaline, they may be conscripted to increase both heart rate and force of contraction (Brodde et al 1992). A knowledge base of adrenoceptors and corresponding antagonists has grown steadily over the past 50 years through countless studies and clinical …show more content…
β-blockers were however indicated for some cases of hyperthyroidism (Levy et al 1970). The first generation beta-blockers such as propranolol, nadolol, timolol and pindolol were non-selective, so resulted in blockage of β2-receptors in smooth muscle within the bronchi. This became an issue when constriction of bronchi in asthmatic patients proved hazardous (Golan, 2008). Furthermore, blocking all β-receptors could conceal hypoglycaemic symptoms in cases of diabetes (Golan, 2008). On these grounds more selective medications became a necessity. By 1970, although classification of varying β-receptors was yet to be announced, practolol was known to selectively target β-adrenoceptors in the heart, but not occupy receptors in the bronchi or peripheral vasculature (Whelton et al 1970). Lipid solubility was suggested as the mechanism for this action at the time and practolol was found to be an effective therapeutic for arrhythmias, particularly for asthma sufferers (Whelton et al 1970). Unfortunately 27 patients (Table 1) suffered Oculomucocutaneous syndrome as a consequence of its use (Wright, 1975). Systemic lupus erythrematosis syndrome was also linked to the drug, which was removed from clinical use in the UK in 1975 (Raftery and Denman, 1973; Cobert,