activity but large ortho-groups retain some activity. polysubstitution on carbon 2 and 6 makes the compound inactive but when the substitution is on carbon 3 and 5 there's some activity. for the highest cardioselectivity, the substituents should be as following: para > meta > ortho. all the β-blockade is in one isomer, (s)-aryloxypropylamine and (r)-ethanolamine. clinical use cardiovascular indications for decades β-blockers have been used in cardiovascular medicine. they have proved to reduce morbidity and mortality. in acute coronary syndrome, β-blockers have been recommended as a class i-a indication in clinical practice guidelines, because the treatment decreases the mortality rate. β-blockers, along with calcium channel blockers, reduce the workload of the heart and its oxygen requirement. β-blockers are sometimes used in a combination therapy to treat angina, if a β-blocker doesn't work well enough on its own. they are used as anti-arrhythmic drugs in patients with hyperthyroidism, cardiac dysrhythmia, atrial fibrillation, atrial flutter and ventricular tachycardia. the treatment with β-blockers reduces the incidence of sudden heart failure when the patient has already had a myocardial infarction. the reason is probably because of their anti-arrhythmic effects and also anti-ischemic effects. a β-blocker therapy is also useful in myocardial infarction, independent to heart failure. the therapy has been very helpful for high-risk patients. although beta-blockers effectively lower blood pressure, they are not recommended as a first-line agent in the treatment of hypertension, as thiazides diuretics, ace inhibitors, and calcium channel blockers show greater benefit. therefore, β-blockers are usually used alongside other blood pressure medications such as calcium channel blockers. they also have an effect on cardiomyopathy, postural orthostatic tachycardia syndrome and portal hypertension, to name a few. other indications there are few diseases, other than cardiovascular diseases, that β-blockers have a clinical effect on. these diseases are mentioned in the following sub-chapters. in addition, there are diseases which β-blockers have a clinical effect but are not the first choice of treatment. they won't be mentioned in the sub-chapters. essential tremor when symptoms of the essential tremors are considerably high, non-selective β-blockers are an important treatment option and usually the first choice. studies have shown that propranolol did reduce symptoms the most in that category. the β-blockers can be used alone or in a combination. glaucoma glaucoma is caused by high intra-ocular pressure (iop). β-blockers reduce iop and are the most common therapy. most of the patients, who use the topical β-blockers, need adjunctive therapy to achieve a target iop lowering. one of the most used drug in adjunctive therapy is dorzolamide. teratogenicity hypertension is reported to complicate one out of ten pregnancies, which makes it the most common medical disorder in pregnancy. it is important to have a correct diagnosis of hypertension during pregnancy, with the emphasis on differentiating pre-existing hypertension from pregnancy induced hypertension (gestational and the syndrome of pre-eclampsia). during pregnancy, the challenge is to determine when to use antihypertensive medications and which level of blood pressure to target. a balance has to be found between the potential risk to the health of the baby related to drug-exposure and the risk to the mother and baby due to an untreated medical condition (severe hypertension). antihypertensive drug use during pregnancy is relatively common and increasing. only a small proportion of available antihypertensive drugs have been tested in pregnant women, and many are contraindicated. it is important to make the exposure of medications to the baby as small as possible. it is not clear if treating women who have mild or moderate hypertension during pregnancy with anti-hypertensive medication is beneficial. the most common first trimester antihypertensive are β-blockers. the consequences of treatment with β-blocker during pregnancy are disputable. some studies report a connection between β-blocker treatment and small for-gestational-age (sga) of newborns and pre-term birth, while others do not. based on meta-analyses, first trimester oral β-blocker use showed no increase in odds of major congenital anomalies. however, analyses examining organ-specific malformations observed increased odds of cardiovascular defects, cleft lip and neural tube defects. the u.s. food and drug administration (fda) categorises β-blockers into different pregnancy categories depending on the safety of the drugs and they range from category b to d, that is, no β-blockers is completely safe for using during pregnancy categories of β-blockers according to the fda non-selective fda category β1-selective fda category labetalol c atenolol d pindolol b acebutolol b propranolol c bisoprolol c timolol c nebivolol c sotalol b metoprolol c