Betablockers are used in cardiology since the middle of the sixties They are used in hypertension but not only they are also used in heart failure in arrhythmia and other cardiopathies like angina and heart stroke They are not limited to cardiovascular pathologies I will tell you about the others further in the video Let's talk first about bêta adrenergic receptors physiology which are bêta blockers target this adrenergic receptor in blue is composed of 7 transmembrane patterns it is linked to a G protein through which it stimulates the adenylate cyclase that transforms the ATP in AMPc so that it can transduce the signal The agonists or activators of the bêta adrenergic receptors are for example the adrenaline the noradrenaline dopamine dobutamine and salbutamol the bêta receptor is not these molecules principal target which explains their side effects The AMPc obtained after the ATP transformation is a second messenger that will activate the PKA or kinase protein A this protein will phosphorylate many different proteins which explains the diversity of the bêta blockers effects and their multiple indications There is 3 types of bêta adrenergic receptors The beta 1 receptors located in the heart and the kidney's juxtaglomerular apparatus then the beta 2 receptors located in the blood vessels and the lungs there is also the Bêta 3 receptors which are located in the adipocytes and after their stimulation the lipolysis is increased I will focus here on the bêta 1 and 2 receptors The bêta 1 stimulation results in a positif inotropic effects which means an increase of the contraction's strength but also a positif chronotrope effect which means the increase of the heart frequency a positif dromotropic effect which means an increase of the atrioventricular conduction speed and finally a positif bathmotropic effect which means an increase of the ventricular excitability so in general this will lead to a heart stimulating effect and on top of it there will be an increase of the renin secretion from the kidney's juxtaglomerular apparatus The bêta 2 receptor activation will lead to a cardiac stimulation effect but this is effect is not predominant we will mostly find an effect on the muscular fibres relaxation which are found in many organs the consequences will be a vasorelaxation an intestinal relaxation a bronchorelaxation put to use in asthma with the bêta 2 mimetics for example salbutamol and terbutaline Then there is also a uterine relaxation put to use in the premature deliveries Those are the obtained effects after the stimulation of these tree receptors with for exemple the adrenaline the bêta blockers will block these receptor and have opposite effects The bêta blockers are a major class very used of great therapeutic interest in the vascular field they are catecholamine competitive antagonists which are the adrenaline and noradrenaline Only the levorotatory isomer hold the bêta blocker activity these molecules don't block only the bêta receptors they can also block the alpha receptors like the labetolol which is used for pregnant women because it's less powerful than the others the bêta blockers are ranked in two groups the cardioseletive and the non-cardioselective among these two groups we can either find those with an ASI and those without the ASI I will explain the ASI later As for the selectivity the cardioselective bêtablockers are selective of the bêta 1 receptors which means that they only act and this type of adrenergic receptors this helps avoid the side effects provoked by the bêta 2 receptors they help reduce the cardiac work and heart oxygen consumption which translates in negative inotropic, chronotropic, dromotropic and bathmotropic effects the heart effect is to reduce the cardiac output, the blood pressure and reduce the peripheral resistance in the renal side they will reduce the renin secretion which will lead to the inhibition of the renin angiotensin aldosterone system In this system the live synthesizes the angiotensinogen which will be transformed in angiotensine 1 the renin will transforme this angiotensine in the angiotensine 2 which will leas to the aldosterone secretion the aldosterone effects are the water-soluble retention the volemia increase and then hypotension which will all be prevented by the betablockers The non cardioselectiv will block the bêta 1 and 2 receptors so they are responsible for many side effects because of this bêta 2 receptor blockage The side effects are for exemple hypoglycemia by the way it increase hypoglycemia in diabetic patients and hides the adrenergic signs of hypoglycemia like anxiety, sweating palpitations and trembling other side effects can occur like vasoconstriction Raynaud' syndrome a bronchoconstriction that's why there are forbidden for patients with asthma or BPCO but also an intraocular pressure decrease put to use in the glaucoma treatment About the ASI mentioned earlier it is actually an intrinsic sympathomimetic activity which means that the bêta blocker has a partiel agonist activity this allows to limit the bradycardic effect and the risks of Raynaud's syndrome aggravation Atenolol is cardioselective we can see it on the molecule with the benzene cycle in para and found in all the cardioselectives Oxprenolol has an ASI activity and we can see it with the benzene cycle in ortho Acebutolol is cardioselective and has an ASI activity at the same time we can see on the molecule that the benzene cycle is ortho and para I am going to share with my mnemonic means to remember the cardioselective bêta blockers remember the phrase : New Exclusive Bêta Blockers Act in Majority As Cardioselective each words majuscule represents a bêta blocker as you can see with Acebutolol Celiprolol For those with an ASI the phrase to remember is Contains Partial Agonist Like Properties and again each majuscule represents a bêta blocker As for the pharmacokinetics the bêta blockers are divided into two groupe the lipophilic bêta blockers and the hydrophilic bêta blockers the lipophilic have a good digestive absorption a strong tissue distribution so they can pass through the blood-brain barrier and the fetal-placenta barrier which leads to neurologic effects and a fetal toxicity They have a small half-life time so they need to be taken 2 to 3 times a day their hepatic first pass effect is important so they have a strong interindividual variability The urinary elimination is in form of an inactive metabolite so we have to adapt the posology for patients with kidney failure An example of lipophilic bêta blockers are propranolol and metoprolol On the other hand hydrophilic bêta blockers have a small digestive absorption a small tissue distribution so less side effects their half-life time is longer so they can be taken one time a day they are little metabolized so there is less interindividual variability also they have an unchanged renal elimination for example we have sotalol and labetolol the lipophilic disadvantage is that they can lead to many side effects like nightmares insomnia to avoid them we have to take the betablockers in the morning but also hallucinations and fatigue If the patient doesn't tolerate them and has these side effects we can tell him to switch to the hydrophilic bêta blockers As I said in the beginning bêta blockers are used in many illnesses like hypertension where they act as anti-hypertensive they are also used in heart failure, angina, and also in arrhythmia Bêta blockers are part of the second class except sotalol that is part of the third class with amiodarone In migraine propranolol is used as a background treatment they are also used in glaucoma where timolol allows to reduce the intraocular pressure we can also find them in the treatments of essentials trembling and hyperthyroid in Asthma we use the beta 2 mimetic in other terms bêta 2 adrenergic receptor agonists which are the opposite of bêta blockers that are forbidden in asthma and BPCO Thank you for watching I 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