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The adrenergic antagonists are also known as adrenergic blockers or sympatholytics are those agents that bind reversibly or irreversibly to adrenergic receptors but do not trigger the usual receptor-mediated intracellular effects they are divided to two main groups the alpha receptors antagonists and the beta receptors antagonists and each group is further subdivided
To non-selective and selective agents in this lecture we’ll discuss the alpha receptors antagonists we already know that alpha-1 receptors are located in the blood vessels when activated by endogenous catechol means or agonists it produces vasoconstriction increasing peripheral resistance and blood pressure so we can conclude that blocking alpha adrenoceptors mainly
Affects blood pressure resulting in decreased peripheral vascular resistance and this induces a reflex tachycardia resulting from the lowered blood pressure the non-selective alpha transceptors antagonists are phenoxy benzamine and phentolamine phenoxy benzamine binds covalently to both alpha-1 and alpha-2 receptors so the block is irreversible and non-competitive
And the only way the body can overcome the block is to synthesize new adrenoceptors and that may require a day or longer so the actions of phenoxybenzamine last for about 24 hours after the drug is injected a delay of a few hours occurs before a blockade develops on the other hand phantolamine is a reversible competitive blocker for alpha-1 and alpha-2 receptors
It lasts for approximately four hours after a single injection both agents block alpha-1 receptors preventing vasoconstriction of peripheral blood vessels by endogenous catecholamines so decreasing peripheral resistance which provokes a reflex tachycardia they also block presynaptic inhibitory alpha-2 receptors in the heart resulting in more norepinephrine release
Which stimulates beta-1 receptors on the heart increasing cardiac output and both agents produce what is called epinephrine reversal all alpha adrenergic blockers reverse the alpha agonist actions of epinephrine for example we already know from the previous lectures that epiphan acts on alpha 1 receptors in the blood vessels causing vasoconstriction and also acts
On beta 2 in the skeletal muscle’s blood vessels causing vasodilatation so by using the non-selective alpha antagonists the vasoconstrictive action of epinephrine is interrupted but viscitilation due to beta-2 receptors is not blocked so in the presence of phenoxybenzamine or phentolamine the systemic blood pressure decreases in response to epinephrine and we
Can conclude that the actions of norepinephrine are not reversed but are diminished because norepinephrine has only alpha one the suppressor action and lacks significant beta agonist action on the vasculature and they have no effect on the actions of isoproterenol which is a pure beta agonist phenoxy benzamine is used in the treatment of pheochromocytoma which
Is a catecholamine secreting tumor of cells derived from the adrenal medulla it is sometimes effective in treating raynaud disease and frostbite phantolamine is used for the short-term management of phyochromocytoma it is also used locally to prevent dermal necrosis following extravasation of norepinephrine phentolamine is also useful to treat hypertensive crisis
Their adverse effects are similar both cause postural hypotension and both induce tachycardia that is mediated by the borrow receptor reflex and by blocking the alpha-2 receptors as we mentioned before so they should be used with caution in patients with cardiovascular disease and they are not useful in the treatment of hypertension phenoxy benzamine can cause
Nasal stuffiness nausea and vomiting it may also inhibit ejaculation let’s now talk about the selective blockers for alpha-1 receptors prazosin terazosin and doxazosin are selective competitive blockers of the alpha-1 receptor so all of these agents decrease peripheral vascular resistance and lower blood pressure they cause minimal changes in cardiac output renal
Blood flow and glomerular filtration rate so we can conclude that they are used in the treatment of hypertension the first dose of these drugs may produce an exaggerated orthostatic hypertensive response this action is known as first dose effect it can be minimized by adjusting the first dose to one-third or one-fourth of the normal dose and by giving the drug
At bedtime tamsuya lawson and alpha ozosen are other selective alpha-1 antagonists indicated for the treatment of benign prostatic hyperplasia they are more selective for alpha 1a receptors in the prostate and bladder so they decrease tone in the smooth muscle of the bladder neck and prostate improving urine flow with the least effect on blood pressure because
It is less selective for alpha-1b receptors found in the blood vessels alpha-1 blockers such as brazosin and doxazosin may cause dizziness a lack of energy nasal congestion headache drowsiness and orthostatic hypotension but lesser than that observed with phenoxybenzamine and phentolamine they may also cause inhibition of ejaculation and retrograde ejaculation
And the last agent we’ll talk about is a selective competitive alpha 2 blocker it is called yohimbine it is found as a component of the bark of the yohamp tree and has been used as a sexual stimulant and in the treatment of erectile dysfunction it works at the level of the cns to increase sympathetic outflow to the periphery it is contraindicated in cardiovascular
Disease psychiatric conditions and renal dysfunction all of the clinically available beta blockers are competitive antagonists from our previous knowledge we can conclude how they work and what their actions we already know that beta 1 receptors are located in the heart and their activation causes tachycardia and increases cardiac output well their blockade would
Cause bradycardia and decrease cardiac output subsequently decrease blood pressure so of course that would be useful in the treatment of hypertension in contrast to alpha blockers they do not induce postural hypotension because the alpha adrenoceptors remain functional we also know that beta-2 receptors are located in the skeletal muscle’s blood vessels and their
Activation causes vesitilation so their blockade would cause vasoconstriction and increase peripheral resistance they are also located in the lungs and their activation causes bronchitisation so their blockade would cause bronchoconstriction their activation is also responsible for glycogenolysis and glucagon release so their blockade would inhibit glycogenolysis
And glucagon release so we can conclude from the last two points that agents that block beta-2 receptors should not be used for patient with chronic obstructive pulmonary disease or asthma and should be used with caution for diabetic patients there are three main types of beta blockers the non-selective beta blockers that act at both beta 1 and beta 2 receptors
The cardioselective beta antagonists that primarily block beta-1 receptors and antagonists with partial agonist activity take a notice that their names end in the letters alol except for law beta lowell and carvida law let’s discuss the first type the non-selective beta blockers that act at both beta1 and beta2 receptors such as propranolol as we said by blocking
Beta-1 receptors in the heart propranolol diminishes cardiac output having both negative inotropic and chronotropic effects so it is used in the treatment of hypertension in addition workload and oxygen consumption decrease and these effects are useful in the treatment of angina pectoris propranolol and other beta blockers have a protective effect on the myocardium
So it can be used for myocardial infarction as prophylaxis and treatment and blocking beta-2 mediated vicidulation in skeletal muscles increased peripheral vascular resistance in patients with hypertension total peripheral resistance returns to normal or decreases with long-term use of propranolol and as expected blocking beta-2 receptors in the lungs of susceptible
Patients causes bronchoconstriction therefore beta blockers particularly the non-selective ones are contraindicated in patients with chronic obstructive pulmonary disease or asthma as we said beta blockade leads to decreased glycogenolysis and decreased glucagon secretion that means with diabetic patient receiving insulin propranolol would cause pronounced hypoglycemia
After insulin injection and it also masks the normal physiologic response to hypoglycemia such as tachycardia tremors and anxiety which is a really dangerous side effect propranolol is a lipophilic compound so it can penetrate the cns and this allows it to be used prophylactically in reducing migraine episodes migraine will be discussed in details in a separate
Lecture propranolol and other beta blockers are effective in diminishing the widespread sympathetic stimulation that occurs in hyperthyroidism also known as thyrotoxicosis and thyroid storm beta blockers may be life-saving in protecting against serious cardiac arrhythmias its adverse effects include bradycardia and hypotension heart failure in case of inadequate
Myocardial function arrhythmias upon abrupt withdrawal so it should be stopped gradually at a period of at least a few weeks bronchoconstriction due to blocking beta-2 receptors in the lungs augmenting the hypoglycemic effect of insulin as we mentioned before propranolol has numerous cns mediated effects including depression fatigue dizziness and nightmares and it
Also causes sexual impairment and cold extremities the second non-selective beta blocker is not alol it also block beta 1 and beta 2 adrenoceptors and are more potent than propranolol nattolol has a very long duration of action it is available with the brand name core guard and is indicated for the long-term management of angina the third non-selective beta blocker
Is a group that is applied topically in the eye for the treatment of chronic open-angle glaucoma they reduce the production of aqueous humor in the eye temolol bataxolol and cartel cartolol note that bataxolol is a selective beta-1 blocker unlike the cholinergic drugs such as bilocrapene that we discussed before these agents neither affect the ability of the eye
To focus for near vision nor change pupil size but in an acute attack of glaucoma palicropin is still the drug of choice for emergency lowering of intraocular pressure when these agents administered intraocularly the onset is about 30 minutes and the effects last for 12 to 24 hours glaucoma will be discussed in a separate lecture now let’s move to the selective
Beta 1 blockers acebutolol atenolol batoxylol biciprolol esmolol medoprolol and nebivolol they are selective beta-1 antagonists but they still can antagonize beta-2 receptors at high doses so we can conclude that these agents in contrast to propranolol have fewer effects on pulmonary function peripheral resistance and carbohydrate metabolism that were mediated by
Beta2 receptors blockade these drugs lower blood pressure and hypertension and increase exercise tolerance in angina so they are useful in hypertensive patients with impaired pulmonary function and they are also first-line therapy for chronic stable angina nebolol has another mechanism to decrease blood pressure it releases nitric oxide from endothelial cells and
Causes facilitation remember it by in letter of nebivolol and of nitric oxide esmolol has a very short half-life due to metabolism of an ester linkage it is only available intravenously and is used to control blood pressure or heart rhythm during surgery or diagnostic procedures bicyperlole and the extended release formulation of metoprolol are indicated for the
Management of chronic heart failure these agents will be discussed in details in the cvs lectures let’s move to the agents that have antagonists with partial agonist activity or also said to have intrinsic sympathomimetic activity acebutylol which is a beta-1 selective blocker and pindulole which is a non-selective beta blocker are not pure antagonists these partial
Agonists stimulate the beta receptor to which they are bound and they inhibit stimulation by the more potent endogenous catechol amines such as epinephrine and norepinephrine leading to diminished effect on cardiac rate and cardiac output compared to that of beta blockers without intrinsic sympathomimetic activity they are effective in hypertensive patients with
Moderate bradycardia because a further decrease in heart rate is less pronounced with these drugs but they can’t be used for stable angina or arrhythmias due to their partial agonist effect and the last part of this lecture will be about the drugs that block both beta and alpha receptors law beta lowell and carvedilol they are non-selective beta blockers causing
Decrease in the cardiac output and they also have alpha-1 blocking actions causing vesitilation and decreasing peripheral vascular resistance thereby reducing blood pressure if you remember we said that beta blockers produce initial peripheral vasoconstriction so a beta lull and carvedilol are useful in treating hypertensive patients for whom increased peripheral
Vascular resistance is undesirable intravenous law beta lol is also used to treat hypertensive emergencies because it can rapidly lower blood pressure carvedilol as well as meteoprolol and biciprolol are beneficial in patients with stable chronic heart failure they have some adverse effects such as orthostatic hypotension and dizziness that are associated with alpha-1
Blockade the adrenergic neuron blockers are those agents that act by inhibition of the release of catecholamines such as quantity dean the storage of catecholamines such as rezapine the synthesis of catecholamines such as alpha methyl dopa let’s discuss them one by one guayanathi dean is transported across the sympathetic nerve membrane by the same mechanism that
Transports norepinephrine itself so in this step it competes with norepinephrine so it can potentiate exogenously applied norepinephrine once guayanothi dean has entered the nerve it is concentrated in transmitter vesicles where it replaces norepinephrine this leads to a gradual depletion of norepinephrine stores in the nerve endings once inside the terminal
It blocks the release of norepinephrine in response to arrival of an action potential so we can conclude that this agent can be used in the treatment of hypertension rezapine inhibits granular uptake and storage of biogenic amines such as norepinephrine dopamine and serotonin from the cytoplasm into storage vesicles in the adrenergic nerve terminals in all body
Tissues and this causes depletion of biogenic amines so of course the sympathetic function is impaired because of decreased release of norepinephrine it has been used for the management of hypertension but has largely been replaced with newer agents with better side effect profiles and fewer drug interactions and the last one alpha methyl dopa acts by inhibition of
Dopamine carboxylase enzyme which converts dopa into dopamine and as we know dopamine is a precursor for norepinephrine and subsequently epinephrine this inhibition results in reduced dopaminergic and adrenergic neurotransmission in the peripheral nervous system it is converted to alpha methyl norepinephrine by dopamine beta-hydroxylase alpha-methyl norepinephrine
Is an agonist of pre-synaptic central nervous system alpha-2 adrenergic receptors activation of these receptors in the brainstem appears to inhibit sympathetic nervous system output and lower blood pressure it is used in the treatment of hypertension and the most important thing you should know about alpha methyl dopa is that it is one of the preferred treatments
For high blood pressure in pregnancy
Transcribed from video
Pharmacology ANS 4 – Alpha Blockers and Beta Blockers ( Adrenergic Antagonists ) By Medical Videos [ ANIMATED ]
