We are searching data for your request:
Upon completion, a link will appear to access the found materials.
Amiodarone is potassium channel blocker but also voltage-gated Na+ channel blocker according to Pubchem. However, upon reading my notes I discovered
Amiodarone blocks potassium channels and block alpha and beta channels.
I think it must be alpha and beta receptors here, instead of channel. Pubchem proposes that there may beta-blocker-like properties in amiodarone. However, its alpha-like properties are obscure to me as I cannot find any sources. How is amiodarone working as alpha and beta blocker?
Amiodarone inhibits sodium, potassium and calcium currents. Its major antiarrhythmic properties are thought to be related to prolongation of the action potential duration. Amiodarone also exerts an antiadrenergic effect by non competitively inhibiting alpha- and beta-receptors (Ghuran & Camm, 2000).
Alpha blockers relax certain muscles and help small blood vessels remain open by antagonizing norepinephrine's tightening effects on the muscles in the walls of smaller arteries and veins, which improves blood flow and lowers blood pressure (Mayo Clinic). Beta blockers decrease the effects of epinephrine (adrenaline), reducing heart rate and reducing its force, thereby reducing blood pressure. Beta blockers also help blood vessels open up to improve blood flow (Mayo Clinic).
Alpha-adrenergic receptors and Beta-adrenergic receptors are G-protein coupled receptors (Wallukat, 2002). Hence, they do not form channels and your notes are incorrect. The ion currents are mediated by channels, though.
- Ghuran & Camm, J Clin Basic Cardiol (2000); 3: 206
- Wallukat, Herz (2002); 27(7): 683-90
Alpha-Beta Adrenergic Blockers
Alpha-beta adrenergic blockers combine the effects of the alpha blocker medicines and beta-blocker medicines.
Common Names of Alpha-beta Blockers
The following table lists some of the common brand and generic names for alpha-beta blockers.
How Alpha-beta Blockers Work
Alpha-beta blockers belong to a larger class of medicines called adrenergic inhibitors. They combine the effects of two types of medicines. They behave like alpha blocker medicines when they affect special receptor cells in the smooth muscles of your blood vessels. This action stops your cells from receiving chemicals called catecholamines. These chemicals narrow your arteries. This makes your blood pressure go up. When these chemicals are blocked, your blood vessels can relax. This in turn allows your blood to flow more easily, resulting in lower blood pressure.
These medicines act like beta-blockers when they block these same catecholamines in your brain, heart, and blood vessels. The result is that your heart beats more slowly and with less force. Plus, your blood vessels relax and widen so that blood flows through them more easily. Both of these actions make your blood pressure go down.
Precautions and Possible Side Effects
Precautions you should take if you are on alpha-beta blockers:
- Talk with your doctor if you experience faintness or dizziness when you are taking alpha-beta blockers. Blood pressure medicines can occasionally cause dizziness. This is most likely when you change position suddenly. But this may also be caused by other physical or medical problems that have nothing to do with your medicines.
- Do not stop taking this medicine suddenly unless your doctor tells you to stop. Stopping suddenly may bring on the chest pain known as angina. It can also make chest pain worse. Stopping suddenly may even cause a heart attack.
Possible side effects of alpha-beta blockers that you may notice:
- dizziness or faintness
- dry eyes
- slow heart rate
- scalp tingling
- sexual problems
- skin rash
- swelling of feet and legs
- wheezing or shortness of breath in people who have asthma
Possible side effects of alpha-beta blockers that you may not notice: Some people may have problems with the electrical system of their heart. Not everyone who takes an alpha-beta adrenergic blocker will have these side effects. You should not be afraid to take your medicine because of the side effects listed. They are listed so that you can watch out for them and tell your doctor right away if you experience any of them.
Possible Drug Interactions With Alpha-beta Blockers
Before you take an alpha-beta blocker, tell all of your doctors and your pharmacist about all the medicines you take. Include medicines you take for your blood pressure as well as for any other problem. Tell them about everything you take and how much you take each day, including all of the following:
- prescription medicines
- over-the-counter medicines
- vitamin and mineral supplements
It's best to keep an updated list of these and bring a copy to give to your doctor. That way you can add to it whenever you take something new or delete the types you no longer take. Make a copy for each of your doctors so that they can keep it in your file. This complete list helps your doctor be better prepared to prescribe an alpha-beta adrenergic blocker that is the least likely to interact with your other treatments.
The Influence of Beta Blocker Therapy on the Hemodynamic Response to Inotrope Infusion in Patients With Acute Decompensated Heart Failure
Purpose: To compare the hemodynamic effects of dobutamine and milrinone in hospitalized patients who are receiving Beta Blocker Participants: Patients who are admitted to the General Cardiology and Heart Failure Services at the University of North Carolina Hospitals with acute decompensated heart failure, who have maintained steady state concentrations of beta blocker therapy (carvedilol or metoprolol), and who are deemed by the health care team to require pulmonary artery catheter placement and inotropic therapy with dobutamine or milrinone by continuous infusion. Patients that are not currently receiving beta blocker therapy will be enrolled for comparative purposes however, any patient not at steady state (on or off beta blocker therapy) will not be enrolled.
Procedures: After obtaining informed consent, patients will be assigned to the appropriate sub-study group based on beta blocker use (Study A: patients on stable doses of metoprolol and Study B: patients on stable doses of carvedilol). All patients should receive dobutamine followed by milrinone as outlined in the dosing algorithm (see inotrope dosing algorithm attached, as part of the usual standard of practice). Baseline pulmonary artery catheter hemodynamic parameters will be collected prior to administration of inotrope trial of dobutamine followed by milrinone. Hemodynamic parameters will be recorded per the dosing algorithm following initiation and dose titration. Dose titration will be determined by the health care team based upon patient response or lack thereof and tolerability. Changes in hemodynamic parameters in response to dobutamine or milrinone will be compared within study groups. Additionally, data will continue to be collected on patients receiving not beta blocker therapy for comparative purpose.
First-line management of chronic heart failure includes beta blockers and angiotensin converting enzyme (ACE) inhibitors, as these agents have been shown to have significant benefits on morbidity and mortality in large clinical trials. Therefore, a substantial number of patients with chronic heart failure are receiving chronic beta blocker therapy, most commonly metoprolol succinate and carvedilol. However, despite significant advancements in the treatment of chronic heart failure, the natural history of the disease remains progressive and many patients develop acute decompensations requiring hospitalization. In the setting of acute decompensated heart failure, the use of inotropic agents may be required for hemodynamic support. The two most widely used inotropes are dobutamine and milrinone. Dobutamine primarily acts as a beta-1 receptor agonist with some effects on beta-2 and alpha-1 receptors. Milrinone is a phosphodiesterase III inhibitor, thus inhibiting the breakdown of cyclic adenosine monophosphate. As such, milrinone works at a site that is distal to beta receptors and may be less influenced by chronic beta blocker therapy. As such, one may speculate that the presence of a beta blocker would influence the hemodynamic response to dobutamine, but to a much lesser extent to milrinone, if at all.
Two small studies have assessed the hemodynamic response to dobutamine in the presence and absence of beta blocker therapy in patients with chronic heart failure. In addition, one of these studies assessed the response to enoximone, another phosphodiesterase III inhibitor. Both studies demonstrated that metoprolol did not significantly affect the hemodynamic response to dobutamine infusion, including its effect on cardiac index, heart rate, stroke volume, and systemic vascular resistance. Conversely, carvedilol was shown to have significant inhibitory effects on cardiac index, heart rate, and stroke volume during dobutamine infusion. In addition, carvedilol appeared to increase mean arterial pressure at higher doses of dobutamine. In the setting of an enoximone infusion, metoprolol increased the cardiac index and stroke volume responses, while maintaining other hemodynamic parameters. There was no significant difference in the hemodynamic response to enoximone infusion in the presence of carvedilol.
Published studies that assessed the hemodynamic response to inotropes in the presence and absence of beta blockers included less than 50 patients combined. As such, the replication of their results is warranted in order to use this data to drive changes in clinical practice. Additionally, and equally as important, no study has been published, to the best of our knowledge, which has assessed the hemodynamic response to milrinone in the presence of metoprolol. . Although enoximone is a phosphodiesterase III inhibitor and is theoretically similar to milrinone, it is not approved for use in the United States, thus making it difficult to extrapolate these findings to milrinone. Lastly, the severity of illness in patients included in current literature does not reflect individuals who will receive the most benefit from therapy i.e. patients with acute decompensated heart failure.
|Study Type :||Observational|
|Actual Enrollment :||50 participants|
|Official Title:||The Influence of Beta Blocker Therapy on the Hemodynamic Response to Inotrope Infusion in Patients With Acute Decompensated Heart Failure|
|Study Start Date :||December 2010|
|Actual Primary Completion Date :||September 2017|
|Actual Study Completion Date :||October 2018|
Adrenoceptors: Alpha- and Beta-Receptors
- Location: at the gastrointestinal tract and bladder sphincter, vascular smooth muscles of skin and splanchnic regions, and radial muscle of iris
- Function: generally produce smooth muscle constriction
- Mechanism of action: act via stimulation of IP3/Ca3+
- Present in presynaptic nerve terminals, platelets, fat cells, and the wall of the gastrointestinal tract
- Function: generally produce relaxation/dilation
- Mechanism of action: act via inhibition of adenylate cyclase and decreasing the concentration of cAMP (cyclic adenosine monophosphate)
- Location: sinoatrial node, atrioventricular node, atrial and ventricular muscle, His-Purkinje system, and kidney
- Mechanism of action: act via stimulation of adenylate cyclase and thereby increasing the concentration of cAMP (cyclic adenosine monophosphate)
- Location: smooth vessels of skeletal muscle, blood vessels , gastrointestinal tract, uterus, liver , and urinary tract
- Mechanism of action: act via stimulation of adenylate cyclase and increasing the concentration of cAMP
Effect of Adrenoceptors on Organ Systems
Understanding the action of alpha- and beta-receptors on various organ systems will aid in remembering the effect of alpha- and beta-blockers on those organ systems because they have opposite actions to the alpha-/beta-agonists.
|Eyes||Contraction (mydriasis) of the iris dilator muscle|
|Bladder||Constriction of bladder sphincter|
Control of micturition and urine flow
α-blockers are used to treat benign prostatic hyperplasia (BPH) induced urinary obstructions because they cause relaxation of the bladder muscles (the opposite actions to the alpha agonists).
High blood pressure (hypertension) is a disease in which pressure within the arteries of the body is elevated. About 75 million people in the US have hypertension (1 in 3 adults), and only half of them are able to manage it. Many people do not know that they have high blood pressure because it often has no has no warning signs or symptoms. Systolic and diastolic are the two readings in which blood pressure is measured. The American College of Cardiology released new guidelines for high blood pressure in 2017. The guidelines now state that blood normal blood pressure is 120/80 mmHg. If either one of those numbers is higher, you have high blood pressure. The American Academy of Cardiology defines high blood pressure slightly differently. The AAC considers 130/80 mm Hg. or greater (either number) stage 1 hypertension. Stage 2 hypertension is considered 140/90 mm Hg. or greater. If you have high blood pressure you are at risk of developing life threatening diseases like stroke and heart attack.REFERENCE: CDC. High Blood Pressure. Updated: Nov 13, 2017.
Anxiety is a feeling of apprehension and fear characterized by symptoms such as trouble concentrating, headaches, sleep problems, and irritability. Anxiety disorders are serious medical illnesses that affect approximately 19 million American adults. Treatment for anxiety may incorporate medications and psychotherapy.
Difference Between Alpha and Beta Blockers
Alpha and beta blockers are drugs or medications that are used for the treatment of hypertension, blood pressure, and other related symptoms. Both these types of drugs work to allow smooth flow of blood in veins inside our bodies, thus helping to lower the blood pressure. However, despite their same objective, alpha and beta blockers have many differences that will be harped upon in this article.
The smooth muscles of peripheral arteries throughout our bodies contain alpha as well as beta receptors. Together, they make up what is called sympathetic nervous system. The basic difference between these two types of receptors is that while alpha receptors work to constrict or narrow down the peripheral arteries, beta work in just the opposite manner as they serve to widen these arteries.
Alpha blockers work to soothe and calm the muscles. They help in smooth flow of blood by opening the blood vessels. Working of beta blocker drugs is totally different. Instead of having an effect on the muscles, they work to lower the heart rate of a person. Lowering of heart rate has the effect of a corresponding lowering off blood pressure. It is clear then that alpha and beta blockers achieve the same objective through different routes.
Of late, research on the working of alpha blockers has suggested that though these drugs lower blood pressure, they actually tend to increase the risk of heart attacks and strokes. This has led to doctors first trying beta blockers and using alpha blockers either in conjunction with them or alone only as a last resort.
Beta blockers work to stop epinephrine and norepinephrine from attaching to beta receptors found all over our bodies. There are three types of beta receptors called beta 1, beta 2, and beta 3. Beta blocker drugs work on beta 1 and beta 2 receptors but have no effect on beta 3 receptors found mainly in fat cells.
Beta blockers have many more purposes than alpha blockers as they have been found to be useful in many ailments such as abnormal heart rate, heart failure, high blood pressure, angina, tremors and migraines. They are used to prevent further heart attacks after a person has suffered an attack.
Alpha blocker vs Beta blocker
• Alpha and beta blockers are drugs that are so named because of their effect on alpha and beta receptors found inside our bodies.
• While both types of blockers help in lowering blood pressure, they work differently
• While alpha blockers work to relax smooth muscles to allow uninterrupted flow of blood in the vessels, beta blockers work to lower the heart rate of a person which translates into reduction of blood pressure
• Doctors are of the view that alpha blockers should not be used alone as they tend to increase the risk of heart attacks.
Why Are There Different Classes of Antiarrhythmic Drugs?
Each class of antiarrhythmic drugs has different “selective affinities” for different cardiac ion channels and/or adrenergic receptors.
Note that the drugs in each class are only “selective” for blocking each ion channel or receptor subtype, and frequently affect more than one channel or receptor. In particular, there is heterogeneity within the Class I drugs with regards to their selectivity of effect on blocking Na channels vs K channels. These differences resulted in their grouping by Vaughn-Williams into Class 1a, 1b & 1c subclasses based upon their in vitro effects on the ventricular action potential upstroke velocity (dV/dt-max) and action potential duration (APD) observed under normal physiological conditions. These in vitro effects result in corresponding effects on the QRS and QT durations in vivo:
Figure 1. The effect of the subtypes of Class I drugs on the cardiac action potential & ECG intervals in the normal heart in sinus rhythm. Drug effects on the action potential upstroke and conduction parameters in ischemic tissue, and/or at high heart rates is typically more significant.
TABLE 2: Class 1 Subclasses
|Ia||↑||↑||Na & Kr||Large block of both open Na & K Channels at normal heart rates, hence both QRS & QT affected|
|Ib||→||→↓||Na||High affinity for open & inactivated Na channels with rapid unbinding during diastole, hence little cumulative effect on QRS in NSR also blocks the small Na plateau current which shortens the APD|
|Ic||↑↑||→||Na||Large block of open Na channels & very slow unbinding during diastole, QRS markedly prolonged during NSR|
Class Ia drugs are those which prolong both the QRS and QT of the normal heart. These drugs prolong the QT and cellular APD because they block the rapid potassium current (IKr) at therapeutic concentrations. In addition, these drugs also block cardiac Na channels in the open state, and then dissociate slowly & incompletely during diastolic intervals in-between beats. Hence block accumulates with each successive beat, resulting in enough Na channel block at normal sinus rates to significantly widen the QRS.
Class Ib drugs are those which have little effect on the QRS of normal heart hearts at normal heart rates , and slightly shorten the QT . These drugs interact with sodium channels in both the open and inactivated state, but because the time that Na channels spend in the open state is so brief (
1 msec) under normal conditions, and because Na channels remain inactivated for several hundred milliseconds during each action potential, the contribution of drug interaction with inactivated channels is much greater than with open channels (Matsubara et al, 1987 Clarkson et al., 1988). Because most drug binding occurs after the upstroke, when Na channels are inactivated, and these drugs rapidly unbind at normal diastolic potentials, there is little residual Na channel block by the time of the next action potential at normal heart rates (see below). (However, block can accumulate at very high heart rates, when the diastolic interval is short, or when the diastolic membrane potential becomes significantly depolarized, as this slows the rate of drug dissociation from Na channels)(Hume & Grant, 2012). In addition, because most of the interaction of class Ib drugs occurs during the plateau, they have very little effect on tissue with short action potential durations, such as atrial tissue. In addition, atrial tissue is unlikely to become ischemic (due to differences in wall thickness & vessel physiology). As a result, Class Ib drugs are ineffective in treating atrial tachy-arrhythmias at non-toxic concentration . The slight reduction of the QT by Class Ib drugs results from their effect to block the small residual “plateau” Na current (resulting from a small number of Na channels that do not fully inactivate during the action potential plateau). Reduction of this inward current, while not affecting outward K currents results in a shortening of the ventricular action potential duration (and QT interval).
Point of View: Shortening of the APD & QT by Class Ib drugs is not Therapeutically Relevant
Class Ic drugs are those which have a very large effect to prolong the QRS of normal hearts at normal heart rates, with little effect on the QT. These drugs are very potent blockers of open Na channels and dissociate very slowly and incompletely from Na channels in-between heart beats (e.g. having dissociation time constants of many seconds).
Further Comments on Drug Selectivity
With regards to “selectivity”, some Class IV drugs (e.g. verapamil) also block cardiac Na channels to some extent at therapeutic doses, and some Class Ia drugs (e.g. quinidine) also dose-dependently block a percentage of L-type Ca channels at therapeutic levels. In addition, Class Ia drugs have antimuscarinic (or vagolytic) actions as well. These drugs are not highly specific “silver bullets” for each target, due in part to the high degree of sequence homologies between the multiple ion channels involved.
Inappropriate Sinus Tachycardia
The incidence of inappropriate sinus tachycardia (IST) in patients with COVID-19 is uncertain. By definition, IST is a diagnosis of exclusion. Therefore, it is very unlikely to be diagnosed in the setting of acute infection as patients with hypoxemia may be in sinus tachycardia. Persistent tachycardia after infection may represent as IST and has been shown in patients recovering from SARS, suggesting it may be seen in patients recovering from COVID-19 as well [44, 45]. The mechanism of IST is likely multifactorial including intrinsic sinus node hyperactivity, autonomic dysfunction, and a hyperadrenergic state [46•]. Inflammatory cytokines released by patients with COVID-19 may affect the function of myocardial ion channels and perpetuate tachyarrhythmia including sinus tachycardia . Ongoing symptomatic IST may be treated with beta-blockers and/or ivabradine (Table (Table2 2 ) , although treatment efficacy is unknown in patients with COVID-19. It is of note that ivabradine usage in IST is not FDA approved and is off label.
Azilsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II at tissue receptor sites. It may induce more complete inhibition of the renin-angiotensin system than ACE inhibitors, and it does not affect the response to bradykinin (less likely to be associated with cough and angioedema).
Inotropic agents such as milrinone, digoxin, dopamine, and dobutamine are used to increase the force of cardiac contractions. Intravenous positive inotropic agents should only be used in inpatient settings — and then only in patients who manifest signs and symptoms of low cardiac output syndrome (volume overload with evidence of organ hypoperfusion).
How Do Beta-adrenergic Antagonists Work
The term ‘mechanism of action’ is used with reference to the specific biochemical interaction that helps a drug produce its pharmacological effect. Beta-adrenergic blocking agents work by blocking the beta-receptors, thereby preventing epinephrine and norepinephrine from binding to these beta receptors. Given below is some information on the ways in which these drugs help in the treatment of certain diseases.
The specific biochemical interaction of these drugs in hypertension is not very clear, but it is believed that blood pressure is lowered due to lowering of the cardiac output. In many cases, it has been observed that an increased blood volume and cardiac output raises the blood pressure. The effect of these drugs in the treatment of hypertension is attributed to a reduced cardiac output. Dilation of small arteries or blood vessels due to use of these drugs may also have an effect on blood pressure. It is also believed that these drugs affect the production of renin, thereby lowering the production of angiotensin-II, which is a substance that constricts the blood vessels. This causes an increase in blood pressure.
Cardioselective beta blockers have long been used for treating heart problems such as cardiac arrhythmia, angina, increased heart rate, and heart failure. The pharmacological effect of these drugs on people affected by angina, heart failure, or arrhythmia is again associated with the inability of norepinephrine and epinephrine to bind themselves to the beta-1 and beta-2 receptors present in the heart and blood vessels respectively. The use of these drugs limits the physiologic responses that exercise, stress, or such situations can have on the heart rate and force of contraction. Since the use of these drugs lowers the cardiac output or the amount of blood heart pumps out, the symptoms associated with these heart conditions are alleviated to a great extent. The lowering of the heart rate, force of contraction, and arterial pressure improves the cardiac function, which in turn reduces the possibility of a heart attack.
Glaucoma is an eye condition that occurs when the intraocular pressure, which is the pressure exerted by the fluids in the eyeball, increases. This increase in eye pressure can cause damage to the optic nerve. This could give rise to blindness. To prevent a slow progression towards loss of vision, it is essential that the intraocular pressure be restored to normal. The stimulation of beta-2 receptors in the eyes can cause an increase in aqueous humor. Beta-adrenergic antagonists can prevent this response and help in decreasing production of aqueous humor, which in turn helps in stabilizing the intraocular pressure.
Beta blockers compete with epinephrine and norepinephrine for the receptor sites and prevent them from binding to these sites. Thus, all the physiological responses that result from the stimulation of receptors can be prevented. Besides the aforementioned medical conditions, these drugs are also being used for the treatment of migraine and anxiety.
The accelerated heart rate that is experienced due to nervousness and fear can be tackled with the use of these drugs. This is why performers who wish to prevent stage fright from affecting their performance might be recommended the use of these drugs. Though these drugs can help in alleviating the symptoms of serious diseases, one must watch out for side effects. These must always be taken under medical supervision.
Disclaimer: The information provided in this article is solely for educating the reader. It is not intended to be a substitute for the advice of a medical expert.