Propranolol
Propranolol (INN) is a non-selective beta blocker mainly used in the treatment ofhypertension. It was the first successful beta blocker developed. Propranolol is available in generic form as propranolol hydrochloride, as well as an AstraZeneca and Wyethproduct under the trade names Inderal, Inderal LA, Avlocardyl (also available in prolonged absorption form named "Avlocardyl Retard"), Deralin, Dociton, Inderalici, InnoPran XL, Sumial, Anaprilinum (depending on marketplace and release rate), Bedranol SR (Sandoz).
Propranolol is one of the banned substances in the Olympics, presumably for its use in controlling stage fright and tremors. It was taken by Kim Jong Su, a North Korean pistol shooter who won two medals at the 2008 Olympic Games. He was the first Olympic shooter to be disqualified for drug use.
Indications
Propranolol is indicated for the management of various conditions including:
§ Control of tachycardia/tremor associated with anxiety, hyperthyroidism or lithium therapy.
§ Migraine prophylaxis
§ Cluster headaches prophylaxis
§ Tension headache (Off the label use)
§ Shaky hands
§ There has been some experimentation in psychiatric areas:
§ Treating the excessive drinking of fluids in psychogenic polydipsia,
§ Antipsychotic-induced akathisia,
§ Aggressive behavior of patients with brain injuries
§ Glaucoma
§ Primary exertional headache
While once first-line treatment for hypertension, the role for beta-blockers was downgraded in June 2006 in the United Kingdom to fourth-line as they perform less well than other drugs, particularly in the elderly, and evidence is increasing that the most frequently used beta-blockers at usual doses carry an unacceptable risk of provoking type 2 diabetes.
Propranolol is also used to lower portal vein pressure in portal hypertension and prevent esophageal variceal bleeding.
Off-label and investigational use
Propranolol is often used by musicians and other performers to prevent stage fright. It has been taken by surgeons to reduce their own innatehand tremors during surgery.
Propranolol is currently being investigated as a potential treatment for post-traumatic stress disorder. Propranolol works to inhibit the actions of norepinephrine, a neurotransmitter that enhances memory consolidation. Studies have shown that individuals given propranolol immediately after a traumatic experience show less severe symptoms of PTSD compared to their respective control groups that did not receive the drug (Vaiva et al., 2003). Propranolol reduces the effects of nightmare-related cardiac activity by keeping sinus rhythm low during nightmares, as a higher pulse and increased adrenaline are associated with severe nightmares. However, results remain inconclusive as to the success of propranolol in treatment of PTSD, including nightmares experienced by those with PTSD.
Propranolol in combination with etodolac is currently being investigated in a Phase 3 trial of 400 colorectal cancer patients as a potential treatment for prevention of colorectal cancer recurrence. The aim of this study is to assess the use of perioperative medical intervention using a combination of a propranolol and etodolac in order to attenuate the surgically induced immunosuppression and other physiological perturbations, aiming to reduce the rate of tumor recurrence and distant metastatic disease.
Recent evidence (June 2008) suggests that propranolol can be used to treat severe infantile hemangiomas (IHs).[ This treatment has proven superior to corticosteroids, as propranolol has fewer side effects and is more effective when treating IHs.
Propranolol was investigated for possible effects on resting energy expenditure and muscle catabolism in patients with severe burns.[In children with burns, treatment with propranolol during hospitalization attenuated hypermetabolism and reversed muscle wasting.
Propranolol along with a number of other membrane-acting drugs have been investigated for possible effects on Plasmodium falciparum and so the treatment of malaria. In vitro positive effects until recently had not been matched by useful in vivo anti-parasite activity against P. vinckei,or P. yoelii nigeriensis. However a single study from 2006 has suggested that propranolol may reduce the dosages required for existing drugs to be effective against P. falciparum by 5- to 10-fold, suggesting a role for combination therapies.[18]
Precautions and contradications
Propranolol should be used with caution in patients with:
§ Diabetes mellitus or hyperthyroidism, since signs and symptoms of hypoglycaemia may be masked.
§ Peripheral vascular disease and Raynaud's syndrome, which may be exacerbated
§ Phaeochromocytoma, as hypertension may be aggravated without prior alpha blocker therapy
§ Myasthenia gravis, may be worsened
§ Other drugs with bradycardic effects
Propranolol is contraindicated in patients with:
§ Reversible airways disease, particularly asthma or chronic obstructive pulmonary disease (COPD)
§ Bradycardia (<60 beats/minute)
§ Atrioventricular block (second or third degree)
§ Shock
§ Severe hypotension
§ Cocaine toxicity [per American Heart Association guidelines, 2005]
Adverse effects
Adverse drug reactions (ADRs) associated with propranolol therapy are similar to other lipophilic beta blockers (see beta blocker).
Pregnancy and lactation
Propranolol, like other beta blockers, is classified as Pregnancy category C in the United States and ADEC Category C in Australia
Most beta-blocking agents appear in the milk of lactating women. This is especially the case for a lipophilic drug like propranolol. Breastfeeding is not recommended in patients receiving propranolol therapy
Pharmacokinetics
Propranolol is rapidly and completely absorbed, with peak plasma levels achieved approximately 1–3 hours after ingestion. Co-administration with food appears to enhance bioavailability. Despite complete absorption, propranolol has a variable bioavailability due to extensive first-pass metabolism. Hepatic impairment will therefore increase its bioavailability. The main metabolite 4-hydroxypropranolol, with a longer half-life(5.2–7.5 hours) than the parent compound (3–4 hours), is also pharmacologically active.
Propranolol is a highly lipophilic drug achieving high concentrations in the brain. The duration of action of a single oral dose is longer than the half-life and may be up to 12 hours, if the single dose is high enough (e.g., 80 mg). Effective plasma concentrations are between 10–100 ng/mL.
Toxic levels are associated with plasma concentrations above 2000 ng/ml.
Mechanism of action
Propranolol is a non-selective beta blocker, that is, it blocks the action of epinephrine and norepinephrine on both β1- and β2-adrenergic receptors. It has little intrinsic sympathomimetic activity (ISA) but has strong membrane stabilizing activity (only at high blood concentrations, e.g. overdosage). Research has also shown that propranolol has inhibitory effects on the norepinephrine transporter and/or stimulates norepinephrine release (present experiments have shown that the concentration of norepinephrine is increased in the synapse but do not have the ability to discern which effect is taking place). Since propranolol blocks β-adrenoceptors, the increase in synaptic norepinephrine only results in α-adrenergic activation, with the α1-adrenoceptor being particularly important for effects observed in animal models. Therefore, some have suggested that it be looked upon as an indirect α1 agonist as well as a β antagonist. Probably owing to the effect at the α1-adrenoceptor, the racemate and the individual enantiomers of propranolol have been shown to substitute for cocaine in rats, with the most potent enantiomer being S-(–)-propranolol. In addition, some evidence suggests that propranolol may function as a partial agonist at one or more serotonin receptors (possibly 5-HT1B).
Both enantiomers of the drug have a local anesthetic (topical) effect, which is normally mediated by blockade of voltage-gated sodium channels. Few studies have demonstrated propranolol's ability to block cardiac, neuronal, and skeletal voltage-gated sodium channels, accounting for its known “membrane stabilizing effect” and anti-arrhythmic and other central nervous system effects.
Interactions
Beta blockers, including propranolol, have an additive effect with other drugs which decrease blood pressure, or which decrease cardiac contractility or conductivity. Clinically-significant interactions particularly occur with:
§ Fluvoxamine slows down the metabolism of propranolol significantly leading to increased blood levels of propranolol.
Dosage
The usual maintenance dose ranges for oral propranolol therapy vary by indication:
§ Hypertension, angina, essential tremor
§ 120–320 mg daily in divided doses
§ Sustained-release formulations are available in some markets.
§ Migraine Prophylaxis
§ The initial dose is 80 mg Inderal daily in divided doses. The usual effective dose range is 160 mg to 240 mg per day.
§ The dosage may be increased gradually to achieve optimum migraine prophylaxis. If a satisfactory response is not obtained within four to six weeks after reaching the maximum dose, Inderal therapy should be discontinued.
§ Tachyarrhythmia, anxiety (GAD), hyperthyroidism
§ 10–40 mg 3–4 times daily
§ Performance anxiety
§ 5–10 mg 30min or 1.5hrs before and after performance, optionally 5–10 mg night before. Up to 40 mg if necessary, but side-effects may present.
Intravenous (IV) propranolol may be used in acute arrhythmia or thyrotoxic crisis.
Chemistry
Propranolol, 1-(iso-propylamino)-3-(1-naphthyloxy)-2-propanol, is synthesized in two ways from the same initial substance. The first way consists of reacting 1-naphthol with epichlorohydrin. Opening of the epoxide ring gives 1-chloro-3-(1-naphthyloxy)-2-propanol, which is reacted further with iso-propylamine, giving propranolol. The second method uses the same reagents in the presence of a base and consists of initially making 3-(1-naphthyloxy)propylenoxide, the subsequent reaction with isopropylamine which results in epoxide ring opening leading to the formation of propranolol.
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Sotalol
USES: This medication is used to treat a serious (possibly life-threatening) type of fast heartbeat called sustained ventricular tachycardia. It is also used to treat certain fast/irregular heartbeats (atrial fibrillation/flutter) in patients with severe symptoms such as weakness and shortness of breath. Sotalol helps to lessen these symptoms. It slows the heart rate and helps the heart to beat more normally and regularly. This medication is both a beta blocker and an anti-arrhythmic.
HOW TO USE: See also Warning section.Read the Patient Information Leaflet (provided by your pharmacist for some sotalol products used to treat atrial fibrillation/flutter) before you start using sotalol and each time you get a refill. If you have any questions, consult your doctor or pharmacist.Take this medication by mouth, usually twice a day or as directed by your doctor. You may take it with or without food, but it is important to choose one way and take it the same way with each dose.Dosage is based on your medical condition and response to treatment. In children, dosage is also based on age, height, and weight.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.If you use antacids (such as products containing aluminum, magnesium, calcium), do not take them at the same time as sotalol. Antacids can bind to sotalol and decrease its absorption and effectiveness. Separate doses of antacids and sotalol by at least 2 hours to reduce this interaction.Do not take more of this drug than prescribed because you may increase your risk of side effects, including a new serious abnormal heartbeat. Do not take less of this medication or skip doses unless directed by your doctor. Your fast/irregular heartbeat is more likely to return if you do not take sotalol properly. Also, do not run out of this medication. Order your refills several days early to avoid running out of pills.Tell your doctor if your condition does not improve or if it worsens.
SIDE EFFECTS: See also Warning section.Tiredness, slow heartbeat, anddizziness may occur. Less common side effects include headache, diarrhea, and decreased sexual ability. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.To lower your risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor immediately if any of these unlikely but serious side effects occur: new or worsening symptoms of heart failure (such as swelling ankles/feet, severe tiredness, shortness of breath, unexplained/sudden weight gain).Seek immediate medical attention if any of these unlikely but serious side effects occur: severe dizziness, fainting, sudden change in heartbeat (unusually faster/slower/more irregular), chest/jaw/left arm pain.A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects.
PRECAUTIONS: See also Warning section.Before taking sotalol, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: certain heart rhythm problems (such as a slow heartbeat, second- or third-degree atrioventricular block unless you have a heart pacemaker), severe heart failure, breathing problems (such as asthma, chronic bronchitis, emphysema).Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney problems, treated stable heart failure, very recent heart attack (within 2 weeks), other irregular heartbeat problems (such as sick sinus syndrome), overactive thyroid disease(hyperthyroidism), serious allergic reactions needing treatment with epinephrine.Sotalol may cause a condition that affects the heart rhythm (QT prolongation in the EKG). QT prolongation can infrequently result in serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that require immediate medical attention. The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may affect the heart rhythm (see also Drug Interactions section). Before using sotalol, tell your doctor or pharmacist if you have any of the following conditions: certain heart problems (QT prolongation in the EKG, history of torsade de pointes), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills"), if you are unable to eat or drink fluids as you normally would, or if you have conditions such as severe/prolonged sweating, diarrhea, or vomiting. Talk to your doctor about using sotalol safely.If you havediabetes, this product may prevent the fast/pounding heartbeat you would usually feel when your blood sugar level falls too low (hypoglycemia). Other symptoms of a low blood sugar level, such as dizziness and sweating, are unaffected by this drug. This product may also make it harder to control your blood sugar levels. Check your blood sugar levels regularly as directed by your doctor. Tell your doctor immediately if you have symptoms of high blood sugar such as increased thirst/urination. Your diabetes medication or diet may need to be adjusted.Before having surgery, tell your doctor or dentist that you are taking this medication.This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.Kidney function declines as you grow older. This medication is removed by the kidneys. Therefore, older adults may be more sensitive to the side effects of this drug, including dizziness and tiredness.During pregnancy, this medication should be used only when clearly needed. It may harm an unborn baby. Discuss the risks and benefits with your doctor.This medication passes into breast milk and may have undesirable effects on a nursing infant. Discuss the risks and benefits with your doctor before breast-feeding.
DRUG INTERACTIONS: See also How to Use and Precautions sections.Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.Many drugs besides sotalol may affect the heart rhythm (QT prolongation in the EKG), includingamiodarone, dofetilide, jpimozide, procainamide, quinidine, macrolide antibiotics (such as erythromycin), among others.Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use.Check the labels on all your medicines (such as cough-and-cold products,allergy products, diet aids) because they may contain ingredients that could increase your heart rate. Check with your doctor or pharmacist first before taking any other medications.This medication may interfere with certain medical/laboratory tests, possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.
OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada
NOTES: Do not share this medication with others.Laboratory and/or medical tests (such as EKG, kidney function tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.
MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.
Acebutolol
Pharmacology
Acebutolol is a cardioselective beta blocker with ISA (Intrinsic Sympathomimetic Activity, see article on Pindolol). It is therefore more suitable than non cardioselective beta blockers, if a patient with Asthma or chronic obstructive pulmonary disease (COPD) needs treatment with a beta blocker. In doses lower than 800mg daily its constricting effects on the bronchial system and smooth muscle vessels are only 10% to 30% of those observed under Propranololtreatment, but there is experimental evidence that the cardioselective properties diminish at doses of 800mg/day or more.
The drug has lipophilic properties, and therefore crosses the Blood-Brain Barrier. Acebutolol has no negative impact on serum lipids (cholesterol and triglycerides). No HDL decrease has been observed. In this regard, it is unlike many other beta blockers which have this unfavourable property.
The drug works in hypertensive patients with high, normal, or low renin plasma concentrations, although acebutolol may be more efficient in patients with high or normal renin plasma concentrations. In clinically relevant concentrations, a membrane-stabilizing effect does not appear to play an important role.
Pharmacokinetics
Acebutolol is well absorbed from the GI tract, but undergoes substantial first-pass-metabolization, leading to a bioavailability of only 35% to 50%. Peak plasma levels of acebutolol are reached within 2 to 2.5 hours after oral dosing. Peak levels of the main active metabolite, diacetolol, are reached after 4 hours. Acebutolol has a halflife of 3 to 4 hours, and diacetolol a halflife of 8 to 13 hours.
Acebutolol undergoes extensive hepatic metabolization resulting in the desbutyl amine acetolol which is readily converted into diacetolol. Diacetolol is as active as acebutolol (equipotency) and appears to have the same pharmacologic profile. Geriatric patients tend to have higher peak plasma levels of both acebutolol and diacetolol and a slightly prolonged excretion. Excretion is substantially prolonged in patients with renal impairment, and so a dose reduction may be needed. Liver cirrhosis does not seem to alter the pharmacokinetic profile of the parent drug and metabolite.
Indications
§ ventricular and atrial cardiac arrhythmia
§ acute myocardial infarction in high-risk patients
§ Stable or Unstable Angina (due to its partial agonist or ISA activity)
Contraindications and Precautions
Acebutolol may not be suitable in patients with Asthma bronchiale or COPD due to its bronchoconstricting (β2 antagonistic) effects.
Side effects
The development of anti-nuclear antibodies (ANA) has been found in 10 to 30% of patients under treatment with acebutolol. A systemic disease with arthralgic pain and myalgias has been observed in 1%. A lupus erythematosus-like syndrome with skin rash and multiforme organ involvement is even less frequent. The incidence of both ANA and symptomatic disease under acebutolol is higher than underPropranolol. Female patients are more likely to develop these symptoms than male patients. Some few cases of hepatotoxicity with increased liver enzymes (ALT, AST) have been seen. Altogether, 5 to 6% of all patients treated have to discontinue acebutolol due to intolerable side effects. When possible, the treatment should be discontinued gradually in order to avoid a withdrawal syndrome with increased frequency of angina and even precipitation of myocardial infarction.
Dosage
The daily dose is 200mg - 1,200mg in a single dose or in 2 divided doses as dictated by the severity of the condition to be treated. Treatment should be initiated with low doses, and the dose should be increased cautiously according to the response of the patient. Acebutolol is particularly suitable for antihypertensive combination treatment with diuretics, if acebutolol alone proves insufficient. In some countries injectable forms for i.v.-injection with 25mg acebutolol exist, but these are only for cases of emergency under strict clinical monitoring. The initial dose is 12.5 to 25mg, but additional doses may be increased to 75 to 100mg, if needed. If further treatment is required, it should be oral.
Metoprolol
Metoprolol is a selective β1 receptor blocker used in treatment of several diseases of the cardiovascular system, especially hypertension. The active substance metoprolol is employed either as metoprolol succinate or metoprolol tartrate (where 100 mg metoprolol tartrate corresponds to 95 mg metoprolol succinate), respectively as prolonged-release or conventional-release formulation.
Physical properties
Metoprolol has a very low melting point, around 45 °C. Because of this metoprolol is always manufactured in a salt-based solution, as drugs with melting points below 100 °C are difficult to work with in a manufacturing environment. The free base exists as a waxy white solid, and the tartrate salt is finer crystalline material.(Metox-Wockhardt)
Pharmacology
§ Selective
§ Moderately lipophilic
§ Without intrinsic sympathomimetic activity (ISA)
§ With weak membrane stabilizing activity
§ Short half-life, therefore must be taken at least twice daily or as a slow-release preparation
§ Decreases heart rate, contractility and cardiac output, therefore decreasing blood pressure
§ Metabolized in the liver to inactive metabolite
Indications
§ Coronary heart disease (prevention of angina attacks)
§ Secondary prevention after a myocardial infarction
§ Treatment of heart failure.[1]
§ Adjunct in treatment of hyperthyroidism
§ Long QT syndrome, especially for patients with asthma, as metoprolol's β1 selectivity tends to interfere less with asthma drugs which are often β2-adrenergic receptor-agonist drugs
Due to its selectivity in blocking the beta1 receptors in the heart, metoprolol is also prescribed for off-label use in performance anxiety, social anxiety disorder, and other anxiety disorders.
Precautions
Metoprolol may worsen the symptoms of heart failure in some patients. Check with your doctor right away if you are having chest pain or discomfort; dilated neck veins; extreme fatigue; irregular breathing; an irregular heartbeat; shortness of breath; swelling of the face, fingers, feet, or lower legs; weight gain; or wheezing.[
This medicine may cause changes in your blood sugar levels. Also, this medicine may cover up signs of low blood sugar, such as a rapid pulse rate. Check with your doctor if you have these problems or if you notice a change in the results of your blood or urine sugar tests.
This medicine may cause some people to become less alert than they are normally. If this side effect occurs, do not drive, use machines, or do anything else that could be dangerous if you are not alert while taking metoprolol .
Side effects
Transient effects include dizziness, drowsiness, fatigue, diarrhea, unusual dreams, ataxia, trouble sleeping, depression, and vision problems. It may also reduce blood flow to the hands and feet, causing them to feel numb and cold; smoking may worsen this effect.
Serious side effects which are advised to be reported immediately include, but are not limited to, symptoms of bradycardia (a very slow heartbeat (less than 50 bpm)), persistent symptoms of dizziness, fainting and unusual fatigue, bluish discoloration of the fingers and toes, numbness/tingling/swelling of the hands or feet, sexual dysfunction, erectile dysfunction (impotence), hair loss, mental/mood changes, depression, trouble breathing, cough, dyslipidemia, and increased thirst. Other highly unlikely symptoms include easy bruising or bleeding, persistent sore throat or fever, yellowing skin or eyes, stomach pain, dark urine, and persistent nausea. Symptoms of an allergic reaction include: rash, itching, swelling, and severe dizziness. Taking it with alcohol might cause mild body rashes and therefore is not recommended.[
Overdosage
Excessive doses of metoprolol can cause severe hypotension, bradycardia, metabolic acidosis, seizures and cardiorespiratory arrest. Blood or plasma concentrations may be measured to confirm a diagnosis of poisoning in hospitalized patients or to assist in a medicolegal death investigation. Plasma levels are usually less than 200 μg/L during therapeutic administration, but can range from 1-20 mg/L in overdose victims
Chemistry
Metoprolol, 1-(iso-propylamino)-3-[4′(2-methoxyethyl)phenoxy]-2-propanol, is synthesized by reacting 4-(2-methoxyethyl)phenol with epichlorhydride in the presence of a base, isolating 1,2-epoxy-3-[4′(2-methoxyethyl)phenoxy]propane, the subsequent reaction with iso-propylamine, gives an opening of the epoxide ring and leads to the formation of metoprolol.
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Atenolol
Atenolol (Tenormin) is a selective β1 receptor antagonist, a drug belonging to the group of beta blockers (sometimes written β-blockers), a class of drugs used primarily incardiovascular diseases. Introduced in 1976, atenolol was developed as a replacement forpropranolol in the treatment of hypertension. The chemical works by slowing down the heart and reducing its workload. Unlike propranolol, atenolol does not pass through the blood-brain barrier thus avoiding various central nervous system side effects.
Atenolol is one of the most widely used β-blockers in the United Kingdom and was once the first-line treatment for hypertension. The role for β-blockers in hypertension was downgraded in June 2006 in the United Kingdom
Indications
Atenolol can be used to treat cardiovascular diseases and conditions such ashypertension, coronary heart disease, arrhythmias, angina (chest pain) and to treat and reduce the risk of heart complications following myocardial infarction (heart attack). It is also used to treat the symptoms of Graves Disease, until antithyroid medication can take effect.
Due to its hydrophilic properties, the drug is less suitable in migraine prophylaxis compared to propranolol, because, for this indication, atenolol would have to reach the brain in high concentrations, which is not the case (see below).
Cardioselectivity and asthma
Atenolol is classified as a β1-selective (or 'cardioselective') drug, one that exerts greater blocking activity on myocardial β1-receptors than on β2 receptors in the lung. The β2receptors are responsible for keeping the bronchial system open. If these receptors are blocked, bronchospasm with serious lack of oxygen in the body can result. However, due to its cardioselective properties, the risk of bronchospastic reactions if using atenolol is reduced compared to nonselective drugs as propranolol. Nonetheless, this reaction may also be encountered with atenolol at high doses. Although traditionally B-blockers have been contraindicated when a person carries a diagnosis of asthma, recent studies have revealed that at moderate doses selective B blockers such as Atenolol are well tolerated.
Provisional data suggests that antihypertensive therapy with atenolol provides weaker protective action against cardiovascular complications (e.g. myocardial infarction and stroke) compared to other antihypertensive drugs. In some cases, diuretics are superior. However, controlled studies are lacking.
Unlike most other commonly-used β-blockers, atenolol is excreted almost exclusively by the kidneys. This makes it attractive for use in individuals with end-stage liver disease.
Combination treatment of hypertension
If atenolol alone fails to control arterial hypertension, the drug can be combined with a diuretic (e.g. with chlortalidone in co-tenidone) and/or a vasodilator (hydralazine, or in severe cases minoxidil). Central alpha-agonists (e.g. clonidine), ACE Inhibitors or Angiotensin II receptor antagonists such as losartan can also be given additionally. Exert caution with calcium-antagonists of the verapamil-type as adjunct therapy because of additional negative impact on the muscular strength of the heart. Use of calcium-antagonists of the nifedipine-type is controversial..
Contraindications
§ bradycardia (pulse less than 50 bpm)
§ asthma (may cause broncho-constriction), although unlikely as atenolol is cardioselective
§ symptomatic hypotension (blood pressure of less than 90/60 mm Hg with dizziness, vertigo etc.)
§ angina of the Prinzmetal type (vasospastic angina)
§ metabolic acidosis (a severe condition with a more acidic blood than normal)
§ severe disorders in peripheral arterial circulation
§ AV-Blockage of second and third degree (a particular form of arrhythmia)
§ acutely decompensated congestive heart failure (symptoms may be fluid retention with peripheral edema and/or abdominal fluid retention (ascites), and/or lung edema)
§ sick sinus syndrome (a particular form of arrhythmia)
§ hypersensitivity and/or allergy to atenolol
§ pheochromocytoma (a rare type of tumor of the adrenal glands)
Caution: patients with preexisting bronchial asthma
Caution: only if clearly needed during pregnancy, as atenolol may retard fetal growth and possibly cause other abnormalities.
Side effects
Atenolol causes significantly fewer central nervous system side effects (depression, nightmares) and fewer bronchospastic reactions, both due to its particular pharmacologic profile.
It was the main β-blocker identified as carrying a higher risk of provoking type 2 diabetes, leading to its downgrading in the United Kingdom
In addition, β-blockers blunt the usual sympathetic nervous system response to hypoglycemia (i.e. sweating, agitation, tachycardia). These drugs therefore have an ability to mask a dangerously low blood sugar, which further decreases their safety and utility in diabetic patients.
Side effects include:
§ dry mouth
§ dizziness or faintness (especially cases of orthostatic hypotension)
§ cold extremities
§ hair loss
§ impotence
§ rhinitis
§ depression
§ confusion
§ insomnia, nightmares
§ fatigue, weakness or lack of energy
These side effects may or may not be experienced, but if they are, you should notify your doctor.
More serious side effects can include:
§ low blood pressure (hypotension)
§ sensation of 'pins and needles' hands or feet
§ irritated eyes, visual disturbances
§ difficulty hearing
§ difficulty speaking
§ unsteadiness when walking
Serious side effects may require urgent medical attention. Some of these side effects are rare and others (not mentioned in the above list) can occur in some people.
Dosage
In patients with normal renal function, the daily dose is 25 to 50 mg for the management of hypertension depending on the indication and severity of the disease. In most patients, the physician will start with a low initial dose and make increments in weekly intervals as tolerated. Dosage can vary from as little as 25 mg to 200 mg a day. In cases of doses over 100 mg, the dosage is usually divided and taken twice daily.
For the management of angina, 100 mg daily may be given.
Celiprolol
Celiprolol is a medication in the class of beta blockers, used in the treatment of high blood pressure. It has a unique pharmacodynamics: it is a selective β1 antagonist, but a β2 partialagonist. It is also a weak α2 antagonist.
A recent clinical trial has suggested a use for this medication in the prevention of vascular complications of a rare inherited disease called Ehlers-Danlos Syndrome. This study demonstrated decreased incidence of arterial rupture or dissection (a specific type of arterial rupture in which the layers of the vessel separate prior to complete failure of the artery wall).
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