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Nadolol is a non-selective beta-adrenergic antagonist with antihypertensive and antiarrhythmic activities. Nadolol competitively blocks beta-1 adrenergic receptors located in the heart and vascular smooth muscle, inhibiting the activities of the catecholamines epinephrine and norepinephrine and producing negative inotropic and chronotropic effects. This agent exhibits antiarrhythmic activity via the impairment of atrioventricular (AV) node conduction and a corresponding reduction in sinus rate. In the kidney, inhibition of the beta-2 receptor within the juxtaglomerular apparatus results in the inhibition of renin production and a subsequent reduction in angiotensin II and aldosterone levels, thus inhibiting angiotensin II-dependent vasoconstriction and aldosterone-dependent water retention. Nadolol is a nonselective beta-adrenergic receptor blocker that is widely used for the therapy of hypertension, angina pectoris, and vascular headaches. Nadolol has yet to be convincingly associated with clinically apparent liver injury.
Nadolol is a non-selective beta blocker used in the treatment of high blood pressure and chest pain. Additionally, it is often prescribed in the treatment of atrial fibrillation, nausea, or light sensitivity. সহজ বাংলা: বারবার হওয়া বিশেষ ধরনের মাথাব্যথা।" data-rx-term="migraine" data-rx-definition="Migraine is a recurring headache disorder often with throbbing pain, nausea, or light sensitivity. সহজ বাংলা: বারবার হওয়া বিশেষ ধরনের মাথাব্যথা।">migraine headaches, and complications of cirrhosis. A non-selective beta-adrenergic antagonist with a long half-life, used in cardiovascular disease to treat arrhythmias, angina pectoris, and hypertension. Nadolol is also used for migraine disorders and for tremor.
Mechanism of Action of Nadolol
Like other beta-adrenergic antagonists, nadolol competes with adrenergic neurotransmitters such as catecholamines for binding at sympathetic receptor sites. Like propranolol and timolol, nadolol binds at beta(1)-adrenergic receptors in the heart and vascular smooth muscle, inhibiting the effects of the catecholamines epinephrine and norepinephrine and decreasing heart rate, cardiac output, and systolic and diastolic blood pressure. It also blocks beta-2 adrenergic receptors located in bronchiole smooth muscle, causing vasoconstriction. By binding beta-2 receptors in the juxtaglomerular apparatus, nadolol inhibits the production of renin, thereby inhibiting angiotensin IIand aldosterone production. Nadolol, therefore, inhibits the vasoconstriction and water retention due to angiotensin II and aldosterone, respectively.
Nadolol is a non-selective beta blocker; that is, it non-selectively blocks both beta-1 and beta-2 receptors. It has a preference for beta-1 receptors, which are predominantly located in the heart, thereby inhibiting the effects of catecholamines and causing a decrease in heart rate and blood pressure. Its inhibition of beta-2 receptors, which are mainly located in the bronchial smooth muscle of the airways, leads to airway constriction similar to that seen in asthma. Inhibition of beta-1 receptors in the juxtaglomerular apparatus of the kidney inhibits the renin–angiotensin system, causing a decrease in vasoconstriction and a decrease in water retention. Nadolol’s inhibition of beta-1 receptors in the heart and kidney leads to its effects on lowering blood pressure.The drug impairs AV node conduction and decreases sinus rate. Nadolol may also increase plasma triglycerides and decrease HDL-cholesterol levels.
Indications of Nadolol
- Angina pectoris
- Gastroesophageal variceal hemorrhage prophylaxis
- High blood pressure (Hypertension)
- Used in cardiovascular disease to treat arrhythmias,
- Nonvalvular atrial fibrillation
- Thyrotoxicosis
- Esophageal variceal hemorrhage prophylaxis
- Anxiety
- Benign essential tremor
- Migraine prevention
- Mitral valve prolapse
- Parkinsonian tremor
- Portal hypertension
- Supraventricular tachycardia
Therapeutic Uses
- Mitral valve prolapse
- Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Antihypertensive Agents; Sympatholytics
- Nadolol is indicated in the treatment of hypertension when used alone or in combination with other antihypertensive medication.
- Nadolol has been used in a limited number of patients with atrial flutter or fibrillation for the management of frequent ventricular premature contractions, paroxysmal atrial tachycardia, and sinus tachycardia and to decrease heart rate. Nadolol has been used with some success in a limited number of patients for the prophylaxis of a common pain, nausea, or light sensitivity. সহজ বাংলা: বারবার হওয়া বিশেষ ধরনের মাথাব্যথা।" data-rx-term="migraine" data-rx-definition="Migraine is a recurring headache disorder often with throbbing pain, nausea, or light sensitivity. সহজ বাংলা: বারবার হওয়া বিশেষ ধরনের মাথাব্যথা।">migraine headache.
- This investigation reports pilot data on two points originally raised in the earliest reports of the efficacy of beta-blockers in akathisia: their potential utility in the akathisia of idiopathic Parkinson’s disease and the possibility of determining a central vs a peripheral site of action by comparing the time course of the effects of lipophilic and hydrophilic agents. Akathisia improved in 4 patients with idiopathic Parkinson’s disease after low dose propranolol treatment. Six patients with neuroleptic-induced akathisia were treated with the hydrophilic beta-blocker nadolol. Effects on akathisia occurred, but evolved much more slowly than after treatment with lipophilic agents, such as propranolol and metoprolol, thus suggesting a central site of action.
- The effectiveness of nadolol as an adjunct to antipsychotic medication in the treatment of aggressive behavior associated with schizophrenia was studied in 2 patients (aged 36 and 45 yr) who received nadolol titrated to a maximum dose of 120 mg/day for 21 days, then tapered down (for a total active drug period of 34 days); patients also received a placebo for two phases (before and after the nadolol treatment phase). Results showed that mean aggression scores fell 65% and 55%, respectively, during nadolol therapy and remained low during the second 3 wk placebo phase. Both patients had a mild drop in blood pressure while receiving nadolol, but the decrease did not result in any clinically important symptoms of hypotension.
- Nadolol is indicated in the treatment of classic angina pectoris, also referred to as “effort-associated angina”.
- Nadolol is used in the treatment of mitral valve prolapse syndrome.
- Nadolol is useful for prophylaxis of a pain, nausea, or light sensitivity. সহজ বাংলা: বারবার হওয়া বিশেষ ধরনের মাথাব্যথা।" data-rx-term="migraine" data-rx-definition="Migraine is a recurring headache disorder often with throbbing pain, nausea, or light sensitivity. সহজ বাংলা: বারবার হওয়া বিশেষ ধরনের মাথাব্যথা।">migraine
- Nadolol may be used/ in the management of symptoms of tachycardia due to excessive beta-receptor stimulation in pheochromocytoma. However, it should be used only after primary treatment with an alpha-adrenergic blocking agent (since use without concomitant alpha-blockade could lead to serious blood pressure elevation).
- Nadolol is indicated in clinically stable patients recovering from an initial definite or suspected acute myocardial infarction in order to reduce cardiovascular mortality and to decrease the risk of reinfarction.
- Nadolol is indicated in the management of angina, palpitations, and syncope associated with hypertrophic subaortic stenosis.
- Nadolol is used for their antiarrhythmic effects, especially in supraventricular arrhythmias and ventricular tachycardias.
Dosage of Nadolol
Strengths: 40 mg; 120 mg; 20 mg; 80 mg; 160 mg
Angina Pectoris
- Initial dose: 40 mg orally once a day; may be increased by 40 to 80 mg every 3 to 7 days until optimum response is obtained or pronounced heart rate reduction occurs
- Maintenance dose: 40 to 80 mg orally once a day; up to 240 mg once a day may be required
- Maximum dose: 240 mg/day
Hypertension
- Initial dose: 40 mg orally once a day; may be increased in 40 to 80 mg increments until optimum blood pressure reduction is achieved
- Maintenance dose: 40 to 80 mg orally once a day; up to 320 mg once a day may be required.
Side Effects of Nadolol
The most common
- Blurred vision or other vision problems
- Fever, chills, or a sore throat
- Shortness of breath
- Chest pain or discomfort
- Slow or irregular heartbeat
- Dry mouth
- muscle trembling, jerking, or stiffness
- anxiety
- changes in vision, including blurred vision
- dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
- stomach pain or cramping
- diarrhea
- a headache
- stomach pain;
- back pain, joint or muscle pain.
- problems with your vision (including color vision);
- sudden chest pain or trouble breathing;
- pain or swelling in one or both legs;
- a migraine headache;
- pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating; or
More common
- Abdominal or stomach pain, discomfort, or pain when an area is touched or pressed. সহজ বাংলা: চাপ দিলে ব্যথা।" data-rx-term="tenderness" data-rx-definition="Tenderness means pain when an area is touched or pressed. সহজ বাংলা: চাপ দিলে ব্যথা।">tenderness
- chills or fever
- difficulty with moving
- a headache, severe and throbbing
- joint or back pain
- muscle aching or cramping
- muscle pains or stiffness
- chest pressure or squeezing pain in the chest
- discomfort in arms, shoulders, neck or upper back
- excessive sweating
- feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
- sudden tingling or coldness in an arm or leg
- sudden slow or difficult speech
- sudden drowsiness or need to sleep
- fast breathing
- sharp pain when taking a deep breath
- fast or slow heartbeat
- coughing up blood
- rust colored urine
- decreased amount of urine
Rare
- Anxiety
- change in vision
- chest pain or tightness
- confusion
- a cough
- Agitation
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- convulsions
- extra heartbeats
- fainting
- hallucinations
- a headache
- irritability
- lightheadedness
- mood or mental changes
- muscle pain or cramps
- muscle spasm or jerking of all extremities
- nervousness
Drug Interactions of Nadolol
Nadolol may interact with the following drug, supplements, & may change the efficacy of the drug
- alpha-1 blockers (e.g., doxazosin, prazosin, tamsulosin)
- alpha-2 blockers (e.g., clonidine, dexmedetomidine, methyldopa)
- angiotensin-converting enzyme inhibitors (ACEIs; e.g., captopril, ramipril)
- angiotensin II receptor blockers (i.e., irbesartan, losartan, valsartan)
- antipsychotics (e.g., clozapine, olanzapine, quetiapine, risperidone)
- atorvastatin
- azole antifungals (e.g., itraconazole, ketoconazole, posaconazole)
- barbiturates (e.g., phenobarbital)
- benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
- beta-agonists (e.g., formoterol, salbutamol, salmeterol)
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- carbamazepine
- cyclosporine
- dexamethasone
- diuretics (water pills; e.g., furosemide, hydrochlorothiazide)
- duloxetine
- levodopa
- lidocaine
- MAO inhibitors (e.g., phenelzine, moclobemide, selegiline)
- macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin)
- nilotinib
- nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, naproxen)
- other beta-blockers (e.g., atenolol, metoprolol, propranolol)
- pentoxifylline
- phosphodiesterase-5-inhibitors (e.g. sildenafil, tadalafil)
- sunitinib
- theophyllines (e.g.aminophylline, oxtriphylline, theophylline)
Pregnancy Catagory of Nadolol
FDA Pregnancy Category C
Pregnancy
In animal reproduction studies with nadolol, evidence of embryo- and fetotoxicity was found in rabbits, but not in rats or hamsters, at doses 5 to 10 times greater (on an mg/kg basis) than the maximum indicated human dose.There are no adequate and well-controlled studies in pregnant women. Nadolol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonates whose mothers are receiving nadolol at parturition have exhibited bradycardia, hypoglycemia, and associated symptoms.
Lactation
Nadolol is excreted in human milk. Because of the potential for adverse effects in nursing infants, a decision should be made whether to discontinue nursing or to discontinue therapy taking into account the importance of CORGARD (nadolol) to the mother.
References
- https://www.drugs.com/cdi/nadolol.html
- https://www.webmd.com/drugs/2/drug-11755/nadolol-oral/details/list-contraindications
