Nadolol

BRAND NAMES
Corgard: It contains nadolol, commonly used for hypertension and to help people with chest pain. It is available in the form of oral tablets with strengths of 20 mg, 40 mg, and 80 mg 
MECHANISM OF ACTION
Nadolol is a synthetic, non-selective β-adrenergic receptor blocker and inverse agonist. Nadolol competitively inhibits catecholamine's influence on β-1 receptors in the heart and vascular smooth muscles without sympathomimetic or membrane-stabilizing properties, resulting in negative inotropic and chronotropic effects. This impact on vascular smooth muscle decreases peripheral vascular resistance while simultaneously reducing systolic and diastolic blood pressure at rest and during exercise. The drug's antiarrhythmic impact prevents conduction via the atrioventricular node and suppresses automaticity, reducing heart rate and cardiac output at rest and during exercise. Inhibiting the β-2 receptor in the juxtaglomerular apparatus decreases renin production, angiotensinogen, vasoconstriction, and aldosterone-induced water retention.
PHARMACOKINETICS
Absorption: Approximately 30% of nadolol is absorbed after an oral dose. Studies found that nadolol had a Tmax of 2.7 hours and a Cmax of 69±15 mg/mL after a 60 mg oral dosage and 132±27 mg/mL after a 120 mg oral dose.
Distribution: The volume of distribution for Nadolol ranges between 147 and 157 L. Approximately 30% of the medication is linked to plasma α-1-acid glycoprotein.
Metabolism: Following quick first-pass metabolism in the liver, nadolol is minimally hepatically metabolized, has little to no influence on the CYP450 system, and is unlikely to induce liver harm. Nadolol's exact metabolic route is unknown. 
Elimination: After an intravenous (IV) injection, 60% of the nadolol is removed in the urine and 15% in the feces 72 hours later. The drug's half-life ranges between 20 and 24 hours. The intrinsically prolonged duration of action allows for daily treatment and is equally effective as propranolol, which requires four times the daily dose. Nadolol, unlike other β-blockers, is eliminated through the kidneys.
PHARMACODYNAMICS
As a non-selective beta blocker, nadolol inhibits both beta-1 and beta-2 receptors without preference. It prefers to bind to beta-1 receptors, which are mostly found in the heart. This inhibits the effects of catecholamines, which lower blood pressure and heart rate. It causes constriction of the airways akin to asthma by inhibiting beta-2 receptors, which are mostly found in the bronchial smooth muscle of the airways. Vasoconstriction and water retention are reduced when beta-1 receptors in the kidney's juxtaglomerular apparatus are inhibited. This also suppresses the renin-angiotensin system. Because it inhibits beta-1 receptors in the kidney and heart, nadolol lowers blood pressure. 
DOSAGE AND ADMINISTRATION
Oral administration is the primary method of administering naprolol. There are tablet forms with strengths of 20 mg, 40 mg, and 80 mg.
According to the FDA, in patients with angina pectoris and hypertension, nadolol should be initiated as a 40 mg once-daily oral formulation and subsequently raised in 40 to 80 mg increments to obtain the requisite therapeutic concentration and be customized to the patient's response. The maximal doses for hypertension and angina are 320 and 240 mg, respectively.
The recommended starting dose for primary and secondary prevention of gastric variceal hemorrhage in patients is 40 mg/day. Individuals with ascites can increase their dose to 80 mg/d, while those without ascites can increase it to 160 mg/d. To attain the maximal acceptable dose in these patients, dosing should be gradually increased every 2 to 3 days. The heart rate should be maintained between 55 and 60 beats per minute, and the dosage should be discontinued or lowered if the blood pressure falls below 90 mm Hg. The American Thyroid Association recommends an oral dosage of 40 to 160 mg for persons with thyrotoxicosis.
CONTRAINDICATIONS
Nadolol is not recommended for bronchial asthma, sinus bradycardia, conduction block (more than first-degree), cardiogenic shock, or overt heart failure.

SIDE EFFECTS

The most common adverse effects of nadolol

• fainting
• Pain in the chest 
• The inability to breathe 
• An uneven or sluggish heartbeat 
• Atypical weight increase 
• Hand, foot, ankle, or lower leg swelling 

TOXICITY

The majority of nadolol poisonings result from the purposeful intake of the pill. No instances of substantial toxicity are found in the literature. The majority of cases of nadolol poisoning are minor. These individuals can be examined in an emergency room for four hours before being discharged if no indications of poisoning appear. If moderate-to-severe toxicity continues, activated charcoal can be administered for early cleaning, followed by stomach lavage if considerable ingestion is anticipated. After stabilizing the patient's airway, breathing, and circulation, increased elimination with hemodialysis is conceivable, given nadolol's limited distribution volume and extended half-life.