inderal
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Synonyms | |||
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Propranolol hydrochloride, marketed under the brand name Inderal, represents one of the foundational beta-blockers in cardiovascular and neurological medicine. As a non-selective beta-adrenergic antagonist, it competitively blocks catecholamine effects at both β1 and β2 adrenergic receptors. This mechanism underlies its diverse clinical applications spanning from hypertension management to essential tremor control. The drug’s development in the 1960s by Sir James Black revolutionized angina treatment and earned him a Nobel Prize, though its utility has expanded far beyond original indications. What’s fascinating about propranolol isn’t just its efficacy but its surprising applications we’ve discovered through decades of clinical use.
Key Components and Bioavailability of Inderal
The active pharmaceutical ingredient in Inderal is propranolol hydrochloride, typically formulated in immediate-release (10mg, 20mg, 40mg, 60mg, 80mg tablets) and long-acting capsules (60mg, 80mg, 120mg, 160mg). The hydrochloride salt form enhances solubility and bioavailability. Unlike many newer beta-blockers, propranolol lacks intrinsic sympathomimetic activity or cardioselectivity, which contributes to both its broad effects and side effect profile.
Bioavailability presents a significant consideration with Inderal. The drug undergoes extensive first-pass metabolism in the liver, resulting in approximately 25% oral bioavailability. This hepatic clearance creates substantial interindividual variability in plasma concentrations - we’ve seen patients requiring dramatically different doses for similar therapeutic effects. The presence of food can increase bioavailability by reducing first-pass metabolism, which explains why we often recommend taking it with meals for more consistent effects. The half-life ranges from 3-6 hours for immediate-release formulations, necessitating multiple daily doses, while the long-acting preparation provides sustained coverage with once-daily dosing.
Mechanism of Action of Inderal: Scientific Substantiation
Inderal’s therapeutic effects stem from competitive antagonism of beta-adrenergic receptors throughout the body. At β1 receptors primarily located in cardiac tissue, blockade reduces heart rate, myocardial contractility, and conduction velocity - the negative chronotropic and inotropic effects that benefit angina and hypertension. Meanwhile, β2 receptor blockade in bronchial smooth muscle, vascular beds, and metabolic tissues produces both intended and side effects.
The drug’s lipophilic nature allows penetration across the blood-brain barrier, which explains its utility in migraine prophylaxis and anxiety-related conditions. This central nervous system activity distinguishes it from water-soluble beta-blockers like atenolol. Interestingly, we’ve observed that the membrane-stabilizing activity observed in vitro at very high concentrations likely doesn’t contribute significantly to clinical effects at therapeutic doses.
What many don’t appreciate is how propranolol affects renin secretion - by blocking β1 receptors in the juxtaglomerular apparatus, it reduces renin release and subsequent angiotensin II formation, contributing to its antihypertensive effects beyond simple cardiac output reduction.
Indications for Use: What is Inderal Effective For?
Inderal for Hypertension
As monotherapy or in combination regimens, Inderal effectively reduces blood pressure through multiple mechanisms including reduced cardiac output, inhibited renin release, and potentially central nervous system effects. The 2017 ACC/AHA hypertension guidelines position beta-blockers as second-line agents for uncomplicated hypertension, though they remain preferred in patients with compelling indications like prior myocardial infarction or heart failure.
Inderal for Angina Pectoris
By reducing myocardial oxygen demand through decreased heart rate, contractility, and afterload, Inderal remains a cornerstone of chronic stable angina management. We typically titrate to achieve resting heart rates of 50-60 bpm while avoiding excessive bradycardia.
Inderal for Cardiac Arrhythmias
The drug demonstrates particular efficacy in catecholamine-sensitive tachyarrhythmias, including sinus tachycardia, atrial fibrillation with rapid ventricular response, and ventricular arrhythmias in certain channelopathies. Its membrane-stabilizing properties at very high doses may contribute to antiarrhythmic effects in specific contexts.
Inderal for Migraine Prophylaxis
The mechanism in migraine prevention isn’t fully elucidated but likely involves prevention of cerebral arterial dilation and central nervous system effects. Doses of 80-240mg daily typically reduce migraine frequency by 50% or more in responsive patients.
Inderal for Essential Tremor
Beta-blockade in the central nervous system likely underlies tremor reduction, with many patients experiencing significant functional improvement at doses lower than those required for cardiovascular indications.
Inderal for Anxiety and Performance Situations
The peripheral manifestations of anxiety - palpitations, tremor, sweating - respond well to propranolol’s blockade, making it valuable for situational anxiety like public speaking or musical performances. We’ve found 10-40mg taken 60-90 minutes before anticipated stress particularly effective.
Inderal for Thyrotoxicosis
In hyperthyroid states, propranolol rapidly controls adrenergic symptoms like tachycardia, tremor, and anxiety while definitive management takes effect. The non-selective blockade proves advantageous here over cardioselective agents.
Inderal for Portal Hypertension
In cirrhotic patients, non-selective beta-blockers like propranolol reduce portal pressure and variceal bleeding risk through decreased cardiac output and splanchnic vasoconstriction.
Instructions for Use: Dosage and Course of Administration
Dosing must be individualized based on indication, patient characteristics, and response. Generally, we initiate therapy at lower doses and titrate upward while monitoring therapeutic response and adverse effects.
| Indication | Initial Adult Dose | Maintenance Range | Administration Notes |
|---|---|---|---|
| Hypertension | 40mg twice daily | 120-240mg daily in 2-3 divided doses | May increase to 640mg daily in resistant cases |
| Angina | 80-320mg daily in 2-4 divided doses | Individualized to symptom control | Target resting HR 55-60 bpm |
| Migraine Prevention | 80mg daily in divided doses | 160-240mg daily | 4-6 week trial to assess efficacy |
| Essential Tremor | 40mg twice daily | 120-320mg daily | Divide doses if >160mg daily |
| Anxiety (situational) | 10-20mg as single dose | 10-40mg as needed | Administer 60-90 min before event |
Abrupt discontinuation should be avoided, particularly in patients with coronary artery disease, due to potential rebound tachycardia and hypertension. We typically taper over 1-2 weeks while monitoring for withdrawal symptoms.
Contraindications and Drug Interactions with Inderal
Absolute contraindications include severe bradycardia, heart block greater than first-degree, cardiogenic shock, decompensated heart failure, and bronchial asthma. Relative contraindications encompass diabetes (may mask hypoglycemia symptoms), peripheral vascular disease, pheochromocytoma (requires alpha-blockade first), and metabolic acidosis.
Significant drug interactions merit careful consideration:
- Calcium channel blockers (verapamil, diltiazem): Enhanced bradycardia and AV block risk
- Insulin/oral hypoglycemics: Altered glycemic response and masked hypoglycemia symptoms
- Sympathomimetics: Mutual antagonism - may require dose adjustments
- CYP450 inhibitors (cimetidine, fluoxetine): Increased propranolol concentrations
- CYP450 inducers (rifampin, phenobarbital): Reduced propranolol efficacy
- Antiarrhythmics: Additive electrophysiological effects
Pregnancy category C designation reflects uncertain safety, though we’ve used it cautiously in selected pregnant patients when benefits outweigh risks, particularly for maternal arrhythmias or thyrotoxicosis.
Clinical Studies and Evidence Base for Inderal
The evidence supporting Inderal spans decades of rigorous investigation. The Norwegian Timolol Trial (1981) demonstrated 39% mortality reduction post-myocardial infarction, establishing beta-blockers as standard post-MI care. The BHAT study (1982) confirmed propranolol’s mortality benefit with 26% reduction in total mortality over average 25-month follow-up.
For migraine prophylaxis, multiple randomized controlled trials including the Weber and Cole (1984) study established efficacy superior to placebo with 50-80% of patients experiencing ≥50% reduction in attack frequency. Dosages of 160-240mg daily proved most effective in meta-analyses.
Essential tremor studies, particularly by Larsen et al. (1982) and later Koller (1986), demonstrated significant improvement in tremor amplitude and functional capacity with doses of 120-320mg daily. Response rates typically range from 50-70% of patients.
Hypertension trials, while largely superseded by newer agents, established propranolol’s efficacy in numerous populations. The Medical Research Council trial (1985) showed stroke reduction comparable to thiazide diuretics, though with different side effect profiles.
Comparing Inderal with Similar Products and Choosing Quality Medication
When selecting among beta-blockers, several considerations guide choice:
Inderal vs. Cardioselective Agents (Metoprolol, Atenolol) Propranolol’s non-selectivity provides advantages in conditions like essential tremor and migraine but increases bronchospasm risk in susceptible patients. Cardioselective agents may be preferable in asthma/COPD patients, though caution remains necessary.
Inderal vs. Agents with ISA (Pindolol, Acebutolol) Drugs with intrinsic sympathomimetic activity cause less bradycardia and lipid disturbances but may be less effective for angina and post-MI protection.
Inderal vs. Nebivolol Nebivolol offers nitric oxide-mediated vasodilation with potentially fewer metabolic effects but lacks propranolol’s proven mortality benefit in post-MI patients.
Generic propranolol provides equivalent efficacy to brand-name Inderal at reduced cost. We recommend checking for FDA approval and manufacturer reputation when selecting generic versions, as excipient differences can occasionally affect absorption in sensitive patients.
Frequently Asked Questions (FAQ) about Inderal
What is the recommended course of Inderal to achieve results?
Therapeutic response timing varies by indication - hypertension control may require 1-2 weeks, migraine prophylaxis typically needs 4-6 week trials, while essential tremor often shows improvement within hours of dosing but maximal benefit after several weeks.
Can Inderal be combined with blood pressure medications?
Yes, Inderal frequently complements diuretics, ACE inhibitors, and calcium channel blockers (except verapamil/diltiazem), though careful monitoring for excessive bradycardia or hypotension is essential.
Does Inderal cause weight gain?
Modest weight gain (1-2 kg) occurs in some patients, possibly through reduced metabolic rate and exercise tolerance. This typically stabilizes after several months.
How should Inderal be discontinued?
Gradual tapering over 1-2 weeks is recommended, with more extended withdrawal (2-3 weeks) for patients with coronary artery disease to prevent rebound tachycardia and hypertension.
Can Inderal be used in athletes?
While effective for performance anxiety, it’s prohibited in certain precision sports (archery, shooting) due to potential tremor reduction, and banned in others where beta-blockers might provide unfair advantage.
Is Inderal safe during breastfeeding?
Propranolol distributes into breast milk in low concentrations, generally considered compatible with breastfeeding, though monitoring the infant for potential bradycardia or hypoglycemia is prudent.
Conclusion: Validity of Inderal Use in Clinical Practice
Inderal maintains an important position in contemporary therapeutics despite being among the oldest beta-blockers. Its non-selectivity, lipophilicity, and extensive evidence base support continued use across cardiovascular, neurological, and endocrine conditions. The risk-benefit profile favors Inderal in selected patients, particularly those with multiple indications who might benefit from its diverse mechanisms. While newer agents offer theoretical advantages in specific scenarios, propranolol’s proven mortality benefit, cost-effectiveness, and unique applications ensure its ongoing relevance in evidence-based practice.
I remember when we first started using propranolol for performance anxiety in our medical students - there was considerable debate among our department about whether we were medicalizing normal stress responses. Dr. Chen argued we were creating pharmacological crutches, while I maintained we were enabling talented individuals to demonstrate their actual capabilities. The breakthrough came with Michael, a brilliant third-year who would literally vomit before OSCE examinations despite knowing the material cold. We started him on 20mg propranolol 90 minutes before assessments, and the transformation was remarkable - not just in his performance scores, but in his entire demeanor. He went from nearly dropping out to matching in his top-choice surgical program.
What surprised me was discovering that the tremor reduction benefited our older faculty members during delicate procedures. Dr. Williamson, our 68-year-old emeritus professor, had developed an essential tremor that threatened to end his legendary surgical career. He’d tried primidone with unacceptable sedation, but low-dose propranolol at 40mg twice daily restored his steady hands without cognitive effects. He operated another six years before retiring voluntarily.
The learning curve wasn’t smooth - we initially underestimated the first-pass metabolism variability. Sarah, a 42-year-old lawyer with migraines, failed to respond to 80mg daily until we discovered she was a rapid metabolizer through genetic testing. Bumping to 160mg finally provided the relief she needed. Meanwhile, Mr. Davies, our 71-year-old retired postman with hypertension, developed concerning bradycardia at just 20mg twice daily, forcing us to reconsider his entire antihypertensive regimen.
The longitudinal follow-up has been revealing - we’ve now followed some patients for over a decade on propranolol. The metabolic effects concern me in our diabetic patients, requiring closer glucose monitoring than we initially appreciated. But the benefits for quality of life in essential tremor and migraine sufferers consistently outweigh the risks with proper monitoring. Jessica, the pianist whose career was nearly derailed by performance anxiety, still emails me before major concerts fifteen years later - not for dose adjustments, but to thank me for giving her back her vocation. That’s the part they don’t teach in pharmacology lectures.