Beta Adrenoceptor Blockers PDF

PHARMACOLOGY | TRANS 4 LE Beta Adrenoceptor Blockers ALFARETTA LUISA T. REYES, MD, FPSECP |...

PHARMACOLOGY | TRANS 4 LE Beta Adrenoceptor Blockers ALFARETTA LUISA T. REYES, MD, FPSECP | Lecture Date (September 24, 2024) | Version 1 02 C OUTLINE ✔ Apply the process of rational drug use in choosing and I. Classification of Beta VIII. Selective Beta-1 Receptor prescribing drugs for given conditions such as glaucoma Receptor Blockers Blockers ✔ As a future primary care practitioner, identify conditions II. Distinguishing A. Metoprolol when to refer patients to proper healthcare Pharmacologic B. Atenolol professionals/health facilities Properties C. Esmolol A. Beta Blockers D. Nebivolol III. Pharmacokinetics of IX. Mixed Alpha and Beta I. CLASSIFICATION OF BETA RECEPTOR Beta Receptor Blockers Blockers BLOCKERS A. Labetalol A. Absorption and B. Carvedilol Bioavailability C. Bucindolol B. Distribution and Clearance X. Drug Interactions of Beta C. Metabolism Blockers IV. Pharmacodynamics of XI. Therapeutic Uses of Beta Beta Receptor Blockers Blockers A. Mechanism o fAction A. Cardiovascular System B. Cardiovascular System B. Neuropsychiatric C. Respiratory System C. Endocrine D. Metabolic Effect D. Glaucoma and Ocular E. Eyes Hypertension V. Clinical Toxicity and XII. Contraindications/ Adverse Effects of Beta Precautions Receptor Blockers XII. Schematic Presentation of A. Cardiovascular System Figure 1. Adrenoceptor antagonist[Katzung] Effects of Adrenergic Agonists B. Central Nervous and Receptor Blockers System XIV. Summary Generally classified as non-selective or cardio-selective C. Respiratory System XV. Review Questions beta blockers. D. Endocrine System XVI. References Grouped based on distinguishing pharmacologic VI. Effects Not Related to XVII. Appendix properties. Beta-Blockade VII. Non Selective Beta → Relative affinity for β1 and β2 receptors Receptor Blockers ▪ Nonselective (1st and 3rd generation) A. Propranolol ▪ Selective (2nd and 3rd generation) B. Nadolol → Intrinsic sympathetic affinity (ISA) C. Timolol ▪ Partial agonistic action D. Pindolol → Degree of lipid solubility Must Lecturer Book Previous Youtube ▪ Lipophilic, Unionized, Nonpolar, High Vd ▪ There are also some beta blockers with moderate ❗️ Know 💬 📖 📋 Trans 🔺 Video and low lipid solubility → Membrane stabilizing activity (MSA) SUMMARY OF ABBREVIATIONS ▪ Local anesthetic or quinidine-like action BBB Blood Brain Barrier ▪ In general, beta blockers with MSA produce Na+ BP Blood Pressure channel blockade CNS Central Nervous System → Vasodilating action CO Cardiac Output ▪ Some are utilized in the treatment of ocular ISA Intrinsic Sympathetic Activity hypertension and glaucoma MOA Mechanism of Action → Mixed adrenoceptor blockade ▪ ɑ1, β1, and β2 receptor blockade MSA Membrane Stabilizing Activity → Differences in other pharmacokinetic properties PVR Peripheral Vascular Resistance ▪ Oral bioavailability t 1/2 Half-life ▪ Half-life LEARNING OBJECTIVES ▪ Duration of action ✔ Classify the beta receptor blockers according to ▪ Percentage of Protein binding generation and receptor affinities ✔ Differentiate the important receptor blockers based on their distinguishing pharmacologic properties ✔ Discuss the significant pharmacokinetic characteristics of the beta receptor blockers Space intentionally blank ✔ Explain the MOA and the important pharmacologic actions and effects of the beta receptor blockers on the different organ systems ✔ Analyze the effects of the beta receptor blockers based on their therapeutic indications, contraindications, drug interactions LE 2 TG 10 | P. Borromeo, G. Buenaventura, M. TE | K. Biscocho AVPAA | E. Chan PAGE 1 of 16 TRANS 10 Bulusan, K. Burac, F. Burahim, P. Carbonel VPAA | Arcega, Camba PHARMACOLOGY | LE 2 Beta Adrenoceptor Blockers | Alfaretta Luisa T. Reyes, MD, FPSECP II. DISTINGUISHING PHARMACOLOGIC → Cannot traverse the BBB PROPERTIES → Nebivolol, Nadolol, Atenolol, Esmolol, Labetalol, Betaxolol, Acebutolol, Bisoprolol D. MEMBRANE STABILIZING ACTIVITY (MSA) Local anesthetic or quinidine-like action ❗️ Caused by Sodium Channel Blockade → Propranolol, Carvedilol, Acebutolol, Labetalol, Metoprolol, Pindolol In order for a β blocker to be good treatment for glaucoma, 📋 it must be devoid of MSA, otherwise you would be removing the protective corneal reflex 📋 Useful in patients who just had acute myocardial infarction to reduce mortality by 25-39% E. CAPACITY TO INDUCE VASODILATION Carvedilol, Labetalol, Nebivolol, Celiprolol, Nipradilol, Figure 2. Adrenergic Receptor Antagonist ❗️ Carteolol, Betaxolol, Bevantolol, Bopindolol, Dilevalol Classification[Brunton] 💬 Carvedilol A. GENERATION AND RELATIVE AFFINITY FOR B-1 and → Mixed ɑ1 and non-selective β1, β2 receptor blockade B-2 RECEPTORS → Vasodilating action is attributed to its nitric oxide production, not due to its ɑ-receptor blockade Non-selective (1st and 3rd Generation) st Labetalol 1 Generation ❗️ → Vasodilation due to ɑ1 blockade → Classical non-selective β-receptor blockers Nebivolol → Propranolol, Nadolol, Timolol, Pindolol, Penbutolol → Most highly cardioselective β1 receptor blocker 3rd Generation → Vasodilation due to production of nitric oxide as a result → Non-selective β-receptor blockers with additional of stimulation of endothelial nitric oxide synthase actions Betaxolol, Nipradilol, Carteolol → Carvedilol, Labetalol, Carteolol, Bucindolol → Used in the management of patients with ocular Selective (2nd and 3rd Generation) hypertension and glaucoma Cardio-selective (β1 > β2) 💬 F. ALPHA-1 AND BETA-RECEPTOR BLOCKADE Selectivity is dose-related. It tends to diminish at higher drug concentrations β > ɑ1 2nd Generation → Carvedilol, Labetalol, Bucindolol → Selective beta-receptor blockers ▪ Can be used in treatment of glaucoma as a beta → Metoprolol (prototype), Atenolol, Esmolol, blocker 📋 Acebutolol, Bisoprolol G. DIFFERENCES IN PHARMACOKINETIC → Esmolol PROPERTIES ▪ Ultra short acting selective β1 receptor blocker t1/2 ▪ Used to treat essential hypertension and in → Longest: Nebivolol & Nadolol critically-ill patients who require beta-blockers (can be → Shortest: Esmolol easily titrated). ▪ Ultrashort acting β1 blocker 3rd Generation ▪ Used in critically ill patients confined in ICU → Selective beta-receptor blockers with additional actions Duration of action 📋 Refer → Nebivolol, Betaxolol, Celiprolol B. INTRINSIC SYMPATHETIC ACTIVITY (ISA) to appendix lifted from 2025 for the full Beta-blockers with partial agonistic action ❗️ pharmacologic properties of beta adrenoceptor Useful in treating patients with certain conditions blockers Inhibit activation of β-receptors in the presence of high concentrations of catecholamines PINDOLOL ❗️ MUST KNOW Moderately activate receptors in the absence of → Drug prototype of a β blocker with ISA or partial ❗️ endogenous agonists (catecholamines) Pindolol (prototype) , Acebutolol, Labetalol, Carteolol, agonistic activity. Oxprenolol, Penbutolol, Celiprolol CELIPROLOL → A selective β1 receptor blocker but also has a β2 C. DIFFERENCES IN LIPID SOLUBILITY receptor partial agonistic effect and a weak ɑ2 Important chemical characteristics 💬 receptor antagonistic action → Non-polar, non-ionized, large Vd, extensive tissue NEBIVOLOL uptake, can traverse BBB → β3 agonist to some extent High Lipid Solubility PROPRANOLOL, CARVEDILOL and ACEBUTOLOL → Propranolol, Penbutolol → β blockers with local anesthetic or quinidine-like Moderate Lipid Solubility action (MSA). → Metoprolol, Carvedilol, Timolol, Pindolol PROPRANOLOL and PENBUTOLOL Low Lipid Solubility → Highly lipid soluble and have extensive tissue uptake → Hydrophilic β-blockers PHARMACOLOGY Beta Adrenoceptor Blockers PAGE 2 of 16 PHARMACOLOGY | LE 2 Beta Adrenoceptor Blockers | Alfaretta Luisa T. Reyes, MD, FPSECP METOPROLOL, CARVEDILOL, PINDOLOL, and → Highly lipophilic: Propranolol, Penbutol TIMOLOL → Moderately lipophilic: Metoprolol, Carvedilol → Moderate lipid solubility Hydrophilic NADOLOL, NEBIVOLOL, BETAXOLOL, ATENOLOL → Poorly lipid soluble and ESMOLOL → Lower volume of distribution 💬 → Low lipid solubility → Does not traverse BBB → Hydrophilic drugs → Very effective anti-hypertensive drugs ESMOLOL → Eg. Nadolol, Atenolol, Esmolol → Has the shortest half-life (10 minutes) Half lives → When used in IV, discontinuation of drug will → Range from 3-10 hours immediately terminate pharmacologic action → Exception: Esmolol with t1/2 of 10-15 minutes after IV NADOLOL and NEBIVOLOL infusion → Have relatively long half-lives Nadolol NADOLOL → Excreted unchanged in urine → A pure non-selective beta receptor blocker → Nonselective beta blocker → Hydrophilic with long duration of action → Long t1/2 = approx. 14-24 hours (long-acting) → Devoid of ISA and MSA. ▪ May be prolonged in renal failure PROPRANOLOL Nebivolol → A pure non-selective beta receptor blocker → Has an active metabolite in the liver → Highly lipid soluble and has a relatively short half-life → t1/2 = 11- 30 hrs (long-acting) → Exhibits MSA Elimination of drugs may be prolonged in the TIMOLOL presence of: → First used in treatment of glaucoma since no MSA → Liver disease and ISA ▪ Drug will be poorly metabolized → Hepatic enzyme inhibitors III. PHARMACOKINETICS OF BETA RECEPTOR ▪ ↓ metabolism of beta blockers → higher free drug BLOCKERS levels A. ABSORPTION AND BIOAVAILABILITY → ↓ Hepatic blood flow Most are orally well absorbed → Renal dysfunction Peak concentration in 1-3 hours after intake C. METABOLISM Bioavailability is limited to varying degrees for most of the beta blockers P450 CYP2D6 genotype ❗️ → Major determinant of interindividual differences in ❗️ → Exception: Betaxolol, Pindolol, Penbutolol, Sotalol plasma clearance of beta receptor blockers such as Propranolol Metoprolol → Low bioavailability due to extensive hepatic first-pass Propranolol, Metoprolol effect → Extensively metabolized in the liver, small amounts are ▪ Hepatic extraction mechanism may become excreted unchanged in the urine saturated Atenolol, Pindolol 💬 → Plasma level increases as dose is increased due to → Less completely metabolized in the liver saturation of hepatic extraction mechanism Nadolol, Carteolol → Greater inter-individual variability in plasma → Not appreciably metabolized concentration after oral dose → varying degree of → Excreted unchanged in the urine bioavailability Poor metabolizers exhibit 3-10 fold higher plasma ▪ Exception: Betaxolol, Pindolol, Penbutolol and Sotalol concentration after Metoprolol administration than the → Bioavailability following oral administration is much extensive metabolizers lower than IV route given the same dose IV. PHARMACODYNAMICS OF BETA RECEPTOR ▪ undergoes extensive first pass metabolism BLOCKERS → Propranolol and Metoprolol have sustained-release A. MECHANISM OF ACTION 💬 preparations Chemically, most of the β-adrenoceptor blockers are structurally similar to catecholamines like isoproterenol General mechanism: Competitive (equilibrium type) blockade of β receptors → inhibits adenylyl cyclase to some degree even though they have OPPOSITE activity → ↓ cAMP Some have partial agonist actions, membrane 💬 actions They have some form of bulky alkyl substitutions on the stabilizing activity, local anesthetic action, and vasodilating ability 💬 Nitrogen L-isomers are relatively more active Inverse agonists → Reduce constitutive (intrinsic or basal) activity of the B. DISTRIBUTION AND CLEARANCE β receptors in some tissues Lipophilic → Bind to the same receptor as agonists but induce a → Lipid soluble pharmacologic response opposite to the agonist → Absorbed across body membranes and have large ▪ They inactivate receptor activity beyond baseline volume of distribution due to extensive extravascular value tissue uptake → Example: Betaxolol, Metoprolol, Propranolol, Nadalol → Can readily traverse the BBB and may produce CNS effects B. CARDIOVASCULAR SYSTEM PHARMACOLOGY Beta Adrenoceptor Blockers PAGE 3 of 16 PHARMACOLOGY | LE 2 Beta Adrenoceptor Blockers | Alfaretta Luisa T. Reyes, MD, FPSECP BP = CO x PVR ❗️ Opening of K+ channels: Tilisolol Negative inotropic and chronotropic effects Antioxidant activity: Carvedilol → Due to β1 receptor blockade NON SELECTIVE BETA BLOCKERS Do not usually reduce BP in individuals with normal BP but Recall: BP = CO x PVR will lower BP in patients with higher catecholamine → α1 receptor stimulation → Vasoconstriction → Increase concentration like in hypertension PVR → When the tonic stimulation of beta receptors is low, a → β2 receptor stimulation → Vasodilation → Decreases modest effect is observed. PVR → Exercise or stress (SNS activated) → reduce expected Nonselective beta blockers augment pressor response to rise in HR Epinephrine, inhibit vasodilation produced by Isoproterenol Short-term Use by blocking β2 receptors → ↓ CO = decreased BP resulting in the compensatory → Effects of β receptor blockers are significant in patients reflex mechanism due to direct blockade of β1 receptors ❗️ with pheochromocytoma → ↑ PVR = result of β2 receptor blockade by ▪ Use only AFTER adequate α receptor blockade is nonselective beta blockers, leaving the 𝝰1 receptor established activity unopposed (vascular smooth muscle ▪ May cause Rebound Phenomenon otherwise from contraction, leading to vasoconstriction) ⇒ increased sympathetic discharge compensatory reflexes mechanism Long-term Use MEMBRANE STABILIZING ACTIVITY (MSA) → Total peripheral resistance returns to initial value or ↓ Sinus rate decrease in patients with hypertension ↓ Spontaneous rate of depolarization of ectopic ▪ Appears to account for much of the antihypertensive pacemakers effect slow AV node and atrial conduction → This is attributed to the adaptation of resistance vessels ↑ Functional refractory period of AV node → generalized and alteration of baroreceptor sensitivity suppression of myocardial function MOA: sodium channel blockade ❗️ ▪ Accounts for much of their anti-hypertensive activity Remember β blockers with MSA are not desirable for topical use on → α1 activation → Vasoconstriction the eye → β2 activation → Vasodilation → local anesthetic effect on the cornea may eliminate the protective reflexes CONTRIBUTING MOA FOR THEIR Advantages ANTI-HYPERTENSIVE ACTIONS → As prophylaxis to prevent recurrent MI and sudden 1. β receptor blockade → sustained ↓ total PVR death With long term use and produces ↓ BP which is also the result in ↓ CO ▪ 25% decreased mortality rate, improves survival to 2. ↓ renin release from JG cells patients Anti hypertensive effect of beta blockers most marked if ▪ Eg. Metoprolol, Atenolol, Pindolol plasma renin concentration is elevated; effective even in → Limits size of infarct patients with low renin ▪ ↓ Myocardial O2 demand, redistribution of myocardial → α2 receptor activation produces a decrease in Renin blood flow, antiarrhythmic actions release as a result of decreased adenylyl cyclase activity ▪ Eg. Propranolol, Alprenolol, Oxprenolol, Carvedilol, Acebutolol (PALOCA) ❗️ Labetalol, ▪ Use of metoprolol for this condition is detectable only → β1 receptor activation leads to a increase in renin release, so blocking β1 receptors leaves β2 receptor at doses much higher than the dose required for beta activity unopposed blockade → Pindolol: little or no effect in plasma renin activity Disadvantage 3. ↓ central sympathetic outflow (little evidence to support this possibility) CHF ❗️ → These drugs may convert a latent CHF to an overt 4. ↓ release of NE resulting from blockage of presynaptic CARDIOSELECTIVE ACTION OF β1 BLOCKERS beta receptors as possible action Advantages Activation of presynaptic beta receptors produces → As prophylaxis to prevent recurrent MI and sudden facilitatory death action by enhancing release of NE from nerve terminals ▪ 25% 5. Peripheral vasodilation produced by some beta blockers Preferred among beta blockers in patients with: May be attributed to nitric oxide production → Bronchospasm Leads to: enhancing hypotension, ↑ peripheral blood → Diabetes flow, and ↓ afterload → Peripheral vascular disease or Raynaud’s phenomenon ❗️ Nebivolol (β3 agonist), Celiprolol, and Carvedilol also ↓ Nebivolol, Atenolol, Metoprolol, Esmolol, Celiprolol, preload Acebutolol, Betaxolol (Mnemonic: NAME CAB) 6. Proposed Mechanisms ▪ Promotes vasodilation Nitric oxide production: Celiprolol, Nebivolol → Metoprolol is equipotent to propranolol in inhibiting β1 →Causes increased guanylyl cyclase activity and receptor stimulation, but it is 50-100 fold less potent vasodilation of human coronary microvessels blocking β2 receptors β2 receptor agonism: Celiprolol ▪ drug prototype α1 receptor antagonism: Betaxolol Blockade of calcium entry: Carvedilol, Betaxolol PHARMACOLOGY Beta Adrenoceptor Blockers PAGE 4 of 16 PHARMACOLOGY | LE 2 Beta Adrenoceptor Blockers | Alfaretta Luisa T. Reyes, MD, FPSECP INTRINSIC SYMPATHETIC ACTIVITY (ISA) β receptor blockade may: → Partially inhibit hepatic glycogenolysis (particularly Partial agonist action β2 blockade) → Inhibit the activation of the β receptors in the presence → Delay recovery from insulin-induced hypoglycemia of a high catecholamine concentration, but can (infrequently in Type 2 diabetes mellitus) moderately activate in the absence of endogenous ▪ β blockers are much safer to use in patients with agonist Type 2 diabetes mellitus without hypoglycemic Less likely to cause bradycardia and plasma lipid episodes abnormalities ▪ Non-selective β blockers (Eg. Propranolol) causes Advantage is that it is useful in patients with: more prolonged hypoglycemia than selective β1 → Diminished cardiac reserve (CHF) receptor blockers (Eg. Metoprolol) → Propensity to develop symptomatic bradycardia ▪ β2 receptors in the alpha islet cells of the pancreas → Asthma due to the blockade of β2 receptors which are responsible for glucagon secretion are also → Peripheral vasospastic diseases due to the blocked by non-selective β blockers blockade of β2 receptors − Glucagon is the primary hormone that is used to ▪ Such as Raynaud’s phenomenon due to blockade combat hypoglycemia. of β2 receptors leaving the action of alpha1 receptors − Catecholamines are major factors in stimulating unopposed 📋 glucose release from the liver in response to → Diabetes hypoglycemia [2026 TRANS] ▪ As this will not block the action of β2 receptors in the β ▪ Thus, use of non-selective β blockers may blunt islet cells of the pancreas, responsible for increases perception/warnings of hypoglycemia or even insulin secretion impending signs of hypoglycemic coma (such as Disadvantages of β Receptor Blockers with ISA: tremor, tachycardia, sweating, and nervousness) → Precipitates angina Used with great caution in: ▪ May increase oxygen demand as a result of → Diabetic patients who are insulin-dependent tachycardia that may occur and increase in myocardial → Those prone to hypoglycemic reactions workload → Pancreatectomy patients → Eg. Alprenolol, Pindolol, Oxprenolol, Carteolol, Acebutolol, Penbutolol (Mnemonic: APO CAP) ❗️ → Those with inadequate glucagon reserves ▪ Selective β1 blockers may be preferred to be used ABRUPT DISCONTINUATION OF β BLOCKERS AFTER in these conditions, especially those who may require LONG TERM TREATMENT the use of a β blocker for the management of another Should be avoided to prevent: condition → Exacerbation of angina − Less prone to inhibit recovery from hypoglycemia → ↑ Risk of sudden death LIPID Leads to withdrawal syndrome (Rebound Phenomenon) Beta blockers attenuate release of FFA into circulation possibly related to upregulation of β receptors → ↑ sensitivity → Due to blockade of β1 and β3 receptors to β adrenergic stimulation (denervation sensitivity) → Due to a decreased adenylyl cyclase activity leading to → Need to gradually decrease dose (over several decreased cAMP production → decreased activity of weeks) and to restrict exercise during this period triglyceride lipase → decreased conversion of ▪ To avoid sympathetic discharge triglycerides to FFA Manifestation of withdrawal syndrome: Non-selective and selective beta blockers ↑ risk of → nervousness coronary artery disease: → tachycardia → ↓ HDL ↑ VLDL, ↑ triglycerides → ↑ high blood pressure → LDL generally do not change → ↑ intensity of angina → ↓ HDL/ LDL ratio → ↑ risk of coronary artery disease ▪ Less likely to occur with beta blockers with ISA RESPIRATORY SYSTEM (intrinsic sympathomimetic activity) Major adverse effect is bronchoconstriction resulting from − Selective β1 blockers with ISA (Eg. Nebivolol) may β2 receptor blockade in bronchial smooth muscle improve serum lipid profile of dyslipidemic patients → Little effect in normal individuals o Does not adversely affect lipid profile of patients → In patients with asthma or COPD, this can be due to increased insulin sensitivity. life-threatening ▪ Selective β1 receptor blockers or those with ISA at the METABOLIC EFFECTS OF β RECEPTOR BLOCKERS β2 receptors be administered for patients with COPD or In general, β receptor blockers have negative metabolic even asthma that require the use of beta blockers effects but their beneficial effects may outweigh these Selective β1 blockers and those with ISA at β2 receptors risks such as in heart failure → Less likely to induce bronchospasm Newer β receptor blockers are less likely to have → Limited clinical experience with β1 blockers → should negative metabolic effects be avoided if possible → Carvedilol → Nebivolol → Metoprolol → Bisoprolol EYES METABOLIC EFFECTS MOA: ↓ production of aqueous humor from the ciliary CARBOHYDRATES epithelium PHARMACOLOGY Beta Adrenoceptor Blockers PAGE 5 of 16 PHARMACOLOGY | LE 2 Beta Adrenoceptor Blockers | Alfaretta Luisa T. Reyes, MD, FPSECP → Leads to ↓ IOP (intraocular pressure) unopposed α1 receptor ▪ Due to ↓ cAMP production stimulation Useful in treatment of ocular hypertension, chronic or Heart Failure When toxic effects occur in 📋 open-angle glaucoma cardioselective beta blockers with → It may now be used for angle-closure glaucoma [2026 MSA TRANS] Cardiac Due to low myocardial → Non cardioselective blockers: Timolol, Levobunolol, Decompensation contractility and excitability (β1 Carteolol, Metipranolol receptor blockade) → Cardioselective blockers: Betaxolol, Levobetaxolol Ischemic Heart May occur when drug on long Ophthalmic β blockers used should have NO significant Disease term use is abruptly stopped MSA (membrane stabilizing activity or local anesthetic Involves Withdrawal syndrome effect) or ISA (intrinsic sympathomimetic activity) or Rebound phenomenon with → MSA activities: will block the protective corneal abrupt discontinuation of chronic mechanism use of β blocker (due to 📋 → ISA activities: continuous contraction will occur that will up-regulation of β receptors) worsen the condition [2026 TRANS] Drugs that decrease aqueous humor secretion: CENTRAL NERVOUS SYSTEM → ɑ2 agonists: Brimonidine and Apraclonidine Mild sedation → β blockers: (mentioned above) → Similar to centrally acting ɑ2 agonists ▪ Commonly used, fewer adverse effects Vivid dreams → Carbonic anhydrase inhibitors Nightmares Drugs that enhance aqueous outflow: Fatigue → Cholinomimetics Depression (rare) → Prostaglandin F2 alpha analogs, Rho kinase inhibitors → In patients who developed with psychiatric depression, it ▪ Commonly used; fewer adverse effects than advisable not to give these drugs or to discontinue its cholinomimetics use if feasible ▪ More expensive Less likely to occur with hydrophilic beta blockers and CONCEPT CHECKPOINT [2026 TRANS] 📋 with low lipid solubility (Eg. Nadolol, Atenolol, Esmolol) RESPIRATORY SYSTEM 1. Which of the following is a cardioselective β blocker? Worsening of pre-existing asthma and other forms of a. Propranolol airway obstructive diseases b. Metoprolol → In the use of non-selective beta blockers c. Timolol ENDOCRINE SYSTEM d. Carvedilol Hypoglycemia 2. True or False. Nonselective beta blockers can be → Occurs more with the use of non-selective beta administered before adequate alpha blocker is adrenoceptor blockers established. Slight weight gain 3. Which of the following is a disadvantage of using Mild negative changes in metabolism and lipids beta receptor blockers with ISA? → Not seen with vasodilating beta blockers a. May convert latent CHF to overt CHF Sexual dysfunction b. Precipitates angina c. Limits size of infarct CONCEPT CHECKPOINT [2026 TRANS] 📋 4. What is the general mechanism of action of beta 1. True or False. The metabolic effect of β blockers is receptor blockers? hyperglycemia. 2. Give 3 adverse effects of β blockers on the CNS. ANS: 3. What is the most common cardiovascular adverse 1. B. Other choices are nonselective beta blockers. 2. False. Non selective beta blockers can be used ONLY AFTER adequate alpha effect of β receptor blockers? receptor blockade is established otherwise it may cause rebound phenomenon. a. Ischemic heart disease 3. B. Choice A is a disadvantage of beta blockers with MSA while choice C is an advantage of β blockers with ISA b. Bradycardia 4. Inhibits adenylyl cyclase activity resulting to low cAMP production c. Heart failure CLINICAL TOXICITY AND ADVERSE EFFECTS OF ANS: BETA RECEPTOR BLOCKERS 1. False. It should be HYPOglycemia. CARDIOVASCULAR SYSTEM 2. Mild sedation, vivid dreams, nightmares, fatigue, depression 3. B. Bradycardia is the most common adverse cardiac effect. Table 1. Clinical Toxicity & Adverse Effects of Beta Receptor Blockers on CVS EFFECTS NOT RELATED TO BETA BLOCKADE NOTE: Not discussed in Dr. Reyes’ powerpoint but discussed in Katzung and Adverse Effect Cause and Treatment Bradycardia Most common adverse cardiac effect 2022A trans Partial β agonist activity [2022 TRANS] 📋 → Used in prevention of precipitation of asthma and/or Tx: Atropine, cardiac pacemaker excessive bradycardia is often required → Not effective as pure antagonists in the secondary Cold Extremities Due to vasoconstriction of the prevention of myocardial infarction blood vessels as a result of β2 → Drugs include: receptor blockade and ▪ Acebutolol, Carteolol, Celiprolol, Labetalol, Hypotension Due to chronic use of β blockers Penbutolol, Pindolol (Drugs with ISA: APO CAP) PHARMACOLOGY Beta Adrenoceptor Blockers PAGE 6 of 16 PHARMACOLOGY | LE 2 Beta Adrenoceptor Blockers | Alfaretta Luisa T. Reyes, MD, FPSECP 📋 Local anesthetic action (MSA) [2022 TRANS] → Prolonged hypoglycemiaα → Prominent effect in: acebutolol, pindolol, propranolol, ▪ Being a non-selective beta blocker (β2 blockade) babetolol, metoprolol → Uterine contraction → Slight effect in betaxolol ▪ Blocking the β2 receptor leaves the α1 receptors in → Results in typical local anesthetic blockade of Na+ the uterine smooth muscles unopposed therefore 📋 channels causing contraction → Not prominent after systemic administration → Increased risk of atherosclerosis [2026 TRANS] ▪ Plasma concentrations are too low to produce ▪ Increased LDL/HDL ratio, increased VLDL evident effects ▪ Blocking the β2 receptor leaves the α1 receptor → Not used as topical drug for eyes unopposed, leading to increased PVR ▪ Can cause elimination of the protective corneal reflex − Precipitate hypertensive crisis NON-SUBTYPE / NON-SELECTIVE BETA RECEPTOR → Withdrawal syndrome with sudden cessation of BLOCKERS drug after chronic administration These are exemplified by: propranolol, nadolol, timolol, THERAPEUTIC USES and pindolol Hypertension PROPRANOLOL → Full anti-hypertensive effect may not develop for several weeks PHARMACOKINETICS ❗️Highly lipophilic with a very large volume of distribution ▪ NOT used in patients with hypertensive emergencies or crises due to extensive tissue uptake Angina pectoris → Readily enters the CNS → Causes decreased heart rate → ALMOST completely absorbed after oral administration → Given together with nitrites or nitrates ❗️ Disadvantage: Arrhythmias → Low bioavailability after an oral administration: → Propranolol has MSA acitivity ▪ Hence, its oral dose is substantially higher than its IV Myocardial infarction dose caused by extensive hepatic first pass → Due to its MSA (Membrane stabilizing activity) metabolism. → Associated with a 26% decrease in mortality ▪ The IV dose in one third of the oral dose Chronic heart failure: Carvedilol, Metoprolol, Bisoprolol 90% bound to plasma proteins; half life of 3-5 hours Thyroid storm (severe hyperthyroidism): Propranolol Undergoes extensive hepatic first-pass metabolism; → It inhibits conversion of thyroxine (T4) to triiodothyronine low BA of 30% (T3) → Improves with increased dosage because hepatic → It suppresses peripheral sympathetic manifestations ❗️ extraction mechanism becomes saturated due to beta receptor blockade (reducing palpitations, Hepatic extraction is saturable tachycardia, anxiety, and tremulousness) → Degree of hepatic extraction declines as dose is Prophylaxis for migraine: Propranolol, Metoprolol, increased Atenolol, Nadolol, Timolol → Degree of hepatic extraction is inversely proportional to → NOT indicated for acute migraine the oral dose ❗️ ▪ Ergot alkaloids and triptans are more preferred There is greater inter-individual variation in hepatic → Eg. MANT: Metoprolol, Atenolol, Nadolol, Timolol clearance ▪ Used as off-label prophylaxis for migraine → Contributes to approximately 20x variability in plasma Other “off-label” indications concentration after an oral administration → Parkinsonian tremors → Dose-dependent bioavailability ▪ Especially those given antipsychotic drugs Oral bioavailability is increased as the dose is increased, → Akathisia or by concomitant ingestion of food, and with long-term ▪ Movement disorder characterized by a subjective administration of the drug feeling of inner restlessness accompanied by mental → Directly proportional distress and/or an inability to sit still. → Large Vd (volume of distribution) → Variceal bleeding in portal HPN (hypertension) Active metabolite: 4-hydroxypropranolol → Performance anxiety disorder (Eg. stage fright) → Has some weak beta antagonistic activity PHARMACODYNAMICS NADOLOL 📋 No selective beta receptor blockade [2026 TRANS] PHARMACOKINETICS & PHARMACODYNAMICS Long-acting ❗️ → Negative chronotropic, inotropic, and dromotropic ❗️ effects Devoid of Membrane-Stabilizing Activity (MSA) and → Initial increase in peripheral resistance which slowly Intrinsic Sympathetic Activities (ISA) decreases with prolonged administration Low lipid solubility, water-soluble (hydrophilic) → May cause bronchospasm in patients with asthma and Incompletely absorbed from the GIT → Bioavailability: 35% after an oral administration 📋 COPD (contraindicated) → Long t½ of 33 hours 📋 Has MSA (Membrane stabilizing activity) [2026 TRANS] Metabolized by CYP2D6 in the liver 📋 Can lower renin activity [2026 TRANS] CNS [2026 TRANS] Largely excreted unchanged in the urine → Effective in prophylaxis of migraine → There is a need to decrease the dosage in patients with ▪ Propranolol as a core drug renal failure to avoid drug accumulation and toxicity → Central lowering of sympathetic outflow THERAPEUTIC USES Other important actions and effects PHARMACOLOGY Beta Adrenoceptor Blockers PAGE 7 of 16 PHARMACOLOGY | LE 2 Beta Adrenoceptor Blockers | Alfaretta Luisa T. Reyes, MD, FPSECP 📋 📋 Treatment of: Prototype drug [2026 TRANS] → Hypertension Second-generation beta blocker [2026 TRANS] → Angina pectoris Selective β1 receptor blocker “Off-label” uses: 50-100 fold less potent in blocking β2 receptors than → Migraine prophylaxis Propranolol → Parkinsonian tremors No ISA but has low MSA in larger dose → Variceal bleeding in portal hypertension Low bioavailability after oral administration TIMOLOL → Due to extensive first-pass hepatic metabolism Greater inter-individual variation in plasma concentration of PHARMACOKINETICS & PHARMACODYNAMICS Metoprolol after oral administration No ISA → Due to differences in CYP2D6 activity. No MSA Poor metabolizers of Metoprolol have 5x or more risk for → No local anesthetic or quinidine-like activity developing adverse effects than extensive metabolizers ▪ Makes it desirable as a topical agent in the Half-life: 4-6 hours management of intraocular hypertension or even Compared to Propranolol, Metoprolol has faster recovery glaucoma 📋 from hypoglycemia due to β1 receptor blockade by − It will not eliminate the protective corneal or Propranolol, thereby affecting hepatic glycogenolysis [2026 blinking reflexes TRANS] Recall: Drugs with MSA are undesirable because it has a Does not cross blood-brain barrier 📋 local anesthetic effect to the cornea → eliminates the protective or blinking reflex [2026 TRANS] THERAPEUTIC USES Essential hypertension THERAPEUTIC USES Angina pectoris Hypertension Tachycardia Congestive heart failure Heart failure Acute myocardial infarction (AMI): Secondary prevention after acute MI → According to a Norwegian Multicenter study, it has been → Due to having low MSA shown that timolol can decrease by 39% the mortality Adjunct in treatment of hyperthyroidism rate in patients with AMI. Prophylaxis for migraine Migraine prophylaxis → but NOT acute migraine → But not in acute migraine Recovery from hypoglycemia is faster than with Chronic open-angle glaucoma and intraocular propranolol hypertension: → Decreases aqueous humor production by the ciliary epithelium through beta receptor blockade. ATENOLOL PHARMACOKINETICS & PHARMACODYNAMICS 📋 To some extent, it is also now used in the treatment of acute-angle (or angle-closure) glaucoma [2026 TRANS] Very hydrophilic → Fewer CNS effects PINDOLOL Lacks ISA as well MSA PHARMACOKINETICS & PHARMACODYNAMICS → Similar to Nadolol (non selective drug) Nonselective beta receptor blocker Half-life: 6-9 hours Partial agonistic action or ISA → Shorter compared to Nadolol that has a long half-life → induce less bradycardia → Longer than metoprolol Low MSA Not extensively metabolized (unlike Pindolol and Has low lipid solubility Celiprolol) 📋 BA: 90%; t½ of 3-4 hours Little interindividual variation in plasma concentrations Drug prototype [2026 TRANS] ESMOLOL THERAPEUTIC USES PHARMACOKINETICS & PHARMACODYNAMICS Therapeutically indicated in the treatment of patients with Ultra-short acting; very rapid onset of action hypertension and angina pectoris. Hydrophilic (like Nadolol & Atenolol) → Preferred in individuals with low cardiac reserve or → Low lipid solubility those with a propensity for bradycardia. No MSA, little if any ISA It also blocks exercise-induced increase in HR and CO Rapidly metabolized through hydrolysis by RBC esterases BETA-1 SELECTIVE ADRENOCEPTOR BLOCKERS Half-life: 10-15 minutes (shortest) Exemplified by Metoprolol, Atenolol, Esmolol, and → Ranges from 9-10 minutes, average 10 mins Nebivolol Administered through IV infusion Safer in patients with bronchoconstriction in response to → Steady state concentration is rapidly achieved Propranolol but should be used with caution in patients Therapeutic actions are rapidly terminated upon with history of asthma[KATZUNG] discontinuation of the drug In some with COPD, benefits may exceed risks, as in THERAPEUTIC USES those with MI[KATZUNG] Critically ill patients requiring beta blocker Preferred in patients with diabetes or peripheral vascular Supraventricular arrhythmia disease when beta blocker is required[KATZUNG] Arrhythmia associated with thyrotoxicosis METOPROLOL Intraoperative and postoperative hypertension PHARMACOKINETICS & PHARMACODYNAMICS HPN emergencies PHARMACOLOGY Beta Adrenoceptor Blockers PAGE 8 of 16 PHARMACOLOGY | LE 2 Beta Adrenoceptor Blockers | Alfaretta Luisa T. Reyes, MD, FPSECP → Associated with tachycardia Greater beta than α1 to almost equal blocking potency → Myocardial ischemia 10:1 (𝛃:𝝰1 affinity) → In acutely ill patient No ISA, has MSA[Bruton, 2017] NEBIVOLOL Classified as 3rd generation non selective blocker similar to labetalol and carteolol PHARMACOKINETICS & PHARMACODYNAMICS Most highly selective β1 adrenoceptor blocker PHARMACOKINETICS & PHARMACODYNAMICS 3rd generation β blocker Half-life: 7-10 hours → as it activates nitric oxide synthase Bioavailability: 25-35% Some partial agonist action in β3 receptors Extensively metabolized in the liver by CYP2D6 No MSA, ISA, and α1 receptor blocking properties Produces vasodilation, antioxidant, and Half-life: 11-30 hours (average of 11-12 hours); long-acting antiproliferative effects L-isomer → Useful in treatment of chronic/congestive heart failure → Elicits vasodilation due to increased endothelial release → Attenuates oxygen free radical-initiated lipid of nitric oxide via induction of endothelial NO synthase peroxidation (eNOS); not mediated by alpha blockade → Inhibits vascular smooth muscle mitogenesis → Increase guanylyl cyclase activity independent of its sympathetic blockade. Decreases PVR compared to increased PVR of older → Vasodilation due to calcium antagonistic action (calcium generation β receptor blockers entry blockade) and alpha receptor blockade May increase insulin sensitivity Has no MSA[Katzung, 2018] Lipid profile is not adversely affected → but we will consider it as having MSA Commonly prescribed by cardiologist THERAPEUTIC USES THERAPEUTIC USES Hypertension Used for hypertension Reduces mortality in MI as prophylaxis when combined with conventional therapy MIXED ALPHA & BETA BLOCKERS Reduces mortality in patients with both congestive heart Competitively block beta receptors and to a lesser affinity failure and HPN the α1receptors. Includes Labetalol, Carvedilol, and Bucindolol BUCINDOLOL 3rd generation LABETALOL Non-selective Beta antagonist (like carvedilol and α1 & non-selective β blocker with partial agonist activity medroxaxol) at β2 receptors Weak α1 blocking properties → Affinity in blocking α1:β receptors after an oral dose: 1:3 Has ISA to 1:5-10 Reversible antagonist[Katzung] PHARMACOKINETICS & PHARMACODYNAMICS Well absorbed if given orally PHARMACOKINETICS & PHARMACODYNAMICS Highly protein bound (87%) Completely absorbed from gut after oral administration Peak levels: 2 hours Extensive first-pass metabolism Half-life: 8 hours Increased oral availability by food intake Decreases PVR → Reduces afterload Has cocaine-like effect in inhibiting neuronal uptake of ↑ Plasma HDL may be affected ❗️ norepinephrine (uptake 1) by inhibiting norepinephrine → Does not affect triglycerides transporter (NET) Blocking actions α1 and β2 receptors → Reduced BP by: X. DRUG INTERACTIONS OF BETA BLOCKERS → Decreasing PVR through α1 receptor blockade ▪ HR and CO are not significantly altered Beta blockers may interact with other drugs when → Relaxation of arterial smooth muscles causing administered together vasodilation of blood vessels. Table X. Drug Interactions of Beta Blockers → Blockade of reflex sympathetic stimulation of heart. Drugs Effects → ISA at β2 receptors produces vasodilation of blood Aluminum salts, ↓ absorption of β blockers vessels. Cholestyramine Hypotension induced is accompanied by less tachycardia Phenytoin, ↓ plasma concentration of β Rifampin, blockers (enzyme inhibitors) THERAPEUTIC USES Phenobarbital, Hypertensive emergencies Smoking → Other drugs include Esmolol & Nitrates Cimetidine, ↑ bioavailability of propranolol, Hypertension of pheochromocytoma Hydralazine metoprolol → Due to combined α1 & beta blocking activity Lidocaine Impair lidocaine clearance Chronic hypertension during pregnancy Ca2+ channel Additive effect = ↓ blood pressure → Commonly used: Methyldopa blockers NOTE: Diuretics such as furosemide are also administered (Verapamil) to prevent volume expansion during administration of powerful vasodilators. Other Additive effect = ↓ blood pressure antihypertensive CARVEDILOL drugs α1 & non-selective beta blocker Cardiac ↑ bradycardia glycosides PHARMACOLOGY Beta Adrenoceptor Blockers PAGE 9 of 16 PHARMACOLOGY | LE 2 Beta Adrenoceptor Blockers | Alfaretta Luisa T. Reyes, MD, FPSECP Phenytoin, Additive cardiac depression Table X. Drugs used in open-angle glaucoma Quinidine Drugs Routes Mechanisms (Anti-arrhythmic Cholinomimetics drugs) Pilocarpine Topical Ciliary muscle XI. THERAPEUTIC USES OF BETA BLOCKERS Carbachol contraction, A. CARDIOVASCULAR SYSTEM Physostigmine opening of Echothiophate trabecular Hypertension Demecarium meshwork, → Not the first-line drug now increase → Better drugs are use such as ACE inhibitors and ARBs aqueous Ischemic heart disease (angina pectoris) outflow → Decrease cardiac work slowing and regularization of HR → Decrease oxygen demand Alpha adrenergic agonists Arrhythmias: Nonselective: Topical Increase → Supraventricular tachyarrhythmias Epinephrine, drainage of ▪ Esmolol (critically ill patients) Dipivefrin aqueous humor → Ventricular arrhythmias Alpha2-selective: Topical, Decrease ▪ Digitalis-induced Apraclonidine Post-laser only aqueous humor − Phenytoin and Lidocaine secretion o Lesser side effects Brimonidine Topical → Triggered by exercise or emotion β blockers → With prolonged Q-T syndrome Timolol Topical Decrease → Symptomatic ventricular depolarization without Levobunolol aqueous humor structural heart disease Metipranolol secretion Myocardial infarction Carteolol → Esmolol (acutely ill patients) Betaxolol → β blockers with MSA such as Carvedilol, Metoprolol Levobetaxolol Chronic heart failure Prostaglandins → Bisoprolol, Carvedilol, Metoprolol, Nebivolol Latanoprost Topical Increase Obstructive cardiomyopathy Bimatoprost aqueous → Slowing of ventricular ejection with decrease in outflow Travoprost outflow resistance Tafluprost Dissecting aortic aneurysm = ↓ rate of development of Unoprostone systolic pressure Carbonic Anhydrase Inhibitors B. NEUROPSYCHIATRIC Dorzolamide Topical Decrease Prophylaxis for migraine Brinzolamide aqeuous → NOT for acute migraine secretion due to → Propranolol, Metoprolol, Atenolol, Nadolol, Timolol lack of HCO3 (PMANT) Acetazolamide Oral Decrease → Note: Calcium channel blockers (e.g., Flunarizine) have Methazolamide aqeuous been used, anticonvulsants (valproic acid, topiramate) secretion due to have some prophylactic efficacy lack of HCO3 Acute anxiety states Rho Kinase Inhibitors → Acute panic symptoms (e.g. performance anxiety or Netarsudil Topical Increase “stage fright”) aqeuous Essential tremor outflow Alcohol withdrawal Physostigmine Probably schizophrenia → Indirectly acting anticholinesterase C. ENDOCRINE Alpha2-selective Severe thyrotoxicosis as adjunct to definitive treatment → Used more often → Useful in thyroid storm E. OTHER MISCELLANEOUS USES → Propranolol may be used here Cirrhosis Pheochromocytoma → Diminish portal vein pressure → Not used as a 1st line drug ▪ Decrease mortality associated with bleeding → Other better drugs are used with lesser adverse effects → Nadolol and Propranolo → Must be used only when alpha receptors blockade has Esophageal varices been done. → Decreases the incidence of the first episode of bleeding D. GLAUCOMA AND OCULAR HYPERTENSION ▪ Prevent rebleeding: nadolol with isosorbide Timolol (nonselective), Levobunolol, Metipranolol, mononitrate Carteolol, Betaxolol (selective), Levobetaxalol Infantile hemangioma Chronic wide angle (open-angle) glaucoma and acute → Common vascular tumor in infancy angle glaucoma → Reduces volume, color, and elevation of the tumor Aphakic glaucoma ▪ Infants less than 6 months and children at 5 years of Secondary glaucoma age PHARMACOLOGY Beta Adrenoceptor Blockers PAGE 10 of 16 PHARMACOLOGY | LE 2 Beta Adrenoceptor Blockers | Alfaretta Luisa T. Reyes, MD, FPSECP → Propranolol Melanoma XIV. SUMMARY 📋 Beta receptor blockers are generally classified according XII. CONTRAINDICATIONS to their generation and receptor affinities for the adrenergic Asthma and other obstructive airway disease receptors: → Due to β2 blockade → 1st generation are the classical nonselective beta Acute congestive heart failure blockers (e.g., Propranolol, Nadolol, Pindolol) Heart block due to digitalis or other factors → 2nd generation are the selective beta blockers (e.g., → Beta blockers may further aggravate this condition due Metoprolol, Esmolol, Atenolol) to β1 blockade → 3rd generation are the nonselective and selective Diabetes or in patients susceptible to episodes of beta blocker with additional actions (e.g., Carvedilol, hypoglycemia Labetalol, Nebivolol, Betaxolol) → Insulin dependent diabetes In addition to competitive beta receptor blockade some → Especially with the use of non-selective beta receptor have distinguishing pharmacologic properties like MSA, blockers ISA, degree of lipid solubility, differences in t1/2, Peripheral vascular or vasospastic disorders bioavailability, duration of action. → Raynaud’s disease Some beta receptor blockers have vasodilating actions Symptomatic bradycardia and sinus node dysfunction → Stimulating nitric oxide production (e.g., Carvedilol, Abrupt cessation of beta blocker on chronic administration Labetalol, Nebivolol). → Causes withdrawal syndrome Some of these block alpha 1 and to a greater degree the ▪ Result of upregulation of the number of receptors beta (B1 and B2) receptors (mixed blockade) (e.g., − Becomes super sensitive to catecholamines Carvedilol, Labetalol, Bucindolol) ▪ Lead to rebound phenomenon/withdrawal syndrome → MOA: As competitive blockers to the beta receptors. Inhibits the AC → Low cAMP production XIII. SCHEMATIC REPRESENTATION OF THE EFFECTS Beta receptor blockers produce significant pharmacologic OF ADRENERGIC AGONISTS AND ADRENORECEPTOR BLOCKERS 📋 When Norepinephrine is given, reflex bradycardia occurs actions and effects on certain organ systems like the CVS, respiratory, ocular, endocrine, and the metabolic processes → Some of these may be beneficial or hazardous. at the height of the rise in blood pressure. Avoid abrupt cessation of beta blockers on chronic → Reflex bradycardia due to higher affinity α1 receptor administration to prevent withdrawal syndrome. where you have contraction of the smooth muscle. Beta blockers are therapeutically indicated in conditions Given alpha blockers will not totally decrease alpha effect like hypertension, angina, Grave’s disease, glaucoma, and but it will only suppress it. migraine prophylaxis. Given Epinephrine, biphasic response occurs due to the CVS: Reduction of sympathetic-stimulation increases in α1 effect which is more pronounced but it is fleeting. Once HR, contractility, and CO. BP is diminished as a result of it has waned there is already unmasking of the β2 effect. effects of the heart, RAAS and CNS; slowing of AV → β2 receptors are more sensitive even with low doses of conduction and increased refractory period. epinephrine. Thus, we have a decline in BP due to Respiratory System: Bronchoconstriction of bronchial vasodilation. smooth muscle particularly in asthmatic patients, is the Given an α blocker and Epinephrine will only suppress major adverse effect resulting from β2 blockade due to the alpha effect and will leave the β2 effect unopposed increase in airway resistance. Little effect in normal → Βecomes more pronounced here (dip before individuals. isoproterenol) compared to the previous one (dip on the Selective blockers and those with ISA at receptors are less 2nd alpha blocker & red epinephrine). likely to induce bronchospasm. However, blockers should → Called epinephrine blocker since it’s blocking the beta be avoided if possible in asthmatic patients. receptor effect. Eyes: Topical Beta blockers decrease the production of → Epinephrine reversal aqueous humor by the ciliary body → Low IOP, this is due ▪ Alpha blocker suppresses alpha effect and β2 to low cAMP. becomes more pronounced = ↓BP These drugs are indicated in the treatment of Given Isoproterenol which is a pure beta receptor agonist chronic/open angle glaucoma and in ocular with no alpha effect hypertension eg. Timolol, Levo-bunatol, Betaxolol, → There may be a rise in the blood pressure (BP) due to Levobetaxolol, Carteolol, Metipranolol an increase in cardiac output because isoproterenol is a Beta blockers are commonly used in combination therapy very potent agonist on the β1 receptors and in patients who can not afford prostaglandins in the → BP decreases more due to isoproterenol (dip after treatment of chronic/open-angle glaucoma. isoproterenol before beta blocker) as compared to Carbohydrate Metabolism: epinephrine (dip on the 2nd alpha blocker & red → Partially inhibits hepatic glycogenolysis due to B2 epinephrine); due to β2 effects blockade. → Norepinephrine does not activate any β1 → Nonselective B blockers increase the incidence and Given a beta blocker followed by isoproterenol, decline in severity and delay recovery from hypoglycemia in BP is blunted insulin dependent diabetic patients. Use with caution in → The cardiac output may be decreased initially or it may pancreatectomized patients and in those with go back to its initial value inadequate glucagon reserve → Effect on the peripheral vascular resistance (last dip on Lipid Metabolism: the figure) due to the β2 blockage → β blockers ↑ risk of coronary artery disease as a result → May leave α1 effects unopposed of ↓ HDL, ↑ VLDL 0 LDL change, ↑ triglycerides and a PHARMACOLOGY Beta Adrenoceptor Blockers PAGE 11 of 16 PHARMACOLOGY | LE 2 Beta Adrenoceptor Blockers | Alfaretta Luisa T. Reyes, MD, FPSECP variable & HDL /LDL ratio. These are less likely to occur Katzung, B.G. (2004). Basic & Clinical Pharmacology (14th Ed). New York: Lange Medical Books/McGraw Hill. with drugs with ISA (pindolol, acebutolol, carteolol, Reyes, A. (2022) Beta Adrenoreceptor Blockers Powerpoint penbutolol) In general β receptor blockers have negative metabolic effects but their beneficial effects may outweigh these risks such as in heart failure Newer β receptor blockers are less likely to have negative metabolic effects (carvedilol, nebivolol, metoprolol, bisoprolol). Clinical Toxicity and Adverse Effects: → CVS: bradycardia ( most common), cold extremities, hypotension, heart failure, ischemic heart disease with abrupt cessation → CNS: Lipid soluble β blockers (eg. propranolol) may cause mild sedation, vivid dreams, fatigue and rarely depression → Respiratory System: worsening of pre-existing asthma → Metabolic Effects: hypoglycemia, T risk of coronary artery disease → Withdrawal syndrome (rebound phenomenon) with abrupt discontinuation of chronically use of B blocker Precautions or relative contraindications to the use of Beta blockers include asthma, acute congestive heart failure, heart block, Diabetes or in patients susceptible to episodes of hypoglycemia, peripheral vascular or vasospastic disorders, symptomatic bradycardia and sinus node dysfunction, acute withdrawal of beta blocker on chronic administration. The major clinical uses for β adrenoceptor blockers include hypertension, ischemic heart disease ( angina pectoris), cardiac arrhythmias, glaucoma, chronic heart failure, hyperthyroidism. In general ß1 blockers are preferred in patients with asthma, COPD, diabetes mellitus, or peripheral vascular disease. β blockers with ISA may be preferred in patients with resting bradycardia. Vasodilating β blockers may be preferred in patients with hypertension or heart failure. Patient compliance may be improved by the use of B blockers with a longer half-life. Figure 3. Schematic representation of the effects of adrenergics agonists and adrenoreceptor blockers[PPT] V. REFERENCES 2026 Transcription PHARMACOLOGY Beta Adrenoceptor Blockers PAGE 12 of 16 PHARMACOLOGY | LE 2 Beta Adrenoceptor Blockers | Alfaretta Luisa T. Reyes, MD, FPSECP VI. FORMATIVE QUIZ Question & Choices Answer & Rationale 1. Metoprolol is selective for which adrenoreceptor? β1: selectively antagonized by metoprolol 50-100 fold less potent in blocking β2. A. α1