 ββ-Adrenergic Blocking Agents-Adrenergic Blocking Agents
 All the clinically availableAll the clinically available ββ -...
 Therefore,Therefore, normal sympathetic controlnormal sympathetic control of theof the
vasculature is maintainedvasculat...
 A. Propranolol(Inderal)A. Propranolol(Inderal)
 AA nonselectivenonselective ββ antagonistantagonist
 Propranolol :Prop...
• Actions:Actions:
• Cardiovascular:Cardiovascular:
• PropranololPropranolol diminishesdiminishes cardiac output,cardiac o...
• Peripheral vasoconstriction:Peripheral vasoconstriction:
– TheThe reduction in cardiac outputreduction in cardiac output...
No postural hypotension occursNo postural hypotension occurs,,
because thebecause the αα11-adrenergic receptors-adrenergic...
• Bronchoconstriction:Bronchoconstriction:
• BlockingBlocking ββ 22 receptorsreceptors inin
the lungs of susceptiblethe lu...
• Increased NaIncreased Na++
retentionretention::
• Reduced blood pressureReduced blood pressure causescauses a decrease i...
• Disturbances in glucose metabolism:Disturbances in glucose metabolism:
• ββ-blockade leads to :-blockade leads to :
• 1-...
• Therapeutic effects:Therapeutic effects:
1- In Hypertension:1- In Hypertension:
 PropranololPropranolol doesdoes not re...
2- Glaucoma:2- Glaucoma:
•ββ-Blockers, topically applied-Blockers, topically applied Timolol,Timolol,
•are effective in di...
• TheyThey neitherneither affect theaffect the ability of the eyeability of the eye
to focus for near visionto focus for n...
3-Migraine:3-Migraine:
•Propranolol is also effective inPropranolol is also effective in reducingreducing
migrainemigraine...
4- Hyperthyroidism:4- Hyperthyroidism:
• Propranolol and otherPropranolol and other ββ -blockers are-blockers are
effectiv...
5- Angina pectoris:5- Angina pectoris:
•PropranololPropranolol decreases the oxygendecreases the oxygen
requirement of hea...
6- Myocardial infarction:6- Myocardial infarction:
•Propranolol and otherPropranolol and other ββ -blockers-blockers have ...
• Propranolol alsoPropranolol also reduces thereduces the
incidence of sudden arrhythmicincidence of sudden arrhythmic dea...
• Adverse effects:Adverse effects:
1-1- Bronchoconstriction:Bronchoconstriction:
Propranolol has aPropranolol has a seriou...
2- Arrhythmias:2- Arrhythmias:
•Treatment withTreatment with ββ-blockers must-blockers must
never benever be stopped quick...
3- Disturbances in metabolism:3- Disturbances in metabolism:
• ββ -Blockade leads to decreased-Blockade leads to decreased...
4- Drug interactions:4- Drug interactions:
•Drugs thatDrugs that interfere with the metabolisminterfere with the metabolis...
B- Timolol and Nadolol:B- Timolol and Nadolol:
 NonselectiveNonselective ββ antagonistsantagonists
Timolol and Nadolol a...
 C-C- Acebutolol, Atenolol, and Esmolol:Acebutolol, Atenolol, and Esmolol:
SelectiveSelective ββ11 antagonistsantagonists...
• Therapeutic use in hypertension:Therapeutic use in hypertension:
• TheThe cardioselectivecardioselective ββ -blockers ar...
Pindolol and Acebutolol:Pindolol and Acebutolol:
(Antagonists with partial agonist(Antagonists with partial agonist
activi...
• Decreased metabolic effects:Decreased metabolic effects:
• Blockers withBlockers with ISAISA minimize theminimize the
di...
• Therapeutic use in hypertension:Therapeutic use in hypertension:
• ββ -Blockers with ISA-Blockers with ISA are effective...
 Drugs Affecting NeurotransmitterDrugs Affecting Neurotransmitter
Release or UptakeRelease or Uptake
 amphetamine and ty...
 A. ReserpineA. Reserpine
 Reserpine a plant alkaloid,Reserpine a plant alkaloid, blocks theblocks the
MgMg2+2+
/adenosi...
 Sympathetic functionSympathetic function, in general, is, in general, is impairedimpaired
because of decreased release o...

This leads to gradual depletion ofThis leads to gradual depletion of
norepinephrine in nerve endings exceptnorepinephrin...
 C. CocaineC. Cocaine
 Although cocaine inhibits norepinephrineAlthough cocaine inhibits norepinephrine
uptake, it is an...
Autonomic nervous system lecture 8
Autonomic nervous system lecture 8
Autonomic nervous system lecture 8
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Autonomic nervous system lecture 8

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Autonomic nervous system

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Autonomic nervous system lecture 8

  1. 1.  ββ-Adrenergic Blocking Agents-Adrenergic Blocking Agents  All the clinically availableAll the clinically available ββ -blockers are-blockers are competitive antagonistscompetitive antagonists..  NonselectiveNonselective ββ-blockers act at both-blockers act at both ββ11 andand ββ22 receptors, whereasreceptors, whereas cardioselectivecardioselective ββ antagonists primarilyantagonists primarily blockblock ββ 11 receptors.receptors.  [Note:There are[Note:There are no clinically usefulno clinically useful ββ22 antagonistsantagonists]]  Although allAlthough all ββ -blockers lower blood pressure-blockers lower blood pressure in hypertension,in hypertension, they do not induce posturalthey do not induce postural hypotension, because thehypotension, because the αα-adrenoceptors-adrenoceptors remain functional.remain functional.
  2. 2.  Therefore,Therefore, normal sympathetic controlnormal sympathetic control of theof the vasculature is maintainedvasculature is maintained..  ββ -Blockers are also effective-Blockers are also effective in treating:in treating:  angina,angina,  cardiac arrhythmias,cardiac arrhythmias,  myocardial infarction,myocardial infarction,  congestive heart failure,congestive heart failure,  hyperthyroidism,hyperthyroidism,  and glaucoma,and glaucoma,  as well as serving in theas well as serving in the prophylaxis of migraineprophylaxis of migraine headaches.headaches.
  3. 3.  A. Propranolol(Inderal)A. Propranolol(Inderal)  AA nonselectivenonselective ββ antagonistantagonist  Propranolol :Propranolol : is theis the ββ-adrenergic-adrenergic antagonistantagonist and blocks bothand blocks both ββ11 andand ββ22 receptors.receptors.  Sustained-release preparationsSustained-release preparations forfor once-a-day dosing are available.once-a-day dosing are available.
  4. 4. • Actions:Actions: • Cardiovascular:Cardiovascular: • PropranololPropranolol diminishesdiminishes cardiac output,cardiac output, having bothhaving both negative inotropic andnegative inotropic and chronotropic effects.chronotropic effects. The resultingThe resulting bradycardia .bradycardia . • Cardiac output, work, and oxygenCardiac output, work, and oxygen consumptionconsumption areare decreaseddecreased by blockade ofby blockade of ββ11 receptors;receptors; these effects arethese effects are useful in theuseful in the treatment of angina .treatment of angina .
  5. 5. • Peripheral vasoconstriction:Peripheral vasoconstriction: – TheThe reduction in cardiac outputreduction in cardiac output leads toleads to decreased blood pressure.decreased blood pressure. • ThisThis hypotensionhypotension triggerstriggers a reflex peripherala reflex peripheral vasoconstrictionvasoconstriction that is reflected inthat is reflected in reduced blood flow to the periphery.reduced blood flow to the periphery. • On balance, there is a gradualOn balance, there is a gradual reductionreduction of both systolic and diastolicof both systolic and diastolic bloodblood pressurespressures in hypertensive patients.in hypertensive patients.
  6. 6. No postural hypotension occursNo postural hypotension occurs,, because thebecause the αα11-adrenergic receptors-adrenergic receptors that control vascular resistancethat control vascular resistance areare unaffected.unaffected.
  7. 7. • Bronchoconstriction:Bronchoconstriction: • BlockingBlocking ββ 22 receptorsreceptors inin the lungs of susceptiblethe lungs of susceptible patients causespatients causes contractioncontraction of the bronchiolar smooth muscleof the bronchiolar smooth muscle .. • This can precipitate a respiratory crisis inThis can precipitate a respiratory crisis in patients withpatients with chronic obstructivechronic obstructive pulmonary disease (COPD) or asthma.pulmonary disease (COPD) or asthma. • are thusare thus contraindicated in patients withcontraindicated in patients with COPD or asthma.COPD or asthma.
  8. 8. • Increased NaIncreased Na++ retentionretention:: • Reduced blood pressureReduced blood pressure causescauses a decrease ina decrease in renal perfusionrenal perfusion, resulting in an, resulting in an increase in Naincrease in Na++ retention and plasma volume .retention and plasma volume . • In some cases, this compensatory responseIn some cases, this compensatory response tends totends to elevate the blood pressureelevate the blood pressure.. • For these patients,For these patients, ββ -blockers are often-blockers are often combined with acombined with a diuretic to prevent Nadiuretic to prevent Na++ retention.retention. • By inhibitingBy inhibiting ββ receptors,receptors, renin productionrenin production isis also preventedalso prevented,, contributing to Nacontributing to Na++ retention.retention.
  9. 9. • Disturbances in glucose metabolism:Disturbances in glucose metabolism: • ββ-blockade leads to :-blockade leads to : • 1-1-decreaseddecreased glycogenolysisglycogenolysis andand decreaseddecreased glucagon secretion.glucagon secretion. • Therefore, if a Type I (insulin-dependent)Therefore, if a Type I (insulin-dependent) diabeticdiabetic is to be given propranololis to be given propranolol,, veryvery careful monitoring of blood glucosecareful monitoring of blood glucose isis essential,essential, because hypoglycemia may occurbecause hypoglycemia may occur after insulin injection.after insulin injection. 2-2- ββ -Blockers also-Blockers also attenuateattenuate thethe normalnormal physiologic response to hypoglycemia.physiologic response to hypoglycemia.
  10. 10. • Therapeutic effects:Therapeutic effects: 1- In Hypertension:1- In Hypertension:  PropranololPropranolol doesdoes not reduce blood pressurenot reduce blood pressure in people with normal blood pressure.in people with normal blood pressure.  Propranolol lowers blood pressurePropranolol lowers blood pressure inin hypertension patients by several differenthypertension patients by several different mechanisms of action:mechanisms of action: 1.1.Decreased cardiac outputDecreased cardiac output is the primaryis the primary mechanism.mechanism. 2. decreased sympathetic2. decreased sympathetic outflow from theoutflow from the CNS .CNS .
  11. 11. 2- Glaucoma:2- Glaucoma: •ββ-Blockers, topically applied-Blockers, topically applied Timolol,Timolol, •are effective in diminishing intraocularare effective in diminishing intraocular pressure in glaucoma.pressure in glaucoma. •This occurs byThis occurs by decreasing the secretiondecreasing the secretion of aqueous humorof aqueous humor by theby the ciliary body.ciliary body. •Many patients with glaucoma have beenMany patients with glaucoma have been maintained with these drugs for years.maintained with these drugs for years.
  12. 12. • TheyThey neitherneither affect theaffect the ability of the eyeability of the eye to focus for near visionto focus for near vision • nornor changechange pupil size,pupil size, as do theas do the cholinergic drugs.cholinergic drugs. • However, in anHowever, in an acute attack ofacute attack of glaucoma,glaucoma, pilocarpinepilocarpine is still the drug ofis still the drug of choice.choice. • TheThe ββ -blockers are only used to treat this-blockers are only used to treat this disease chronically.disease chronically.
  13. 13. 3-Migraine:3-Migraine: •Propranolol is also effective inPropranolol is also effective in reducingreducing migrainemigraine when used prophylactically.when used prophylactically. •ββ-Blockers are valuable in the treatment-Blockers are valuable in the treatment ofof chronic migraine,chronic migraine, in which theyin which they decrease thedecrease the incidence and severity ofincidence and severity of the attacks.the attacks.
  14. 14. 4- Hyperthyroidism:4- Hyperthyroidism: • Propranolol and otherPropranolol and other ββ -blockers are-blockers are effective ineffective in blunting the widespreadblunting the widespread sympathetic stimulation that occurs insympathetic stimulation that occurs in hyperthyroidism.hyperthyroidism. •In acute hyperthyroidism,In acute hyperthyroidism, ββ -blockers-blockers may bemay be lifesavinglifesaving in protecting againstin protecting against serious cardiac arrhythmias.serious cardiac arrhythmias.
  15. 15. 5- Angina pectoris:5- Angina pectoris: •PropranololPropranolol decreases the oxygendecreases the oxygen requirement of heart musclerequirement of heart muscle and,and, therefore, is effective in reducing thetherefore, is effective in reducing the chest pain on exertionchest pain on exertion that is common inthat is common in angina.angina. • PropranololPropranolol is therefore useful in theis therefore useful in the chronic management ofchronic management of stable angina,stable angina, but notbut not for acute treatment.for acute treatment.
  16. 16. 6- Myocardial infarction:6- Myocardial infarction: •Propranolol and otherPropranolol and other ββ -blockers-blockers have ahave a protectiveprotective effect on theeffect on the myocardium.myocardium. •Thus, patients who haveThus, patients who have one myocardialone myocardial infarction appear to beinfarction appear to be protected against aprotected against a second heart attacksecond heart attack by prophylactic use ofby prophylactic use of ββ-- blockers.blockers. •In addition, administration of aIn addition, administration of a ββ-blocker-blocker immediately following aimmediately following a myocardialmyocardial infarctioninfarction reducesreduces infarct size and hastensinfarct size and hastens recovery.recovery.
  17. 17. • Propranolol alsoPropranolol also reduces thereduces the incidence of sudden arrhythmicincidence of sudden arrhythmic deathdeath after myocardial infarction.after myocardial infarction.
  18. 18. • Adverse effects:Adverse effects: 1-1- Bronchoconstriction:Bronchoconstriction: Propranolol has aPropranolol has a seriousserious andand potentiallypotentially lethal sidelethal side effect when administered toeffect when administered to anan asthmaticasthmatic .. •Deaths by asphyxiationDeaths by asphyxiation for asthmaticsfor asthmatics administered the drug.administered the drug. •Therefore, propranolol must never be used inTherefore, propranolol must never be used in treating any individual with COPD or asthma.treating any individual with COPD or asthma.
  19. 19. 2- Arrhythmias:2- Arrhythmias: •Treatment withTreatment with ββ-blockers must-blockers must never benever be stopped quicklystopped quickly becausebecause of the risk of precipitatingof the risk of precipitating cardiaccardiac arrhythmiasarrhythmias, which may be severe., which may be severe. •TheThe ββ-blockers must-blockers must be tapered offbe tapered off gradually for 1 week.gradually for 1 week. •Long-term treatment with aLong-term treatment with a ββ antagonist leadsantagonist leads toto up-regulation of theup-regulation of the ββ-receptor-receptor.. •On stop of therapy, the increased receptorsOn stop of therapy, the increased receptors can worsen angina or hypertension.can worsen angina or hypertension.
  20. 20. 3- Disturbances in metabolism:3- Disturbances in metabolism: • ββ -Blockade leads to decreased-Blockade leads to decreased glycogenolysis and decreased glucagonglycogenolysis and decreased glucagon secretion.secretion. Fasting hypoglycemia mayFasting hypoglycemia may occur.occur.
  21. 21. 4- Drug interactions:4- Drug interactions: •Drugs thatDrugs that interfere with the metabolisminterfere with the metabolism ofof propranolol, such as cimetidine, fluoxetinepropranolol, such as cimetidine, fluoxetine (inhibit(inhibit metabolismmetabolism), may), may potentiate itspotentiate its antihypertensive effects.antihypertensive effects. • Conversely, those thatConversely, those that stimulate itsstimulate its metabolism,metabolism, such as barbiturates, phenytoin,such as barbiturates, phenytoin, and rifampin,and rifampin, can decrease its effectscan decrease its effects..
  22. 22. B- Timolol and Nadolol:B- Timolol and Nadolol:  NonselectiveNonselective ββ antagonistsantagonists Timolol and Nadolol also blockTimolol and Nadolol also block ββ11- and- and ββ22-- adrenoceptors and are moreadrenoceptors and are more potent thanpotent than propranolol.propranolol.  Nadolol has a very long duration of actionNadolol has a very long duration of action ..  Timolol reducesTimolol reduces the production of aqueousthe production of aqueous humor in the eye. It is usedhumor in the eye. It is used topicallytopically in thein the treatment oftreatment of chronic open-angle glaucomachronic open-angle glaucoma and,and, occasionally, foroccasionally, for systemicsystemic treatment oftreatment of hypertension.hypertension.
  23. 23.  C-C- Acebutolol, Atenolol, and Esmolol:Acebutolol, Atenolol, and Esmolol: SelectiveSelective ββ11 antagonistsantagonists  Drugs that block theDrugs that block the ββ11 receptorsreceptors have beenhave been developed to eliminatedeveloped to eliminate the unwantedthe unwanted bronchoconstrictor effect (bronchoconstrictor effect (ββ 22 effect)effect) ofof propranolol seen amongpropranolol seen among asthmatic patients.asthmatic patients.  This cardioselectivity is thus most at lowThis cardioselectivity is thus most at low doses and is lost at high doses.doses and is lost at high doses.
  24. 24. • Therapeutic use in hypertension:Therapeutic use in hypertension: • TheThe cardioselectivecardioselective ββ -blockers are useful in-blockers are useful in hypertensive patients withhypertensive patients with impairedimpaired pulmonary function.pulmonary function. • Because these drugs haveBecause these drugs have less effect onless effect on peripheral vascularperipheral vascular ββ22 receptorsreceptors, the, the coldnesscoldness of extremitiesof extremities (a common side effect of(a common side effect of ββ -blocker therapy)-blocker therapy) is less frequent.is less frequent. • CardioselectiveCardioselective ββ -blockers are useful in-blockers are useful in diabetic hypertensivediabetic hypertensive patients who arepatients who are receivingreceiving insulin or oral hypoglycemic agents.insulin or oral hypoglycemic agents.
  25. 25. Pindolol and Acebutolol:Pindolol and Acebutolol: (Antagonists with partial agonist(Antagonists with partial agonist activity)activity) Actions:Actions: • Cardiovascular:Cardiovascular: areare not pure antagonistsnot pure antagonists;; they have thethey have the ability to weakly stimulate bothability to weakly stimulate both ββ11 andand ββ22 receptors and are said to havereceptors and are said to have intrinsic sympathomimetic activity (ISA).intrinsic sympathomimetic activity (ISA). • These partial agonistsThese partial agonists stimulate thestimulate the ββ receptor to which they are bound,receptor to which they are bound, yet theyyet they inhibit stimulationinhibit stimulation by the more potentby the more potent endogenous catecholamines, epinephrine andendogenous catecholamines, epinephrine and
  26. 26. • Decreased metabolic effects:Decreased metabolic effects: • Blockers withBlockers with ISAISA minimize theminimize the disturbancesdisturbances of lipid and carbohydrateof lipid and carbohydrate metabolism that are seen with othermetabolism that are seen with other ββ -blockers.-blockers.
  27. 27. • Therapeutic use in hypertension:Therapeutic use in hypertension: • ββ -Blockers with ISA-Blockers with ISA are effective in hypertensiveare effective in hypertensive patientspatients withwith moderate bradycardia,moderate bradycardia, • because abecause a furtherfurther decrease in heartdecrease in heart raterate isis less pronounced with these drugs.less pronounced with these drugs. • Carbohydrate metabolismCarbohydrate metabolism isis less affectedless affected with Acebutolol and pindololwith Acebutolol and pindolol than it is withthan it is with propranolol, making them valuable in thepropranolol, making them valuable in the treatment of diabetics.treatment of diabetics.
  28. 28.  Drugs Affecting NeurotransmitterDrugs Affecting Neurotransmitter Release or UptakeRelease or Uptake  amphetamine and tyramine,amphetamine and tyramine, they exert theirthey exert their effectseffects indirectly on the adrenergic neuronindirectly on the adrenergic neuron byby causing thecausing the release of neurotransmitter fromrelease of neurotransmitter from storage vesicles.storage vesicles.  Similarly, some agents act on theSimilarly, some agents act on the adrenergicadrenergic neuron :neuron :  either to interfere witheither to interfere with neurotransmitter releaseneurotransmitter release  or to alter theor to alter the uptake of the neurotransmitter intouptake of the neurotransmitter into the adrenergic nerve.the adrenergic nerve.
  29. 29.  A. ReserpineA. Reserpine  Reserpine a plant alkaloid,Reserpine a plant alkaloid, blocks theblocks the MgMg2+2+ /adenosine triphosphate/adenosine triphosphate (dependent(dependent transport of biogenic amines)transport of biogenic amines) norepinephrine, dopamine, and serotoninnorepinephrine, dopamine, and serotonin from the cytoplasm intofrom the cytoplasm into storage vesiclesstorage vesicles in the adrenergic nervesin the adrenergic nerves of all bodyof all body tissues.tissues.  This causes the ultimate depletion of biogenicThis causes the ultimate depletion of biogenic amines.amines.
  30. 30.  Sympathetic functionSympathetic function, in general, is, in general, is impairedimpaired because of decreased release ofbecause of decreased release of norepinephrine.norepinephrine.  The drug has aThe drug has a slow onset, a long durationslow onset, a long duration ofof action, andaction, and effects that persist for many dayseffects that persist for many days after discontinuation.after discontinuation.  GuanethidineGuanethidine  blocks the releaseblocks the release ofof stored norepinephrinestored norepinephrine asas well aswell as displacesdisplaces norepinephrine from storagenorepinephrine from storage vesiclesvesicles (thus producing a transient increase(thus producing a transient increase inin blood pressure).blood pressure).
  31. 31.  This leads to gradual depletion ofThis leads to gradual depletion of norepinephrine in nerve endings exceptnorepinephrine in nerve endings except for those in the CNS.for those in the CNS.  Guanethidine commonly causesGuanethidine commonly causes orthostatic hypotensionorthostatic hypotension ..  Supersensitivity to norepinephrine due toSupersensitivity to norepinephrine due to depletion of the amine can result indepletion of the amine can result in hypertensive crisis in patients withhypertensive crisis in patients with pheochromocytoma.pheochromocytoma.
  32. 32.  C. CocaineC. Cocaine  Although cocaine inhibits norepinephrineAlthough cocaine inhibits norepinephrine uptake, it is an adrenergic agonist.uptake, it is an adrenergic agonist.  norepinephrine accumulate in thenorepinephrine accumulate in the synaptic space ,resulting in enhancementsynaptic space ,resulting in enhancement of sympathetic activity and potentiationof sympathetic activity and potentiation the action of epinephrine, norepinephrine.the action of epinephrine, norepinephrine.

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