• Actions of epinephrine:Actions of epinephrine:
1- Cardiovascular:1- Cardiovascular:
• TheThe major actions of epinephrin...
• EpinephrineEpinephrine constrictsconstricts arteriolesarterioles
inin thethe skin, mucous membranes, andskin, mucous mem...
2-2- Respiratory:Respiratory:
• Epinephrine causes powerful bronchodilator byEpinephrine causes powerful bronchodilator by...
3- Hyperglycemia:3- Hyperglycemia:
•Epinephrine has aEpinephrine has a significantsignificant
hyperglycemichyperglycemic e...
4- Lipolysis:4- Lipolysis:
•EpinephrineEpinephrine initiates lipolysisinitiates lipolysis throughthrough
its agonist activ...
• Biotransformations:Biotransformations:
• Epinephrine, like the otherEpinephrine, like the other
catecholamines, is metab...
• Therapeutic usesTherapeutic uses
1- In Bronchospasm:1- In Bronchospasm:
•EpinephrineEpinephrine is the primary drug used...
• Administration may be repeated after aAdministration may be repeated after a
few hours.few hours.
• However, selectiveHo...
2- Glaucoma:2- Glaucoma:
•In ophthalmology, 2% epinephrineIn ophthalmology, 2% epinephrine
solution may be used topically ...
3- Anaphylactic shock:3- Anaphylactic shock:
Epinephrine is the drug of choice for theEpinephrine is the drug of choice fo...
5- With local anesthesia5- With local anesthesia
•Local anesthetic solutions usually contain 1:100,000Local anesthetic sol...
Adverse effectsAdverse effects
1- CNS disturbances:1- CNS disturbances: Epinephrine can produceEpinephrine can produce
adv...
InteractionsInteractions::
1-Hyperthyroidism:1-Hyperthyroidism:
•EpinephrineEpinephrine enhancedenhanced cardiovascularcar...
2-Cocaine:2-Cocaine:
•In the presence ofIn the presence of cocainecocaine, epinephrine, epinephrine
producesproduces exagg...
3- Diabetes:3- Diabetes:
•Epinephrine increases the releaseEpinephrine increases the release
of endogenousof endogenous st...
4-4- ββ-Blockers:-Blockers:
These agents (These agents (ββ-Blockers-Blockers)) preventprevent epinephrine'sepinephrine's
e...
B. NorepinephrineB. Norepinephrine
 Because norepinephrine is theBecause norepinephrine is the
neuromediator of adrenergi...
• Cardiovascular actions:Cardiovascular actions:
• Vasoconstriction:Vasoconstriction:
• Norepinephrine causes a rise inNor...
• NorepinephrineNorepinephrine causes greatercauses greater
vasoconstrictionvasoconstriction thanthan epinephrineepinephri...
Therapeutic usesTherapeutic uses::
1- Norepinephrine is used to treat1- Norepinephrine is used to treat
shockshock, becaus...
Norepinephrine is a potentNorepinephrine is a potent vasoconstrictorvasoconstrictor
and will causeand will cause extravasa...
PharmacokineticsPharmacokinetics::
• Norepinephrine may beNorepinephrine may be given IVgiven IV forfor
rapid onsetrapid o...
• Adverse effects:Adverse effects:
• These are similar to those ofThese are similar to those of epinephrine.epinephrine.
I...
C-IsoproterenolC-Isoproterenol
 Isoproterenol is aIsoproterenol is a direct-acting syntheticdirect-acting synthetic
catec...
• Actions:Actions:
• Cardiovascular:Cardiovascular:
• IIsoproterenolsoproterenol producesproduces intenseintense
stimulati...
IsoproterenoIsoproterenol alsol also dilates thedilates the
arterioles of skeletal musclearterioles of skeletal muscle ((β...
• Pulmonary:Pulmonary:
• AA profound and rapid bronchodilationprofound and rapid bronchodilation
is produced by the drug (...
• Other effects:Other effects:
• Other actions onOther actions on ββ receptors, such asreceptors, such as
increased blood ...
• Pharmacokinetics:Pharmacokinetics:
• Isoproterenol can be absorbedIsoproterenol can be absorbed
systemically by thesyste...
 D. DopamineD. Dopamine
 TheThe immediate metabolic precursorimmediate metabolic precursor ofof
norepinephrine, occurs n...
 In addition,In addition, DD11 and Dand D22 dopaminergicdopaminergic
receptors, occur in thereceptors, occur in the perip...
• Actions:Actions:
• Cardiovascular:Cardiovascular:
• DopamineDopamine exerts aexerts a stimulatory effectstimulatory effe...
• Renal and visceral:Renal and visceral:
• DopamineDopamine dilates renal and splanchnicdilates renal and splanchnic
arter...
Therapeutic usesTherapeutic uses::
• 1- Dopamine is the drug of choice for1- Dopamine is the drug of choice for
shock and ...
• 3-3- enhances perfusionenhances perfusion to theto the kidney andkidney and
splanchnicsplanchnic areas.areas.
• AnAn inc...
• Adverse effects:Adverse effects:
• An overdose of dopamine produces theAn overdose of dopamine produces the
same effects...
DobutamineDobutamine
•Actions:
•Dobutamine is a synthetic, direct-acting
catecholamine that is a β1-receptor agonist.
• It...
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Autonomic nervous system lecture 6

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Autonomic nervous system

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Autonomic nervous system lecture 6

  1. 1. • Actions of epinephrine:Actions of epinephrine: 1- Cardiovascular:1- Cardiovascular: • TheThe major actions of epinephrinemajor actions of epinephrine areare on theon the cardiovascular system.cardiovascular system. • Epinephrine strengthens theEpinephrine strengthens the contractilitycontractility ofof thethe myocardiummyocardium (positive inotropic:(positive inotropic: ββ11 action)action) and increases itsand increases its rate of contractionrate of contraction (positive(positive chronotropicchronotropic:: ββ11 action). Cardiac outputaction). Cardiac output therefore increases.therefore increases. •With these effects comes increasedWith these effects comes increased oxygenoxygen demandsdemands on theon the myocardium.myocardium.
  2. 2. • EpinephrineEpinephrine constrictsconstricts arteriolesarterioles inin thethe skin, mucous membranes, andskin, mucous membranes, and visceraviscera ((αα effects), and iteffects), and it dilatesdilates vesselsvessels going to thegoing to the liver and skeletalliver and skeletal muscle (muscle (ββ22 effects).effects). –RenalRenal blood flow isblood flow is decreaseddecreased.. Therefore, the cumulative effect is anTherefore, the cumulative effect is an increaseincrease inin systolic blood pressuresystolic blood pressure,, coupled with acoupled with a slight decreaseslight decrease inin diastolic pressure .diastolic pressure .
  3. 3. 2-2- Respiratory:Respiratory: • Epinephrine causes powerful bronchodilator byEpinephrine causes powerful bronchodilator by acting directly onacting directly on bronchial smooth muscle (bronchial smooth muscle (ββ22 action).action). •This action relieves all knownThis action relieves all known allergic orallergic or histamine-induced bronchoconstriction.histamine-induced bronchoconstriction. •In the case ofIn the case of anaphylactic shockanaphylactic shock, this can be, this can be lifesaving.lifesaving. •epinephrine rapidly relievesepinephrine rapidly relieves thethe dyspneadyspnea andand increases volume ofincreases volume of gases inspired and expired.gases inspired and expired. •EpinephrineEpinephrine alsoalso inhibitsinhibits thethe releaserelease ofof allergyallergy mediators such as histaminesmediators such as histamines from mast cells.from mast cells.
  4. 4. 3- Hyperglycemia:3- Hyperglycemia: •Epinephrine has aEpinephrine has a significantsignificant hyperglycemichyperglycemic effect because of :effect because of : A-A- increase glycogenolysisincrease glycogenolysis in the liver (in the liver (ββ22 effect).effect). B-B- increasedincreased release ofrelease of gglucagonlucagon ((ββ22 effect).effect). C-C- decreaseddecreased release ofrelease of insulininsulin ((αα22 effect).effect). These effects are mediated via the cAMPThese effects are mediated via the cAMP mechanismmechanism..
  5. 5. 4- Lipolysis:4- Lipolysis: •EpinephrineEpinephrine initiates lipolysisinitiates lipolysis throughthrough its agonist activity on theits agonist activity on the ββ receptors ofreceptors of adipose tissue, which stimulation aadipose tissue, which stimulation a hormone-sensitive lipase,hormone-sensitive lipase, whichwhich hydrolyzeshydrolyzes triacylglycerols totriacylglycerols to free fattyfree fatty acids and glycerol.acids and glycerol.
  6. 6. • Biotransformations:Biotransformations: • Epinephrine, like the otherEpinephrine, like the other catecholamines, is metabolized by twocatecholamines, is metabolized by two enzymatic pathways:enzymatic pathways: • 1- MAO1- MAO • 2- COMT,2- COMT, • The final metabolites found in the urine .The final metabolites found in the urine .
  7. 7. • Therapeutic usesTherapeutic uses 1- In Bronchospasm:1- In Bronchospasm: •EpinephrineEpinephrine is the primary drug used inis the primary drug used in the emergency in treatment of acutethe emergency in treatment of acute asthma and anaphylactic shock.asthma and anaphylactic shock. •epinephrine is theepinephrine is the drug of choicedrug of choice;; within a few minutes afterwithin a few minutes after subcutaneoussubcutaneous administrationadministration, greatly improved, greatly improved respiration.respiration.
  8. 8. • Administration may be repeated after aAdministration may be repeated after a few hours.few hours. • However, selectiveHowever, selective ββ22 agonists, such asagonists, such as AlbuterolAlbuterol are favored in theare favored in the chronicchronic treatment of asthmatreatment of asthma because:because: 1-1- longer durationlonger duration of actionof action 2-2- minimal cardiacminimal cardiac stimulatory effect.stimulatory effect.
  9. 9. 2- Glaucoma:2- Glaucoma: •In ophthalmology, 2% epinephrineIn ophthalmology, 2% epinephrine solution may be used topically tosolution may be used topically to reducereduce intraocular pressure in open-intraocular pressure in open- angle glaucoma.angle glaucoma. •ItIt reduces the production ofreduces the production of aqueous humoraqueous humor byby vasoconstrictionvasoconstriction of theof the ciliary bodyciliary body blood vessels.blood vessels.
  10. 10. 3- Anaphylactic shock:3- Anaphylactic shock: Epinephrine is the drug of choice for theEpinephrine is the drug of choice for the treatment oftreatment of Type I hypersensitivityType I hypersensitivity reactionsreactions in response to allergens.in response to allergens. 4- Cardiac arrest:4- Cardiac arrest: Epinephrine may be used toEpinephrine may be used to restorerestore cardiac rhythmcardiac rhythm in patients within patients with cardiaccardiac arrestarrest..
  11. 11. 5- With local anesthesia5- With local anesthesia •Local anesthetic solutions usually contain 1:100,000Local anesthetic solutions usually contain 1:100,000 parts epinephrine.parts epinephrine. •The effect of the drug is to:The effect of the drug is to: • 1-1-increase the duration of the local anesthesiaincrease the duration of the local anesthesia byby producingproducing vasoconstriction at the site of injectionvasoconstriction at the site of injection,, therebythereby allowingallowing the local anestheticthe local anesthetic to persistto persist atat the injection sitethe injection site before being absorbedbefore being absorbed into theinto the circulation and metabolized.circulation and metabolized. •2-Very weak solutions of epinephrine (1:100,000)2-Very weak solutions of epinephrine (1:100,000) can also be usedcan also be used topically to vasoconstrict mucoustopically to vasoconstrict mucous membranes to controlmembranes to control oozingoozing of capillary blood.of capillary blood.
  12. 12. Adverse effectsAdverse effects 1- CNS disturbances:1- CNS disturbances: Epinephrine can produceEpinephrine can produce adverse CNS effects that include anxiety, fear,adverse CNS effects that include anxiety, fear, tension, headache, and tremor.tension, headache, and tremor. 2-Cerebral hemorrhage:2-Cerebral hemorrhage: The drug may induceThe drug may induce cerebral hemorrhage as a result ofcerebral hemorrhage as a result of elevation bloodelevation blood pressure.pressure. 3- Cardiac arrhythmias:3- Cardiac arrhythmias: Epinephrine can triggerEpinephrine can trigger cardiaccardiac arrhythmias.arrhythmias. 4- Pulmonary edema:4- Pulmonary edema: Epinephrine can induce pulmonaryEpinephrine can induce pulmonary
  13. 13. InteractionsInteractions:: 1-Hyperthyroidism:1-Hyperthyroidism: •EpinephrineEpinephrine enhancedenhanced cardiovascularcardiovascular actionsactions in patients within patients with hyperthyroidism.hyperthyroidism. •IfIf epinephrine is requiredepinephrine is required in such anin such an individual,individual, the dose must be reduced.the dose must be reduced. •The mechanism appears to involveThe mechanism appears to involve increasedincreased productionproduction of adrenergicof adrenergic receptorsreceptors on theon the vasculature of the hyperthyroid individualvasculature of the hyperthyroid individual,, leading to aleading to a hypersensitivehypersensitive response.response.
  14. 14. 2-Cocaine:2-Cocaine: •In the presence ofIn the presence of cocainecocaine, epinephrine, epinephrine producesproduces exaggerated cardiovascularexaggerated cardiovascular actions.actions. •This is due to the ability of cocaine toThis is due to the ability of cocaine to preventprevent reuptakereuptake of catecholaminesof catecholamines intointo the adrenergic neuron;the adrenergic neuron; thus, likethus, like norepinephrine,norepinephrine, epinephrine remains atepinephrine remains at the receptor site forthe receptor site for longer periods oflonger periods of time.time.
  15. 15. 3- Diabetes:3- Diabetes: •Epinephrine increases the releaseEpinephrine increases the release of endogenousof endogenous stores ofstores of glucoseglucose. In. In the diabetic,the diabetic, dosages of insulindosages of insulin administrationadministration may have to bemay have to be increased.increased.
  16. 16. 4-4- ββ-Blockers:-Blockers: These agents (These agents (ββ-Blockers-Blockers)) preventprevent epinephrine'sepinephrine's effects oneffects on ββ receptorsreceptors, leaving, leaving αα- receptor- receptor stimulation.stimulation. This may lead to anThis may lead to an increase in peripheralincrease in peripheral resistanceresistance and anand an increase in blood pressureincrease in blood pressure.. 5- Inhalation anesthetics:5- Inhalation anesthetics: • Inhalational anestheticsInhalational anesthetics sensitize the heart tosensitize the heart to the effects of epinephrinethe effects of epinephrine, which may lead to, which may lead to tachycardia.tachycardia.
  17. 17. B. NorepinephrineB. Norepinephrine  Because norepinephrine is theBecause norepinephrine is the neuromediator of adrenergic nerves,neuromediator of adrenergic nerves, it shouldit should theoreticallytheoretically stimulatestimulate allall types of adrenergic receptorstypes of adrenergic receptors..  In practice, when the drug is given inIn practice, when the drug is given in therapeutic doses to humans,therapeutic doses to humans, thethe αα-- adrenergic receptor is mostadrenergic receptor is most affectedaffected..
  18. 18. • Cardiovascular actions:Cardiovascular actions: • Vasoconstriction:Vasoconstriction: • Norepinephrine causes a rise inNorepinephrine causes a rise in peripheral resistanceperipheral resistance due to intensedue to intense vasoconstriction of most vascularvasoconstriction of most vascular beds,beds, including theincluding the kidneykidney ((αα11 effect).effect). • BothBoth systolic and diastolicsystolic and diastolic bloodblood pressures increase.pressures increase.
  19. 19. • NorepinephrineNorepinephrine causes greatercauses greater vasoconstrictionvasoconstriction thanthan epinephrineepinephrine,, because : it does not inducebecause : it does not induce vasodilationvasodilation viavia ββ22 receptors on blood vesselsreceptors on blood vessels supplying skeletalsupplying skeletal muscles.muscles. • TheThe weakweak ββ22 activity of norepinephrineactivity of norepinephrine also explains why it is not useful in thealso explains why it is not useful in the treatment oftreatment of asthma.asthma.]]
  20. 20. Therapeutic usesTherapeutic uses:: 1- Norepinephrine is used to treat1- Norepinephrine is used to treat shockshock, because it, because it increases vascularincreases vascular resistanceresistance and, therefore,and, therefore, increasesincreases blood pressure.blood pressure. •Other actions of norepinephrine are not considered toOther actions of norepinephrine are not considered to bebe clinically significant.clinically significant. • It isIt is nevernever used forused for asthmaasthma or in combinationor in combination
  21. 21. Norepinephrine is a potentNorepinephrine is a potent vasoconstrictorvasoconstrictor and will causeand will cause extravasationextravasation (discharge of(discharge of bloodblood from vessel into tissues)from vessel into tissues) along thealong the injection site.injection site.
  22. 22. PharmacokineticsPharmacokinetics:: • Norepinephrine may beNorepinephrine may be given IVgiven IV forfor rapid onsetrapid onset of action.of action. • TheThe durationduration of action isof action is 1 to 21 to 2 minutesminutes following thefollowing the end of the infusion periodend of the infusion period.. • It is poorly absorbed afterIt is poorly absorbed after subcutaneoussubcutaneous injectioninjection.. • and isand is destroyed in the gutdestroyed in the gut if administeredif administered orally.orally. • MetabolismMetabolism is similar to that of epinephrine.is similar to that of epinephrine.
  23. 23. • Adverse effects:Adverse effects: • These are similar to those ofThese are similar to those of epinephrine.epinephrine. In addition, norepinephrine mayIn addition, norepinephrine may causecause blanching and sloughingblanching and sloughing of skin alongof skin along injectedinjected vein(due to extreme vasoconstriction).vein(due to extreme vasoconstriction).
  24. 24. C-IsoproterenolC-Isoproterenol  Isoproterenol is aIsoproterenol is a direct-acting syntheticdirect-acting synthetic catecholamine that predominantlycatecholamine that predominantly stimulates bothstimulates both ββ11- and- and ββ22-adrenergic-adrenergic receptors.receptors.  Its non selectivityIts non selectivity is one of the reasonis one of the reason why it iswhy it is rarely used therapeutically.rarely used therapeutically.  Its action onIts action on αα receptors isreceptors is insignificant.insignificant.
  25. 25. • Actions:Actions: • Cardiovascular:Cardiovascular: • IIsoproterenolsoproterenol producesproduces intenseintense stimulationstimulation of theof the heartheart to increase itsto increase its rate and force of contractionrate and force of contraction, causing, causing increasedincreased cardiac output .cardiac output . • It isIt is as active as epinephrineas active as epinephrine in thisin this action and, therefore, is useful in theaction and, therefore, is useful in the treatment oftreatment of atrioventricular block oratrioventricular block or cardiac arrest.cardiac arrest.
  26. 26. IsoproterenoIsoproterenol alsol also dilates thedilates the arterioles of skeletal musclearterioles of skeletal muscle ((ββ22 effect), resulting ineffect), resulting in decreaseddecreased peripheral resistance.peripheral resistance.
  27. 27. • Pulmonary:Pulmonary: • AA profound and rapid bronchodilationprofound and rapid bronchodilation is produced by the drug (is produced by the drug (ββ22 action).action). • Isoproterenol is as active as epinephrineIsoproterenol is as active as epinephrine and rapidlyand rapidly alleviates an acute attackalleviates an acute attack of asthmaof asthma when taken bywhen taken by inhalationinhalation (which is the recommended route).(which is the recommended route). • This action lasts aboutThis action lasts about 1 hour1 hour and mayand may be repeated by subsequent doses.be repeated by subsequent doses.
  28. 28. • Other effects:Other effects: • Other actions onOther actions on ββ receptors, such asreceptors, such as increased blood sugar and increasedincreased blood sugar and increased lipolysis, can be demonstrated but arelipolysis, can be demonstrated but are not clinically significant.not clinically significant. • Therapeutic uses:Therapeutic uses: • IsoproterenolIsoproterenol is nowis now rarelyrarely used as aused as a bronchodilator in asthma.bronchodilator in asthma. • It can be employed toIt can be employed to stimulate thestimulate the heart in emergency situationsheart in emergency situations..
  29. 29. • Pharmacokinetics:Pharmacokinetics: • Isoproterenol can be absorbedIsoproterenol can be absorbed systemically by thesystemically by the sublingual mucosasublingual mucosa but is morebut is more absorbed when givenabsorbed when given parenterallyparenterally or as anor as an inhaled aerosolinhaled aerosol.. • It is a marginal substrate for COMT andIt is a marginal substrate for COMT and is stable to MAO action.is stable to MAO action. • Adverse effects:Adverse effects: • The adverse effects of isoproterenol areThe adverse effects of isoproterenol are similar to those of epinephrine.similar to those of epinephrine.
  30. 30.  D. DopamineD. Dopamine  TheThe immediate metabolic precursorimmediate metabolic precursor ofof norepinephrine, occurs naturally in thenorepinephrine, occurs naturally in the CNSCNS functions as a neurotransmitter, asfunctions as a neurotransmitter, as well as in thewell as in the adrenal medulla.adrenal medulla.  Dopamine can activateDopamine can activate αα- and- and ββ-- adrenergic receptorsadrenergic receptors. For example, at. For example, at higher doseshigher doses,, it canit can cause vasoconstrictioncause vasoconstriction by activatingby activating αα11 receptors, whereas atreceptors, whereas at lower doseslower doses,, itit stimulatesstimulates ββ11 cardiac receptorscardiac receptors..
  31. 31.  In addition,In addition, DD11 and Dand D22 dopaminergicdopaminergic receptors, occur in thereceptors, occur in the peripheral mesentericperipheral mesenteric and renal vascular beds,and renal vascular beds, where binding ofwhere binding of dopamine producesdopamine produces vasodilationvasodilation..
  32. 32. • Actions:Actions: • Cardiovascular:Cardiovascular: • DopamineDopamine exerts aexerts a stimulatory effectstimulatory effect onon thethe ββ11 receptorsreceptors of the heart, having bothof the heart, having both inotropic and chronotropic effects.inotropic and chronotropic effects. • At veryAt very high doses,high doses, dopamine activatesdopamine activates αα 11 receptorsreceptors on the vasculature,on the vasculature, resulting inresulting in vasoconstriction.vasoconstriction.
  33. 33. • Renal and visceral:Renal and visceral: • DopamineDopamine dilates renal and splanchnicdilates renal and splanchnic arteriolesarterioles by activatingby activating dopaminergicdopaminergic receptorsreceptors, thus, thus increasing blood flowincreasing blood flow toto the kidneys and other viscera .the kidneys and other viscera . • Therefore,Therefore, dopamine is clinically useful indopamine is clinically useful in the treatment of shockthe treatment of shock,.,.
  34. 34. Therapeutic usesTherapeutic uses:: • 1- Dopamine is the drug of choice for1- Dopamine is the drug of choice for shock and is given by continuousshock and is given by continuous infusion.infusion. 2-2- ItIt raises the blood pressureraises the blood pressure byby stimulating:stimulating: • A-A- ββ11 receptors on the heartreceptors on the heart to increaseto increase • cardiac output,cardiac output, • B-B- αα11 receptorsreceptors on blood vessels toon blood vessels to • increase total peripheral resistance.increase total peripheral resistance.
  35. 35. • 3-3- enhances perfusionenhances perfusion to theto the kidney andkidney and splanchnicsplanchnic areas.areas. • AnAn increased blood flowincreased blood flow to the kidneyto the kidney enhances the glomerular filtration rate andenhances the glomerular filtration rate and causescauses sodium diuresis.sodium diuresis.
  36. 36. • Adverse effects:Adverse effects: • An overdose of dopamine produces theAn overdose of dopamine produces the same effects as sympathetic stimulation.same effects as sympathetic stimulation. • Dopamine is rapidly metabolized by MAODopamine is rapidly metabolized by MAO or COMT.or COMT. • adverse effectsadverse effects • (nausea, hypertension, arrhythmias)(nausea, hypertension, arrhythmias)
  37. 37. DobutamineDobutamine •Actions: •Dobutamine is a synthetic, direct-acting catecholamine that is a β1-receptor agonist. • It increases cardiac rate and output with few vascular effects. •Therapeutic uses: • Dobutamine is used to increase cardiac output in congestive heart failure as well as for inotropic support after cardiac surgery.

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