Autonomic nervous system

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. • 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. 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. 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. 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. • 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. • 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. • 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. • 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. • 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. 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. 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. 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. • 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. 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. • 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. 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. • 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. • 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. • 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.  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.  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. • 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. • 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. 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. • 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. • 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. 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.