 Group – B -Group – B - ‫ثامر‬ ‫حسان‬‫ثامر‬ ‫حسان‬
 PhenylephrinePhenylephrine
 Phenylephrine is aPhenylephrine is a di...
 Phenylephrine is aPhenylephrine is a vasoconstrictorvasoconstrictor
that raises boththat raises both systolic and diasto...
 It is often usedIt is often used topically on thetopically on the nasalnasal
mucous membranes and inmucous membranes and...
 ClonidineClonidine
 Clonidine is anClonidine is an αα22 agonistagonist that is used inthat is used in
essential hyperte...
 Albuterol, and TerbutalineAlbuterol, and Terbutaline
 areare short-actingshort-acting ββ22 agonists usedagonists used
p...
 Indirect-Acting Adrenergic AgonistsIndirect-Acting Adrenergic Agonists
 Indirect-acting adrenergic agonistsIndirect-act...
 A.A. AmphetamineAmphetamine
 the drug canthe drug can increase blood pressureincrease blood pressure
significantly bysi...
 The CNS stimulant effects of amphetamineThe CNS stimulant effects of amphetamine
and its derivatives have led to theiran...
 B-TyramineB-Tyramine
 Tyramine isTyramine is not anot a clinically useful drugclinically useful drug, but it, but it
is...
 Like amphetamines, tyramine canLike amphetamines, tyramine can enter theenter the
nerve terminal and displace storednerv...
 Consequently, norepinephrineConsequently, norepinephrine accumulatesaccumulates
in thein the synaptic space,synaptic spa...
 Mixed-Action Adrenergic AgonistsMixed-Action Adrenergic Agonists
 Mixed-action drugsMixed-action drugs induceinduce the...
Ephedrine andEphedrine and
pseudoephedrinepseudoephedrine
 are plant alkaloids, that are now madeare plant alkaloids, tha...
 Ephedrine and pseudoephedrineEphedrine and pseudoephedrine are notare not
catechols and arecatechols and are poor substr...
 EphedrineEphedrine raises systolic and diastolicraises systolic and diastolic
blood pressures by vasoconstriction andblo...
Therapeutic uses:Therapeutic uses:
1- Ephedrine has been used to treat asthma1- Ephedrine has been used to treat asthma,,
...
Adrenergic AntagonistsAdrenergic Antagonists
(blockers or sympatholytic(blockers or sympatholytic agents)agents)
 The adr...
 TheThe adrenergic antagonistsadrenergic antagonists areare
classified according to theirclassified according to their re...
 αα-Adrenergic Blocking Agents-Adrenergic Blocking Agents
 Drugs thatDrugs that blockblock αα -adrenoceptors-adrenocepto...
 [Note:[Note: ββ receptors, includingreceptors, including ββ 11--
adrenoceptors on the heart, are not affected byadrenoce...
 A. PhenoxybenzamineA. Phenoxybenzamine
 PhenoxybenzaminePhenoxybenzamine is nonselective,is nonselective,
linkinglinkin...
 Therefore, the actions ofTherefore, the actions of
phenoxybenzaminephenoxybenzamine last about 24 hourslast about 24 hou...
• Actions:Actions:
• Cardiovascular effects:Cardiovascular effects:
ByBy blockingblocking αα receptors, phenoxybenzaminere...
• Therapeutic uses:Therapeutic uses:
 Phenoxybenzamine is used in the treatment ofPhenoxybenzamine is used in the treatme...
 PhentolaminePhentolamine
 In contrast to phenoxybenzamine,In contrast to phenoxybenzamine,
phentolamine producesphentol...
 Phentolamine-induced reflexPhentolamine-induced reflex cardiaccardiac
stimulation and tachycardiastimulation and tachyca...
 C.C. Prazosin.Prazosin.
 areare selective competitive blockers of theselective competitive blockers of the αα11 recepto...
• Therapeutic uses:Therapeutic uses:
• the first dose of these drugs produces anthe first dose of these drugs produces an
...
• Adverse effects:Adverse effects:
• αα11 BlockersBlockers may cause dizziness, a lack ofmay cause dizziness, a lack of
en...
 YohimbineYohimbine
 Yohimbine is aYohimbine is a selective competitiveselective competitive αα 22
blocker.blocker.
 us...
Autonomic nervous system lecture 7
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Autonomic nervous system

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Autonomic nervous system lecture 7

  1. 1.  Group – B -Group – B - ‫ثامر‬ ‫حسان‬‫ثامر‬ ‫حسان‬  PhenylephrinePhenylephrine  Phenylephrine is aPhenylephrine is a direct-acting,direct-acting, synthetic adrenergicsynthetic adrenergic drug that bindsdrug that binds primarily toprimarily to αα receptorsreceptors ( favors( favors αα11 receptors overreceptors over αα 22 receptors).receptors).  It is not aIt is not a catechol derivativecatechol derivative and,and, therefore, not a substrate fortherefore, not a substrate for COMT.COMT.
  2. 2.  Phenylephrine is aPhenylephrine is a vasoconstrictorvasoconstrictor that raises boththat raises both systolic and diastolicsystolic and diastolic blood pressuresblood pressures..  It has no effect on theIt has no effect on the heart itselfheart itself butbut ratherrather induces reflex bradycardiainduces reflex bradycardia when given parenterallywhen given parenterally..
  3. 3.  It is often usedIt is often used topically on thetopically on the nasalnasal mucous membranes and inmucous membranes and in ophthalmicophthalmic solutionssolutions forfor mydriasis.mydriasis.  PhenylephrinePhenylephrine actsacts as a nasalas a nasal decongestantdecongestant and produces prolongedand produces prolonged vasoconstriction.vasoconstriction.  Large doses can causeLarge doses can cause hypertensivehypertensive headache and cardiac irregularheadache and cardiac irregular..
  4. 4.  ClonidineClonidine  Clonidine is anClonidine is an αα22 agonistagonist that is used inthat is used in essential hypertensionessential hypertension to lowerto lower bloodblood pressurepressure because of its action in the CNS.because of its action in the CNS.  ClonidineClonidine acts centrally to produce :acts centrally to produce : 1-1- inhibitioninhibition ofof sympathetic vasomotorsympathetic vasomotor centers.centers. 2- decreasing sympathetic outflow to the2- decreasing sympathetic outflow to the periphery.periphery.
  5. 5.  Albuterol, and TerbutalineAlbuterol, and Terbutaline  areare short-actingshort-acting ββ22 agonists usedagonists used primarily asprimarily as bronchodilatorsbronchodilators andand administered by aadministered by a metered-dose inhaler.metered-dose inhaler.
  6. 6.  Indirect-Acting Adrenergic AgonistsIndirect-Acting Adrenergic Agonists  Indirect-acting adrenergic agonistsIndirect-acting adrenergic agonists cause:cause: 1. norepinephrine release1. norepinephrine release fromfrom presynaptic terminalspresynaptic terminals 2. or2. or inhibitinhibit thethe uptake of norepinephrine.uptake of norepinephrine. 3. They3. They potentiate the effects ofpotentiate the effects of norepinephrinenorepinephrine producedproduced endogenouslyendogenously..  These agents do not directly affectThese agents do not directly affect postsynaptic receptors.postsynaptic receptors.
  7. 7.  A.A. AmphetamineAmphetamine  the drug canthe drug can increase blood pressureincrease blood pressure significantly bysignificantly by αα-agonist-agonist action on theaction on the vasculature as well asvasculature as well as ββ-stimulatory-stimulatory effects on the hearteffects on the heart..  Its peripheral actions are mediatedIts peripheral actions are mediated primarily through theprimarily through the blockade ofblockade of norepinephrine uptake and cellular releasenorepinephrine uptake and cellular release of stored catecholamines;of stored catecholamines; thus, amphetaminethus, amphetamine is an indirect-acting adrenergic drug.is an indirect-acting adrenergic drug.
  8. 8.  The CNS stimulant effects of amphetamineThe CNS stimulant effects of amphetamine and its derivatives have led to theirand its derivatives have led to their use foruse for  treatingtreating hyperactivity in children,hyperactivity in children, narcolepsynarcolepsy,,  appetite controlappetite control..  Its use in pregnancyIts use in pregnancy should be avoidedshould be avoided because of adverse effects onbecause of adverse effects on developmentdevelopment of the fetus.of the fetus.
  9. 9.  B-TyramineB-Tyramine  Tyramine isTyramine is not anot a clinically useful drugclinically useful drug, but it, but it is important because it is found inis important because it is found in fermentedfermented foods, such as ripe cheesefoods, such as ripe cheese..  Normally, it isNormally, it is oxidized by MAO in theoxidized by MAO in the gastrointestinal tract,gastrointestinal tract, but if the patient isbut if the patient is takingtaking MAO inhibitorsMAO inhibitors, it can precipitate, it can precipitate serious vasopressor episodes.serious vasopressor episodes.
  10. 10.  Like amphetamines, tyramine canLike amphetamines, tyramine can enter theenter the nerve terminal and displace storednerve terminal and displace stored norepinephrine.norepinephrine. The released catecholamineThe released catecholamine then acts on adrenoceptors.then acts on adrenoceptors.  C. CocaineC. Cocaine  Cocaine is a local anesthetics in having theCocaine is a local anesthetics in having the ability toability to block the Nablock the Na++ / K/ K++ -activated-activated ATPaseATPase (required for cellular(required for cellular uptake of norepinephrine)uptake of norepinephrine) on the cell membrane of the adrenergicon the cell membrane of the adrenergic neuron.neuron.
  11. 11.  Consequently, norepinephrineConsequently, norepinephrine accumulatesaccumulates in thein the synaptic space,synaptic space, resulting inresulting in enhancement ofenhancement of sympathetic activitysympathetic activity andand potentiation of the actions of epinephrinepotentiation of the actions of epinephrine and norepinephrine.and norepinephrine.  In addition, theIn addition, the duration of actionduration of action ofof epinephrine and norepinephrineepinephrine and norepinephrine is increasedis increased..  Cocaine can increase blood pressure byCocaine can increase blood pressure by αα-- agonist actions andagonist actions and ββ-stimulatory effects.-stimulatory effects.
  12. 12.  Mixed-Action Adrenergic AgonistsMixed-Action Adrenergic Agonists  Mixed-action drugsMixed-action drugs induceinduce thethe release ofrelease of norepinephrinenorepinephrine fromfrom presynaptic terminalspresynaptic terminals,,  and theyand they activateactivate adrenergic receptorsadrenergic receptors onon the postsynaptic membrane.the postsynaptic membrane.
  13. 13. Ephedrine andEphedrine and pseudoephedrinepseudoephedrine  are plant alkaloids, that are now madeare plant alkaloids, that are now made synthetically.synthetically.  TheyThey not onlynot only releaserelease stored norepinephrinestored norepinephrine from nerve endings butfrom nerve endings but also directlyalso directly stimulate bothstimulate both αα andand ββ receptorsreceptors..  Thus, produce adrenergic actions that areThus, produce adrenergic actions that are similar to those of epinephrine,similar to those of epinephrine, althoughalthough less potent.less potent.
  14. 14.  Ephedrine and pseudoephedrineEphedrine and pseudoephedrine are notare not catechols and arecatechols and are poor substrates forpoor substrates for COMT and MAOCOMT and MAO;;  thus, these drugs have athus, these drugs have a long duration oflong duration of action.action.  Ephedrine and pseudoephedrine haveEphedrine and pseudoephedrine have excellent absorption orallyexcellent absorption orally and penetrateand penetrate into the CNS; however,into the CNS; however, pseudoephedrinepseudoephedrine hashas fewer CNS effects.fewer CNS effects.
  15. 15.  EphedrineEphedrine raises systolic and diastolicraises systolic and diastolic blood pressures by vasoconstriction andblood pressures by vasoconstriction and cardiac stimulation.cardiac stimulation.  EphedrineEphedrine producesproduces bronchodilationbronchodilation, but, but it is less potent thanit is less potent than epinephrine orepinephrine or isoproterenolisoproterenol and produces its actionand produces its action moremore slowly.slowly.  It is therefore sometimes usedIt is therefore sometimes used prophylacticallyprophylactically in chronic treatmentin chronic treatment of asthma toof asthma to preventprevent attacks rather than to treatattacks rather than to treat the acute attack.the acute attack.
  16. 16. Therapeutic uses:Therapeutic uses: 1- Ephedrine has been used to treat asthma1- Ephedrine has been used to treat asthma,, 2- as a nasal2- as a nasal decongestantdecongestant (due to its local(due to its local vasoconstrictor action),vasoconstrictor action), 3- to raise blood pressure.3- to raise blood pressure.  [Note: The clinical use of ephedrine is[Note: The clinical use of ephedrine is declining due to :declining due to : a- the availability ofa- the availability of better drug.better drug.  b- more potentb- more potent agents that causeagents that cause fewerfewer adverse effects.adverse effects.
  17. 17. Adrenergic AntagonistsAdrenergic Antagonists (blockers or sympatholytic(blockers or sympatholytic agents)agents)  The adrenergic antagonistsThe adrenergic antagonists bind tobind to adrenoceptorsadrenoceptors but do not trigger the usualbut do not trigger the usual receptor-mediated intracellular effectsreceptor-mediated intracellular effects..  These drugs act by eitherThese drugs act by either reversibly orreversibly or irreversibly attaching to the receptorirreversibly attaching to the receptor, thus, thus preventingpreventing its activation byits activation by endogenousendogenous catecholamines.catecholamines.
  18. 18.  TheThe adrenergic antagonistsadrenergic antagonists areare classified according to theirclassified according to their relativerelative affinities foraffinities for αα oror ββ receptors in thereceptors in the peripheral nervous systemperipheral nervous system..
  19. 19.  αα-Adrenergic Blocking Agents-Adrenergic Blocking Agents  Drugs thatDrugs that blockblock αα -adrenoceptors-adrenoceptors profoundlyprofoundly affect blood pressureaffect blood pressure..  BecauseBecause normal sympatheticnormal sympathetic control of thecontrol of the vasculature throughvasculature through actions onactions on αα-adrenergic-adrenergic receptors,receptors, blockade of theseblockade of these receptorsreceptors reducesreduces the sympatheticthe sympathetic tonetone of theof the blood vesselsblood vessels,, resultingresulting in decreasedin decreased peripheral vascularperipheral vascular resistance.resistance.  This induces aThis induces a reflex tachycardia resultingreflex tachycardia resulting from thefrom the lowered blood pressure.lowered blood pressure.
  20. 20.  [Note:[Note: ββ receptors, includingreceptors, including ββ 11-- adrenoceptors on the heart, are not affected byadrenoceptors on the heart, are not affected by αα blockade.]blockade.]
  21. 21.  A. PhenoxybenzamineA. Phenoxybenzamine  PhenoxybenzaminePhenoxybenzamine is nonselective,is nonselective, linkinglinking covalentlycovalently to bothto both αα11-- postsynaptic andpostsynaptic and αα22-presynaptic-presynaptic receptors .receptors .  The block isThe block is irreversible and noncompetitiveirreversible and noncompetitive  And the only mechanism the body has forAnd the only mechanism the body has for overcomingovercoming thethe blockblock is tois to synthesizesynthesize newnew adrenoceptors, whichadrenoceptors, which requires a dayrequires a day or moreor more..
  22. 22.  Therefore, the actions ofTherefore, the actions of phenoxybenzaminephenoxybenzamine last about 24 hourslast about 24 hours after a single administration.after a single administration.  After the drug is injected,After the drug is injected, a delay ofa delay of aa few hours occurs before afew hours occurs before a blockadeblockade develops,develops, because thebecause the molecule mustmolecule must undergo biotransformationundergo biotransformation to theto the activeactive form.form.
  23. 23. • Actions:Actions: • Cardiovascular effects:Cardiovascular effects: ByBy blockingblocking αα receptors, phenoxybenzaminereceptors, phenoxybenzamine prevents vasoconstrictionprevents vasoconstriction of peripheralof peripheral blood vessels byblood vessels by endogenous catecholamines.endogenous catecholamines. – The decreased peripheralThe decreased peripheral resistanceresistance provokes a reflex tachycardiaprovokes a reflex tachycardia.. • Thus, the drug has beenThus, the drug has been unsuccessful inunsuccessful in maintaining lowered blood pressuremaintaining lowered blood pressure inin hypertensionhypertension and has beenand has been discontinued fdiscontinued foror this purpose.this purpose.
  24. 24. • Therapeutic uses:Therapeutic uses:  Phenoxybenzamine is used in the treatment ofPhenoxybenzamine is used in the treatment of pheochromocytomapheochromocytoma ((a catecholamine-a catecholamine- secreting tumor of cells derived from thesecreting tumor of cells derived from the adrenal medulla)adrenal medulla).. • Adverse effects:Adverse effects: • Phenoxybenzamine can causePhenoxybenzamine can cause postural hypotension,postural hypotension, nausea, and vomiting.nausea, and vomiting. • The drug also mayThe drug also may induce reflex tachycardiainduce reflex tachycardia, and, and is contraindicated in patients withis contraindicated in patients with decreaseddecreased coronary perfusion.coronary perfusion.
  25. 25.  PhentolaminePhentolamine  In contrast to phenoxybenzamine,In contrast to phenoxybenzamine, phentolamine producesphentolamine produces a competitivea competitive block ofblock of αα11 andand αα 22 receptorsreceptors..  The drug's action lasts forThe drug's action lasts for approximatelyapproximately 4 hours4 hours after a single administration.after a single administration.  Like phenoxybenzamine, it producesLike phenoxybenzamine, it produces postural hypotension .postural hypotension .
  26. 26.  Phentolamine-induced reflexPhentolamine-induced reflex cardiaccardiac stimulation and tachycardiastimulation and tachycardia are mediatedare mediated by the baroreceptor reflex and by blocking theby the baroreceptor reflex and by blocking the αα 22 receptors of the cardiac sympatheticreceptors of the cardiac sympathetic nerves.nerves.  Phentolamine is used for thePhentolamine is used for the short-termshort-term management of pheochromocytoma.management of pheochromocytoma.
  27. 27.  C.C. Prazosin.Prazosin.  areare selective competitive blockers of theselective competitive blockers of the αα11 receptorreceptor.. These drugs are useful in the treatment ofThese drugs are useful in the treatment of hypertension.hypertension. • Cardiovascular effects:Cardiovascular effects: • this agentthis agent decrease peripheraldecrease peripheral vascular resistancevascular resistance andand lower arterial bloodlower arterial blood pressure bypressure by causing thecausing the relaxation of both arterial and venous smoothrelaxation of both arterial and venous smooth muscle.muscle.  These drugs, unlike phenoxybenzamine andThese drugs, unlike phenoxybenzamine and phentolamine,phentolamine, cause minimal changescause minimal changes in cardiacin cardiac output, renal blood flow, and the glomerularoutput, renal blood flow, and the glomerular filtration rate.filtration rate.
  28. 28. • Therapeutic uses:Therapeutic uses: • the first dose of these drugs produces anthe first dose of these drugs produces an exaggeratedexaggerated orthostatic hypotensiveorthostatic hypotensive response that can result in syncoperesponse that can result in syncope (fainting).(fainting). • This action, termed aThis action, termed a (first-dose effect)(first-dose effect) may be minimized by :may be minimized by : 1.1. adjusting the first dose toadjusting the first dose to one-third or one-one-third or one- fourthfourth of the normal doseof the normal dose 2.2. and by giving theand by giving the drug at bedtime.drug at bedtime.
  29. 29. • Adverse effects:Adverse effects: • αα11 BlockersBlockers may cause dizziness, a lack ofmay cause dizziness, a lack of energy, nasal congestion, headache,energy, nasal congestion, headache, drowsiness, and orthostatic hypotension .drowsiness, and orthostatic hypotension . • An additive antihypertensiveAn additive antihypertensive effect occurseffect occurs when prazosin is given with either awhen prazosin is given with either a diureticdiuretic or aor a ββ-blocker,-blocker, thereby necessary tothereby necessary to reduction inreduction in its dose.its dose. • Due to a tendency toDue to a tendency to retain sodium and fluidretain sodium and fluid,, prazosin is frequently usedprazosin is frequently used along with aalong with a diuretic.diuretic.
  30. 30.  YohimbineYohimbine  Yohimbine is aYohimbine is a selective competitiveselective competitive αα 22 blocker.blocker.  used as a sexual stimulant.used as a sexual stimulant.  Yohimbine works at the level of theYohimbine works at the level of the CNS toCNS to increaseincrease sympathetic outflowsympathetic outflow to the periphery.to the periphery.  ItIt directly blocksdirectly blocks αα22 receptorsreceptors..  Yohimbine is contraindicated inYohimbine is contraindicated in CNS andCNS and cardiovascular conditionscardiovascular conditions because it is abecause it is a CNS and cardiovascular stimulant.CNS and cardiovascular stimulant.

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