Group – B -Group – B - ثامر حسانثامر حسان
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.
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..
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
Large doses can causeLarge doses can cause hypertensivehypertensive
headache and cardiac irregularheadache and cardiac irregular..
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
2- decreasing sympathetic outflow to the2- decreasing sympathetic outflow to the
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.
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.
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.
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,
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.
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.
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++
(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
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.
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.
Ephedrine andEphedrine and
are plant alkaloids, that are now madeare plant alkaloids, that are now made
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.
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
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.
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
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.
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.
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
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..
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
This induces aThis induces a reflex tachycardia resultingreflex tachycardia resulting
from thefrom the lowered blood pressure.lowered blood pressure.
[Note:[Note: ββ receptors, includingreceptors, including ββ 11--
adrenoceptors on the heart, are not affected byadrenoceptors on the heart, are not affected by
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..
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
• 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.
• 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.
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 .
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
Phentolamine is used for thePhentolamine is used for the short-termshort-term
management of pheochromocytoma.management of pheochromocytoma.
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
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.
• 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
• 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.
• 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
Yohimbine is aYohimbine is a selective competitiveselective competitive αα 22
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.