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AUTONOMICS. MA. JANETTH B. SERRANO, M.D. DPBA. SYMPATHETIC DRUGS. Site and Mode of Action: 1. Direct Acting Epinephrine- Dobutamine Phenylephrine- Norepinephrine Isoproterenol- Clonidine 2. Indirect Acting Tyramine, Amphetamine, Cocaine 3. Mixed Acting Agonists - PowerPoint PPT PresentationTRANSCRIPT
AUTONOMICAUTONOMICSS
MA. JANETTH B. SERRANO, M.D. DPBA
Site and Mode of Action:Site and Mode of Action:1. Direct Acting1. Direct Acting
– EpinephrineEpinephrine - Dobutamine- Dobutamine– PhenylephrinePhenylephrine - Norepinephrine - Norepinephrine – IsoproterenolIsoproterenol - Clonidine- Clonidine
2. Indirect Acting2. Indirect Acting– Tyramine, Amphetamine, CocaineTyramine, Amphetamine, Cocaine
3. Mixed Acting Agonists3. Mixed Acting Agonists– DopamineDopamine - Ephedrine- Ephedrine– AmphetamineAmphetamine - -
PhenylpropanolaminePhenylpropanolamine– MetaraminolMetaraminol
SYMPATHETIC DRUGSSYMPATHETIC DRUGS
Sympathetic Sympathetic AgonistsAgonists
SYMPATHOMIMETICSYMPATHOMIMETICSS
αα11 αα22 αα and and ββ ββ11 ββ22
αα11 and and αα22 ββ1 1 and and ββ22
Sympathetic Sympathetic AgonistsAgonists
(Sympathomim(Sympathomimetics) etics)
EPINEPHRINENOREPINEPHRINE
DOPAMINEIBOPAMINE
AMPHETAMINEMETHAMPHETAMINE
EPHEDRINEPSEUDOEPHEDRINE
DOBUTAMINE
ISOPROTERENOL
αα11 αα22 αα and and ββ ββ11 ββ22
αα11 and and αα22 ββ1 1 and and ββ22
Sympathetic Sympathetic AgonistsAgonists(Sympathomi(Sympathomimetics) metics)
PHENYLEPHRINE
METHOXAMINEMEPHENTERMINE
METARAMINOLMITODRINE
αα11 αα22 αα and and ββ ββ11 ββ22
αα11 and and αα22 ββ1 1 and and ββ22
Sympathetic Sympathetic AgonistsAgonists(Sympathomi(Sympathomimetics) metics)
METHYLDOPACLONIDINE
GUANABENZGUANFACINEGUANFACINE
αα11 αα22 αα and and ββ ββ11 ββ22
αα11 and and αα22 ββ1 1 and and ββ22
Sympathetic Sympathetic AgonistsAgonists
(Sympathomi(Sympathomimetics) metics)
NAPHAZOLINETETRAHYDROZOLINE
OXYMETAZOLINEXYLOMETAZOLINE
αα11 αα22 αα and and ββ ββ11 ββ22
αα11 and and αα22
ββ1 1 and and ββ22
Sympathetic Sympathetic AgonistsAgonists
(Sympathomi(Sympathomimetics) metics) METAPROTERENOL
TERBUTALINE, ALBUTEROL
RITODRINEISOETHARINE, PILBUTEROL
BITOLTEROL, FENOTEROL
FORMOTEROL, SALMETEROL
PROCATEROL
Special sympathomimetics:Special sympathomimetics:
COCAINECOCAINE– Local anestheticLocal anesthetic– Inhibits uptake 1 Inhibits uptake 1 Peripheral Peripheral
sympathomimetic actionsympathomimetic action– CNS CNS inhibits reuptake of inhibits reuptake of
dopamine into neurons in the dopamine into neurons in the “pleasure centers” of the brain“pleasure centers” of the brain
Sympathetic Sympathetic AgonistsAgonists
(Sympathomi(Sympathomimetics) metics)
Special sympathomimetics:Special sympathomimetics:TYRAMINETYRAMINE
– Normal by-product of tyrosine Normal by-product of tyrosine metabolismmetabolism
– Fermented foods Fermented foods cheese, red wine cheese, red wine– Metabolized by MAOMetabolized by MAO– Release of stored catecholamines Release of stored catecholamines
indirect sympathomimetic action indirect sympathomimetic action
Sympathetic Sympathetic AgonistsAgonists
(Sympathomi(Sympathomimetics) metics)
Sympathetic Sympathetic AntagonistsAntagonists
SYMPATHOLYTICSSYMPATHOLYTICS
1.1. Adrenergic Neuron Blockers (ANB)Adrenergic Neuron Blockers (ANB)- Guanethedine, ReserpineGuanethedine, Reserpine
2.2. Adrenergic Receptor Blockers (ARB)Adrenergic Receptor Blockers (ARB) ReversibleReversible – – Prazosin, Phentolamine, Prazosin, Phentolamine,
Tolazoline, Labetalol, Tolazoline, Labetalol, Ergot alkaloidsErgot alkaloids IrreversibleIrreversible – – Phenoxybenzamine, Phenoxybenzamine,
DibenamineDibenamine
Sympathetic Sympathetic AntagonistsAntagonists
(Sympatholytics(Sympatholytics) )
Sympathetic Sympathetic AntagonistsAntagonists
(Sympatholytics(Sympatholytics) )
αα11 αα22 αα and and ββ ββ11 ββ22
αα1 1 and and αα22 ΒΒ1 1 and and ββ22
YOHIMBINE BUTOXAMINELABETALOL
CARVEDILOL
αα11 αα22 αα and and ββ ββ11 ββ22
ββ11 and and ββ22
αα1 1 and and αα22
Sympathetic Sympathetic AntagonistsAntagonists(Sympatholytics(Sympatholytics) ) PRAZOSIN, TERAZOSIN
DOXAZOSIN, TRIMAZOSININDORAMIN, URADIPIL
KETANSERIN, ALFUZOSINBUNAZOSIN, TAMSULOSIN
αα11 αα22 αα and and ββ
ββ11 ββ22
αα1 1 and and αα22 ΒΒ1 1 and and ββ22
Sympathetic Sympathetic AntagonistsAntagonists(Sympatholytics) (Sympatholytics)
PHENOXYBENZAMINEPHENTOLAMINE
ERGOT ALKALOIDS
NEUROLEPTIC DRUGS
PHENOXYBENZAMINEPHENOXYBENZAMINE irreversible noncompetetive blockade (14-48
hrs) inhibits NE reuptake Blocks H1, Ach and serotonin receptors Blocks catecholamine-induced vasoconstriction Epinephrine- reversal Cl. Indication: pheochromocytoma
male erectile dysfunctionperipheral vascular diseases
Adv. Eff: postural hypotension, tachycardia
PHENTOLAMINEPHENTOLAMINE Competetive antagonist (4 hrs)Competetive antagonist (4 hrs) Epinephrine- reversal Epinephrine- reversal reduce PVRreduce PVR Cardiac stimulation Cardiac stimulation baroreflex & baroreflex & ↑ NE ↑ NE
releaserelease Inhibits serotonin responsesInhibits serotonin responses Indic: Pheochromocytoma, male erectile Indic: Pheochromocytoma, male erectile
dysfunctiondysfunction Adv. Eff: severe tachycardia, arrhythmia, Adv. Eff: severe tachycardia, arrhythmia,
myocardial ischemia, GI stimulationmyocardial ischemia, GI stimulation
Beta-AdrenergicBeta-AdrenergicBlocking AgentsBlocking Agents
BETA - BLOCKERSBETA - BLOCKERS
αα11 αα22 αα and and ββ ββ11 ββ22
αα1 1 and and αα22 ΒΒ1 1 and and ββ22
Sympathetic Sympathetic AntagonistsAntagonists
(Sympatholytics(Sympatholytics) )
METOPROLOLATENOLOL
ACEBUTOLOLBETAXOLOLCELIPROLOL
ESMOLOL
αα11 αα22 αα and and ββ ββ11 ββ22
αα1 1 and and αα22 ΒΒ1 1 and and ββ22
Sympathetic Sympathetic AntagonistsAntagonists
(Sympatholytics(Sympatholytics) )
PROPRANOLOL
NADOLOL, TIMOLOLPINDOLOL, LEVOBUNOLOL
CARTEOLOL, BISOPROLOL
Beta- Beta- blockersblockers
Pharmacokinetics:Pharmacokinetics:
– oral: peak in 1-3 hrsoral: peak in 1-3 hrs– extensive first-pass extensive first-pass
metabolismmetabolism– half- lives: 3 to 10 hrshalf- lives: 3 to 10 hrs
* Esmolol – 8 – 10 min* Esmolol – 8 – 10 min* Nadolol – 24 hrs* Nadolol – 24 hrs
PHARMACODYNAMICS:PHARMACODYNAMICS:
– CVS: (-) chronotropic, (-) inotropic CVS: (-) chronotropic, (-) inotropic effectseffects
– Respiratory: bronchoconstrictionRespiratory: bronchoconstriction– Eye: reduce IOPEye: reduce IOP– Metabolic & Endocrine:Metabolic & Endocrine:
inhibits lipolysisinhibits lipolysis partial inhibition of glycogenolysispartial inhibition of glycogenolysis ↑ ↑ VLDL and ↓ HDLVLDL and ↓ HDL ↓ ↓ HDL: LDL ratioHDL: LDL ratio
– ISA; MSAISA; MSA
Beta- Beta- blockersblockers
Properties of Beta-receptor Properties of Beta-receptor blocking agents: blocking agents:
Partial Partial Agonist Agonist Activity Activity
((ISA)ISA)
Local Local AnesthetAnesthet
ic ic Activity Activity (MSA)(MSA)
Lipid Lipid Solu-Solu-bilitybility
EliminatioElimination n
Half-lifeHalf-life
Approxi-Approxi-mate mate
Bioavai-Bioavai-labilitylability
Selective Selective ββ11
blockersblockers
AcebutolAcebutololol
++ ++ LowLow 3-4 hrs3-4 hrs 5050
AtenololAtenolol -- -- LowLow 6-9 hrs6-9 hrs 4040BetaxololBetaxolol -- SlightSlight LowLow 14-22 hrs14-22 hrs 9090EsmololEsmolol -- -- LowLow 8-10 8-10
minmin00
CeliprololCeliprolol ++ -- No No datadata
4-5 hrs4-5 hrs 7070
MetoprolMetoprololol
-- ++ ModMod 3-4 hrs3-4 hrs 5050
ISAISA(Partial (Partial Agonist Agonist ActivityActivity))
MSAMSA(Local (Local
AnesthetAnesthetic ic
Activity)Activity)
Lipid Lipid Solu-Solu-bilitybility
Elimina-Elimina-tion tion
Half-lifeHalf-life
Approxi-Approxi-mate mate
Bioavai-Bioavai-labilitylability
NonSelective NonSelective ββ1 1 BlockersBlockers
PropranolPropranololol
-- ++ HighHigh 3.5-6 hrs3.5-6 hrs 3030
CarteololCarteolol ++ -- LowLow 6 hrs6 hrs 8585CarvedilolCarvedilol -- -- No No
DataData6-8 hrs6-8 hrs 25-3525-35
LabetalolLabetalol ++ ++ ModMod 5 hrs5 hrs 3030NadololNadolol -- -- LowLow 14-24 14-24
hrshrs3333
PindololPindolol ++ ++ ModMod 3-4 hrs3-4 hrs 9090TimololTimolol -- -- ModMod 4-50 hrs4-50 hrs 5050
Properties of Beta-receptor Properties of Beta-receptor blocking agents: blocking agents:
CLINICAL INDICATIONS:CLINICAL INDICATIONS: HypertensionHypertension Cardiac arrhythmiasCardiac arrhythmias AnginaAngina CHF: Metoprolol, Bisoprolol, CarvedilolCHF: Metoprolol, Bisoprolol, Carvedilol Glaucoma: Timolol, Betaxolol, Carteolol, Glaucoma: Timolol, Betaxolol, Carteolol,
Levobunolol, MetipranololLevobunolol, Metipranolol Neurologic: Migraine, somatic mgt. of Neurologic: Migraine, somatic mgt. of
anxiety, alcohol withdrawalanxiety, alcohol withdrawalMisc: reduce portal vein pressure in Misc: reduce portal vein pressure in
cirrhosiscirrhosis
Beta- Beta- blockersblockers
Clinical toxicities:Clinical toxicities:
1.1. Drug allergy – rareDrug allergy – rare2.2. CNS effects – sedation, sleep CNS effects – sedation, sleep
disturbances, depression, psychotic rxnsdisturbances, depression, psychotic rxns3.3. Worsening of preexisting asthma & Worsening of preexisting asthma &
airway obstructionairway obstruction4.4. Depress myocardial contractility & Depress myocardial contractility &
excitabilityexcitability5.5. Hypoglycemic episodesHypoglycemic episodes
Beta- Beta- blockersblockers
DRUG DRUG INTERACTION:INTERACTION:– Calcium- channel Calcium- channel VERAPAMILVERAPAMIL Severe Severe
hypotensionhypotension BradycardiaBradycardia CHFCHF arrhythmiaarrhythmia
Beta- Beta- blockersblockers
“A heartfelt apology can’t change the past, but it can brighten the future.”
QUIZQUIZ1.1. Major neurotransmitter of the Major neurotransmitter of the
Sympathetic Nervous SystemSympathetic Nervous SystemWrite A if Agonist or B if Write A if Agonist or B if
Antagonist:Antagonist:2. Epinephrine2. Epinephrine7. Phentolamine7. Phentolamine3. Labetalol3. Labetalol 8. Cocaine8. Cocaine4. Clonidine4. Clonidine 9. 9.
PhenylephrinePhenylephrine5. Prazosin5. Prazosin 10. Ephedrine10. Ephedrine6. Terbutaline6. Terbutaline