adrenergic drugs (vk)
TRANSCRIPT
SYMPATHETIC SYMPATHETIC NERVOUS NERVOUS SYSTEMSYSTEM
(ADRENERGICS)(ADRENERGICS)
SYMPATHOMIMETICSYMPATHOMIMETIC
Sympathomimetic drugs mimic the Sympathomimetic drugs mimic the
effects of sympathetic nerve stimulation effects of sympathetic nerve stimulation
Also adrenergic agonistsAlso adrenergic agonists
Adrenergic receptorsAdrenergic receptors
Adrenergic AgonistsAdrenergic Agonists Chemical classificationChemical classification
CatecholaminesCatecholamines Non-catecholaminesNon-catecholamines
Adrenergic AgonistsAdrenergic AgonistsDifferences Differences
CatecholamineCatecholamine
Cannot use orallyCannot use orally Cannot cross BBBCannot cross BBB
Short- Short-half livehalf live
Examples:Examples:
NorepinephrineNorepinephrine
EpinephrineEpinephrine
IsoproteronolIsoproteronol
DopamineDopamine
DobutamineDobutamine
NoncatecholaminesNoncatecholamines Can use orallyCan use orally Can cross BBBCan cross BBB
Longer half lifeLonger half life
Examples:Examples:
EphedrineEphedrine
PhenylephrinePhenylephrine
TerbutalineTerbutaline
ENDOGENOUS ENDOGENOUS CATECHOLAMINESCATECHOLAMINES
Naturally occurring in body:Naturally occurring in body: Norepinephrine -Norepinephrine -Sites:Sites: postganglionic postganglionic
sympathetic sites (except sweat glands , sympathetic sites (except sweat glands , erector pillorie, hair follicles, )erector pillorie, hair follicles, )
Epinephrine- Epinephrine- Secreted by adrenal medullaSecreted by adrenal medulla Dopamine- Dopamine- Major transmitter in basal Major transmitter in basal
ganglia, CTZ, limbic system, anterior ganglia, CTZ, limbic system, anterior pitutory.pitutory.
SYNTHESISSYNTHESIS
Catecholamine sCatecholamine s
TyrosineTyrosine
↓↓
DopaDopa
↓↓
DopamineDopamine
↓↓
NorepinephrineNorepinephrine
↓↓
EpinephrineEpinephrine
In dopaminergic In dopaminergic neurons, synthesis neurons, synthesis stops herestops here
In noradrenergic neurons, synthesis stops here
Final step only in adrenal medulla and CNS neurons
STORAGE, RELEASE, STORAGE, RELEASE, UPTAKEUPTAKEL-L-
PhenylalaninePhenylalanine Hepatic Hepatic hydroxylase hydroxylase
Adrenergic ReceptorsAdrenergic Receptors
These are mainly 2 typesThese are mainly 2 types
((αα) Alfa) Alfa
((ββ) Beta) Beta
These are again subdivided into These are again subdivided into various typesvarious types
ADRENERGIC ADRENERGIC RECEPTORSRECEPTORS
ADRENERGIC DRUGSADRENERGIC DRUGSSymphathomimeticsSymphathomimetics
DIRECT SYMPHATHOMIMETICSDIRECT SYMPHATHOMIMETICS AdrenalineAdrenaline NoradrenalineNoradrenaline IsoprenalineIsoprenaline PhenylephrinePhenylephrine MethoxamineMethoxamine SalbutamolSalbutamol XylometazolineXylometazoline
INDIRECT SYMPHATHOMIMETICSINDIRECT SYMPHATHOMIMETICS TyramineTyramine AmphetamineAmphetamine
MIXED SYMPHATHOMIMETICSMIXED SYMPHATHOMIMETICS EphedrineEphedrine DopamineDopamine MephenteramineMephenteramine
Pressor agentsPressor agentsNoradrenalineNoradrenaline PhenylephrinePhenylephrine
Ephedrine Ephedrine MethoxamineMethoxamine
DopamineDopamine MephentermineMephentermine
Cardiac stimulantsCardiac stimulantsAdrenalineAdrenaline DobutamineDobutamineIsoprenalineIsoprenaline
BronchodilatorsBronchodilatorsAdrenalineAdrenaline TerbutalineTerbutalineIsoprenalineIsoprenaline SalmeterolSalmeterolSalbutamolSalbutamol FormoterolFormoterol(Albuterol) Bambuterol(Albuterol) Bambuterol
THERAPEUTIC CLASSIFICATION THERAPEUTIC CLASSIFICATION OF ADRENERGIC DRUGSOF ADRENERGIC DRUGS
Nasal decongestantsNasal decongestantsPhenylephrine NaphazolinePhenylephrine NaphazolineXylometazoline PseudoephedrineXylometazoline PseudoephedrineOxymetazoline Phenyl propanolamineOxymetazoline Phenyl propanolamine
CNS stimulantsCNS stimulantsAmphetamine Dexamphetamine Amphetamine Dexamphetamine MethamphetamineMethamphetamine
Anorectics Anorectics Fenfluramine Dexfenfluramine SibutramineFenfluramine Dexfenfluramine Sibutramine
Uterine relaxant and vasodilatorsUterine relaxant and vasodilatorsRitodrineRitodrine SalbutamolSalbutamol
IsoxsuprineIsoxsuprine TerbutalineTerbutaline
PHARMACOLOGICAL PHARMACOLOGICAL ACTIONSACTIONS
Cardiac effectsCardiac effects Positive chronotropic effectPositive chronotropic effect
An action that increases heart rateAn action that increases heart rate Positive dromotropic effectPositive dromotropic effect
An action that speeds conduction of An action that speeds conduction of electrical impulses (electrical impulses (↑ conduction ↑ conduction velocityvelocity through AV node) through AV node)
Positive inotropic effectPositive inotropic effect An action that increases the force of An action that increases the force of
contraction of cardiac musclecontraction of cardiac muscle
Cardiac effects of Cardiac effects of epinephrineepinephrine
Cardiac output is determined by heart Cardiac output is determined by heart rate and stroke volumerate and stroke volume
EpiEpi→ → ββ11receptors at SA node→↑HRreceptors at SA node→↑HR
Epi→ Epi→ ββ11receptors on ventricular receptors on ventricular myocytes→ myocytes→
↑↑ force of contractionforce of contraction
CO = HR x SVCO = HR x SV
vascular smooth musclevascular smooth muscle
In blood vessels In blood vessels supplying skin, supplying skin, mucous membranes, mucous membranes, viscera and kidneys, viscera and kidneys, vascular smooth vascular smooth muscle has almost muscle has almost exclusively alphaexclusively alpha11--adrenergic receptorsadrenergic receptors
Also biphasic Also biphasic response response
αα11
αα1+1+ββ1 effect1 effect
ββ2 effect (at low 2 effect (at low doses)doses) Mainly Mainly αα - -
actionaction
ββ Blocker Blocker ββ2 effect2 effect
αα Blocker Blocker EEEE
(A)(A)
(B)(B)
Biphasic Biphasic Response Response
vascular smooth musclevascular smooth muscle
In blood vessels supplying skeletal In blood vessels supplying skeletal muscle, vascular smooth muscle has both muscle, vascular smooth muscle has both alphaalpha11 and beta and beta22 adrenergic receptors adrenergic receptors
αα11
ββ22
α1 stimulation β2 stimulation
Effects of epinephrine on blood Effects of epinephrine on blood vessel calibervessel caliber
Blood vessels to Blood vessels to skin, mucous skin, mucous membranes, membranes, viscera and viscera and kidneyskidneys
Stimulation of Stimulation of αα11-adrenergic -adrenergic receptors causes receptors causes constriction of constriction of vascular smooth vascular smooth musclemuscle
αα11
Effects of epinephrine on blood vessel Effects of epinephrine on blood vessel caliber: skeletal musclecaliber: skeletal muscle
At low plasma concentrations of Epi, At low plasma concentrations of Epi, ββ22 effect predominates→ vasodilationeffect predominates→ vasodilation
At high plasma concentrations of Epi, At high plasma concentrations of Epi, αα11 effect predominates→ vasoconstrictioneffect predominates→ vasoconstriction
αα11
ββ22
Effects of Epi on arterial blood Effects of Epi on arterial blood pressurepressure
Arterial BP = CO x PVRArterial BP = CO x PVR
Epinephrine: Epinephrine: ↑ ↑ COCO Low doses ↓ PVR (arteriolar Low doses ↓ PVR (arteriolar
dilation in skeletal muscle)dilation in skeletal muscle) High doses ↑PVRHigh doses ↑PVR
Effects of epinephrine on Effects of epinephrine on airwaysairways
Epi→Epi→ββ22-adrenergic -adrenergic
receptors on receptors on
airway smooth airway smooth
muscle→ rapid, muscle→ rapid,
powerful powerful
relaxation→ relaxation→
bronchodilationbronchodilation
Effects of epinephrine in the eyeEffects of epinephrine in the eye Epi at Epi at αα11--
adrenergic adrenergic receptors receptors on radial on radial smooth smooth muscle → muscle → contractioncontraction→ mydriasis→ mydriasis
Epi at B2-Epi at B2-adrenergic adrenergic receptors→ receptors→ relaxation relaxation of ciliary of ciliary musclemuscle
αα11
ββ22
OTHER SYSTEMSOTHER SYSTEMS
GITGIT: Peristalsis is reduced, sphincters are : Peristalsis is reduced, sphincters are contracted.contracted.
BladderBladder : Detrusors relaxed, trigone contracted : Detrusors relaxed, trigone contracted Splenic capsuleSplenic capsule : Contracts (alpha action), RBCs are : Contracts (alpha action), RBCs are
poured poured Skeletal muscleSkeletal muscle : : Neuromuscular transmission is Neuromuscular transmission is
facilitated. (Tremors due to beta 2 actions)facilitated. (Tremors due to beta 2 actions) CNSCNS: Restlessness , tremors , fall in BP and : Restlessness , tremors , fall in BP and
bradycardiabradycardia MetabolicMetabolic : Hyperglycemia, lipolysis : Hyperglycemia, lipolysis
Mnemonic for Mnemonic for therapeutic uses of therapeutic uses of adrenaline adrenaline ABCDEGABCDEG
AA-- Anaphylactic shock Anaphylactic shock
BB-- Bronchial asthma Bronchial asthma
CC-- CardiacCardiac arrestarrest
DD- - Delay absorption of local anestheticsDelay absorption of local anesthetics
EE-- Epistaxis, Elevate BPEpistaxis, Elevate BP
GG-- GlaucomaGlaucoma
OthersOthers : : Reduce nasal congestion, Reduce nasal congestion, Induces mydriasisInduces mydriasis
Epinephrine (contd..)Epinephrine (contd..)
Adverse effects of Adverse effects of epinephrineepinephrine
Hypertensive crisis Hypertensive crisis DysrhythmiasDysrhythmiasAngina pectorisAngina pectorisNecrosis following Necrosis following extravasationextravasation
HyperglycemiaHyperglycemia
DopamineDopamine (DA)(DA)
Dopaminergic neurons in brain, Dopaminergic neurons in brain,
enteric nervous system and kidneyenteric nervous system and kidney
Dopaminergic receptors in brain, Dopaminergic receptors in brain,
mesenteric and renal vascular beds mesenteric and renal vascular beds
DopamineDopamine
Moderate doses DA:Moderate doses DA: Stimulate DA receptors in Stimulate DA receptors in
mesenteric and renal vascular beds mesenteric and renal vascular beds → → vasodilationvasodilation
Stimulate Stimulate ββ11 receptors in heart → receptors in heart → ↑HR and ↑force of contraction↑HR and ↑force of contraction
High doses DA:High doses DA: Stimulate Stimulate αα11 receptors → receptors →
vasoconstrictionvasoconstriction
Therapeutic usesTherapeutic uses
Shock (moderate doses)Shock (moderate doses) ↑ ↑ blood flow to kidney and blood flow to kidney and
mesenterymesentery ↑ ↑ cardiac outputcardiac output
Refractory congestive heart Refractory congestive heart failurefailure Moderate doses ↑ cardiac output Moderate doses ↑ cardiac output
without ↑PVRwithout ↑PVR
ββ11SA nodal cellsSA nodal cells→→↑↑HHRR
ββ11AV nodal cellsAV nodal cells→↑→↑
conduction velocityconduction velocity
ββ11 Ventricular muscle Ventricular muscle cellscells→ ↑ → ↑ force of force of contractioncontraction
Synthetic Catecholamines: Synthetic Catecholamines: IsoproterenolIsoproterenol
Very powerfully Very powerfully stimulates stimulates ββ11- - and and ββ22--adrenergic adrenergic receptorsreceptors No significant No significant
effect at effect at αα11--adrenergic adrenergic receptorsreceptors
Very powerful Very powerful ββ-adrenergic receptor agonist; -adrenergic receptor agonist; no effect at no effect at αα-adrenergic receptors-adrenergic receptors
αα11
ββ22
α1 stimulation β2 stimulation
Synthetic Catecholamines: Synthetic Catecholamines: IsoproterenolIsoproterenol
IsoproterenolIsoproterenol
↓↓arterial BP = ↑CO x ↓↓PVRarterial BP = ↑CO x ↓↓PVR
Decreased arterial blood pressure Decreased arterial blood pressure triggers autonomic reflex arctriggers autonomic reflex arc
Autonomic reflex arc: baroreceptor Autonomic reflex arc: baroreceptor reflexreflex
Carotid and aortic baroreceptors
↓BP
Cardiovascular control center in medulla
↑ ↑ SympatheticSympathetic
outflow→↑NEpioutflow→↑NEpi
↓ ↓ Parasympathetic Parasympathetic outflow→↓AChoutflow→↓ACh
↓↓BPBP
Carotid and aortic baroreceptors
ββ11
IsoproterenolIsoproterenol
↑↑↑↑HRHR
↑↑↑↑SVSV
+ dromo-+ dromo-tropic effecttropic effect
Reflex tachycardiaReflex tachycardia
Effects of isoproterenol on Effects of isoproterenol on airwaysairways
Powerfully Powerfully stimulates stimulates ββ22--adrenergic adrenergic receptors on receptors on airway smooth airway smooth muscle→ rapid, muscle→ rapid, powerful powerful relaxation→ relaxation→ bronchodilationbronchodilation
Therapeutic uses: Therapeutic uses: isoproterenolisoproterenol
BronchodilatorBronchodilator Complete AV block (3Complete AV block (3rdrd degree heart degree heart
block)block)
Synthetic Catecholamines: Synthetic Catecholamines: DobutamineDobutamine
It’s a derivative of DA but not a D1 It’s a derivative of DA but not a D1 or D2 receptor agonist or D2 receptor agonist
Stimulates Stimulates ββ11- and - and ββ22-adrenergic -adrenergic receptors, but at therapeutic doses, receptors, but at therapeutic doses, ββ11-effects-effects predominatepredominate
Increases force of contraction more Increases force of contraction more than increases heart ratethan increases heart rate
↑↑CO = ↑HR x ↑ ↑ SVCO = ↑HR x ↑ ↑ SV
Dobutamine: Therapeutic Dobutamine: Therapeutic usesuses
ShockShock MIMI Cardiac surgery Cardiac surgery Refractory congestive heart failureRefractory congestive heart failure
Major toxic effects of Major toxic effects of catecholaminescatecholamines
All are potentially arrhythmogenicAll are potentially arrhythmogenic Epi and isoproterenol more Epi and isoproterenol more
arrhythmogenic than dopamine and arrhythmogenic than dopamine and dobutaminedobutamine
Some can cause hypertensionSome can cause hypertension Epinephrine, in particular, can cause Epinephrine, in particular, can cause
CNS effects – fear, anxiety, CNS effects – fear, anxiety, restlessnessrestlessness
Dobutamine can cause vomiting and Dobutamine can cause vomiting and seizures in cats – must be used at very seizures in cats – must be used at very low doseslow doses
Adverse effectsAdverse effects
CNS: CNS: RestlessnessRestlessness PalpitationPalpitation Anxiety, tremorsAnxiety, tremors
CVS: CVS: Increase BP….cerebral haemmorrhageIncrease BP….cerebral haemmorrhage Ventricular tachycardia, fibrillationVentricular tachycardia, fibrillation May precipitate angina or AMIMay precipitate angina or AMI
Non-catecholamine Non-catecholamine direct-acting adrenergic direct-acting adrenergic
agonistsagonistsEphedrineEphedrine
Stimulates Stimulates αα11-, -, ββ1 1 and and ββ22-adrenergic -adrenergic receptors and ↑ NE release from receptors and ↑ NE release from noradrenergic fibersnoradrenergic fibers
Repeated injections produce Repeated injections produce tachyphylaxistachyphylaxis
It is resistant MAO, orally It is resistant MAO, orally Longer acting (4-6), cross BBBLonger acting (4-6), cross BBB
Marketed as dietary supplement Marketed as dietary supplement promoted to aid weight loss, ↑ sports promoted to aid weight loss, ↑ sports performance and ↑ energy. Ingredient performance and ↑ energy. Ingredient in OTC nasal decongestants and in OTC nasal decongestants and bronchodilatorsbronchodilators
Uses : Uses : Mild chronic Bronchial asthma, Mild chronic Bronchial asthma, hypotension during spinal anaesthesia hypotension during spinal anaesthesia ,occasionally for postural hypotension ,occasionally for postural hypotension
Sale prohibited by FDA in 2004 Sale prohibited by FDA in 2004 due to risks of life-threatening due to risks of life-threatening cardiac arrhythmias, stroke and cardiac arrhythmias, stroke and deathdeath
Non-catecholamine direct-acting Non-catecholamine direct-acting adrenergic agonists: adrenergic agonists:
Phenylpropanolamine (PPA)Phenylpropanolamine (PPA) Actions much like ephedrine in the Actions much like ephedrine in the
PNSPNS In veterinary medicine, used to treat In veterinary medicine, used to treat
urinary incontinence in dogsurinary incontinence in dogs Available in OTC products for Available in OTC products for
treatment of nasal decongestion and treatment of nasal decongestion and as appetite suppressantas appetite suppressant
FDA has requested all companies FDA has requested all companies discontinue marketing products discontinue marketing products containing PPA due to risk of containing PPA due to risk of hemorrhagic strokehemorrhagic stroke
αα11 ––adrenergic adrenergic receptor receptor agonist- agonist- contraction contraction urethral urethral smooth smooth muscle muscle
ββ2 2 ––adrenergic adrenergic receptor receptor agonist –agonist –relaxation relaxation detrusor detrusor musclemuscle
ββ22-selective adrenergic -selective adrenergic agonistsagonists
β2-adrenergic receptors on bronchial smooth muscle
Preferential affinity for β2-adrenergic receptors, but at sufficiently high doses, can stimulate β1
terbutaline , albuterol inhalation aerosolRelax bronchial smooth muscle→bronchodilationTreatment of asthma, chronic bronchitis
Due to selectivity for Due to selectivity for ββ22 receptors at receptors at
recommended doses, little-to-no direct recommended doses, little-to-no direct
stimulation of stimulation of ββ11 receptors in heart receptors in heart
Inhalant administration maximizes local Inhalant administration maximizes local
effect and minimizes systemic effectseffect and minimizes systemic effects
ββ22-selective adrenergic -selective adrenergic agonistsagonists
MephenteramineMephenteramine
It is mixed sympathomimeticIt is mixed sympathomimetic
COP, BP, heart rate are increasedCOP, BP, heart rate are increased
Active orally with longer DOA (2-6 hrs),can Active orally with longer DOA (2-6 hrs),can
crosses BBBcrosses BBB
UsesUses: : To treat hypotension due to spinal anesthesia and To treat hypotension due to spinal anesthesia and
surgical proceduressurgical procedures Shock in MI and other hypotensive states Shock in MI and other hypotensive states
USESUSES
VascularVascular Hypotensive statesHypotensive states
Shock: hemorrhagic/ hypovolemic, Shock: hemorrhagic/ hypovolemic, spinal, neurogenic, cardiogenic, spinal, neurogenic, cardiogenic, anaphylactic shock.anaphylactic shock.
Postural hypotension- in parkinsonism, Postural hypotension- in parkinsonism, diabetes mallitusdiabetes mallitus
Along with local anaestheticsAlong with local anaesthetics To control local bleedingTo control local bleeding Nasal decongestantsNasal decongestants Peripheral vascular diseasesPeripheral vascular diseasesCardiacCardiac Cardiac arrestCardiac arrest Partial AV blockPartial AV block Congestive heart failureCongestive heart failure
Bronchial asthmaBronchial asthma AcuteAcute severe bronchial asthmasevere bronchial asthmaAllergic disordersAllergic disorders Urticaria, angiodema, anaphylaxisUrticaria, angiodema, anaphylaxisMydriaticsMydriatics Fundus examinationFundus examination Wide angle glaucomaWide angle glaucomaCNS usesCNS uses ADHDADHD NarcolepsyNarcolepsy EpilepsyEpilepsy ParkinsonismParkinsonism ObesityObesityUterine relaxantUterine relaxant
Adrenergic AgonistsAdrenergic Agonists Indirect:Indirect:
Cause NE release Cause NE release onlyonly
Example:Example: AmphetamineAmphetamine
CNS stimulantCNS stimulant Increases BP by Increases BP by
alpha effect on alpha effect on vasculature, beta vasculature, beta effect on hearteffect on heart