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Adrenotropic drugsAdrenotropic drugs (adrenomimetics, (adrenomimetics, adrenoblockers)adrenoblockers)

Lecture Lecture №№22

Adrenergic Adrenergic drugs - drugs - medical substances medical substances

which act in adrenergic which act in adrenergic synapsessynapses

Adrenergic synapseAdrenergic synapseAdrenergic synapseAdrenergic synapse

NoradrenalineNoradrenaline

ThyrosineThyrosine

КОМТКОМТКОМТКОМТ

О-methylationО-methylation

NaNa++NaNa++

CaCa2+2+CaCa2+2+

-, -adrenoreceptorspostsynaptic membrane-, -adrenoreceptorspostsynaptic membrane

NoradrenalineNoradrenaline

Presynaptic membranePresynaptic membraneThyrosineThyrosine

DOPADOPA

DopamineDopamine

PhenilalaninePhenilalanine

DesaminationDesamination

МАО

Adrenergic receptor typesAdrenergic receptor types

Name Typical locations

α 1

Postsynaptic effector cells of the smooth muscles of small vessels of the skin, mucosal membranes, kidneys, mesenterial vessels, muscle dilatator of the pupil, myometrium, sphincters of the GI tract.

α 2

Presynaptic adrenergic nerve terminals, platelets, lipocytes, smooth muscle.

Especially – CNS on the brake neurons.

β 1Postsynaptic effector cells, especially heart; lipocytes.

β 2

Postsynaptic effector cells, especially smooth muscles of the bronchi, myomethrium, vessels of skeletal muscles.

β -specific Liver (hepatocytes), lyposytes, skeletal muscles

Main effects mediated by alpfa and beta-adrenoreceptorsMain effects mediated by alpfa and beta-adrenoreceptors

Alpha 1Alpha 1 Alpha 2Alpha 2 Beta1Beta1 Beta 2 Beta 2 Beta-Beta-specific specific

Vasoconstric-tion

Increased peripheral resistance

Increase blood pressure

MydriasisIncreased closure of internal sphincter of

the bladder

Sedative effect on CNS, decrease BP Inhibition of the insulin release

Increase of the

all function of

the heart

(tachycardia

increase BP,

myocardium

contractility,

increase

oxygen

demands of

the

myocardium

Broncho-dilatation

Relax myometrium

Relax smooth muscles of sleletal muscles

Increase muscle and liver glycogenoly-sis

Increase release of glucagonum

Increase of

the

methabolic

processes

in the

organism

(glycolysis,

lypolysis,

glycogeno-

lysis)

І. І. AdrenomimeticsAdrenomimetics 1. 1. ----adrenomimeticsadrenomimetics ((Adrenalini hydrochloridumAdrenalini hydrochloridum))

22. . --adrenomimeticsadrenomimetics ((Noradrenalini hydrotartrasNoradrenalini hydrotartras MesatonumMesatonum, , NaphtizinumNaphtizinum))

33. . --adrenomimeticsadrenomimetics ((SalbutamolSalbutamol, , PhenoterolPhenoterol, , Dobutaminum Dobutaminum))

ІІ.ІІ. Sympathomimetics Sympathomimetics ((Ephedrini hydrochloridumEphedrini hydrochloridum))

ІІІ. ІІІ. AdrenoblockersAdrenoblockers 1. 1. --adrenoblockersadrenoblockers ((PrasosinumPrasosinum, , DoxasosinumDoxasosinum))

2.2. --adrenoblockersadrenoblockers ((AnaprilinumAnaprilinum, , AtenololumAtenololum,, TalinololumTalinololum,, Metoprololum Metoprololum))

3. 3. - і - і --adrenoblockersadrenoblockers ((LabetalolumLabetalolum))

ІІІ. ІІІ. Sympatholytics Sympatholytics ((Reserpinum, OctadinumReserpinum, Octadinum))

Classification of adrenotropic drugs Classification of adrenotropic drugs

Direct-acting adrenergic Direct-acting adrenergic agonistsagonists

These drugs act directly on α and β These drugs act directly on α and β receptors, producing effects similar receptors, producing effects similar to those than occur following to those than occur following stimulation of sympathetic nerves. stimulation of sympathetic nerves. As a group these agents are widely As a group these agents are widely used clinically.used clinically.

Adrenalini hydrochloridum Adrenalini hydrochloridum (Epinephrinum)(Epinephrinum)

is a hormone of medullar layer is a hormone of medullar layer of adrenal glands which is used in of adrenal glands which is used in a form of a remedya form of a remedy

It is an adrenomimetic which It is an adrenomimetic which stimulates stimulates 11,- ,- 22-- and and 11,- ,- 22--adrenoreceptorsadrenoreceptors

Pharmacological effects of AdrenalinumPharmacological effects of Adrenalinum

Cardiovascular system Constriction of the small vessels and increasing the blood pressure (short effect – 5 minutes only). Cardiac output increases, increasing oxygen demands on the myocardium.

Respiratory system: Bronchodilatation (β2 receptors)

Hyperglycemia: Significant hyperglycemic effect because of increased glycogenolysis in liver (β2 effect), and the decreased release of insulinum. Thus it can be used in causes of acute hypoglycemia.

Metabolic processes: Initiation lypolysis through agonist activity on the β receptors of adipose tissue, which upon stimulation, activate adenylatcyclase to increase 3,5cyclic AMP levels. Cyclic AMP stimulates a hormone-sensitive lipase, which hydrolyses fat. This process leads to secrete of high quantity of energy.

Eye: The radial pupillary dilator muscle of the iris contains α receptors; activation by adrenaline causes mydriasis. This drug also can decrease the intraocular pressure.

Administration of adrenalinumAdministration of adrenalinum Cardiac arrest,Cardiac arrest, for examplefor example, , during during

surgical narcosis, electric trauma surgical narcosis, electric trauma sudden cardiac death (intracardial sudden cardiac death (intracardial

administration). administration). shock and collapse conditionsshock and collapse conditions bronchial spasmbronchial spasm hypoglycemic comahypoglycemic comafor prolongation of anesthetics action for prolongation of anesthetics action

due to vasoconstriction and for due to vasoconstriction and for reduction reduction of regional blood flow of regional blood flow is desirable is desirable for achieving hemostasis for achieving hemostasis in surgery.in surgery.

treatment of open-angle glaucomatreatment of open-angle glaucoma

ContraindicationsContraindications hypertension,hypertension, severe atherosclerosis, severe atherosclerosis,

coronarocardiosclerosis, coronarocardiosclerosis, cardiogenic and cardiogenic and

posthemorragic shocks, posthemorragic shocks, diabetes mellitus, diabetes mellitus,

thyreotoxicosisthyreotoxicosis

Noradrenalini hydrotartrasNoradrenalini hydrotartras ((norepinephrinenorepinephrine))

Is an adrenomimetic of direct action which Is an adrenomimetic of direct action which stimulates preferentially stimulates preferentially -adrenoreceptors-adrenoreceptors

Administration Administration in cases of acute decreasing of blood in cases of acute decreasing of blood

pressure - shock and collapse pressure - shock and collapse conditions, surgeries, traumasconditions, surgeries, traumas

NB! The drug is absolutely NB! The drug is absolutely contraindicated for subcutaneous contraindicated for subcutaneous and intramuscular introductionsand intramuscular introductions

DopaminumDopaminum

Drug of first choice for Drug of first choice for treatment of treatment of

shock and collapseshock and collapse of of different ethiology, including different ethiology, including cardiogenic and hemorrhagiccardiogenic and hemorrhagic

Mesatonum Mesatonum ((phenylephrinphenylephrin))Is a syntheticIs a synthetic a a11--adrenomimetic drug of adrenomimetic drug of

direct actiondirect action

AdministrationAdministration acute hypotensive conditionsacute hypotensive conditions,, prophylaxis of decreasing of blood prophylaxis of decreasing of blood

pressure in case of infectious diseases, pressure in case of infectious diseases, poisoningspoisonings,,

decreasing of blood pressure during decreasing of blood pressure during narcosis with fluorothan and cyclopropannarcosis with fluorothan and cyclopropan

nose drops in case of rhinitsnose drops in case of rhinits

NaphtisinNaphtisin

XylometazolinXylometazolinareare a a22--adrenomimetics of direct actionadrenomimetics of direct action

Usage Usage for rhinitis in a form of nose drops – for rhinitis in a form of nose drops – 1-21-2 dropsdrops 2-3 2-3 times a daytimes a day

NB! It is not recommended to use the NB! It is not recommended to use the drug in case of chronic colddrug in case of chronic cold

DobutaminumDobutaminum

Is a synthetic Is a synthetic 11--adrenomimeticadrenomimeticCardiotonic effects of dobutamin is 5 Cardiotonic effects of dobutamin is 5 times stronger than action of times stronger than action of dopaminedopamine

AdministrationAdministrationsome forms of acute and chronic some forms of acute and chronic cardiac insufficiency intravenous cardiac insufficiency intravenous transfusion with the speed oftransfusion with the speed of

2,5-10 2,5-10 mkg mkg // ((kgkg..minmin))

SalbutamolSalbutamol ((ventolinventolin))

selective selective

bb22--adrenomimetic adrenomimetic of direct actionof direct action

AdministrationAdministration inhalations during attacks of bronchial inhalations during attacks of bronchial

asthma and bronchial spasms of other asthma and bronchial spasms of other etiologyetiology,,

premature child deliverypremature child delivery, , rapid rapid (vigorous)(vigorous) child deliverychild delivery

FenoterolFenoterol ( (berotekberotek, , partusistenpartusisten))

Is stimulant of mostlyIs stimulant of mostly 22--adreno adreno receptors. Posses broncholytic and receptors. Posses broncholytic and tokolytic activitytokolytic activity

SympathomimeticsSympathomimetics

Ephedrini hydrochloridumEphedrini hydrochloridumIt has indirect It has indirect a-, b-a-, b-adrenomimeticadrenomimetic ( (sympathomimeticsympathomimetic) ) actionaction

Administration Administration collapse conditions, for prophylaxis of decreasing of collapse conditions, for prophylaxis of decreasing of

blood pressure before spinal anesthesiablood pressure before spinal anesthesia,, infection infection diseasesdiseases

treatment of rhinitistreatment of rhinitis (2%, 3% (2%, 3% solution of nasal dropssolution of nasal drops)) prophylaxis and elimination of bronchial spasm prophylaxis and elimination of bronchial spasm

((inhalationsinhalations 0,5%-1% 0,5%-1% solutions of drugsolutions of drug))SIDE EFFECTSSIDE EFFECTS

agitation,agitation, excitementexcitement, , tremortremor, , inconsiderable inconsiderable euphoriaeuphoria, , insomniainsomnia, , seizuresseizures

drug addictiondrug addiction tachyphylaxytachyphylaxy

Classification of the adrenergic blockersClassification of the adrenergic blockers

II.. AdrenoblockersAdrenoblockers11) α - ) α - adrenoblockersadrenoblockers – – PrazosinumPrazosinum

DoxazosinumDoxazosinum 22) β – ) β – adrenoblockersadrenoblockers

Systemic (non-selective) - Systemic (non-selective) - AnaprilinumAnaprilinum

(Propranololum)(Propranololum)

Cardioselective -Cardioselective - Metoprololum, AtenololumMetoprololum, Atenololum

33) α ) α andand β – β – adrenoblockersadrenoblockers - - LabetalolumLabetalolum

IIII. . SympatholyticsSympatholyticsReserpinumReserpinum

OctadinumOctadinum

Alfa-Alfa-adrenoblockersadrenoblockers

PrazosinumPrazosinum, (, (AdversutenumAdversutenum, , PratisolumPratisolum) – ) – tabltabl. 0,0005; . 0,0005;

0,001; 0,002; 0,0050,001; 0,002; 0,005

DoxazosinumDoxazosinum ( (KarduraKardura)) – tabl. – tabl. 0,001; 0,002; 0,004; 0,0080,001; 0,002; 0,004; 0,008

Pharmacologic effects of alfa-Pharmacologic effects of alfa-adrenoblockersadrenoblockers

lowering of peripheral vascular lowering of peripheral vascular resistanceresistance

improving of microcirculation and improving of microcirculation and trophicstrophics

decrease of blood pressure, postural decrease of blood pressure, postural hypotension hypotension

reflex tachycardiareflex tachycardia

Therapeutic uses of alfa-Therapeutic uses of alfa-adrenoblockersadrenoblockers

Complex treatment of hypertensive Complex treatment of hypertensive diseasedisease

Disturbances of peripheral Disturbances of peripheral microcirculationmicrocirculation

Migraine headache, vertigoMigraine headache, vertigo

Prostatic hypertrophy Prostatic hypertrophy ((1-antagonists block 1-antagonists block -receptors and decrease tone in the smooth -receptors and decrease tone in the smooth muscle of the bladder neck and prostate and muscle of the bladder neck and prostate and improves urine flow)improves urine flow)

Adverse effects of Adverse effects of αα-adrenoblockers-adrenoblockers ortostatic hypotension, ortostatic hypotension, ““phenomenon of first phenomenon of first

dosedose”: ”: sudden decreasing of blood pressure and sudden decreasing of blood pressure and

even development of orthostatic collapse after even development of orthostatic collapse after

first administrations of the drugfirst administrations of the drug

ProphylaxisProphylaxis:: administration of half-dose before sleepadministration of half-dose before sleep

tachycardiatachycardia

vertigo, dizziness, vertigo, dizziness,

nasal congestion,nasal congestion,

headache, headache, drowsinessdrowsiness

Beta-Beta-adrenoblockersadrenoblockers

Note! The name of all β-blockers end in Note! The name of all β-blockers end in “-olol”, except for labetalol, which has “-olol”, except for labetalol, which has a component of α1-blocking actions.a component of α1-blocking actions.

Pharmacological effects of beta-adrenoblockersPharmacological effects of beta-adrenoblockers

Cardiovascular systemCardiovascular system - - lower blood pressure. lower blood pressure.

Decrease the heart rate, cardiac outputDecrease the heart rate, cardiac output

HeartHeart - - decrease all functions of the heart, work and decrease all functions of the heart, work and oxygen consumption of the oxygen consumption of the

myocardiummyocardium

Respiratory tractRespiratory tract - - contraction of the bronchiolar contraction of the bronchiolar smooth muscles (bronchospasm)smooth muscles (bronchospasm)

UterusUterus – – stimulating of the contractility of pregnant stimulating of the contractility of pregnant uterusuterus

Eye Eye - - reducing intraocular pressure, due to decreasing reducing intraocular pressure, due to decreasing of aqueous humor production.of aqueous humor production.

Metabolic and endoMetabolic and endoccrine effectsrine effects - - decreasing of decreasing of glucogenolysis and glucagons secretion. glucogenolysis and glucagons secretion.

Inhibition of Inhibition of sympathetic nervous system’ sympathetic nervous system’ stimulation of lipolysisstimulation of lipolysis

Administration of beta-adrenoblockersAdministration of beta-adrenoblockers Ischemic heart disease Ischemic heart disease Long-term prophylaxis after myocardium Long-term prophylaxis after myocardium

infarction and prevention of sudden cardiac infarction and prevention of sudden cardiac deathdeath

Hyperthyreoidism and anxiety states Hyperthyreoidism and anxiety states (decrease of heart rate)(decrease of heart rate)

Essential hypertension Essential hypertension Cardiac tachyarrhythmias (extrasystolies, Cardiac tachyarrhythmias (extrasystolies,

paroxysmal tachycardia, fibrillation and paroxysmal tachycardia, fibrillation and scintillation of atria)scintillation of atria)

Prophylaxis of migraine headache Prophylaxis of migraine headache Some causes of glaucoma (timolol)Some causes of glaucoma (timolol)

Adverse effects of beta-adrenoblockersAdverse effects of beta-adrenoblockers

Heart failureHeart failureBronchospasmBronchospasmAllergic reactionsAllergic reactions (rash, fever, purpura) (rash, fever, purpura)Heart arrythmiasHeart arrythmias (bradicardia, atrio- (bradicardia, atrio-

ventricular ventricular blockade)blockade)

CNSCNS disordersdisorders (sedation, fatigue, sleep (sedation, fatigue, sleep disturbances, depression, sexual disturbances, depression, sexual disfunctions)disfunctions)

Disturbance of metabolism:Disturbance of metabolism: hypoglycemic hypoglycemic actionaction

Risk of premature interruption of Risk of premature interruption of pregnancy pregnancy

Anaprilin (Propranololum)Anaprilin (Propranololum) is the prorotype β-adrenergic is the prorotype β-adrenergic

antagonist and blocks both βantagonist and blocks both β11 and and

ββ22 receptors. receptors.

AdministrationAdministration ischemic heart diseaseischemic heart disease essential hypertensionessential hypertension cardiac tachyarrhythmiascardiac tachyarrhythmias acute myocardium infarctionacute myocardium infarction

Cardioselective β -adrenoblockersCardioselective β -adrenoblockers

Metoprololum (Cоrvitol) - tab. 0,05; 0,1; Metoprololum (Cоrvitol) - tab. 0,05; 0,1; amp. 1% - 5 mlamp. 1% - 5 ml

Atenololum (Tenormin) - tab. 0,05; 0,1Atenololum (Tenormin) - tab. 0,05; 0,1Talinonololum (Cordanum)- dr.0,05; tab. 0,1.Talinonololum (Cordanum)- dr.0,05; tab. 0,1.

Main speculiarities:Main speculiarities:

Preferentially block the β1 receptors without blocking of Preferentially block the β1 receptors without blocking of

β2- receptors. Thus their side effects expect β2- receptors. Thus their side effects expect

bronchoobstruction, hypoglycemia and premature laborbronchoobstruction, hypoglycemia and premature labor

Talinololum (Cordanum)Talinololum (Cordanum)

AdministrationAdministration disorders of cardiac rhythmdisorders of cardiac rhythm

((extrasystoliesextrasystolies,, paroxysmal paroxysmal tachycardiatachycardia, , fibrillation and fibrillation and scintillation of atriascintillation of atria))

stenocardiastenocardia arterial hypetensionarterial hypetension

Atenolol Atenolol ((tenormin)tenormin)cardioselelctivecardioselelctive --adrenoblocker of long adrenoblocker of long

actionaction

AdministrationAdministration ischemic heart diseaseischemic heart disease essential hypertensionessential hypertension cardiac arrhythmiascardiac arrhythmias acute myocardium infarctionacute myocardium infarction

LabetalolLabetalol

-, -, --adrenoblockeradrenoblocker. . The drug blocksThe drug blocks 11, , 22, , 1 1 andand 22--adrenoreceptorsadrenoreceptors

AdministrationAdministration treatment of patients with essential treatment of patients with essential hypertensionhypertension hypertensive crisishypertensive crisis

ContraindicationsContraindications Atrio-ventricular blockadeAtrio-ventricular blockade,,

cardiac insufficiencycardiac insufficiency

SympatholyticsSympatholytics

ReserpinReserpinIs a sum of Rauvolfia (plant) alkaloidsIs a sum of Rauvolfia (plant) alkaloids. . Maximal hypotensive Maximal hypotensive

actionaction developsdevelops afterafter 5-7 5-7 daysdays of regular administration of the of regular administration of the drugdrug. . After the treatment coarsed effect can still stay for two After the treatment coarsed effect can still stay for two weeksweeks..

AdministrationAdministration treatment of different forms of essential treatment of different forms of essential

hypertension (preparations of a second choise)hypertension (preparations of a second choise)

((combined drugs trirezidcombined drugs trirezid, , cristepincristepin, , adelfanadelfan, , brinerdinbrinerdin))

Side effectsSide effects manifestations of parkinsonismmanifestations of parkinsonism fatiguefatigue, , somnolencesomnolence, , depressiondepression,, bradycardiabradycardia increasing of motor and secretory activity of gastro-increasing of motor and secretory activity of gastro-

intestinal tractintestinal tract, , acute attacks of ulcer diseaseacute attacks of ulcer disease, , diarrheadiarrhea

OctadinumOctadinum Is a sympatholytic with strong hypotensive effectIs a sympatholytic with strong hypotensive effect. . During administration of the drug decreasing of During administration of the drug decreasing of blood pressure develops graduallyblood pressure develops gradually, , afterafter 2-3 2-3 daysdays. . After abolition of drug administration the effect still After abolition of drug administration the effect still stays forstays for 2 2 weeksweeks..

Administration Administration heavy forms of arterial hypertensionheavy forms of arterial hypertension

Side effectsSide effects general weaknessgeneral weakness,, nauseanausea, , vomitingvomiting,, swelling of nose mucous membraneswelling of nose mucous membrane,, diarrheadiarrhea,,orthostatic collapseorthostatic collapse

Thanks for Thanks for attention!attention!

Good-byeGood-bye ! !