medicamente inotrop pozitive
TRANSCRIPT
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MEDICAMENTE INOTROP MEDICAMENTE INOTROP POZITIVEPOZITIVE
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DIGITALICE (TONICARDIACE, GLICOZIZI DIGITALICE (TONICARDIACE, GLICOZIZI CARDIACI)CARDIACI)
INHIBITORII FOSFODIESTERAZEIINHIBITORII FOSFODIESTERAZEI
SIMPATICOMIMETICE (ADRENERGICE SI SIMPATICOMIMETICE (ADRENERGICE SI DOPAMINERGICE): DOPAMINERGICE):
Adrenalina Adrenalina Dopamina Dopamina Dobutamina Dobutamina DopexaminaDopexamina
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DIGITALICEDIGITALICE
ORIGINE:ORIGINE:
1775 - Dr. William Withering1775 - Dr. William Withering • DIGOXINDIGOXIN <= Digitalis lanata <= Digitalis lanata• DIGITOXINADIGITOXINA <= Digitalis <= Digitalis
purpureeapurpureea• STROFANTINASTROFANTINA <= Strofantus <= Strofantus
gratusgratus• ββ-METIL-DIGOXIN-METIL-DIGOXIN <= <=
semisintezasemisinteza
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UTILIZARI TERAPEUTICEUTILIZARI TERAPEUTICE
Insuficienta cardiacaInsuficienta cardiaca acuta (EPA) acuta (EPA)Insuficienta cardiaca cronica clasa NYHA III Insuficienta cardiaca cronica clasa NYHA III si IV, dupa instituirea trat diuretic, cu si IV, dupa instituirea trat diuretic, cu antagonisti SRAA si betablocanteantagonisti SRAA si betablocanteInsuficienta cardiaca cronica (orice clasa Insuficienta cardiaca cronica (orice clasa NYHA) + FiA rapidaNYHA) + FiA rapidaTahi-aritmii supraventriculare:Tahi-aritmii supraventriculare:– Fibrilatie atrialaFibrilatie atriala– Flutter atrialFlutter atrial– TPSVTPSV
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INSUFICIENTA CARDIACA (IC)INSUFICIENTA CARDIACA (IC)
= sindromul care apare = sindromul care apare când capacitatea când capacitatea inimii de a pompa sânge este scăzută sub inimii de a pompa sânge este scăzută sub valoarea necesară pentru a menţine valoarea necesară pentru a menţine circulaţia adecvatăcirculaţia adecvată
2 subtipuri:2 subtipuri:
Sistolică (FE<40%): Digoxinul se Sistolică (FE<40%): Digoxinul se administrează doar în IC sistolicăadministrează doar în IC sistolică
Diastolică: nu se administrează DigoxinDiastolică: nu se administrează Digoxin
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Rata supravietuirii in ICRata supravietuirii in ICRata supravietuirii in ICRata supravietuirii in IC
Rata supravietuirii (%)Rata supravietuirii (%)
1 an 2 ani 3 ani1 an 2 ani 3 ani
Cancer de sanCancer de san 88% 88% 80%80% 72%72%
Cancer de prostataCancer de prostata 75%75% 64%64% 55%55%
Cancer de colon 70% 48% 31%Cancer de colon 70% 48% 31%
Insuficienta cardiacaInsuficienta cardiaca 67% 67% 41%41% 24%24%
Cancer pulmonar Cancer pulmonar 18%18% 8%8% 6%6%
Modificat dupa McMurray (1998)
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Vasodilatatoare (IECA)
Restrictie aport de Na
Restrictie activitate fizica
Digoxin
Diuretice
Inotrop pozitive I.V.
Masuri speciale(balon intraaortic, transplant)
Clasa functionala NYHA (New York Heart Assoc.)
I II III IV
(Heart Failure. Colucci WS & Braunwald E. 1995)
Tratamentul ICTratamentul IC
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STRUCTURA CHIMICA A DIGITALICELORSTRUCTURA CHIMICA A DIGITALICELOR
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STRUCTURA CHIMICA A DIGITALICELORSTRUCTURA CHIMICA A DIGITALICELOR
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FARMACOCINETICAFARMACOCINETICA
DIGITOXINA – foarte liposolubilDIGITOXINA – foarte liposolubil
DIGOXIN – uDIGOXIN – uşşor liposolubilor liposolubil
STROFANTINA - hidrosolubilSTROFANTINA - hidrosolubil
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FARMACOCINETICAFARMACOCINETICAAbsorbAbsorbţţia:ia:
DIGITOXINA: 90 – 100%DIGITOXINA: 90 – 100%
DIGOXIN: 55 – 75%DIGOXIN: 55 – 75%
STROFANTINA: 1 – 3%STROFANTINA: 1 – 3%
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FARMACOCINETICAFARMACOCINETICADistribuDistribuţţia:ia:
Fixarea pe proteinele plasmatice:Fixarea pe proteinele plasmatice:
DIGITOXINA – 95%DIGITOXINA – 95%
DIGOXIN – 25%DIGOXIN – 25%
STROFANTINA – 0,5%STROFANTINA – 0,5%
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FARMACOCINETICAFARMACOCINETICATimpul de injumatatire:Timpul de injumatatire:
DIGITOXINA = 7 zile DIGITOXINA = 7 zile
DIGOXIN = 40 ore = 1,6 zileDIGOXIN = 40 ore = 1,6 zile
STROFANTINA = 21 oreSTROFANTINA = 21 ore
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FARMACOCINETICAFARMACOCINETICAEliminarea:Eliminarea:
DIGITOXINA – DIGITOXINA – metabolizat hepatic metabolizat hepatic 90%90%
DIGOXIN – DIGOXIN – eliminat renaleliminat renal
STROFANTINA – STROFANTINA – eliminat renaleliminat renal
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FARMACOCINETICA DIGITALICELOR FARMACOCINETICA DIGITALICELOR DE UZ CLINICDE UZ CLINIC
O
CH3
OH CH3
OH
C=O
(sugar)3
O
CH3
CH3
OH
C=O
(sugar)3
Digoxin Digitoxin
Liposolubilitate Absorbtie oralaLegare de PPTimp injumatatireEliminareConc. plasmatica
Medie Mare55-75% >90%25% 95%1.6 zile 7 zileRinichi Ficat0,5 - 1 ng/ml 15 - 20 ng/ml0,5 - 1 ng/ml 15 - 20 ng/ml
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FACTORI CE POT MODIFICA FACTORI CE POT MODIFICA FARMACOCINETICA DIGITALICELORFARMACOCINETICA DIGITALICELOR
VVârsta bolnavuluiârsta bolnavului
Insuficienta renala – DIGOXINInsuficienta renala – DIGOXIN
Insuficienta hepatica – DIGITOXINInsuficienta hepatica – DIGITOXIN
Hipokaliemia – ↑ toxicit. dig. - KCl – oral, i.v.Hipokaliemia – ↑ toxicit. dig. - KCl – oral, i.v.
Hipomagnezemia – tulb. de ritmHipomagnezemia – tulb. de ritm
Hipertiroidia – rezistenta la trat. digitalicHipertiroidia – rezistenta la trat. digitalic
Hipotiroidia - ↓ toleranta la digitaliceHipotiroidia - ↓ toleranta la digitalice
Alcaloza – efect proaritmogenAlcaloza – efect proaritmogen
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DIGOXINDIGOXIN
Absorbtie digestiva bunAbsorbtie digestiva bunăă
Adm oral sau I. V.Adm oral sau I. V.
T ½ mai scurt – risc T ½ mai scurt – risc ↓ de supradozaj↓ de supradozaj
Fixare pe p.p. ↓ - efect după 90’Fixare pe p.p. ↓ - efect după 90’
Eliminare renalăEliminare renală
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DIGITOXINDIGITOXIN
Absorbtie digestiva foarte bunAbsorbtie digestiva foarte bună=>adm ă=>adm numai oralnumai oral
T ½ lung => nu se adm. in urgenteT ½ lung => nu se adm. in urgente
Adm. la bolnavi cu IC + IRCAdm. la bolnavi cu IC + IRC
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ACTIUNE FARMACODINAMICAACTIUNE FARMACODINAMICA
Efecte cardiaceEfecte cardiace
Efecte extracardiace:Efecte extracardiace:– Asupra rinichiuluiAsupra rinichiului– Asupra vaselorAsupra vaselor– Asupra SNCAsupra SNC
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EFECTE CARDIACEEFECTE CARDIACE
Inotrop +Inotrop +
Cronotrop – Cronotrop –
Dromotrop – Dromotrop –
Batmotrop –Batmotrop –
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EFECTE CARDIACEEFECTE CARDIACEInotrop +Inotrop +
Forta si viteza de contractie a miocardului Forta si viteza de contractie a miocardului normal si insuficientnormal si insuficient
durata ejectiei ventricularedurata ejectiei ventriculare
volumul de ejectie ventricularvolumul de ejectie ventricular
timpul de umplere diastolicatimpul de umplere diastolica
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EFECTE CARDIACEEFECTE CARDIACEInotrop +Inotrop +
Semnificativ pe cordul insuficientSemnificativ pe cordul insuficient ~ doza administrata si digoxinemia~ doza administrata si digoxinemia Este principala proprietate farmacologica a Este principala proprietate farmacologica a
digitalei => digitalei => DC si DC si eficacitatea pompei eficacitatea pompei cardiacecardiace
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EFECTE CARDIACEEFECTE CARDIACECronotrop – Cronotrop –
= efect bradicardizant= efect bradicardizant
Stimularea directa a centrilor vagaliStimularea directa a centrilor vagali Activare baroreceptori din sinus carotidian Activare baroreceptori din sinus carotidian
si crosa aorteisi crosa aortei
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EFECTE CARDIACEEFECTE CARDIACEDromotrop – Dromotrop –
Incetinirea vitezei de conducere atrio-Incetinirea vitezei de conducere atrio-ventriculara => efect in fibrilatia atriala cu ventriculara => efect in fibrilatia atriala cu ritm rapidritm rapid
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EFECTE CARDIACEEFECTE CARDIACEBatmotrop –Batmotrop –
= efect proaritmic= efect proaritmic miocard indemn, doze terapeutice–>efect miocard indemn, doze terapeutice–>efect
neglijabilneglijabil miocard lezat, doze mari sau terapeutice miocard lezat, doze mari sau terapeutice
–> efect proaritmic–> efect proaritmic
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EFECTE EKGEFECTE EKG
frecventei cardiacefrecventei cardiace
PRPR
QTQT
Subdenivelare ST, Subdenivelare ST, uneori cu concavitatea uneori cu concavitatea in susin sus
Aplatizarea sau Aplatizarea sau inversarea undei Tinversarea undei T
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EFECTE EXTRACARDIACEEFECTE EXTRACARDIACE
Pe rinichi: efect diureticPe rinichi: efect diuretic
Pe vase: Pe vase: – Vasoconstrictie arteriolara => Vasoconstrictie arteriolara => RPT RPT tonusul venos => tonusul venos => presarcina presarcina
SNC: activare tonus vagalSNC: activare tonus vagal
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MECANISM DE ACTIUNEMECANISM DE ACTIUNE
Na+ Ca2+
K+
2K+
3Na+3Na+
Ca2+
Na+
Ca2+
Actina & miozina
DigoxinCa2+ Ca2+ Ca2+ Ca2+
Ca2+
K+o
+
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MECANISM DE ACTIUNEMECANISM DE ACTIUNE
Na+ Ca2+
K+
2K+
3Na+3Na+
Ca2+
Na+
Ca2+
Actina & miozina
DigoxinCa2+ Ca2+ Ca2+ Ca2+
Ca2+
K+o
+
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Schimbul Na-CaSchimbul Na-CaNa+Na+
K+K+
K+K+
Na+Na+
Na+Na+ Ca++Ca++
Ca++Ca++
Na-K ATPazaNa-K ATPaza
MiofilamenteMiofilamente
DigoxinDigoxin
CONTRACTILITATECONTRACTILITATE
-
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MECANISM DE ACTIUNEMECANISM DE ACTIUNE
Na+K+ATP aza
Pompa Na+K+
Na+ intracelular
Ca2+ liber intracelular
forta contractila
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MECANISM DE ACTIUNEMECANISM DE ACTIUNE
DIGOXINDIGOXIN Na+K+ATP aza
Pompa Na+K+
Na+ intracelular
Ca2+ liber intracelular
forta contractila
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UTILIZARI TERAPEUTICEUTILIZARI TERAPEUTICE
Insuficienta cardiaca acuta (EPA)Insuficienta cardiaca acuta (EPA)Insuficienta cardiaca cronica clasa NYHA III Insuficienta cardiaca cronica clasa NYHA III si IV, dupa instituirea trat diuretic, cu si IV, dupa instituirea trat diuretic, cu antagonisti SRAA si betablocanteantagonisti SRAA si betablocanteInsuficienta cardiaca cronica (orice clasa Insuficienta cardiaca cronica (orice clasa NYHA) + FiA rapidaNYHA) + FiA rapidaTahi-aritmii supraventriculare:Tahi-aritmii supraventriculare:– Fibrilatie atrialaFibrilatie atriala– Flutter atrialFlutter atrial– TPSVTPSV
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CONTRAINDICATIICONTRAINDICATII
Intoxicatia digitalicaIntoxicatia digitalica
BradicardieBradicardie
Bloc AVBloc AV
Aritmii ventriculare grave: TV, ExVAritmii ventriculare grave: TV, ExV
IC prin disfunctie diastolica (SA sau HTA)IC prin disfunctie diastolica (SA sau HTA)
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EFECTE ADVERSE EFECTE ADVERSE INTOXICATIA DIGITALICAINTOXICATIA DIGITALICA
IT mic = 2 – 3IT mic = 2 – 3
Frecventa reactiilor adverse: 2% - 10-20%Frecventa reactiilor adverse: 2% - 10-20%
Factori favorizanti:Factori favorizanti:– Doze inadecvateDoze inadecvate– Cardiopatie veche: D terapeutice –> D toxiceCardiopatie veche: D terapeutice –> D toxice– Varsta inaintata: Varsta inaintata: FG FG– Hipokaliemia Hipokaliemia
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INTOXICATIA DIGITALICAINTOXICATIA DIGITALICA
Simptomatologie:Simptomatologie: Manifestari cardiace:Manifestari cardiace: bradicardie sinusala, bradicardie sinusala,
tulb. de conducere AV (BAV), aritmii tulb. de conducere AV (BAV), aritmii atriale/ventriculare, bigeminism ventricularatriale/ventriculare, bigeminism ventricular
Manifestari extracardiace:Manifestari extracardiace: anorexie, anorexie, greata, varsaturi, tulburari de tranzit, dureri greata, varsaturi, tulburari de tranzit, dureri abdominale, tulb. neuro-senzoriale, vedere abdominale, tulb. neuro-senzoriale, vedere monocromaticamonocromatica
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INTOXICATIA DIGITALICAINTOXICATIA DIGITALICA
Tratament:Tratament: Oprirea digitalizariiOprirea digitalizariiSpalaturi gastrice cu carbune medicinalSpalaturi gastrice cu carbune medicinalFortarea diurezei cu FurosemidFortarea diurezei cu FurosemidPotasiu: KCl casete, Aspacardin, Kalinor, Potasiu: KCl casete, Aspacardin, Kalinor,
SpironolactonaSpironolactonaAnticorpi antidigoxinici ce inactiveaza Anticorpi antidigoxinici ce inactiveaza
rapid digitala – DIGIBIND – 1 f: 0,6 mg Digrapid digitala – DIGIBIND – 1 f: 0,6 mg Dig
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INTOXICATIA DIGITALICAINTOXICATIA DIGITALICA
Trat. bradicardiei: Trat. bradicardiei:
Atropina i.v. 0,5 – 1 mgAtropina i.v. 0,5 – 1 mg Trat. aritmiilor ventriculare:Trat. aritmiilor ventriculare:
Xilina i.v. apoi perfuzieXilina i.v. apoi perfuzie
Fenitoin i.v.Fenitoin i.v. Trat. tahiaritmiilor supraventriculare:Trat. tahiaritmiilor supraventriculare:
Beta-blocanteBeta-blocante
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ADMINISTRAREA DIGITALICELORADMINISTRAREA DIGITALICELOR
= DIGITALIZARE= DIGITALIZARE
Gradul urgenteiGradul urgentei
I renala / I hepaticaI renala / I hepatica
Cr ser, Cl crCr ser, Cl cr
Digitalizare prealabilaDigitalizare prealabila
Farmacocinetica preparatuluiFarmacocinetica preparatului
Calea de administrareCalea de administrare
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ADMINISTRAREA DIGITALICELORADMINISTRAREA DIGITALICELOR
DOZA DE INCARCARE (D inc)DOZA DE INCARCARE (D inc)
– 24 h: digitalizare rapida24 h: digitalizare rapida– 2-3 zile: digitalizare medie2-3 zile: digitalizare medie– 6-7 zile: digitalizare lenta6-7 zile: digitalizare lenta
Eficienta: Eficienta: FC, FC, edemelor, edemelor, hepatomegaliei, hepatomegaliei, turg. jugularelor, ameliorarea dispneei,turg. jugularelor, ameliorarea dispneei,
diurezeidiurezei
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ADMINISTRAREA DIGITALICELORADMINISTRAREA DIGITALICELOR
DOZA DE INTRETINERE (D intr)DOZA DE INTRETINERE (D intr)
= doza / zi care mentine o concentratie = doza / zi care mentine o concentratie plasmatica eficientaplasmatica eficienta
= cantitatea de digitalice inactivate si = cantitatea de digitalice inactivate si eliminate pe zieliminate pe zi
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ADMINISTRAREA DIGITALICELORADMINISTRAREA DIGITALICELOR
DIGOXINDIGOXIN
cp. 0,25 mg, f. 0,5 mgcp. 0,25 mg, f. 0,5 mg
D inc D inc pt. i.v.: 0,5 – 1,5 mgpt. i.v.: 0,5 – 1,5 mg
ex. 2f.: ora 0 – 1f.ex. 2f.: ora 0 – 1f.
ora 12 – ½ f.ora 12 – ½ f.
ora 24 – ½ f.ora 24 – ½ f.
D inc D inc pt. oral: 1 – 1,5 mg pt. oral: 1 – 1,5 mg
ex. 6 cp.: 1 cp/zi, 6 zileex. 6 cp.: 1 cp/zi, 6 zile
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ADMINISTRAREA DIGITALICELORADMINISTRAREA DIGITALICELOR
D intrD intr– se adm. oral:– se adm. oral:
0,125-0,25 mg/zi0,125-0,25 mg/zi (1/2–1 cp/zi) (1/2–1 cp/zi) daca valoarea creatininemiei e daca valoarea creatininemiei e normala normala
0,0625-0,125 mg/zi0,0625-0,125 mg/zi (1/4 – ½ (1/4 – ½ cp/zi) la varstnicicp/zi) la varstnici
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INTERACTIUNI MEDICAMENTOASEINTERACTIUNI MEDICAMENTOASE
EFECT DIGITALIC EFECT DIGITALIC AMPLIFICATAMPLIFICAT
MM Amplitudine Amplitudine RecomandariRecomandariCHINIDINACHINIDINA 100%100% doza D cu 50%doza D cu 50%
AMIODARONAAMIODARONA 70-100%70-100% doza D cu 50%doza D cu 50%VERAPAMILVERAPAMIL 70-100%70-100% doza D cu 50%doza D cu 50%
PROPAFENONAPROPAFENONA 100%100% doza D cu 50%doza D cu 50%ERITROMICINAERITROMICINA 43-116%43-116% doza D cu 50%doza D cu 50%
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INTERACTIUNI MEDICAMENTOASEINTERACTIUNI MEDICAMENTOASE
REDUCERE EFECT REDUCERE EFECT DIGITALICDIGITALIC
MM AmplitudineAmplitudine RecomandariRecomandari
COLESTIRAMINACOLESTIRAMINA 25%25% Adm. D cu 8 Adm. D cu 8 ore inaintea Core inaintea C
ANTIACIDEANTIACIDE 25%25% Administrare Administrare separataseparata
FENITOINFENITOIN 30%30% Cresterea dozeiCresterea dozei
SULFASALAZINASULFASALAZINA 18%18% Cresterea dozeiCresterea dozei
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UTILIZARI TERAPEUTICEUTILIZARI TERAPEUTICE
Insuficienta cardiacaInsuficienta cardiaca acuta (EPA) acuta (EPA)Insuficienta cardiaca clasa NYHA III si IV, Insuficienta cardiaca clasa NYHA III si IV, dupa initierea trat diuretic, cu antagonisti dupa initierea trat diuretic, cu antagonisti SRAA si betablocanteSRAA si betablocanteInsuficienta cardiaca (orice clasa NYHA) cu Insuficienta cardiaca (orice clasa NYHA) cu FiA rapidaFiA rapidaTahi-aritmii supraventriculare:Tahi-aritmii supraventriculare:– Fibrilatie atrialaFibrilatie atriala– Flutter atrialFlutter atrial– TPSVTPSV
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ALGORITM PENTRU ADM. DIGOXINULUI IN ICALGORITM PENTRU ADM. DIGOXINULUI IN IC
IC sistolica (FE ≤ 40%)
Pacient cu IC
IC diastolica
NU se adm DigoxinDeterminarea severitatii IC (clasa NYHA)
NYHA I sau II NYHA III sau IV
Digoxinul se administreaza doar daca pac se afla in fibrilatie atriala
Administrarea de doze mici de Digoxin (C plasm 0,5-1 ng/ml) la pacientii la care persista simptomele in ciuda tratamentului optim
cu IECA, betablocante si diuretice
C plasm a digoxinului ≥ 1 ng/ml
Evaluarea cauzelor: functia renala, doza de digoxin, medicatia concomitenta: amiodarona, verapamil, chinidina, macrolide, tetracicline
C plasm a digoxinului revine intre 0,5 si 1 ng/ml
Continuarea trat cu dozele curente si monitorizarea progreselor
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INHIBITORII FOSFODIESTERAZEIINHIBITORII FOSFODIESTERAZEI
TEOFILINA, AMINOFILINATEOFILINA, AMINOFILINA
AMRINONA, MILRINONA, ENOXIMONAAMRINONA, MILRINONA, ENOXIMONA
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MECANISM DE ACTIUNEMECANISM DE ACTIUNE
Inhiba fosfodiesterazaInhiba fosfodiesteraza
Catabolizarea AMPcCatabolizarea AMPc
AMPc in celula miocardica AMPc in celula miocardica
Influxul de Ca++ in celulaInfluxul de Ca++ in celula
Ca++Ca++
contractilitateacontractilitatea
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AMRINONAAMRINONA
Actiune inotrop pozitivaActiune inotrop pozitiva::creste fractia de ejectie => creste fractia de ejectie => ↑ DC↑ DC
Vasodilatatie arterialaVasodilatatie arteriala –> scade postsarcina–> scade postsarcina
Indicatii terapeutice:Indicatii terapeutice:Insuficienta cardiaca acuta – adm. i.v. pe termen scurt, in Insuficienta cardiaca acuta – adm. i.v. pe termen scurt, in
spitalspital
MILRINONAMILRINONA~ Amrinona, mult mai bine suportata~ Amrinona, mult mai bine suportata
ENOXIMONAENOXIMONA~ Milrinona~ Milrinona