FARMACOLOGIA CARDIOVASCULAR

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FARMACOLOGIA CARDIOVASCULAR
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Principais Doenças Cardiovasculares
 Hipertensão Arterial Sistêmica
 Insuficiência Cardíaca
 Doença Arterial Coronariana
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Categoria 		PA Sistólica 	PA Diastólica
Normal		 <120	 e	 <80
Pré-hipertenso	 120-139	 ou	 80-90
	
HIPERTENSO
 Estágio 1	 140-159	 ou	 90-99
 Estágio 2	 >160	 ou	 >100	
Fonte: 7th Report of the Joint National Comittee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure
Classificação em Adultos (em mmHg)
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Hipertensão Arterial
Terapia Medicamentosa
Princípios Gerais
Medicamento eficaz VO e bem tolerado
Menor número de tomadas diárias
Inicio com menores doses efetivas
Terapêutica escalonada
Respeitar intervalo de 3 a 4 sem. para aumento de doses ou associação
Considerar condições sócio-econômicas
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Hipertensão Arterial
Objetivos da Terapia
Reduzir a morbi - mortalidade cardiovascular e renal
Reduzir a PA para níveis < 140/90 mmHg 
Em diabéticos e renais crônicos < 130/80
Atingir a meta de PA sistólica, principalmente em indivíduos a partir dos 50 anos de idade
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Hipertensão Arterial
Tratamento Medicamentoso
Classes de Anti-hipertensivos
Diuréticos
Agentes Simpaticolíticos (- bloqueadores, 1-bloqueadores, agonistas 2 adrenérgicos, ação central )
Moduladores do SRA (Inibidores da ECA e ARA II)
Antagonistas dos Canais de Cálcio
Vasodilatadores Diretos 
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Diuréticos
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Hipertensão Arterial
 Diuréticos
Principal mecanismo
 Excreção de Na Cl e NaHCO3 
 eliminação de água
1. Redução da volemia e do DC (inicialmente)
2. Normalização do DC e queda na RVP
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Néfron
Terapia Medicamentosa
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Hipertensão Arterial
Diuréticos
Tiazídicos
Diuréticos de Alça
Poupadores de Potássio
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Hipertensão Arterial
Tiazídicos e afins 
Mecanismo de ação:
Agem no túbulo distal
Aumentam a excreção de Na, K e Mg
Aumentam a eliminação de água
. Efeitos Adversos
Fármacos:
Hidroclorotiazida (Clorana ) – 12,5 a 50 mg/dia
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Hipertensão Arterial
Diuréticos de alça 
Mecanismo de ação:
Agem na porção espessa da alça de Henle
Aumentam a eliminação de K+ e Ca++
Aumentam a eliminação de água
. Efeitos Adversos
Furosemida (Lasix) – 40 a 240 mg/dia
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Hipertensão Arterial
Poupadores de Potássio 
Mecanismo de ação:
	-Agem no túbulo coletor
	-Reduzem a excreção K+
	-Aumentam discretamente a diurese
Efeitos Adversos
Fármacos:
Amilorida (Moduretic ) – 5 a 10 mg/ dia
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Agentes Simpaticolíticos
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Hipertensão Arterial
Agentes Simpaticolíticos
Classificação:
 - bloqueadores 	
 1-bloqueadores 
agonistas  2 adrenérgicos
ação central 
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 - Bloqueadores
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 Mecanismo de ação: 
1. Agem em receptores cardíacos e renais
2. Reduzem a frequência cardíaca e a liberação de renina pelos rins 
Redução de Angiotensina II
Queda na RVP
 retenção de água e Na+
 volemia
 Hipertensão Arterial Tratamento Medicamentoso
 - bloqueadores
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 - bloqueadores
Bloqueiam receptores 1 e 2
Sem Cardioseletividade  propranolol
 Com Cardioseletividade  atenolol
 Atividade  e  - bloqueadora  labetalol
Efeitos adversos:
	Bradicardia, bloqueio AV, hipotensão, parestesias, asma, insuf. Cardíaca, hipersensibilidade
	
 
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1 - Bloqueadores
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1. Mecanismo de ação:
 Bloqueio competitivo dos receptores adrenégicos 1, 
com redução da RV arterial e venosa.
2. Drogas:
	- Prazosin (Minipress) – 2 a 30 mg/dia
3. Efeitos Adversos
	- Cefaléia, tontura, síncope
	- Taquicardia reflexa
Hipertensão Arterial Tratamento Medicamentoso  1 -bloqueadores
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Agonistas 2 - Adrenérgicos
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 Mecanismo de ação:
1. Estimulam o sub-tipo  2A, reduzindo a resistência arteriolar e venosa 
2. Drogas:
	- Clonidina (Atensina ) – 0,1 a 1,2 mg/dia
		
Hipertensão Arterial Tratamento Medicamentoso Agonista  -adrenérgicos
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Ação Central
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 Mecanismo de ação:
Falso neuro transmissor (metabólito), - metildopamina, convertido em - metilnoradrenalina.
2. Em nível central, agonista 2, similar a clonidina,  o influxo neuroadrenérgico,  resistência arteriolar e venosa e  PA
 Drogas:
	- Metildopa (Aldomet) – 500 a 3000 mg/dia
Uso: Hipertensão na Gravidez
	
Hipertensão Arterial Tratamento Medicamentoso Ação Central
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Hipertensão Arterial
Tratamento Medicamentoso
 Ação Central
 Efeitos Adversos
	- Sedação, adinamia, depressão 
	- Tonturas
	-Hiperprolactinemia (ginecomastia e galactorréia)
	- Impotência
	- hepatotoxicidade
	- Anemia hemolítica
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Antagonistas de Canais de Cálcio
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1. Agem em canais de Ca voltagem - dependentes (canais L) 
2. Inibem o influxo de cálcio para as células musculares lisas da parede vascular causando dilatação arteriolar e queda da PA.
Mecanismos de ação:
Hipertensão Arterial Tratamento Medicamentoso Antagonistas de Canais de Cálcio
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Hipertensão Arterial Tratamento Medicamentoso Antagonistas de Canais de Cálcio
Classificação:
Dihidropiridínicos:
	Anlodipina ( Norvasc) - 2,5 a 10,0 mg/dia
	Nifedipina ( Adalat ) – 30 a 120 mg/dia
2. Não - dihidropiridínicos:
		Diltiazem ( Cardizen ) – 120 a 360 mg/dia
	 Verapamil (Dilacoron ) – 	80 a 480 mg/dia 	 
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 Efeitos adversos:
	-Cefaléia, 
	-edema, 
	- rubor facial, 
	- hipotensão
	- artralgias 
Hipertensão Arterial
Tratamento Medicamentoso
 Antagonistas de Canais de Cálcio
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Moduladores do SRA
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Angiotensinogênio
Angiotensina I
Angiotensina II
Angiotensina III
Liberação
Renina
Beta Bloqueadores
Inibidores da ECA
ECA
Efeitos nos Receptores
Antagonistas do Receptor de AT
Modulação do SRA
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Inibidores da ECA
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Mecanismos de ação:
	* Inibem a produção de angiotensina II
	* Reduzem a secreção de aldosterona
 Fármacos:
	* Captopril (Capoten )- 25 a 150 mg/dia
	* Enalapril (Renitec ) – 5 a 40 mg/dia
	
Hipertensão Arterial Tratamento Medicamentoso Inibidores da ECA
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Efeitos Adversos:
	* Hipotensão arterial
	* Tosse
	* Potencial fetopático
	* Insuficiência renal aguda
	* Hiperpotassemia
	* Rash cutâneo
Hipertensão Arterial Tratamento Medicamentoso Inibidores da ECA
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ANTAGONISTAS DA ANGIOTENSINA II
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Mecanismo de ação:
	* Inibição das ações da angiotensina II, mediadas pelos receptores AT 1, determinando  da RVP,  da liberação de aldosterona
Fármacos:
	* Losartana(Cozaar ) – 25 a 100 mg/dia
	
	* Candesartana (Blopress ) – 8 a 32 mg/dia
	
Hipertensão Arterial Tratamento Medicamentoso ARA II
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Efeitos Adversos:
	* Hipotensão arterial.
	* Hiperpotassemia
	* Potencial fetopático
	* Sintomas gastrointestinais
	* Mialgias
	
Hipertensão Arterial Tratamento Medicamentoso ARA II
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Vasodilatadores diretos
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Mecanismos de ação:
	* relaxamento da musculatura lisa arteriolar com  da RVP
Fármacos:
	* Hidralazina (Apresolina ) – 50 a 300 mg/dia
	* Minoxidil (Loniten ) – 5 a 100 mg/dia
 * Nitro Prussiato de Sódio	
Hipertensão Arterial Tratamento Medicamentoso Vasodilatadores Diretos
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Efeitos Adversos:
	* Palpitações (taquicardia reflexa)
	* Angina do Peito
	* Hipotensão ortostática
	* Cefaléia, tonturas
	* Síndrome Lupus-Like
	
Hipertensão Arterial Tratamento Medicamentoso Vasodilatadores Diretos
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Insuficiência Cardíaca
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INSUFICIÊNCIA CARDÍACA
Incapacidade de manter um Débito Cardíaco (DC) suficiente para atender as necessidades metabólicas
Sistólica e Diastólica
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INSUFICIÊNCIA CARDÍACA
Princípios da Terapia
		Anormalidade
		Terapia
		Pós-carga (
		Vasodilatadores arteriais, Inibidores da ECA, ARA II
		Pré-carga (
		Restrição hidrosalina,
Diuréticos, Nitratos,
		Contratilidade (
		Agentes inotrópicos
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Inotrópicos positivos
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Agentes Inotrópicos Positivos Classificação
Digitálicas: digoxina, digitoxina, lanatosídeo C 
Não digitálicas: agonistas  adrenérgico, agonista  e  adrenérgico, inibidores da fosfodiesterase
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Digitálicos
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Farmacologia
Inibe a bomba Na+-K+-ATPase
 Aumenta [Na+]i
 Aumenta a disponibilidade de [Ca++]i 
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Farmacologia Clínica
Inotropismo positivo
 Efeito na condução de fibras excitáveis: 
 -  a automaticidade e  pot. diastólico max da membrana em repouso - nódulos atrial e AV.
		-  velocidade de condução AV e  período refratário.
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Relação Efeito-Concentração
 Digoxina:
Correlação terapêutica: 0,8 - 2,0 ng/mL
Concentração > 2,0 ng/mL  toxicidade
 Digitoxina:
Correlação terapêutica: 10 - 20 ng/mL
Concentração > 20 ng/mL toxicidade
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Drogas Inotrópicas Positivas Agonistas -adrenérgicos
Receptor		Sítio		Ação
-1			 		 contração atrial e ventric. 			NSA  FC 						 NAV		 condução AV
-2			arteríolas	 vasodilatação					pulmão	 broncodilatação
			arteríolas	 vasoconstricção			
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Agonistas - adrenérgicos
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Drogas Inotrópicas Positivas Dopamina
Mec. de ação: 
 diretamente em -1  contratilidade 
 indiretamente liberando NA das terminações nervosas  -1
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Drogas Inotrópicas Positivas Nor-adrenalina
Mec. de ação: 
estímulo -1 :  contratilidade e FC
 estímulo :  RVP
estímulo -1< estímulo 
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Drogas Inotrópicas Positivas Nor-adrenalina
Indicação: tratamento de choque após reposição de volume
Reações adversas: arritmias, isquemia periférica.
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Doença Arterial Coronariana
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DESEQUILÍBRIO :
 Consumo de O2 x oferta de O2
ISQUEMIA MIOCÁRDICA
 Determinantes do consumo de O2
 Frequência Cardíaca
 Contratilidade Cardíaca
 Tensão da Parede: Espessura 					  Diâmetro Ventricular
			  Pressão intraventricular
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Isquemia Miocárdica
Etiologia principal
Aterosclerose coronária
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Desenvolvimento da Aterosclerose
Fatores de Risco
Hipertensão Arterial
Hipercolesterolemia
Tabagismo 
Obesidade
Sedentarismo 
Antecedentes Familiares, Sexo , Idade
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Quadros Clínicos
Angina do Peito Estável
 Angina do Peito Instável
 Infarto do Miocárdio
 Morte Súbita
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OBJETIVOS DA TERAPÊUTICA
 Aumentar a oferta de O2
 Reduzir necessidades de O2
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TRATAMENTO
Medidas Gerais
 Redução dos fatores de risco
 Controle de patologias associadas
 Atividade física
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TRATAMENTO FARMACOLÓGICO
 NITRATOS
 ANTAGONISTAS DO CÁLCIO
 BETA-BLOQUEADORES
 ANTIAGREGANTES PLAQUETÁRIOS
 ESTATINAS
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NITRATOS ORGÂNICOS
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MECANISMO DE AÇÃO
Nitratos
  (R’ - SH)
NO

Ativação da Guanilatociclase (GC) 

GMPCc

Relaxamento da Musculatura Vascular
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EFEITOS FARMACOLÓGICOS
Relaxamento: músculo liso
Vasodilatação periférica (veias, artérias e arteríolas)
EFEITOS HEMODINÂMICOS
 Venodilatação
 Vasodilatação arterial e arteriolar
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FÁRMACOS
Nitroglicerina
 Dinitrato de isossorbida (ISDN)
 5-Mononitrato Isossorbida (5-ISMN)
VIAS DE ADMINISTRAÇÃO
Sublingual: ataque agudo 
Oral: doses maiores
IV: angina instável / Infarto agudo
Transmucosa ou bucal
Transcutânea: efeito prolongado
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EFEITOS ADVERSOS
Cefaléia 
Hipotensão postural
Palpitações
Tonturas, Síncope
Rubor
Metemoglobinemia
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Antagonistas de Canais de Cálcio
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Antagonistas de Canais de Cálcio
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 Tensão da Parede
Antagonistas de Canais de Cálcio
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 - Bloqueadores
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Betabloqueadores
Mecanismo de ação na isquemia miocárdica
  Fluxo Coronariano
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Betabloqueadores
Mecanismo de ação na isquemia miocárdica
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Antiagregantes Plaquetários
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Antiagregantes Plaquetários
 Aspirina
 Ticlopidina
 Clopidogrel
Antagonistas de receptores da Glicoproteína IIb/IIIa
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Inibe a ciclooxigenase
 Prostaglandinas e TXA2
 Agregação Plaquetária:
	- Resposta ao colágeno
	- Resposta ao ADP
	- Resposta a Trombina
	- Resposta a TXA2 		 
ASPIRINA 
Mecanismo de Ação
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Sangramento
Gastrite
Reações anafiláticas
Insônia
 Dependem da dose, duração da terapia, doenças associadas ( H. pylori, úlcera péptica, doenças hematológicas)
ASPIRINA Efeitos Adversos
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Agentes Trombolíticos
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1. Ativadores convertem plasminogênio em plasmina
2. Plasmina degrada o fibrinogênio e lisa a fibrina do trombo
3. Se a geração de Plasmina > inativação Plasmina :
	↓ fibrinogênio, Fator V e Fator VIII
Vias da Trombólise
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Estreptoquinase (SK) - Streptase®
Proteina secretada por estreptococo do grupo C
Só tem atividade lítica quando forma o complexo SK-PLGN
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Ou
BRA
BCC
IECA
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OBRIGADO
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