FARMACOLOGIA II

ANGINA ESTVEL

OBJECTIVO

- resoluo de casos prticos, trabalho realizado na aula e em grupo, sob

superviso do docente

- discusso conjunta de cada caso; partindo desta discusso, reviso dos

principais conceitos da Farmacologia Bsica e Clnica dos frmacos usados
na resoluo e na profilaxia da crise de angina de peito e elaborao do
Formulrio Pessoal numa lgica de prescrio racional, sempre que possvel
articulada com as normas de orientao da DGS

OBJECTIVO

Para cada caso:

- definio do problema e do objectivo teraputico

- estabelecimento de estratgias teraputicas, farmacolgicas e no

farmacolgicas (comparar medicamentos em termos de eficcia,
segurana, adequao e custo)

instituio de teraputica farmacolgica (definio de regime

posolgico, forma e via de administrao, durao da teraputica)

- dar indicaes sobre monitorizao

DOENA CARDACA ISQUMICA_ANGINA ESTVEL

padro reprodutvel de angina associado a determinado nvel de actividade fsica
Aterosclerose

Aporte O2
- fluxo coronrio
- extraco/disponibilidade
(saturao, Hb, hematcrito) de O2

Necessidade O2
- frequncia
- contractilidade
- tenso intramiocrdica
(volume e presso ventricular)

Isqumia
miocrdica
OBJECTIVO TERAPUTICO
ALVIO (E PREVENO) DE EPISDIOS AGUDOS
PREVENO DE RECORRNCIAS
RISCO EM E SOBREVIDA (longo prazo)

DOENA CARDACA ISQUMICA_ANGINA ESTVEL

ALVOS FARMACOLGICOS/TERAPUTICOS

IMP CONTROLO/TRATAMENTO DOS FACTORES DE RISCO

(RELEMBRAR ANTIAGREGAO PLAQUETAR)

Aterosclerose

IMP MELHORAR PERFUSO

HTA
TABAGISMO
DISLIPIDMIA
DM
OBESIDADE
SEDENTARISMO

IMP TRABALHO

Aporte O2

Necessidade O2

- fluxo coronrio
- extraco/disponibilidade
(saturao, Hb, hematcrito) de O2

- frequncia
- contractilidade
- tenso intramiocrdica
(volume e presso ventricular)

CASO PRTICO_1

JP, homem de 62 anos, jardineiro. Procura o seu mdico de famlia para avaliao de uma
dor no peito, que sinto h cerca de 3 semanas, ao levantar objectos pesados e ao caminhar,
especialmente em subidas. Refere que a dor cessa alguns minutos aps interrupo da
actividade e no surge em repouso. Refere ainda que no est associada s refeies ou a
situaes de stress emocional. At h 3 semanas atrs executava tarefas sem quaisquer
queixas.
A me e a irm morreram de ataque cardaco aos 62 e 57 anos de idade, respectivamente. O
pai, ainda vivo, com 86 anos de idade, sobreviveu a uma ataque cardaco e a um acidente
vascular cerebral. Ningum na famlia /foi diabtico.
JP no fumador e segue dieta de restrio salina. Porm, consome com regularidade a sua
refeio rpida preferida, 2 cheeseburguers e batatas fritas. obeso.
Outros problemas mdicos: HTA h 10 anos, DM h 4 anos, amputao traumtica da mo
direita.
Medicao crnica: atenolol 50 mg, losartan 50 mg, glipizida 5 mg 2 id.

CASO PRTICO_1
Na consulta no aparenta sinais de stress. PA na consulta 164/98 mmHg. Auscultao cardaca
e pulmonar e exame abdominal normais. Sem edemas perifricos.
ECG pedido revela ritmo sinusal, com todos os intervalos dentro dos limites normais e sem
evidncia de EM prvio. Perfil lipdico (LDL, HDL e TG) dentro de valores de referncia.
Estudo subsequente completo, que culmina em angiografia, permite identificar leses em 2
vasos coronrios (55 e 70%), sem envolvimento da descendente anterior lateral. Indicao
para teraputica farmacolgica do problema identificado: angina de peito estvel.

DOENA CARDACA ISQUMICA_ANGINA

ESTVEL

FRMACOS
Dilatao
coronria

Contractilidade

++

NITRATOS

++

Vasodilatador,
NO

(mesmo na
presena de
aterosclerose)

BB

Frequncia

Ps-carga

Pr-carga

(resistncia arteriolar)

(retorno venoso)

++

++

++

++

++

++

bloqueio adrenrgico

BCC
bloqueio
canais Ca2+ (L)

circunstancialmente CONSIDERAR
NICORANDIL (NO + potssio)
IVABRADINA (bloqueio canais Na+/K+)
RANOLAZINA (bloqueio corrente tardia de Na+)
TRIMETAZIDINA (inibio da FOX; fatty acid oxidation)

CIDOS GORDOS vs. GLUCOSE

(CONSUMO O2 vs. PRODUO ATP)
INIBIDORES OXIDAO CIDOS GORDOS

NORMA DA DGS_ALGORITMO CLNICO

BB, eficcia clnica e prognstica

ADEQUAO TERAPUTICA FARMACOLGICA-OBJECTIVOS TERAPUTICOS

NITRATOS

nitroglicerina, nitrato de isossorbido

aco rpida
via sublingual

BB

atenolol, bisoprolol, carvedilol, nebivolol, metoprolol, propranolol

ATENO

DPOC
conduo AV
IC aguda
sndrome metablico

CASO PRTICO_1 (continuao)

JP mantm-se a teraputica durante alguns meses, mas refere episdios de dor 1 a 4 vezes por
semana. Como anteriormente, as crises so precipitadas pela actividade fsica e aliviam aps
administrao sublingual de NTG.
PA controlada e FC normal.
O cardiologista decide prescrever um nitrato de longa durao de aco (dinitrato de
isossorbido 30 mg 3 id oral), bem como manter o BB.
QUESTES A DISCUTIR
- comentar prescrio de um BCC em vez de um nitrato
- principal cuidado com administrao crnica de um nitrato? como prevenir?

NORMA DA DGS_ALGORITMO CLNICO

BB, eficcia clnica e prognstica

CASO PRTICO_2

RO, homem de 65 anos.

Fumador h 40 anos.
DM insulino-dependente h 13 anos.
Capacidade limitada para andar por doena vascular perifrica e angina estvel.
Qual o BB indicado como teraputica de manuteno?

CASO PRTICO_2

BB
ATENO
DPOC
conduo AV
IC aguda
sndrome metablico

IMPORTNCIA CARDIOSELECTIVIDADE
atenolol, metoprolol, bisoprolol, nebivolol, propranolol
(ex. obviar efeito broncoconstrictor mediado por 2)

CASO PRTICO_3

BN, homem de 56 anos de idade.

Doena coronria. Recusa nitratos por dores de cabea severas.
Asma e hiperlipidmia.
Cardiologista inicia nifedipina 10 mg 3id.
Aps introduo da nifedipina queixa-se de aumento da frequncia das crises e de
taquicardia cerca de 90 minutos aps toma.
Comentar opo teraputica por BCC e no BB.
Efeitos descritos (exacerbao e taquicardia) relacionados com nifedipina?
Sugerir alternativa.

CASO PRTICO_3

ACC

DIHIDROPIRIDNICOS
amlodipina, nifedipina, lecarnidipina, felodipina

> selectividade vascular

aco longa, ex. amlodipina
ou
aco curta, mas libertao prolongada, ex. nifedipina aco prolongada
+ BB (controlo taquicardia reflexa)
NO DIHIDROPIRIDNICOS
verapamil, diltiazem
contractilidade e frequncia, inibio NAV
CI: IC, bradicardia, bloqueio AV

NO + com BB

NORMA DA DGS_ALGORITMO CLNICO

BB, eficcia clnica e prognstica

 resumindo
1) alvio (e preveno) de episdios agudos
NITRATOS aco rpida
IMP tempo de latncia, via/forma de administrao
2) profilaxia de recorrncias

BCC

1 linha

BB eficcia clnica e prognstica 1 opo teraputica

se sintomas no controlados + NITRATOS aco prolongada

se cronotropismo negativo insuficiente + IVABRADINA
se CI ou intolerncia alternativa:
NITRATOS longa durao, NICORANDIL, IVABRADINA, TRIMETAZIDINA e RANOLAZINA
(incluidos no algoritmo da Sociedade Europeia de Cardiologia)

IMP seleco de acordo com efeitos conhecidos na morbilidade/mortalidade, co-morbilidades e

perfil de reaces adversas
IMP monoterapia ou associaes

vascular disease.
Traditional anti-ischaemic drugs are the first step in medical treatment.52 Short-acting nitrates can be used to treat anginal attacks, but
Figure 4 summarizes the medical management of SCAD patients. This
common strategy might be adjusted according to patient comorbidoften they are only partially effective. b-Blockers seem a rational apities, contra-indications, personal preference and drug costs. The
proach because the dominant symptom is effort-related angina; they
medical management consists of a combination of at least a drug
were indeed found to improve symptoms in several studies and
Algoritmo
da
Sociedade
Europeia de
for angina relief plus drugs to improve prognosis, as well as use of
should constitute the first choice of therapy, particularly in patients

7.4 Strategy

Cardiologia

Angina relief

Event prevention

1st line
Short-acting Nitrates, plus
Beta-blockers or CCB-heart rate
Consider CCB-DHP if low heart rate or
intolerance/contraindications
Consider Beta-blockers + CCB-DHP if
CCS Angina > 2

Lifestyle management
Control of risk factors

May add or
switch (1st line
for some cases)

Aspirineb
Statins
Consider ACEI or ARBs

Ivabradine
Long-acting nitrates
Nicorandil
Ranolazinea
Trimetazidinea

2nd line

+ Educate the patient

+ Consider Angio
PCI
Stenting or CABG

Figure 4 Medical management of patients with stable coronary artery disease. ACEI angiotensin converting enzyme inhibitor; CABG

coronary artery bypass graft; CCB calcium channel blockers; CCS Canadian Cardiovascular Society; DHP dihydropyridine; PCI
percutaneous coronary intervention.
a
Data for diabetics.
b
if intolerance, consider clopidogrel

2013 ESC guidelines on the management

2980
of stable coronary artery disease

ESC Guidelines

The Task Force on the management of stable coronary artery disease

of the European Society of Cardiology

Table 28 Pharmacological treatments in stable coronary artery disease patients

Indication

Class a

Level b

Ref. C

General
considerations
Task
Force
Members: Gilles Montalescot* (Chairperson) (France), Udo Sechtem*
I
C
Optimal medical treatment indicates at least one drug for angina/ischaemia relief plus drugs for event prevention.
(Chairperson) (Germany), Stephan Achenbach (Germany), Felicita
Andreotti
(Italy),
I
C
It is recommended to educate patients about the disease, risk factors and treatment strategy.
Chris Arden (UK), Andrzej Budaj (Poland), Raffaele Bugiardini (Italy), Filippo Crea
C
It is indicated
to review theCuisset
patients response
soon after startingCarlo
therapy. Di Mario (UK), J. RafaelI Ferreira
(Italy),
Thomas
(France),
(Portugal),
Angina/ischaemia relief
Bernard
J. Gersh (USA), Anselm K. Gitt (Germany), Jean-Sebastien Hulot (France),
I
B
Short-acting nitrates are recommended.
3, 329
Nikolaus Marx (Germany), Lionel H. Opie (South Africa), Matthias
Pfisterer
I
A
First-line treatment is indicated with -blockers and/or calcium channel blockers to control heart rate and symptoms.
3, 331
(Switzerland),
Eva Prescott (Denmark), Frank Ruschitzka (Switzerland),
Manel
Sabate
177, 307, 3,
(Spain), Roxy Senior (UK), David Paul Taggart (UK), Ernst E. van der Wall199, 284,
For second-line treatment it is recommended to add long-acting nitrates or ivabradine or nicorandil or ranolazine,
IIa
B
286, 308,
(Netherlands),
Christiaan
J.M. Vrints (Belgium).
according to heart rate, blood
pressure and tolerance.
319-321,
disease
d

Downloaded from by guest on March 19, 2015

328
ESC Committee for Practice Guidelines (CPG): Jose Luis Zamorano (Chairperson) (Spain), Stephan Achenbach
IIb
B
For second-line
treatment,Baumgartner
trimetazidine may be(Germany),
considered.
313, 315 Dean
(Germany),
Helmut
Jeroen J. Bax (Netherlands), Hector Bueno
(Spain),
Veronica
(France), Christi Deaton (UK), Cetin Erol (Turkey), Robert Fagard (Belgium), Roberto Ferrari (Italy), David Hasdai
I
C
patients.
(Israel),
Arno W. Hoes (Netherlands), Paulus Kirchhof (Germany/UK), Juhani Knuuti (Finland), Philippe Kolh (Belgium),
Patrizio
Lancellotti
Linhart
(Czech
Republic),
Petros Nihoyannopoulos (UK),
Massimo
F. Piepoli
(Italy),
IIa
C
In asymptomatic
patients(Belgium),
with large areasAles
of ischaemia
(>10%)
-blockers
should be considered.
Piotr Ponikowski (Poland), Per Anton Sirnes (Norway), Juan Luis Tamargo (Spain), Michal Tendera (Poland),
In patients with vasospastic angina, calcium channel blockers and nitrates should be considered and beta-blockers
B
3, 365
Adam
Torbicki (Poland), William Wijns (Belgium), Stephan Windecker (Switzerland). IIa
avoided.

It is recommended to use ACE inhibitors (or ARBs) if presence of other conditions (e.g. heart failure, hypertension or
diabetes).

348, 349,
351, 352

ACE
angiotensinauthors.
converting
SCADcontributed
stable coronary
* Corresponding
Theenzyme;
two chairmen
equallyartery
to the disease.
documents. Chairman, France: Professor Gilles Montalescot, Institut de Cardiologie, Pitie-Salpetriere University
a
Class
of recommendation.
Hospital,
Bureau
2-236,
47-83
Boulevard
de
lHopital,
75013
Paris,
France. Tel: +33 1 42 16 30 06, Fax: +33 1 42 16 29 31. Email: gilles.montalescot@psl.aphp.fr. Chairman, Germany:
b
Level
of evidence.
Professor
Udo Sechtem, Abteilung fur Kardiologie, Robert Bosch Krankenhaus, Auerbachstr. 110, DE-70376 Stuttgart, Germany. Tel: +49 711 8101 3456, Fax: +49 711 8101 3795, Email:
c
Reference(s)
supporting levels of evidence.
udo.sechtem@rbk.de
d
No demonstration of benefit on prognosis
Entities having participated in the development of this document:

ESC Associations: Acute Cardiovascular Care Association (ACCA), European Association of Cardiovascular Imaging (EACVI), European Association for Cardiovascular Prevention &
Rehabilitation (EACPR), European Association of Percutaneous Cardiovascular Interventions (EAPCI), Heart Failure Association (HFA)

Downloaded from by guest on March 19, 2015

Event prevention
Document
Reviewers: Juhani Knuuti (CPG Review Coordinator) (Finland), Marco Valgimigli (Review Coordinator)
333, 334,

(Italy),
He
ctor
(Spain), in
Marc
J. Claeys
I
ACetin Erol (Turkey),
Low-dose aspirinBueno
daily is recommended
all SCAD
patients. (Belgium), Norbert Donner-Banzhoff (Germany),
366
Herbert Frank (Austria), Christian Funck-Brentano (France), Oliver Gaemperli (Switzerland),
I
B
is indicated as an alternative
in caseMichalis
of aspirin intolerance.
335
JoseClopidogrel
R. Gonzalez-Juanatey
(Spain),
Hamilos (Greece), David Hasdai (Israel), Steen
Husted
(Denmark),
Stefan
K.
James
(Sweden),
Kari
Kervinen
(Finland),
Philippe
Kolh
(Belgium),
Steen
Dalby
Kristensen
(Denmark),
I
A
Statins are recommended in all SCAD patients.
62
Patrizio Lancellotti (Belgium), Aldo Pietro Maggioni (Italy), Massimo F. Piepoli (Italy), Axel R. Pries (Germany),

2013 ESC guidelines on the management

of stable coronary artery disease
2976

The Task Force on the management of stable coronary artery disease

Dieta
of the European Society of Cardiology

<5 g of salt per day.

ESC Committee for Practice Guidelines (CPG): Jose Luis Zamorano (Chairperson) (Spain), Stephan Achenbach
(Germany), Helmut Baumgartner (Germany), Jeroen J. Bax (Netherlands), Hector Bueno (Spain), Veronica Dean
(France), Christi Deaton (UK), Cetin Erol (Turkey), Robert Fagard (Belgium), Roberto Ferrari (Italy), David Hasdai
(Israel), Arno W. Hoes (Netherlands), Paulus Kirchhof (Germany/UK), Juhani Knuuti (Finland), Philippe Kolh (Belgium),
Patrizio Lancellotti (Belgium), Ales Linhart (Czech Republic), Petros Nihoyannopoulos (UK), Massimo F. Piepoli (Italy),
Piotr Ponikowski (Poland), Per Anton Sirnes (Norway), Juan Luis Tamargo (Spain), Michal Tendera (Poland),
Adam Torbicki (Poland), William Wijns (Belgium), Stephan Windecker (Switzerland).

3
vegetables.

200 g of fruit per day (23 servings).

Document Reviewers: Juhani Knuuti (CPG Review Coordinator) (Finland), Marco Valgimigli (Review Coordinator)
(Italy), Hector Bueno (Spain), Marc J. Claeys (Belgium), Norbert Donner-Banzhoff (Germany), Cetin Erol (Turkey),
Herbert Frank (Austria), Christian Funck-Brentano (France), Oliver Gaemperli (Switzerland),
Jose R. Gonzalez-Juanatey (Spain), Michalis Hamilos (Greece), David Hasdai (Israel), Steen Husted (Denmark),
Stefan K. James (Sweden), Kari Kervinen (Finland), Philippe Kolh (Belgium), Steen Dalby Kristensen (Denmark),
Patrizio Lancellotti (Belgium), Aldo Pietro Maggioni (Italy), Massimo F. Piepoli (Italy), Axel R. Pries (Germany),

200 g of vegetables per day (23 servings).

F

Consumption of alcoholic beverages should be limited to 2 glasses

per day (20 g/day of alcohol) for men and 1 glass per day (10 g/day
* Corresponding authors.
The two chairmenfor
contributed
equally to the documents.women.
Chairman, France: Professor Gilles Montalescot, Institut de Cardiologie, Pitie-Salpetriere University
of alcohol)
non-pregnant

Hospital, Bureau 2-236, 47-83 Boulevard de lHopital, 75013 Paris, France. Tel: +33 1 42 16 30 06, Fax: +33 1 42 16 29 31. Email: gilles.montalescot@psl.aphp.fr. Chairman, Germany:
Professor Udo Sechtem, Abteilung fur Kardiologie, Robert Bosch Krankenhaus, Auerbachstr. 110, DE-70376 Stuttgart, Germany. Tel: +49 711 8101 3456, Fax: +49 711 8101 3795, Email:
udo.sechtem@rbk.de
Entities having participated in the development of this document:
ESC Associations: Acute Cardiovascular Care Association (ACCA), European Association of Cardiovascular Imaging (EACVI), European Association for Cardiovascular Prevention &
Rehabilitation (EACPR), European Association of Percutaneous Cardiovascular Interventions (EAPCI), Heart Failure Association (HFA)

Downloaded from by guest on March 19, 2015

Task Force Members: Gilles Montalescot* (Chairperson) (France), Udo Sechtem*

(Chairperson) (Germany), Stephan Achenbach (Germany), Felicita Andreotti (Italy),
Table 25 Recommended diet intakes
Chris Arden (UK), Andrzej Budaj (Poland), Raffaele Bugiardini (Italy), Filippo Crea
(Italy), Thomas Cuisset (France), Carlo Di Mario (UK), J. Rafael Ferreira (Portugal),
Bernard J. Gersh (USA), Anselm K. Gitt (Germany), Jean-Sebastien Hulot (France),
Saturated fatty acids to account for <10% of total energy intake,
Nikolaus Marx (Germany), Lionel H. Opie (South Africa), Matthias Pfisterer
through
by polyunsaturated
fatty acids.
(Switzerland),
Evareplacement
Prescott (Denmark),
Frank Ruschitzka
(Switzerland), Manel Sabate
(Spain), Roxy Senior (UK), David Paul Taggart (UK), Ernst E. van der Wall
Trans unsaturated fatty acids <1% of total energy intake.
(Netherlands), Christiaan J.M. Vrints (Belgium).

antihy
zides
Life
exerc
ED.26
(PDE
safe a
as de
work
tions
dinitr
becau
tensio
mend
failure
Patien
betw

 Caso Formulrio Pessoal

AMNG, 49 anos
Deputado. Hbitos alcolicos moderados. Consumidor frequente de fastfood e de 6 cafs expresso/ dia . Frequenta ginsio uma vez por semana.
Prcordialgia sbita com irradiao direita
AP: Dislipidmia, medicada com estatina 20mg id noite; HTA controlada
com diurtico tiazdico e BCC, desde h 5 anos.
Medicado com Dinitrato de Isossorbido, os sintomas mantiveram-se.
Sugestes para teraputica farmacolgica (alvio sintomatolgico e de
manuteno) e no farmacolgica?