TRATAMENTUL MEDICAMENTOS

IN
BOLILE CARDIO-VASCULARE
2015

1. DIURETICE

Diuretics
Diuretics
Inhibition of
Sodium Reabsorption
Reduced Circulating Volume
Reduced Preload
Reduced Cardiac Output

Mechanism of action:

DIURETICS
= lower blood pressure by reduction of blood volume
and by direct vascular effect
- inhibition of sodium chloride transport in the early segment
of the distal convoluted tubule natriuresis, decrease in
preload and cardiac output - renal effect
- slow decrease of total peripheral resistance (raised
initially) during chronic treatment, suggesting an action on
resistance vessels - extrarenal effects
- compensatory responses to pressor agents,
including angiotensin II and noradrenaline, are reduced
during chronic treatment with thiazides
- used with loop diuretic - synergistic effect occurs

Thiazides
Thiazides
Initial effects: natriuresis, diuresis,

reduced extracellular and circulating

volume)
Chronic effect: reduction in peripheral
vascular resistance (direct vasodilating
effect)
Max eff.: African Americans, elderly, obese
Combination with ACEIs and BBs
Given once daily

Thiazides
Thiazides
Side Effects: at low doses thiazides
are well tolerated

Hypokalemia
Lipid elevation
Glucose intolerance
Hyperuricemia
Hypercalcemia
Very rarely: severe rash,
tombocitopenia and leucopenia.

Thiazides
Thiazides
YES: (useful in)
Elderly patients
African Americans
Patient with mild or

incipient heart failure

When cost is crucial
When salt intake is high
Sexually active females
Combined with other
first line antiHTA drugs

No: (avoid in)

Patients with NIDDM
Patients with
hyperlipidemia

Patients with gout

Sexually active
males

Glomerular Filtration
Rate < 30ml/min

CONTRAINDICATII
Absolute
1. IR grava
2. Intoleranta la tiazide
3. Sarcina tulburari hematologice grave la NN
si mama
Relative - diabet zaharat, hiperuricemie, guta
Prudenta - IR moderata, ciroza hepatica, cardiaci

INTERACTIUNI MEDICAMENTOASE
1. Antidiabetice reduc eficacitatea tiazidelor
2. Litiu cresc cardio- si neurotoxicitatea Li
3. Doze mari cresc toxicitatea digitalicelor (aritmii)
4. AntiHTA, psihotrope risc de hTA
5. AINS scad efectul diuretic al tiazidelor

Loop Diuretics:
Indications
Edema associated with HF or hepatic
or renal disease
Control of hypertension
Increase renal excretion of calcium in
patients with hypercalcemia
Useful when rapid diuresis is desired
because of rapid onset of action

INDICATII
1. Toate tipurile de edeme IC, ciroza, IR
de electie in edemele grave, rezistente la
tiazide
se pot asocia cu tiazidele - creste eficienta
sunt eficiente si in situatiile cu FG
2. HTA monoterapie, in asociere cu alte antiHTA
3. IRA cu oligurie
4. EPA iv
5. Edem cerebral
6. Intoxicatii acute medicamentoase Intoxicatii cu
bromuri, ioduri, floruri

REACTII ADVERSE
1. Dezechilibre hidroelectrolitice
Risc mai mare decat la tiazide
Scaderea - Na+, K+ cu sau fara alcaloza,
Mg2+
2. Scaderea marcata a TA
3. Deshidratare si hiperazotemie tratament
prelungit cu doze mari, dieta hiposodata stricta
4. Hiperuricemie

REACTII ADVERSE
5.
6.
7.
8.

5. Hiperglicemie, agravarea diabetului

6. Hipercolesterolemie
7. Tulburari digestive
8. Rar pancreatita, nefrita interstitiala,
eruptii cutanate, leucopenie,
trombocitopenie,
9. 9.Surditate trecatoare sau definitiva

CONTRAINDICATII
1. Hipokaliemie, hiponatriemie marcate
2. Hipovolemie cu deshidratare
3. Ciroza decompensata
4. Intoxicatia digitalica
5. Prudenta IC severa, DZ, guta, obstacol pe
caile urinare, sarcina trim I
6.Necesar controlul electrolitilor, uree, creatinina
serica

INTERACTIUNI MEDICAMENTOASE
1. Asocierea cu tiazide - in edemele refractare

efect sinergic cu reducerea toxicitatii furosemidului

2. AINS, indometacin reduc efectul diuretic (reduc

sinteza de PG la nivel renal)
3. Aminoglicozide: risc de oto- si nefrotoxicitate
4.Curarizante, miorelaxante efect crescut de furosemid
5.Tratament cu Li monitorizarea Li, poate creste
6. Nu se amesteca cu alte medicamente si cu solutii acide
in aceeasi seringa

TERTENSIF SR - mod complet de aciune

- Reglarea influxului de calciu n

peretele vascular
- Stimularea sintezei de PGE2 i
PGI1

Efect vascular direct

- Corectarea suprancrcrii de sodiu

din peretele arterial la pacienii
hipertensivi

Efect renal saluretic

Corectarea hiperreactivitii vasculare la

catecolamine
Vasorelaxare la pacienii
hipertensivi

Eficacitate AntiHTA

Excelent acceptabilitate
Bine tolerat
Incidena efectelor secundare majore (%)
Placebo

Tertensif

SR
Cefalee

8.6

5.2

Ameeal

6.9

7.0

Astenie

5.2

3.5

Pierdere n greutate i poliurie

1.7

1.7

Rash

1.7

1.7

Mialgii

1.7

Fr modificari semnificative ale:

Glicemiei
Creatininei serice
Colesterolului seric Acidului uric seric
Guez D, Mallion JM, Degaute JP. Arch Mal Cur Vaiss. 1996;89:2-8.
Asmar R, Amah G, Crisan O, et al. Eur Heart J.
J. 1999;1(suppl P):21-31.

Potassium-Sparing Diuretics

EFFECTS:
Prevent potassium from being pumped into the tubule, thus
preventing its secretion
Competitively block the aldosterone receptors and inhibit its
action
The excretion of sodium and water is promoted
INDICATIONS: SPIRONOLACTONE
Hyperaldosteronism
Hypertension
Reversing the K+ loss caused by potassium-losing drugs
SPIRONOLACTONE: SIDE EFFECTS
Gynecomastia, Amenorrhea, Irregular menses
Postmenopausal bleeding

CONTRAINDICATII SI INTERACTIUNI
MEDICAMENTOASE
Hiperpotasemie
IRA si IH grava
Prudenta IRC, DZ,
Asocierea cu alte diuretice care economisesc K sau
administrare de KCl risc de hiperpotasemie
Asocierea cu IEC controlul K-emiei
AINS reduc efectul spironolactonei
Creste efectul antiHTA

Types and Names of Diuretics

Type

Osmotic agents

Thiazides

Example

Mannitol

Hydrochlorothiazide

Sites of Action
Proximal tubule
Descending loop
Collecting duct

Distal convoluted
tubule

Loop diuretic

Ethacrynic acid
Furosemide

Loop of Henle

K+ - sparing

Spironolactone
Amiloride

Collecting tubule

Diuretic Resistance: What is it?

Inadequate response to diuretic therapy

Represents an extension of cardiorenal syndrome
Failure to respond to IV loop diuretics
Decreased efficacy of diuretics with prolonged
treatment

Pe 20 februarie 1937
Maria Tnase i face
debutul la radio.
Milioane de romni,
de la Majestatea sa,
pn la oamenii din
mahalale, rmn
vrjii de glasul ei.
n afar de
compozitorul Rogalsky,
niciunul dintre invitaii
din studio nu auzise de
ea nainte.

2. BETABLOCANTELE

Where -Blockers Work

Sudden
death
Angina
Ventricular
arrhythmias

Hypertension
Coronary
artery
disease

Diabetes

Myocardial
LV
infarction dysfunction

Hyperlipidemia
Hypertrophic
cardiomyopathy

Heart
failure

Atrial
Cardiac
Pump
fibrillation
rupture
failure
Mechanical death

Beta
Beta Blockers
Blockers

Mechanisms
Mechanisms and
and Sites
Sites of
of Action
Action
______________________________

Negative Chronotropic
& Inotropic Effects

Inhibition of
Renin Release

- Reduction in cardiac output

- Inhibition of renin release
- CNS effects
- Reduction in venous return
and plasma volume
- Reduction in peripheral resistance
- Improvement in vascular compliance
- Effects on prejunctional receptors
- Attenuation of pressor response to
catecholamines (stress, exercise)

______________________________

Beta Blockers
There are 15 Beta blockers
Approved for:
Hypertension
Angina pectoris
Myocardial Infarction
Ventricular arrhythmia
Migraine prophylaxis
Heart Failure
Perioperative Hypertension

Beta Blockers
YES: (useful in)
Younger
Anxious
Angina pectoris
Post-MI patient

No: (avoid in)

COPD
IDDM
Peripheral Vasc.D
Raynauds S.
2nd and 3rd degree
block
Energetic patients

Beta-Blockers:
therapeutic uses

Coronary artery disease

Hypertension
Arrhythmias
Congestive heart failure
Hypertrophic
obstructive
cardiomyopathy
Dissecting aortic
aneurysm

Pheochromocytoma
Hyperthyroidism
Migraine -prophylaxis
Essential tremor
Anxiety stage fright
Glaucoma (topical)

Cardiac (mechanical;
electrical)
Vascular (decreased
perfusion)
Pulmonary
(bronchocostriction)
Metabolic (diabetes
mellitus)
Central Nervous System
(depression, nightmares)
Withdrawal Syndrome

Side Effects:
Bronchospasm
Bradicardia/heart block
Mask and prolong the symptoms of

hypoglycemia
Abrupt withdrawal can precipitate
MI
Cold extremities, Raynauds
phenomenon, intermittent
claudication
Decreased exercise tolerance;
fatigue, depression and impotence
CNS: sleep disturbance, vivid
dreams, nightmares
Effects of plasma lipids

Antihypertensive Effect of Beta-Blockers:

mechanisms
1. Decreased cardiac output
2. Inhibition of renin-angiotensin system
3. Decreased central sympathetic outflow
4. Resetting of baroreceptor
5. Others: prejunctional receptors,
prostaglandins, etc.

Nebilet -- combina
combinaie
ie unic
unic
de
de 2
2
Nebilet
izomeri
izomeri
l-l-Nebivolol
Nebivolol

Nebivolol
Nebivolol

dd-Nebivolol
Nebivolol

2 izomeri optici
8 stereoizomeri

8 stereoizomeri
16 izomeri diferii,
n proporii necunoscute

Vasodilataie endotelial NO
Vasodilataie endotelial NO
Vasodilataie endotelial NO
mediat
Vasodilataie endotelial NO
mediat
mediat
1-blocare
mediat
-blocare
De Cree. J Drug Investigation 1991; 3:40-50.; Himmelman A. Eur J Clin Pharmacol 1996; 51:259-264.
1

Ritter JM. Br J Clin Pharmacol 1999; 48:460-463.; Siebert CD et al.Chirality DOI 10.1002/chir.10-nov-07

3. ACE Inhibitors ( pril)

Captopril [CAPOTEN]
Enalapril [VASOTEC]
Lisinopril [ZESTRIL]
Benazepril [LOTENSIN]
Fosinopril [MONOPRIL]
Quinapril [ACCUPRIL]
Ramipril [ALTACE]
Perindopril [ACEON]
Trandolapril [MAVIK]

ACE Inhibitors
Indications
80s -

Hypertension

90s -

Heart Failure

95

Left Ventricular Dysfunction

95

Diabetic Nephropathy

96

Acute Myocardial Infarction

Cardiovascular disease as a
sequence of related pathological
events
Coronary
Myocardial
thrombosis

Myocardial
ischemia

Coronary artery
disease

Atherosclerosis

Endothelial
dysfunction

Role
of
RAS

Risk factors:
Hypertension
Dyslipidemia
Insulin resistance
Smoking

infarction

Arrhythmia and
loss of muscle

Cardiac
remodeling

Ventricular dilation

Congestive heart
failure
End-stage heart
disease

From Circulation 2006;114:28

Where ACE Inhibitors Work

Sudden
death

Angina

Ventricular
arrhythmias

Hypertension

Diabetes

Coronary
artery
disease

Myocardial
LV
infarction dysfunction

Hyperlipidemia
Hypertrophic
cardiomyopathy

Heart
failure

Atrial
Cardiac
Pump
fibrillation
rupture
failure
Mechanical death

IECA i sartanii blocheaz sistemul

renin-angiotensin pe ci diferite
Bradikinina/NO

Angiotensina I
Inhibitor
ACE

Formarea Angiotens.II
independent de ACE
(chimaza, etc.)

ACE

Fragmente inactive

Angiotensina II
SARTAN

RECEPTOR AT1
Vasoconstrictie
Retentie de Sodiu
Activarea SNS, Inflamatie
Stimularea proliferarii celulare
Aldosteron, Apoptoza

RECEPTOR AT2
Vasodilatie
Natriureza
Regenerare tisulara
Inhibarea proliferarii celulare
Diferentiere
Efecte anti-inflamatorii
Apoptoza

Hurairah H, et al. Int J Clin Pract 2004;58:173183; Steckelings UM, et al. Peptides 2005;26:14011409

ACE Inhibitors: Classification

Chemical
classification

Sulfhydryl-group
Captopril
Carboxyl-group
benazepril,

enalapril, lisinopril,
ramipril,
Phosphoryl -group
fosinopril

Pharmacokinetic
classification
Class I : Captopril - like
Captopril
Class II : Pro-Drug
benazepril, enalapril,
fosinopril, quinapril,
ramipril,
Class III: not
metabolized

lisinopril

ACE Inhibitors ( pril)

YES: (useful in)

Younger patients
Post MI LV dysfunction
Patient with HF
Diabetic patients
Non-diabetic nephropathy
Metabolic disorders
(hyperlipidemia, gout)

No: (avoid in)

Renal artery stenosis

Fluid-depleted patients
Pregnancy
Premenopausal women
who may become
pregnant

ACE Inhibitors: ( pril)

SIDE EFFECTS

Cough
Hypotension
Hyperkalemia
Angioedema
Renal Insufficiency
Fetal injury (2nd & 3rd
trimesters)

Major
Hypotension
Renal insufficiency
Cough
Hyperkalemia,
Hyperreninemia
Minor
Skin rash
Proteinuria,
Neutropenia

First dose hypotension - particularly in those receiving

diuretic therapy; the first dose should preferably be given
at bedtime.
Dry cough - the most frequent (5-30%) symptom; could be
reduced by treatment with sulindac (inhibits prostaglandin
biosynthesis)
Urticaria and angioneurotic edema - kinin
concentrations urticarial reactions and angioneurotic
edema)
Functional renal failure - occurs predictably in patients
with hemodynamically bilateral renal a. stenosis, and in
patients with renal a. stenosis in the vessel supplying a
single functional kidney
Fetal injury- results in oligohydramnios, craniofacial
malformations, contraindication in pregnancy

Therapeutic combination:
- useful interaction ACEIs with diuretics:
converting enzyme inhibitors interrupt by diuretics
increased plasma renin activity (and the consequent
activation of ANG II and aldosterone) and enhance the
antihypertensive efficacy of diuretics, as well as
reducing thiazide-induced hypokalemia.
-adverse interaction ACE inhibitors with
potassium-sparing diuretics and potassium
supplements, leading to hyperkalemia especially in
patients with renal impairment and so on

Cardiorenal Prioritization

1. Vascular Protection
2. Hypertension Control
3. Control of Nephropathy

In all people with diabetes

1. ACE inhibitor
2. ASA
3. Lipid Control (statin)
4. BP Control
5. Also as required:
Glycaemic control
Lifestyle
Smoking cessation

S-a nscut lng Tur

a fost vndut ca scl
la trgul din Vidin ,
scpat din haremul Pa
A devenit o lady la
curtea Reginei Victo
i e cunoscut de toa
lumea ca una din
primele femei-explora
din lume.
Florica Sas.

4. ANG II RECEPTOR BLOCKERS

Ang II Receptor Blockers (...sartans)

Losartan
Valsartan
Irbesartan
Candesartan
Telmisartan

inhibitori ai receptorilor
AT1 de angiotensina II)
moduleaza sistemul Renina
Angiotensina-Aldosteron
apartin clasei antiHTA
vasodilatatoare

These drugs lower blood pressure as the ACE

inhibitors and have the advantage of much lower
incidence of adverse effects resulting from accumulation
of bradykinin (cough, angioneurotic oedema);
- they cause fetal renal toxicity (like that of the ACE
inhibitors);
- these drugs reduce aldosterone levels and cause
potassium accumulation (attainment of toxic levels
- hazardous in patients with renal impairment).

Clinical Indications for ATII Antagonists

Hypertension
Heart failure
Prevention of
restenosis following
angioplasty

Evidence of benefit: ACEI vs ARB

ACE
High risk condition
Heart failure
Post-MI
High CAD risk
Diabetes
Chronic kidney disease
Recurrent stroke
prevention

inhibitor

ARB

Ang II Receptor Blockers

(...sartans)
Side effects
Angioedema has been reported rarely
Hyperkalemia, comparable with that seen

in patients treated with ACEIs

Risk of fetal injury and death; should not
be use during the 2nd and 3rd trimester of
pregnancy
Risk of symptomatic hypotension in
hypovolemic patients

Factors determining BP
Volume/Diuretics
Vasoconstrictors
BB, Catechols,
Endothelin, etc.

Central Nervous
System/Sartans

Peripheral
Nervous System
BCC

Vasodilators
NO, PG, etc.
Local Factors
Renal, Cardiac,
Adrenal/IECA

n 1930,

Lizica Codrean

deschidea prima sa
Hatha Yoga din Pa
Lumea bun er
nnebunit de no
descoperire a rom
i revista Vogu
scria despre baler
clasic, avangard
dansului moder
prietena lui Tzar
i muza lui Brnc

5. CALCIUM CHANNEL BLOCKERS

Calcium
Calcium Channel
Channel Blockers
Blockers

Dihydropyridines *
Amlodipine [NORVASC]
Felodipine [PLENDIL]
Nimodipine [NIMOTOP]
Nifedipine [ADALAT]

Phenylalkylamine
Verapamil [ISOPTIN]
Benzothiazepine
Diltiazem [DIACORDIN]

Calcium
Calcium Channel
Channel Blockers
Blockers
Pharmacologic Effects of Calcium Channel Blockers
Effect

Verapamil

Diltiazem

Dihydropyridines

Peripheral
Vasodilation

Heart Rate

Cardiac
Contractility

0/

SA / AV Nodal
Conduction

Coronary
Blood Flow

Calcium
Calcium Channel
Channel Blockers
Blockers
YES: (useful in)
Elderly patients
African Americans
Peripheral
vascular disease
Cerebrovascular
disease
Angina pectoris

No: (avoid in)

heart failure
heart block
-blockers
Short-acting
dihydropiridines:
Unstable angina
Recent MI

Calcium Channel Blockers

Side effects
Facial Flushing
Headaches
Non-pitting ankle edema
Constipation
Increased CHD mortality / controversy:
1995 vs. 1997-2000 data (SYST-EUR
study):Nifedipine

Lola Bobescu

Diva cu vioara
Incredibil de
talentat i
att de chic.
Cea despre
care maestru
Yehudi Menuhi
spunea c e
"cea mai mare
violonist a
secolului XX"

"Un pahar de
ampanie cu
lacrimi la final".
Elvira Popescu,
cea efervescent
i nvluitoare
A fost distins cu premiul "Molire"
i de dou ori cu ordinul Legiunea
de Onoare, una dintre cele mai
nalte dinstincii ale statului francez.
A ncetat din via la venerabila
vrst de 99 de ani, la Paris.
Este nmormntat ntr-un splendid
cavou n marmur pe o alee
lturalnic, aproape de ieirea
din Cimitirul Pre-Lachaise din
Paris

Simt c
slbiciunea
mea este
ndoiala (iar
ndoiala nu
trebuie s
apar n
balet nici
mcar pentru
o fraciune
de secund!),
iar fora,
punctul meu
tare este
sinceritatea
fa de mine
Alina Cojocaru,
i ceilali".
una dintre cele mai mari balerine ale lumii.

Multumesc pentru atentie !!