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SISTEMA CIRCULATORIO:
FUNCIONES PRINCIPALES
• Transportar y distribuir sustancias
esenciales a los tejidos
• Remover desechos metabólicos
• Ajustar la provisión de oxígeno y
nutrientes en diferentes estados
metabólicos
• Regulación de la temperatura corporal
• Comunicación humoral
Un sistema complicado
Que se puede simplificar
CIRCUITOS EN SERIE
Y EN PARALELO
CICLO CARDIACO
Potencial de acción cardíaco
ATRIUM VENTRICLE
0 0
mv
mv
-80mv
-80mv
0
mv
SA NODE
-80mv
time
Conductancias
del PA cardíaco
Corrientes y PA cardíaco
Fast K reopens
Fast K closes Slow K opens
("Delayed rectifier")
Del PA al ECG
AV NODE AND AV BLOCKS
FOCUS ON N REGION
NORMA ECG
L
1ST DEGREE
PROLONGUED AV
CONDUCTION TIME
2ND DEGREE
1/2 ATRIAL IMPULSES
CONDUCTED TO VENTRICLES
3RD DEGREE
VAGAL MEDIATION
IN N REGION/COMPLETE
BLOCK
Patologías cardiovasculares que
requieren farmacoterapia
• Hipertensión
• Arritmia
• Falla cardíaca
• Trastornos de flujo vascular
Cardiac Output
• Heart rate
– Function of
• sympathetic, vagal nervous activity
• Neuro-hormonal substances
– 1° angiotensin II
– 2º vasopression (anti-diuretic hormone = ADH)
• Stroke volume
– Function of
• Venous return (function of venous tone [contractile state] and
circulating blood (vascular) volume)
– Venous tone function of sympathetic activity (α1, α2 receptors)
– Vascular volume depends on
» Intake of fluids (thirst)
» Output of fluids (urine, sweat, etc)
» Distribution of fluids (Starling’s law)
• Myocardial contractility (MC proportional to sympathetic tone [β1
receptors])
Characteristics of some adrenoceptors
Tissues (sympatheticreceptors
nerves)
and effects
α1 α2 β1 β2
Smooth
muscle
Arteries/ constrict constrict/ dilate
veins dilate
Skeletal dilate
muscle
Heart
Rate (increase)
Force of increase
contraction
Autonomic Regulation of the Heart
• Heart Rate
– Parasympathetic input via vagus nerve
causes decrease in HR (dominates)
– Sympathetic input to sino-atrial node causes
increase in HR (usually minor)
• Heart contractility
– Increased by sympathetic activity causing
release of epinephrine, norepinephrine from
adrenal gland
Hipertensión
Antihypertensive Classes
• diuretics
• beta blockers
• angiotensin-converting enzyme (ACE)
inhibitors
• calcium channel blockers
• vasodilators
Alpha1 Blockers
Stimulate alpha1 receptors -> hypertension
Block alpha1 receptors -> hypotension
• doxazosin (Cardura®)
• prazosin (Minipress®)
• terazosin (Hytrin®)
Central Acting Adrenergics
• Stimulate alpha2 receptors
– inhibit alpha1 stimulation
• hypotension
• clonidine (Catapress®)
• methyldopa (Aldomet®)
Peripheral Acting Adrenergics
• reserpine (Serpalan®)
• inhibits the release of NE
• diminishes NE stores
• leads to hypotension
• Prominent side effect of depression
– also diminishes seratonin
Adrenergic Side Effects
• Common
– dry mouth, drowsiness, sedation &
constipation
– orthostatic hypotension
• Less common
– headache, sleep disturbances, nausea, rash
& palpitations
Sistema renina-angiotensina
ACE Inhibitors RAAS
Angiotensin I
.
ACE
Angiotensin II
1. potent vasoconstrictor
- increases BP
2. stimulates Aldosterone
- Na+ & H2O
reabsorbtion
Angiotensin Converting Enzyme
Inhibitors
• captopril (Capoten®)
• enalapril (Vasotec®)
• lisinopril (Prinivil® & Zestril®)
• quinapril (Accupril®)
• ramipril (Altace®)
• benazepril (Lotensin®)
• fosinopril (Monopril®)
Calcium Channel Blockers
• Used for:
• Angina
• Tachycardias
• Hypertension
Antagonistas de calcio
como vasodilatadores
Calcium Channel Blockers
• diltiazem (Cardizem®)
• verapamil (Calan®, Isoptin®)
• nifedipine (Procardia®, Adalat®)
Diuretics
• Thiazides:
• chlorothiazide (Diuril®) & hydrochlorothiazide (HCTZ®,
HydroDIURIL®)
• Loop Diuretics
• furosemide (Lasix®), bumetanide (Bumex®)
• Potassium Sparing Diuretics
• spironolactone (Aldactone®)
Diuretic Site of Action
Distal
tubule
proximal
tubule
Collecting
duct
loop of Henle
Mechanism
• Because CO is a function of
– Heart Rate – determined by pacemaker cells in the sinoatrial node
– Stroke volume – determined by fill rate and contractile force
– Atrial/ventricular/valvular coordination
• Capillaries
– Tiny but contain greatest cross-sectional area to allow high exchange rate
– Contain precapillary sphincters to regulate blood flow
– 5% of blood volume
nifedipine
(and other
dihydropyridines)
CCB Action