1 / 20

Cardiovascular Pharmacology

Cardiovascular Pharmacology. Review of Cardiovascular Form and Function. Introduction and Background. Cardiovascular disease is the major cause of death in the US (>50% of all deaths) Cardiovascular function based on Cardiac pumping ability Pace-making electrical signals

silvanaj
Télécharger la présentation

Cardiovascular Pharmacology

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Cardiovascular Pharmacology Review of Cardiovascular Form and Function

  2. Introduction and Background • Cardiovascular disease is the major cause of death in the US (>50% of all deaths) • Cardiovascular function based on • Cardiac pumping ability • Pace-making electrical signals • Force of contraction • Height of ventricle discharge pressure • Integrity of vasculature • Presence of blockage • Muscular tone/structural integrity • Pressure drop needed to move blood to and through capillary beds • Blood volume/composition • Water, electrolyte, iron balances • Lipid and protein composition

  3. Major Cardiovascular Pathologies Requiring Pharmacological Intervention • Hypertension • Arrhythmia • Heart failure • Reduced vascular blood flow

  4. I. Background to Hypertension -Regulation of Blood Pressure • Arterial blood pressure due to combination of cardiac output (CO) and total peripheral resistance (TPR) • CO – regulated by heart rate and stroke volume (CO = HR x SV) • TPR function of • Viscosity of blood (hematocrit) • Length of blood vessels • Blood vessel luminal diameter (especially precapillary arterioles)

  5. 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])

  6. Characteristics of some adrenoceptors (sympathetic nerves) Tissues and effects receptors

  7. Beat-to-Beat Modulation of Blood Pressure Controlled by baroreceptor reflex arch • Baroreceptors located in aortic arch • Increased stretching due to higher aortic arch pressure  increased vagal nerve activity  decreased heart rate decreased cardiac output  decreased blood pressure • Fast acting

  8. Autonomic Regulation of Blood Pressure • Coordinates and integrates all regulators of cardiovascular function • Can regulate both cardiac output and blood vessel size via sympathetic and parasympathetic innervation of cardiovascular end-organs (heart, vasculature, kidneys, adrenal glands, etc)

  9. 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

  10. II. Background to Arrhythmia - Rhythm of the Heart • Human heart is four-chambered • Chambers need to contract sequentially (atria, then ventricles) and in synchronicity • Also need relaxation between contractions to allow refilling of chambers • Above controlled electrically (Purkinje fibers allow rapid, organized spread of activation)

  11. Regulation of Heart Rate • Primarily accomplished by sinoatrial node (SA) • Located on right atrium • Receives autonomic input • When stimulated, SA signals atrial contractile fibers  atria depolarization and contraction (primes ventricles with blood) • Depolarization picked up by atrioventricular node (AV node)  depolarizes ventricles  blood discharged to pulmonary artery and dorsal aorta  eventually rest of body

  12. Sequential Discharge of SA and AV nodes

  13. III. Background to Congestive Heart Failure Maintenance of Normal Heart Function • Normal cardiac output needed to adequately perfuse peripheral organs • Provide O2, nutrients, etc • Remove CO2, metabolic wastes, etc • Maintain fluid flow from capillaries into interstitium and back into venous system  if flow reduced or pressure increased in venous system  build up of interstitial fluid = edema • 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 Any negative change on above can lead to inadequate perfusion and development of the syndrome of heart failure

  14. IV. Background to Reduced Vascular Blood Flow: Blood Vessel Anatomy and Function • Arterial blood vessels • Smooth muscle (slow, steady contraction) • elastic tissue (stretch on systole, recoil on diastole) • Contain about 10% of blood volume • Arterioles have sphincters which regulate 70% of blood pressure • Venous blood vessels • Highly distensible, some contractility • Contain over 50% of blood volume • Capillaries • Tiny but contain greatest cross-sectional area to allow high exchange rate • Contain precapillary sphincters to regulate blood flow • 5% of blood volume All vasculature under ANS and humeral control

  15. Quantification of Total Peripheral Resistance TPR = _L · η_ for sum of all blood vessels r4 (Poiseuille’s equation) Where r = radius of blood vessel L = length of blood vessel η = viscosity of blood (function of hematocrit) hematocrit = Therefore: change in blood vessel radius has greatest effect on TPR Note: 70% of TPR produced/controlled by arterioles  target of drug treatment

  16. Relationship between blood flow and radius of a blood vessel 0.063 0.5

  17. Relationship between blood pressure, velocity and total area of vasculature

  18. Humeral Regulation of Blood Pressure: Renin-Angiotensin-Aldosterone System • Renin:secreted by the kidney in response to reduced blood pressure or blood volume • Angiotensin:Renin converts Angiotensinogen  Angiotensin I • Angiotensin Converting-Enzyme (ACE): converts Angiotensin I  Angiotensin II in lung • Angiotensin II: • Actions: • Intense vasoconstriction  increase TPR • Causes release of Aldosterone from adrenal gland  promotes Na+ and water reabsorption in kidney  cause increased blood volume. • Regulatory negative feedback on the release of Renin. • CNS: Stimulate thirst in hypothalamus, stimulate sympathetic outflow. - All above designed to bring arterial blood pressure back up to normal set-point

  19. Autonomic regulation of the vasculature • Increased sympathetic activity  reduction in blood vessel opening (caliber)  increase in vascular resistance  etc.  etc  increase blood pressure

  20. Stop talking now and let them go! I’m outta’ here!

More Related