cardiovascular pharmacology.ppt

8/11/2019 Cardiovascular Pharmacology.ppt

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Cardiovascular Pharmacology

Review of Cardiovascular Form

and Function


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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 contractionHeight of ventricle discharge pressure

Integrity of vasculaturePresence of blockage

Muscular tone/structural integrity

Pressure drop needed to move blood to and throughcapillary beds

Blood volume/compositionWater, electrolyte, iron balances

Lipid and protein composition


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I. Background to Hypertension -

Regulation of Blood Pressure

Arterial blood pressure due to combinationof cardiac output (CO) and total peripheralresistance (TPR)

CO regulated by heart rate and strokevolume (CO = HR x SV)

TPR function of

Viscosity of blood (hematocrit)

Length of blood vessels

Blood vessel luminal diameter (especiallyprecapillary arterioles)


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Cardiac Output

Heart rate

Function ofsympathetic, vagal nervous activityNeuro-hormonal substances

1 angiotensin II 2 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 (1, 2receptors)

Vascular volume depends onIntake of fluids (thirst)Output of fluids (urine, sweat, etc)Distribution of fluids (Starlings law)

Myocardial contractility (MC proportional to sympathetic

tone [1 receptors])


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Characteristics of some adrenoceptors

(sympathetic nerves)

1 2 1 2

Smoothmuscle

Arteries/

veins

constrict constrict/

dilate

dilate

Skeletal

muscle

dilate

Heart

Rate (increase)

Force of

contraction

increase

Tissues

and effects receptors


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Beat-to-Beat Modulation of Blood

Pressure

Controlled by baroreceptor reflex arch

Baroreceptors located in aortic arch

Increased stretching due to higher aortic archpressure increased vagal nerve activity decreased heart rate decreased cardiac

output decreased blood pressure

Fast acting


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Autonomic Regulation of Blood Pressure

Coordinates and integrates allregulators of cardiovascular function

Can regulate both cardiac output andblood vessel size via sympatheticand parasympathetic innervation of

cardiovascular end-organs (heart,vasculature, kidneys, adrenal glands,etc)


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Autonomic Regulation of the Heart

Heart RateParasympathetic input via vagus nerve

causes decrease in HR (dominates)

Sympathetic input to sino-atrial nodecauses increase in HR (usually minor)

Heart contractility Increased by sympathetic activity

causing release of epinephrine,norepinephrine from adrenal gland


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II. Background to Arrhythmia -

Rhythm of the Heart

Human heart is four-chambered

Chambers need to contractsequentially (atria, then

ventricles) and insynchronicity

Also need relaxationbetween contractions to

allow refilling of chambers

Above controlledelectrically (Purkinje fibersallow rapid, organizedspread of activation)


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Regulation of Heart Rate

Primarily accomplished by sinoatrial node (SA)

Located on right atrium

Receives autonomic input

When stimulated, SA signals atrial contractile fibersatria depolarization and contraction (primes

ventricles with blood)

Depolarization picked up by atrioventricular

node (AV node) depolarizes ventriclesblood discharged to pulmonary artery and

dorsal aorta eventually rest of body


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III. Background to Congestive Heart Failure

Maintenance of Normal Heart FunctionNormal cardiac output needed to adequately perfuseperipheral 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 invenous 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 inadequateperfusion and development of the syndrome of heart failure


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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


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Quantification of Total Peripheral Resistance

TPR = _L _ for sum of all blood vessels

r4 (Poiseuilles equation)

Where r = radius of blood vesselL = length of blood vessel= viscosity of blood (function of

hematocrit) hematocrit =

Therefore: change in blood vessel radius hasgreatest effect on TPR

Note: 70% of TPR produced/controlled byarterioles target of drug treatment


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Relationship between blood flow

and radius of a blood vessel

0.5

0.063


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Relationship between blood pressure,

velocity and total area of vasculature

H l R l ti f Bl d P


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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 IAngiotensin II in lung

Angiotensin II: Actions:

Intense vasoconstriction increase TPRCauses release of Aldosterone from adrenal gland promotes Na+ andwater 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 pressureback up to normal set-point


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Autonomic regulation

of the vasculature

Increased sympathetic activity

reduction in blood vessel opening(caliber) increase in vascular

resistance etc. etc increaseblood pressure


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Stop talking now and

let them go!

Im outtahere!

cardiovascular pharmacology.ppt

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