SBI242 Week 5 - Pharmacology of the Cardiovascular System part 1

What does cardiac output (CO) represent?

Volume of blood pumped by the heart per minute

What is the average resting heart rate for a healthy adult?

60-100 bpm

What is the average stroke volume in a healthy adult at rest?

70-100 mL/beat

What is the formula for calculating cardiac output (CO)?

CO = Heart Rate (HR) x Stroke Volume (SV)

What is the average cardiac output in a healthy adult at rest?

5-6 L/min

The sympathetic nervous system typically:

Increases Heart Rate

The parasympathetic nervous system typically:

Decreases heart rate

Circulating catecholamines (e.g., adrenaline, norepinephrine) typically:

Increase Heart Rate

Thyroid hormones typically:

Increase Heart Rate

Hypokalemia (low potassium levels) typically:

Causes irregular heart rhythms

Preload refers to:

Initial stretching of the cardiac myocytes prior to contraction; also referred to as Ventricular End-Diastolic Volume

Increased venous return typically:

Increases preload

Hypovolemia (hemorrhage) typically:

Decreases preload

Factors that increase Preload

Increased blood volume, increased venous return, Increased venous pressure, increased ventricular compliance, increased force of contraction, reduced HR, pathological conditions such as ventricular systolic failure and valve defects

Factors that decrease Preload

Decreased venous blood pressure, impaired atrial contraction, increased heart rate, decreased ventricular afterload, ventricular diastolic failure, inflow valve stenosis

Afterload

The resistance the ventricle must overcome to eject blood into the circulation

The afterload of the left ventricle is closely related to:

Systemic vascular resistance (SVR) and aortic pressure

An increase in afterload typically:

Decreases stroke volume

The following factors can increase afterload:

Increased aortic pressure, increased systemic vascular resistance, aortic valve stenosis, and ventricular dilation

Increased preload typically:

Increases stroke volume

Increased afterload during systole typically:

Decreases stroke volume

Regular exercise training can:

Increase stroke volume

Causes of left heart failure (systolic) include:

Myocardial infarction, hypertension, cardiomyopathy

In left heart failure (systolic), the effect on contractility is:

Decreased contractility

In left heart failure (systolic), the effect on cardiac output is:

Decreased cardiac output

In left heart failure (systolic), activation of the Renin-Angiotensin-Aldosterone System (RAAS) leads to:

Increased peripheral vasoconstriction, sodium retention, and fluid overload

The formula that represents cardiac output (CO) is:

CO = Stroke Volume (SV) x Heart Rate (HR)

Stroke Volume (SV) is dependent on:

Preload, contractility, and afterload

Describe the Frank-Starling Law:

The stroke volume of the heart increases in response to an increase in ventricular preload

What is the main action of Digoxin?

Increases the force of contraction (positive inotropism) and slows the heart rate (negative chronotropism)

Digoxin is primarily excreted:

80% in the urine and 20% biliary excretion

The cause of abnormality in automaticity related to cardiac dysrhythmia can be:

Enhanced or suppressed automaticity due to electrolyte imbalance, ischemia, or increased sympathetic tone

The cause of abnormality in conductivity related to cardiac dysrhythmia can be:

Altered ion channel function, damage to the conduction system, or myocardial disease

What is the major action of Class I Antidysrhythmic Drugs?

Sodium channel blockade, reducing automaticity and slowing conduction

The action of Class II antiarrhythmic drugs is:

Beta-adrenergic receptor blockade, reducing sympathetic activity

The general action of Class III antiarrhythmic drugs is:

Potassium channel blockade, prolonging repolarization

The action of Class IV antiarrhythmic drugs is:

Blocking L-type calcium channels, reducing calcium influx

The main action of Class III antiarrhythmic drugs is:

Blocking potassium channels, prolonging repolarization, and increasing action potential duration

Calcium channel blockers' mechanism of action on the myocardium involves:

Blocking L-type calcium channels, reducing calcium influx, and decreasing contractility

Outline the mechanism of action of Calcium channel blocker drugs on the SA and AV junction:

Decreasing calcium ion influx across the cell membrane of the AV junction slows AV conduction (negative dromotropic effect) and prolongs AV refractory time therefore decreasing heart rate (negative chronotropic effect).

Name 3 types of Calcium channel blocker drugs:

Amlodipine, Phenylalkylamine, Benzothiazepine, Dihydropyridine

What are the resistance vessels and what do they regulate?

Arterioles, regulating blood flow and peripheral resistance

What are the capacitance vessels and what do they contribute to?

Veins, contributing to blood storage, venous return, and preload

Name the 3 layers of the arterial wall:

Tunica intima, tunica media, and tunica adventitia (or externa)

What is SVR/TPR?

Systemic vascular resistance (SVR) or total peripheral resistance (TPR) - The combined resistance of the systemic blood vessels

Name two important conditions that affect vascular smooth muscle.

Angina and Hypertension

Stable angina is characterized by:

Predictable chest pain or discomfort during exertion or stress, relieved by rest or nitroglycerin

Unstable angina is characterized by:

Is a progressive form of angina in which pain occurs more frequently and becomes more severe with time

Describe Variant Angina

Is uncommon and is caused by focal spasm of coronary arteries. Usually not associated with atherosclerosis

Organic nitrates work by:

NO activates guanyl cyclase which activates cGMP and leads to decreased phosphylation. Dephosphorylation of the myosin light chain leads to smooth muscle relaxation and dilation

How do potassium channel activators work as direct acting vasodilators?

Antagonising the action of ATP, prevents closure of the channel. This results in hyperpolarisation and relaxation ofthe vascular smooth muscle

What is the main action of Clonidine?

Reduces systolic and diastolic blood pressure by stimulating central α2 receptors, which decreases sympathetic outflow from the brain to the blood vessels and heart

What is the proposed mechanism of action of Methyldopa?

A metabolite of methyldopa (α-methylnoradrenaline) stimulates the central α2 adrenergic receptors, which results in a reduction in sympathetic outflow to the heart, kidneys and peripheral vasculature

What is the significance of Methyldopa pertaining to pregnancy?

One of the safest anti-hypertensive drug for treating pregnant women (safety rating A)

What is the mechanism of action of Moxonidine?

Agonism at central imidazoline I1 receptors, reducing sympathetic outflow and blood pressure

Outline what the RAAS system results in when activated.

Vasoconstriction; Aldosterone release; Na+/water retention; BP increase; Blood volume increase; GFR increase

What do ACE inhibitors result in pertaining to the RAAS system

A decrease in vascular tone, thereby directly lowering blood pressure; inhibition of aldosterone release, reducing sodium and water reabsorption; and an increase in plasma renin activity, caused by a loss of negative feedback on renin release

What do ARB's result in pertaining to the RAAS system?

Blockade of angiotensin II type 1 receptors, reducing vasoconstriction and aldosterone-mediated effects

What do aldosterone-receptor antagonists result in pertaining to the RAAS system?

Reduced aldosterone-mediated sodium retention and potassium excretion, increasing BP

Preload is:

The degree of stretch of heart fibres in the ventricles before contraction

Digoxin:

Is a positive inotrope, negative chronotrope, and a negative dromotrope

The positive inotropic action of digoxin is due to:

Increased intracellular calcium ions

Class 1 antidysrhythmic drugs:

Block voltage-sensitive sodium channels interfering with sodium influx

Calcium channel blockers:

Block the inward movement of calcium therefore decrease the force of myocardial contraction

Dihydropiridines:

Act principally on vascular smooth muscle, reducing peripheral vascular resistance

Prinzmetal angina is:

Caused by focal spasm of coronary arteries

Direct-acting vasodilator drugs include:

Glyceryl trinitrate (GTN)

Which is the safest anti-hypersensitive for pregnant women?

Methyldopa

Angiotensin converting Enzyme inhibitors:

Competitively block the angiotensin-converting enzyme necessary for the conversion
of angiotensin I to angiotensin II

What is stroke volume?

The end-diastolic volume minus the end-systolic volume

What effect would calcium-channel blockers have on cardiac output?

Dilate coronary and peripheral arterioles, reducing afterload and improving CO

How does dihydropyridine calcium-channel blocker drug reduce blood pressure and improve cardiac output?

The dihydropyridine calcium-channel blocker decreases peripheral vascular resistance which leads to sustained vasodilation. This results in decreased afterload and improved cardiac output

What is the mechanism of action of angiotensin converting enzyme inhibitors?

Competitively block the angiotensin-converting enzume necessary for the conversion of angiotensin I to angiotensin II

What is the mechanism of action of calcium channel blockers?

Block the inward movement of calcium therefore decreasing the force of myocardial contraction

What is the mechanism of action of class I antidysrhythmic drugs?

Block voltage-sensitive sodium channels interfering with sodium influx

Where is the main site of action for the calcium channel blockers known as ‘dihydropyridines’?

They act principally on vascular smooth muscle reducing peripheral vascular resistance

If afterload is increased, what happens to overall stroke volume?

Stroke volume is decreased because systemic vasular resistance is increased due to valve stenosis or hardened, thickened or obstructed arteries

A 56 year-old male with a history of coronary heart disease and hypertension was recently prescribed a calcium channel blocker as prophylaxis. Which type of calcium channel blocker would be most appropriate for this patient?

Non-dihydropyridine