Cardiovascular Pharmacology Flashcards
What is the cardiac output produced by the left ventricle at rest
5L/min
What is the result of the loss of elasticity of arteries as you grow older
Increased blood pressure and increased strain on the left ventricle.
What is the importance of the elastic recoil of arteries
To maintain blood pressure during diastole.
What vessels are the major source of resistance to blood flow
Arterioles
What dictates where cardiac output is directed
Changes in resistance as a result in change of vessel tone and diameter
What factors regulate muscle tone
Hormones such as angiotensin II and local factors such as nitric oxide.
Where does gas exchange into tissues occur
Capillary beds
What products enter the capillary beds
Oxygen and nutrients
What products are removed from the capillary beds
Carbon dioxide and waste products
What equilibrium do capillaries have a role In controlling
Water in the intravascular compartment and water in the interstitial space of every tissue.
Down what kind of gradient does blood flow from the arteriole end to the venular end
A large hydrostatic pressure gradient
What gradient tends to favour reabsorption of water from interstitial fluid back into the plasma
An oncotic gradient
What creates the oncotic pressure
The high concentration of albumin and other proteins in the plasma
What does oncotic pressure cause
Reabsorption of water
How do hydrostatic and oncotic pressures compare to one another
They are usually equally matched
At what end does hydrostatic pressure dominate
The arterial end
At what end does the osmotic pressure dominate
The venular end
How do the hydrostatic and osmotic pressures work moving from the arterial end to the venular end
At the arterial end the hydrostatic pressure dominates and water filters into the interstitial fluid. At the venular end the osmotic pressure dominates and this is reversed - the water is reabsorbed
What is the role of lymphatic vessels
To return excess fluid to the circulation
What does the disruption of the equilibrium of hydrostatic and osmotic pressure lead to
Excess interstitial fluid and therefore oedema.
What pulls the water back from the interstitial fluid to the plasma
The high concentration of proteins left in the plasma at the venular end.
What are the four things which can disrupt the equilibrium between hydrostatic and osmotic pressure
1) A reduction in oncotic pressure due to low plasma protein conditions such as malnutrition, chronic liver disease or nephrotic syndrome
2) An increased in interstitial oncotic pressure due to leakage of protein from the plasma
3) An increase in venous hydrostatic pressure due to venous obstruction
4) An increase in arteriolar hydrostatic pressure due to vasodilators
How do hydrostatic and oncotic pressure work to increase blood volume if this is deplete
If circulation is deplete or arteriolar pressure falls, hydrostatic pressure is lower so oncotic pressure is dominant and this causes fluid to be pulled out of the interstitial space and back into the plasma to increase blood volume.
Which organs are the most vital to keep perfused
The heart and the brain. These can only last without perfusion for a very short period of time and this results in a great loss of function.
Which tissues will survive hours without perfusion before becoming permanently damaged
Muscles and skin
Where does afferent information for the regulation of blood pressure come from
Arterial baroreceptors in the carotid sinus and aortic arch
Where does afferent information for the regulation of blood volume come from
Stretch receptors in the right heart and juxtaglomerular cells in the kidney
What factors bring about an efferent response to effect blood pressure
Hormones such as those in the renin-angiotensin system (angiotensin II), adrenaline and ADH as well as local factors such as nitric oxide and endothelin
What are the factors which bring about an efferent response to effect blood volume
The sympathetic and parasympathetic nervous system. Circulating hormones such as those in the renin-angiotensin system (aldosterone), natriuretic peptides and ADH.
What are the effector organs for blood pressure
The heart and the arterioles.
What is the response time for the change in blood pressure by the heart and the arterioles
Almost instantaneous
What is the effector organ for the change in blood volume
The kidney which influences the water and salt content of the body
What is the response time for change in blood volume
The influence may take a while.
What are responses to need for change in blood pressure and blood volume brought about by
Receptors to which agonists bind and bring about signal transduction
Give three examples of G-protein coupled receptors
Beta-adrenergic, alpha-adrenergic and muscarinic cholinergic receptors.
What is an example of an intermediate molecule that may be produced by signal transduction
cAMP
What does an intracellular cascade do in signal transduction
Amplifies the signal and brings about an intracellular response.
What is blood pressure
The hydrostatic pressure of the circulatory system
What is the typical blood pressure for an adult (systolic/diastolic)
120/80 mmHg
How do you work out arterial blood pressure
Blood pressure - cardiac output X systemic vascular resistance
How do you work out cardiac output
CO = HR X SV
What is arterial blood pressure dependent upon
Heart rate, contractility and arteriolar tone
What molecules act to increase heart rate
Noradrenaline released from sympathetic post ganglionic fibres and acting as an agonist of beta-1 receptors and adrenaline released from the adrenal medulla and acting as a beta-1 agonist.
What molecules act to decrease heart rate
Acetylcholine which agonises muscarinic cholinergic receptors.
What is the effect of increasing contractility on stroke volume
Stroke volume increases
What innervates smooth muscle of blood vessels
Postganglionic sympathetic nerve endings which release noradrenaline to act on alpha-1 adrenoceptors ion the surface of blood vessels.
What is the effect of the binding of noradrenaline to alpha-1 adrenoceptors on blood vessels
Vasoconstriction
What factors act on smooth muscle to cause vasodilation
Adrenaline, vasopressin, angiotensin II
Where does adrenaline bind to cause vasodilation
Beta-2 adrenoceptors
What afferent information is received from the baroreceptors in the carotid sinus
The blood pressure seen by the cerebral circulation
What afferent information is received from the baroreceptors in the aortic arch
The blood pressure seen by the heart and other major organs
What do baroreceptors respond to
Stretch in the adventitial layer of blood vessels.
What nerve do signals from the carotid baroreceptors travel along
The glossopharyngeal nerve
What nerve do signals from the aortic arch baroreceptors travel along
The vagus nerve
Where do signals from the baroreceptors travel to
The vasomotor centre in the medulla oblongata
What is the vasomotor centre in the medulla oblongata responsible for
Homeostatic reflexes
What will the efferent response to decreased blood volume and pressure include
- reduced blood pressure will be sensed
- the heart rate and contractility will increase due to the effect of noradrenaline at the beta-1 receptors in the heart
- systemic vascular resistance will be increased by the action of noradrenaline at alpha-1 receptors on the blood vessels
How does the sympathetic nervous system affect the kidneys
The arteriolar contraction by the action of noradrenaline at alpha-1 receptors will decrease renal blood flow and glomerular capillary pressure and this will decrease glomerular filtration and urine production to increase blood volume and pressure.
How does the sympathetic nervous system affect the renin-angiotensin system
The secretion of renin at juxtaglomerular cells is stimulated. This increases the concentration and action of angiotensin II - a vasoconstrictor and aldosterone - a sodium retaining hormone to increase blood volume and pressure.
What effect does lower blood pressure have on the parasympathetic nervous system
It decreases the activity of the parasympathetic nervous system.
What pharmalogical means can be used to increase blood pressure
Use of a vasoconstrictor such as phenylepherine
What pharmalogical means can be used to decrease blood pressure
Use of a vasodilator such as glycerylnitrate.
At what age is the baroreceptor reflex most sensitive
In younger people. The elderly have less sensitive baroreceptor reflexes so are less able to respond to drop in blood pressure,
How does hypertension develop with the baroreceptor reflex
Because the baroreceptors must reset to maintain blood pressure at a higher baseline.
What is blood volume
The volume of blood in all of the circulation
What is the typical blood volume of a 70kg male
4L
Around how much of the blood volume is found in the venous system at rest
Half - it acts as a reservoir
What is the intravascular volume in equilibrium with across capillaries
Interstitial volume
Which compartment - interstitial or intracellular - fluid contains most of the body’s water content
The intracellular compartment
What is the volume of interstitial (extracellular) fluid
12L
What is the volume of the intracellular fluid
32L
What is the organ with the greatest control over fluid loss and hydration
The kidney
What is the average daily urine output
Around 1.5L
What is one of the waste products excreted in the urine
Urea
Why is regulation of blood volume important
To maintain the venous return to the heart and enable it to produce enough cardiac output to support perfusion of all the body organs
Which two sources does afferent information regarding control of blood volume come from
the juxtaglomerular cells in the kidney and low pressure stretch receptors in the right atrium of the heart
What do juxtaglomerular cells sense in relation to blood pressure
Sodium and water delivery to the distal tubule of the kidney
How do juxtaglomerular cells respond to low delivery of sodium and water to the distal tubule of the kidney
They release renin which activates the renin-angiotensin system for the production of angiotensin II
What happens when the stretch receptors in the right atrium detect low blood volume
The sympathetic nervous system is activated.
What are the efferent responses to a detection of low blood volume
The activation of the renin-angiotensin system and the sympathetic nervous system.
What are the main products of the renin-angiotensin system
Aldosterone and angiotensin II
What does angiotensin II do
Causes vasoconstriction and release of aldosterone from the adrenal cortex. Also stimulates the release of vasopressin from the pituitary gland and thirst.
What does aldosterone do
Conserves sodium in the body often in exchange for loss of potassium and hydrogen ions.
What are the sites of action of aldosterone
The distal tubules of the kidney and to a lesser extent the gastrointestinal tract.
What does vasopressin do
Conserves water and causes vasoconstriction
What happens when the sympathetic nervous system is activated due to detection of low blood volume by stretch receptors in the right atrium
Noradrenaline is released which acts on beta-1 receptors in the heart to increase contractility and rate.
Which receptors does noradrenaline act at to cause increased systemic vascular resistance
Alpha-1 receptors on blood vessels.
How does the constriction of veins help in increasing blood volume
It reduces the reservoir function of the veins and expands the blood volume in the arterial circulation.
What effect does the sympathetic nervous system have on the kidney when blood volume is detected to be low
Postganglionic neurons have the effect of arteriolar constriction which decreases blood flow and glomerular capillary pressure. This reduced glomerular filtration and urine production.
What effect do ANP and BNP have on the kidney
Retention of sodium and water
What is the macula densa
An area of tightly packed cells lining the wall of the ascending limb at the transition to the distal convoluted tubule of the kidney
What system is the macula densa part of
The renin-angiotensin system
What is the role of the macula densa in increasing glomerular capillary hydrostatic pressure
When there is a decrease in sodium chloride concentration, the macula densa signals for a decreased resistance to flood flow in the afferent arterioles by vasodilatation which increases glomerular capillary hydrostatic pressure.
What is the role of the macula densa in the renin angiotensin system
The macula densa causes an increase in renin production from juxtaglomerular cells and subsequent increased concentration and action of angiotensin II, aldosterone and vasopressin.
What are the causes of excessive fluid loss that threaten intravascular volume
Haemorrhage, vomiting, diarrhoea, burns and excessive use of diuretics.
What are the subsequent effects of rapid loss of blood
Decreased venous return to the heart, decreased ventricular filling, reduced cardiac output, reduced arterial blood pressure and reduced renal perfusion.
The perfusion of which organs are sacrificed first
Organs which are less vital for survival such as skin, muscle and the GI tract before the kidney, heart and brain which are more important.
What are all the systems which detect and act up reduced blood volume
- Baroreceptors in the carotid sinus
- Baroreceptors in the aortic arch
- Stretch receptors in the right atrium of the heart
- Juxtaglomerular cells which activate the renin-angiotensin system
What causes sweating in the response to decreased blood volume
The action of the sympathetic nervous system on the adrenal medulla.
What are the early signs and symptoms of haemorrhage
Tachycardia, palpitation, pallor, coldness of the skin, sweating
What causes the early signs and symptoms of haemorrhage
The sympathetic nervous system
What happens in the blood vessels when there is decreased arteriolar and venular pressure
The oncotic pressure dominates and this favours reabsorption of fluid back into the intravascular compartment to increase the depleted blood volume.
What will be the result of continued blood loss due to haemorrhage
Hypotension which may then reduce renal perfusion leading to reduction or halting of urine output. It can ultimately lead to confusion and reduced consciousness.
What is hypovolemic shock
Failure to preserve sufficient intravascular volume to maintain blood pressure.
How do you treat hypovolemic shock
IV fluid infusion and if there is a haemorrhage then blood transfusion.
What is the most important risk factor for cardiovascular disease
Hypertension
What are the risk factors for atherosclerosis
Age, male sex, genetics, smoking, cholesterol, diabetes
What is the result of a stable atheroma
Obstruction to blood flow that limits amount of blood and oxygen that can be delivered to tissue.
What is the result of a stable atheroma in the coronary arteries
Angina pectoris.
What may happen when a stable atheroma becomes unstable
Rupture
What does an unstable atheroma lead to in the coronary arteries
Unstable angina or a myocardial infarction
What does an atheroma lead to in the cerebral circulation
Stroke or TIA.
What is preload
The end diastolic volume of the heart
What is afterload
The peripheral resistance to blood flow.
What are the key pathological problems underlying cardiovascular disease
- maladaptive increases in the activity of the sympathetic nervous system and renin-angiotensin system
- endothelial dysfunction of blood vessels
- volume overload
- hypertension
- cardiac ischaemia
- changes in structure of blood vessels
- high levels of circulating cholesterol
- platelet stickiness
- tendency to thrombosis
What are the drug solutions for cardiac disease that target the underlying pathologies
Diuretics, beta-blockers, alpha-blockers, calcium channel blockers, ACE inhibitors, angiotensin II receptor blockers, lipid-lowering drugs, anti-platelets, anti-coagulants, nitrates
What do diuretics do
Reduce water and sodium overload - increase loss of water and sodium.
What is an example of a diuretic
Furosemide
What do beta-blockers do
Act to inhibit the beta-1 receptors of the heart therefore reducing the effects of the sympathetic nervous system on the heart
What is an example of a beta-blocker
Atenolol
What do alpha blockers do
Act to inhibit the alpha-1 receptors on blood vessels to reduce the effect of the sympathetic nervous system in vasoconstriction of arterioles.
What is an example of an alpha-blocker
Doxazosin
What do calcium channel blockers do
Block the entry of calcium through voltage gated calcium channels in myocytes, therefore reducing contractility of the heart. They also cause relaxation of arteriolar smooth muscle.
What is an example of a calcium channel blocker
Amlodipine
What do ACE inhibitors do
Inhibit the action of angiotensin converting enzyme, therefore reducing the concentration of angiotensin II in the blood and reducing the effects of the renin-angiotensin system
What is an example of ACE inhibitor
Ramipril
What do nitrates do
Relax veins and arteries to reduce the resistance against which the heart has to work. This works as they are cleaved to produce nitric oxide, the vasodilator.
What is an example of a nitrate
Glyceryl trinitrate
What do lipid-lowering drugs do
Reduce cholesterol levels in the circulation
What are two examples of lipid lowering drugs
Statins and fibrates
What do anti-platelet drugs do
Reduce platelet adherence to the vascular wall
What is an example of an anti-platelet drug
Aspirin
How does aspirin work
It is a COX inhibitor
What do anti-coagulant drugs do
Reduce the tendency towards blood clot formation in diseased vessles
What is an example of an anti-coagulant drug
Warfarin
How does warfarin work
It is a vitamin K inhibitor which means it inhibits the vitamin K dependent clotting factors in the clotting cascade. These are factors 2, 7, 9 and 10.
