Cardiovascular Drugs And Exercise Flashcards
Compare CO while at rest and while exercising
At rest - 5L/min
Exercise - 25L/min
How do you work out CO
CO = stroke volume x heart rate
What three factors affect CO?
-Sympathetic loading
-Parasympathetic unloading
Hormones
Starling forces
What happens during increased CO?
Vasodilation in metabolically active muscle
Metabolites
- K+
- pH
- adenosine
- EDRF - potent vasodilator
What is EDRF?
Endothelium derived relaxing factor
What happens to TPR during exercise?
It will decrease but remain constant even as intensity continues to increase
How do you calculate BP?
BP = CO x TPR
What will happen to BP when CO increases
It will decrease as TPR decreases dramatically
What happens during dynamic exercise?
Systolic BP increase
diastolic BP may decrease
What happens during static exercise?
Systolic BP increases
Diastolic BP also increases
Physical compression of muscle blood vessels increases TPR and therefore Diastolic pressure
What does circulation depend on?
Perfusion pressure
Vascular resistance
What does control of vascular resistance depend on?
Intrinsic factors
Extrinsic factors
What are intrinsic factors?
Auto regulation
- myogenic
- metabolic
- endothelial
Mechanical compression
- cardiac muscle
- skeletal muscle
What are extrinsic factors?
Nervous
Hormonal
What is autoregulation?
The ability of an organ to maintain blood flow despite changes in perfusion pressure
Occurs in the absence of extrinsic factors
What are the features of coronary blood flow?
High basal flow
High basal O2 consumption
High myocardial O2 extraction
High density of myocardial capillaries
O2 transport increases by myoglobin in myocyte
Describe control of coronary blood flow
Flow is closely linked to O2 demand
Decreased O2, increased CO2, NO, H+, K+, lactate, PGs, and adenosine cause vasodilation
Sympathetic vasoconstrictor tone also present
Vasodilators dominate
Increased sympathetic activity to sinus node increases HR
Indirectly causes vasodilation due to increased metabolism
What percentage of CO does the heart get?
At rest - 5%
Moderate exercise - 5%
What percentage of CO does skeletal muscle get?
At rest - 18%
Moderate exercise - >70%
Describe the neurohormonal control scene at skeletal muscle
Action of sympathetic nerves and hormones
- alpha adrenoreceptors
- important at rest
- adrenaline
- beta 2 adrenoreceptors
- supports local metabolites during exercise
Describe local metabolic control of skeletal muscle
Metabolic vasodilation
-k+, PO4(3-), pH, hypoxia and lactic acid (H+)
Dominates as exercise increases
What areas are splanchnic?
GIT
liver
Pancrease
Spleen
What percentage of CO do splanchnic beds get?
At rest - 30%
Moderate exercise - 5%
What sort of regulation is there for splanchnic areas?
Autoregulation
Nervous control - sympathetic vasoconstrictor nerves
- hypotension or exercise
What CO does pulmonary circulation get
Blood flow through lungs
Heavy exercise - 4-7 fold
What is pulmonary circulation characterised by?
High compliance
High flow
Low resistance
Low pressure
What control is there over pulmonary circulation?
Local gas tension
Hypoxic pulmonary vasoconstriction
Allow perfusion/ventilation matching
What percentage of CO does cutaneous circulation get?
At rest - 4-10%
Moderate exercise - <20%
What is non-acral skin?
Trunk and upper limbs
What is acral skin?
Extremities of hands, feet and ears
What percentage of CO does cerebral blood flow get?
At rest - 14%
Moderate exercise - 14%
Only accounts for 2% of body mass though
What control is over cerebral blood flow?
Metabolic
- low O2, adenosine, low pH and high CO2 - vasodilation
Myogenic
- protect from changes in BP
- decreased MAP
- cerebral vessels constrict
What are the unique features of cerebral blood flow?
Active regions receive increased BP
Blood brain barrier
Brain enclosed in skull
- intracranial pressure influences cerebral perfusion
What effect does intracranial pressure have on blood vessels?
Increased pressure can compress blood vessels which reduces cerebral blood flow
E.G
- increased brain volume = oedema
- increased CSF = hydrocephalus
- increased cerebral blood volume = blockage in venous drainage or vasodilation
What are the cardiovascular changes when moving from supine to standing?
Initial venous pooling
Reduces venous return
Reduction in SV/CO
reduction in arterial BP
Detected by barorecptors
Increases HR
Causes arterial vasoconstriction
Increases TPR
Vasoconstriction restores venous return
Arterial BP quickly restored
When does fainting occur?
When baroreceptors do not detect the change in BP
Cerebral BP continues to fall
What should you do if someone faints?
Lie them down horizontally
Raise legs to restore cerebral blood flow
Turn head to side
Loosen tight clothing
Apply cold moist towels to face and neck
What is systemic hypertension?
Systolic BP - >140mmHg
Diastolic BP - >90mmHg
What are the ratios of primary and secondary hypertension?
Primary - 90-95%
Secondary - 5-10%
What are the risk factors of hypertension?
Increasing age
Obesity
Lack of exercise
High salt diet
Alcohol
Smoking
Stress
Secondary causes
What are the treatments of hypertension
Modifications of lifestyle
Pharmacological intervention
- diuretics - decreases blood volume
- thiazides - increases K+ channel activity in VSM, hyperpolarisation increases Ca2+ entry, decreases vascular resistance
What are sympatholytics?
Block action of sympathetic nervous system
Give two examples of sympatholytics
Guanethidine
Trimetaphan
How does guanethidine work?
Fill synaptic storage vesicles in preference to NA
Block fusion of storage vesicles with neurolema
Decreases NA release from sympathetic nerves
How does trimetaphan work?
Blocks ganglia in SNS and PNS
Nicotinic receptor antagonist
Give examples of Adrenergic drugs
Alpha 1 antagonists - prazosin
Alpha 2 agonist - clonidine
How do alpha 1 antagonists work?
Block postganglionic alpha 1 receptors on VSM
Decrease peripheral resistance and venous pressure
Decreases low density lipoprotein
Increases high density lipoprotein
How do alpha 2 agonists work?
CNS action
- decreases presynaptic inhibition of NA release in vasomotor pathways
- decreases sympathetic drive
Peripheral action
- inhibition of releases of NA from postganglionic nerves
- decreases vasoconstriction
What do Beta adrenoreceptor Amat agonists do?
Decreases sympathetic drive
Decreases HR and CO
Decreases renin production
Decreases TPR
How do calcium channel antagonists work?
Interfere with opening/closing of L-type Ca2+ channels
Give examples of both vascular selective and less vascular selective calcium channel anatagonists
Nifedipine (vascular)
- little effect on cardiac conduction
Verapamil and diltiazem (less vascular)
- more prone to cardiac conduction defects
Give examples of renin-angiotensin cascade modulators
ACE inhibitors
Angiotensin ll antagonists
How do ACE inhibitors work?
Decreases Angiotensin ll production
Causes vasodilation
Reduced sodium retention
Decreases breakdown of endogenous
Vasodilator, bradykinin
How do angiotensin ll antagonists work?
Blocks direct agonist vasoconstrictor effect
Blocks indirect presynaptic potentiation of transmitter release
How does sodium nitroprusside work?
Given IV for rapid BP decrease in emergencies
Effects are short term - minutes
Decrease in cGMP activity causes relaxation
What is cardio vascular disease (CVD)?
An umbrella term for all diseases of the heart and circulation
List the types/causes of heart failure
Coronary artery diseases
Valve disease
Aneurysm
Cardiac arrhythmia
Cardiomyopathy
Pericarditis
What is heart failure?
A complex syndrome that can result from any structural of functional cardiac disorder that impairs the ability of the heart to function as a pump to support circulation
How is the frank starling mechanism affected during heart failure?
It fails to the point heart muscle contraction becomes less efficient even though the heart is filled with blood
What are the symptoms of heart failure?
Dyspnoea
Fatigue
Exercise intolerance
Palpitations
Swelling
What are the clinical signs of heart failure?
Tachycardia
Elevated jugular venous pressure
Displaced apex beat
Basal lung crepitations
Oedema, ascites
What are the pathophysiological changes during heart failure?
Reduced left ventricle ejection fraction
Fluid retention
increased right atrial pressure
Reduced venous return
How many classifications of heart failure are there?
Four
What happens to the stroke volume during heart failure?
Decreased inotropic properties
Decreased ESPVR
= Decreased stroke volume
What happens during myocardial adaptation?
Loss of myocardium decreases CO
decreased arterial pressure causes barorecptor activation
Which causes increased ADH secretion
This raises blood volume
Increased venous return
What happens during neurohumoral activation?
Sympathetic nervous system activation
Increases sympathetic innervation
Increases HR and contractility
Which increases CO
Which which causes vasoconstriction
And increases venous return
What happens to renal blood flow during heart failure?
RAAS activation
Angiotensin ll
AT1R
Vasoconstriction
Aldosterone
- sodium/water retention
Increased blood volume
What are strategies for improving pump function in heart failure?
Preload reduction
After load reduction
Action potential modulator
Increasing myocardial contractility
How does preload reduction work?
Remove sodium and water
Decreases peripheral oedema, pulmonary congestion l, dyspnoea and syncope
Diuretics
ACE inhibitors
Angiotensin receptor blockers
Mineralocorticoid receptor anatagonists
How does afterload reduction work?
Decreases end diastolic volume
Which decreases ventricular dilatation
Hydralazine
nitrates
ACE inhibitors
Beta antagonists
Alpha 1 antagonists
Alpha 2 agonists
How does action potential modulation work?
Decrease pacemaker depolarisation slope
Which decreases HR reduction
Which stabilises electrical activity
And reduces abnormal electrical function
Anti-arrhythmics
HCN channel inhibitors
How does increasing myocardial contractility work?
Maintains stroke volume
Digoxin
Ivabradine
Beta 1 agonist
How do diuretic help with preload reduction?
Promote renal excretion of sodium and water by blocking reabsorption of sodium and chlorine
- decreases ventricular filling filling pressure
- decreases peripheral oedema
What are the mechanisms of action for k sparing diuretics?
Mineralocorticoid receptor anatagonists
Inhibit action of aldosterone
Epithelial sodium channel anatagonists reduce sodium reabsorption in collecting duct
Reduced renal excretion of potassium
What are the side effects of using diuretics?
Electrolyte disturbances
Metabolic alkalosis
Utica acid retention - gout
Hyperkalaemia
Dehydration
Hypotension, syncope
Renal impairment
What are the mechanisms of action for ACE inhibitors?
Inhibition of ACE
Prevents the convergence of angio l to angio ll
Decreased systemic vascular resistance
Decreased venous pressure
Increased cardiac output
What are the side effects of ACE inhibitors?
Dry cough
Increased bradykinin levels in lungs
What are the mechanisms of action for beta blockers?
Inhibition if beta 1 and beta 2 adrenoreceptors
Reduced production of cAMP
Decreased HR, decreased force of contraction but increased relaxation of the heart
Decreased renin from kidney, decreased water retention
Increased vasodilation of peripheral arterioles, decreased diastolic BP
What are venodilators?
Short and long acting nitrates
Arteriolar vasodilators - reduce after load and increase CO
Venodilators - decrease preload, decrease venous pressure means decreased LVEDP
What are the mechanisms of action for action potential modulation?
Inhibition of If channel
Decreased pacemaker depolarisation slope
Decreased HR, more time for filling
Increased efficiency
What are the side effects of action potential modulation?
Can cause bradycardia or AV block
Unhelpful for patients with AF
Give examples of anti-arrhythmic drugs
Class lll - K+ channel blockers
- prolong AP and refractors period
- no effect on sodium channels
- normal conduction velocity
Class iv- L-type calcium channel blockers
- decreased conduction velocity through AV node
- mean decreased plateau phase of cardiac AP and decreased contractility
How do you increase contractility?
Positive inotropes
For short term support of myocardial function in patients with acute heart failure when maximal drug therapy has failed
What are the mechanisms of action for positive inotropes?
Anatagonist of cardiomyocyte Na+/K+ ATPase = increased intracellular sodium
Inhibition of Na+/Ca2+ exchanger
Increased intracellular calcium mean increased force of contraction
How do you work out the ejection fraction?
EF = SV / EDV
