Lecture 32 - Cardiovascular Therapeutics Flashcards
What is the function of the cardiovascular system?
o Distribution of essential substances
o Removal of metabolic by-products
o Circulation of hormones and neurotransmitters
o Heat distribution
o Mediation of inflammatory and host defence responses
pulmonary circulation
Right atrium and ventricle pumps deoxygenation blood to lungs for O2/CO2 exchange
systemic circulation
Left atrium and ventricle pumps blood to tissues of the body
blood vessels
o Distributing tubes = arteries/arterioles
o Exchange tubes = capillaries
o Collecting tubes = veins/venules
how is blood pressure controlled?
Short-term regulation via neural reflex’s
- Moment to moment regulations
- Seconds to minutes
- Effectors are the heart, vessels an adrenal medulla
Long-term regulation
- Involves changes in extracellular fluid
- Targets blood vessels and kidneys
baroreceptors
o Detect changes in blood pressure
o Located at high pressure sites
o Increased stretch = activation of baroreceptors = increased firing of afferent sensory nerves which transmit information to the cardiovascular control centre.
blood pressure is a function of:
TPR and CO
cardiac output (CO) is a function of:
stroke volume (SV) and heart rate (HR)
stroke volume involves:
o Preload (load placed on cardiac muscle before contraction)
o Contractility (strength of contraction – intrinsic to cardiac muscle fibres
heart rate is controlled by:
o Positive feedback of sympathetic activity
o Negative feedback of parasympathetic activity
how does preload influence SV?
o Depends on ventricular filled and thus venous inflow
o Increased venous flow = increased ventricular filling = increased cardiac muscle fibre length
o Thus greater force generated
why should we treat hypertension?
o Elevated BP can cause pathological changes in vascular and hypertrophy of left ventricle
o Leading cause of stoke, coronary artery disease, MI and sudden death, heart failure, renal insufficiency and more
hypertension causes
Primary/essential hypertension (90-95%)
No apparent cause
Diet, obesity, high alcohol consumption, physical inactivity
Secondary essential hypertension (5-10%)
Identifiable cause
Renal disease
Endocrine disorders
Preeclampsia in pregnancy
hypertension treatment
o First choice therapy = lifestyle modifications (i.e. increase exercise, decrease alcohol, better diet)
o Drugs (long-term) but all have some adverse effects
how to lower CO
o Decrease heart rate and contractility
o Decrease blood volume and therefore preload
B-adrenoceptor antagonists mechanism of action
o Bind but do not activate B-adrenoceptors, thus inhibit activation of cardiac B1-adrenoceptors by noradrenaline and ciruclarion adrenaline
o Bind to and inhibit activation of kidney B1-adrenoceptors
adverse effects of B-adrenoceptor antagonists
o Decreases exercise capacity
o Muscle fatigue
o Cold extremities
o Bronchoconstriction
o Dreams and insomnia
How to minimise adverse effects of b-adrenoceptor antagonists
Use B1-selective antagonists (cardio selective) that are more hydrophilic
determinants of resistance
o Vessel length (constant)
o Blood viscosity (relatively constant)
o Vessel diameter i.e. radius (easily changed)
what happens if internal radius falls by 10%
o Smaller arteries and arterioles gave a greater capacity to affect TPR than larger arteries
o Decreasing radius increases blood flow but large amount
Regulators of arterial tone – passive factors
o Pressure
o Architecture/structure of blood vessels
Regulators of arterial tone – active factors
o Sympathetic nerves
o Circulating factors e.g. catecholamines
o Local vasoactive factors e.g. released from endothelial cells
why is TPR elevated during hypertension?
o Due to functional imbalance between constriction and relaxation and structural changes
o As blood pressure rises, blood vessels undergo structural changes (remodelling)
consequences of vascular remodelling
o Resting vascular resistance is raised
o For a given constrictor stimulus, there is a greater increase in R and thus BP
