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
how can we lower TPR?
o By inhibiting sympathetic activation of blood vessels
o By inhibiting the renin-angiotensin system
o By inhibiting signalling pathways involved in smooth muscle contraction
a1=adrenoceptor antagonists’ mechanisms of action
o Bind to and inhibit vascular a1-adrenoceptors
o Inhibit noradrenaline-mediated vasoconstriction (inhibit sympathetic vascular tone)
o Decrease TPR
o Decrease BP
a1-adrenoceptor antagonist side effects
o 1st dose hypotension
o Nasal congestion
o Postural hypotension
o Initial reflex tachycardia
Renin-angiotensin-aldosterone system
Altering levels of enzymes in this system has implications for BP
RAAS inhibitors mechanisms of action
both orally available
same adverse effects as ACE inhibitors except for dry cough
ACE inhibitors mechanism of action
o Less angiotensin II formation
o Inhibit bradykinin breakdown thus more vasodilation, lower TPR and BP
o Long term mechanism
May in inhibit or decrease morbid influences of angiotensin II on cardiovascular structure, independently of BP lowering effects
RAAS inhibitors adverse effects
o 1st dose hypotension
o Hyperkalaemia (increase in K+)
o Acute renal failure (reversible)
o Dry cough
RAAS inhibitors advantages
o Less effect on cardiovascular reflexes
o Safe in asthmatics
o Beneficial effects on cardiovascular remodelling
