Lecture 32 - Cardiovascular Therapeutics

Question 1

What is the function of the cardiovascular system?

Answer 1

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

Question 2

pulmonary circulation

Answer 2

Right atrium and ventricle pumps deoxygenation blood to lungs for O2/CO2 exchange

Question 3

systemic circulation

Answer 3

Left atrium and ventricle pumps blood to tissues of the body

Question 4

blood vessels

Answer 4

o Distributing tubes = arteries/arterioles
o Exchange tubes = capillaries
o Collecting tubes = veins/venules

Question 5

how is blood pressure controlled?

Answer 5

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

Question 6

baroreceptors

Answer 6

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.

Question 7

blood pressure is a function of:

Answer 7

TPR and CO

Question 8

cardiac output (CO) is a function of:

Answer 8

stroke volume (SV) and heart rate (HR)

Question 9

stroke volume involves:

Answer 9

o Preload (load placed on cardiac muscle before contraction)
o Contractility (strength of contraction – intrinsic to cardiac muscle fibres

Question 10

heart rate is controlled by:

Answer 10

o Positive feedback of sympathetic activity
o Negative feedback of parasympathetic activity

Question 11

how does preload influence SV?

Answer 11

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

Question 12

why should we treat hypertension?

Answer 12

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

Question 13

hypertension causes

Answer 13

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

Question 14

hypertension treatment

Answer 14

o First choice therapy = lifestyle modifications (i.e. increase exercise, decrease alcohol, better diet)
o Drugs (long-term) but all have some adverse effects

Question 15

how to lower CO

Answer 15

o Decrease heart rate and contractility
o Decrease blood volume and therefore preload

Question 16

B-adrenoceptor antagonists mechanism of action

Answer 16

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

Question 17

adverse effects of B-adrenoceptor antagonists

Answer 17

o Decreases exercise capacity
o Muscle fatigue
o Cold extremities
o Bronchoconstriction
o Dreams and insomnia

Question 18

How to minimise adverse effects of b-adrenoceptor antagonists

Answer 18

Use B1-selective antagonists (cardio selective) that are more hydrophilic

Question 19

determinants of resistance

Answer 19

o Vessel length (constant)
o Blood viscosity (relatively constant)
o Vessel diameter i.e. radius (easily changed)

Question 20

what happens if internal radius falls by 10%

Answer 20

o Smaller arteries and arterioles gave a greater capacity to affect TPR than larger arteries
o Decreasing radius increases blood flow but large amount

Question 21

Regulators of arterial tone – passive factors

Answer 21

o Pressure
o Architecture/structure of blood vessels

Question 22

Regulators of arterial tone – active factors

Answer 22

o Sympathetic nerves
o Circulating factors e.g. catecholamines
o Local vasoactive factors e.g. released from endothelial cells

Question 23

why is TPR elevated during hypertension?

Answer 23

o Due to functional imbalance between constriction and relaxation and structural changes
o As blood pressure rises, blood vessels undergo structural changes (remodelling)

Question 24

consequences of vascular remodelling

Answer 24

o Resting vascular resistance is raised
o For a given constrictor stimulus, there is a greater increase in R and thus BP

Question 25

how can we lower TPR?

Answer 25

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

Question 26

a1=adrenoceptor antagonists’ mechanisms of action

Answer 26

o Bind to and inhibit vascular a1-adrenoceptors
o Inhibit noradrenaline-mediated vasoconstriction (inhibit sympathetic vascular tone)
o Decrease TPR
o Decrease BP

Question 27

a1-adrenoceptor antagonist side effects

Answer 27

o 1st dose hypotension
o Nasal congestion
o Postural hypotension
o Initial reflex tachycardia

Question 28

Renin-angiotensin-aldosterone system

Answer 28

Altering levels of enzymes in this system has implications for BP

Question 29

RAAS inhibitors mechanisms of action

Answer 29

both orally available
same adverse effects as ACE inhibitors except for dry cough

Question 30

ACE inhibitors mechanism of action

Answer 30

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

Question 31

RAAS inhibitors adverse effects

Answer 31

o 1st dose hypotension
o Hyperkalaemia (increase in K+)
o Acute renal failure (reversible)
o Dry cough

Question 32

RAAS inhibitors advantages

Answer 32

o Less effect on cardiovascular reflexes
o Safe in asthmatics
o Beneficial effects on cardiovascular remodelling