Treatment of hypertension Flashcards
What is blood pressure?
The pressure exerted by blood on the blood vessels
How is blood pressure regulated in the short term?
- use of baroreceptors
- sympathetic and parasympathetic outflow
How is blood pressure regulated in the long term?
- hormonal control
- degree of vasoconstriction
How does hormonal control regulate blood pressure in the long term?
- Through the control of blood volume, via the ECFV
- ECFV is controlled indirectly by the kidneys, but it is the amount of Na that is controlled, not the concentration
- If ECFV drops, there is more sodium retention by the kidneys which brings water with it, therefore restoring ECFV
How is Mean Arterial Blood Pressure (MABP) calculated?
MABP = CO x TPR
CO= Cardiac output TPR= Total peripheral resistance
What is hypertension?
High blood pressure:
defined as having a BP reading of more than 140/90 mmHg over a number of weeks
(currently hypertension is defined as a threshold)
Stage 1 hypertension
BP greater than or equal to 140/90 mmHg
Stage 2 hypertension
BP greater than or equal to 160/100 mmHg
Severe hypertension
BP greater than or equal to 180/110 mmHg
Healthy BP
120 systolic or lower
What is hypertension a risk factor for?
- Stroke, Ischaemic heart disease
- Left ventricular hypertrophy, heart failure
- Renal failure
- Retinopathy
What are the two main causes of hypertension?
- Primary or essential (when there is an unknown cause)
2. Secondary (when there is an identifiable cause)
What percentage of hypertension cases are primary?
> 90%
What percentage of hypertension cases are secondary?
<10%
What is primary hypertension?
Genetic pre-disposition and environmental factors are proposed to cause essential hypertension through many mechanisms
List some examples of how secondary hypertension can occur?
- Renal disease
- Vascular, e.g. renal artery stenosis
- Hormonal, e.g. Conn’s syndrome, Cushing’s syndrome
- Monogenic genetic diseases, e.g. Liddle’s
List possible mechanisms and risk factors that are involved with essential hypertension?
- Increased SNS
- Increased RAAS
- Endothelial dysfunction
- Defect in vascular smooth muscle contraction
- Defects in renal Na handling, increased salt intake
- Obesity/insulin resistance
- Age (Increases with age)
- Ethnicity, e.g. more common in Afro-Caribbean groups
- Family history
What are the three main reasons why we should treat hypertension?
- Risk reduction
- Goals of anti-hypertensive treatment
- Treatment pathways
How lifestyle can be adapted to minimize risk of developing hypertension?
- Quit smoking
- Weight control
- Eat less salt
- Regular exercise
- Reduce alcohol intake
- Behavioural therapies, e.g. CBT
What are the major classes of anti-hypertensive drugs?
- ACE inhibitors
- Angiotensin II receptor blockers
- Diuretics
- Drugs acting on SNS
- Vasodilators
Describe the mechanism of action of ACE (Angiotensin Converting Enzyme):
- Angiotensionogen is first converted by Renin in the kidney to Angiotensin 1
- Angiotensin 1 is converted by ACE (found in high conc in the lungs) into active form Angiotensin 2
- This acts on Angiotensin 1 receptors
- The two major effects being strong vasoconstriction and aldosterone secretion
How do ACE inhibitors and AT1 receptor blockers treat hypertension?
Decrease in vasoconstriction and aldosterone secretion to reduce blood pressure
What are the side effects of ACE inhibitors?
- Cough (common) due to decrease in bradykinin breakdown
- Angiodema (rare but serious)
- if patient suffers from these symptoms, AT1 RBs are used instead
What are the side effects of both ACEi and ARBs?
Hyperkalaemia (K+ level in blood higher than normal)
How do diuretics treat hypertension?
- Increase in sodium and water excretion
- Reduce blood volume -> reduces CO -> reduce BP
(BP ~ CO x TPR)
Describe sympathetic neural effects on CVS:
B1: increases heart rate and contractility - increases cardiac output - increases blood pressure
a1: vasoconstriction - TPR - increases BP
Beta blockers (B1 blockers, e.g. atenolol): reduction in CO and renin release
Mechanism of action of vasodilators?
K+ channel openers
Structural features of arterioles that make them a good target for vasodilators?
Arterioles normally have significant smooth muscle tone: scope for relaxation
Examples of vasodilators (K channel openers)
Minoxidil, Diazoxide
Action of vasodilators (K channel openers)
- Increased outward K current
- Hyper-polarization
- Reduced VGCC activity
- Reduced [Ca]i
- Less MLCK activity -> increased relaxation (vasodilation)
Action of vasodilators (voltage-dependent Ca2+ channel blocker)
- Block VGCC activity in VSMCs
- Reduced [Ca]i
- Less MLCK activity -> increased relaxation (vasodilation)
Example of a voltage-dependent Ca2+ channel blocker vasodilator?
Nifedipine
What are the factors that need to be taken into consideration when deciding which drug to use?
- Essential vs secondary hypertension
- Evidence of efficacy
- Side effects of drug
- Drug interactions
- Individual demographics
- Co-existing diseases
- Quality of life
- Economic considerations
