51) Treatment of hypertension

Question 1

How is blood pressure regulated in the short term?

Answer 1

• Baroreceptors in the aorta and carotid arteries respond to changes in pressure causing them to increase or decrease parasympathetic and sympathetic outflow

Question 2

How is blood pressure regulated in the long term?

Answer 2

• There is a hormonal control by controlling the amount of total body Na+
• The kidney is involved in this regulation as it is the site of RAAS activation and the effector which modifies Na+ renal retention
• This causes changes in ECF volume and hence the blood volume
• The degree of vasoconstriction can also aid long term blood pressure regulation and is under the control of NO, prostaglandins and other hormonal factors

Question 3

What is hypertension?

Answer 3

• A blood pressure above 140/90 mm Hg

Question 4

What are the different degrees of hypertension?

Answer 4

• Stage 1 hypertension: BP above 140/90 mm Hg
• Stage 2 hypertension: BP above 160/100 mm Hg
• Severe hypotension: BP above 180/110 mm Hg

Question 5

What is hypertension a risk factor of?

Answer 5

• Stroke
• Ischemic heart disease
• Left ventricular hypertrophy leading to heart failure
• Renal failure
• Retinopathy

Question 6

What are the subdivisions of the causes of hypertension?

Answer 6

• Primary/Essential: when there is no identifiable cause and makes up majority of the cases
• Secondary: when there is an identifiable cause and make up minority of cases

Question 7

What are examples of secondary causes of hypertension?

Answer 7

• Renal disease
• Vascular disease (e.g. renal artery stenosis)
• Hormonal (e.g. Conn’s syndrome)
• Monogenic genetic disorders (e.g. Liddle’s)

Question 8

How is primary/essential hypertension caused?

Answer 8

• Caused by a combination of genetic and environmental factors to cause essential hypertension through many mechanisms

Question 9

Why do we treat hypertension?

Answer 9

• It reduces the risk of strokes, heart attacks and vascular mortality

Question 10

What is the goal of anti-hypertensive treatment?

Answer 10

• Achieve adequate blood pressure control (reduce blood pressure below 140/90)
• Prevention of target organ damage
• Control orther cardiovascular risk factors

Question 11

What are the different treatment pathways for hypertension?

Answer 11

• Non-pharmacological: lifestyle modifications
• Pharmacological treatment
• Surgery (if cause is known)

Question 12

What lifestyle alterations can be made to combat hypertension?

Answer 12

• Quit smoking
• Weight control
• Eat less salt
• Regular exercise
• Reduce alcohol intake
• Behavioural therapies

Question 13

What pharmacological treatments are used to combat hypertension?

Answer 13

• ACE inhibitors (ACEi)
• Angiotensin II receptor blockers (ARBs)
• Diuretics
• Drugs acting on SNS (normally adrenergic blockers)
• Vasodilators

Question 14

What is the mechanisms in which ACE inhibitors combat hypertension?

Answer 14

• ACE inhibitors interrupt RAAS by inhibiting ACE
• ACE activates angiotensin I by cleaving it into angiotensin II (which is the active hormone) causing vasoconstriction and aldosterone secretion
• Hence by inhibiting ACE little to no angiotensin II is present

Question 15

What are the side effects of ACE inhibitors?

Answer 15

• Cough (common) due to decrease in bradykinin breakdown
• Angioedema (rare but serious)
• Hyperkalaemia

Question 16

What is an alternative medicine to ACE inhibitors?

Answer 16

• AT1 (Angiotensin II Type 1) receptor blocker (ARB) which will block angiotensin II from binding to its receptor
• As a result it will block RAAS from causing vasoconstriction and secretion of aldosterone decreaes

Question 17

What are the side effects of ARBs?

Answer 17

• Hyperkalaemia as aldosterone secretion is decreased

Question 18

What is the mechanism in which diuretics combat hypertension?

Answer 18

• Diuretics increase salt and water excretion which reduces the extracellular fluid volume
• This reduces blood volume causing CO to be reduced (as there is less venous return)
• There is less Starling effect (less stretching) so will reduce blood pressure

Question 19

What is the mechanism by which drugs that act on the SNS combat hypertension?

Answer 19

• Drugs that target the SNS are normally antagonists of adrenergic receptors
• When the β1 receptors (found on the SAN) are activated they increase HR and contractility.
• Together these increase CO which in turn increases BP
• β1 blockers act on these receptors by blocking them causing reduced CO and hence reducing BP. There is also a reduction in renin release
• α1 in smooth muscles of vasculature cause vasoconstriction when activated causing increased TPR and so increases BP
• α1 blockers act on these receptors by blocking them causing reduced vasoconstriction and hence decreasing BP

Question 20

What is the mechanism by which vasodilators that act on K+ channels combat hypertension?

Answer 20

• Some vasodilators open K channel located on smooth muscles and causing K+ efflux from the cell
• This causes hyperpolarisation of the cell which leads to increased closure of Ca2+ channels and so less Ca2+ influx
• Hence there is less intracellular Ca2+ leading to less Myosin Light Chain Kinase activity and thus increased relaxation/vasodilation

Question 21

What is the mechanism by which vasodilators that act on Voltage gated Calcium channels (VGCC) to combat hypertension?

Answer 21

• Some vasodilators are able to block VGCCs which means at any given voltage fewer VGCCs are open so less Ca influx takes place
• This means there is lower intracellular Ca2+ levels and so less Myosin Light Chain Kinase activity
• This causes increased relaxation (vasodilation)

Question 22

What must be considered when deciding which drug to use?

Answer 22

• Essential vs secondary hypertension
• Evidence of efficacy (how well it works)
• Side effects
• Drug interactions (as drugs can interact with others that a patient may take)
• Individual demographics (gender, ethnicity)
• Co-existing diseases
• Quality of life (how well the patient can handle the drug)
• Economic consideration