51) Treatment of hypertension Flashcards
How is blood pressure regulated in the short term?
- Baroreceptors in the aorta and carotid arteries respond to changes in pressure causing them to increase or decrease parasympathetic and sympathetic outflow
How is blood pressure regulated in the long term?
- 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
What is hypertension?
- A blood pressure above 140/90 mm Hg
What are the different degrees of hypertension?
- 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
What is hypertension a risk factor of?
- Stroke
- Ischemic heart disease
- Left ventricular hypertrophy leading to heart failure
- Renal failure
- Retinopathy
What are the subdivisions of the causes of hypertension?
- 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
What are examples of secondary causes of hypertension?
- Renal disease
- Vascular disease (e.g. renal artery stenosis)
- Hormonal (e.g. Conn’s syndrome)
- Monogenic genetic disorders (e.g. Liddle’s)
How is primary/essential hypertension caused?
- Caused by a combination of genetic and environmental factors to cause essential hypertension through many mechanisms
Why do we treat hypertension?
- It reduces the risk of strokes, heart attacks and vascular mortality
What is the goal of anti-hypertensive treatment?
- Achieve adequate blood pressure control (reduce blood pressure below 140/90)
- Prevention of target organ damage
- Control orther cardiovascular risk factors
What are the different treatment pathways for hypertension?
- Non-pharmacological: lifestyle modifications
- Pharmacological treatment
- Surgery (if cause is known)
What lifestyle alterations can be made to combat hypertension?
- Quit smoking
- Weight control
- Eat less salt
- Regular exercise
- Reduce alcohol intake
- Behavioural therapies
What pharmacological treatments are used to combat hypertension?
- ACE inhibitors (ACEi)
- Angiotensin II receptor blockers (ARBs)
- Diuretics
- Drugs acting on SNS (normally adrenergic blockers)
- Vasodilators
What is the mechanisms in which ACE inhibitors combat hypertension?
- 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
What are the side effects of ACE inhibitors?
- Cough (common) due to decrease in bradykinin breakdown
- Angioedema (rare but serious)
- Hyperkalaemia
What is an alternative medicine to ACE inhibitors?
- 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
What are the side effects of ARBs?
- Hyperkalaemia as aldosterone secretion is decreased
What is the mechanism in which diuretics combat hypertension?
- 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
What is the mechanism by which drugs that act on the SNS combat hypertension?
- 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
What is the mechanism by which vasodilators that act on K+ channels combat hypertension?
- 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
What is the mechanism by which vasodilators that act on Voltage gated Calcium channels (VGCC) to combat hypertension?
- 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)
What must be considered when deciding which drug to use?
- 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
