1. Hypertension Flashcards
What is Hypertension?
Persistent elevation of blood pressure at or above 140/90 mmHg, confirmed by multiple readings over time or 24-hour ambulatory monitoring.
What characterises stage 1 hypertension?
Clinic blood pressure ranging from 140/90 - 159/99mmHg and ABPM daytime average ranging from 135/85 - 149/94 mmHg
What characterises stage 2 hypertension?
Clinic blood pressure ranging from 160/100 - 180/120mmHg and ABPM daytime average of 150/95 or higher
What is Ambulatory Blood Pressure Monitoring (ABPM)?
-Ambulatory Blood Pressure Monitoring (ABPM) involves measuring blood pressure over 24 hours
-A small, portable device automatically takes readings at regular intervals
What is the benefit of ABPM?
-Detects white coat hypertension
-Identifies masked hypertension
-Assesses BP variations throughout the day and night
Describe the reflex through which high blood pressure is controlled?
-Baroreceptors in carotid sinus and aortic arch sense increased arterial pressure
-Activates the medulla oblangata, increasing parasympathetic output (slowing the heart rate)
Why does the baroreceptor reflex fail in those with hypertension?
In chronic hypertension, barorecetpros adapt to the elevated blood pressure, treating it as the new normal.
What do
-⍺1
-β1
adrenergic receptor stimulation lead to?
-⍺1: Vasoconstriction
-β1: Increased force of contraction
What is essential (primary) hypertension caused by?
-Unknown cause
-Hereditary links help predict it
What is accelerated (malignant) hypertension?
-Severe, rapidly progressing hypertension (BP >180/120mmHg)
-Leads to organ damage, cardiovascular events
What is secondary hypertension caused by?
-Sleep apnoea
-Kidney disease (eg CKD)
-Thyroid disease (eg hyper/hypothyroidism)
-Diabetes
What releases Renin, and what is the action of this?
-Kidney releases renin
-Renin converts angiotensinogen to angiotensin I
What creates angiotensin II?
ACE enzyme converts angiotensin I to angiotensin II
What is the action of angiotensin II?
-Stimulates aldosterone release from adrenal cortex (promotes sodium retention)
-Causes release of ADH from pituitary (promotes water retention)
-Stimulates thirst (fluid and blood volume increase)
-Causes vasoconstriction
-Cardiac and vascular hypertrophy
What are the targets for the treatments of hypertension?
-Renin Angiotensin Aldosterone pathway
-Angiotensin II receptors
-Na reabsorption mechanisms in kidney
-Adrenergic receptors
-Calcium channels
Describe ACE inhibitors as a treatment for hypertension
-Inhibits the angiotensin converting enzyme in the renin-angiotensin-aldosterone pathway
-Decreases vasoconstriction and salt retention
-Also inhibits bradykinin breakdown, leading to extra vasodilation
Give an example of an ACE inhibitor, and describe its pharmacokinetics
-Lisinopril
-Absorbed slowly from GI tract, with 25% bioavailability, and peak plasma concentration reached in 6-8 hours
-Water soluble, meaning it is not metabolised and undergoes renal excretion.
Give some side effects associated with lisinopril
-DRY COUGH
-Postural disorders
-Hallucination
-Altered mood
-Raynaud’s phenomenon
-Anaemia
-Hypersensitivity
-Hypoglycaemia
Describe ARBs as a treatment for hypertension
-Angiotensin II Receptor Blockers
-Selectively blocking AT1 receptors, preventing the effects of angiotensin II, which include
-Vasoconstriction, aldosterone release and sympathetic activation
Give an example of an ARB, and its pharmacokinetics
-Losartan
-Orally administered, with 33% bioavailability, and peak plasma conc reached in 1-3 hours
-Metabolised in liver to form its active metabolite which has half life of 3-9 hours
-Extensive albumin binding, and excreted in urine and bile
Give some side effects associated with losartan
-Anaemia
-Hypoglycaemia
-Postural disorders
-Hyperkalaemia
Describe calcium channel blockers as a treatment for hypertension
-Calcium voltage gated channel blockers, inhibiting the influx of calcium ions
-Acting on myocardial muscle (inhibiting contractility)
-Acting on myocardial conducting system (inhibiting CICR)
-Acting on vascular smooth muscle (vasodilation)
Give an example of a calcium channel blocker, and its pharmacokinetics
-Amlodipine
-Orally administered with 60% bioavailability, half life of 30-50 hours
-Steady state plasma concentrations reached after 7 days of daily dosing
-Poorly eliminated
Which groups are ARBs or ACE inhibitors used in to treat hypertension?
-Age <55 and not of black African or African–Caribbean family origin
-Type II diabetics with hypertension
Which groups are CCBs used in to treat hypertension?
-Aged 55 and over
-Black African or African–Caribbean family origin (any age)
How may diabetes lead to hypertension?
-Diabetes damages the kidneys, reducing their ability to excrete sodium and water, increasing blood volume and hypertension
-May also damage peripheral micro vessels
If the first treatment (ACEi or ARB or CCB) in hypertension is ineffective, what should be done after?
-Kept on preexisting treatment
-Add extra treatment (ACEi, ARB or CCB or thiazide like diuretic)
-If this is ineffective, if low K+ levels add sprinonolactone and/or alpha/beta blockers
Describe the mechanism of action of thiazide-like diuretics
-Inhibit the Na+/Cl- symporter in the distal convoluted tubule, preventing reabsorption, leading to increased sodium excretion in the urine
-Water follows sodium osmotically, leading to diuresis, increasing urine output and frequency
-This reduces plasma volume, lowering blood pressure
-Thiazide like diuretics also induce vasodilation, reducing peripheral vascular resistance
Give an example of thiazide like diuretic, and its pharmacokinetics
-eg Indapamide
-Orally administered with high bioavailability, and 1-2 hours to reach peak plasma conc
-Metabolised by CYP3A4, with elimination half life of 14-18 hours, supporting once-daily dosing
Give some of the adverse reactions associated with thiazide like diuretics
-Elderly are particularly sensitive to hypokalaemia (dangerous in severe cardiovascular disease and being treated with cardiac glycosides)
-Elderly are also sensitive to constipation, electrolyte imbalance, headache and postural hypotension
-INDAPAMIDE specifically causes hypersensitivity and skin reactions
Why do thiazide like diuretics cause hypokalaemia?
-Thiazide like diuretics increase concentration of sodium in the tubule
-More sodium hence reaches the collecting duct, where Na+/K+ exchangers are present, driving exchange of sodium for potassium (more is excreted in urine)
Describe the mechanism of action of spironolactone diuretics
-Potassium sparing diuretic
-Competitive antagonist of aldosterone to the mineralocorticoid receptor
-Aldosterone is unable to activate the Na+/K+ ATPase pump, reducing sodium reabsorption and potassium secretion
-This reduces blood volume, reducing blood pressure, as well as reducing aldosterone mediated vasoconstriction
Who should spironolactone diuretics NOT be used in?
Those with high serum levels of potassium
Describe the mechanism of action of Alpha-1 receptor blockers in the treatment of hypertension
-Alpha 1 receptors located in smooth muscle of blood vessels are blocked, preventing noradrenaline mediated vasoconstriction
-This leads to vasodilation and a reduction in systemic vascular resistance and blood pressure
-Also helps to prevent the baroreceptor reflex, preventing vasoconstriction
Describe the mechanism of action of Beta 1 receptor blockers in the treatment of hypertension
-Beta 1 receptors located in SAN, AVN and myocardial cells are blocked, preventing noradrenaline and adrenaline binding, reducing the sympathetic response.
-This reduces heart rate, contractility and cardiac output, leading to a reduction in blood pressure
-ALSO when beta 1 receptors in kidneys are blocked, renin secretion is reduced, leading to lower angiotensin II levels.
Give side effects associated with alpha 1 receptor blockers
-Postural hypotension
-Reflex tachycardia
-Dizziness and fatigue
-Headache
Give side effects associated with beta 1 receptor blockers
-Bradycardia
-Fatigue and exercise intolerance
Why may beta 1 receptor blockers be considered in younger people?
-Intolerance or contraindication of ACE inhibitors and ARBs
-Women of childbearing potential
-Evidence of increased sympathetic drive
