Hypertension + Heart failure Flashcards
Define blood pressure
Force per unit area acting on vessels
Cyclical
MAP = CO X TPR
CO = SV X HR
What is the role of autocoids in blood pressure regulation?
Eg bradykinin, nitric oxide; act on vascular smooth muscle + endothelium
Acute BP maintenance working along with sympathetic NS + RAAS
Describe the relationship between the radius of a vessel and the resistance to flow
4th power relationship
Resistance to flow inversely proportional to vessel radius
Vasoconstriction- increased smooth muscle tone thus smaller lumen diameter - increased TPR- increased BP
Describe the pathophysiology and effects of hypertension (particularly on vasculature)
- Vascular remodelling, hypertrophy, thickening
- Hyperinsulinaemia and hyperglycaemia leading to endothelial dysfunction + ROS formation
- Downregulation of NO signalling
- Permanent hypertrophy of vasculature leading to increased TPR + reduced compliance
Increased morbidity + mortality
Give some examples of end organ damage due to hypertension
- Renal disease
- Peripheral vascular disease
- Anueurysms
- Vascular dementia
- Retinal disease (retinopathy)
Hypertensive heart disease- left ventricular hypertrophy seceondary to increased afterload; dilated heart failure
Why is there a greater prevalence of hypertension in men?
Women have cardioportective effects pre-menopause from high oestrogen levels
Post-menopause, the risk of hypertension in women catches up to men
Despite hypertension often persenting asymptomatically, why is it necessary to treat?
To slow down/prevent progression of acute coronary syndromes, chronic heart disease, strokes
Reducing CVD risk
What is the NICE guideline for defining hypertension?
140/90 mmHg = hypertension
What are the main types of hypertension and which is most prevalent?
Primary/essential/idiopathic- most common
Secondary- phaeochromocytoma, thyroid disease
Pre-hypertensive state
Isolated systolic/diastolic hypertension
White coat/clinic hypertension
Describe the best practice for a clinical diagnosis of hypertension
Sitting, relaxed, arm supported
If there is a >15 mmHg difference between both arms, repeat measure + use arm with higher reading
ABPM/HBPM for white coat syndrome patients
CVD risk + end organ damage assessed
When may emergency treatment be required for hypertension ie what is considered a hypertensive emergency?
BP > 180/120 mmHg
+
Clinical signs eg papilloedema, retinal haemorrhage
What is the target BP for someone <80 yrs of age and for someone with T2DM? (ie at what BP should treatment be initiated?)
140/90
What is the target BP for someone >80 yrs of age? (ie at what BP should treatment be initiated?)
150/90
What is the target BP for someone with T1DM?
135/85 (lower if experiencing severe T1DM complications)
Define stage 1 hypertension
STAGE 1:
Clinic BP 140/90- 159/99
ABPM/HBPM 135/85 - 149/94
Define stage 2 hypertension
Clinic BP 160/100 - <180/120
ABPM/HBPM:
150/95 or higher
Define stage 3 (severe/resistant) hypertension
Clinic systolic <180
OR
Clinic diastolic > 120 mmHg
Define the BP ranges for pre-hypertension and give some lifestyle modifications to reduce CVD risk
>120/80 + <140/90 mmHg
Lifestyle advice
Reduced dietary sodium intake
List the main therapeutic agents used for primary hypertension
- ACE inhibitors
- Angiotensin (AT1) receptor blockers- ARBs
- Calcium channel blockers- CCBs
- Diuretics- thiazide, thiazide like
Targetting RAAS
Where is ACE found and what does it do?
Luminal surface of capillary endothelial cells, predominantly in LUNGS
Catalyses conversion of angiotensin 1 to POTENT VASOCONSTRICTOR angiotensin 2
In the presence of ACE inhibitors, how else can angiotensin 2 be produced from angiotensin 1?
Via chymases; angiotensin 2 production independent of ACE
Give 2 examples of ACE inhibitors
- Ramipril
- Lisinopril
Give some side effects of ACE inhibitors
Hypotension
Dry cough
Hyperkalaemia (low aldosterone)
Renal failure; renal artery stenosis where efferent arteriole constriction is required
Angioedema
Give 2 examples of Angiotensin 2 receptor antagonists
- Candesartan
- Losartan
Describe the action of CCBs
Target calcium initiated smooth muscle contraction
Interact with different sites on alpha 1 sub-unit of VOCC
Have a selectivity for vascular smooth muscle or the myocardium (pacing cells)
Classify the calcium channel blockers into 3 types
- Dihydropyridines - used for hypertension
- Non-dihydropyridine: phenylalkylamines + benzothiazapines
Which type of CCBs are selective for peripheral vasculature?
Dihydropyridines
Little inotropic/chronotropic effects; little effect on myocardium/pacing cells of heart
1st line CCBs for hypertension
Which type of CCBs are selective for the myocardium + pacing cells of heart?
Non-digydropyridines; phenylalkylamines
Depresses SA + AV nodal conduction, negative inotropy (reduced force of contraction of heart)
Which type of CCBs are selective to the myocardium and the vasculature?
Benzothiazapines (non-dihydropyridines)
Give 3 examples of CCBs
- Amlodipine
- Nifedipine
- Nimodipine (cerebral vasculature selectivity; sub-arachnoid haemorrhage)
Give some side effects of the dihydropyridine class of CCBs (used for hypertension)
Ankle swelling
Flushing
Headache (vasodilation)
PALPITATIONS; REFLEX/COMPENSATORY TACHYCARDIA - thus contraindication with unstable angina, severe aortic stenosis
Describe the drug interaction between amlodipine (CCB) and simvastatin
Amlodipine increases the effect of simvastatin, thus need to lower the dose of statins if taken with amlodipine
Also contraindications with other anti-hypertensives (eg hypotension)
What is the main use of phenylalkylamines and how do they work?
Class 4 anti-arrhythmic (angina, hypertension)
Prolongs action potential + effective refractory period
Negative inotropic + chronotropic effects
Give an example of a phenylalkylamine
Verapamil
Give an example of a benzothiazapine
Diltiazem
Give 2 examples of thiazide diuretics
Bendroflumethiazide
Indapamide
What is the mechanism of action of thiazide diuretics?
Used for oedema
Inhibit Na+/Cl- co-transporter in DCT, thus increased Na+ and H20 EXCRETED
Give some side effects and contraindications of thiazide diuretics
- Hypokalaemia
- Hyponatraemia
- Hyperuricaemia
- Arrhythmia (K+ disturbances)
- Raised glucose
- Raised cholestrol + triglyceride levels
Thus, contraindicated in hypokalaemia, hyponatraemia, gout, NSAIDS, K+ lowering drugs
What is the 1st line medication for primary hypertension in patients with diabetes or those <55yrs age + not black?
ACE inhibitor or ARB
Then, add CCB, thiazide-like diuretic later if needed
What is the 1st line medication for primary hypertension in a patient >55yrs age or black origin?
CCB; as they have low renin levels thus no point targetting RAAS
Then add ACEi/ARB, thiazide-like diuretic later if needed
(step 3 for all pt’s = ACEi OR ARB + CCB + thiazide-like diuretic)
Why are ACE inhibitors always 1st line for primary hypertension in patients with diabetes? - regardless of their age/ethnicity
2 pronged approach
ACEi/ARB reduced risk of diabetic nephropathy + CKD with proteinuria due to dilation of efferent glomerular arteriole;
Reduced peripheral vascular resistance- reduced BP + DILATION of efferent glomerular arteriole– REDUCED INTRAGLOMERULAR PRESSURE- beneficial for T2DM
What medication can be added at step 4 for resistant hypertension and what are some of its contraindications?
- Spironolactone; aldosterone/mineralocorticoid receptor antagonist
- Contraindicated in hyperkalaemia, Addison’s
- Not with other drugs increasing K+ levels, ACEi’s, ARBs– monitoring needed
If patient is hyperkalaemic, consider adding SYMPATHETIC BLOCKERS- alpha/beta blockers, instead of spironolactone
Give 3 examples of B-adrenoceptor blockers
- Labetalol
- Bisoprolol
- Metoprolol
Describe the mechanism of action of B-adrenoceptor blockers
Decrease sympathetic tone by blocking noradrenaline
Reducing myocardial contractility, thus decreasing CO
Give an example of an alpha-adrenoceptor blocker
Doxazosin
Describe the mechanism of action of alpha-adrenoceptor blockers
Selective antaagonist of alpha-1 adrenoceptors
Reduce peripheral vascular resistance, thus lower BP
(May lead to postural hypotension- dizziness, syncope, headache, fatigue)
Contraindicated in pre-existing postural hypotension, dihydropyridine CCBs- oedema)
List some factors which can vary the cardiac output
- Preload (filling pressure); LVEDP- sarcomere length - Starling’s curve
- Afterload- load ventricle has to pump against
- Contractility
- Heart rate
Give some symptoms of heart failure
- Reduced exercise tolerance
- Dyspnoea
- Fatigue
- Oedema- swelling; peripheral, pulmonary
List some mangement options for heart failure; heart failure with reduced ejection fraction (<45%)
- Diuretics (congestive symptoms + fluid retention); furosemide- loop diuretic
- B-blockers; bisoprolol
- ACEi’s; ramipril, lisinopril
- Mineralocorticoid receptor antagonists; spironolactone
- Angiotensin receptor blockers (ARBs); candesartan, losartan
AIM: reduce preload, reduce sympathetic stimulation, reduce blood volume– reduce workload on heart
Why do you want to reduce sympathetic stimulation in heart failure by giving B-blockers?
To slow down heart rate and allow more time for contraction of the heart- with aim of increasing CO
What is the usual type of heart failure?
LV systolic dysfunction; reduced LV ejection fraction <45%
