Htn And Heart Failure Flashcards
How is resistance related to radius of vessels
Ss, Small changes on the radius have big changes in resistance and hence blood pressure (r^4)
Descrbe the pathophysiology of H&n
- Elevated blood pressure (essential/primary/idiopathic) still not completely understood - debated
- Leads to vascular changes inc. remodelling and thickening, hypertrophy
- Increased vasoactive substances inc. ET-1, Nad, angII
- Vascular remodelling as direct result of local salt sensitivity
- Hyperinsulinemia and hyperglycaemia – endothelial dysfunction and reactive oxygen species (ROS) ↓NO
- ….culminating in permanent and maintained medial hypertrophy of vascularture → ↑↑TPR and ↓↓compliance
- End organ damage (renal, peripheral vascular disease, aneurysm, vascular dementia, retinal disease)
- “Hypertensive heart disease” LVH → dilated cardiac failure
- ↑ Morbidity and mortality
Why does H&n need to be treated
Increase above normal increases risk of chd and stroke. Needs to be treated. Precursor to cardiovascular diseases
Define Htn
• Labile, age, sex and population differences makes defining HT difficult
• “An elevation in blood pressure that is associated with an increase in
risk of some harm”
• “Significantly high to cause end organ damage”
• “An elevated blood pressure that treated will do more good than harm”
• NICE suggest that 140/90 mmHg defines hypertension - ≥ 40% population of England
• Reduction in BP – both SBP and DBP reduces CVD risk
• Essential/primary/idiopathic – 90% secondary
prehypertensive
isolated systolic/diastolic
white coat/clinic - is real phenomenon
Desribe the diagnosis and treatment of htn
• Screening those at risk
• Increasing public awareness of risk factors
• Reliable diagnoses based on clinical guidelines
• Promote appropriate lifestyle changes to limit risk – no immediate gain
• Regular monitoring and refinement of medication – resistant HT, increasing risk of CHD/stroke, adherence!
• SILENT KILLER!
• Current UK guidelines:
British hypertension society
SIGN No. 49 (Scotland)
NICE CG 127 and clinical evidence update 32
Describe th best practices for diagnosing htn
- Measure blood pressure whilst patient is sitting, relaxed and arm is supported
- Measurements in both arms, >20 mmHg difference repeat measurement and use arm with higher reading
- diagnosis of stage 1 or stage 2 hypertension should follow elevated BP measurements made over several visits and or addition of ABPM. HBPM an alternative if ABPM not tolerated
- If severe hypertension is observed, urgent or emergency treatment should be initiated
- Cardiovascular risk and end organ damage should be assessed whilst waiting for HT confirmation
- How patient will be managed following diagnosis will vary but aiming to achieve target BP and reduce risk of CVD is primary aim
- Target BP will vary according to associated risk, age, end organ damage and complications of diabetes and other peripheral vascular disease
Define stage 1 2 and severe htn
1: 140/90 or 135/85
Clinic vs home
2: 160/100 C or 150/95 H
Severe: systolic 180 higher C do diastolic 110 or higher C
• Diabetic and renal compromise stage 1 >130/80 as a starting point
• Isolated systolic hypertension mild >140 SBP <90 DBP, moderate >160 SBP <90 DBP
What ispre hypertesion
- Elevated BP below stage 1 diagnoses with no end organ damage can be treated in the first instance with lifestyle changes
- Promotion of regular exercise
- Modified healthy/balanced diet
- Reduction in stress and increased relaxation
- Limited/reduced alcohol intake
- Discourage excessive caffeine consumption
- Smoking cessation
- Reduction in dietary sodium
- Should be promoted to all patient groups
What are primary htn therapeutic agents
- Angiotensin converting enzyme (ACE) inhibitors Angiotensin (AT1) receptor blockers (ARBs)
- Calcium channel blockers (CCBs) • Diuretics
- Other agents used in specific circumstances
Describe the actions of ace and ang ii
• ACE - luminal surface of capillary endothelial cells, predominantly in the lungs
• ACE catalyses conversion of angiotensin-I to potent active vasoconstrictor angiotensin-II
• Angiotensin-II affords action through AT1 and AT2 receptors
• AT1 receptor subtype typical of classic angiotensin-II actions
- vasoconstriction, stimulation of aldosterone, cardiac and vascular muscle cell growth and vasopressin (ADH) release from posterior pituitary
What are ace inhibitor moas
Eg ramipril
•
• • • • •
• •
Limit the conversion of Angiotensin-I to Angiotensin-II by inhibiting circulating and tissue ACE
Thus a reduction in Angiotensin-II effects, resulting in vasodilation
reduction in aldosterone release reduced vasopressin (ADH) release reduced cell growth and proliferation
All can contribute to antihypertensive effects
NB. Angiotensin-II can also be produced from angiotensin-I independently of ACE via chymase interaction – (see ARB’s)
What are the side effects/contraindications to acei
Bradykinin (BK) also a substrate for ACE
• ACE is kininase-II – breaks down kinins - inc. BK
• Use of ACE inhibitors therefore potentiates BK - vasodilatation via NOS/NO and PGI2
- ACE inhibitor vasodilation in low-renin hypertensives (see later slides A/CD)
• Well tolerated but associated with persistent dry cough (10-15%) (BK), angioedema (more common in black population), renal failure (inc. renal artery stenosis) and hyperkalaemia.
Describe arbs
Eg losartan • AT1 and AT2 receptors - AT1 important in relation to cardiovascular regulation
• Confusing nomenclature – Angiotensin-II blockers, AT1-receptor blockers or ARB’s
• ARB’s have no effect on BK- less effective in low-renin hypertensives, but aren’t associated with dry cough
• Directly targeting AT1 receptors therefore more effective at inhibiting Ang-II mediated vasoconstriction (chymase production)
• As with ACE inhibitors: renal failure and hyperkalaemia are side effects
Describe ltccs and ccbs
- LTCCs allow inward Ca2+ flux into cells – voltage operated calcium channel (VOCC)
- Expressed throughout the body - inc. vascular smooth muscle cells AND cardiac myocytes
- Large calcium flux into cell, further calcium from SR and activation of contractile proteins (myosin, actin)
- CCBs target calcium initiated smooth muscle contraction
- Three classes of CCB that interact with different sites on (α1) subunit of VOCC’s selectivity for VSMC or myocardium
Whar er the classes of ltccs and ccbs
• - Dihydropyridine class
- non-dihyropyridine - Phenylalkylamines and Benzothiazapines
• Dihydropyridine class more selective for peripheral vasculature, show little chronotropic or inotropic effects (first line CCB for HT)
• Phenylalkyamine depresses SA node and slows AV conduction, negative inotropy
• Benzothiazapines sit in the middle
• CCBs – primary choice antihypertensive in low renin hypertensives
What are the properties of dihydropyridines
Eg amlodipine Properties: • Good oral absorption • Protein bound > 90% • Metabolised by the liver • Few have active metabolite
What are the adverse effects of dihydropyridies
Adverse effects:
• Sympathetic nervous system activation – tachycardia - rare
• Palpitations
• Flushing, sweating, throbbing headache
• Oedema
• Amlodipine and simvastatin (increased Cp of simvastatin)
Wha are the actions of phenylalkylamines
Eg verapamil
Phenylalkylamines
Action:
• Impedes calcium transport across the myocardial and vascular smooth muscle cell membrane
• Class IV anti-arrhythmic agent/prolongs the action potential/effective refractory period
• Less peripheral vasodilatation, negative chronotropic and inotropic effects
• Arrhythmia, angina, (hypertension)
What are the adverse effects of penylalkylamines
Adverse effects:
• Constipation
• Risk of bradycardia
• Negative inotrope - can worsen heart failure - additive with beta blockers
What are the properties of benzothiapines
Eg diltiazen
Properties:
• Impedes calcium transport across the myocardial and vascular smooth muscle cell membrane
• Prolongs the action potential/effective refractory period
• Sits between amlodipine et al. and verapamil in vascular and cardiac
effects
• Angina (hypertension)
What are the adverse effects o benzothiazapines
Adverse effects:
• Risk of bradycardia
• Negative inotropic effect less than verapamil - can worsen heart failure
Describe thiazides
Eg benxoflumethiazide
• Moderately potent, inhibit Na+ reabsorption in distal convoluted tubule
• Diuresis resulting in lower blood and extracellular volume ↓TPR
• Useful over CCBs in odema
• Long term effects mediated by sensitivity of VSM to
vasoconstrictors Ca2+/Nad – we think!
What are the adverse elects o diazides
Adverse effects:
• Hypokalaemia
• Increased urea and uric acid levels
• Impaired glucose tolerance (especially with beta-blockers)
• Cholesterol and triglyceride levels increased
• Activates RAAS
Describe the nice guidelines for treating 1o htn
S
What are the other options
Spironolactone, labetalol
• If A, C or D are not effective or contraindicated then several other classes can be considered
• ACE inhibitor first line for hypertension in HF and DM patients
• Alpha-adrenoceptor blockers
• Beta-adrenoceptor blockers
• Spironolactone – mineralocorticoid/aldosterone receptor antagonist
• Amiloride – K+ sparing acting on distal tubule
• Direct renin inhibitor – aliskirin
• Other direct vasodilators – nitrates e.g. SNP (hypertensive emergency i.v.)
• Centrally acting drugs – labetalol (pregnancy, hypertensive
emergency i.v.) - reduce sympathetic outflow - not typically in primary practice but p.o. labetalol in pregnancy
Describe alpha adrenoceptor blockers
Eg doxazosin • Selective antagonism at post-synaptic α-1 adrenoceptors and antagonise the contractile effects of noradrenaline on vascular smooth muscle • Reduce peripheral vascular resistance • Benign effect on plasma lipids/glucose • Safe in renal disease
What are the adverse effects of alph blockers
Adverse effects:
• Postural hypotension………Dizziness
• Headache and fatigue
• Oedema (especially if combined with dihydropyridine)
Describe beta blockers
Eg bishop roll
Decrease sympathetic tone by blocking Nad and reducing myocardial contraction → ↓ CO (↓ renin secretion) affording antihypertensive effects
What are teh adverse effects of beta blockers
- Can cause bronchoconstriction so contraindicated in asthmatics and COPD also in 2nd/3rd degree heart block
- Also mask tachycardia – sign of insulin induced hypoglycaemia – caution in diabetics
- Lethargy and impaired concentration
- Reduce exercise tolerance
- Bradycardia
- Raynaud’s (cold hands)
What is heart failure briefly
• Cardiac output (CO) ~ 5L/min in a typical adult
• CO varies in response to both physiological and pathological factors - preload – filling pressure (LVEDP – surrogate for sarcomere length) - afterload – “load” that ventricle must eject blood against
- contractility
- heart rate
• Abnormality in cardiac function which is responsible for the failure of the heart to pump blood at a rate commensurate with the requirements of metabolising tissues
• Characterised by symptoms that may present and often in later stages of HF
- exercise intolerance, breathlessness, fatigue (swelling)
• Acute heart failure – the result of sudden circulatory collapse – haemorrhagic shock or cardiogenic shock during AMI, sepsis
Describe teh aetiology of hf
• •
Usually, there is some form of cardiomyopathy
“disease of the myocardium associated with cardiac dysfunction” (WHO,
1995)
many causes of cardiomyopathy
-inherited
congenital hypertrophic CM arrhythmogenic RV CM
-acquired
ischaemic cardiomyopathy pressure overload
valve disease infection/inflammation/alcohol
What is the self perpetuating @spiral”
Physiological neurohormonal response in its attempt to compensate will eventually lead to further pathology- ss
Describe management of h
• Usually dealing with LV systolic dysfunction associated with reduced LV ejection fraction (<45%)
• Where there is preserved EF (e.g. diastolic heart failure or high output failure), optimal treatment is not clearly defined
• Correct underlying cause (replace valve, angioplasty)
• Non pharmacological management – ↓↓salt intake, liquid reduction
~ 1.5L
AIMS of treatment are:
• reduction in symptoms (dyspnoea, fatigue, oedema)
• Managed increase in exercise tolerance
• decreased mortality
• address arrhythmias, hyperlipidaemia, diabetes
Diuretics, typically furosemide, are used in most patients symptomatically (congestive symptoms) but have little impact on survival
furosemide
Describe acei and arb in hf
• useful in ALL grades of LV dysfunction and there is a drug class effect
• LOW INITIAL DOSE reduces risk of sudden rapid fall in BP, especially in
patients already taking diuretics
• monitor renal function within first few weeks
• if ACE inhibitor not tolerated, an AT1 antagonist (ARB) may be used as alternative
• ARBs have essentially similar benefit as ACE inhibitor in HF, typically
start with ACE inhibitor, if not tolerated then ARB (under close supervision of cardiologist can be used together)
Desribe teh use of spironolactoe in hf
- In some individuals refractory hyperaldosteronism occurs (RAAS gene polymorphism?) (sometimescalledaldosteroneescape)
- Typically used as adjunct to max ACE inhibitor and diuretic
- 1663 patients NYA class III/IV
- LVEF ≤ 35%
- ACE inhibitor, loop diuretic and digoxin (most)
- 25 mg spironolactone SID
- All cause mortality
Describe the usage of beta antagonists in hf
• recommended for ALL patients with stable CHF unless contraindicated or not tolerated
• introduce once ACE inhibitor or AT1 antagonist (ARB) therapy is initiated
• benefit is related to blunting of sympathetic influences especially on
heart rate
• slower HR → longer diastolic filling period → better filling→ more output
• may also stabilise electrical conduction (class I antiarrhythmic effect) reducing arrhythmia
• may also blunt circulating RAAS directly inhibiting renin, but probably minor effect since ACE inhibitors already used
• LOW initial dose which may cause transient worsening of symptoms (e.g. fatigue, poor exercise tolerance)
