Htn And Heart Failure Flashcards
(36 cards)
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