6.1- Hypertension and Heart Failure Flashcards
Name 3 mechanisms of physiological control
ANS; baroreceptors
RAAS
Vasoactive agents; metabolites, bradykinin, endothelium, nitric oxide
Which 3 diuretics are used in treating hypertension and heart failure
Loop diuretics: ___ semides and ___tanides
Thiazides
K+ sparing/ aldosterone antagonists: spironolactone and__renones
Name 5 drugs which treat HTN and heart failure
Diuretics ACE inhibitors \_\_\_renones ARB’s \_\_\_\_ sartans CCB’s\_\_\_\_\_dipines ie DIHYDROPYRIDINES Beta blockers
What is hypertension clinically defined as?
140/90 mmHg or above
Distinguish between primary and secondary hypertension
Primary hypertension: is WITHOUT a single evident cause
Secondary hypertension: high BP WITH a discrete underlying cause
Give 4 causes of secondary HTN
Endocrine:
Cushing’s Syndrome; Adrenocortical Hyperplasia
Phaeochromocytoma
Conn’s Syndrome; Primary Hyperaldosteronism
Mechanical: coarctation of aorta
Renal: glomerulonephritis, renal artery stenosis
Pregnancy: Pre-eclampsia
Classify the 3 stages of hypertension
Stage 1: BP> 140/90 mmHg
Stage 2: BP> 160/100 mmHg
Stage 3: BP> 180/120 mmHg
What does the QRISK score do?
Estimates a patient’s % chance of having CVD in the next 10 years
What makes up lifestyle therapy for HTN?
Patient education Maintain normal weight (BMI) Keep dietary sodium low Limit alcohol consumption Reduce intake of total and saturated fat Smoking cessation Discourage excessive caffeine consumption
What does ACD stand for?
ACE inhibitors/ ARB’s
Calcium channel blockers
Diuretics
What are ACE inhibitors?
Competitive inhibitors of ACE
-reduced formation of angiotensin II
- mainly arteriolar vasodilators but some venodilation
- circulating aldosterone is reduced
POTENTIATE the action of BRADYKININ
How often should ACE inhibitors be given and give 2 examples
E.g. ramipril, enalapril
Oral, once daily titrate dose
Describe the PK of ACEi’s
Variable bioavailability
Enalapril and ramipril are prodrugs metabolised in the liver to ___prilats an active metabolite
Give 4 Main Side effects of ACE inhibitors
Dry cough
Angioedema ( common in black pop) ( bc of bradykinin making capillaries leaky)
Renal failure ( including renal artery stenosis)
Hyperkalaemia
When are ACE inhibitors contraindicated?
Pregnancy
Renal artery stenosis
Why do you get dry cough when you take ACE inhibitors?
Due to lack of bradykinin by ACE enzymes
Therefore unmetabolised bradykinin causes CONSTRICTION of non-vascular smooth muscle in the bronchus—-> leading to cough
What are ARB’s?
Angiotensin Receptor Blockers
Bind to angiotensin II type 1 (AT1) receptor
Inhibit vasoconstriction and aldosterone stimulation caused by angiotensin II
E.g. losartan
Describe the PK of ARB’s
Oral once daily, titrate dose as required
Low availability, high protein binding
Well tolerated
a) Give 2 side effects of ARB’s
b) Give 2 contraindications of ARB’s
a) hyperkalaemia
Renal failure
b) pregnancy
Renal artery stenosis
Name 5 ways in which Angiotensin II increases blood volume and blood volume
Arteries (smooth muscle)—>vasoconstriction
Adrenal Cortex; aldosterone release; reabsorption of Na+
SNS; NA release
Brain; stimulates ADH, Vasopressin, thirst
Kidney; Na+ reabsorption in renal tubule
Heart; increases contractility; ventricular hypertrophy
How do calcium channel blockers work?
-bind to specific alpha subunit of L-type calcium channel, reducing cellular calcium entry
Name the 3 main groups of CCB’s and which are anti-arrhythmics?
1) Dihydropines e.g. Felodipine and Amlodipine
2) Benzothiazepines ( anti-arrhythmic)
3) Phenylalkylamines e..g Verapamil anti-arrhythmic
Describe the PK of CCB’s
good oral absorption
protein bound>90%
metabolised by the liver ( many by CYP3A4)
Give 5 adverse effects of CCB’s
SNS activation; tachycardia and palpitations Flushing, sweating Throbbing headache Oedema Gingival hyperplasia( rare)
Describe the effect of CCB’s on vessels?
Vasodilates peripheral, coronary and pulmonary arteries
NO significant effect on veins
Short acting dihydropyridines –> baroreflex mediated tachycardia
How do thiazide diuretics work?
reduce distal sodium tubular reabsorption
sustained action
blood pressure reduction
How do thiazides reduce blood pressure?
act in DCT on Na/Cl transporter
initial blood volume decrease
later; TPR falls
dose-blood pressure response curve flat ie ALL OR NOTHING
Name 5 side effects of bendroflumethiazide
HYPOKALAEMIA Increased uric acid and urea acid levels Impaired glucose tolerance Cholesterol and TG levels increased Activates RAAS
Describe treatment for HTN under 55 yrs?
ACE inhibitor or ARB then A+CCB then A+ CCB+diuretic
Describe HTN treatment if over 55 yrs and black
C
then
C+A or D
A+C+D
How would you treat resistant hypertension?
A+C+D
consider spironolactone or an alpha or beta blocker
What is a hypertensive emergency vs urgency?
Urgency>180/120
Emergency> 200/130
What complications arise from malignant hypertension?
Pulmonary oedema
Renal failure
Aortic dissection
Papilloedema
How does NO cause rapid vasodilation?
causes rapid vasodilation–>decreased preload–> reduces EDV–> reduces SV–> Reduces BP
How is rapid reduction in BP achieved?
IV THERAPIES
for GTN/ Sodium nitroprusside
How does Sodium Nitroprusside work for malignant HTN?
releases NO; a potent vasodilator of arterioles and venules
- IV use with powerful rapid onset and offset
- BREAKDOWN to CYANIDE; caution in liver disease, but renal excretion.
What is dangerous about Sodium Nitroprusside?
it gets broken to CYANIDE; therefore caution in liver disease but renal excretion
Avoid prolonged use >72 hours
How does GTN treat malignant HTN?
Glceryl Trinitrate
Exogenous source of NO
More powerful venous vasodilator than arterial
iV use with powerful rapid onset and offset
What are some side effects of GTN?
Headache
Hypotension
TACHYPHYLAXIS
What is tachyphylaxis and where is it seen?
seen as a side effect of GTN
Reduced efficacy due to tolerance after approx 48 hours
Name 3 generals symptoms of HEART failure
breathlessness
ankle swelling
fatigue
Give 5 investigative signs of HF
Cardiomegaly Third heart sound Cardiac murmurs ECHO abnormalities RAISED NT-proBNP
Give 4 causes of LHF
mitral and aortic valve stenosis
Coronary Heart Disease (CHD)
Hypertension (HTN)
Cardiomyopathy
Give 3 causes of RHF
Intrinsic; RV infarction
Volume overload ( shunts; VSD or ASD/ pulmonary and tricuspid regurg)
Increased afterload
Give 4 causes of increased afterload in RHF
Left heart failure
Pulmonary Embolus (PE)
Chronic lung disease
Cor pulmonale
What type of heart failure is worse, systolic or diastolic?
DIASTOLIC; preserved ejection fraction
i.e. less volume pumped out per contraction
problem filling the heart
What are the 3 main principles for treating HF?
1) Treat signs and symptoms, improve QOL
2) Prevent hospital admissions
3) Reduce mortality
What is the main drug of choice for heart failure?
DIURETICS
loop diuretics mainly; for patient comfort ie reduce symptoms like oedema
Which 2 loop diuretics are mainly used in HF?
Furosemide
Bumetanide; alternative to furosemide
40 mg Furosemide= 1 mg po bumetanide
Describe 5 ADR’s of loop diuretics
hyponatraemia hypokalaemia postural hypotension syncope hyperuricaemia/gout
How is SYSTOLIC HF treated?
RAAS antagonists; ie ACE inhibitors, ARB’s and aldosterone antagonists
Beta-blockers
What is the significance of ABBAA
ACE inhibitor
Beta blocker
Aldosterone antagonist
In systolic HF, why do you need further therapy of an aldosterone antagonist in addition to an ARB or ACE inhibitor?
bc despite use of ARB or ACEi, you get aldosterone escape
there is still some aldosterone that is produced–> this causes endothelial dysfunction+ leads to myocardial fibrosis—> coronary events–> MI
How do aldosterone antagonists work and give 2 examples
block endothelial dysfunction and myocardial fibrosis that result from aldosterone escape therefore no coronary events
mild diuretic effect
e.g. Spironolactone, Eplerenone
How do beta blockers reduce myocardial oxygen demand?
1) Reduce heart rate and negative inotropic effect via Beta1 adrenorceptor to reduce CO
2) Reduce BP–> less afterload on heart
Give 4 physiological effects of Beta blockers
Reduce HR and negative inotropic effect to reduce CO
Reduce BP–> decreased afterload
Reduce mobilisation of glycogen
Negate unwanted effects of catecholamines
Name 3 BNP recommended beta blockers
BISOPROLOL; high beta1 selectivity
CARVEDILOL
NEBIVOLOL; B1 selective at low doses also NO potentiating–> also a vasodilator
How do Beta blockers aid HF?
Failing myocardium is dependent on HR so beta blockers aid this
Initiate at low does
Titrate SLOWLY
may have to alter concomitant meds e..g diuretic
What is IVABRADINE?
If (funny current) channel inhibitor at the SAN
reduces heart rate
ie slower upstroke of SAN potential
What is VASARTAN?
ARB/ Neprilysin inhibitor
NEPRILYSIN degrades BNP and bradykinin, both vasodilators
How to manage disease modifying therapies?
Titrate up to max possible doses ( start low)
Monitor HR, renal function and BP when uptitrating
Benefits of disease modifying therapies?
Improve symptoms and QOL
Improve ventricular function
Reduce hospital admission and death
