4.2 Hypertension and Heart Failure Flashcards
What is the consequence of higher blood pressure causing increased arterial thickening?
Smooth muscle cell hypertrophy
Accumulation of vascular matrix
What BP defines hypertension?
140/90mmHg
What is primary/essential hypertension?
High BP without any single evident cause
90% patients
What is secondary hypertension?
High BP with a discrete, identifiable underlying cause
What is grade 1 hypertension?
140/90
Mild
What is grade 2 hypertension?
160/100
Moderate
What is grade 3 hypertension?
180/110
Severe
Lifestyle therapy for hypertension
Patient education Maintain normal body weight (BMI 20-25) Reduce salt intake <6g/day Limit alcohol Exercise Fruit and veg Eat less fat
What is the first line pharmacological therapy for hypertension?
ACE inhibitor/Angiotensin receptor blocker
Calcium channel blocker
Diuretics
A C D
How do ACE inhibitors work?
Prevent generation of AngII
Potentiates action of bradykinin
Less vasoconstriction, less aldosterone release so less salt and water retention, less sympathetic activity
Name some ACE inhibitors
lisinopril
ramipril
What is the main side effect of ACE inhibitors? Why?
Dry cough
Bradykinin accumulates in the lung causing irritation
What are some important but less common side effects of ACE inhibitors?
Angio-oedema
Renal failure incl renal artery stenosis
Hyperkalaemia
Name two angiotensin receptor blockers
Losartan
Candesartan
How do angiotensin receptor blockers work?
Bind to angiotensin AT1 receptor (blocking effects of AngII)
Inhibits vasoconstriction and aldosterone stimulation caused by AngII
What is the difference between angiotensin receptor blockers and ACE inhibitors in terms of side effects?
No effect on bradykinin
Well tolerated with few side effects because doesn’t cause a cough
What are some important side effects of angiotensin receptor blockers?
Renal failure
Hyperkalaemia
How do calcium channel blockers work?
Bind to specific alpha subunit of L-type calcium channel
Reduces cellular calcium entry
What are the three main groups of calcium channel blockers?
Dihydropyridines - nifedipine, amlodipine
Benzotthiazepines - diltiazem
Phenylalkylamines - verapamil
What do calcium channel blockers do?
Vasodilate peripheral, coronary and pulmonary arteries
No significant effect on veins
What does verapamil do?
Depresses SAN and slows AV conduction
What are some properties of calcium channel blockers dihydropyridines? e.g. amlodipine
Good oral absorption
Protein bound >90%
Metabolised by the liver
Few have active metabolites
What are some side effects of dihydropyridines?
Sympathetic nervous system activation leading to tachycardia and palpitations
Flushing, sweating, throbbing headache
Oedema e.g. ankle swelling
Gingival hyperplasia
What are some properties of phenylalkylamines? e.g. verapamil
Impedes calcium transport across the myocardial and vascular smooth muscle cell membrane
Class IV prolongs AP and RP
Peripheral vasodilation
Reduction in cardiac preload and myocardial contractility
Adverse effects of phenylalkylamines?
Constipation
Bradycardia
Reduce myocrdial contractility as negative inotrope which can worsen HF
What are some properties of benzothiazepines? e.g. diltiazem
Impedes calcium transport across myocardial and vascular SM cell membrane
Prolonges AP and RP
Peripheral vasodilation and reduction in preload and contractility
Adverse effects of benzothiazepines
Bradycardia
Less negative inotropic effect than verapamil
Would you give diltiazem or verapamil to a patient with angina or heart failure?
Diltiazem
Less negative inotropic effect
What do thiazides/thiazide like diuretics do?
Reduce distal tubular sodium reabsorption
What is the mechanism of blood pressure reduction when using thiazides?
Complex
Initial blood volume decrease
Later TPR falls
What does the dose-blood pressure response curve look like for thiazides?
Flat
What are some adverse effects of thiazides?
Hypokalaemia Increased urea/uric acid Impaired glucose tolerance Increased cholesterol an TG Activates RAAS
Dirty drug
Name an alpha blocker
Doxazosin
Name some properties of alpha blockers
Selective antagonists at post synaptic a1 adrenoceptors
Antagonise the contractile effects of NA on vascular SM
= reduce peripheral vascular resistance
What are some adverse effects of alpha blockers?
Postural hypotension (more effect in upright position)
Headache and fatigue
Oedema
Why are beta blockers useful for high blood pressure?
Reduce HR and CO
Inhibit renin release (less RAAS)
What are some adverse effects of beta blockers?
Lethargy, impaired concentration Reduced exercise tolerance Bradycardia Raynauds Impaired glucose tolerance
What is a contraindication for beta blockers?
Asthma
But is safe for COPD
What is aliskiren?
Direct renin inhibitor
What does aliskiren do?
Binds to a pocket in renin which blocks the cleavage of angiotensinogen to Ang I
(Prevents breakdown of angiotensinogen)
How does aliskiren work to lower BP?
Reduces plasma renin activity
Vasodilatory
BP reduction
How do centrally acting agents lower blood pressure?
methyldopa, clonidine, moxonidine
Reduce sympathetic output
When is methldopa commonly used?
To treat hypertension in pregnancy
Name some side effects on centrally acting agents to lower BP? Why do they cause these effects?
Tiredness/lethargy
Depression
Because work in the brain
What is a contraindication for thiazides?
Gout
What is a contraindication for ACE inhibitors and ARBs?
Pregnancy
Renovascular hypertension
What is the aetiology of HF?
Ischaemic Heart Disease
Hypertension
Cardiomyopathies (alcohol, chemo, iron overload)
Valve disease
What is prognosis after MI related to?
Inversely related to amount of LV damage/dysfunction
What lifestyle modifications can be made to manage HF?
Reduce salt
Decrease alcohol
Increase aerobic exercise
Decrease BP
What drugs could be prescribed to treat HF?
ACE inhibitor/ARB Beta blocker Spironolactone Ivabradine (Funny channel receptor causing bradycardia) Sacubitril (increases natriuresis)
nitratesm digoxin, inotropes, phosphodiesterase inhibitors)
What are the physiological effects of beta blockers?
Reduce HR Reduce BP due to reduced CO Reduces myocardial O2 demand Reduced mobilisation of glycogen Negate unwanted effects of catecholamines
Why must you be careful with giving b blockers in HF?
The failing myocardium may be dependent on HR
