S4) Hypertension and Heart Failure Flashcards
What is the 1st line pharmacological therapy for treating hypertension in the UK?
- ACE inhibitors / ARBs
- Calcium channel blockers
- Diuretics
Which drug would one prescribe for the following patients presenting with hypertension:
- <55 y/o and not Afro-Caribbean
- > 55 y/o or any age Afro-Carribean
- < 55 y/o and not Afro-Caribbean – ACE inhibitor
- > 55 y/o or any age Afro-Carribean – Ca2+ channel blocker
(they have reduced renin
Describe the action of ACE inhibitors
Competitive inhibitors of Angiotensin Converting Enzyme:
- Reduce formation of angiotensin II
- Arteriole vasodilation → reduce peripheral resistance
- Reduce circulating aldosterone so less Na and K reabsorbed and urinate more
Provide two examples of ACE inhibitors
- Lisinopril
- Ramipril
Identify some important side effects of ACE inhibitors
- Dry cough (main) → unable to break down bradykinin
- Angio-oedema (rare, common in black patients)
- Renal failure (incl. renal artery stenosis)
- Hyperkalaemia as K isn’t excreted
Describe the action of ARBs
Bind to angiotensin AT1 receptor: (so inhibit angiotensin 11 at receptor)
- Inhibit vasoconstriction better than ACEi as they directly target the receptor
- Inhibit aldosterone stimulation
Provide two examples of ARBs
- Losartan
- Candesartan
Identify two important side effects of ARBs
- Renal failure
- Hyperkalaemia
they don’t cause dry cough as they don’t have any effect on bradykinin
Describe the action of CCBs
Bind to alpha subunit of L-type calcium channel, reducing cellular calcium entry into the heart and arteries :
- Ca causes heart to pump harder and faster - blocking means they can relax
- Vasodilates peripheral, coronary and pulmonary arteries
- No significant effect on veins
Identify the three main groups of CCBs and provide an example for each
- Dihydropyridines e.g. nifedipine, amlodipine
- Benzothiazepines e.g. diltiazem
- Phenylalkylamines e.g. verapamil
Describe the properties and adverse effects of Dihydropyridines (calcium channel blockers) e.g. amlodipine
- Properties: good oral absorption, protein bound > 90%, metabolised by the liver, good half life
- Adverse effects: oedema, SNS activation – tachycardia and palpitations, flushing, sweating
they
Describe the properties and adverse effects of Phenylalkylamines (calcium channel blockers) e.g. verapamil
- Properties: impedes calcium transport across the myocardial and vascular smooth muscle cell membrane, peripheral vasodilation, ↓ myocardial contractility
- Adverse effects: constipation, bradycardia, can worsen heart failure
Describe the properties and adverse effects of Benzothiazepines (calcium channel blockers) e.g. diltiazem
- Properties: impedes calcium transport across the myocardial and vascular smooth muscle cell membrane, peripheral vasodilation, ↓ myocardial contractility
- Adverse effects: bradycardia, can worsen heart failure
Describe the action of thiazide diuretics
Reduce distal tubular sodium reabsorption:
- Initial blood volume decrease
- Later, total peripheral resistance falls
Identify four adverse effects of thiazide diuretics
- Hypokalaemia (Na/K pump)
- Increased urea and uric acid levels
- Impaired glucose tolerance
- Increased cholesterol and triglyceride levels
Describe the actions of alpha blockers
Selective antagonism at post-synaptic α-1 adrenoceptors:
- Antagonise contractile effects of NA on vascular smooth muscle
- Reduce peripheral vascular resistance
- Benign effect on plasma lipids / glucose
Provide an example of an alpha blocker
Doxazosin
Identify 3 adverse effects of alpha blockers
- Postural hypotension
- Headache and fatigue
- Oedema
Describe the action of beta blockers
- Reduce HR and CO
- Inhibit renin release
- Initially TPR increases later falls to normal
Provide three examples of beta blockers
- Bisoprolol
- Atenolol
- Nebivolol
Identify five adverse effects of beta blockers
- Lethargy
- Reduced exercise tolerance
- Bradycardia
- Impaired glucose tolerance
- Contraindication – asthma
Provide three examples of centrally acting agents
- Methydopa
- Clonidine
- Moxonidine
Describe the action of the following centrally acting agents:
- Methydopa
- Clonidine
- Moxonidine
- Methydopa: converted to α-methyl-noradrenaline – a potent α2 adrenoceptor agonist
- Clonidine: direct pre-synaptic α2 adrenoceptor agonist
- Moxonidine: imidazoline I1 receptor agonist and some α2 agonist effect
Identify 2 adverse effects of centrally acting agents
- Tiredness/lethargy
- Depression
In four steps, describe the clinical management of heart failure
⇒ Correct underlying cause
⇒ Non-pharmacological measures
⇒ Pharmacological therapy – symptomatic improvement, delay progression of HF, reduce mortality
⇒ Treat complications / associated conditions / CV risk factors e.g. arrhythmias
What are the five main drugs used in the pharmacological management of heart failure?
- Diuretics
- ACE inhibitor
- ARB
- β-blocker
- Spironolactone
Describe the effects of beta blockers on heart failure
- Reduce HR (cardiac beta receptor + myocardial oxygen demand)
- Reduce BP (reduced CO + myocardial oxygen demand)
- Reduce mobilisation of glycogen
- Negate unwanted effects of catecholamines
what conditions that patients have mean they shouldn’t be prescribed ACEi and ARB
- renal artery stenosis (kidney already low perfused, ACE inhibitor will prevent more blood entering kidney)
- AKD
- Pregnancy
- idiopathic angioedema (ACIi)
who should you not prescribe Dilydropyridine to?
unstable angina, severe aortic stenosis
who should you not prescribe Phenylalkylamines to?
poor LV function and AV conduction delay as it prolongs the action potential
staging of hypertension
- STAGE 1: bp ranging from 140/90 to 159/99
- STAGE 2: 160/100 to 180/120
- STAGE 3: 180 or higher
what is the order of treatment for treating hypertension
how do ACEi help diabetes
- reduces diabetic neuropathy and CKD
- it dilates the efferent arteriole of the glomerulus so reduces proteinuria
- two pronged approach: reduces peripheral vascular resistance → vasodilation → reduced intraglomerular pressure
what to do if blood pressure isn’t controlled after prescribing both ACEi, ARB and CCB and thiazide like diuretic
- spironolactone - aldosterone receptor antagonist
- adverse effects: hyperkalemia, gynaecomastia (men grow breast)
- people to avoid: hyperkalemia, Addisons
if someone has high K then you can give them a and b blockers
what to do if blood pressure isn’t controlled after prescribing both ACEi, ARB and CCB and thiazide like diuretic
- spironolactone - aldosterone receptor antagonist
- adverse effects: hyperkalemia, gynaecomastia (men grow breast)
- people to avoid: hyperkalemia, Addisons
if someone has high K then you can give them a and b blockers
what is the last resort to treating someone with high blood pressure
B-adrenoceptor blockers
- decrease sympathetic tone so reduce myocardial contractility, also reduce renin secretion
- adverse effects: bronchospasm, heart block, cold hands, lethargy
- people to avoid: asthma, haemodynamic instability, hepatic failure
non pharmaceutical things to do to reduce blood pressure
- regular exercise
- balanced diet
- reduced stress
- reduce alcohol
- stop smoking
diagnosis of hypertension
- take blood pressure when sitting and standing
- AMBP - Ambulatory blood pressure (device you attach to measure Bp regularly)
- HBPM - home blood pressure is where you measure bp frequently
what is the pathophysiology of hypertension
- high Bp
- vascular changes / remodelling, thickening and hypertrophy
- increased vasoactive substances
- vascular remodelling due to salt sensitivity
- endothelial dysfunction and increased ROS
CAN lead to:
→ permanent and maintained hypertrophy
→ end organ damage
→ hypertensive heart disease (dilated cardiac failure)
what is the white coat effect
- when someone visits the doctor their Bp rises
what is the white coat effect
- when someone visits the doctor their Bp rises
target blood pressure
- <140/90 for under 80 including type 2 diabetes
- <150/90 over an including 80 yrs
- <135/85 type 1 diabetes
