Session 3: Hypertension & Heart Failure Flashcards
Explain how activation of beta1-adrenoceptors on the heart cause increase in BP.
Increased inotropy in heart -> increased CO -> increased BP
Explain how activation of alpha1 adrenoceptors on smooth muscle lead to increased BP.
Increased venous return and increased peripheral resistance via vasoconstriction -> increased BP
Explain how activation of b1 adrenoceptors on kidney lead to increased BP.
Increased production of renin -> angiotensin II -> increased peripheral resistance via vasoconstriction -> increased BP
How does radius of blood vessel relate to resistance and mean arterial pressure.
A decreased radius leads to increased resistance to flow.
This explains why vasoconstriction causes increased peripheral resistance and increased BP.
NICE guidelines to define hypertension.
140/90 mmHg
Explain how to make a clinical diagnosis of hypertension.
Sitting relaxed and arm is supported.
Test both arms. If there is a >15 mmHg difference then repeat measurement and use the arm with a higher reading.
Can do measurements over period of visits +/- ABPM/HBPM
Assess CVD risk and end organ damage.
Stage 1 hypertension.
140/90 minimum
Subsequent ABPM daytime average or HBPM average BP ranging from 135/85 - 149/94
Stage 2 hypertension.
160/100 mg or higher
Subsequent ABPM daytime average or HBPM average BP of 150/95 or higher.
Stage 3/Severe Hypertension
Clinic systolic BP of 180 mmHg or higher
or
Clinic diastolic BP of 120 mmHg or higher
What is prehypertension?
>120/80<140/90 mmHg
Interventions in prehypertension.
Promotion of regular exercise
Diet
Reduction in stress and increased relaxation
Limit alcohol
Limit caffeine
Smoking cessation
Limit dietary sodium
Primary hypertension therapeutic agents
Ace inhibitors
Angiotensin receptor blockers (AT1)
Calcium channel blockers (CCBs)
Diuretics (thiazide and thiazide-like)
Other agents
Where can ACE be found?
Luminal surface of capillary endothelial cells predominantly in lungs.
Briefly explain how ACE inhibitors work.
They inhibit the conversion of angiotensin I to angiotensin II (the active form) by ACE.
What does a reduction in angiotensin-II cause?
Vasodilation (lower afterload)
Reduction in aldosterone release (More Na+ and H2O excreted)
Reduced ADH release (More H2O excreted + less vasoconstriction)
Reduced cell growth and proliferation
Can angiotensin I be converted into angiotensin II without ACE?
Yes it can, via chymases.
Give example of ACE inhibitors.
Lisinopril
Ramipril
Explain ACE inhibitors interaction with bradykinin.
ACE inhibitors inhibit the degradation of bradykinin causing an increase in bradykinin.
ACEi therefore potentiates bradykinin.
Functions of bradykinin.
Vasodilatory effect via NOS/NO and PGI2
Side-effects of ACEi.
Hypotension
Dry cough
Hyperkalaemia (low aldosterone leading to increased K+)
Renal failure
Angioedema
When should you not give ACEi?
Renal artery stenosis
Acute kidney injury
Pregnancy
Breastfeeding
CKD
Give examples drugs with important interactions with ACEi and when you should be wary of their effects.
K+ sparing drugs
NSAIDs
Other anti-hypertensive agents
Why should you not give ACEi in renal artery stenosis?
Because in renal artery stenosis there is a requirement of efferent arteriole to be able to constrict.
ACEi would dilate the efferent arteriole.
In which people should you not give ACEi?
Black African population
African-Carribean population
Age >55
Why should you not give ACEi in Black African or African - Carribean population?
Because their are more sensitive to bradykinin so the ACEi will have an increased effect.
This can lead to life-threatening angioedema.
What are angiotensin II receptor blockers also called?
ARBs
Angiotensin II blockers
AT1-receptor blockers.
Give examples of ARBs
Candesartan
Losartan
Explain the difference between ARBs and ACEi.
In ARBs you will still have angiotensin II but ARBs block AT1 receptors and inhibit the action of Ang-II mediated vasoconstriction.
There is also no production of bradykinin meaning no dry cough and angioedema.
It is more effective in high-renin hypertensives as Ang-II can still be produced by chymases.
When should you not give ARBs?
Renal artery stenosis
Acute kidney injury
Pregnancy
Breastfeeding
CKD
Give examples of drugs with important interactions with ARBs.
K+ sparing drugs
NSAIDs
Other antihypertensive agents.
Explain action and location of L-type calcium channels.
LTCCs allow influx of Ca2+ into cells. They are VOCCs.
They can be found throughout the body including vascular smooth muscle and cardiac myocytes + SA node and AV node.
Give the subclasses of CCBs.
Dihydropyridines
Non-dihydropyridines
Subclasses of non-dihydropyridines.
Phenylaklylamines
Benzothiazapines
Explain the action of dihydropyridines.
Selective for peripheral vasculature and will not have much of chronotropic and inotropic effect as it does not affect LTCCs on cardiomyocytes, AV node and SA node.
They will block calcium channel and prevent influx of Ca2+. This leads to inhibition of vasoconstriction and reduced peripheral resistance.
3 classes of CC interact with different sites on alpha1 subunit of VOCC. This means there is a selectivity for vascular smooth muscle or myocardium.
Explain the action of phenylalkylamines.
Depresses SA node and slows AV conduction leading to lower inotropy.
Prolongs the action potential/effective refractory.
Less peripheral vasodilation, neg. chronotropic and inotropic.
Explain the action of benzothiazapines.
Sits in the middle and blocks both cardiac activity as well as vascular.
What is the first line CCB for hypertension?
Dihydropyridines.
What is the primary choice of antihypertensive in low renin patients?
CCBs
Examples of dihydropyridines.
Amlodipine
Nifedipine
Nimodipine
How does amlodipine differ to other dihydropyridine class drugs?
It has a long half life whereas other tned to have a shorter.
Selectivity for nimodipine.
For cerebral vasculature meaning it is effective in prevention of subarachnoid haemorrhage.
Side effects of dihydropyridines class.
Ankle swelling
Flushing
Headaches
All due to vasodilation
Palpitations due to compensatory tachycardia.
Diseases when to be wary of dihydropyridines.
Unstable angina
Severe aortic stenosis
Interactions of dihydropyridines with other drugs.
Amlodipine + simvastatin (causing increased effect of statin)
Other anti-hypertensive agents.
What are phenylalkyamines used for?
Arrhythmia, angina and hypertension
Side effects of phenylalkylamines.
Constipation
Bradycardia
Heart block
Cardiac failure
Diseases when to be wary of phenylalkylamines.
Poor LV function
AV nodal conduction delay
Interactions of phenylalkylamines with other drugs.
Beta blockers
Other antihypertensives
Other antiarrhythmic agents
Example of benzothiazapines.
Diltiazem
Example of phenylalkylamines.
Verapamil
Action of thiazide and thiazide-like diuretics.
Inihibit Na+/Cl- co-transporter in DCT leading to lower Na+ in blood and H2O (i.e. more excretion)
When are thiazide and thiazide-like diuretics preferred instead of CCB.
In oedema
Side effects of thiazide and thiazide-like diuretics.
Hypokalaemia
Hyponatraemia
Hyperuricaemia
Arrhythmia
Increased glucose
Increased cholesterol and triglycerides
Diseases when to be wary of thiazide and thiazide-like diuretics.
Hypokalaemia
Hyponatraemia
Gout
Interactions of thiazide and thiazide-like diuretics with other drugs.
NSAIDs
K+ wasting drugs
Example of thiazide and thiazide-like drugs.
Bendroflumethiazide
Indapamide
In the case of BP not being controlled after step 3 i.e. resistant hypertension.
What is the first thing to consider?
Administering an aldosterone receptor antagonist like spironolactone.
Diseases when to be wary of spironolactone.
Hyperkalaemia
Addison’s
Interactions of spironolactone with other drugs.
K+ sparing drugs including ACEi and ARBs
If a patient has resistant hypertension and hyperkalaemia. What is given instead of spironolactone?
Alpha and beta-blockers
Centrally acting drugs like labetalol (in pregnancy and hypertensive emergency) to reduce the sympathetic outflow
Explain the action of beta-blockers.
Decrease sympathetic tone by blocking NAd and reducing myocardial contraction (reduced inotropy). This causes lower CO and decrease in renin secretion as well via beta-1.
Side-effects of beta-blockers.
Bronchospasm
Heart block
Raynaud’s
Lethargy
Impotence
Masking of tachycardia as a sign of insulin induced hypoglycaemia.
Diseases of when to be wary of beta-blockers.
Asthma and COPD
Haemodynamic instability
Hepatic failure
Interactions of beta-blockers and other drugs.
Non-dihydropyridine CCB like verapamil and diltiazem causing asystole
Examples of beta blockers.
Labetalol
Bisoprolol
Metoprolol
Action of alpha-blockers.
Selective antagonism of alpha-1 adrenoceptors to reduce peripheral vascular resistance and also has an effect in urinary tract including bladder neck and prostate.
They are also relatively safe in renal disease.
Explain why alpha1-blockers can be given in BPH
Tamsulosin can be given in BPH to relax IUS and also the muscles of the prostate in order to relieve the urinary retention and increase urine flow
Side-effects of alpha-blockers.
Dizziness
Syncope
Headache
Fatigue
Diseases of when to be wary of alpha-blockers
Postural hypertension
Interactions of alpha-blockers with other drugs.
Dihydropyridine CCBs causing oedema
Explain the self perpetuating spiral of heart failure.
Decreased arterial blood pressure as the CO goes down in HF.
Baroreceptors respond to the fall in BP and cause increase in sympathetic outflow.
Beta will cause increased renin, increased ATII, increased aldosterone, Na+ retention, vasoconstriction via ADH, and therefore more volume of blood and increased preload.
Alpha will cause vasoconstriction and increased afterload.
Both lead to an increased myocardial O2 demand and worsening of the heart failure.
First line treatment of heart failure.
Diuretics such as furosemide
Management of heart failure with reduced ejection fraction.
ACEi like lisonopril or ramipril
Beta-blocker like bisoprolol
Spironolactone
If intolerant to ACEi then consider ARBs like candesartan or losartan.
Aims of treatment of HFREF.
Reduction in symptoms such as dyspnoea, fatigue and oedema
Managed increased in exercise tolerance
Address arrhythmias, hyperlipidaemia and diabetes
Decreased mortality
Non-pharmacological management of HFREF.
Reduce salt intake
Liquid reduction
What can happen if you give spironolactone.
Refractory hyperaldosteronism that is adjunct to ACEi/ARB + diuretic
Why do ACEi and ARB precipitate hyperkalaemia?
Because they block the angiotensin II causing an increase in aldosterone.
Aldosterone is potassium wasting and if that doesn’t work then potassium will be spared and can cause hyperkalaemia.
Explain the two-pronged approach of to ACEi/ARB use in type 2 diabetes with hypertension.
In diabetic nephropathy and CKD with proteinuria there is less dilation of efferent glomerular arteriole.
Therefore a two pronged approach is used where ACEi and ARBs cause lower peripheral vascular resistance leading to lowered BP.
There is also dilation of efferent glomerular arteriole to cause reduced intraglomerular pressure which is good for T2DM.
Why are ACEis more beneficial in low-renin hypertensives than ARBs?
Because ACEis also causes vasodilation via bradykinin and doesn’t entirely rely on the RAAS system.
