Hypertension And Heart Failure

Question 1

What is blood pressure?

Answer 1

Blood pressure provides a driving force to defuse organs with blood - it determines the tissue perfusion pressure.

It is not uniform throughout the body and, as result of the cardiac cycle, is cyclical.

Question 2

What is mean arterial pressure equal to?

Answer 2

MAP = CO X TPT

Question 3

What is CO equal to?

Answer 3

CO = SV x HR

Question 4

Describe the relationship between resistance and increased maBP

Answer 4

Smooth muscle tome changes TPR.

Vasoconstriction causes an increase in TPR and therefore an increase in BP.

Question 5

Why does elevated BP cause an increase in morbidity and mortality?

Answer 5

Leads to vascular changes inc. remodelling and thickening and hypertrophy.

Increase vasoactive substances inc. ET-1, NAD, angII

Vascular remodelling as direct result of local salt sensitivity

Hyperinsulinemia and hyperglycaemia - endothelial dysfunction and ROS cause decreased NO. Resulting in permanent and maintained medial hypertrophy of vasculature causing increased TPR and decreased compliance.

End organ damage (renal, peripheral vascular disease, aneurysm, vascular dementia, retinal disease)

LVH - dilated cardiac failure

All causing increasing morbidity and mortality.

Question 6

Why is the incidence of hypertension lower in women?

Answer 6

As they are protected until menopause (not sure why)

Question 7

Why do you treat HT even when it presents asymptoatically?

Answer 7

Because the risk of CHD and stroke increases.

Question 8

Define Hypertension

Answer 8

An elevation in blood pressure that is associated with an increase in risk of harm. .

Question 9

What level of BP defines hypertension?

Answer 9

Over 140/90

Question 10

How do you diagnose and treat HT?

Answer 10

Screen those at risk

Increase 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.

Question 11

What is the best practise for clinically diagnosing BP?

Answer 11

Measure BP while patient is sitting, relaxed and arm is supported.

Measure in both arms and if there is >20mmHg difference then repeat and use higher reading.

Question 12

What is stage 1 hypertension?

Answer 12

> 140/90 mmHg

Question 13

What is stage 2 hypertension?

Answer 13

> 160/100 mmHg

Question 14

What is severe hypertension?

Answer 14

> 180 mmHg systolic or > 100 mmgHg diastolic

Question 15

How does diabetes and renal change BP criteria?

Answer 15

Stage 1 = > 130/80

Question 16

What is prehypertension?

Answer 16

Elevated BP below stage 1 diagnoses with no end organ damage.

Question 17

What do you recommend for people in a prehypetensive stage?

Answer 17

Lifestyle changes:

Regular exercise

Healthy / balanced diet

Reduce stress and relaxation

Limit / reduce alcohol intake

Discourage excessive caffeine consumption

Smoking cessation

Reduction in dietary sodium

Question 18

What are the primary HT therapeutic agents?

Answer 18

Angiotensin converting enzyme (ACE) inhibitors
Angiotensin (AT1) receptor blockers (ARBs)
Calcium channel blockers (CCBs)
Diuretics
Others in specific circumstances

Question 19

How does ACE work?

Answer 19

ACE is present on the luminal surface of capillary endothelial cells, predominantly in the lungs.
ACE catalyses the conversion of Ang-I to Ang-II, a potent active vasoconstrictor.

Ang-II works through AT1 and AT2 receptors.

Question 20

How do ACE inhibitors work?

Answer 20

Limit conversion of AngI-AngII by inhibiting circulating and tissue ACE

So:
Vasodilation
Reduced aldosterone release
Reduced ADH release
Reduced cell growth and proliferation

All can contribute to antihypertensive effects.

Question 21

Give exampleof ACE inhibitors

Answer 21

Ramipril
Lisinopril
Enalapril
Captopril

Question 22

What are some common side effects of ACE inhibitors?

Answer 22

Dry cough (bradykinin)

Angiodema (more common in black people)

Renal failure (inc. renal artery stenosis)

Hyperkalaemia

Question 23

What is losartan?

Answer 23

An ARB (angiotensin receptor blocker)

Question 24

Describe how ARBs work

Answer 24

They directly target AT1 receptors so are more effective than ACEi at inhibiting Ang-II mediated vasoconstriction.

Question 25

Why no cough on ARBs?

Answer 25

As don’t make bradykinin because directly act onAT1 receptor. But, means less effective in low-renin hypertensives.

Question 26

What are the side effects of ARBs?

Answer 26

Renal failure | Hyperkalaemia

Question 27

Where are L-type calcium channels?

Answer 27

They are expressed through the body including: Vascular smooth muscle cells Cardiac myocytes

Question 28

How do CCBs work (broadly)?

Answer 28

LTCCs allow inward Ca2+ influx into cells via VOCCs. Large Ca flux into cell, further Ca from ST and activation of contractile proteins (actin and myosin). CCBs target Ca initiated smooth muscle contraction.

Question 29

What are the classes of CCBs?

Answer 29

Dihydropyridine Phenylalkylamines (non-dihydropyridine) Benzothiazapines (non-dihydropyridine)

Question 30

What are dihydropyridies class selective for?

Answer 30

Selective for vascular smooth muscle. They show little chronotropic or inotropic effects (first line CCB for HT)

Question 31

What do phenylalkamines do?

Answer 31

They depress SA node and slow AV conduction, they express negative inotropy.

Question 32

When are CCBs used?

Answer 32

They are the primary choice in low-renin hypertensives.

Question 33

What is amlodipine?

Answer 33

CCB (dihydropyridine) Nifedipine and nicardipine are also CCBs.

Question 34

What are the properties of dihydropyridines

Answer 34

Good oral absorption Protein bound >90% Metabolised by the liver Few have active metabolites

Question 35

What are the adverse effects of dihydropyridines?

Answer 35

Sympathetic nervous system activation -tachycardia (rare) Palpitations Flushing, sweating, throwing headache Oedema Amlodipine and simvastatin react.

Question 36

What is verapamil?

Answer 36

A phenylalkylamine

Question 37

Describe the action of phenylalkylamines

Answer 37

Impedes calcium transport across the myocardial and vascular smooth muscle cell membrane. Classic IV anti-arrhythmic agent / prolongs the AP / effective refractory period. Less peripheral vasodilation, negative chronotropic and inotropic effects. Arrhythmia, angina (hypertension)

Question 38

What are the adverse effects of phenylkylamines?

Answer 38

Constipation Risk of bradycardia Negative inotrope -can worse HF -additive with B blocker.

Question 39

What is diltiazem?

Answer 39

Benzothiazapine

Question 40

Describe the properties of benzothiazapines (diltiazem)

Answer 40

Impedes Ca transport across the myocardial and vascular smooth muscle cell membrane. Prolongs the action potential / effective refractory period Sits between amlodipine and verapamil in vascular and cardiac effects. Angina (hypertension)

Question 41

What are the adverse effects of diltiazem?

Answer 41

Risk of Bradycardia | Negative inotropic effect (but less than verapamil). Can worsen HF

Question 42

How do thiazide diuretics work?

Answer 42

Moderately potent, inhibit Na+ reabsorption in DCT. Diuresis resulting in lower blood and extracellular volume - low TPR Useful over CCBs in oedema. Long term effects mediated by sensitivity of VSM to vasoconstrictors Ca2+ - we think

Question 43

What are the adverse effects of thiazide diuretics?

Answer 43

Hypokalaemia Increased urea and uric acid levels Impaired glucose tolerance Cholesterol and triglyceride levels increased Activates RAAS

Question 44

What other therapeutic agents can treat hypertension?

Answer 44

alpha-adrenoreceptor blockers beta-adrenoreceptor blockers Spironolactone Amiloride (K+ sparing diuretic on DCT) Direct renin inhibitor (aliskirin) Other direct vasodilators e.g. nitrates (hypertensive emergency - I.V.) Centrally acting drugs - labetalol - reduce sympathetic outflow.

Question 45

What is spironolactone

Answer 45

Mineralcorticoid / aldosterone receptor antagonist

Question 46

What is labetalol?

Answer 46

A centrally acting drug that reduces sympathetic outflow.

Question 47

What is doxazosin?

Answer 47

alpha-adrenoreceptor antagonist.

Question 48

How do alpha-adrenoreceptors work?

Answer 48

Selective antagonism at post-synaptic a-1 adrenoreceptors and antagonise the contractile effects of noradrenaline on vascular smooth muscle. Reduces peripheral vascular resistance Benign effect on plasma lipids / glucose Safe in renal disease

Question 49

What a re the adverse effects of a-adrenoreceptor blockers?

Answer 49

Postural hypertension Headache and fatigue Oedema (especially if combined with dihydropyridine)

Question 50

What is bisoprolol?

Answer 50

Beta-adrenoreceptor blocker

Question 51

How do B blockers work?

Answer 51

Decrease sympathetic tone by blocking Nad and reducing myocardial contraction - Decrease CO (decrease renin secretion) affording antihypertensive effects.

Question 52

What are the adverse effects of B blockers?

Answer 52

``` Bronchoconstriction Tachycardia Lethargy and impaired concentration Reduced exercise tolerance Bradycardia Raynaud’s syndrome (cold hands) ```

Question 53

What is heart failure?

Answer 53

Abnormality in cardiac function which is responsible for the failure of the heart to pump blood at a rate commensurate with the requirements of metabolising tissues.

Question 54

What ate the symptoms of heart failure?

Answer 54

Firstly asymptomatic Exercise intolerance, breathlessness, fatigue

Question 55

Describe the aetiology of Herat failure

Answer 55

Usually cardiomyopathy Inherited: Congenital hypertrophic CM Arrhythmogenic RV CM ``` Acquired: Ischaemic cardiomyopathy Pressure overload Valve disease Infection / inflammation / alcohol ```

Question 56

Why is heart failure a self perpetuating spiral?

Answer 56

Because the physiological neurohormonal response in its attempt to compensate will eventually lead to further pathology.

Question 57

How do you manage HF?

Answer 57

Usually dealing with LV systolic dysfunction associated with reduced LV ejection fraction (<45%). Where there is preserved ejection fraction the optimal treatment is not clearly defined. Correct underlying cause (e.g. valve replacement) Non pharmacological - reduce salt, liquid reduction

Question 58

What are the aims of the treatment of heart failure?

Answer 58

Reduction in symptoms Managed increase in exercise tolerance Decreased mortality Address arrhythmias, hyperlipodaemia, diabetes

Question 59

What is almost always ued to treat HF?

Answer 59

Diuretics - furosemide This reduces symptoms but has almost no impact on survival.

Question 60

How are ACEi and ARBs used to treat HF?

Answer 60

Used in all grades of LV dysfunction. Low initial dose to reduce the risk a sudden rapid fall in BP, especially if already on diuretics. If ACEi not tolerated,ARBs may be used as they have a similar benefit.

Question 61

How is spironolactone used to treat HF?

Answer 61

Amazing benefits, used in all later stage HF patients. Use alongside ACEi and diuretic.

Question 62

When are B-blockers used to treat HF?

Answer 62

Recommended for all patients with CHF unless contraindicated or not tolerated. Introduced once ACEi or AT1 antagonists is initiated.

Question 63

How do B blockers work to treat HF?

Answer 63

Benefit is related to blunting of sympathetic influences especially on heart rate. Slower HR = longer diastolic filling period = better filling = more output. May also stabilise electrical condition - reducing arrhythmias. May blunt circulating RAAS directly inhibiting renin, but properly minor effect as already on ACEi Low initial dose which may cause transient worsening of symptoms.

Question 64

Why is a persistent dry cough a common side effect fo ACEi?

Answer 64

Bradykinin is a substate for ACE. ACE is kininase-II -breaks down kinins inc. BK. ACEi therefore make more bradykinin. So, it causes vasodilation via NOS/NO and PGI2 Causing a persistent dry cough.