L8: Essential Hypertension

Question 1

How do you define hypertension?

Answer 1

An “artificial” concept i.e. a cut-off value applied to a risk continuum, the value can change and can be applied differently in different populations.

Question 2

Definition of hypertension

Answer 2

• Sustained elevation of systolic and diastolic blood pressure (> 140/90 mmHg)

Question 3

Causes of hypertension:

Answer 3

-Primary (idiopathic/essential): No identifiable cause

Secondary Hypertension, secondary to (can identify cause):
- renal disease (salt/H2O imbalance)
- adrenal tumours (aldosterone)
- aortic coarctation (narrowing of aorta)
- Steroids, Rx

Question 4

Hypertension-related end organ disease

Answer 4

Infarction: thrombotic = ischaemic damage within the cerebral vessels

Question 5

Examples of organ damage by hypertension

Answer 5

Question 6

What has happened here?

Answer 6

Hypertensive Heart Disease

= Increased load causes concentric left ventricular hypertrophy
(increase in cell and muscle size in the heart) –> causes weakening of the heart and reduced contractility = Hypertensive Heart Disease ->can lead to heart failure

Question 7

What has happened here?

Answer 7

Question 8

How is BP regulated?

Answer 8

Question 9

why must we understand factors that contribute to BP?

Answer 9

• To understand how BP drugs work

Question 10

How is high BP arised from?

Answer 10

Question 11

Essential Hypertension Prevalance + Cause

Answer 11

• unknown cause; ~ 90% of cases)
• Prevalence in urban-based populations increased by 20%

Question 12

Risk Factors of Essential Hypertension

Answer 12

Depends on:
- BP cut off value (Usual value >140 and/or > 90 mmHg)
- Age (increases with age)
- Ethnic group (e.g. more common in African Americans)

Question 13

Some potentially important factors for essential (primary) hypertension include:

Answer 13

Cause(s) of essential hypertension is still not known but genetic and environmental factors are believed to be important.

• Increased activity of hormonal system such as:
  -Sympathetic nervous system (SNS)
  -Renin-angiotensin-aldosterone system (RAA)
  -Obesity/ Insulin resistance – can lead to inflammatory changes
• Endothelial dysfunction – big impact on atherosclerosis development
  -Capillary rarefaction – decrease in density of vessels, can have impact on vascular resistance
  -Defect in vascular smooth muscle contraction/relaxation (vasodilator/vasoconstrictor agents)
  -Defects in renal sodium handling (altered kidney function)

Question 14

Why is treatment of hypertension important?

Answer 14

Reduction in blood pressure level reduces relative risk of consequences

A 5-mmHg reduction in diastolic BP for 5 years will:
- Reduce strokes by 42%
- Reduce MI by 16%
- Reduce vascular mortality by 21%

= significant reductions thus vital to reduce BP levels

Question 15

What are the goals of anti-hypertensive therapy

Answer 15

• Adequate Blood Pressure Control (< 140/90 mmHg) (sometimes difficult to do this)
• Prevention of Target Organ Damage
• Controlling other cardiovascular risk factors
• No detrimental metabolic side-effects

Question 16

Classification of Hypertension

Answer 16

This can impact care pathway (whether to use lifestyle measures or when to use antihypertensive drugs)

Question 17

Care pathways briefly by NHS

Answer 17

Question 18

Types of Hypertension treatment + Management

Answer 18

• Nonpharmacological (Life-style modification)
• Pharmacological treatment
• Surgical e.g. for Conn’s syndrome (adrenal gland increases in aldosterone)

Question 19

Targets for lifestyle measures

Answer 19

In red shows reduction in BP

For stage 1 patients + 2,3 patients (alongside their pharmacological treatments)

Question 20

Pharmacological treatment: major classes of antihypertensive drugs: (give examples of drugs)

Answer 20

• Renin inhibitors (not/rarely used)
• ACE inhibitors (first-line)
• Angiotensin II receptor blockers
• Calcium channel antagonists
• Diuretics (Na handling)(loop diuretics, thiazides, potassium sparing)
• Adrenergic (a1 /b1) receptor antagonists
• Drugs acting on sympathetic system
• Centrally acting a2 receptor agonists (rarely used for essential e.g. pregnancy)
• Other vasodilators (used for severe or resistant hypertension when other primary, first-line drugs are not effective.)

Question 21

Key issues to consider in selecting drug therapy

Answer 21

• Essential vs secondary hypertension
• Evidence of efficacy
• Side effects of drug
• Drug interactions
• Individual demographics
• Coexisting diseases
• Quality of life
• Economic considerations

Question 22

NICE guidelines regarding initiating antihypertensive treatment

Answer 22

If no sign of efficacy = step 2
still resistant = step 3
still resistant = step 4

Under 55: ace inhibtors/angiotensin receptor blocker
Ca channel blocker added if ACE inhibitor wasn’t effective
Drugs are usually added to the already existing prescription until one works

Over 55/ Caribbean/ African patient: Ca channel blocker prescribed first because limited activity of drugs against the RAAS pathway
Combined with diuretic if it doesn’t work

Question 23

RAAS system

Answer 23

Aldosterone section = increase BP + inhibit H20 loss

Question 24

Give examples of drugs that can be used to treat hypertension via targeting the renin-angiotensin system?

Answer 24

1. Renin inhibitors (rarely used) e.g. Aliskiren (risk of stroke)
2. ACE inhibitors (e.g. enalapril, ramipril)
   Some side effects & contraindications:
   - Hyperkaelemia
   - Dry cough: decrease quality of life - ACE in lung + it breaks down bradykinin (thus high levels when ACE inhibitor present = irritation -> cough; patients offered ATII antagonists instead)
   - Angioedema
   - Contraindicated in pregnancy
3. Angiotensin 2 receptor (type 1) antagonists e.g. losartan, valsartan

Question 25

What is the 2 families of calcium channel blockers + examples of drugs + their MOA?

Answer 25

• Increase vasodilation
• Divided into 2 classes (see diagram)
• By decreasing Ca influx – inhibition of the myosin light chain kinase
• Dihydropyridines: high selectively for smooth muscle cells
• Non-dihydropyridines are usually used for arrhythmias; predominately myocardium selective

Question 26

Diuretics MOA, classes + side effects

Answer 26

Main effects: Increase Na + H20 excretion (but also direct effects on VSM tone)

Main classes of diuretics:
- Loop diuretics: act on Na/Cl transporter in the thick ascending limb, inhibit Na reabsorption into epithelial cell; lost through urine
- Thiazides: most commonly used, act on Na/Cl transporter to prevent Na reabsorption
- Potassium sparing: antagonises the aldosterone receptor to inhibit Na reabsorption in the collecting ducts, less Na/K transporter activity

Major side effects:
- Hypokalaemia (loop and thiazide diuretics, but not K+ sparing diuretics)
- Lipid abnormalities
- Glucose intolerance/Hyperglycemia

Question 27

Drugs acting on sympathetic + adrenergic receptors

Answer 27

Adrenoreceptor blockers important

B blockers: These drugs are important in resistant hypertension + heart failure

Question 28

Major side effects of B blockers

Answer 28

• Acute bronchospasm – dangerous for asthma patients
• Bradycardia
• Raynaud’s syndrome (patients have reduced blood flow to periphery – fingers/toes) – patients who already have this need to be careful when taking the drugs
• Claudication (cramp in leg resulting from reduced blood flow)
• Increased triglycerides
• Decreased HDL
• Glucose intolerance
• Lethargy
• Nightmares
• Impotence

Question 29

Other vasodilator examples

Answer 29

Question 30

K+ Channel agonists/openers examples

Answer 30

Question 31

Indications and contra-indications for major classes of antihypertensive drugs

Answer 31

Shows what the drugs are usually used for