Treatment of hypertension Flashcards
what happens if BP is too low?
Poor perfusion of tissues/end organs
What happens if BP is too high?
-Poor perfusion too (excessive vasoconstriction ‘shutting off’ flow)
-Excessive afterload (opposing ejection of blood from heart)
-Damage to blood vessels – part of plaque formation
What is the definition of hypertension?
Hypertension is defined according to increased risk 140/90 mmHg < 50 years
160/95 mmHg for older individuals
What is hypertension a strong risk factor for?
Hypertension is a strong risk factor for:
Stroke, Ischemic heart disease, Renal failure, Retinopathy, Left ventricular hypertrophy, Heart failure
What are possible causes of secondary hypertension?
Hormonal abnormalities, e.g., Conn’s syndrome (excess aldosterone),
Cushing’s syndrome (excessive mineralocorticoids), phaeochromocytoma
(excessive release of adrenaline from adrenal gland tumor)
Genetic conditions – e.g., Liddle’s Disease (Increased Na/H2O
reabsorption)
Renal diseases
Vascular causes, e.g., renal artery stenosis
Drugs - contraceptive pill
Pregnancy - pre-eclampsia
What are possible mechanisms that cause essential hypertension?
Increased sympathetic nervous system
Increased renin-angiotensin-aldosterone system (RAAS)
Obesity / Insulin resistance
Endothelial dysfunction
Defect in vascular smooth muscle contraction
Defects in renal Na handling, increased salt intake
Age
Ethnicity
Why do we treat essential hypertension?
Reduction in blood pressure level reduces relative risk of consequences
What are the 2 main treatment pathways for essential hypertension?
-Non-pharmacological, e.g., Life-style modifications
-Pharmacological treatment
What are examples of non-pharmacological treatment for essential hypertension?
Quit smoking – What help is available?
Weight control – Can you name high / low fat foods?
Eat less salt – Can you name high / low salt foods?
Regular exercise – How much is sufficient?
Reduce alcohol intake – What are the recommended levels?
Behavioural therapies – What is CBT?
What are major classes of antihypertensive drugs?
-RAAS modulation
-Calcium channel blockers
-Diuretics
-Drugs acting on sympathetic nervous system
What are examples of RAAS modulation drugs?
ACE inhibitors (ACEi, e.g., enalapril)
and
Angiotensin II receptor blockers (ARB, e.g., losartan)
What are examples of calcium channel blockers?
Dihydropyridines (e.g., amlopidine)
What are examples of diuretics?
Loop, thiazides, K-Sparring
What are examples of drugs acting on sympathetic nervous system?
Brain, Autonomic ganglia, 1- and 1-adrenoceptor blockers
What do ACEi do?
ACEi reduce production of Ang II
What do ARB act as?
ARB as competitive antagonists at AT1
receptors, reducing effects of Ang II
What do both ACEi and ARB reduce and mediate?
Both drug types reduce Ang II-induced vasoconstriction and Ang II-mediated aldosterone actions
What are the side effect of ACEi?
Angiotensin-converting enzyme also
breaks down bradykinin – which is a substance associated with
inflammation that stimulates sensory nerves
So ACEi will decrease bradykinin breakdown
Can cause dry cough - non-compliance issue
Due to raised bradykinin levels stimulating sensory nerves
What is a very rare side effect of ACEi?
Causes angioedema (swelling under skin)
Often around lips
Can prevent breathing
What can be done if the patient is non-compliant in taking ACEi due to a dry cough?
Can often change to anti-hypertensive drug
What do calcium channel blockers do?
Voltage-dependent Ca2+ channel blockers
e.g., dihydropyridines (amlodipine)
Target VGCCs in Vascular smooth muscle cells
Vascular selective
What does a reduction in calcium concentration lead to?
Reduction in [Ca]i in VSMCs
Less Ca-CaM-MLCK activity
-Increased relaxation
-Vasodilatation
What are the side effects of Ca2+ channel blockers?
Increased heart rate – response to lowering BP
Headache/ankle swelling/flushing - excessive vasodilation
What are contraindications of Ca channel blockers?
Heart failure, as drug reduces ability of heart to contract
What do diuretics do?
These drugs increase
Na and H2O excretion from the kidneys
How does a reduced blood volume reduce BP?
Reduce blood volume → reduces CO →
reduce BP (BP = CO x TPR)
What effect does diuretics have on blood vessels?
Produces vasodilation
What are examples of loop diuretics?
furosemide
What are examples of thiazides?
Bendroflumethiazide
What are examples of K-sparing drugs?
Spironolactone
How does stimulation of beta 1 receptors in sympathetic nervous system increase BP?
Stimulate β1 – Increase HR and Contractility
→ Increase CO → Increase BP
How does stimulation of alpha 1 receptors in sympathetic nervous system increase BP?
Stimulate α1 – Vasoconstriction →
Increase TPR → Increase BP
What drugs decrease sympathethic activity through the CNS?
CNS : α2 adrenoceptor agonists, e.g., Clonidine (Hypertensive crisis)
What are example of alpha 1 blockers and what do they do?
relaxation of vascular smooth muscle,
e.g., prazosin (hypertensive crisis, drug-resistance hypertension)
What are examples of beta 1 blockers and what do they do?
reduction in CO and renin release, e.g., atenolol, bisoprolol
What guidelines are used when choosing a drug?
NICE guidelines
What is step 1, step 2 and step 3 in NICE guidelines for patients age<55 and not of black african or african-caribbean family origin?
Step 1:
-ACEi or ARB
Step 2:
-ACEi or ARB + Calcium channel blockers(CCB) or thiazide-like diuretic
Step 3:
-ACEi or ARB + CCB + thiazide-like diuretic
What is step 1. step 2 and step 3 in NICE guidelines for patients age 55 or over, or black african or african-caribbean family origin(any age)?
Step 1:
-CCB
Step 2:
-CCB + ACei or ARB or thiazide like diuretic
Step 3:
-ACEi or ARB + CCB + thiazide-like diuretic
