Essential hypertension Flashcards
What is hypertension?
sustained elevation of systolic and diastolic blood pressure (> 140/90 mmHg)
What are the causes of hypertension?
Causes:
• primary (idiopathic/essential)
o No identifiable cause
• secondary: o renal disease (salt/H2O imbalance) o adrenal tumours (aldosterone) o aortic coarctation (narrowing of aorta) o Steroids, Rx
What are some hypertension related diseases?
Cerebrovascular
• Infarction: thrombotic – will cause ischaemic damage within the cerebral vessels
Cardiac
• Angina/MI
• CHF (congestive heart failure)
• Sudden death
Renal
• Chronic renal failure
• End stage renal disease
Retinopathy
• Sclerosis/Arterial
• Haemorrhage/Exudate
Large artery disease
• Carotid artery stenosis
How does hypertension cause organ damage in the blood vessels?
Blood vessels themselves undergo atheroma and aneurysm formation in large vessels, elastic reduplication in small vessels due to increased blood pressure
How does hypertension cause organ damage in the heart?
left ventricular hypertrophy, left heart failure (LHF).
How does hypertension cause organ damage in the lungs?
pulmonary oedema due to LHF
How does hypertension cause organ damage in the kidney?
nephrosclerosis, renal failure
How does hypertension cause organ damage in the eye?
retinal capillary damage, haemorrhages, exudates.
How does hypertension cause organ damage in the brain?
microaneurysms and stroke, ischaemic cortical atrophy/ dementia
What is 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, can lead to heart failure
How can a hypertensive patient experience massive intracerebral haemorrhage?
Massive intracerebral haemorrhage due to ruptured microaneurysm in the hypertensive patient
What affects blood pressure?
Cardiac output and the peripheral resistance
- CO x TPR = BP
What can high blood pressure arise from?
- Increased ECFV (extracellular fluid volume) – venous return to the heart can affect it
- Increased production of vasoconstrictor agents
- Reduction in production of vasodilator agents
What are some of the factors to be considered when diagnosing hypertension?
- BP cut off value (Usual value >140 and/or > 90 mmHg)
- Age (increases with age)
- Ethnic group (e.g. more common in African Americans
What are the causes of hypertension?
Causes of essential hypertension is still not known but genetic and environmental factors are believed to be important
What are important genetic/environmental factors for essential (primary) hypertension?
• Increased activity of hormonal system such as :
o Sympathetic nervous system (SNS)
o 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
- Defects in renal sodium handling
Why is treatment of hypertension important?
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%
What are the goals of antihypertensive therapy?
- Adequate Blood Pressure Control (< 140/90 mmHg)
- Prevention of Target Organ Damage
- Controlling other cardiovascular risk factors
- No detrimental metabolic side-effects
Why is the classification of hypertension important?
It can impact on the care pathway
What are the treatments and management for hypertension?
- Nonpharmacological (Life-style modification)
- Pharmacological treatment
- Surgical e.g. for Conn’s syndrome (adrenal gland increases in aldosterone)
What are the targets for life-style management for hypertension?
- Maintain normal weight (BMI 20-25%): can reduce by 1-2 mmHg/Kg
- ↓ Salt intake (≤ 100 mmol/day = 6 g NaCl): can reduce by 2-8 mmHg
- ↓ Alcohol intake (≤ 3 u/day men, ≤ 2 u/day women): can reduce by 2-4 mmHg
- Increase Fruits & vegetables intake (≥ 5 portions/day): can reduce by 8-14 mmHg
- Increase Regular exercise (≥ 30 min/day x 3 days/wk): can reduce by 4-9 mmHg
What are the pharmacological treatments/major classes of antihypertensive drugs?
- Renin inhibitors
- ACE inhibitors
- Angiotensin II receptor blockers
- Calcium channel antagonists
- Diuretics (loop diuretics, thiazides, potassium sparing)
- Adrenergic (a1 /b1) receptor antagonists
- Centrally acting a2 receptor agonists (rarely used for essential e.g. pregnancy)
- Other vasodilators
Some key issues to consider in selecting drug therapy?
- Essential vs secondary hypertension
- Evidence of efficacy
- Side effects of drug
- Drug interactions
- Individual demographics
- Coexisting diseases
- Quality of life
- Economic considerations
What drugs are prescribed to under 55s?
- 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
What drugs are prescribed to over 55s/Caribbean/African patients?
- Ca channel blocker prescribed first because limited activity of drugs against the RAAS pathway
- Combined with diuretic if it doesn’t work
Examples of inhibitors of the renin-angiotensin system?
- Renin inhibitors (rarely used) e.g. Aliskiren (risk of stroke)
- ACE inhibitors (e.g. enalapril, ramipril)
When should RAAS inhibitors not be used?
During pregnancy
Why are RAAS inhibitors used for primary hypertension?
RAAS causes vasoconstriction and aldosterone secretion - causes increase in BP
RAAS inhibitors intervene and prevent vasoconstriction and aldosterone secretion
How do calcium channel blockers treat hypertension?
- Increase vasodilation
* By decreasing Ca influx – inhibition of the myosin light chain kinase
What are the different types of Calcium channels blockers?
• Divided into 2 classes: Non-dihydropyridines and dihydropyridines
Which calcium channel blockers are usually use for arrhythmias?
Non-dihydropyridines are usually used for arrhythmias
What is the main effect of diuretics?
Increase in sodium and water excretion (but also direct effects on VSM tone)
What are the different classes of diurectics?
- Loop diuretics
- Thiazides
- Potassium sparing –
How do loop diuretics act?
act on Na/Cl transporter in the thick ascending limb, inhibit sodium reabsorption into the epithelial cell and it’s lost through urine
How do thiazides act?
most commonly used, act on Na/CL transporter to prevent Na reabsorption
How do potassium-sparing diuretics act?
antagonises the aldosterone receptor to inhibit Na reabsorption in the collecting ducts, less Na/K transporter activity
What are the side effects of diuretics?
- Hypokalaemia (loop and thiazide diuretics, but not K+ sparing diuretics)
- Lipid abnormalities
- Glucose intolerance/Hyperglycemia
What are the pharmacological targets for drugs acting on the sympathetic system and adrenergic receptors?
- Centrally acting agents
- Ganglion blockers
- Post ganglionic sympathetic neuron blocker
- Adrenoceptor blocker
How do centrally acting agents work?
they’re a2 selective agonists
examples: methyldopa
- stimulates adrenoceptors in the brain stem and induces peripheral sympathoinhibition (vasodilation), reduces elevated BP and HR
How do ganglion blockers work?
They’re nAChR (nicotinic acetylcholine receptor) antagonists
examples: Trimethaphan
How do postganglionic sypmathetic neuron blockers work?
They block neurotransmission
Example: Reserpine
How do adrenoceptor blockers work?
alpha and beta receptor antagonists
- blocking the alpha receptors: relaxes the vascular smooth muscles (example: prazosin)
- blocking the beta receptors: reduces cardiac output and inhibits renin release (examples: atenolol)
What are the (10) side effects for beta blockers?
- 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
What are some other vasodilators used for hypertension?
- Nitrovasodilators
- K+ channel openers/agonists
Examples of nitrovasodilators and what is their mechanism?
Drugs: Nitroprusside
(Less frequently used, replaced by newer agents)
Mechanism of action:
• NO “donors”/NO enhancing effect
• Increase activation of soluble guanylate cyclase activity
• Increase in [cyclic GMP]
• Reduction in voltage-dependent Ca2+ channel activity
• Reduction in [Ca2+]
• Increased relaxation
• Inhibit myosin light chain kinase activity – reduce contractions
Examples of K+ channel openers/agonists and what is their mechanism?
• Drugs: Minoxidil (severe hypertension)
Mechanism of action:
• Cause vascular smooth muscle hyperpolarization
• Reduction in voltage-dependent Ca2+ channel activity
• Reduction in [Ca2+]i
• Increased relaxation
