Treatment of Hypertension Flashcards
How do we calculate BP?
BP = CO x TPR
What is the significance of BP?
Important for organ perfusion
How would we calculate blood flow?
Flow = Art. BP / TPR
What is blood pressure?
Pressure exerted by blood on blood vessels
What are the short term controls of BP?
Baroreceptors (neural systems)
What is the long term control of BP?
Vasoconstriction and ECFV
hormonal Na balance
What are the causes of High BP?
Increase in ECFV
Increase in vasoconstrictor agents
Reduction in vasodilator agents
How is hypertension defined as?
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?
Stroke Ischemic heart disease Renal failure Retinopathy Left ventricular hypertrophy Heart failure
What are the causes of secondary hypertension?
10 % of cases - Identifiable causes:
Renal diseases
- e.g. glomerulonephritis, diabetic nephropathy
Vascular causes
- e.g. renal artery stenosis
Hormonal abnormalities
- e.g. Conn’s syndrome, Cushing’s syndrome,
phaechromocytoma
Drugs
- contraceptive pill
Pregnancy
- pre-eclampsia
Monogenic genetic diseases
– Liddle’s syndrome
What are the causes of primary hypertension?
90% of cases
due to unknown cause
Prevalence in urban-based populations ~ 20%
Genetic pre-disposition and environmental factors thought to cause essential hypertension
What mechanisms are involved in essential hypertension?
Increased sympathetic nervous system (SNS)
Increased renin-angiotensin-aldosterone system (RAA)
Obesity / Insulin resistance
Endothelial dysfunction
Defect in vascular smooth muscle contraction
Defects in renal Na handling, increased salt intake
Age
What is the significance of treating hypertension?
Reduction in blood pressure level reduces relative risk of consequences 5 mmHg drop in diastolic BP for 5 yrs Reduce strokes by 42% Reduce heart attacks by 16% Reduce vascular mortality by 21%
What are the aims of anti-hypertensive treatments?
Adequate blood pressure control - < 140/90 mmHg, alter relative risk
Prevention of target organ damage
Controlling other cardiovascular risk factors
What are the 3 main treatment pathways for hypertension?
- Non-pharmacological, e.g. Life-style modifications
- Pharmacological treatment
- Surgical, e.g. Conn’s syndrome
What non-pharmacological treatments are there?
Lifestyle changes: Quit smoking Weight control Eat less salt Regular exercise Reduce alcohol intake Behavioural therapies
What are the major classes of anti-hypertensive drugs?
ACE inhibitors Angiotensin II receptor blockers Diuretics Drugs acting on Sympathetic Nervous System Vasodilators
How do ACE inhibitors (e.g. enalapril) and AT1 receptor blockers (iosartan) decrease BP?
ACE inhibitors prevent the converison of Ag I → Ag II
AT II antagonists block AT1 receptors to stop Ag II binding
- less vasoconstriction
- less aldosterone secretion
What are the effects of ACE inhibitors and AT1 antagonists?
decrease in vasoconstriction and aldosterone actions to reduce blood pressure
what are the side effects of ACEi?
Caused by ↓ Ang II effects
Cough (common) - ↓ bradykinin breakdown (non-compliance issue)
Angioedema (rare) - ↓ bradykinin breakdown (very serious, prevent breathing)
can cause fetal problems if taken during pregnancy
What are the side effects of ACEi/ARBs?
Hyperkalaemia
(Opposite to loop and thiazide diuretics)
Due to ↓ aldosterone, ↓ Na reabsorption and hence ↓ K excretion
How does renal stenosis affect ACEi?
↓ efferent renal arteriole constriction
↓ pressure gradient across bowman’s capsule → ↓ GFR
What is the effect of diuretics?
Increase in sodium and water excretion
Reduce blood volume → reduces CO → reduce BP (BP = CO x TPR)
Name examples of diuretics
Loop diuretics
Thiazides
Potassium-sparing
What are the major side effects of diuretics?
Hypokalaemia (Loop and thiazide diuretics but not K sparing diuretics)
Lipid abnormalities
Glucose intolerance/hyperglycemia
- ↓ insulin release
How does sympathetic nerves stimulation of CVS affect BP?
β1 – increase HR + contractility → increase CO → increase BP
α1 – vasoconstriction → TRP → increase BP
How can we decrease sympathetic activity?
CNS : α2 adrenoceptor agonists, e.g. Clonidine (Hypertensive crisis)
Ganglion blockers : NIC blockers, e.g. Trimethapan (hypertensive crisis)
Synaptic blockade : e.g. reserpine (old anti-hypertensive)
What adrenoceptor blockers are used for hypertension?
α1 blockers : relaxation of vascular smooth muscle,
e.g. prazosin (hypertensive crisis)
β1 blockers : reduction in CO and renin release, e.g. atenolol
What vasodilators do we use to treat hypertension?
K channel openers
Ca2+ channel blockers
Give examples of K+ channel openers
e.g. Minoxidil, Diazoxide
Explain the mechansim of action of K channel openers
- K channels open, K efflux
- Vascular smooth muscle hyperpolarization
- Reduction in voltage-gated Ca channel activity
- Reduction in [Ca]i
- Less MLCK activity → Increased relaxation →
vasodilatation
What Ca2+ channel blockers are there?
Voltage-dependent Ca2+ channel blockers
e.g. dihydropyridines (amlodipine)
More vascular selective
How do Ca2+ channel blockers work?
- Block voltage-gated Ca channel activity in VSMCs
- Reduction in [Ca]i
- Less MLCK activity → Increased relaxation →
Vasodilatation
What issues are to be taken into consideration in selecting drug therapy?
Essential vs. secondary hypertension Evidence of efficacy Side effects of drug Drug interactions Individual demographics Co-existing diseases Quality of life Economic considerations
What is NICE?
NICE – National Institute for Health and Clinical Excellence
