S2: Treatment of Hypertension Flashcards
What is blood pressure?
Pressure exerted by blood on blood vessels
What is the short term and long term regulation of blood pressure?
Short term - Neural systems e.g. baroreceptors
Long term - Hormones, Na+ balance e.g. ECFV, degree of vasocontriction
What can cause high blood pressure?
- Increase in ECFV
- Increase in vasoconstrictor agents
- Reduction in vasodilator agents e.g. NO
Limits for hypertension
Hypertension is defined according to increased risk
· - 140/90 mmHg < 50 years
·- 160/95 mmHg for older individuals
What is hypertension a risk factor for?
· Stroke · Ischemic heart disease · Renal failure · Retinopathy · Left ventricular hypertrophy (increased afterload) Heart failure
What is isolated systolic hypertension?
With age, there is reduced aorta compliance which increases pressure in aorta during ejection. This causes isolated systolic BP
- High systolic
- Normal Diastolic
Causes of secondary hypertension (identifiable cause)
· 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 e.g. contraceptive pill
· Pregnancy e.g. pre-eclampsia
Monogenic genetic diseases e.g. Liddle’s
Risk fir essential hypertension (no known cause)
- Prevalent in urban based populations
Genetic pre-disposition and environments factors are proposed to cause essential hypertension through many mechanisms
· 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
Ethnicity, e.g. more common in Afro-Caribbean groups
What consequences does reduction in BP reduce?
· 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 goals in anti-hypertensive treatment?
· Adequate blood pressure control - < 140/90 mmHg, alter relative risk
· Prevention of target organ damage
Controlling other cardiovascular risk factors
What are the three main treatment pathways?
· Non-pharmacological, e.g. Life-style modifications
· Pharmacological treatment
Surgical, e.g. Conn’s syndrome
List some lifestyle changes that can help manage hypertension
- Quit smoking
- Weight control - high fat foods
- Eat less salt
- Regular exercise
- Reduce alcohol intake
- Behavioural therapies e.g. CBT
What are the major classes of hypertensive drugs?
· ACE inhibitors · Angiotensin II receptor blockers · Diuretics · Drugs acting on Sympathetic Nervous System Vasodilators
What for ACE inhibitors and AT1 receptor blockers do?
Reduce RAAS system but in different ways
Give an example of ACE inhibitors
Enalapril
Give an example of AT1 Receptor Blockers
Losartan
Side effects/contraindications of ACE inhibitors caused by decreased Ang II effects
ACE is also an enzyme that breaks down bradykinin (inflammatory mediator) as well as converting Ang I to Ang II
- Cough (common) - so ACE inhibitor decreases bradykinin breakdown. This causes a dry cough due to small stimuluses causing inflammation as there is increased bradykin
- Angioderma (rare) - can prevent breathing if oedema is around face due to increased brakykinin
Side effects/contraindications of ACE inhibitors and AT1 Receptor blockers
- Hyperkalaemia (due to decreased aldosterone, Na+ reabsorption and hence decreased K+ excretion and it builds up)
- Contraindicated in pregnancy - foetal problems
- Contraindicated in renal stenosis as Ang II causes vasoconstriction (decreased efferent renal arteriole constriction and decreased pressure gradient across bowman’s capsule which decreases GFR)
What do diuretics do?
- Increase in sodium and water excretion
- Reduce blood volume - reduces CO - reduce BP (BP= CO x TPR)
3 types of diuretic
- Loop diuretics
- Thiazides
- Potassium sparing
Major side effects of diuretics
- Hypokalaemia (loop and thiazide diuretics but not K+ sparing diuretics
- Lipid abnormalities
- Glucose intolerance/hyperglycermia due to decrease in insulin release
What effect does stimulating the B1 and a1 receptors have?
B1 - increase HR and contractility - increase CO - increase BP
a1 -vasoconstriction - increase TPR - Increase BP
Name 3 type of drugs that decrease sympathetic activity
CNS: a2 adrenoreceptor agonists e.g. Clonidine (hypertensive crisis)
Ganglion blockers: Nicotinic blockers e.g. Trimethapan
Synaptic blockade: e.g. reserpine - reduces release of NA to try and reduce BP
Describe what a1 and B1 blockers do
· α1 blockers : relaxation of vascular smooth muscle, e.g. prazosin (hypertensive crisis)
β1 blockers : reduction in CO and renin release, e.g. atenolol
Give the mechanism of K+ channel openers
e.g. minoxidil, diazoxide
Vasodilators
- VGK channels open, K+ efflux
- VSM hyperpolarisation inside cell
- Reduction in VGCa2+ activity (further away from threshold to activate these)
- Reduction in [Ca2+] i
- Less MLCK
- increased relaxation
- Vasodilation
Give the mechanism of voltage dependent Ca2+ blockers
e.g. dihydropyridines (amlodipine)
Vasodilators
- Block VGCa2+ activity is VSMCs
- Reduction in [Ca] i
- Less MLCK activity
- Increased relaxation
- Vasodilation
Which is more vascular selective?
K+ channel openers
Voltage dependent Ca+ blockers
Voltage dependent Ca+ blockers
Problems with Voltage dependent Ca+ blockers
Constant decrease in BP affects baroreceptor reflex - reflex tachycardia and overtime threshold changes.
With increased vasodilation blood can also pool in extremities
What factors need to be taken into consideration when choosing a drug?
· Essential vs. secondary hypertension · Evidence of efficacy · Side effects of drug · Drug interactions · Individual demographics · Co-existing diseases · Quality of life · Economic considerations Complicated – so there are guidelines NICE – National Institute for Health and Clinical Excellence
