Hypertension Flashcards
What is hypertension?
An elevation of systolic and/or diastolic blood pressure to the point where it increases the risk of CVD (more than 140/90 mmHg)
How does hypertensions damage the CV system?
- High pressure damages the endothelium of main arteries (aorta, coronary, renal, etc.) = promotes atherosclerosis
- Hypertension increases afterload (the force of LV needed to expel blood into aorta = cardiac hypertrophy and ischaemia
- In isolated, systolic hypertension, the fall in diastolic pressure may compromise coronary blood flow to the wall of LV
- Brain and kidney have high flow/low resistance systems = easily damaged microcirculation. High blood pressure = damaged microcirculation = renal failure/stroke
What are the 2 types of hypertension?
Midlife HT - caused by mechanisms that regulate BP are dysfunctional, it is thought to be either caused by a defect in Na+ excretion or neurohormonal abnormalities
Old-age HT - caused by age-related arterial stiffening = isolated systolic hypertension
How does the resistance in the microcirculation different in normotensive and hypertensive systems?
In normal vessels, the resistance increases in the microcirculation = pressure decreases from artery to vein
In HT, the resistance is high in all the vessels = there’s higher upstream pressure = less flow to the organs = less venous flow to the heart
What are the 2 types of midlife hypertension?
Primary - no identifiable cause in the patient (usually polygenetic predisposition and lifestyle influences)
Secondary - cause can be definitely identified in the patient (renal or endocrine problems, monogenic syndromes)
What are the 3 systems in the body that affect your blood pressure?
- Autonomic nervous system - baroreceptor reflex
- Renin-angiotensin-aldosterone system (RAAS) - kidneys and blood vessels
- Pressure natriuresis - kidneys
What does the ANS/baroreceptor reflex alter to affect blood pressure?
It regulates vascular tone (dilation/constriction) and cardiac output in the short term.
What does the RAAS alter to affect blood pressure?
Regulates renal function = indirectly stablising blood volume = vascular tone
What does the pressure natriuresis alter to affect blood pressure?
Regulates renal function = stablising blood volume
What are the main determinants of MABP?
Cardiac output - CVP (central venous pressure) and preload, blood volume (Na+ excretion)
Total peripheral resistance - arterial tone
According to Guyton, what are the mechanisms causing hypertension?
Due to an impairment of pressure natriuresis = decreases Na+ and water excretion.
BV increases = BP increases = TPR increases to bring BP down (autoregulation to maintain BP) = BV decreases but TPR is still high because of renal function impairment = BP remains high
What supports Guyton’s hypothesis?
Arterioles that bring blood into renal glomeruli are always narrowed in hypertensives = reduced pressure natriuresis = more BV and HT
Why do most drugs that are used against hypertension have natriuretic and vasodilating effects?
It targets Na+/water excretion and neurohormonal problems (as most HT in people are primary)
How does aortic stiffening cause isolated systolic hypertension?
Less elasticity of vessels = less capacity of vessels & less elastic recoil to support diastolic pressure = more pressure from the heart to pump it with more pressure
ACE inhibitors: mechanism of action, adverse effects, and contraindications
MoA - block the production of AT2 = lower AT2 levels = lower Na+ and H2O reabsorption & less ADH release = lower blood volume = lower blood pressure
AE - dry cough and angioedema (inihibition of bradykinin), hypotension, deterioration of renal function
CI - pregnancy, renal failure, bilateral renal stenosis
Why does dry cough and angioedema occur when taking ACE inhibitors?
ACE degrades bradykinin to an inactive peptide. If inihibitors are taken, it leads to cough and angioedema.
Angiotensin receptor blockers (losartan): mechanism of action, adverse effects, and contraindications
MoA - blocks type 1 AT2 receptors = lower AT2 efficacy = inhibits vascular SM contraction
AE - hypotension, deterioration of renal function, upper respiratory tract infections, dizziness, back pain
CI - similar to ACE inhibitors (pregnancy, renal failure, bilateral renal stenosis)
What is the ACE escape and its mechanism?
ACEI and ARBs taken = less AT2 is produced = more renin release as AT2 inhibits renin release = more AT1 produced = overcome the ability of the drugs to suppress ACE activity = less effective over time
Renin antagonist (aliskiren): mechanism of action, adverse effects, and contraindications
MoA - blocks binding of angiotensinogen to renin = prevents AT1 synthesis
AE - cough, angioedeme, hyperkalaemia
CI - similar to ACE inhibitors
Not widely used as it is not superior at lowering CV risk and causes more adverse effects in some groups
Calcium channel blockers (amplodipine, verapamil): mechanism of action, adverse effects, and contraindications
MoA - iinhibit constriction of arterioles by NA and AT2 by blocking Ca2+ channels = decreases TPR, non-selective CCBs also cause negative inotropy and chronotropy = reduce CO
AE - vascular: tachycardia, headache, peripheral oedema (typical vasodilator effects); non-selective: bradycardia, excessively negative inotropy
CI - heart failure, pregnancy
Why is it okay to combine a beta-blocker with amlodipine but not verapamil?
Verapamil is a selective CCB but have some effects on the ventricular muscle = affects vascular SM cells and cardiac cells = can cause negative chronotropic effects (similar to beta-blockers) = effect is pronounced and can cause great decrease in CO
Amlodipine is a selective CCB that only affects the vascular SM, not the cardiac cells
Thiazide-like diuretics (chlortalidone): mechanism of action, adverse effects, and contraindications
MoA - reduce Na+ reabsorption by blocking Na/Cl co-transporter in DCT = increase salt and water excretion = reduces BV and CO, TPR falls by unknown mechanism
AE - hypokalaemia, increased plasma cholesterol
CI - gout
How do thiazide-like diuretics cause hypokalaemia? How can this be prevented?
Na+ reabsorption in DCT is blocked = Na+ is more reabsorbed in the Na/K antiporter in the collecting duct = more Na+ back in the blood, more K+ out the blood
Prevent by using K+ sparing diuretic
Mineralcorticoid receptor (aldosterone) antagonists: mechanism of action, adverse effects, and contraindications
MoA - inihibits aldosterone = reduced Na+ reabsorption in CD, also reduce vascular stiffness
AE - hyperkalaema and gynecomastia
CI - hyperkalaemia, renal impairment
Beta1-adrenergic receptor blockers: mechanism of action, adverse effects, and contraindications
MoA - block B1 receptors in the heart = noradrenaline can’t bind = less CO; blocks B1 receptors on juxtaglomerular cells = reduce renin secretion = lower AT2 levels = vasodilation/lower blood volume
AE - bronchospasm (due to b2 receptor), cardiac depression, fatigue, slower HR and less CO & constrict vessels at the extremeties = tingling and coldness of extremities, sleep disturbances, hypoglycaemia
Alpha1-adrenergic blockers: mechanism of action, adverse effects, and contraindications
MoA - blocks a1 receptors from noradrenaline = vasodilation and reduced TPR
AE - orthostatic hypotension, ankle oedema, drowsiness
CI - mild heart failure, pre-existing orthostatic hypotension
Centrally acting antihypertensives: mechanism of action, adverse effects, and contraindications
Methyldopa - reduces firing os SNS nerves and inhibits noradrenaline production, can be used in pregnant women
K+ channel agonist (minoxidil): mechanism of action, adverse effects, and contraindications
MoA - opens K+ channels in vascular SM cells = K+ efflux = hyperpolarisation = voltage-gated Ca+ channels don’t open = no contraction
AE - tachycardia, oedema
Usually used with diuretic and b-blocker
