anti-hypertensives Flashcards
what is hypertension?
high blood pressure
what makes up the double circulatory system?
pulmonary and systemic circulation
what is systemic circulation?
it is the system that provides the functional blood supply for all body tissues
what is pulmonary circulation?
its the system made up of blood travelling to and from the lungs
what is bronchial circulation?
its complimentary to the pulmonary circulation and it supplies lung cells with oxygen and nutrients
what is the vascular system made up of?
endothelial cells
smooth muscle cells
fibroblasts
PVAT
what does blood pressure depend on?
peripheral vascular resistance
cardiac output
what is cardiac output?
its the amount of blood ejected by the heart each min
HR x stroke volume
what is peripheral vascular resistance?
its the resistance in the circulatory system
what factors affect arterial blood pressure?
stroke volume
heart rate
peripheral resistance
elastic vessels
blood volume
ventricular ejection
what factors affect systemic blood pressure?
autonomic nervous system
renin-angiotensin-system
local mediators released from the vascular endothelium such as NO
beta-1-adrenoceptors
vasoconstriction via alpha-1-adrenoceptors
stimulation of alpha-adrenoceptors - vasoconstriction
how do beta-1-adrenoceptors affect hypertension?
they increase cardiac contractility and heart rate therefore increasing cardiac output and blood pressure
what does vasoconstriction via alpha-1-adrenocptors cause?
it increases blood pressure and afterload on the heart
in a healthy heart, how is cardiac output maintained?
its maintained by beta-1-adrenoceptor stimulation and increased contractility
what does stimulation of alpha-adrenoceptors cause?
it causes an increase in venous return to the heart (preload) and increase in cardiac output and blood pressure
what are some examples of beta blockers?
atenolol and propranolol
what effects do beta blockers cause in the systemic nervous system?
they decrease cardiac output
reduce renin production (reduce angiotensin II)
can indirectly cause vasodilation of peripheral arteries
what are some examples of alpha blockers?
prazosin
what effects do alpha blockers cause in the systemic nervous system?
block post-synaptic alpha-1 adrenoceptors leading to the dilation of arteriolar resistance vessels and lower peripheral resistance
they dilate venous capacitance vessels reducing venous return and cardiac output
what are endothelium derived factors? (EDRFs)
they’re endogenous factors produced by endothelial cells released in response to various changes to normal physiological and pathophysiologic changes
they modulate vascualr smooth muscle and therefore vessel diameter
what are some examples of endothelium derived relaxing factors?
Nitric oxide (NO)
Prostacyclin (PGI2)
Hyperpolarising factor (EDHF)
what are the two types of endothelium derived factors?
EDRFs- endothelium derived relaxing factors
EDCFs - endothelium derived contracting factors
what are some examples of endothelium derived contracting factors?
endothelin (ET-1)
thromboxane A2 (TxA2)
what happens when vessels are dilated?
dilated > low resistance to flow > low peripheral vascular resistance > low blood pressure
what can hypertension increase the risk of?
heart, brain, kidney and other diseases
name some of the factors that interact to raise blood pressure and cause end-organ damage?
altered redox signalling/ oxidative stress
innate and adaptive immunity
genetics
sodium intake/ storage
sympathetic activation
microbiome
renal mechanisms
vascular/ endothelial dysfunction
what is systolic pressure?
(SP) its the maxiumum arterial pressure reached during peak ventricular ejection
what is diastolic pressure?
its the minimum arterial pressure just before ventricular injection begins
what is pulse pressure (PP)?
its the difference between systolic and diastolic pressure
what is mean arterial pressure (MAP)?
its the average pressure in the cardiac cycle
how do you measure blood pressure? and how does it work
using a sphygmomanometer
it works by pressure being released from an inflatable cuff on the upper arm while listening via stethoscope (placed over the brachial artery) as blood flow returns to the lower arm
what is the blood pressure guidelines for normal blood pressure?
systolic- <130mmHg
diastolic- <85mmHg
what is the blood pressure guidelines for high-normal BP?
systolic - 130-139mmHg and/or
diastolic 85-89mmHg
what is the blood pressure guidlines for grade I hypertension?
systolic- 140-159 and/or
diastolic - 90-99mmHg
what is the blood pressure guidelines for grade II hypertension?
systolic- >160mmHg and/or
diastolic- >100mmHg
what are the symptoms for systematic hypertension?
its usulally asymptomatic and often diagnosed when patient presents with another condition and with age, the monitoring of blood pressure becomes more important
who most commonly has pulmonary hypertension? and what symptoms come with it?
in patients with COPD where the pulmonary vasculature has been affected leading to increased vascular resistance
shortness of breath and sometimes chest pain
sustained increase in pulmonary vascular resistance leads to progressive right heart failure
what are the primary risk factors of hypertension?
high salt consumption
excessive alcohol use
overweight
age
sex
lack of exercise
tobacco
diabetes
lipid disorders
what are the secondary risk factors for blood pressure initiated by other diseases?
Aortic coarctation
Renal disease
Mineralocorticoid excess
Thyroid disease
Eclampsia
Cancer treatment
what are the effects of hypertension?
-Progressive structural changes in vasculature – thickening and narrowing of lumen of arteries
-Acceleration of atherosclerosis
-Kidney failure
-Left ventricular hypertrophy (risk factor for ischaemic heart disease and heart failure
-Stroke, aneurisms, vascular dementia
what causes the remodelling of an artery?
hypertension
what happens in the remodelling of an artery?
- proliferation of fibroblasts and infiltration of immune cells in adventitial layer
- Vascular smooth muscle cell proliferation and migration in media
- Double elastic lamina develops due to increased muscularisation
- Proliferation of apoptosis-resistant endothelial cells
- Narrowing/ occlusion of vessel lumen
what are the four categories of antihypertensive drugs?
- vasodilators
- sympathetic inhibitors
- RAAS inhibitors
- diuretics
what are the sites of action for beta blockers?
the heart and kidney
what are some examples of beta blockers?
propanolol and atenolol
what are the effects of beta blockers?
they deacrease cardiac output, reduce renin production (reduce ang II)
can indirectly cause vasodilation of peripheral arteries
what is an example of an alpha blocker?
prazosin
what effects do alpha blockers cause?
they block post-synaptic alpha-1-adrenoceptors leading to dilation of arteriolar resistance vessels and lower peripheral resistance
they dilate venous capacitance vessels reducing venous return and cardiac output
what antihypertensive drugs act on the renin-angiotensin-aldosterone system?
ACE inhihitors
Ang II receptor antagonists (ARB- angiotensin recpeptor blocker)
diuretics
what is an example of an ACE inhibitor?
captopril or rampril
how do ACE inhibitors work?
Ang I is cleaved by ACE into Ang II when it passes through the lungs, Ang II constricts blood vessels, raising the blood pressure, inhibiting ACE reduces the levels of Ang II being produced`
what is Ang II implicated in in hypertension?
its implicated in the development of left ventricular hypertrophy
name some angiotensin recepor blockers?
losartan and valsartan
what does ARB stand for?
angiotensin receptor blockers
they can also be called angiotensin II receptor antagonists
how do angiotensin II receptor antagonists work?
they selectively block AT1 receptors which mediate the vasoconstrictive, cardiac/ vascular hypertrophy effects of angiotensin II
whats and example of a diuretic?
thiazide
how do diuretics work?
they act on varying sites in the kidney to increase Na+ and water depletion leading to a hypotensive effect
what are some examples of calcium channel blockers?
verapamil, amlodipine and Diltiazem
how do calcium channel blockers work?
they block Ca2+ entry into vascular smooth muscle cells and/or cardiac muscle cells. this promotes relaxation of the muscle and vasodilation
what are some examples of vasodilators?
Hydralazine, Minoxidil, Nitrates, Nitroprusside, calcium channel blockers and angiotensin I receptor antagonists
once you get an established diagnosis of hypertension, what is the first advice you get?
lifestyle advice
what does HMOD stand for?
hypertension-mediated organ damage
what is step one of treatment for people under 55?
treatment with an angiotensin converting enzyme or angiotensin II receptor blocker
what is step one of treatment for people over 55 and all back people or people of caribbean or african decent?
calcium channel blocker is preferred but thiazide-like diuretics in people with oedema or high risk of heart failure must be considered
what is step 2 of treatment guidelines for hypertension?
ACE inhibitor or angiotensin II recpceptor blocker AND calcium channel blocker
what is step 3 of hypertension treatment?
ACE inhibitor, calcium channel blocker and thiaside-like diuretic
what type of hypertension is treated in step 4 of hypertension treatment?
resistant hypertension
what is the treatment for resistant hypertension?
ACE inhibtor, calcium channel blocker, thiazide-like diuretic and a further diuretic such as low dose spironolactone or a higher dose of thiazide-like diuretic
or an alpha or beta blocker if further diuretic treatment isnt tolerated or is contradicted or ineffective
what is the memory tool ABCD-ARB?
A–ACE inhibitor (e.g.,ramipril)
B–Beta blocker (e.g.,bisoprolol)
C–Calcium channel blocker (e.g.,amlodipine)
D– Thiazide-likeDiuretic (e.g.,indapamide)
ARB –Angiotensin IIReceptorBlocker (e.g.,candesartan)
how do vasopeptidase inhibitors work?
they simultaneously inhibit both neutral endopeptidase and angiotensin-converting enzyme (ACE). They increase the availability of peptides that have vasodilatory and other vascular effects; they also inhibit production of angiotensin II, reducing the contraction of the blood vessels, reducing blood pressure`
if theres an 88-year old female being treated for long-term hypertension which has been well managed with losartan, whats its mechanism of action to lower blood pressure?
it blocks angiotensin II effects by the prevention of angiotensin II binding causes vascular smooth muscle relaxation, lowering blood pressure. Angiotensin II would otherwise bind to the AT1 receptor and induce vasoconstriction, raising blood pressure.
what can happen if hypertension remains untreated?
it increases the risk of arthleroscleorsis, coronary thrombosis, stroke and heart failure
