L12-antihypertensive drugs; MOA for drugs acting on RAAS

what is hypertension

• it is a condition where the force of blood pushing against the artery walls is consistently too high making the heart work harder to circulate blood 

what  are the risk factors associated with untreated hypertension/ why should we worry about it 

• high blood pressure is an independent risk factor for cardiovascular diseases and strokes 

• the high blood pressure produces damage to the endothelial cells which can provoke cardiovascular diseases e.g. atherosclerosis 

• it can cause internal organ damage. kidney, eyes nerves 

• the extra strain on the heart can lead to heart failure 

what are the factors that increase the risk of getting hypertension 

explain how the body senses volume 

• the body has no mechanism to measure volume so it relies on measuring pressure instead 

what are the three main types of hypertension

• essential ( primary ) hypertensions- most people, no apparent cause 

• secondary hypertension- hypertension caused by another identifiable medical condition e.g. endocrine gland like cushing’s disease  disorders, kidney diseases or drug induced like using anti-inflammatory corticosteriods e.g. prednisone 

• " white coat hypertension- when a persons blood pressure increases when being checked at doctors but then at home its fine 

what are the stages of systemic hypertensions and its treatment/ when should we intervene 

when treating systemic hypertension what factors are we aiming to change with the treatment to reduce blood pressure 

• reduce the total peripheral resistance- promote vasodilation

• reducing stroke volume- we want drugs that can cause less filling of the heart 

• reducing the heart rate- lower heart rate = lower cardiac output and blood pressure drugs that can do this will be effective 

• the renal artery in the kidney senses low blood pressure and the endothelium on the kidney will secrete renin, an enzyme used to cleave angiotensin to angiotensinogen -> angiotensin one 

• the angiotensin one travels in the blood to the lung tissue and it encounters angiotensin converting enzyme which converts it into angiotensin 2, this is the active molecule that is responsible for effecting the blood pressure 

• it goes into systemic circulation and impacts the adrenal gland to cause aldosterone release 

• it also impacts the pituitary to cause ADH release

what happens to cause renin release

• when the blood pressure falls 

• when blood volume decreases 

• when sympathetic activation occurs 

• the production of prostaglandin E2 and I2

what are the effects of angiotensin 2

what are some of the pharmaceutical targets of the RAAS system + examples 

• ace inhibitors-which block the conversion of angiotensin 1 ->2 e.g.ramipril

• renin inhibitore.g aliskerin

• diuretics- increase the water and salt loss to decrease the volume e.g thiazide,carbonic anhydrase inhibitors 

• mineralcorticoid receptor antagonists e.g spironolactone 

why are ace inhibitors often  the first choice to treating hypertension  compared to ARBs

• they only need to target  one tissue/the lungs and they have an effect earlier  on in the pathway compared to ARBs which need to target individual tissues/receptors and have an effect later on.

• but ace inhibitors have a potential to increase bradykinin relases, increasing the cough response which reduced patient compliance 

• whist ARBs demonstrate fewer intrusive side effects.

why are ace inhibitors often  the first choice to treating hypertension  compared to ARBs

• they only need to target  one tissue/the lungs and they have an effect earlier  on in the pathway compared to ARBs which need to target individual tissues/receptors and have an effect later on.

• but ace inhibitors have a potential to increase bradykinin releases, increasing the cough response which reduced patient compliance 

• whist ARBs demonstrate fewer intrusive side effects.

when cant ace inhibitors and ARBs be used to treat hypertension.

what are some of the common side effects ace inhibitors and ARBS/drugs that impact hypertension 

hypotension,potential hypokalemia, cough reflex tachycardia