Hypertension Flashcards
what is the first line treatment for hypertension
lifestyle changes
in which cases do drug treatment start straight away
organ damage, cardiovascular disease, renal disease and diabetes
where do antihypertensive drugs work?
sympathetic nervous system and cerebral acting blood vessels AND the kidney (RAAS)
what does RAAS stand for?
Renin-angiotensin-aldosterone-system
what does RAAS do?
regulate blood pressure
what triggers RAAS
low blood pressure or certain nerve impulses (e.g. in stressful situations), the kidneys release an enzyme called renin.
end result of RAAS activation
increased blood pressure
what does Renin do?
converts angiotensinogen –> angiotensin 1
what does ACE do
convert angiotensin 1 –> angiotensin 2
what can angiotensin 2 do?
activate AT1 receptors
4 ways AT1 receptors increase BP
heart, hypertrophy/fibrosis
vascular growth, hyperplasia/hypertrophy
vasoconstriction, direct on the blood vessels due to sympathetic NA release
Salt retention, increases aldosterone, increasing bp
primary effect of aldosterone
increased reabsorption of sodium, sodium loss in urine is decreased under aldosterone stimulation.
3 targets in RAAS for drugs
renin inhibitors
ACE inhibitors
AT1 receptor antagonists/blocker
renin inhibitor
aliskiren
ACE inhibitor
captopril and enalapril
adverse effects of ACE inhibitors
hypotension, palpitations, skin rush, hyperkalaemia, dry cough
AT1 receptor blockers
losartan and candesartan
what is the normal effect of bradykinin
potent endothelium-dependent vasodilator and mild diuretic, which may cause a lowering of the blood pressure
what effect does ACE have on bradykinin
decreases it, therefore decreasing the vasodilation effect and increasing blood pressure
side effect of ACE inhibitors
dry cough, ACE inhibited = more bradykinin, increased B2 activation and increased vasodilation
what symptom do you get with ACE inhibitors but not with AT1 receptor blockers
dry cough
2 main effects of activating AT1 receptors
increased aldosterone and increased vasoconstriction
with AT1 receptor blockers, what is there a reduced risk of
angioedema
what are ACE inhibitors usually used with
diuretics
what is the triple whammy
ACEI (dilate efferent arteriole, reducing glomerular filtration rate)
diuretic (reduce plasma volume and reduce glomerular filtration rate)
NSAID (restrict blood flow into glomerulus via afferent arteriole, reducing glomerular filtration rate)
what does the triple whammy often lead to
kidney failure
normally, how is the GFR monitored
when it is reduced, due to lower blood volume, the RAAS is activated, causing angiotensin 2 to constrict the efferent arteriole, causing blood to flow out of the glomerulus, increasing the pressure in the glomerulus and increasing the GFR.
when can drugs acting on the RAAS not be used
pregnancy
drugs acting on the RAAS can be used for…
systemic hypertension, ischaemic heart disease, myocardial infarction, heart failure
when are drugs acting on the RAAS not first choice therapy
over 55 year olds
African-American or Caribean origin
name 2 direct-acting vasodilators
Calcium channel blockers
K channel activators
what are the preferred 1st line treatment in elderly and patients of African-American or Caribbean family origin and severe hypertension in pregnancy
Ca channel blockers
name 2 vascular calcium channel blockers
nifedipine and amlodipine
are diltiazem and verapamil used for hypertension?
no, (but they are Ca channel blockers)
verapamil is selective for where?
heart
adverse effects of Ca channel blockers
hypotension, postural hypotension, reflex tachycardia, peripheral oedema
how do K+ channel activators work as a vasodilator
membrane hyperpolarised, L-type VACCs close, vasodilation
example of a K+ channel activator
minoxidil
adverse effects of K channel activators
reflex tachycardia (which can be treated with beta blockers) fluid retention (can be treated with diuretics) diabetes mellites
name another vasodilator (not Ca channel blocker or K channel activator)
hydralazine
what is hydralazine usually taken with
beta blocker and a diuretic
Calcium channel blockers and K channel activators work where?
directly on smooth muscle cells
there are antihypertensive drugs that work…
sympathetic nervous system
what kind of drugs can help with hypertension that act on the SNS
beta blockers, alpha1 adrenoreceptor antagonist, alpha2 agonists
how do beta blockers work as an antihypertensive
block beta1 on the heart and kidneys, thus reducing reflex tachycardia, reducing renin release and less activation of RAAS.
some beta blockers can release NO (a vasodilator)
what beta blocker can release NO
nebivolol
non-selective beta blockers can also act as …
alpha1 adrenoreceptor antagonist
name 2 non-selective beta blockers that can also act as an alpha1 antagonist
carvedilol and labetalol
how would alpha 1 antagonists work as an antihypertensive drug
antagonist, so inhibit postsynaptic alpha1 adrenoreceptors on vascular SMC causing arterial dilation
name 2 alpha1 adrenoreceptor antagonists
doxazosin and prazosin
another category of antihypertensive drugs that work on the sympathetic nervous system
alpha2 adrenoreceptor agonist
2 examples of alpha2 agonists
clonidine and methyldopa
how to alpha2 agonists help in hypertension
increase parasympathetic output/effect, and decrease sympathetic output
name 1 imidazoline 1 receptor agonist and what it does
moxonidine, decrease sympathetic output
name 1 ganglionic blocking drug and how it works
trimetaphan, competitive nAChR antagonist at the autonomic ganglia (this is not used very much as an antihypertensive)
where else can antihypertensives work?
autonomic ganglia (nAChR) adrenergic neurone
name 2 adrenergic blocking drug
guanethidine (only used in hypertensive emergency) and reserpine (not used much at all)
