hypertension pharmacology Flashcards
why does hypertension need treating?
accounts for more CV deaths than any other modifiable cardiac risk factor. It is responsible for over half of the deaths due to coronary heart disease and stroke
stage 1 hypertension
clinical BP = 140/90mmHg
home BP = 135/85mmHg or higher
what is ambulatory BP monitoring?
constant BP monitoring
stage 2 hypertension
clinical BP = 160/100mmHg or higher and home BP = 150/95mmHg
severe hypertension
clinical BP = 180mmHg or higher systolic or diastolic over 110mmHg
what to do if someone has severe hypertension?
look for concerning signs of hypertension emergency
what are concerning signs of severe hypertension?
papilloedema retinal haemorrhage MI aortic dissection Stroke rapid renal failure
when to treat stage 1 hypertension with anti-hypertensives?
patients younger than 80 and target-organ damage. Those with other cardiovascular risks - renal disease, diabetes or a 10 year cardiovascular risk over 20%
when to treat stage 2 hypertension?
always treat, regardless of age
when/ how to treat severe hypertension?
treat promptly
lifestyle modification
smoking cessation weight reduction reduction of excessive intake of alcohol and caffeine reduction of dietary salf reduction of total and saturated fat increasing exercise increasing fruit and veg intake
what determines cardiac output?
heart rate
contractility - stroke volume
arterial pressure - afterload
filling pressure - preload
how to calculate BP?
Cardiac output x total peripheral resistance
how to calculate cardiac output?
HR x stroke volume
what is a decrease in blood volume?
hypovolaemia
what happens during hypovolaemia?
decreases cardiac filling - preload
reduces stroke work, cardiac output and arterial BP
what is starling’s law?
stroke volume of the heart increases in response to an increase in the volume of blood in the ventricles before contraction when all other factors remain constant
as a larger volume of blood flows into the ventricle the blood stretches the cardiac muscle fibres leading to an increase in force of contraction
what is hypervolaemia?
increase in blood volume
what happens during hypervolaemia?
increases cardiac filling
increases stroke work, cardiac output and arterial BP
what is preload?
initial stretching of cardiac myocytes prior to contraction. related to ventricular filling
what is after load?
force or load against which the heart has to contract to expel blood
how to decrease BP?
decrease arterial pressure - afterload decrease filling - preload decrease blood volume decrease HR decrease sympathetic activity
NICE guidelines - 1st step for hypertension in <55
ACE inhibitor
NICE guidelines - 2nd step for hypertension in <55
ACE inhibitor and calcium channel blocker or ACE inhibitor and thiazide-type diuretic
NICE guidelines - 3rd step for hypertension in <55
ACE inhibitor, calcium channel blocker and thiazide-type diuretic
NICE guidelines - 1st step for hypertension in >55 or black patients of any age
calcium-channel blocker or thiazaide-type diuretic
NICE guidelines - 2nd step for hypertension in >55 or black patients of any age
add an ACE inhibitor to calcium -channel blocker or thiazide-type diuretic
NICE guidelines - 3rd step for hypertension in >55 or black patients of any age
ACE inhibitor, calcium channel blocker and thiazide- type diuretic
NICE guidelines for if all 3 drug types doesn’t work for hypertension?
add more diuretic therapy or alpha blocker or beta blocker
prescribing ACE inhibitors
if not tolerated offer angio-tensin 2 receptor antagonist, if both are not tolerated consider beta blocker.
considerations when prescribing beta blockers
especially in combination with thiazide-type diuretics beta blockers should not be given to people with uncomplicated hypertension and diabetes or those who have a high risk of developing diabetes
renin angiotensin aldosterone system
RAAS
liver secretes angiotensinogen which causes the kidney to release renin.
angiotensinogen forms angiotensin 1 due to renin which then forms angiotensin 2 in response to ACE
what does angiotensin 2 do?
increases sympathetic activity
increases tubular sodium and chlorine ion reabsorption and potassium excretion
causes H2O retention
causes the adrenal cortex to produce aldosterone
increases arteriolar vasoconstriction to increase BP
increases release of ADH from posterior pituitary
what does aldosterone do?
increases H2O retention
what does ADH do?
increase H2O absorption from collecting duct
what is the overall result of RAAS?
water and salt retention
effective circulating volume increases
perfusion of juuxtaglomerular apparatus increases
examples of ACE inhibitors
ramipril and enalapril
how do ACE inhibitors work?
interfere with renin-angiotensin-aldosterone system
block conversion of angiotensin 1 to 2
reduces circulating angiotensin 2
causing arterial dilation
ACE also converts bradykinin so reduced ACE increases bradykinin increasing vasodilation so reduces vascular resistance
cautions of ACE inhibitors
common cause of dry cough
beware of use in renal artery stenosis
cannot be used in pregnancy
examples of Angiotensin 2 receptor blockers
losartan and candesartan
when are ARBs used?
as an alternative to ACE inhibitors
how do ARBs work?
block angiotensin 2 receptors
angiotensin 2 normally causes constriction of blood vessels and released of aldosterone which increases sodium and water reabsorption from kidney so these drugs prevent this
how do calcium channel blockers work?
prevents calcium entry so smooth muscle contraction cannot occur and relaxes arterioles, coronary arteries and heart muscle - vasodilation
how do smooth muscles contract?
increase in free intracellular calcium
calcium binds to calmodulin binding protein
calcium-calmodulin activates myosin light chain kinase which phosphorylates myosin light chain in the presence of ATP
this leads to cross-bridge formation between myosin heads and actin filaments so causes smooth muscle contraction
examples of calcium channel blockers
amlodipine
nifedipine
cautions of calcium channel blockers
commonly cause ankle swelling
beware in heart failure as reduces contractility and heart failure already shows reduced contractility
effect of calcium channel blockers on heart
some types - verapamil and dilitiazem slow HR and decrease contractility
what do diuretics do?
lead to reduced sodium and less water reabsorption so reduces blood volume
examples of thiazide-type diuretics
indapamide
chlortalidone
normally end in -ide
how do thiazide diuretics work?
block NaCl co-transporter
reduce sodium ion absorption at distal convoluted tubule in kidney
results in higher osmolarity of urine and decreased water reabsorption
effect is self-limiting as lower blood volume activates RAAS
beta 1 receptors in the heart
noradrenaline or adrenaline bind to the receptors in the heart. They are GPCRs - Gs so activate adenyl cyclase to form cAMP from ATP . cAMP activates a cAMP-dependent protein kinase A which phosphorylates L-type calcium channels and cause increased calcium entry into the cell. This increases contractility and heart rate.
how do beta blockers work?
block sympathetic activation of beta 1 receptors, prevent binding of adrenaline or noradrenaline. reduce HR reduce strength of contractions decrease conduction velocity decrease relaxation rate
what is chronotropy?
heart rate
what is inotropy?
contractility
what is dromotropy?
electrical conduction
what is lusitropy?
relaxation
contraindications of beta blockers
avoid in asthma
don’t give with rate limiting calcium channel blocker - risk of complete heart block
alpha 1 antagonist examples
doxazosin
how do alpha 1 antagonists work?
block alpha 1 receptors so noradrenaline cannot bind
reduces the sympathetic response
relative vasodilation so reduces stroke volume
when are alpha 1 antagonists used?
in conjunction with other medications
examples of alpha 2 agonists
methyldopa
how do alpha 2 agonists work?
act on presynaptic autoreceptors in CNS inhibit release of noradrenaline reduces sympathetic outflow increases vagal outflow reduces peripheral arterial and venous tone
when are alpha 2 agonists used?
mainly for hypertension in pregnancy
unwanted side effects so rarely used
side effects of alpha 2 agonists
exertion/ postural hypotension dry mouth diarrhoea sedation/ drowsiness fluid retention/ oedema
hypertension in pregnancy
hypertensive complications in pregnancy can be hazardous for the mother and fetus and are associated with a significant risk of morbidity and mortality
can cause premature labour
