treatment of hypertension Flashcards
hypertension?
persistent elevation of BP in the systemic arterial circulation to a level higher than expected for age, sex, race and of the individual.
lifestyle interventions for treatment of hypertension?
stage 1 hypertension is usually managed through lifestyle interventions alone
- exercise
- smoking cessation
- dietary modification
(limit alcohol and caffeine intake)
why are the different types of therapeutic agents?
- ACE inhibitors
- angiotensin 2 receptor blockers (ARBs)
- diuretics (decrease water retention)
- calcium channel blocker
- B1 adrenergic receptor blockers
what is the difference in step 1 therapeutic intervention between:
1- those with diabetes and <55 yrs old
2- >55 yrs old, Afro-caribean descent?
1- give ACE inhibitor
2- give CCB
step 1 medical management of hypertension?
ACE inhibitor (ramipril) or CCB (candesartan or nifedipine) depending on the group you are treating.
step 2 medical management of hypertension?
- if max dose of step 1 has failed or not tolerated:
= combine CCB and ACE
if CCB are not tolerated in step 2 what should you give?
thiazide diuretic
step 3 medical management of hypertension?
add thiazide diuretic
step 4 medical management of hypertension?
this is now RESISTANT HYPERTENSION:
- all medications and add a further diuretic or B1 blocker
- seek specialist advise
in step 4, what further diuretic are you going to use?
low dose spironolactone
only do this if blood patssium is <4.5mmol/L
patients with hypertension should be monitored for what?
patients should be monitored for end organ damage
what is given for CV risk management in patients with hypertension?
statins for primary prevention is 10-year CV is >20%
what are the blood pressure targets for:
1- <80 yrs
2- 80 yrs
3- diabetics
1- <80 years: clinic BP <140/90 mmHg (or <135/85 AMPM/HBPM)
2- 80 years: clinic BP <150/90 mmHg (or <145/85 AMPM/HBPM)
3- Diabetics: clinic BP <130/80 mmHg
where is blood filtered?
glomerulus of the kidney
where does reabsorption of ions take place
reabsorption of solutes, ions and water will take place along the length of the tubule
what does the movement of Na do in the kidney?
it creates an osmotic gradient for H20 to follow
where in the kidney is bulk reabsorption uncontrolled?
the proximal convoluted tubule
1- what does angiotensin 2 bind to?
2- what are its effects on:
- vascular smooth muscle
- hypothalamus
- renal tubules of the kidney
1- AT1 receptors
2- increased smooth muscle constriction, increasing TPR
- on the hypothalamus:
increased release of vasopressin (ADH), reabsorption of H20 in kidneys, increased ECV - renal tubules of kidneys:
increased secretion of aldosterone from adrenal glands, Na reabsorption in the kidney, increased ECV
angiotensin 2 effect in the proximal convoluted tubule?
it stimulates Na reabsorption, particularly here.
what effect does angiotensin 2 stimulating aldosterone release?
it will further stimulate Na reabsorption in the cortical collecting duct.
1- ACE inhibitor example?
2- mechanism of action?
1- ramipril
2- inhibitor of ACE=
= no angiotensin 2
- decreased vasoconstriction = decreased TPR
- decreased water retention = decreased ECV
- decreased Na retention = decreased ECV
DECREASED BP
what other system is ACE involved in?
what is the function of this system?
the kinin-kallikren system
- this will cleave kininogen into bradykinin
- this is a vasodilator
what does ACE do to bradykinin?
it breaks in down into an active metabolite
what does bradykinin do?
- it binds to B2 receptors
- vasodilation
- PGI2 production
- NO production
what can increased bradykinin do?
increased bradykinin can cause bronchoconstriction which can give rise to a dry cough.
why would ARB be given over ACE?
- due to the specific effects it has on AT1 receptors, there will be no effects on bradykinin., therefore no side effects of cough.
1- what are diuretics?
2- what are 3 different types of diuretics?
3- how do they work?
1- substances that help to body get rid of water (targeting Na absorption to do this)
2- loop diuretics, thiazide diuretics, K sparing diuretics
3- they will reduce BP by decreasing ECV
describe loop diuretics?
- most powerful of diuretic
- inhibits NKCC2 (Na/K/2Cl co transporter) in Thick acedning loop of henle
when will loop diuretics be used?
only used when treatment of hypertension where renal function is impaired
- sometimes used in other fluid overload condition
examples of loop dietetics?
furosemide
bumetanide
example of thiazide diertics?
bendroflumethiazide
indapamide
describe thiazide diuretics?
- less powerful than loop diuretics
- inhibits NCC in the distal convoluted tubule (Na/Cl co transporter)
- this is a 2nd/3rd line of treatment
describe K sparing diuretics?
- it has limited diuretic action alone, but powerful in combination with loop/thiazide diuretics
- inhibits ENaC in the cortical collecting duct (epithelial Na channel)
why are k sparing diertics rarely used?
due to the fact that is also blocks K excretion (coupled to ENaC), causing hyperkalaemia
what are the 2 types of K sparing diuretics?
1- aldosterone antagonists (eg: spironolactone, eplerenone)
2- ENaC inhibitors (amiloride, triameterne)
function of CCB?
inhibits contraction of cardiac muscle and vascular smooth muscle
describe the movement of calcium and sodium in the heart?
- Na enters via slow Na channel in pacemaker cells (funny current)
- causing a call depolarisation
- Ca enters via T-type voltage gated Ca channels
- further depolarisation
what does the movement of Na and Ca cause to the heart?
- depolarisation spreads through gap junctions to both pacemaker and contractile cells
- depolarisation will occur in neighbouring cells
what do the contractile cells contain?
they contain L-type Ca channels
- calcium is further released from the SR via RyRs
- causing contraction of the cardiomyocyte
what do CCB do?
they inhibit L-type voltage gated Ca channels
- this is the same concept as vascular smooth muscle
what are the 2 different types of CCB and what which one is most commonly used?
1- non dihydropyridines and dihydropyridines
2- dihyropryridines are most commonly used
2 types of non dihyropridines?
phenylalkylamines (verapamil)
benzothiazepines (diltiazem)
examples of dihyrodypridines?
amlodipine
felodipine
effects of non-dihydropyridines?
Cardiac effects:
- decreased contractility
- decreased hr
- decreased conduction
- decreased CO
- decreased PB
smooth muscle effects:
- decreased coronary artery constriction
- decreased peripheral vessel constriction
- decreased TPR
- decreased BP
effects of dihydropridines?
smooth muscle effects:
- decreased coronary artery constriction
- decreased vessel constriction
- decreased TPR
- decreased BP
side effects of CCB?
flushes
headaches
ankle oedema
dizziness
side effects of thiazide diuretics?
hypokalaemia
hyponatraemia
gout
side effects of ACE inhibitors?
persistent dry cough
dizziness
tiredness
headaches
side effects of ARB’s?
dizziness
headaches
renal impairment
back/leg pain
side effects of K sparing diuretics?
hyperkalaemia
renal impairment
GI upset
what are the side effects of non-selective B-adrenoreceptor antagonists?
bronchoconstriction (bad for asthmatics)
examples of B1 selective antagonists?
bisoprolol
atenolol
how do B1 selective antagonists work?
- decrease force of contraction
- decrease CO
- decrease BP
- decrease TPR
- decrease ECF
- decrease BP
- also inhibits renin release from granular cells= decrease in angiotensin 2= decrease in vasoconstriction, Na and H20 retention
why are b1 blockers not the first line of treatment for hypertension?
- less effective than comparators in reducing CV risk
- less effective then ACE’s and CCB’s at reducing the risk of diabetes
- less well tolerated than ACE inhibitors/ARB’s
when will B1 adrenoreceptor antagonist be used?
they are useful antihypertensive patients with additional need for B blockade including angina and heart failure.
