Pharmacology of hypertension Flashcards
give 4 diff classes of drugs for hypertension
angiotensin converting enzyme inhibitors, calcium channel blockers, thiazide (or thiazide-like-diuretics), angiotensin receptor blockers
give 3 ACE inhibitors
ramipril
lisinopril
perindopril
primary mechanism of action of ACEi’s
Inhibit the angiotensin converting
enzyme.
Prevent the conversion of
angiotensin I to angiotensin II
by ACE
side effects of ACEi’s
Cough
Hypotension
Hyperkalaemia (care with K+ supplements or K+-sparing diuretics)
Foetal Injury (AVOID IN PREGNANT WOMEN)
Renal failure (in patients with renal artery stenosis)-
Urticaria/Angioedema
are ACEi’s prodrugs
most are, but not lisinopril
require hepatic activation
what must u monitor while on ACEi’s
eGFR and serum potassium
give 2 examples of calcium channel blockers
amlodipine
felodipine
primary mechanism of action of calcium channel blockers
Block L-type calcium channels – predominantly on vascular smooth muscle. This results in a decrease in calcium influx, with downstream inhibition of myosin light chain kinase and prevention of cross-bridge formation. The resultant vasodilation reduces peripheral resistance.
drug target for calcium channel blockers
L type calcium channels
side effects of calcium channel blockers
ankle oedema
constipation
palpitation
flushing/headaches
what type of calcium channel blockers show higher degree of vascular selectivity
dihydropyridine type
primary mechanism of thiazides
They block the Na+, Cl- co-transporter in the early DCT.
Therefore Na+ and Cl- reabsorption is inhibited.
As a result the osmolarity of the tubular fluid increases, decreasing the osmotic gradient for water reabsorption in the collecting duct (Na+ and H2O loss)
this mans that blood volume decreases, as does venous return and then cardiac output
drug target of thiazides
sodium chloride transporter
side effects of thiazides
Hypokalemia
Hyponatremia.
Metabolic alkalosis (increased hydrogen ion excretion)
Hypercalcemia.
Hyperglycemia (hyperpolarised pancreatic beta cells).
Hyperuricemia.
give examples of thiazides or thiazide like diuretics
bendro-flumethiazide (thiazide)
indapamide (thiazide like)
when do thiaze and thiazide like diuretics lose diuretic effects
within 1-2 weeks of treatment
kidney becomes tolerant bc there is rebound activation of renin angiotensin system which counteracts diuretic effect due to increasing Na reabsorption
continuing anti hypertensive effect is due to a further vasodilating action
the continuing anti hypertensive action from thiazdes is due to
vasodilating properties which are more pronounced for thiazide like diuretics
give some examples of angiotensin receptor blockers
losartan
irbesartan
candesartan
primary mechnism of action of ARBs
These agents act as insurmountable (i.e. non-competitive) antagonists at AT1 receptor (found on kidneys and on the vasculature)
side effects of ARBs
Hypotension
Hyperkalaemia (care with K+ supplements or K+-sparing diuretics)
Foetal Injury (AVOID IN PREGNANT WOMEN)
Renal failure (in patients with renal artery stenosis)-
which is better ACEi’s or ARBs
most trials indicate ARBs are not as effective
are ARBs pro drugs
losartan and candesartan are, they require hepatic activation
what is clearance
the measure of the ability of the body to eliminate a drug. Clearance by means of various organs of elimination is additive. Elimination of drug may occur as a result of processes that occur in the liver, kidney, and other organs
what is elimination half life
the length of time required for the concentration of a particular drug to decreasetohalf of itsstarting dose in the body.
what is time to peak plasma levels
time required for a drug to reach peak concentration in plasma. The faster the absorption rate, the lower is the time to peak plasma concentration
compare plasma clearance, elimination half life and time to peak plasma levels in amlodipine and felodipine
felodipine is cleared faster (higher plasma clearance, shorter elimination half life) and is absorbed faster (lower time to peak plasma levels)
BP tends to increase most rapidly during early morning hours after waking up, so which calcium channel blocker would be most effective
since amlodipine has a slow onset and longer half life, this helps to mitigate the high BP seen in the morning
felodipine causes what reflex
it causes a decrease in systolic and diastolic BP and additionally a reflex increase in HR (reflex tachycardia)
amlodipine has slow onset and longer half life so mitigates the reflex tachycardia
why are ACEis used over ARBs
they are cheaper and more effective
ARBs used for patients of African or Caribbean descent
what does ACE do
ACE converts angiotensin I to angiotensin II, this causes vasoconstriction and aldosterone secretion which leads to salt and water retention
ACE also converts bradykinin which is a mediator of vasodilation to inactive metabolites (ACEi’s block this so less bradykinin is destroyed and can cause more vasodilation)
why might ACEi’s have a negative effect on eGFR and serum potassium
when ACE inhibited, there is less aldosterone
aldosterone causes sodium to be reabsorption and potassium to be excreted but without this potassium levels will increase giving hyperkalaemia
angiotensin II is the major determinant of efferent vasoconstriction, this maintains GFR when renal perfusion is low but blocking this can cause acute renal failure
why is it vital the thiazide-like diuretics are excreted unchanged in the urine
the site of action is on the apical side of the distal convoluted tubule so the diuretic needs to travel from blood, through basolateral side to the apical side where it can work and will then be excreted from there
why do thiazides increase potassium excretion
there is increased sodium and water delivery to the early distal tubule (bc this is what thiazide diuretics do) and then Na+ will go into the principal cells from the tubular lumen on apical side
it will go to the blood via Na/K ATPase
so more K is going into the cell from blood as a result
this leads to more K secretion on apical side into lumen
