Pharmacology of hypertension

Question 1

give 4 diff classes of drugs for hypertension

Answer 1

angiotensin converting enzyme inhibitors, calcium channel blockers, thiazide (or thiazide-like-diuretics), angiotensin receptor blockers

Question 2

give 3 ACE inhibitors

Answer 2

ramipril
lisinopril
perindopril

Question 3

primary mechanism of action of ACEi’s

Answer 3

Inhibit the angiotensin converting
enzyme.
Prevent the conversion of
angiotensin I to angiotensin II
by ACE

Question 4

side effects of ACEi’s

Answer 4

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

Question 5

are ACEi’s prodrugs

Answer 5

most are, but not lisinopril
require hepatic activation

Question 6

what must u monitor while on ACEi’s

Answer 6

eGFR and serum potassium

Question 7

give 2 examples of calcium channel blockers

Answer 7

amlodipine
felodipine

Question 8

primary mechanism of action of calcium channel blockers

Answer 8

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.

Question 9

drug target for calcium channel blockers

Answer 9

L type calcium channels

Question 10

side effects of calcium channel blockers

Answer 10

ankle oedema
constipation
palpitation
flushing/headaches

Question 11

what type of calcium channel blockers show higher degree of vascular selectivity

Answer 11

dihydropyridine type

Question 12

primary mechanism of thiazides

Answer 12

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

Question 13

drug target of thiazides

Answer 13

sodium chloride transporter

Question 14

side effects of thiazides

Answer 14

Hypokalemia
Hyponatremia.
Metabolic alkalosis (increased hydrogen ion excretion)
Hypercalcemia.
Hyperglycemia (hyperpolarised pancreatic beta cells).
Hyperuricemia.

Question 15

give examples of thiazides or thiazide like diuretics

Answer 15

bendro-flumethiazide (thiazide)
indapamide (thiazide like)

Question 16

when do thiaze and thiazide like diuretics lose diuretic effects

Answer 16

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

Question 17

the continuing anti hypertensive action from thiazdes is due to

Answer 17

vasodilating properties which are more pronounced for thiazide like diuretics

Question 18

give some examples of angiotensin receptor blockers

Answer 18

losartan
irbesartan
candesartan

Question 19

primary mechnism of action of ARBs

Answer 19

These agents act as insurmountable (i.e. non-competitive) antagonists at AT1 receptor (found on kidneys and on the vasculature)

Question 20

side effects of ARBs

Answer 20

Hypotension
Hyperkalaemia (care with K+ supplements or K+-sparing diuretics)
Foetal Injury (AVOID IN PREGNANT WOMEN)
Renal failure (in patients with renal artery stenosis)-

Question 21

which is better ACEi’s or ARBs

Answer 21

most trials indicate ARBs are not as effective

Question 22

are ARBs pro drugs

Answer 22

losartan and candesartan are, they require hepatic activation

Question 23

what is clearance

Answer 23

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

Question 23

what is elimination half life

Answer 23

the length of time required for the concentration of a particular drug to decreasetohalf of itsstarting dose in the body.

Question 24

what is time to peak plasma levels

Answer 24

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

Question 25

compare plasma clearance, elimination half life and time to peak plasma levels in amlodipine and felodipine

Answer 25

felodipine is cleared faster (higher plasma clearance, shorter elimination half life) and is absorbed faster (lower time to peak plasma levels)

Question 26

BP tends to increase most rapidly during early morning hours after waking up, so which calcium channel blocker would be most effective

Answer 26

since amlodipine has a slow onset and longer half life, this helps to mitigate the high BP seen in the morning

Question 27

felodipine causes what reflex

Answer 27

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

Question 28

why are ACEis used over ARBs

Answer 28

they are cheaper and more effective
ARBs used for patients of African or Caribbean descent

Question 29

what does ACE do

Answer 29

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)

Question 30

why might ACEi’s have a negative effect on eGFR and serum potassium

Answer 30

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

Question 31

why is it vital the thiazide-like diuretics are excreted unchanged in the urine

Answer 31

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

Question 32

why do thiazides increase potassium excretion

Answer 32

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