06 The vascular system: vasodilators

Question 1

6.01 ACE INHIBITORS

Captopril, enalapril, lisinopril - actions

Answer 1

lowers blood pressure by decreasing vasoconstrictor tone and reducing cardiac load

Question 2

6.01 ACE INHIBITORS

Captopril, enalapril, lisinopril - MOA

Answer 2

inhibits angiotensin-converting enzyme (ACE), which reduces synthesis of vasoconstrictor angiotensin II
this decreases aldosterone secretion, which increases salt and water excretion, indirectly decreasing plasma volume and cardiac load

Question 3

6.01 ACE INHIBITORS

Captopril, enalapril, lisinopril - abs/distrib/elim

Answer 3

given orally
half-lives: captopril ~2h, lisinopril 12h
enalapril is a prodrug converted to an active moiety by liver enzymes

Question 4

6.01 ACE INHIBITORS

Captopril, enalapril, lisinopril - clinical use

Answer 4

hypertension
heart failure
ventricular dysfunction following MI
diabetic nephropathy
chronic renal insufficiency to prevent progression

Question 5

6.01 ACE INHIBITORS

Captopril, enalapril, lisinopril - adverse effects

Answer 5

hypotension
dry cough
angioedema
renal failure can occur

Question 6

6.01 ACE INHIBITORS

Captopril, enalapril, lisinopril - special points

Answer 6

hyperkalaemia can occur if given with potassium-sparing diuretics
the dry cough and angioedema are due to the drugs producing bradykinin by stimulating the kallikrein-kinin system

Question 7

6.02 ANGIOTENSIN ANTAGONISTS

Losartan, valsartan, candesartan, irbesartan - actions

Answer 7

lowers blood pressure by decreasing vasoconstrictor tone

Question 8

6.02 ANGIOTENSIN ANTAGONISTS

Losartan, valsartan, candesartan, irbesartan - MOA

Answer 8

blocks the action of angiotensin II on the angiotensin II (AT1 subtype) receptor

Question 9

6.02 ANGIOTENSIN ANTAGONISTS

Losartan, valsartan, candesartan, irbesartan - abs/distrib/elim

Answer 9

given orally
half-life 1-2h
half-life of metabolite 3-4h

Question 10

6.02 ANGIOTENSIN ANTAGONISTS

Losartan, valsartan, candesartan, irbesartan - clinical use

Answer 10

hypertension
congestive heart failure
nephropathy

Question 11

6.02 ANGIOTENSIN ANTAGONISTS

Losartan, valsartan, candesartan, irbesartan - adverse effects

Answer 11

hypotension, dizziness
hyperkalaemia can occur

Question 12

6.02 ANGIOTENSIN ANTAGONISTS

Losartan, valsartan, candesartan, irbesartan - special points

Answer 12

does not cause the dry cough or angioedema seen with the ACE inhibitors

Question 13

6.03 CALCIUM CHANNEL BLOCKERS

Amlodipine, nifedipine, verapamil, diltiazem - actions

Answer 13

vascular dilatation lowers blood pressure
amlodipine and nifedipine dilate arterial resistance vessels
(verapamil acts mainly on the heart, slowing the rate)

Question 14

6.03 CALCIUM CHANNEL BLOCKERS

Amlodipine, nifedipine, verapamil, diltiazem - MOA

Answer 14

block voltage-gated calcium channels in vascular smooth muscle, which inhibits calcium influx and thus contraction

Question 15

6.03 CALCIUM CHANNEL BLOCKERS

Amlodipine, nifedipine, verapamil, diltiazem - abs/distrib/elim

Answer 15

given orally
half-lives: amlodipine 35h, nifedipine 2h, verapamil (undergoes first-pass metabolism) ~4h

Question 16

6.03 CALCIUM CHANNEL BLOCKERS

Amlodipine, nifedipine, verapamil, diltiazem - clinical use

Answer 16

hypertension
chronic stable angina pectoris
Prinzmetal’s angina

Question 17

6.03 CALCIUM CHANNEL BLOCKERS

Amlodipine, nifedipine, verapamil, diltiazem - adverse effects

Answer 17

amlodipine and nifedipine: reflex tachycardia, hypotension and headache due to vasodilatation
ankle oedema
constipation

Question 18

6.03 CALCIUM CHANNEL BLOCKERS

Amlodipine, nifedipine, verapamil, diltiazem - special points

Answer 18

grapefruit juice increases the effects

Question 19

6.04 POTASSIUM CHANNEL ACTIVATOR

Minoxidil - actions

Answer 19

marked long-lasting vascular dilatation
lowers blood pressure

Question 20

6.04 POTASSIUM CHANNEL ACTIVATOR

Minoxidil - MOA

Answer 20

opens potassium channels
hyperpolarises smooth muscle cells

Question 21

6.04 POTASSIUM CHANNEL ACTIVATOR

Minoxidil - abs/distrib/elim

Answer 21

given orally
half-life ~4h

Question 22

6.04 POTASSIUM CHANNEL ACTIVATOR

Minoxidil - clinical use

Answer 22

very severe hypertension

Question 23

6.04 POTASSIUM CHANNEL ACTIVATOR

Minoxidil - adverse effects

Answer 23

salt and water retention, and tachycardia and angina (therefore given with a loop diuretic and a β blocker)
hirsutism

Question 24

6.04 POTASSIUM CHANNEL ACTIVATOR

Minoxidil - special points

Answer 24

also used topically to treat baldness

Question 25

6.05 VASODILATOR AND SMOOTH MUSCLE RELAXANT Hydralazine - actions

Answer 25

relaxes arterial smooth muscle, thus lowering blood pressure

Question 26

6.05 VASODILATOR AND SMOOTH MUSCLE RELAXANT Hydralazine - MOA

Answer 26

interferes with the release of Ca2+ from the sarcoplasmic reticulum in vascular smooth muscle cells

Question 27

6.05 VASODILATOR AND SMOOTH MUSCLE RELAXANT Hydralazine - abs/distrib/elim

Answer 27

given orally half-life ~1–3h

Question 28

6.05 VASODILATOR AND SMOOTH MUSCLE RELAXANT Hydralazine - clinical use

Answer 28

very severe hypertension - particularly in pregnancy cardiac failure, in combination with a nitrate

Question 29

6.05 VASODILATOR AND SMOOTH MUSCLE RELAXANT Hydralazine - adverse effects

Answer 29

palpitations, tachycardia, hypotension flushing GIT disturbances dizziness allergic reactions (which can be severe with long-term use) treatment for more than 6 months can provoke a systemic lupus erythematosus-like syndrome

Question 30

6.06 ENDOTHELIN ANTAGONIST Bosentan - actions

Answer 30

decreases both pulmonary and systemic vascular resistance, resulting in increased cardiac output without increasing the heart rate

Question 31

6.06 ENDOTHELIN ANTAGONIST Bosentan - MOA

Answer 31

dual endothelin receptor antagonist - i.e. affinity for both endothelin A and B (ETA and ETB) receptors

Question 32

6.06 ENDOTHELIN ANTAGONIST Bosentan - abs/distrib/elim

Answer 32

given orally half-life ~5h bosentan is eliminated by biliary excretion following metabolism in the liver by the cytochrome P450 iso­enzymes, CYP2C9 and CYP3A4

Question 33

6.06 ENDOTHELIN ANTAGONIST Bosentan - clinical use

Answer 33

idiopathic pulmonary hypertension

Question 34

6.06 ENDOTHELIN ANTAGONIST Bosentan - adverse effects

Answer 34

anaemia diarrhoea flushing gastro-oesophageal reflux disease headache nasal congestion palpitations skin reactions syncope