06 The vascular system: vasodilators Flashcards
6.01 ACE INHIBITORS
Captopril, enalapril, lisinopril - actions
lowers blood pressure by decreasing vasoconstrictor tone and reducing cardiac load
6.01 ACE INHIBITORS
Captopril, enalapril, lisinopril - MOA
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
6.01 ACE INHIBITORS
Captopril, enalapril, lisinopril - abs/distrib/elim
given orally
half-lives: captopril ~2h, lisinopril 12h
enalapril is a prodrug converted to an active moiety by liver enzymes
6.01 ACE INHIBITORS
Captopril, enalapril, lisinopril - clinical use
hypertension
heart failure
ventricular dysfunction following MI
diabetic nephropathy
chronic renal insufficiency to prevent progression
6.01 ACE INHIBITORS
Captopril, enalapril, lisinopril - adverse effects
hypotension
dry cough
angioedema
renal failure can occur
6.01 ACE INHIBITORS
Captopril, enalapril, lisinopril - special points
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
6.02 ANGIOTENSIN ANTAGONISTS
Losartan, valsartan, candesartan, irbesartan - actions
lowers blood pressure by decreasing vasoconstrictor tone
6.02 ANGIOTENSIN ANTAGONISTS
Losartan, valsartan, candesartan, irbesartan - MOA
blocks the action of angiotensin II on the angiotensin II (AT1 subtype) receptor
6.02 ANGIOTENSIN ANTAGONISTS
Losartan, valsartan, candesartan, irbesartan - abs/distrib/elim
given orally
half-life 1-2h
half-life of metabolite 3-4h
6.02 ANGIOTENSIN ANTAGONISTS
Losartan, valsartan, candesartan, irbesartan - clinical use
hypertension
congestive heart failure
nephropathy
6.02 ANGIOTENSIN ANTAGONISTS
Losartan, valsartan, candesartan, irbesartan - adverse effects
hypotension, dizziness
hyperkalaemia can occur
6.02 ANGIOTENSIN ANTAGONISTS
Losartan, valsartan, candesartan, irbesartan - special points
does not cause the dry cough or angioedema seen with the ACE inhibitors
6.03 CALCIUM CHANNEL BLOCKERS
Amlodipine, nifedipine, verapamil, diltiazem - actions
vascular dilatation lowers blood pressure
amlodipine and nifedipine dilate arterial resistance vessels
(verapamil acts mainly on the heart, slowing the rate)
6.03 CALCIUM CHANNEL BLOCKERS
Amlodipine, nifedipine, verapamil, diltiazem - MOA
block voltage-gated calcium channels in vascular smooth muscle, which inhibits calcium influx and thus contraction
6.03 CALCIUM CHANNEL BLOCKERS
Amlodipine, nifedipine, verapamil, diltiazem - abs/distrib/elim
given orally
half-lives: amlodipine 35h, nifedipine 2h, verapamil (undergoes first-pass metabolism) ~4h
6.03 CALCIUM CHANNEL BLOCKERS
Amlodipine, nifedipine, verapamil, diltiazem - clinical use
hypertension
chronic stable angina pectoris
Prinzmetal’s angina
6.03 CALCIUM CHANNEL BLOCKERS
Amlodipine, nifedipine, verapamil, diltiazem - adverse effects
amlodipine and nifedipine: reflex tachycardia, hypotension and headache due to vasodilatation
ankle oedema
constipation
6.03 CALCIUM CHANNEL BLOCKERS
Amlodipine, nifedipine, verapamil, diltiazem - special points
grapefruit juice increases the effects
6.04 POTASSIUM CHANNEL ACTIVATOR
Minoxidil - actions
marked long-lasting vascular dilatation
lowers blood pressure
6.04 POTASSIUM CHANNEL ACTIVATOR
Minoxidil - MOA
opens potassium channels
hyperpolarises smooth muscle cells
6.04 POTASSIUM CHANNEL ACTIVATOR
Minoxidil - abs/distrib/elim
given orally
half-life ~4h
6.04 POTASSIUM CHANNEL ACTIVATOR
Minoxidil - clinical use
very severe hypertension
6.04 POTASSIUM CHANNEL ACTIVATOR
Minoxidil - adverse effects
salt and water retention, and tachycardia and angina (therefore given with a loop diuretic and a β blocker)
hirsutism
6.04 POTASSIUM CHANNEL ACTIVATOR
Minoxidil - special points
also used topically to treat baldness
6.05 VASODILATOR AND SMOOTH MUSCLE RELAXANT
Hydralazine - actions
relaxes arterial smooth muscle, thus lowering blood pressure
6.05 VASODILATOR AND SMOOTH MUSCLE RELAXANT
Hydralazine - MOA
interferes with the release of Ca2+ from the sarcoplasmic reticulum in vascular smooth muscle cells
6.05 VASODILATOR AND SMOOTH MUSCLE RELAXANT
Hydralazine - abs/distrib/elim
given orally
half-life ~1–3h
6.05 VASODILATOR AND SMOOTH MUSCLE RELAXANT
Hydralazine - clinical use
very severe hypertension - particularly in pregnancy
cardiac failure, in combination with a nitrate
6.05 VASODILATOR AND SMOOTH MUSCLE RELAXANT
Hydralazine - adverse effects
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
6.06 ENDOTHELIN ANTAGONIST
Bosentan - actions
decreases both pulmonary and systemic vascular resistance, resulting in increased cardiac output without increasing the heart rate
6.06 ENDOTHELIN ANTAGONIST
Bosentan - MOA
dual endothelin receptor antagonist - i.e. affinity for both endothelin A and B (ETA and ETB) receptors
6.06 ENDOTHELIN ANTAGONIST
Bosentan - abs/distrib/elim
given orally
half-life ~5h
bosentan is eliminated by biliary excretion following metabolism in the liver by the cytochrome P450 isoenzymes, CYP2C9 and CYP3A4
6.06 ENDOTHELIN ANTAGONIST
Bosentan - clinical use
idiopathic pulmonary hypertension
6.06 ENDOTHELIN ANTAGONIST
Bosentan - adverse effects
anaemia
diarrhoea
flushing
gastro-oesophageal reflux disease
headache
nasal congestion
palpitations
skin reactions
syncope
