Organic nitrates Flashcards
What is Sodium Nitroprusside
potent vasodilator and venodilator
MOA of Sodium Nitroprusside
acts on Sulfhydryl groups to produce nitric oxide
NO then stimulates GC to GTP-cGMP
–>vasodilation of arteries+ venodilation
incr. cGMP decr. P-MLC= decr contraction of vessels
Effects of Sodium Nitroprusside
decr. TPR–> decr. afterload
Venodilation= incr. capacitance
Admin of sodium notroprusside
IV infusion
short half-life
metabolised in liver
AEs of Sodium Nitroprusside
Generates CN- groups: caution with hepatic patients
Lactic acidosis
Which is a NO donor
Hydralazine: oral 2nd/3rd line antihypertensive
add-on therapy
MOA of Hydralazine
causes generation of NO=GC stimulation=incr. cGMP
Effects of Hydralazine
incr cGMP=vasodilation of VSM in arterioles
–> decr in TPR
TU of Hydralazine
HTN but usually combined with weak diuretic and a B-Blocker
–>bcos of Na and H20 retention+tachycardia
HF with long acting nitrate in patients who are intolerant to ACEs/ARBs
AEs of Hydralazine
Tachycardia when used with B-Blocker
SLE: systemic lypus erthro…
haemolytic anaemia
Na+H2O retentio when used thiazide
Where do the organic nitrates act
mainly on veins
What is Glyceryl Trinitrate
a short acting organic nitrate
Admin of Glyceryl Trinitrate
Cannot be taken orally: bioav. 0%
Given as oral spray under tongue or IV
MOA of Glyceryl Trinitrate
incr. cGMP levels by stimulating GC
=relaxation of muscle cell in both veins and arteries
Effects of Glyceryl Trinitrate
incr. venous capacitance
more blood is stored=less blood returned to heart–> EDP drops, decr. wall stress and decr. Os consumption–> decr VR= angina relief
-Also shunts blood to ischaemic areas of heart
-causes coronary vasodilation
drop in TPR
reflex incr. in HR
TUs of Glyceryl Trinitrate
-short-term angina stoppage by decr. preload
-Aborts exercise induced angina by rapidly incr. capacitance and decr. VR
-can be used in patients with suspected MI to reduce preload and cardiac congestion
AEs of Glyceryl Trinitrate
Headache: intense vasodilation
Tachycardia
Hypotension
CI of Glyceryl Trinitrate
PDE-5 inhibitors: sildenafil
What is Isosorbide Dinitrate
is a short acting nitric oxide donor
Admin of Isosorbide Dinitrate
given sublingually: intermediate bioav.
not given orally as first pass metabolism can be up to 80%
onset of action: 30s
DOA of 5-10mins
MOA of Isosorbide Dinitrate
incr. cGMP by stimulating GC
–> relaxation of muscle cells in both veins and arteries
effects of Isosorbide Dinitrate
incr. venous capacitance
more blood is stored=less blood returned to heart–> EDP drops, decr. wall stress and decr. Os consumption–> decr VR= angina relief
-Also shunts blood to ischaemic areas of heart
-causes coronary vasodilation
drop in TPR
reflex incr. in HR
TUs of Isosorbide Dinitrate
-short-term angina stoppage by decr. preload
-Aborts exercise induced angina by rapidly incr. capacitance and decr. VR
-can be used in patients with suspected MI to reduce preload and cardiac congestion
AEs of Isosorbide Dinitrate
Headache
Tachycardia
Hypotension
CIs of Isosorbide Dinitrate
Sildenafil
What is Isosorbide mononitrate
long acting nitric oxide donor
Admin of Isosorbide mononitrate
can be taken orally: bioav. 100%
No first pass
DOA of 5-8hrs
MOA of Isosorbide mononitrate
Depletes SH groups in endothelium
incr. cGMP by stimulating GS
–> relaxation of veins and a`rteries
Effects of Isosorbide mononitrate
Same as other organic nitrates
TUs of Isosorbide mononitrate
Prophylaxis in angina
Long term treatment of angina oectoris: taken twice daily
Tachypylaxis: after 8hrs
AEs of Isosorbide mononitrate
Headache
Hypotension
Tachycardia
CI of Isosorbide mononitrate
Sildenafil
MOA of Nitric Oxide
Venodilation> vasodilation
incr. Capacitance
Decr. VR
reduced LV wall stress
Reduced O2 consumption
Coronary vasodilation
Redistribution of oxygenated blood to ischaemic LV
