Nitrates Flashcards
how does nitroglycerine work?
nitroglycerine = nitric oxide donor (NOD)
prodrug, requires enzymatic activation by tissue enzymes to become NO donor
donates nitric oxide —> cGMP —> myosin light chain phosphatase —> smooth muscle relaxation —> vasodilation
how is nitric oxide synthesized, and how does it function to promote vasodilation?
- eNOS converts arginine to NO in endothelial cells
- NO induces cGMP in smooth muscle cells (via guanylyl cyclase)
- cGMP activates myosin light chain phosphatase (via PKG)
- MLCP causes smooth muscle relaxation —> vasodilation
nitroglycerine vs sodium nitroprusside
both are NO donors
nitroglycerine is organic nitrate, must be taken sublingually or parentally, prodrug requiring enzymatic activation
sodium nitroprusside is inorganic nitrate, must be given IV, direct NO donor (no activation required)
how are organic nitrates (such as nitroglycerine) typically administered?
typically sublingual - has rapid onset of action (much less by oral)
provide rapid relief of angina, but SHORT half-life
what is the effect of nitrates on veins?
organic nitrates (such as nitroglycerine) are venodilators at low dose - increase venous capacitance
therefore decrease preload, decrease heart pressures/size, decrease myocardial oxygen demand
primary initial effect of nitrates (at the doses they’re typically given) is decrease volume in the heart via venodilation
do nitrates exert more of an effect on veins or arteries?
at the doses they’re given, nitrates primarily act as venodilators to increase venous capacitance —> decrease heart volume, decrease preload
arterial vasodilation occurs at higher doses to treat coronary artery vasospasm - dilation of large epicardial vessels, mild effect on coronary resistance vessels
what are the adverse effects of organic nitrates?
1 is headache (due to increased cerebral blood flow)
facial flushing, postural hypotension, reflex tachycardia
cause smooth muscle relaxation - gastroesophageal reflux (can be severe), constipation, incontinence, inhibits platelet aggregation
why are nitrates contraindicated in patients with RV infarct?
nitrates largely work by venodilation —> decrease preload
when there is RV infarct, the RV is less able to contract, so decreased preload will exacerbate the condition
why are nitrates contraindicated with use alongside phosphodiesterase (PDE) inhibitors?
phosphodiesterase (PDE) breaks down cGMP to GMP
if nitrate (which increases cGMP) is combined with PDE inhibitor, there will be very high levels of cGMP and therefore profound vasodilation
how does sodium nitroprusside work and when is it used?
sodium nitroprusside (SNP): NO donor, directly reduced by oxyhemoglobin to NO and cyanide
causes BOTH arteriolar and venous dilation (NO specificity)
rapid onset, short duration of action, requires continuous infusion - used for hypertensive emergency
what are 2 problematic metabolites of sodium nitroprusside and the effect of these?
sodium nitroprusside (SNP): NO donor, directly reduced by oxyhemoglobin to NO and cyanide
- SNP induces methemoglobin - ferric form, does not bind O2 (causes left shift of oxygen dissociation curve) —> cyanosis despite normal arterial pO2
- cyanide* - blocks oxidative phosphorylation (last step in ETC) —> metabolic acidosis, cardiac arrhythmias
*antidote is hydroxocobalamin, (B12) which binds free CN and induces its excretion
why might you give a patient hydroxocobalamin following administration of sodium nitroprusside?
sodium nitroprusside (SNP): NO donor, directly reduced by oxyhemoglobin to NO and cyanide
cyanide toxicity causes metabolic acidosis, cardiac arrhythmias
hydroxocobalamin is antidote for cyanide toxicity - bind free CN and induces its excretion
how does hydralazine work and what is it used for?
hydralazine: direct-acting arterial vasodilator (NOT first-line for HTN)
used for severe acute HTN, HTN in pregnancy, or heart failure with reduced EF when combined with nitrates
*can cause drug-induced lupus and increased HR
what kind of drug is nesiritide and what is its effect?
nesiritide: synthetic form of BNP (B-type natriuretic peptide) —> generates cGMP —> myosin light chain phosphatase —> vasodilation
