Organic Nitrates in Angina Flashcards
How common is angina in America
6.4 million in USA
What are some risk factors for angina
cold weather and heavy lifting
Why are general analgesics not used
morphine can relieve pain
pain is important symptom to the patient
old remedy - shot of whisky
TX: nitroglycerine relieves peripheral vasodilation
What organic nitrates are used for diagnosis of angina
chest pain may also occur in hysteria
use amyl nitrate to distinguish
Amyl nitrate is volatile liquid (penetrating, somewhat fruit odor)
What are the sublingual nitrates used for the acute attack of angina
nitroglycerine
onset- 2 min
peak- 4 min
duration- 30 min
facts about sublingual nitrates
local burning under the tongue
if swallowed –> metabolized in liver by organic nitrate reducatase –> therefore 0 effect
analogs used are isosorbide dinitrate
organic nitrates for prevention of angina
nitroglycerine in sustained release: onset 40min; duration 6hr
nitroglycerine as ointment: onset 60min; duration 6hr (rotate size of application)
nitroglycerine as skin patch: onset 90min; duration 24hrs
mechanism by which nitrates relieve angina
dilate veins –> decreases preload
some decrease in after load
increase subendocardial flow
relieve coronary vasospasm
REMEMBER: CCB for arteries; nitrates for veins
Biochemical mechanisms of nitrates
MOA: increases cGMP by 50 fold in veins
the drugs is metabolized to NO in mitochondria by aldehyde dehydrogenase which is high in veins
increases in cGMP –> decrease in phosphorylation of myosin light chains
PKG activates myosin light chain phosphatase
Side effects of nitrates
headache
postural hypotension (increased with ethanol)
skin rash occasionally
DONT USE WITH SILDENAFIL!!!
Tolerance and cross-tolerance with nitrates
decreased effect with continuous use due to decrease in NO release
to restore effect - stop medication for 12 hrs or increase dose
Ranolazine for angina
blocks delated NA+ channel that facilitates Ca++ entry --> reduces Ca++ overload related to ischemia No effect on HR or BP may prolong QT interval (blocks Ikr) constipation, headache, nausea CYP3A4 substrate
Drug use in angina
Nitrates for veins CCBs for arteries and heart B blockers for heart Propranolol/nifed for hypertension verapamil/nifed for hypertensive
DONT USE verap with beta blockers (both decrease heart function)
Placebo effect
50% of angina is relieved by placebo
not easy to evaluate
