Organic Nitrates in Angina Flashcards
Generally, what drugs are not used for angina?
Analgesics
Pain is an important sign that heart is being over worked
What can be used to diagnose angina?
Organic nitrates
Can distinguish b/t angina and hysteria
–if angina, pt will see immediate effect
Amyl nitrate
volatile liquid
penetrating
someone what fruity odor
What is used for acute attacks of angina?
Sublingual nitroglycerine
Onset - ~2 min
Peak - ~4 min
Duration - ~30 min
Ideal, prompt, no injection
Sublingual nitrates use
May cause local burning under the tongue
If swallowed, organic nitrite reductaste in liver will metabolize it
Analogs are used too
–isosorbide mononitrate
What other sorts of organic nitrates can be used for angina?
Nitro sustained release
–onset 40 min, duration 6 hr
Nitro onset
- -onset 60 min, duration 6 hr
- -rotate site of application
Nitro skin patch
–onset 90 min, duration 24 hours
Mechanism by which nitrates relieve angina
Dilate veins –> decrease preload
—This decreases venous return, which decreases filling, which decreases mm contraction
Some decrease in after load
Increase subendocardial flow
Relieve spasm of coronaries
Biochemical mechanisms of nitrates
Increase cGMP 50 fold in veins
Metabolized to NO by mitochondrial aldehyde dehydrogenase which apparently is enriched in venous tissue
NO activates guanylyl cyclase to increase cGMP –> decrease phosphorylation of myosin light chain
- -PKG activated myosin light chain phosphatase
- -good relaxation
S/E of organic nitrates
Headache
Postural hypotension increase by ethanol
Skin rash occasionally
Don’t use with sildenafil
Tolerance and cross tolerance does occur with nitrates. Explain.
Decrease effect with continued use due to decrease NO release
–enzyme inhibition?? we don’t really know
To restore effect, stop med for 12 hr or increase dose
Explosives factors and workers S/E
Monday morning headache, postural hypotension, weakness
Tolerance during week! - nitrates in air
Ranolazine for angina
No effect on HR or BP
Blocks delayed Na+ channel that facilities Ca2+ entry
- -so it reduces Ca2+ overload related to ischemia
- -may prolong QT interval
S/E
- constipation
- headache
- nausea
CYP3A4 substrate
So review, what drugs can be used in angina?
Nitrates (veins)
CCBs (heart/arteries)
Beta blockers/ranolazine (heart)
^^ so notice, all have different site of action and they will work well together
Can we use verapamil and B-blockers together?
NO!
They both depress heart fxn
Is there a placebo effect with angina?
YES
so when you evaluate drugs for angina, have to have good placebo control
