Organic Nitrates in Angina

Question 1

what are not generally used for angina?

Answer 1

Analgesics not used

• morphine can relieve pain
• pain important to patient
• nitro relieves by peripheral vasodilation

Question 2

organic nitrates are used for?

Answer 2

angina diagnosis

• chest pain may occur in hysteria
• amyl nitrite: volatile liquid, penetrating somewhat fruity odor

Question 3

what is used for acute attacks?

Answer 3

sublingual nitrates

-Nitroglycerine

Question 4

nitroglycerine

Answer 4

onset 2 mins
peak of 4 mins
duration of 30 mins
ideal, prompt, no injection

Question 5

sublingual nitrates

Answer 5

• local burning under the tongue
• organic nitrite reductase in liver
• analogs used similarly: isosorbide mononitrate

Question 6

organic nitrates for prevention of angina

Answer 6

1. nitroglycerine sustained release
2. nitroglycerine ointment
3. nitroglycerine skin patch

Question 7

1.nitroglycerine sustained release

Answer 7

-onset 40 mins, duration 6 hours

Question 8

2.nitroglycerine ointment

Answer 8

onset 60 mins, duration 6 hours

-rotate site of application

Question 9

3. nitroglycerine skin patch

Answer 9

onset 90, duration 24 hour

-impregnated in polymer

Question 10

what is the mechanism in which nitrates relieve angina

Answer 10

1. dilate veins-> decrease preload
2. some decrease in afterload
3. increase subednocardial flow
4. relieve spasm of coronaries

Question 11

biochemical mechanisms of nitrates

Answer 11

1. increase cyclic GMP 50 fold in veins
2. metabolized ro nitric oxide (NO) by mitochondria aldehyde dehydrogenase which apparently is enriched in venous tissue
3. NO activates guanylyl cyclase to increase cGMP-> decrease phosphorylation of myosin light chain, PKG activates myosin light chain phosphatase

Question 12

side effects of organic nitrates

Answer 12

headache
postural hypotension increase by ethanol
skin rash occasionally
don’t use with sildenafil

Question 13

what is the tolerance and cross tolerance with nitrates

Answer 13

1. decreased effect with continued use due to decrease NO release-> maybe by enzyme inhibition
2. To restore effect-> stop mediation for 12 hours or increase dose
3. workers in explosive factory: headaches, postural hypotension, weakness

Question 14

ranolazine

Answer 14

• for angina
• no effect on HR and BP
• blocks delayed NA channel that facilitates Ca entry, reduces ca overload related to ischemia
• may prolong QT interval (blocks Ikr)
• constipation, headache, nausea
• CYP3A4 substrate

Question 15

Drug use in angina

Answer 15

Different sites of action

• nitrate-> veins
• CCB’s heart/arteries
• betablockers-> ranolazine heart

Question 16

what are beta-blockers not effective in

Answer 16

hypertensive

-add nitrate

Question 17

verapamil/nifed

Answer 17

good together for hypertensive

-not verap/beta block

Question 18

propranolol/nifed

Answer 18

for hypertensive

Question 19

long acting nitrate or ranolazine

Answer 19

for normotensive

Question 20

placebo effect

Answer 20

• angina relieved by placebo

- drug effectiveness not easy to evaluate