Trigger 4: Therapeutics using NO and inorganic nitrate supplementation

Question 1

give an example of an organic nitrate

Answer 1

isosorbide mononitrate

Question 2

give an example of an inorganic nitrate

Answer 2

nitrate ion

Question 3

organic nitrates as vasodilators

Answer 3

• medicinally synthesised products

- very effective and quick vasodilators

Question 4

the body alone cannot process organic nitrates, what does it need

Answer 4

symbiont bacteria

Question 5

inorganic nitrate are produced

Answer 5

endogenously and also taken in from diet

Question 6

inorganic nitrates have a

Answer 6

slow vasodilatory effect

Question 7

NO donors are

Answer 7

organic

Question 8

example of indirect NO donors

Answer 8

Nitroglycerin, isosorbide mononitrate

Question 9

example of direct NO donor

Answer 9

sydnonimines

molsidomine

Question 10

how do indirect NO donors work

Answer 10

activate soluble guanylate cyclase and reduce Ca2+ uptake –> smooth muscle relaation

Question 11

how do direct NO donors work

Answer 11

activate soluble equaniylate cycle.

lowers ICAM-1 production preventing monocyte infiltration

opens ATP-sensitie potassium channels (casodilator

Question 12

benefits of indirect NO donors

Answer 12

• increased survival in patients with heart failure
• decreases progression of lesion formation, endothelial dysfunction and LDL oxidation
• lowers BP
• reduces atherosclerosis
• Anti-plateles aggregation

Question 13

benefits of direct NO donors

Answer 13

• no tolerance of NO as thiol independent
• reduces BP
• reduces atherosclerosis
• reduces inflammation
• anti-platelet aggregation

Question 14

limitation of indirect NO donors

Answer 14

Tolerance of NO
- increased production of superoxide anion by the endothelium produces NO that is inactivated = loss of responsiveness

• tissue sulfhydryl groups (-SH) required for expression of vasodilator action of organic nitrates (reacting with nitrates to release NO) – repeated administration would lead to the depletion or to the oxidation of tissue thiols

Question 15

who are NO donors for

Answer 15

angina patients

Question 16

what are inorganic nitrate supplements

Answer 16

NO3- in pure form- no carbon

Question 17

what may NO3- come bonded with

Answer 17

K or NA

- although unlikely to be with Na+ as most patients will be on a low Na+ diet anyway.

Question 18

how do inorganic nitrates work

Answer 18

same as if you were eating nitrate from foods such as beetroot

Question 19

when are inorganic nitrates used

Answer 19

Same as organic nitrates, in the presence of angina:

• hypertension
• post-MI and other CVD.

Question 20

benefits of inorganic nitrate supplementation

Answer 20

• reduces systolic BP
• endothelial protective effect
• reduces oxygen cost of exercise
• protects against metabolic syndromes
• protects against schema repression injury

Question 21

reducing oxygen cost of exercise means that

Answer 21

performance is enhanced–> improved endurance

Question 22

harms of inorganic nitrate supp

Answer 22

• cancer

- methemoglobin

Question 23

cancer and inorganic supp

Answer 23

nitrate has the potential to form carcinogenic nitrosamines (implication not fully understood)

Question 24

methemoglobin andinorganic supp

Answer 24

nitrite is reduced to NO which oxidises haemoglobin

Excessive hemoglobin in Fe3+ oxidized state is unable to bind and deliver O2 to tissues

Question 25

Methemoglobinemia

Answer 25

unable to release oxygen to tissue

Question 26

haemoglobinaemia

Answer 26

unable to carry oxygen- blue skin