Nitrovasodilator

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Nitric oxide donor
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Nitrovasodilator
C01DA
Biological targetGuanylate cyclase
Legal status
In Wikidata

A nitrovasodilator is a pharmaceutical agent that causes

angina pectoris
.

This group of drugs includes

reduced
to NO in the body, as well as some other substances.

Examples

Here is a list of examples of the nitrate type (in alphabetical order):[2]

  1. Diethylene glycol dinitrate
  2. Glyceryl trinitrate
    (nitroglycerin)
  3. Isosorbide mononitrate and dinitrate
  4. Itramin tosilate
  5. Nicorandil (which additionally acts as a potassium channel opener)
  6. Pentaerithrityl tetranitrate
  7. Propatylnitrate
  8. Sinitrodil
  9. Tenitramine
  10. Trolnitrate

Nitrovasodilators which aren't nitrates include molsidomine and its active metabolite linsidomine, as well as sodium nitroprusside. These substances do not need to be reduced to donate NO.[2][3]

Medical uses

Glyceryl trinitrate
(nitroglycerine)
Molsidomine
Sodium nitroprusside

The nitrates are used for the treatment and prevention of angina and

soft capsules to be crunched.[4]

hypertensive crises, heart failure, and lowering of blood pressure during surgery.[5][6]

Contraindications

Nitrovasodilators are contraindicated under circumstances where lowering of blood pressure can be dangerous. This includes, with some variation between the individual substances, severe hypotension (low blood pressure),

ischaemia due to an uncontrollably low blood pressure and are therefore contraindicated. Depending on the circumstances, even fast acting substances can be contraindicated – for example, glyceryl trinitrate in patients with obstructive heart failure.[2][4]

These drugs are also contraindicated in patients that have recently taken PDE5 inhibitors such as sildenafil (Viagra).[4]

Adverse effects

Most side effects are direct consequences of the vasodilation and the resultant low blood pressure. They include headache ("nitrate headache") resulting from the widening of blood vessels in the brain,

flush, dizziness, nausea and vomiting. These effects usually subside after a few days if the treatment is continued.[2]

Occasionally, severe hypotension occurs shortly after beginning of treatment, possibly resulting in intensified angina symptoms or syncope, sometimes with bradycardia (slow heart rate).[4]

Interactions

A number of drugs add to the low blood pressure caused by nitrovasodilators: for example, other vasodilators,

tricyclic antidepressantss, antipsychotics, general anaesthetics, as well as ethanol. Combination with PDE5 inhibitors, including sildenafil (Viagra), is contraindicated because potentially life-threatening hypotension may occur.[2][4]

Nitrates increase the

coronary disease.[4]
This interaction is not described for non-nitrate nitrovasodilators.

Mechanism of action

Nitrovasodilators are prodrugs that donate NO by various mechanisms. Nitrates undergo chemical reduction, likely mediated by enzymes. Molsidomine and nitroprusside already contain nitrogen in the right oxidation state (+2) and liberate NO without the aid of enzymes.[3]

NO stimulates the soluble form of the enzyme

phosphorylates various proteins that play a role in decreasing intracellular calcium levels, leading to relaxation of the muscle cells and thus to dilation of blood vessels.[3][7]

The most important effect in angina is the widening of

coronary spasms, increasing the heart's oxygen supply.[2]

PDE5 inhibitors block deactivation of cGMP by the enzyme

phosphodiesterase-5. In combination with the increased cGMP production caused by nitrovasodilators, this leads to high concentrations of cGMP, extensive venous pooling, and potentially life-threatening hypotension.[8][9]

Nitrate tolerance

Nitrates exhibit development of tolerance, or more specifically

angiotensin II and endothelin as the blood vessels' reaction to NO-mediated vasodilation.[2]

Differences in pharmacokinetics

Nitrates mainly differ in speed and duration of their action. Glyceryl trinitrate acts fast and short (10 to 30 minutes), while most other nitrates have a slower onset of action, but are effective for up to six hours. Molsidomine, as has been mentioned, not only acts slowly but also differs from the nitrates in exhibiting no tolerance.[2] Nitroprusside, given intravenously, acts immediately, and after stopping the infusion blood pressure returns to its previous level within ten minutes.[6]

See also

References

  1. PMID 10642303
    .
  2. ^
    ISBN 978-3-8047-1763-3
    .
  3. ^
    ISBN 978-3-7692-3483-1
    .
  4. ^
    ISBN 978-3-85200-181-4
    .
  5. PMID 7598246.{{cite journal}}: CS1 maint: numeric names: authors list (link
    )
  6. ^ a b Sodium nitroprusside: Monograph.
  7. S2CID 14909302
    .
  8. PMID 10078539
    .
  9. PMID 9935041
    .
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