Nitrites and nitrates

These are nitric and nitrous acid esters of glycerol.

Mechanism of action:
1. Nitrates cause relaxation of the coronary vessels resulting in the decreased constriction of coronary vessels. The decreased constriction of the coronary arteries leads to increased transfusion of blood to the muscles of the heart (improved letting of blood).

2. On the other hand, it promotes dilation of the capacitance veins resulting in the decreased venous return to the heart due to pooled effect of blood in the veins. This decreased venous return to the heart decreases oxygen demand of the muscles of the heart.



Actions:

CVS:
Relaxation occurs in all segments of vascular system:
1. Less dilation of the arterioles and precapillary sphincters due to reflex responses.
2. They reduces cardiac output.

3. It effects directly on coronary artery tone resisting coronary artery spasm in variant angina.


4. Organonitrates causes relaxation of the arteries resulting in the reduced systemic arterial pressure causing reduced afterload of the heart leading to the reduced cardiac oxygen requirement.

5. Organonitrates causes relaxation of the veins resulting in the reduced preload causing reduced myocardial wall tension leading to reduced myocardial oxygen requirement.

6. Reduced left ventricular end diastolic volume reduces tissue pressure around subendocardial vessels  promoted coronary blood flow to this area

Other smooth muscle organs:
Organonitrates have short duration of action on the relaxation of the smooth muscles i.e. esophageal and biliary smooth muscle.

Blood:
Nitrite ion may cause pseudocyanosis and tissue hypoxia.

Therapeutic uses:
1. Stable and unstable angina pectoris
2. Variant angina pectoris
3. Orthopnea and Paroxysmal nocturnal dyspnea
4. Cyanide poisoning

Adverse effects:
Facial flushing (due to cutaneous vasodilation), Severe type of headache (due to vasodilation of cerebral vessels leading to elevated intracranial pressure and headache), Orthostatic hypotension, dizziness, weakness