Vasodilators

Vasodilator drugs

Vasodilators are drugs that dilate blood vessels. They affect the muscles in the walls of arteries and veins, preventing the muscles from tightening and the walls from narrowing.

Vasodilators drugs divided into direct and indirect acting vasodilators-

1. Directly acting vasodilators

Directly acting vasodilators produce their action mainly by interfering with the availability of calcium for vasoconstriction. Calcium entry is prevented either by blocking voltage dependent Ca²⁺ channels or by causing hyperpolarization. Drugs produce vasodilator activity by altering Ca²⁺ release from the sarcoplasmic reticulum or reuptake into it and enzymes that determine Ca²⁺ sensitivity. These mechanisms are exemplified by calcium antagonists, potassium channel activators and drugs that influence cytoplasmic concentrations of cyclic nucleotides.

Nitrates

• Amyl nitrate, isosorbide dinitrate, glyceryl trinitrate ( nitroglycerine) are used as vasodilators.
• These are available as oral tablets, buccal tablets, sublingual tablets, inhalation preparations, topical patches (sustained release) and topical ointment.
• Nitroglycerine also helps to dilate coronary blood vessels.
• These drugs cause a direct relaxation of arterial and venous smooth muscles by acting as a source of nitric oxide which is released and causes direct relaxation.
• Toxicity includes hypotension, methemoglobinaemia and dermatitis.

Calcium channel blockers

• These drugs cause generalized vasodilatation, though individual agents differ in regional distribution of the effect by reducing intracellular availability of Calcium ions.
• Drugs under this category include verapamil, diltiazem, nifedipine, nimodipine and amlodipine.

Potassium channel activators

• These drugs relax smooth muscles by selectively increasing the membrane permeability to K⁺.
• This hyperpolarizes the membrane, switching off voltage dependent Ca²⁺ channels and inhibiting action potential generation.
• Drugs under this category include cromokalin, pinacidil, minoridil and diazoxide.

Agents that act by increasing cyclic nucleotide concentration

1. Cyclase activation
   • Many drugs relax vascular smooth muscle by increasing the cellular concentration of either cGMP or cAMP.
   • Dopamine has mixed vasodilator and vasoconstrictor actions, but, is used therapeutically to dilate the renal vasculature where it increases the cAMP by activating adenylate cyclase.
2. Nitroprusside
   • Is a very powerful vasodilator with little effects outside the vascular system.
   • It breaks down under physiological conditions to yield nitric oxide, which produces the vasodilatation effect.
   • Toxicity to nitroprusside includes excessive vasodilatation and accumulation of thiocyanate.
   • This drug also has a very short half life and must be administered by intravenous route as a freshly prepared solution.
3. Natriuretic peptides cause vasodilatation by activating guanylate cyclase.
4. Phosphodiesterase inhibitors like theophylline can also cause vasodilatation.

Vasodilators with unknown mechanism of action

1. Hydralazine
   • Acts mainly on arteries and arterioles causing a fall of blood pressure accompanied by reflex tachycardia.
   • This drug produces an increase in the stroke volume and is useful in mitral insufficiency.
2. Ethanol
   • Dilates cutaneous blood vessels causing the familiar drunkard’s flush.

2. Indirectly acting vasodilator drugs

Indirectly acting vasodilator drugs consists of two groups namely–

1. Those that inhibit sympathetically mediated vasoconstriction. Drugs can inhibit sympathetic pathway at any point from the central nervous system to the peripheral nervous terminal. Prazosin a selective α₁ adrenergic antagonist reduces mean arterial pressure.
2. Those that inhibit rennin-angiotensin system

Renin inhibitors

Several drugs inhibit release of rennin, but this mechanism of action is not of importance. Renin activity inhibitors like enalkiren have been developed. But their clinical use is not appreciable.

ACE inhibitors

Captopril was the first ACE inhibitor to be developed. Other ACE inhibitors include enlapril, lisinopril, ramipril, perindopril and trandolaprl. These drugs are useful in hypertension, cardiac failure, myocardial infarction, diabetic nephropathy and progressive renal failure.

Angiotensin II receptor subtype antagonists

Losartan is a orally active pure antagonist of AT₁ receptor. They are being tried in elderly patients with heart failure.

Clinical uses of vasodilator drugs

vasodilator drugs are used in these clinical manifestation-

1. Hypertension
2. Cardiac failure
3. Shock