VASOACTIVE DRUGS PRESENTED BYMWADZIWANA LOUIS LAW
DEFINATIONS• These are drugs that affect the vasomotor tone.• They are subdivided into two vasoconstrictors and vasodilators
Vasodilators• They are subdivided into arterial (eg hydralazine, nicardipine) or venous (eg nitroglycerine)• Many of them are mixed arteriovenous vasodilators (eg nitropruside, α-adrenoceptor antagonists)
Mechanism of action of VASODILATORS• Stimulation of peripheral β2 adrenoceptor (eg isoproterenol)• Antagonism of α adrenoceptor (phentolamine)• Inhibition of inward flow of calcium ions through calcium channels(nicardipine)• Stimulation of dopaminergic receptors (fenoldopam)• Nitric oxide induced formation of cyclic guanosine monophosphate inhibition of breakdown of cyclic AMP ( milrinone)• Angiotensin converting enzyme inhibition ( enalapril)
Mechanism of Action Of Vasoconstrictors• Stimulation of peripheral α adrenoceptors ( phenylephrine)• Arginine vasopresin V1a receptors ( vasopressin)• Released when there is low blood volume
Direct Cardiac Effects• Many vasoactive drugs directly affect cardiac performance because they act on receptors, ion channels, or enzymes that are located in the vascular system and the heart.• Vasoactive drugs can be a pure vasoconstrictor (phenylephrine),• a combined vasoconstrictor and positive inotrope (norepinephrine),• A pure vasodilator ( isoproterenol)• A combined vasodilator and negative inotrope
Dopamine• Precursor of norepinephrine• In high dosage• In the periphery, dopamine stimulates prejunctional dopaminergic DA2 receptors, which results in the inhibition of norepinephrine release, facilitating vasodilation• At low doses, dopamine stimulates the dopaminergic receptors in the arteries located in the kidneys, abdomen, heart, and brain.• The vasodilation of renal and mesenteric arteries causes an increase in urine output and a decreased preload.
Mixed inotropic vasodilator Drugs (Inodilators)• Milrinone and enoximone are phosphodiesterase inhibitors• They inhibit the breakdown of cAMP in cardiac and peripheral vascular smooth muscle resulting in increased cardiac contractility and arterial and venous vasodilation.
Milrinone• PDE inhibitor• Positive inotropic effect• No effects on the heart rate• Systemic vascular resistance decrease
Nitroglycerin• Dilate the venous system, reducing pressure needed to circulate the blood around.
Dobutamine• Increase contractility and heart rate via β1 receptors• Increase vasodilation resulting in decrease afterload/SVR• Increase in blood pressure
Norepinephrine• Vasoconstrictor via α adrenergic receptors• Severe hypertension• Increase in blood pressure
Phenylephrine• Powerful vasoconstrictor• Increase in blood pressure
Epinephrine• Vasoconstrictor via α adrenergic receptors• Increased heart rate and contractility via β1 receptors• Increased vasodilation via β2 receptors