Pharmacodynamics

Permissiveness

Although cortisol has no direct vasoactive properties, it augments the  vasoconstrictive effects of catecho|amines and angiotensin II. The above graph  shows that administration of norepinephrine produced a limited degree of  vasoconstriction that was markedly increased following pretreatment with cortisol.

This effect is termed permlssiveness and occurs when one hormone allows  another to exert its maximal effect. Cortisol exerts its potentiating effect in part

through upregulation of alpha-1 adrenergic receptors on vascular smooth muscle  cells. In adrenal insufficiency, low glucocorticoid levels can contribute to  hypotensive crisis by decreasing vascular responsiveness to angiotensin II and  norepinephrine.

Additive & Synergistic Effects

The combination of 2 drugs with similar actions can have a  synergistic or additive effect.

When the combined effect of 2 drugs is equal to  the sum of their individual effects, it is termed an additive response.

When the  combined effect exceeds the sum of the individual drug effects, the interaction is  called synergistic.

In this case, cortisol's influence on vascular responsiveness is  best described as permissive rather than synergistic as cortisol has no intrinsic  vasoconstrictive effects.

Antagonism

Competitive = change ED50 = shift right

Non-competitive = change Emax = shift down


Adverse Drug Reactions