Pharmacology Chapter 17

Front 1

MECHANISM
Angiotensin Antagonists

Back 1

ACE inhibitors (eg, captopril ), which inhibit the enzyme variously known as angiotensin-converting enzyme, kininase II, and peptidyl dipeptidase, cause a reduction in blood levels of angiotensin II and aldosterone and an increase in endogenous vasodilators of the kinin family
The second group of angiotensin antagonists, the receptor blockers, are represented by the orally active agents losartan and several analogs, which competitively inhibit angiotensin II at its AT1 receptor site.
The newest drug in the antihypertensive group is aliskiren , an inhibitor of renin's action on its substrate, angiotensinogen. It thus reduces the formation of angiotensin I and, in consequence, angiotensin II

Front 2

MECHANISM
Bradykinin

Back 2

Bradykinin acts through at least 2 receptors (B1 and B2) and causes the production of inositol 1,4,5-trisphosphate (IP 3), diacylglycerol (DAG), cyclic adenosine monophosphate (cAMP), nitric oxide, and prostaglandins in tissues. Bradykinin is one of the most potent vasodilators known

Icatibant, an orally active bradykinin B2 receptor antagonist, is under intense study in various conditions, especially hereditary angioedema,

Front 3

MECHANISM
Natriuretic Peptides

Back 3

Natriuretic peptides activate guanylyl cyclase in many tissues. They act as vasodilators as well as natriuretic (sodium excretion-enhancing) agents. Their renal action includes increased glomerular filtration, decreased proximal tubular sodium reabsorption, and inhibitory effects on renin secretion. The peptides also inhibit the actions of AII and aldosterone
BNP has shown some benefit in the treatment of acute severe heart failure and is currently available for clinical use as nesiritide

Front 4

MECHANISM
Endothelins

Back 4

Endothelins are peptide vasoconstrictors formed in and released by endothelial cells in blood vessels. Endothelins are believed to function as autocrine and paracrine hormones in the vasculature
The ETA receptor appears to be responsible for the vasoconstriction produced by endothelins.
The first antagonist to become clinically available is bosentan, which is approved for use in pulmonary hypertension.

Front 5

MECHANISM
VIP

Back 5

VIP (vasoactive intestinal peptide) is an extremely potent vasodilator but is probably more important as a neurotransmitter

Front 6

MECHANISM
Substance P

Back 6

The neurokinins (substance P, neurokinin A, and neurokinin B) act at NK1 and NK2 receptors in the central nervous system (CNS) and the periphery. Substance P has mixed vascular effects. It is a potent arteriolar vasodilator and a potent stimulant of veins and intestinal and airway smooth muscle. The peptide may also function as a local hormone in the gastrointestinal tract
Neurokinins appear to be involved in certain CNS conditions, including depression and nausea and vomiting. Aprepitant is an oral antagonist at NK1 receptors and is approved for use in chemotherapy-induced nausea and vomiting

Front 7

MECHANISM
CGRP

Back 7

(calcitonin gene-related peptide)
CGRP is the most potent hypotensive agent discovered to date and causes reflex tachycardia.

Front 8

MECHANISM
NPY

Back 8

NPY (neuropeptide Y) is a potent vasoconstrictor peptide that also stimulates the heart. NPY is found in both the CNS and peripheral nerves. In the periphery

Front 9

Vasopeptidase Inhibitors

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