Escolar Documentos
Profissional Documentos
Cultura Documentos
Outline
I. Vasoactive Peptides I is for INACTIVE : Angiotensin I
II. Angiotensin
A. Source & Disposition II is TWO TAKE EFFECT : Angiotensin II
B. Effects & Clinical Role
C. Angiotensin Antagonists
1. ACE Inhibitors
a. Captopril
b. Enalapril EFFECTS & CLINICAL ROLE (ANGII)
2. ANGII Receptor Blockers
a. Losartan Potent arteriolar vasoconstrictor
b. Valsartan o Mediated by Angiotensin AT1 receptor (Gq-coupled
3. Aliskiren
III. Vasopeptidase Inhibitors receptor)
A. Omapatrilat o Directly increases peripheral vascular resistance
IV. Bradykinin
A. Source & Disposition o Increases blood pressure
B. Effects & Clinical Role Stimulant of aldosterone release
1. Ecallantide
2. Ecatibant
o Mediated by Angiotensin AT1 receptor
V. Natriuretic Peptides o Increases tubular reabsorption of Na+, Cl-, and water
A. Source & Disposition
B. Effects & Clinical Role
o Renal Na+ retention
1. Nesiritide o Increases K+ excretion
VI. Endothelins Facilitates release of norepinephrine from adrenergic
A. Source & Disposition
B. Effects & Clinical Role nerve endings via presynaptic heteroreceptor action
1. Bosentan o Mediated by Angiotensin AT1 receptor
2. Ambrisentan
VII. Vasoactive Intestinal Peptides o Increases sympathetic activity
VIII. Substance P Stimulate pituitary gland (posterior lobe) to secrete anti-
A. Capsaicin
B. Aprepitant diuretic hormone (ADH)
IX. Calcitonin Gene-Related Peptide o Mediated by Angiotensin AT1 receptor
X. Neuropeptide Y o Increases water reabsorption on collecting ducts
Vasodilation via nitric oxide
o Mediated by Angiotensin AT2 receptor
o Important during fetal development
Mitogenic
o Plays a role in cardiac remodeling
No longer used for clinical indications.
o Endogenous pathophysiologic mediator in some
cases of hypertension (high-renin
VASOACTIVE PEPTIDES hypertension) and heart failure.
Autacoids with actions on vascular smooth muscle and
other tissues ANGIOTENSIN ANTAGONISTS
o Neurotransmitters
o Local and Systemic Hormones 1. ACE Inhibitors
All act on cell surface receptors
Captopril
o Most act via G-protein-coupled receptor
Enalapril
Use: hypertension, heart failure
ANGIOTENSIN
Given to pts with diabetic nephropathy
SOURCE & DISPOSITION o Renoprotective effects
Renin-Angiotensin-Aldosterone Sytem (RAAS) o Decreases albumin excretion
o Angiotensin I is produced from circulating o Slow progression from micro- to macroalbuminemia
angiotensinogen (from the liver) by renin, an S/E: coughing, hyperkalemia
enzyme released from the juxtaglomerular o Hyperkalemia is due to the reduction of aldosterone
apparatus of the kidney. levels which causes K+ retention
o Angiotensin I is an inactive decapeptide, and is 2. ANGII Receptor Blockers (ARBS)
converted into angiotensin II (ANGII or AII), an Losartan
octapeptide, by angiotensin-converting enzyme Valsartan
(ACE or peptidyl dipeptidase or kininase II) in the
Orally active nonpeptide inhibitors at the ANGII AT 1
lungs.
receptor
o Angiotensin II, the active form of the peptide, is
Accompanied by a compensatory increase in renin
rapidly degraded by peptidases (angiotensinases).
and ANGI
Decrease in renal perfusion : Renin release
S/E: hyperkalemia, coughing
Increase water and salt retention, circulating volume,
o More selective, and reduced coughing (vs. ACE
and renal perfusion: Inhibition of renin release through
inhibitors)
negative feedback to the kidneys.
Capsaicin
“Hot” component of chili peppers
Release substance P from its stores in nerve endings &
depletes the peptide
Topical use: arthritic
Aprepitant
Oral antagonist at NK1 receptors
Use: chemotherapy-induced nausea and vomiting
NEUROPEPTIDE Y (NPY)
Potent vasoconstrictor
Stimulates the heart
Found in the CNS and PNS
Cotransmitter in adrenergic nerve endings
CNS administration
o Stimulates feeding
o Hypotension
o Hypothermia
PNS administration
o Positive chronotropic effect
o Positive inotropic effect
No clinical application.
APPENDIX
G
R