Você está na página 1de 5

PHARMACOLOGY 1

VASOACTIVE PEPTIDES M04L07b


Independent Study

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.

Transcribed by: MADRIDEJOS, MALASO, TORREDA Checked by: TABUZO Page 1 of 5


PHARMACOLOGY 1 VASOACTIVE PEPTIDES M04 L01

3. Aliskiren Effects & Clinical Role


 Orally actvive renin inhibitor  Vasodilators
 Reduces angiotensin I & II  Activate guanylyl cyclase in many tissues via a
 Use: hypertension membrane-spanning enzyme receptor
 Sodium excretion-enhancing agents
ACE Inhibitors : -prils  Renal actions:
o Increase glomerular filtration
ARBS : -sartans
o Decrease proximal tubular sodium reabsorption
Aliskiren : “Alis ka renin” o Inhibitory effects on renin secretion
 Inhibit actions of ANGII and aldosterone
 Compensatory role in congestive heart failure by
VASOPEPTIDASE INHIBITORS limiting sodium retention
 Blood levels of endogenous BNP correlate with the
Omapatrilat severity of heart failure (used as a diagnostic marker)
 Block both vasopeptidase enzymes (neural Nesiritide
endopeptidase 24.11 & ACE)
 BNP
 Reduce concentration of ANGII
 IV administration
 Increase the concentration of natriuretic peptides
 Use: acute severe heart failure
 Considerable efficacy in: hypertension, heart failure
 A/E: angioedema
ENDOTHELINS
 Not approved for clinical use.
 Peptide vasoconstrictors
BRADYKININ o Much more potent than norepinephrine
Source & Disposition o Relatively long-lasting effect
 Vasodilator kinins produced from kininogen by  Formed in and released by endothelial cells in blood
kallikreins vessels
 Rapidly degraded by peptidases (including ACE)  Function as autocrine and paracrine hormones in the
vasculature
Effects & Clinical Role  3 endothelin peptides in humans: ET-1, ET-2, ET-3
 Acts through B1 & B2 receptors (minor variations in amino acid sequence)
 One of the most potent vasodilators known  2 G-coupled protein receptors: ET A, ETB
 Found in saliva  Stimulate the heart
 No therapeutic application, but may play a role in the  Increase natriuretic peptide release
antihypertensive action of ACE inhibitors (promotes  Activate smooth muscle proliferation
vasodilation), inflammation, and hereditary angioedema  Involved in some forms of hypertension and other
cardiovascular
Ecallantide
 Parenteral kallikrein inhibitor Bosentan & Ambrisentan
 Use: angioedema  ETA anatagonists
 Use: pulmonary hypertension
Icatibant
 Oral bradykinin B2 receptor antagonist VASOACTIVE INTESTINAL PEPTIDE (VIP)
 Use: angioedema  Extremely potent vasodilator
 More important as a neurotransmitter
NATRIURETIC PEPTIDES  Found in CNS, PNS, and GI tract
Source & Disposition  No clinical application.
 Atrial natriuretic peptide (ANP) & Brain natriuretic
peptide (BNP) SUBSTANCE P
o Synthesized & stored in the cardiac atria of  Neurokinin
mammals o Other neurokinins: neurokinin A & B
o Released from the atria in response to distention of
 Act at NK1 & NK2 receptors in CNS & PNS
the chambers
 BNP also isolated from the brain, & appears to be the  Mixed vascular effects
most important of these peptides  Potent arteriolar vasodilator
 C-type natriuretic peptide  Potent stimulant of veins, and intestinal and airway
o Isolated from other tissues smooth muscle
 Local hormone in the GI tract

Transcribed by: MADRIDEJOS, MALASO, TORREDA Checked by: TABUZO Page 2 of 5


PHARMACOLOGY 1 VASOACTIVE PEPTIDES M04 L01

 Highest concentrations are found in the parts of the


nervous system that contain neurons subserving pain
 Involved in CNS conditions: depression, nausea and
vomiting

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

CALCITONIN GENE-RELATED PEPTIDE (CGRP)


 Cotransmitter in autonomic nerve endings
o Found in high concentrations in the thyroid, and in
most smooth muscle
 A/E: reflex tachycardia
o Most potent hypotensive agent discovered to date
 Involved in migraine headache
 No clinical application.

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.

Transcribed by: MADRIDEJOS, MALASO, TORREDA Checked by: TABUZO Page 3 of 5


PHARMACOLOGY 1 VASOACTIVE PEPTIDES M04 L01

APPENDIX

Transcribed by: MADRIDEJOS, MALASO, TORREDA Checked by: TABUZO Page 4 of 5


PHARMACOLOGY 1 VASOACTIVE PEPTIDES M04 L01

G
R

Transcribed by: MADRIDEJOS, MALASO, TORREDA Checked by: TABUZO Page 5 of 5

Você também pode gostar