Transcript No Slide Title

Peripheral vasadilators
(Summary)
Assoc. Prof. Iv. Lambev
E-mail: [email protected]
I. Alpha (Alfa)-blockers
 Non-selective alpha-blockers
(used in peripheral vascular disease):
a) Ergot-alkaloids (from Secale cornutum)
and their derivatives: Ergotamine (with ISA)
Ergotoxine, Dihydroergocristine,
Dihydroergotoxine, Dihydroergotamine
b) Synthetic drugs
Nicergolin (used in peripheral vascular
spasms and cerebral vascular disease)
Phentolamine (used in hypertensive
emergencies)
 Postsynaptic 1-blockers
Blockade of postsynaptic 1-receptors
lowers blood pressure by:
•Lowering tone in arteriolar resistance vessels.
•Dilating venous capacitance vessels, which
reduces venous return and cardiac output.
•Selective 1-adrenoceptor antagonists spare
the presynaptic 2-adrenoceptors and do
not produce reflex tachycardia.
Postsynaptic 1-blockers
Doxazosin
Prazosin
Prazosin – indications:
- Arterial hypertension
- Congestive chronic heart failure
•Potentially beneficial effect: an increase
in HDL and a reduction in triglycerides.
•Adverse reactions (ARs)
- Postural hypotension due to venous
pooling (this can be troublesome after
the first dose)
- Lethargy
Selective postsynaptic alpha-1А-blockers:
block alpha-1А-receptors into the smooth
muscles of the prostate gland, and the
prostatic part of the urethra.
Indication:
hyperplasia
of prostate
gland
•Alfuzosin (Xatral SR®), Doxazosin, Tamsulosin (Omnic®)
•Pentoxifylline
II. Phosphodiesterase
•Drotaverine, Papaverine
inhibitors
•Sildenafil, Tadalafil, Vardenafil
(-)
ATP
AC
cAMP
PDE
3’,5’-AMP
(+)
PKA
Effects
 Nonselective inhibitors of PDE
a) Methylxanthines
Pentoxifylline: in cerebrovascular disease
and peripheral vascular disease
Pentoxifylline blocks PDE and TGFβ1receptors. Acting through
TGFβ1 inhibition
in dose 400 mg/24 h
it is also reported to be
Poppy
effective in Peyronie's disease
(induratio penis plastica).
PDGF
VEGF
(+)
(+)
TGF-b
(+)
ANGIOGENESIS
(-)
TNF-b
b) Papaverine and their analogues
(spasmolytics)
- Drotaverine
(No-Spa®)
- Papaverine
(alkaloid,
isolated
from
Poppy)
Poppy
 Selective inhibitors of PDE5
(used to treat erectile dysfunction)
PDE3 (1/4000)
PDE6 (1/10)
•Sildenafil (Viagra®)
®
•Tadalafil (Cialis )
®
•Vardenafil (Levitra )
III. Prostaglandine analogues
(adenylate cyclase activators)
Prostacycline (PGI2) has peripheral
vasodilating and coronary dilating
effects. It also inhibits thrombocyte
aggregation.
Iloprost (Ilomedin) is its PGI2analogue, used i.v. in oblitering
thromboangitis and limb ischemia.
Alprostadil is a prodrug, which is
transformed in the organism to PGE1. It
has a vasodilating effect in the treatment
of trophic ulcers and erectile dysfunction.
Alprostadil is injected intracavernously
in erectile
dysfunction.
•Prostavasin®
•Caverject®
21
IV. PHYTOPREPARATIONS
Extr. Ginkgo bilobae (Tanakan®) –
NO donor, used in peripheral
vascular disease, cerebrovascular
disease, and atherosclerotic
hearing disorders
V. 5-HT2-RECEPTOR BLOCKERS
Naftidrofuryl – used
in peripheral vascular disease and
cerebrovascular disease
Ginkgo biloba
VI. CEREBRAL VASCULAR DILATORS
 Calcium antagonist (used in cerebral vascular
disease, ischemic cerebral stroke, hearing disorders)
Cinnarizine
Flunarizine
Nimodipine
AP
Ca2+
Cell
wall
(–)
NA
Receptor
ROCC
VDCC
Ca2+
Sarcoplasmatic
reticulum
AP – action potential, NA – noradrenaline
VDCC – voltage-dependent calcium channels
ROCC – receptor operating calcium channels
 Combined preparations:
Phezam (cinnarizine/piracetam)
 Methylxantines (PDE inhibitors):
Pentoxyfilline
 Phytopreparations – NO donors:
Extractum Ginkgo bilobae
 Other preparations:
Naftidrofuryl, Vinpocetine
Vinpocetine is an ethylester of apovincaminic
acid, extracted from Vinca minor plant
(Lesser periwinkle).
It increases brain blood flow and inhibits
thrombocyte aggregation. Vinpocetine has
antihypoxic and neuroprotective effect
exerted by NMDA-glutamate receptor
blockade. It increases glucose and oxygen
supply and utilization in the brain prevents
oxidative stress.