Peripheral vasadilators(Summary)

Assoc. Prof. Iv. Lambev E-mail: itlambev@mail.bg

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)

Blockade of postsynaptic 1-receptorslowers 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

Postsynaptic 1-blockersDoxazosin 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

•Alfuzosin (Xatral SR®), Doxazosin, Tamsulosin (Omnic®)

Selective postsynaptic alpha-1А-blockers:block alpha-1А-receptors into the smoothmuscles of the prostate gland, and the prostatic part of the urethra.Indication: hyperplasiaof prostategland

ATP

cAMP 3’,5’-AMPAC PDE

()

(+)

PKA Effects

II. Phosphodiesteraseinhibitors

•Pentoxifylline•Drotaverine, Papaverine•Sildenafil, Tadalafil, Vardenafil

a) Methylxanthines Pentoxifylline: in cerebrovascular disease and peripheral vascular disease

Poppy

Nonselective inhibitors of PDE

Pentoxifylline blocks PDE and TGFβ1-receptors. Acting through TGFβ1 inhibition in dose 400 mg/24 h it is also reported to be effective in Peyronie's disease (induratio penis plastica).

ANGIOGENESISANGIOGENESIS

PDGF TGF-

TNF-

(+) (+)

()

VEGF (+)

b) Papaverine and their analogues (spasmolytics)- Drotaverine (No-Spa®)- Papaverine (alkaloid, isolated from

Poppy)

Poppy

Selective inhibitors of PDE5(used to treat erectile dysfunction)

•Sildenafil (Viagra®) •Tadalafil (Cialis®)•Vardenafil (Levitra®)

PDE3 (1/4000) PDE6 (1/10)

III. Prostaglandine analogues (adenylate cyclase activators)

Prostacycline (PGI2) has peripheral

vasodilating and coronary dilating effects. It also inhibits thrombocyteaggregation. Iloprost (Ilomedin) is its PGI2-

analogue, used i.v. in oblitering thromboangitis and limb ischemia.

•Prostavasin®

•Caverject®

Alprostadil is a prodrug, which is transformed in the organism to PGE1. It has a vasodilating effect in the treatmentof trophic ulcers and erectile dysfunction.Alprostadil is injected intracavernouslyin erectiledysfunction.

21

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IV. PHYTOPREPARATIONS Extr. Ginkgo bilobae (Tanakan®) – NO donor, used in peripheral vascular disease, cerebrovascular disease, and atherosclerotic hearing disordersV. 5-HT2-RECEPTOR BLOCKERS Naftidrofuryl – used in peripheral vascular disease and cerebrovascular disease

Ginkgo biloba

VDCC ROCC

Receptor

AP

Ca2+

Ca2+

Sarcoplasmaticreticulum

Cellwall

NA

(–)

AP – action potential, NA – noradrenalineVDCC – voltage-dependent calcium channelsROCC – receptor operating calcium channels

CinnarizineFlunarizineNimodipine

VI. CEREBRAL VASCULAR DILATORS Calcium antagonist (used in cerebral vasculardisease, ischemic cerebral stroke, hearing disorders)

Combined preparations: Phezam (cinnarizine/piracetam) Methylxantines (PDE inhibitors): Pentoxyfilline Phytopreparations – NO donors: Extractum Ginkgo bilobae Other preparations: Naftidrofuryl, Vinpocetine

Vinpocetine is an ethylester of apovincaminicacid, extracted from Vinca minor plant(Lesser periwinkle). It increases brain blood flow and inhibitsthrombocyte aggregation. Vinpocetine hasantihypoxic and neuroprotective effectexerted by NMDA-glutamate receptorblockade. It increases glucose and oxygensupply and utilization in the brain preventsoxidative stress.