Peripheral vasadilators (Summary) Assoc. Prof. Iv. Lambev

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 -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

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

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

ATP cAMP 3’,5’-AMP AC PDE () () (+) PKAEffects II. Phosphodiesterase inhibitors 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).

ANGIOGENESIS 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 (PGI 2 ) has peripheral vasodilating and coronary dilating effects. It also inhibits thrombocyte aggregation. Iloprost (Ilomedin  ) is its PGI 2 - analogue, used i.v. in oblitering thromboangitis and limb ischemia.

Prostavasin ® Caverject ® Alprostadil is a prodrug, which is transformed in the organism to PGE 1. It has a vasodilating effect in the treatment of trophic ulcers and erectile dysfunction. Alprostadil is injected intracavernously in erectile dysfunction.

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IV. PHYTOPREPARATIONS Extr. Ginkgo bilobae (Tanakan ® ) – NO donor, used in peripheral vascular disease, cerebrovascular disease, and atherosclerotic hearing disorders V. 5-HT 2 -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)

 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.