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Why are drugs that increase regional blood flow used and in which diseases are they relevant?
To enhance perfusion to organs that require more perfusion or has been compmrimised due to vasospasm or atherosclerosis.
Peripheral artery disease, Raynaud phenomenon, erectile dysfunction
What is the steal syndrome?
In cases where one artery is blocked by atherosclerosis, the drugs enhancing blood flow can make blood be routed to other arteries. Blood will be "stolen" from the ischemic region.
Which drugs can be used to treat Raynaud phenomenon?
Dihydropyridines:
nifedipine, nimodipine
Calcium blockers + antihistamines:
cinnarizine, flunarizine,
Adrenergic alpha agonists:
Phentolamine, prazosin
Which drugs can be used to treat peripheral artery disease?
Prostanoid analogues:
Alprostadil, iloprost
PDE inhibitors:
Cilostazol
Which drugs can be used to treat erectile dysfunction?
Sildenafil, alprostadil
Which calcium channel blockers are used to treat vasospastic diseases?
Dihydropyridines like nifedipine and nimodipine.
What is the mechanism of action of sildenafil?
Sildenafil inhibits phosphodiesterase type 5 (PDE5). This isoform of PDE is found in the corpus cavernosum (and the pulmonary circulation).When sexual stimulation the brain signals the corpus cavernosum to release NO. This activates guanylate cyclase, which forms cGMP which causes muscle relaxation in the corpus cavernosum, allowing blood to enter. These drugs inhibit PDE5 and therefore inhibit the degradation of cGMP, causing a stronger and longer-lasting erection.
What is the mechanism of action of cilostazol?
Cilostazol inhibit phosphodiesterase in RBCs, causing an increase in cAMP levels. This increases the deformity of the RBC membrane.
What are the side effects of sildenafil?
Hypotension with reflex tachycardia, headache, dizziness, flush. Sildenafil causes visual disturbances.
What is the mechanism of action of alprostadil?
Alprostadil is a synthetic prostaglandin E1 (PGE1). It increases the deformability of RBCs, inhibit platelet aggregation and enhances fibrinolysis. These changes enhance the microcirculation.
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