Prostaglandin vasodilator

Category Prostaglandin Vasodilator Half-life 20-30 minutes... 

PGlj prostaglandin vasodilator and inhibitor of platelet aggregation. An analog, epoprostenol, is used in primary pulmonary HTN. 

Leukotrienes C, and may also be inpjrtant mediators of inflarmatory processes. LTD. and LTE influence vasopermeability in guinea pig skin and their activities are potentiated by the presence of prostaglandin vasodilators. In addition, LTC. and LTD. increase neutrophil adherence and may also affect release reactions of macrophages. 

In addition to its other properties, interest in the potential use of the vasodilative properties of prostaglandin El, alprostadil ( ), has led to several conceptually different syntheses.For this purpose, the classic Corey process has to be modified by reversing the order of addition of the side chains to allow for convenient removal of the unwanted double bond in the upper side chain. For example, Corey lactone is protected with dihydropyran (acid catalysis), reduced to the lactol with diisobutyaluminum hydride, and then subjected to the usual Wittig reaction to give intermediate This is... 

Vasodilating molecule(s) liberated from vascular endothelial cells in response to chemical substances (i.e., Acetylcholine, bradykinin, substance P, etc.) or mechanical stimuli (i.e., shear stress, transmural pressure, etc.). The EDRF includes NO, prostaglandin J2 (prostacyclin), and endothelium-derived hypeipolarizing factor (EDHF). 

The group C counterirritants methyl nicotinate and histamine dihydrochloride produce vasodilation.24 Methyl nicotinate is a nicotinic acid derivative that produces prostaglandin-mediated vasodilation.46 NSAIDs and aspirin block the production of prostaglandins and decrease methyl nicotinate-induced vasodilation. Application over a large area has been reported to cause systemic symptoms and syncope, possibly due to vasodilation and a decrease in blood pressure.47 Patients should be educated to apply only scant amounts to the affected area to avoid this effect. 

Induction of synthesis of various lipid-based inflammatory mediators, including some prostaglandins and platelet-activating factor, by macrophages and other cells. Many of these promote sustained vasodilation and increased vascular leakage. 

I to angiotensin II, a potent vasoconstrictor and stimulator of aldosterone secretion. ACE inhibitors also block the degradation of bradykinin and stimulate the synthesis of other vasodilating substances including prostaglandin E2 and prostacyclin. The fact that ACE inhibitors lower BP in patients with normal plasma renin activity suggests that bradykinin and perhaps tissue production of ACE are important in hypertension. 

An immediate reaction occurs within seconds to minutes, resulting in the rapid release of preformed mediators and newly generated mediators from the arachidonic acid cascade. Mediators of immediate hypersensitivity include histamine, leukotrienes, prostaglandin, tryptase, and kinins. These mediators cause vasodilation, increased vascular permeability, and production of nasal secretions. Histamine produces rhinorrhea, itching, sneezing, and nasal obstruction. 

Bradykinin is a small peptide that is released from a precursor, kininogen, by the action of the proteolytic enzyme kallikrein, which itself is formed from a precursor, prekallikrein, by the action of the blood clotting factor, Xlla (Figure 17.4). Bradykinin is responsible for the pain, vasodilation and increased permeability of the blood vessels by stimulating formation and release of prostaglandins and prostacyclins from the endothelial cells (see Chapter 11). 

Nicotinic acid and its derivatives (pyridylcarbinol, xanthinol nicotinate, acipimox) activate endothelial lipoprotein lipase and thereby lower triglyceride levels. At the start of therapy, a prostaglandin-mediated vasodilation occurs (flushing and hypotension) that can be prevented by low doses of acetyl-salicylic acid. 

Pharmacology Salicylates have analgesic, antipyretic, anti-inflammatory, and antirheumatic effects. Salicylates lower elevated body temperature through vasodilation of peripheral vessels, thus enhancing dissipation of excess heat. The anti-inflammatory and analgesic activity may be mediated through inhibition of the prostaglandin synthetase enzyme complex. 

Alprostadil JProstaglandin E ] (Prostin VR) [Vasodilator/ Prostaglandin] WARNING Apnea in up to 12% of neonates esp <2 kg at birth Uses Conditions ductus arteriosus blood flow must be maintained sustain puhn/systemic circulation until OR (eg, pulm atresia/stenosis and transposition) Action Vasodilator (ductus arteriosus very sensitive), pit inhibitor Dose 0.05 mcg/kg/min IV to lowest that maintains response Caution [X, -] Contra Neonatal resp distress synd Disp Inj meg SE Cutaneous vasodilation, Sz like activity, jitteriness, T temp, thrombocytopenia, BP may cause apnea Interactions T Effects OF anticoagulants antihypertensives, effects OF cyclosporine EMS Given to newborns in hospital OD May cause apnea, bradycardia, hypotension, and flushing symptomatic and supportive... 

Prostaglandins Various, including uterine stimulants, vasodilators and inhibition of gastric acid secretion Manufactured in most tissues... 

Induction of vasodilation and inhibition of platelet aggregation prostaglandin Ei and its analogues are most commonly employed and are used to treat infants with congenital heart disease ... 

The salicylates are also potent antipyretic agents, with the exception of diflunisal, which is only weakly active. Aspirin acts at two distinct but related sites. It decreases prostaglandin-induced fever in response to pyrogens and induces a decrease in interleukin-1 modulation of the hypothalamic control of body temperature. Thus, the hypothalamic control of body temperature returns, vasodilation occurs, heat dissipates, and fever decreases. Other uses of aspirin include inhibition of platelet aggregation via inhibition of thromboxanes, which has been shown to decrease the incidence of blood clots, myocardial infarction, and transient ischemic attacks. 

Mechanism of Action A prostaglandin that directly affects vascular and ductus arteriosus smooth muscle and relaxes trabecular smooth muscle. Therapeutic Effect Causes vasodilation dilates cavernosal arteries, allowing blood flow to and entrapment in the lacunar spaces of the penis. 

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