Drugs of ED (Pharmacology: Endocrinology)

Alprostadil
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Terms in this set (27)
Alprostadil
Administered IV to prevent or reverse post-natal functional closure of ductus arteriosus
Sildenafil and Tadalafil
approved for both the treatment of erectile dysfunction and pulmonary artery hypertension
Tadalafil
PDE-5 inhibitor used in the treatment of BPH
Alfuzosin
A uroselective alpha-1 antagonist used in the treatment of BPH
Alprostadil MOA
The sole member of a class of synthetic products that mimic naturally occurring PGE1. It activates adenylate cyclase, which synthesizes cAMP from ATP. cAMP acts as a second messenger activating protein kinase A, which results in an efflux of intracellular calcium and subsequent smooth-muscle relaxation and the development of an erection.
Local application of alprostadil
1. Urethral suppository: intra-urethral suppository placed there to dissolve in residual urine and to be absorbed across the urethral wall.

2. Intra-cavernosal injection: direct injection into the corpus cavernosum, taking care to avoid the top or bottom of the penis
Localized action of intra-urethral placement or intra-cavernosal injection of alprostadil
-minimal systematization: complete metabolism with renal elimination of products

-rapid onset (minutes; durable effect (0.5h-several hours)

-penile, urethral, or testicular pain most common adverse effects
Alprostadil cream
Not approved in the US yet, but it is a direct agonist PGE1 product; it will produce an erection without requiring the sexual stimulation that is needed for the effectiveness of the PDE-5 inhibitors.
PDE-5 inhibitors MOA
Sexual stimulation is required to initiate activation of NOS of nitric oxide, which is released from endothelial cells and cavernous nerves to stimulate guanylyl cyclase, resulting in increased levels of cGMP. Subsequent phosphorylation of cellular membrane proteins via protein kinase G results in an efflux of calcium, which leads to vascular smooth-muscle relaxation. By blocking cGMP breakdown, these drugs produce a more profound sustained relaxation of the vascular smooth muscle, leading to an erection.
PDE-5 inhibitors
-orally active drugs administered prn or qd

-relief of ED or PAH occurs via vascular smooth muscle relaxation
PDE-5 inhibitors Adverse effectsflushing and HA rarely: CV issues, sudden loss of hearing and sightWhy is tadalafil used for BPH?Long duration of action compared to the other agents.PDE-5i PharmacokineticsThese drugs undergo extensive hepatic metabolism involving CYP3A4 -potential increase drug effects with CYP3A4 inhibitors, like the "azole" antifungal agents, macrolides, or PIs---*consider lowering PDE-5i doses* -potential decrease drug effects with CYP3A4 inducers, like carbamazepine, phenytoin, rifampin, ritonavir, St. John's Wort--*consider increasing PDE-5i doses*PDE-5i PharmacodynamicsPossible additive vasodilatory actions with concurrent drugs. this would include alpha-1 antagonists and, more significantly the organic nitrates, which are used to treat anginal pain. remember: organic nitrate vasodilator: *absolute CI*VardenafilAdditive toxicity with concurrent QT prolonging drugs. Antiarrhythmics, macrolides, fluoroquinolones, "Azoles", some antipsychotic and antidepressants, serotonin antagonists ("setron"), methadoneWhich two PDE-5i should be not be taken after a meal because bioavailability significantly decreases?Sildenafil and VardenafilFor sex more than once a day, what is the best PDE-5i to use?tadalafilOnset/duration of AvanfilOnset, min: 15-30 Duration, hr: 6-12Onset/duration of SildenafilOnset, min: 30-60 Duration, hr: 4-5Onset/duration of TadalafilOnset, min: 30-45 Duration, hr: 24-36 if it's tadalafil daily, onset/duration is continuousOnset/duration of VardenafilOnset, min: 30-60 Duration, hr: 4-5Does PDE-5i work without sexual stimulation?Nah fam, they all require foreplay to become effectiveCan hormone replacement help with ED?Yes, approximately 65% of hypogonadal men have improvement in erectile function with testosterone replacement therapy.Yohimbine MOAalpha 2 antagonist (alpha-2 receptor inhibitor) -inhibits myosin light chain kinase, thus inhibiting VSM contraction. -increasing NO production and VSM relaxation.YohimbineOrally active, rapid metabolized drug, that crosses BBB easily, potentially producing: anxiety, antidiuresis, dizziness, flushing, HA, HTN, increased motor activity, irritability, nervousness or restlessness, sinus tachycardia, and tremor.Yohimbine interactionMAOI action at supra-clinical doses Tyramine & caffeine interactions possibleCan Yohimbine be given to someone with renal dysfunction?Hell no; it worsens renal function in failure/dysfunction